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>> WE WELCOME YOU TO ANOTHER

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SESSION IN THE 21st YEAR IN A

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COURSE CALLED DEMYSTIFYING

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MEDICINE HELD AT THE NATIONAL

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INSTITUTES OF HEALTH IN

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BETHESDA, MARYLAND.

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THIS IS BASICALLY A COURSE IN

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BRIDGE BUILDING CONNECTING

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VARIOUS DISCIPLINES WITH THE

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IDEA THAT IF PEOPLE COMMUNICATE

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WITH ONE ANOTHER INTERESTING

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IDEAS, NOVEL IDEAS AND PROGRESS

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SMAED  -- IS MADE IN CONNECTING

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BIOLOGY, SCIENCE WITH DISEASE

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AND WITH HUMAN HEALTH.

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THE LOGO SHOWN IN THE UPPER

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RIGHT IS THE BROOKLYN BRIDGE.

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AND THE INDIVIDUALS ON THE

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BRIDGE FOR TODAY'S PURPOSE ARE

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DISCUSSING A SORT OF COMBINATION

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OF BRIDGES.

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ONE IS THE BRIDGE OF

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SERENDIPITY.

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THE OTHER IS THE BRIDGE OF

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ADVANCES IN BASIC VIROLOGY AND

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THE THIRD IS ITS APPLICATION

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INTO SERIOUS ONGOING LIVER

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DISEASE CAUSED BY VIRAL

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HEPATITIS.

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NOW, AS SHOWN ON THE SLIDE THE

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SESSION MEETS FROM JANUARY TO

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MID MAY.

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THE CODE NUMBER FOR CME IS GIVEN

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ON THE SLIDE AND ALSO THE

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WEBSITE.

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ALL THE PREVIOUS SESSIONS FROM

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THE PREVIOUS SESSIONS ARE

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ARCHIVED IN THE NIH VIDEO

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ARCHIVE AND ACCESSIBLE AT ANY

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TIME.

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THE PURPOSE IS BRIDGING OF SILOS

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OF INFORMATION INTO A MORE

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COHESIVE COLLABORATIVE ARENA.

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THIS IS THE INFORMATION FOR

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00:02:30,116 --> 00:02:37,156
THOSE WHO ARE APPLYING FOR CME.

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THE NUMBER IS 52091.

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MY HESITANCE IS AT THIS ANGLE I

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CAN'T READ IT EXACTLY.

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SO, VIRAL HEPATITIS HAS MANY

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MANY LANDMARKS AND I'VE JUST

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SELECTED A FEW OF THEM.

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IT'S IN PART TO SHOW WHAT ROLE

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THE NATIONAL INSTITUTES OF

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HEALTH HAVE PLAYED IN THE

55
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DISEASE.

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IT WAS DESCRIBED BY HIPPOCRATES

57
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AND VIRAL HEPATITIS IS MORE

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ACUTE DUE TO HEPATITIS A.

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IT'S NOT A LETHAL DISEASE YET

60
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ITS ROLE IN HISTORY HAS BEEN

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SUBSTANTIAL.

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IN THE BATTLES OF THE PAST BOTH

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SIDES CONDUCTING WARS HAD VIRAL

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HEPATITIS AND AT THE BATTLE MUCH

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GETTYSBURG NORTH AND SOUTH SIDE

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00:04:14,253 --> 00:04:17,857
THAT SUFFERED THIS DISEASE.

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A REAL INFORMATION AND THE

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00:04:20,994 --> 00:04:23,496
CONCEPT A VIRUS COULD BE CAUSING

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THE DISEASE WAS WRITTEN BY

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LARGELY FRENCH CLINICAL

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HEPATOLOGISTS.

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THE REAL ADVANCE BEGAN IN 1955

73
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WHEN STUDIES WERE CONDUCTED AT

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WILLOW BROOK, AN INSTITUTIONAL

75
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ESTABLISHMENT ON STATEN ISLAND

76
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AND THERE IT WAS DOCUMENTED

77
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THERE WERE TWO FORMS OF VIRAL

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HEPATITIS DEPENDING ON THEIR

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INCUBATION PERIOD.

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THE SHORT FORM WHICH IS WHAT WAS

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PRESENT AT WILLOW BROOK WAS

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TRANSMITTED BY A FECAL-ORAL

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ROUTE AND THE LONG INCUBATION

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FORM WAS TRANSMITTED NOT IN THAT

85
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STUDY BUT OTHERS LARGELY BY

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BLOOD AND BLOOD PRODUCTS.

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IN 1967 THE DISCOVERY OF AN

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AUSTRALIAN ANTIGEN HEPATITIS B

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OPENED THE FLOODGATES AND

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DEFINED THE FIRST DEFINITIVE

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HEPATITIS VIRUS.

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THAT WAS DONE HERE AT THE

93
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NATIONALS OF HEALTH AND

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DR. BLUMBERG RESOURCED A NOBEL

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PRIZE AND THERE'S A VACCINE BUT

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UNFORTUNATELY IT'S NOT USED

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WORLDWIDE FOR OTHER REASONS.

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IN 1973 HERE AT THE NIH, STEVE

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FEINSTONE IDENTIFIED SHORT

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INCUBATION, HEPATITIS A NOW

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00:06:17,210 --> 00:06:20,012
CALLED INFECTIOUS HEPATITIS,

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RARELY LETHAL, NON CHRONIC AND

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00:06:22,782 --> 00:06:28,621
MOST PEOPLE SURVIVE FROM IT.

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ALMOST EVERYONE DOES.

105
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IN 1989 HARVEY ALT PREPARED DICT

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FROM STUDIES IN THE BLOCK BLOOD

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BANK THERE WAS MORE THAN

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HEPATITIS A AND IT WAS LABELLED

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NON-A AND NON-B AND HEPATITIS C

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SAY SERIOUS CHRONIC DISEASE AS

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WELL.

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IT'S ALSO THE ONLY VIRUS KNOWN

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TO MANICURED BY A PHARMACEUTICAL

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BUT THERE ARE PROBLEMS THERE

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TOO.

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SO BOTH HEPATITIS B AND

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HEPATITIS C VIRUSES ARE MAJOR

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CAUSES OF CHRONIC LIVER DISEASE

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AND CHRONIC LIVER CANCER IS NOW

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THE FIFTH MOST COMMON IN THE

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UNITED STATES.

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AND OF GREAT ADVANCE IS THAT THE

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BLOOD BANK WAS RENDERED SAFE BY

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THE HEPATITIS VIRUS.

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THE DAYS OF HEPATITIS AFTER A

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TRANSFUSION WERE ODD.

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IN THINK ABOUT THIS THERE WERE

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SEVERAL THOUGHTS THAT POPPED IN

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MY MIND.

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WE'LL HEAR SOMETHING ABOUT

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TODAY.

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CAN THE HEPATITIS VIRUSES MUTATE

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LIKE A CORONAVIRUS PRODUCING NEW

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INFECTION?

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AND HOW DO THESE VIRUSES ENTER A

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LIVER CELL?

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HOW DO THEY REPLICATE?

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HOW DO THEY LEAVE?

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ARE THESE POTENTIAL THERAPEUTIC

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TARGETS FOR THE FUTURE AND HOW

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DO OTHER HEPATITIS PRODUCE

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CIRRHOSIS AND ARE THERE NO

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VACCINES FOR HEPATITIS B AND C

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AND WHY ARE THEY STILL RAMPANT

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IN THE WORLD DESPITE OUR

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THERAPEUTIC ADVANCES?

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TODAY WE'LL FOCUS ON THE

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QUESTION OF DO WE KNOW THE VIRAL

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HEPATIC CONDITIONS AND ARE THERE

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OTHER HEPATIC HEPATITIS VIRUSES

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FOR MAN AND THE ANSWER IS YES

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THERE'S HEPATITIS D AND E AND

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THEY'RE THE SUBJECT OF TODAY'S

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DEMYSTIFYING MEDICINE.

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SO OUR FIRST SPEAKER WHO WILL

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TALK ABOUT HEPATITIS D IS THEO

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HELLER IN THE TRANSLATIONAL

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HEPATOLOGY SECTION OF THE LIVER

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DISEASE BRANCH AND SENIOR

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INVESTIGATOR.

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HE HAS BEEN INTERESTED IN

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00:09:35,808 --> 00:09:39,078
CLINICAL RESEARCH, MICROBIOLOGY

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AND INFECTIOUS DISEASE, SYSTEMS

164
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OF BIOLOGY, MOLECULAR BIOLOGY

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AND APPLIED BIO CHEMISTRY.

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THEO GRADUATED FROM MEDICAL

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00:09:53,292 --> 00:09:56,162
SCHOOL IN SOUTH AFRICA AND DID

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HIS RESIDENCY AT GEORGETOWN HERE

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IN WASHINGTON, D.C. AND A

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POST-DOCTORAL FELLOWSHIP AT THE

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00:10:07,340 --> 00:10:08,774
NATIONAL INSTITUTE OF HEALTH.

172
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A GASTROENTEROLOGY FELLOWSHIP AT

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THE UNIVERSITY OF MARYLAND AND

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00:10:14,280 --> 00:10:19,285
THEN ANOTHER HEPATOLOGY SPECIFIC

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FELLOWSHIP HERE AT NIDDK.

176
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SO OUR SECOND SPEAKER IS MARK

177
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GHANY WHO RECEIVED HIS MEDICAL

178
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DEGREE FROM IRELAND AND MASTER

179
00:10:39,805 --> 00:10:45,111
OF HEALTH SCIENCES AT DUKE

180
00:10:45,177 --> 00:10:46,212
UNIVERSITY FELLOWSHIP AT TULANE

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AND THERE HE WAS A CLINICAL

182
00:10:50,282 --> 00:10:52,151
INSTRUCTOR THEN CAME TO THE NIH

183
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IN 1996 AS A MEDICAL STAFF

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00:10:55,087 --> 00:10:56,889
FELLOW AND IS A STAFF CLINICIAN

185
00:10:56,956 --> 00:10:59,291
AT THE PRESENT TIME AND SECTION

186
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CHIEF OF THE CLINICAL HEPATOLOGY

187
00:11:02,728 --> 00:11:04,130
RESEARCH SECTION OF THE LIVER

188
00:11:04,196 --> 00:11:05,164
DISEASE BRANCH HERE IN THE

189
00:11:05,231 --> 00:11:12,204
CLINICAL CENTER.

190
00:11:12,271 --> 00:11:14,240
HIS MAIN INTERESTS ARE IN

191
00:11:14,306 --> 00:11:16,776
RESEARCH AND EPIDEMIOLOGY AND

192
00:11:16,842 --> 00:11:21,914
HE'LL BE DISCUSSING HEPATITIS E.

193
00:11:21,981 --> 00:11:30,122
SO WE URGE YOU TO SUBMIT

194
00:11:30,189 --> 00:11:34,393
QUESTIONS ON YOUR COMPUTER

195
00:11:34,460 --> 00:11:35,261
THERE'S AN INDICATION WHERE YOU

196
00:11:35,327 --> 00:11:36,662
CAN SUBMIT IT AND THEY'LL BE

197
00:11:36,729 --> 00:11:37,696
ANSWERED AND DISCUSSED IN A

198
00:11:37,763 --> 00:11:39,532
QUESTION AND ANSWER PERIOD THAT

199
00:11:39,598 --> 00:11:40,633
WILL FOLLOW THE TWO

200
00:11:40,699 --> 00:11:44,637
PRESENTATIONS.

201
00:11:44,703 --> 00:11:47,306
SO THEO, WOULD YOU BEGIN,

202
00:11:47,373 --> 00:11:57,516
PLEASE.

203
00:12:23,576 --> 00:12:26,612
>> IT'S THE LESS APPRECIATED

204
00:12:26,679 --> 00:12:29,615
THOUGHT OF VIRUS BOTH OF THEM

205
00:12:29,682 --> 00:12:31,750
TODAY, HEPATITIS D AND E AND

206
00:12:31,817 --> 00:12:34,253
WE'LL TRY TO HIGHLIGHT SOME OF

207
00:12:34,320 --> 00:12:35,287
THE REASONS WHY THIS SHOULDN'T

208
00:12:35,354 --> 00:12:37,256
BE THE CASE.

209
00:12:37,323 --> 00:12:42,128
MY DISCLOSURES I WANT TO

210
00:12:42,194 --> 00:12:46,799
ELIMINATE HEPATITIS D AND

211
00:12:46,866 --> 00:12:51,370
OBSESSED WITH LIVER DISEASE AND

212
00:12:51,437 --> 00:12:55,074
START THE DAY WITH COFFEE AND

213
00:12:55,141 --> 00:12:58,611
HAVE NO FINANCIAL DISCLOSURES

214
00:12:58,677 --> 00:13:02,281
AND WE LOOK TO APPROACH PATIENTS

215
00:13:02,348 --> 00:13:06,685
WITH HEPATITIS D AND THE

216
00:13:06,752 --> 00:13:07,987
UPCOMING RESOLUTION TO CURE

217
00:13:08,053 --> 00:13:08,821
HEPATITIS D.

218
00:13:08,888 --> 00:13:12,358
THERE'S A PARADIGM SHIFT.

219
00:13:12,424 --> 00:13:15,094
WHAT IS HEPATITIS D IT WAS

220
00:13:15,161 --> 00:13:20,332
DISCOVERED BY SERENDIPITY AND IT

221
00:13:20,399 --> 00:13:23,802
WAS THE STORY WITH THE BRIDGE

222
00:13:23,869 --> 00:13:27,206
AND IT WAS IN A SEMINOLE PAPER

223
00:13:27,273 --> 00:13:30,309
AND BEFORE TALKING ABOUT

224
00:13:30,376 --> 00:13:33,879
HEPATITIS D IT'S ABLE TO SAY

225
00:13:33,946 --> 00:13:36,582
VACCINATION IS AYE THE ULTIMATE

226
00:13:36,649 --> 00:13:40,819
CURE BUT IT IS FOR HEPATITIS D.

227
00:13:40,886 --> 00:13:43,155
IF WE COULD VACCINE EVERYONE FOR

228
00:13:43,222 --> 00:13:46,892
HEPATITIS B WE'D BE RID OF B.

229
00:13:46,959 --> 00:13:52,765
WHY DO WE CARE ABOUT HEPATITIS

230
00:13:52,831 --> 00:13:56,068
D, 50% DEVELOP CIRRHOSIS WITH

231
00:13:56,135 --> 00:13:57,436
HEPATITIS D AND THE HIGHER RANGE

232
00:13:57,503 --> 00:14:00,072
OF 20% TO 20 YEARS INCREASED

233
00:14:00,139 --> 00:14:10,583
RISK OF HCC HEPATOCARCINOMA

234
00:14:10,649 --> 00:14:15,854
THREE FOLD HIGHER AND WHY SHOULD

235
00:14:15,921 --> 00:14:18,090
WE CARE?

236
00:14:18,157 --> 00:14:19,825
IF IT'S SUCH A BAD DISEASE AN

237
00:14:19,892 --> 00:14:20,693
NOTHING TO DO WE COULDN'T CARE

238
00:14:20,759 --> 00:14:23,295
BUT I WANT TO HIGHLIGHT A COUPLE

239
00:14:23,362 --> 00:14:25,164
THINGS ALL FROM THE CLINICAL

240
00:14:25,231 --> 00:14:28,033
CENTER.

241
00:14:28,100 --> 00:14:31,070
THERE WAS A STUDY TREATING 13

242
00:14:31,136 --> 00:14:35,874
PATIENTS AND THREE CONVERTED

243
00:14:35,941 --> 00:14:37,576
WITHIN FIVE YEARS AND AFTER

244
00:14:37,643 --> 00:14:42,448
ALMOST NINE YEAR OF FOLLOW UP

245
00:14:42,514 --> 00:14:45,117
SIX OF SEVEN WERE ALIVE AND

246
00:14:45,184 --> 00:14:46,852
PERHAPS THE FIRST EVIDENCE FOR

247
00:14:46,919 --> 00:14:51,890
RESOLUTION ARE OF SORCIRRHOSIS

248
00:14:51,957 --> 00:14:54,126
SINGLE PATIENT WAS TREATED IN

249
00:14:54,193 --> 00:15:02,334
THE '90s WITH CHRONIC HEPATITIS

250
00:15:02,401 --> 00:15:08,307
D AND THIS WAS PUBLISHED AND IN

251
00:15:08,374 --> 00:15:12,444
PANEL A, YOU CAN SEE THE

252
00:15:12,511 --> 00:15:12,978
NODULES.

253
00:15:13,045 --> 00:15:15,447
IN B YOU SEE BRIDGING FIBROSIS

254
00:15:15,514 --> 00:15:16,548
AND GRADUAL RESOLUTION.

255
00:15:16,615 --> 00:15:21,420
SO YOU GET TO D WHICH IS

256
00:15:21,487 --> 00:15:23,922
ESSENTIALLY A NORMAL LIVER

257
00:15:23,989 --> 00:15:24,156
BIOPSY.

258
00:15:24,223 --> 00:15:26,091
THIS GIVES THE IMPORTANT OF WHY

259
00:15:26,158 --> 00:15:27,526
AND FINDING PATIENTS AND

260
00:15:27,593 --> 00:15:31,597
TREATING AND THE FIRST

261
00:15:31,664 --> 00:15:32,197
ILLUSTRATION DOCUMENTED OF

262
00:15:32,264 --> 00:15:37,736
RESOLUTION OF CIRRHOSIS.

263
00:15:37,803 --> 00:15:39,571
WHY DO WE TREAT?

264
00:15:39,638 --> 00:15:43,108
THE REAL REASON IS TO TREAT FOR

265
00:15:43,175 --> 00:15:43,309
DEATH.

266
00:15:43,375 --> 00:15:47,012
EVERYTHING ELSE IS A SURROGATE

267
00:15:47,079 --> 00:15:50,549
AND WE LOOK AT CONVERSION AND

268
00:15:50,616 --> 00:15:55,954
HEPATITIS D RNA LOSS AS A

269
00:15:56,021 --> 00:15:57,156
FURTHER EMPHASIS, THREE YEARS

270
00:15:57,222 --> 00:16:01,160
AGO THEY PUBLISHED 25% OF

271
00:16:01,226 --> 00:16:03,896
SURFACE ANTIGEN TRANSPLANT

272
00:16:03,962 --> 00:16:05,197
PATIENTS IN EUROPE WERE

273
00:16:05,264 --> 00:16:07,333
HEPATITIS D POSITIVE MORE THAN

274
00:16:07,399 --> 00:16:08,867
FIVE TIMES THE PROPORTION YOU'D

275
00:16:08,934 --> 00:16:09,301
EXPECT.

276
00:16:09,368 --> 00:16:12,137
IT'S VERY SIMPLE.

277
00:16:12,204 --> 00:16:13,572
TEST EVERYONE ONCE AND USE

278
00:16:13,639 --> 00:16:24,149
ANTIBODY AND CONFIRM WITH PCR.

279
00:16:24,383 --> 00:16:26,151
LET'S TALK DEEPER BECAUSE THE

280
00:16:26,218 --> 00:16:26,752
EPIDEMIOLOGY WILL INFORM THE

281
00:16:26,819 --> 00:16:36,462
WHO.

282
00:16:36,528 --> 00:16:39,031
SHOULD WE COMPARE EVERYBODY TO

283
00:16:39,098 --> 00:16:41,033
HIGH RISK VERSUS LOW RISK AND

284
00:16:41,100 --> 00:16:43,001
VARIABILITY AND THE LACK OF

285
00:16:43,068 --> 00:16:45,604
TESTING AND THIS IS ONE OF MY

286
00:16:45,671 --> 00:16:49,575
FAVORITE PARAGRAPHS IN THE FIELD

287
00:16:49,641 --> 00:16:53,545
WRITTEN BY DR. ROSSETTA DESPITE

288
00:16:53,612 --> 00:16:54,980
THE GLOBAL SURVEYS THE GLOBAL

289
00:16:55,047 --> 00:16:58,650
NUMBER REMAIN UNDEFINED AN

290
00:16:58,717 --> 00:17:01,520
ESTIMATES RANGE FROM 12 MILLION

291
00:17:01,587 --> 00:17:03,622
TO 75 MILLION AN TELLS YOU HOW

292
00:17:03,689 --> 00:17:05,758
LITTLE RIGOR THERE'S BEEN IN THE

293
00:17:05,824 --> 00:17:07,659
FIELD AND THE FIGURES EMPHASIZE

294
00:17:07,726 --> 00:17:09,895
THE REPORTS ON HEPATITIS D AND

295
00:17:09,962 --> 00:17:12,231
LACK OF SUFFICIENT QUALITY DATA

296
00:17:12,297 --> 00:17:14,266
THUS INADEQUATE SCREENING AND

297
00:17:14,333 --> 00:17:16,301
LIMITATIONS AND LACK OF TESTING

298
00:17:16,368 --> 00:17:19,438
HAVE IMPANCTED HOW WE SEE

299
00:17:19,505 --> 00:17:21,140
HEPATITIS D.

300
00:17:21,206 --> 00:17:23,108
THIS IS A MAP SHOWING HOT SPOTS

301
00:17:23,175 --> 00:17:26,545
IN RED, YELLOW INTERMEDIATE AND

302
00:17:26,612 --> 00:17:28,781
GREEN LOW AND BLUE VERY LOW AND

303
00:17:28,847 --> 00:17:30,616
DIFFERENT GENOTYPES.

304
00:17:30,682 --> 00:17:33,152
THIS IS IMPORTANT BECAUSE THEY

305
00:17:33,218 --> 00:17:36,955
DIFFER GLOBALLY AND HAVE

306
00:17:37,022 --> 00:17:39,057
DIFFERENT DETECTION RATES WITH

307
00:17:39,124 --> 00:17:41,326
DIFFERENT ASSAYS AND HOT SPOTS

308
00:17:41,393 --> 00:17:43,162
THINK THE PREVALENCE OF

309
00:17:43,228 --> 00:17:44,296
INCIDENTS OF HEPATITIS D.

310
00:17:44,363 --> 00:17:45,898
THIS IS A STUDY FROM THE

311
00:17:45,964 --> 00:17:46,532
CLINICAL CENTER.

312
00:17:46,598 --> 00:17:49,868
WE LOOKED AT 588 PATIENTS WITH

313
00:17:49,935 --> 00:17:53,238
CLEAR RESPECTIVE FOR HEPATITIS D

314
00:17:53,305 --> 00:17:59,111
AND DID A MULTIVARIATE ANALYSIS

315
00:17:59,178 --> 00:18:02,381
AND THERE WERE HEPATITIS D THAT

316
00:18:02,448 --> 00:18:05,050
WAS DOMINANT.

317
00:18:05,117 --> 00:18:05,884
ALT WAS HIGH.

318
00:18:05,951 --> 00:18:08,086
PEOPLE WHO INJECTED DRUGS AND

319
00:18:08,153 --> 00:18:11,356
MOST IMPORTANT TODAY IN EUROPE

320
00:18:11,423 --> 00:18:12,891
AND NORTH AMERICA ENDEMIC

321
00:18:12,958 --> 00:18:13,492
COUNTRY OF ORIGINS THE HOT

322
00:18:13,559 --> 00:18:23,101
SPOTS.

323
00:18:23,168 --> 00:18:25,838
IF YOU'RE SURFACE ANTIGEN

324
00:18:25,904 --> 00:18:29,141
POSITIVE YOU SHOULD BE SCREENED

325
00:18:29,208 --> 00:18:35,347
FOR HEPATITIS D AND/OR HIV.

326
00:18:35,414 --> 00:18:39,952
THE AMERICAN GUIDELINES SAY IF

327
00:18:40,018 --> 00:18:41,320
HEPATITIS B VIRAL LEVELS ARE LOW

328
00:18:41,386 --> 00:18:43,322
OR IF YOU'RE AT RISK FOR

329
00:18:43,388 --> 00:18:45,157
HEPATITIS D AND THERE'S A LONG

330
00:18:45,224 --> 00:18:47,326
LIST OF RISK FACTORS YOU CAN

331
00:18:47,392 --> 00:18:48,994
IMAGINE EVERY PRIMARY CARE GOING

332
00:18:49,061 --> 00:18:59,605
FLEW -- THROUGH WITH PATIENTS IN

333
00:18:59,805 --> 00:19:01,507
THEIR OFFICE WHEN THEY HAVE FIVE

334
00:19:01,573 --> 00:19:02,641
MINUTES WITH THEIR PATIENT.

335
00:19:02,708 --> 00:19:04,376
THIS IS WHERE THE FIELD STANDS.

336
00:19:04,443 --> 00:19:06,912
A PATIENT, 49-YEAR-OLD MAN BORN

337
00:19:06,979 --> 00:19:08,046
IN IDAHO, MARRIED WITH TWO

338
00:19:08,113 --> 00:19:09,948
CHILDREN, UPSTANDING CITIZENS

339
00:19:10,015 --> 00:19:12,484
INVOLVED WITH COMMUNITY

340
00:19:12,551 --> 00:19:17,356
ACTIVITIES HAD HIS COLONOSCOPY.

341
00:19:17,422 --> 00:19:22,261
THE GASTROENTEROLOGIST NOTED HIS

342
00:19:22,327 --> 00:19:24,696
LEVELS WERE ELEVATE AND E

343
00:19:24,763 --> 00:19:27,132
ANTIGEN WAS POSITIVE SO HE

344
00:19:27,199 --> 00:19:29,701
TREATED HIM FOR HEPATITIS B BUT

345
00:19:29,768 --> 00:19:40,312
THE PATIENT WENT ON TO DEVELOP

346
00:19:42,714 --> 00:19:43,482
CHOLANGIOCARCINOMA AND ANOTHER

347
00:19:43,549 --> 00:19:45,050
CLINICIAN FOUND HE WAS HEPATITIS

348
00:19:45,117 --> 00:19:47,753
B POSITIVE AND I KNOW WHAT

349
00:19:47,819 --> 00:19:49,721
YOU'RE THINK.

350
00:19:49,788 --> 00:19:52,591
YOU'RE THINK, THAT'S NICE, THEO

351
00:19:52,658 --> 00:19:53,725
BUT IT'S AN ANECDOTE.

352
00:19:53,792 --> 00:19:57,129
IT'S NOT TRUE.

353
00:19:57,195 --> 00:20:02,100
OKAY.

354
00:20:02,167 --> 00:20:04,670
LET'S LOOK AT THE VIRAL B LEVELS

355
00:20:04,736 --> 00:20:10,809
AND WHICH VIRUS WAS DOMINANT AND

356
00:20:10,876 --> 00:20:12,811
IT WAS ALMOST EVENLY SPLIT THE

357
00:20:12,878 --> 00:20:15,514
BETWEEN B AND D AND THEY LOOKED

358
00:20:15,581 --> 00:20:19,051
AT THE DNA LEVELS AND AGAIN IT

359
00:20:19,117 --> 00:20:22,988
WAS NOT THE SORT OF DOMINANCE

360
00:20:23,055 --> 00:20:24,456
YOU WOULD EXPECT.

361
00:20:24,523 --> 00:20:28,393
44% AND 39% WERE NOT HEPATITIS D

362
00:20:28,460 --> 00:20:28,694
DOMINANT.

363
00:20:28,760 --> 00:20:33,398
IN TERMS OF DOMINANCE AND

364
00:20:33,465 --> 00:20:36,368
HEPATITIS B DNA LEVELS IS NOT

365
00:20:36,435 --> 00:20:37,502
HOW THE VIRUS BEHAVES HALF THE

366
00:20:37,569 --> 00:20:37,803
TIME.

367
00:20:37,869 --> 00:20:42,808
WHAT ABOUT THE RULES AN

368
00:20:42,874 --> 00:20:47,346
GUIDELINE?

369
00:20:47,412 --> 00:20:50,816
T

370
00:20:50,882 --> 00:20:53,452
TATIANA KUSHNER LOOKED AT THE

371
00:20:53,518 --> 00:20:55,153
SYSTEM WITH PATIENT WERE SIR FAS

372
00:20:55,220 --> 00:21:00,092
B POSITIVE AND FOUND 8.5% WERE

373
00:21:00,158 --> 00:21:00,459
SCREENED.

374
00:21:00,525 --> 00:21:03,962
SHE FOUND OF THOSE SCREENED,

375
00:21:04,029 --> 00:21:05,697
3.4% WERE POSITIVE WHICH ISN'T

376
00:21:05,764 --> 00:21:10,068
WHAT WE'D EXPECT, 2 TO 5% AND OF

377
00:21:10,135 --> 00:21:12,504
THOSE POSITIVE ONLY 8.2% HAD RNA

378
00:21:12,571 --> 00:21:13,005
CHECKED.

379
00:21:13,071 --> 00:21:18,443
EVEN WHEN THEY HAD A POSITIVE

380
00:21:18,510 --> 00:21:22,748
RESPONSE THEY IGNORED IT AND 80%

381
00:21:22,814 --> 00:21:27,185
OF PATIENTS WITH A HIGH RISK

382
00:21:27,252 --> 00:21:30,822
PROFILE WERE NOT TESTED.

383
00:21:30,889 --> 00:21:32,858
IT'S 796.25.

384
00:21:32,924 --> 00:21:38,797
I ROUND THE OFF TO 796.

385
00:21:38,864 --> 00:21:41,333
WHAT ABOUT WHEN WE DO FOLLOW THE

386
00:21:41,400 --> 00:21:41,667
RULES?

387
00:21:41,733 --> 00:21:45,137
I SHOWED THE DEFINITION BY

388
00:21:45,203 --> 00:21:46,505
FOLLOWING THIS IT'S NOT USEFUL

389
00:21:46,571 --> 00:21:48,473
AND WE DON'T FOLLOW OUR OWN

390
00:21:48,540 --> 00:21:50,175
RULES OF HIGH RISK PATIENTS BUT

391
00:21:50,242 --> 00:21:53,478
WHEN FOLLOW THE RULES THIS IS A

392
00:21:53,545 --> 00:21:55,447
FANTASTIC STUDY FROM EUROPE.

393
00:21:55,514 --> 00:22:02,688
PRIOR TO REFLEX TESTING ONLY

394
00:22:02,754 --> 00:22:11,496
7.6% WERE TESTED IN THE POSITIVE

395
00:22:11,563 --> 00:22:13,865
TESTING AND THE AMOUNT OF

396
00:22:13,932 --> 00:22:19,738
POSITIVE QUINTUPLES.

397
00:22:19,805 --> 00:22:23,975
MANY DID NOT HAVE A LONG LIST

398
00:22:24,042 --> 00:22:26,178
RISK FACTORS AND THIS IS TEXT

399
00:22:26,244 --> 00:22:28,046
FROM THE VISUAL ABSTRACT.

400
00:22:28,113 --> 00:22:28,847
SCREENING VIRUS FACTORS IS SUB

401
00:22:28,914 --> 00:22:36,254
OPTIMAL.

402
00:22:36,321 --> 00:22:38,490
SO 40% HAVE LEVELS AND DON'T

403
00:22:38,557 --> 00:22:39,691
TEST THOSE WITH DOCUMENTED HIGH

404
00:22:39,758 --> 00:22:41,126
RISK AND 60% HAVE NO RISK

405
00:22:41,193 --> 00:22:43,495
FACTORS.

406
00:22:43,562 --> 00:22:45,630
SO I WANT TO DIGRESS A LITTLE

407
00:22:45,697 --> 00:22:47,099
BIT AND TALK ABOUT THE HEPATITIS

408
00:22:47,165 --> 00:22:52,637
B VACCINATION EFFORT.

409
00:22:52,704 --> 00:22:56,308
IN 1981 IT WAS LICENSED AND

410
00:22:56,374 --> 00:22:59,010
RECOMMENDED FOR HIGH RISK GROUPS

411
00:22:59,077 --> 00:23:01,580
SUCH AS INFANTS WHOSE MOTHERS

412
00:23:01,646 --> 00:23:03,715
WERE POSITIVE AND THINGS LIKE

413
00:23:03,782 --> 00:23:03,915
THAT.

414
00:23:03,982 --> 00:23:05,150
IF YOU LOOK AT THE TIME IT

415
00:23:05,217 --> 00:23:06,752
DIDN'T DO MUCH TO THE INCIDENTS

416
00:23:06,818 --> 00:23:15,193
OF HEPATITIS B.

417
00:23:15,260 --> 00:23:18,964
IN 1991 THEY SAID THIS IS NOT

418
00:23:19,030 --> 00:23:20,499
WORKING LET'S IMMUNIZE EVERYBODY

419
00:23:20,565 --> 00:23:23,335
AND HEPATITIS B WAS VIRTUALLY

420
00:23:23,401 --> 00:23:24,736
ELIMINATED IN CHILDREN LESS THAN

421
00:23:24,803 --> 00:23:27,639
18 YEARS OF AGE AND HPV THE

422
00:23:27,706 --> 00:23:29,641
GUIDELINE SAID LET'S ONLY

423
00:23:29,708 --> 00:23:32,978
VACCINE ADOLESCENT FEMALES?

424
00:23:33,044 --> 00:23:35,847
WELL, WHERE ARE THEY GETTING THE

425
00:23:35,914 --> 00:23:39,451
HPV FROM AND WE REALIZED WE'RE

426
00:23:39,518 --> 00:23:41,453
NOT THAT SMART AND WE CAN GO

427
00:23:41,520 --> 00:23:43,455
THROUGH OTHER ILLUSTRATIONS.

428
00:23:43,522 --> 00:23:45,991
HISTORY DOESN'T ALWAYS REPEAT.

429
00:23:46,057 --> 00:23:46,792
SOMETIMES IT JUST SCREAMS.

430
00:23:46,858 --> 00:23:48,827
WHY DON'T YOU LISTEN TO ME AND

431
00:23:48,894 --> 00:23:56,902
FLY WITH THE BIG STICK.

432
00:23:56,968 --> 00:23:58,670
I HAVE TO SUGGEST THE GUIDELINES

433
00:23:58,737 --> 00:23:59,938
ARE NOT APPROPRIATE.

434
00:24:00,005 --> 00:24:02,874
SO WHO SHOULD BE TESTED?

435
00:24:02,941 --> 00:24:04,743
EVERYONE WITH HEPATITIS B

436
00:24:04,810 --> 00:24:07,579
IMAGINE A WORLD WITH NO DELTA

437
00:24:07,646 --> 00:24:08,113
WOULD BE SOMETHING REALLY

438
00:24:08,180 --> 00:24:17,823
DIFFERENT.

439
00:24:17,889 --> 00:24:22,494
A BOOK THE ARTS AND POLITICS OF

440
00:24:22,561 --> 00:24:24,196
YOU CAN'T STUDY OR TREAT

441
00:24:24,262 --> 00:24:25,163
ANYTHING IF YOU DON'T KNOW HOW

442
00:24:25,230 --> 00:24:32,904
TO MEASURE IT AND MANY KNONO NO

443
00:24:32,971 --> 00:24:37,142
PRIZES HAVE BEEN GIVEN JUST FOR

444
00:24:37,209 --> 00:24:45,150
THE ABILITY TO MEASURE AND GOES

445
00:24:45,217 --> 00:24:55,760
TO UNIVERSAL TESTING AND WE TEST

446
00:25:00,599 --> 00:25:02,500
THE DOG AND WE FOUND IT'S

447
00:25:02,567 --> 00:25:04,469
POSITIVE AND YOU THINK FEDERAL

448
00:25:04,536 --> 00:25:09,007
EMPLOYEES SIP ON MINT TEA AND

449
00:25:09,074 --> 00:25:12,310
EAT GODIVA SO ONE DAY WHILE

450
00:25:12,377 --> 00:25:16,147
SITTING AT HOME WE LOOKED AT A

451
00:25:16,214 --> 00:25:19,284
MALE WHO LIVES AND WORKS IN

452
00:25:19,351 --> 00:25:23,421
CHICAGO AND REFERRED FOR

453
00:25:23,488 --> 00:25:24,723
HEPATI

454
00:25:24,789 --> 00:25:30,362
HEPATITIS B AND WAS SURFACE

455
00:25:30,428 --> 00:25:32,364
ANTIGEN POSITIVE AND ANTIBODY

456
00:25:32,430 --> 00:25:34,299
POSITIVE.

457
00:25:34,366 --> 00:25:39,037
HE'S MORE TYPICAL AND IT WAS

458
00:25:39,104 --> 00:25:40,572
ANTIGEN NEGATIVE AND LIVER

459
00:25:40,639 --> 00:25:43,174
BIOPSY WAS IMPRESSIVE, 14 OF 18

460
00:25:43,241 --> 00:25:46,011
FOR INFLAMMATORY SCORE AND 3 OF

461
00:25:46,077 --> 00:25:50,815
6 BRIDGING FIBROSIS AND IS A

462
00:25:50,882 --> 00:25:52,617
HEPATIC VENOUS PRESSURE GRADIENT

463
00:25:52,684 --> 00:25:55,053
THE PORTAL PRESSURE SURROGATE

464
00:25:55,120 --> 00:25:59,324
WAS 8 MILL METERS WHICH IS

465
00:25:59,391 --> 00:26:00,325
ELEVATED.

466
00:26:00,392 --> 00:26:03,595
NOR THAN 10 TO 12 IS

467
00:26:03,662 --> 00:26:04,329
SIGNIFICANT.

468
00:26:04,396 --> 00:26:05,130
THE FIRST QUESTION THE PATIENT

469
00:26:05,196 --> 00:26:07,599
ASKS IS CAN I GIVE IS TO ANYONE

470
00:26:07,666 --> 00:26:08,233
ELSE.

471
00:26:08,300 --> 00:26:13,138
THAT'S HIS FEAR.

472
00:26:13,204 --> 00:26:15,974
WE SHOULDN'T FORGET THE

473
00:26:16,041 --> 00:26:16,274
GUIDELINES.

474
00:26:16,341 --> 00:26:19,377
BLOOD AND BODY FLUIDS.

475
00:26:19,444 --> 00:26:23,615
CO-INFECTION WHERE PATIENTS GET

476
00:26:23,682 --> 00:26:27,719
HEPATITIS B AND D AT THE SAME

477
00:26:27,786 --> 00:26:29,421
TIME AND PEOPLE BECOME CHRONIC

478
00:26:29,487 --> 00:26:32,791
AND PEOPLE GET HEPATITIS B AND

479
00:26:32,857 --> 00:26:35,093
THEN GET B AND 90% BECOME

480
00:26:35,160 --> 00:26:40,632
CHRONIC AND THAT'S OFTEN MISSED.

481
00:26:40,699 --> 00:26:44,836
WHAT'S NEXT?

482
00:26:44,903 --> 00:26:48,540
WE NEED TO GO BACK TO BASICS.

483
00:26:48,606 --> 00:26:51,977
HEPATITIS B IS DIFFICULT TO

484
00:26:52,043 --> 00:26:52,277
UNDERSTAND.

485
00:26:52,344 --> 00:26:53,445
1700 NUCLEOTIDES.

486
00:26:53,511 --> 00:26:58,950
THE SMALLEST PATHOGENIC VIRUS IN

487
00:26:59,017 --> 00:26:59,351
HUMANS.

488
00:26:59,417 --> 00:27:01,786
IT'S CLOSED AND BROAD SHAPED AND

489
00:27:01,853 --> 00:27:03,221
SURROUNDED BY HEPATITIS D LARGE

490
00:27:03,288 --> 00:27:07,892
AND SMALL ANTIGEN AND THE ONLY

491
00:27:07,959 --> 00:27:08,727
VIRUS IT CODES FOR.

492
00:27:08,793 --> 00:27:12,731
IT DOESN'T CODE FOR ANYTHING

493
00:27:12,797 --> 00:27:12,931
ELSE.

494
00:27:12,998 --> 00:27:16,568
ANY SELF-RESPECTING VIRUS CODES

495
00:27:16,634 --> 00:27:18,303
FOR POLYMERASE AND ALL IT CODES

496
00:27:18,370 --> 00:27:20,405
FOR IS IT'S OWN CODE PROTEINS

497
00:27:20,472 --> 00:27:23,875
AND ENCASED IN HEPATITIS B

498
00:27:23,942 --> 00:27:25,810
ENVELOPE LIKE THE WOLF IN

499
00:27:25,877 --> 00:27:28,213
SHEEP'S CLOTHING NOTE THAT IT'S

500
00:27:28,279 --> 00:27:32,951
A SHEEP BUT HEPATITIS D IS FAR

501
00:27:33,018 --> 00:27:36,021
WORSE AND INSERTS ITSELF IN THE

502
00:27:36,087 --> 00:27:38,757
HEPATITIS B ENVELOPE AND

503
00:27:38,823 --> 00:27:40,058
WHENEVER I HEAR THIS I ALWAYS

504
00:27:40,125 --> 00:27:45,797
WANT TO KNOW HOW DOES THIS

505
00:27:45,864 --> 00:27:47,065
HAPPEN.

506
00:27:47,132 --> 00:27:50,435
THIS IS THE VIRAL RNA AND A

507
00:27:50,502 --> 00:27:56,241
NUCLEOTIDE AND ADAR1 IS AN

508
00:27:56,307 --> 00:27:58,243
PROTEIN MADE IN RESPONSE TO

509
00:27:58,309 --> 00:28:00,345
INTERFERON AND CAUSES CHAOS

510
00:28:00,412 --> 00:28:03,948
MUTATIONS BUT HERE IT CAUSES A

511
00:28:04,015 --> 00:28:09,821
CHANGE FROM UAG TO A TRYPTOPHAN

512
00:28:09,888 --> 00:28:12,791
AND ALLOWS THE PROTEIN TO BE

513
00:28:12,857 --> 00:28:15,293
EXTENDED BY APPROXIMATELY 17 TO

514
00:28:15,360 --> 00:28:19,731
19 AMINO ACIDS DEPENDING ON THE

515
00:28:19,798 --> 00:28:21,166
GENOTYPE AND THAT SITE IS VERY

516
00:28:21,232 --> 00:28:22,734
IMPORTANT IN TERMS OF THERAPY

517
00:28:22,801 --> 00:28:24,969
BUT ALSO IMPORTANT IN TERMS OF

518
00:28:25,036 --> 00:28:26,438
BEING ABLE TO PACKAGE INTO

519
00:28:26,504 --> 00:28:28,239
HEPATITIS B OTHERWISE THE VIRUS

520
00:28:28,306 --> 00:28:30,375
COULDN'T BE PACKAGED.

521
00:28:30,442 --> 00:28:33,144
HOW DID THE VIRUS KNOW TO TAKE

522
00:28:33,211 --> 00:28:43,688
ADVANTAGE OF POLYMERASE AND

523
00:28:47,025 --> 00:28:50,562
REPLICATE IT'S DIABOLICAL.

524
00:28:50,628 --> 00:28:53,565
THE PATIENT IS OTHERWISE

525
00:28:53,631 --> 00:28:53,965
HEALTHY.

526
00:28:54,032 --> 00:28:56,534
SO IDEALLY WE'D LIKE TO TREAT

527
00:28:56,601 --> 00:28:59,404
HIM BUT WITH WHAT THERAPY

528
00:28:59,471 --> 00:29:04,576
>> LET'S GET A LITTLE BIT OF

529
00:29:04,642 --> 00:29:04,809
HISTORY.

530
00:29:04,876 --> 00:29:06,978
AT THE CLINICAL CENTER PATIENTS

531
00:29:07,045 --> 00:29:09,147
TREATED WITH INTERFERON AND THE

532
00:29:09,214 --> 00:29:11,916
FIRST PAPERS THAT CAME OUT IN

533
00:29:11,983 --> 00:29:16,187
1987 AND THIS IS PAGE 291 TO 298

534
00:29:16,254 --> 00:29:19,591
AND 299 TO 303 IN THE FIRST

535
00:29:19,657 --> 00:29:19,858
JOURNAL.

536
00:29:19,924 --> 00:29:23,761
THE FIRST TWO GROUPS WHO

537
00:29:23,828 --> 00:29:26,297
PUBLISHED TREATMENT OF HEPATITIS

538
00:29:26,364 --> 00:29:31,102
D WITH INTERFERON AND I WANT TO

539
00:29:31,169 --> 00:29:34,639
RUN THROUGH SIM KNOLL STUDIES.

540
00:29:34,706 --> 00:29:36,107
INTERFERON WITH AND WITHOUT

541
00:29:36,174 --> 00:29:36,641
HEPATITIS B THERAPIES AN

542
00:29:36,708 --> 00:29:46,885
LONG-TERM.

543
00:29:56,127 --> 00:29:58,730
PATIENTS WERE TREATED WITH A

544
00:29:58,796 --> 00:30:01,966
GIVEN AMOUNT OF UNITS AND THE

545
00:30:02,033 --> 00:30:03,935
VIRAL RNA AND COMPLETE, BOTH

546
00:30:04,002 --> 00:30:04,302
RESPONSES.

547
00:30:04,369 --> 00:30:07,539
AND YOU CAN SEE A CLEAR DOSE

548
00:30:07,605 --> 00:30:12,410
RESPONSE CURVE THERE.

549
00:30:12,477 --> 00:30:17,916
50 PERFORMANCE OF THE HIGH DOSE

550
00:30:17,982 --> 00:30:21,753
COMPLETE RESPONSE AND 0% WITH

551
00:30:21,819 --> 00:30:23,421
PLACEBO AND A RELAPSE IS COMMON

552
00:30:23,488 --> 00:30:23,955
AFTER TREATMENT HAS BEEN

553
00:30:24,022 --> 00:30:26,558
STOPPED.

554
00:30:26,624 --> 00:30:27,926
LONGER FOLLOW-UP OF 36 OF THE

555
00:30:27,992 --> 00:30:29,961
PREVIOUS PATIENTS SURVIVAL WAS

556
00:30:30,028 --> 00:30:31,029
STATISTICALLY IN FAVOR OF THE

557
00:30:31,095 --> 00:30:33,531
HIGH DOSE VERSUS LOW DOSE AND

558
00:30:33,598 --> 00:30:34,933
HIGH DOSE WAS CONTROLS.

559
00:30:34,999 --> 00:30:37,402
IN FACT MOST CONTROLS HAD DIED.

560
00:30:37,468 --> 00:30:39,103
THAT'S WHY THOSE PATIENTS COULD

561
00:30:39,170 --> 00:30:42,707
NOT BE FOLLOWED.

562
00:30:42,774 --> 00:30:46,044
FEW PATIENTS WERE LOST TO FOLLOW

563
00:30:46,110 --> 00:30:52,116
UP AND FOUR WITH CIRRHOSIS

564
00:30:52,183 --> 00:30:53,952
CONFIRM

565
00:30:54,018 --> 00:30:56,254
CONFIRMING WHAT WAS DISCOVERED

566
00:30:56,321 --> 00:30:57,422
IN THE '90s.

567
00:30:57,488 --> 00:30:59,424
THE BOTTOM LINE SIN TERMS OF

568
00:30:59,490 --> 00:31:04,662
WHAT WE USED TO CALL SUSTAINED

569
00:31:04,729 --> 00:31:05,863
VIROLOGICAL RESPONSE AND NOW

570
00:31:05,930 --> 00:31:10,068
DURABLE VIROLOG CAL RESPONSE IS

571
00:31:10,134 --> 00:31:12,337
30% TO 20% WILL RESPOND.

572
00:31:12,403 --> 00:31:14,772
WE CAN DO BETTER.

573
00:31:14,839 --> 00:31:16,574
JUST A REMINDER ABOUT THE

574
00:31:16,641 --> 00:31:18,509
LONG-TERM TREATMENT I SHOWED YOU

575
00:31:18,576 --> 00:31:21,879
IN THE BEGINNING AND WHAT THAT

576
00:31:21,946 --> 00:31:22,747
MEANS, INTERFERON COULD BE

577
00:31:22,814 --> 00:31:25,316
TWEAKED IN DIFFERENT WAYS BUT

578
00:31:25,383 --> 00:31:32,423
AGAIN NOT EVERYONE RESPONDED.

579
00:31:32,490 --> 00:31:34,826
THERE WERE DIFFERENT GENOTYPES.

580
00:31:34,892 --> 00:31:37,395
MANY GENOTYPE 1 WHICH IS MAINLY

581
00:31:37,462 --> 00:31:37,996
THE WEST.

582
00:31:38,062 --> 00:31:40,131
DIFFERENT RNA ASSAYS ARE

583
00:31:40,198 --> 00:31:41,666
DIFFICULT TO COMPARE ACROSS

584
00:31:41,733 --> 00:31:44,068
ASSESSES AND WHAT LOOKS LIKE

585
00:31:44,135 --> 00:31:54,612
RELAPSE IS NOT RELAPSE BUT

586
00:31:55,013 --> 00:31:57,782
ININSENSITIVE ASSAY AND THE

587
00:31:57,849 --> 00:31:59,984
DIFFERENT GENOTYPES ARE 5 TO 8

588
00:32:00,051 --> 00:32:02,253
ARE DIFFICULT TO DETECT WITH THE

589
00:32:02,320 --> 00:32:03,521
RNA ASSAYS.

590
00:32:03,588 --> 00:32:06,824
PATIENTS SHOULD BE SCREENED AND

591
00:32:06,891 --> 00:32:08,526
THEY SHOULD BE WARNED THERE'S NO

592
00:32:08,593 --> 00:32:10,461
VACCINE AND THEY'RE VULNERABLE

593
00:32:10,528 --> 00:32:13,665
TO SUPER INFECTION.

594
00:32:13,731 --> 00:32:16,501
WHAT ABOUT ANTI-HEPATITIS B

595
00:32:16,567 --> 00:32:16,701
STUDY?

596
00:32:16,768 --> 00:32:18,102
THE FIRST WAS DONE AT HERE AT

597
00:32:18,169 --> 00:32:20,171
THE CLINICAL CENTER.

598
00:32:20,238 --> 00:32:21,139
OTHERS INCLUDING IN THE NEW

599
00:32:21,205 --> 00:32:22,473
ENGLAND JOURNAL SO IT MUST BE

600
00:32:22,540 --> 00:32:22,807
TRUE.

601
00:32:22,874 --> 00:32:25,176
ALL OF THEM SHOWED TREATING

602
00:32:25,243 --> 00:32:28,046
HEPATITIS B ALONE DOESN'T WORK.

603
00:32:28,112 --> 00:32:30,581
WHAT ABOUT TREATMENT GUIDELINES?

604
00:32:30,648 --> 00:32:32,884
THERE'S NO CURRENT FDA APPROVED

605
00:32:32,950 --> 00:32:35,987
THERAPY FOR HEPATITIS D.

606
00:32:36,054 --> 00:32:37,689
AND THE AMERICAN ASSOCIATION FOR

607
00:32:37,755 --> 00:32:40,825
THE STUDY OF LOWER DISEASE SAID

608
00:32:40,892 --> 00:32:44,529
A LOW DOSE OF INTERFERON IS

609
00:32:44,595 --> 00:32:47,498
RECOMMENDED FOR IS IT MONTHS AND

610
00:32:47,565 --> 00:32:49,233
IF HEPATITIS B LEVELS ARE

611
00:32:49,300 --> 00:32:54,238
INCREASED TREATMENT SHOULD BE

612
00:32:54,305 --> 00:32:56,441
PERFOR

613
00:32:56,507 --> 00:33:01,145
PERFORMED WE TREAT EVEN WHEN

614
00:33:01,212 --> 00:33:03,481
LEVELS ARE NOT INCREASED AND

615
00:33:03,548 --> 00:33:06,818
GIVEN THE EFFICACY OF CURRENT

616
00:33:06,884 --> 00:33:07,885
THERAPIES IT'S REASONABLE TO

617
00:33:07,952 --> 00:33:09,153
REFER FOR STUDIES AND

618
00:33:09,220 --> 00:33:11,255
EXPERIMENTAL STUDIES.

619
00:33:11,322 --> 00:33:13,424
ALL THE STUDIES, ALL THE DRUGS

620
00:33:13,491 --> 00:33:16,394
I'M GOING DISCUSS HAVE BEEN A

621
00:33:16,461 --> 00:33:18,196
TRIUMPH OF SCIENCE.

622
00:33:18,262 --> 00:33:21,232
REALLY AND TRULY NOT POSSIBLE

623
00:33:21,299 --> 00:33:23,835
WITHOUT A DEEP INFORMATION OF

624
00:33:23,901 --> 00:33:27,205
BASIC SCIENCE AND BIOLOGY AND

625
00:33:27,271 --> 00:33:30,241
THOSE OF US ON THE CLINICAL SIDE

626
00:33:30,308 --> 00:33:33,444
ARE DISMISSIVE OF THE BASIC

627
00:33:33,511 --> 00:33:34,412
SCIENTISTS.

628
00:33:34,479 --> 00:33:37,749
THAT'S A REAL MISTAKE BECAUSE

629
00:33:37,815 --> 00:33:38,783
NONE OF THIS WOULD BE POSSIBLE

630
00:33:38,850 --> 00:33:40,151
WITHOUT THE BASIC SCIENCE AND IT

631
00:33:40,218 --> 00:33:42,153
MAY TAKE A WHILE FOR THE

632
00:33:42,220 --> 00:33:44,622
EVIDENCE TO BECOME CLEAR BUT

633
00:33:44,689 --> 00:33:47,425
EVENTU

634
00:33:47,492 --> 00:33:47,792
EVENTUALLY.

635
00:33:47,859 --> 00:33:50,528
EEL TALK ABOUT A COUPLE

636
00:33:50,595 --> 00:33:54,031
THERAPIES AND NUCLEIC ACID

637
00:33:54,098 --> 00:33:54,665
POLYMERS AND THERE ARE OTHERS

638
00:33:54,732 --> 00:34:01,139
BUT THESE ARE FURTHEST ALONG.

639
00:34:01,205 --> 00:34:06,310
IS MUCH OF THE DATA I'LL PRESENT

640
00:34:06,377 --> 00:34:12,850
IS IN ABSTRACT FORM AND I'LL

641
00:34:12,917 --> 00:34:14,419
FOCUS ON THE HIGHLIGHTS AND

642
00:34:14,485 --> 00:34:15,987
BECAUSE OF THE NATURE OF THE

643
00:34:16,053 --> 00:34:18,122
STUDIES FOCUS HAS BEEN ON

644
00:34:18,189 --> 00:34:19,957
SURROGATES AND REMEMBER THE REAL

645
00:34:20,024 --> 00:34:21,058
END POINT IS DEATH.

646
00:34:21,125 --> 00:34:24,395
THEN THE SURROGATE FOR DEATH

647
00:34:24,462 --> 00:34:26,497
WOULD BE HCG CIRRHOSIS AND THE

648
00:34:26,564 --> 00:34:27,932
SURROGATE WOULD BE ELIMINATING

649
00:34:27,999 --> 00:34:33,805
THE VIRUS AND AS A SURROGATE FOR

650
00:34:33,871 --> 00:34:39,744
THAT, WE USE THE 2 LOG DECLINE

651
00:34:39,811 --> 00:34:44,949
OF HDV AND WHAT ARE DURABLE VIR

652
00:34:45,016 --> 00:34:45,616
LOGIC RESPONSE AND WHEN YOU USE

653
00:34:45,683 --> 00:34:51,055
THE SUR GALT OF A SURROGATE YOU

654
00:34:51,122 --> 00:34:56,828
GET INTO TROUBLE AND -- A LARGE

655
00:34:56,894 --> 00:34:58,896
STUDY WAS STOPPED BECAUSE OF

656
00:34:58,963 --> 00:35:00,198
ADVERSE OUTCOMES.

657
00:35:00,264 --> 00:35:01,332
IT'S NOT CLEAR WHETHER IT WILL

658
00:35:01,399 --> 00:35:03,434
COME BACK OR NOT BUT I'D LIKE TO

659
00:35:03,501 --> 00:35:05,136
STILL GO THROUGH IT BECAUSE IT'S

660
00:35:05,203 --> 00:35:07,738
IMPORTANT.

661
00:35:07,805 --> 00:35:17,949
IT'S A TYPE 3 INTERFERON IT HAS

662
00:35:18,015 --> 00:35:19,383
LESS THOUGHT EFFECTS BECAUSE OF

663
00:35:19,450 --> 00:35:23,421
A GREATER HEPATIC RESTRICTION.

664
00:35:23,488 --> 00:35:33,364
AND THE ONE STUDY FOR HEPATITIS

665
00:35:33,431 --> 00:35:41,405
B WAS A STUDY WITH LAMDA AND 36%

666
00:35:41,472 --> 00:35:43,708
OF PATIENTS HAD CLEARED RNA AND

667
00:35:43,774 --> 00:35:51,415
NORMAL ALT AND THE CURVE SHOWS

668
00:35:51,482 --> 00:35:55,553
THE RESPONSE DIFFERENCES.

669
00:35:55,620 --> 00:35:57,021
WHAT ABOUT INHIBITORS.

670
00:35:57,088 --> 00:36:00,091
THESE ARE LIKELY TO BE THE FIRST

671
00:36:00,157 --> 00:36:03,628
DRUGS APPROVED FOR HEPATITIS B

672
00:36:03,694 --> 00:36:05,129
IN THE UNITED STATES.

673
00:36:05,196 --> 00:36:07,365
THE TRANSPORTER PEPTIDE THE

674
00:36:07,431 --> 00:36:13,271
SYSTEM IS THE RECEPTOR FOR

675
00:36:13,337 --> 00:36:16,574
HEPATITIS B AND IT'S POSSIBLE TO

676
00:36:16,641 --> 00:36:19,710
BLOCK THAT AND BLOCK IT FROM

677
00:36:19,777 --> 00:36:23,414
GOING INTO CELLS THUS BLOCKING

678
00:36:23,481 --> 00:36:26,217
HEPATITIS D AND SHOWED

679
00:36:26,284 --> 00:36:28,786
INHIBITION OF HEPATITIS B AND D

680
00:36:28,853 --> 00:36:28,986
ENTRY.

681
00:36:29,053 --> 00:36:34,091
I'LL SHOW THE NEW ENGLAND STUDY

682
00:36:34,158 --> 00:36:40,865
FROM LAST YEAR.

683
00:36:40,932 --> 00:36:42,900
IF YOU LOOK AT THE TOP CURVE

684
00:36:42,967 --> 00:36:45,169
PLACEBO SHOWED NO DECREASE IN

685
00:36:45,236 --> 00:36:48,706
VIRAL LEVEL AND THE 2 AND 10 MIL

686
00:36:48,773 --> 00:36:53,177
GRAM DOSES HAD 2.5 AND 1.9

687
00:36:53,244 --> 00:37:03,354
LEVEL.

688
00:37:04,055 --> 00:37:05,222
SOME OF PATIENTS STOP CLEAR BUT

689
00:37:05,289 --> 00:37:06,490
FOR THE MAJORITY IT'S NOT THE

690
00:37:06,557 --> 00:37:09,460
CASE AND IF YOU LOOK AT

691
00:37:09,527 --> 00:37:11,195
NORMALIZATION OF ALT IT'S JUST

692
00:37:11,262 --> 00:37:20,605
ABOVE 50% FOR BOTH DOSES.

693
00:37:20,671 --> 00:37:23,574
THIS IS VERY EXCITING AND WE

694
00:37:23,641 --> 00:37:27,712
HAVE ACTIVITIES ACROSS AN ARRAY

695
00:37:27,778 --> 00:37:30,815
OF AGENTS AND MECHANISMS ARE NOT

696
00:37:30,881 --> 00:37:32,016
COMPLETELY UNDERSTOOD.

697
00:37:32,083 --> 00:37:35,419
I WANTED TO HIGHLIGHT ONE STUDY

698
00:37:35,486 --> 00:37:38,856
PUBLISHED SEVEN YEARS AGO USING

699
00:37:38,923 --> 00:37:45,029
REP 2 39 IN IT'S A COMPLICATED

700
00:37:45,096 --> 00:37:47,198
DOSING.

701
00:37:47,264 --> 00:37:50,835
500 MILLIGRAM FOR 15 WEEKS AND

702
00:37:50,901 --> 00:37:54,305
PEG INTERFERON FOR 33 WEEKS AND

703
00:37:54,372 --> 00:38:02,847
THE MEAN DECLINE WAS 5.34 BLOGS

704
00:38:02,913 --> 00:38:04,081
AND SOME WERE HEPATITIS B

705
00:38:04,148 --> 00:38:06,183
NEGATIVE AND SURFACE ANTIGEN

706
00:38:06,250 --> 00:38:06,450
NEGATIVE.

707
00:38:06,517 --> 00:38:11,322
AT ONE YEAR 58% WERE HEPATITIS D

708
00:38:11,389 --> 00:38:17,161
RNA NEGATIVE AND AT 3 1/2 YEARS

709
00:38:17,228 --> 00:38:19,463
7 OF 12 WERE NEGATIVE AND WE'RE

710
00:38:19,530 --> 00:38:21,432
WAITING FOR OTHER STUDIES BUT

711
00:38:21,499 --> 00:38:24,001
THIS WOULD ALSO BE EXCITING.

712
00:38:24,068 --> 00:38:28,005
I MENTIONED WHEN THE PROTEIN

713
00:38:28,072 --> 00:38:29,840
GETS EXTENDED FROM SMALL TO

714
00:38:29,907 --> 00:38:33,844
LARGE ANTIGEN IT HAS A SITE AND

715
00:38:33,911 --> 00:38:40,451
THE INHIBITORS DEVELOP FOR RAS

716
00:38:40,518 --> 00:38:42,219
ONCA GENES AND ADAPTED AND

717
00:38:42,286 --> 00:38:52,763
THERE'S A PAPER FOR RSV AND

718
00:38:57,301 --> 00:38:58,969
THERE'S LIPIDS TO PROTEINS AND

719
00:38:59,036 --> 00:39:05,710
THIS PROMOTES MEMBRANE IN TO

720
00:39:05,776 --> 00:39:10,081
INTERACTIONS AND FOR MULTIPLE

721
00:39:10,147 --> 00:39:20,858
CELLULAR PROTEINS INSERTING

722
00:39:24,862 --> 00:39:26,430
THEMSELVES TO HEPATITIS B AND

723
00:39:26,497 --> 00:39:28,432
THEY AVOID THE G.I. SIDE EFFECTS

724
00:39:28,499 --> 00:39:31,669
OF GIVING A HIGH DOSE OF

725
00:39:31,736 --> 00:39:33,604
RITONAVIR AND IF YOU LOOK AT

726
00:39:33,671 --> 00:39:36,807
THIS, 11 OF 22 PATIENTS AT 24

727
00:39:36,874 --> 00:39:41,679
WEEKS WERE UNDETECTABLE ABOVE

728
00:39:41,746 --> 00:39:43,314
LIMITATION FOR HEPATITIS D RNA

729
00:39:43,380 --> 00:39:45,616
AND SIX WERE MORE THAN A TWO LOG

730
00:39:45,683 --> 00:39:51,288
DECLINE A SURROGATE ACCEPTED

731
00:39:51,355 --> 00:39:55,126
MARKER FOR THE PAPER AND LESS

732
00:39:55,192 --> 00:39:57,428
THAN FIVE HAD A TWO-LOG DECLINE.

733
00:39:57,495 --> 00:39:58,162
THIS IS ALSO PROMISING AND

734
00:39:58,229 --> 00:40:08,105
EXCITING.

735
00:40:08,172 --> 00:40:11,509
THE LIGANDS AND LOTS OF OTHER

736
00:40:11,575 --> 00:40:12,176
SILENCING RNAs AND OTHER THINGS

737
00:40:12,243 --> 00:40:22,386
COMING.

738
00:40:25,723 --> 00:40:29,126
AND THE RNA DE KWLIEND BUT DID

739
00:40:29,193 --> 00:40:29,727
NOT BECOME UNDETECTABLE AND

740
00:40:29,794 --> 00:40:31,529
IMPROVED AND THERAPY AND ALL

741
00:40:31,595 --> 00:40:32,263
RETURNED TO BASELINE AFTER THE

742
00:40:32,329 --> 00:40:32,963
CONTINUING THERAPY.

743
00:40:33,030 --> 00:40:38,068
THIS IS A TYPICAL STORY.

744
00:40:38,135 --> 00:40:40,404
THE PATIENT SIT IN YOUR OFFICE

745
00:40:40,471 --> 00:40:50,915
AND SAYS NOW WHAT, DOCTOR?

746
00:40:54,852 --> 00:40:57,021
AND HE BECAME NEGATIVE BUT

747
00:40:57,087 --> 00:40:58,289
RELAPSED AFTER TREATMENT.

748
00:40:58,355 --> 00:41:08,866
THEN HE SAYS, WHAT'S NEXT NOW?

749
00:41:13,204 --> 00:41:17,641
CLINICAL TRIAL.gov THERE'S ABOUT

750
00:41:17,708 --> 00:41:19,043
61 STUDIES NOW.

751
00:41:19,109 --> 00:41:21,779
NOT ALL ARE ACTIVE, SOME ARE

752
00:41:21,846 --> 00:41:22,446
COMPLETED.

753
00:41:22,513 --> 00:41:24,615
NOT ALL ARE REALLY THERAPEUTIC

754
00:41:24,682 --> 00:41:27,985
BUT THERE'S A BIG DIFFERENCE IN

755
00:41:28,052 --> 00:41:29,420
JUST A FEW YEARS.

756
00:41:29,486 --> 00:41:33,958
SO HEPATITIS D IS FASCINATING.

757
00:41:34,024 --> 00:41:36,126
NEARLY 50 YEARS LATER WE'RE

758
00:41:36,193 --> 00:41:39,263
STILL STRUGGLING.

759
00:41:39,330 --> 00:41:41,098
PEGINTERFERON IS LIKELY TO

760
00:41:41,165 --> 00:41:45,936
BECOME A COMPONENT FOR A WHILE

761
00:41:46,003 --> 00:41:48,505
EVEN WITH THE INTENT TO GIVE

762
00:41:48,572 --> 00:41:55,045
WITH INTERFERON AND WE FLARES

763
00:41:55,112 --> 00:41:56,614
NOT OUTCOMES AND LOOK AT

764
00:41:56,680 --> 00:41:59,884
PROGRESS AND HERE I HAVE TO

765
00:41:59,950 --> 00:42:02,119
MENTION ALSO MATHEMATICAL MODEL

766
00:42:02,186 --> 00:42:04,288
AND WE LOOKED AT LOYOLA AND

767
00:42:04,355 --> 00:42:05,856
THAT'S GUIDED THE APPROACH TO

768
00:42:05,923 --> 00:42:07,992
HOW WE TREAT PATIENTS.

769
00:42:08,058 --> 00:42:13,731
AND THESE NOVEL THERAPIES HOLD

770
00:42:13,797 --> 00:42:20,337
REAL PROMISE.

771
00:42:20,404 --> 00:42:24,975
YOU'LL SEE THIS PAINTING IN THE

772
00:42:25,042 --> 00:42:26,777
BACK WALL WALKING FROM THE BACK

773
00:42:26,844 --> 00:42:29,413
NOT WHERE THE PATIENTS COME IN.

774
00:42:29,480 --> 00:42:30,915
THIS IS A PAINTING HUNG IN THE

775
00:42:30,981 --> 00:42:38,122
CLINIC A PATIENT GAVE HIM.

776
00:42:38,188 --> 00:42:39,690
I WANT YOU TO STOP FOR A SECOND

777
00:42:39,757 --> 00:42:50,301
AN THINK HOW IT MAKES YOU FEEL.

778
00:43:16,927 --> 00:43:18,662
YOU MAY ASK WHY WOULD YOU HANG

779
00:43:18,729 --> 00:43:20,197
SINCE A CLINIC.

780
00:43:20,264 --> 00:43:21,932
IT'S SUCH A DE PRESSING THING.

781
00:43:21,999 --> 00:43:25,636
THE ANSWER IS IT'S NOT DEPR

782
00:43:25,703 --> 00:43:27,604
DEPRESSING IT'S INSPIRING.

783
00:43:27,671 --> 00:43:30,474
OUR FAILURES SHOULD CHALLENGE US

784
00:43:30,541 --> 00:43:31,742
TO DO BETTER.

785
00:43:31,809 --> 00:43:35,212
THERE'S NO DISHONORING FAILURE

786
00:43:35,279 --> 00:43:38,015
BUT IN TRYING AND WE'RE HERE TO

787
00:43:38,082 --> 00:43:40,117
MAKE THE WORLD BETTER AND TO TRY

788
00:43:40,184 --> 00:43:42,286
TO DO THAT AND FOR ME WHEN I

789
00:43:42,353 --> 00:43:43,721
WALK THE PAINTING INTO CLINIC

790
00:43:43,787 --> 00:43:45,923
IT'S AN INSPIRATION TO STRIVE TO

791
00:43:45,990 --> 00:43:47,224
DO BETTER AND THINK BETTER AND

792
00:43:47,291 --> 00:43:47,925
TRY HARDER.

793
00:43:47,992 --> 00:43:50,928
I THINK THIS IS VERY FITTING AND

794
00:43:50,995 --> 00:43:56,200
VERY APPROPRIATE AND BASED ON

795
00:43:56,266 --> 00:43:58,168
THIS, IT'S INCREDIBLE TO STAND

796
00:43:58,235 --> 00:43:59,069
HERE 40 YEARS LATER AND TALK

797
00:43:59,136 --> 00:44:01,038
ABOUT A REVOLUTION IN THERAPY.

798
00:44:01,105 --> 00:44:04,441
I WANT TO THANK THE PATIENTS WHO

799
00:44:04,508 --> 00:44:06,243
REALLY VOLUNTEER EVERYTHING,

800
00:44:06,310 --> 00:44:08,412
GIVE THEMSELVES THE BLOOD, THE

801
00:44:08,479 --> 00:44:10,280
LIVER, THE RESEARCHERS WE WORK

802
00:44:10,347 --> 00:44:10,481
WITH.

803
00:44:10,547 --> 00:44:11,482
NOTHING WITHOUT BEING POSSIBLE

804
00:44:11,548 --> 00:44:12,983
WITHOUT THE RESEARCHERS.

805
00:44:13,050 --> 00:44:14,818
THEY MAKE EVERYTHING HAPPEN.

806
00:44:14,885 --> 00:44:16,887
THE FELLOWS WHO DO THE BULK OF

807
00:44:16,954 --> 00:44:18,389
THE WORK.

808
00:44:18,455 --> 00:44:20,824
ALL THE COLLABORATORS AND MY

809
00:44:20,891 --> 00:44:23,627
PARTNER IN CRIME.

810
00:44:23,694 --> 00:44:28,932
DR. KLEINER AND MY MENTORS I

811
00:44:28,999 --> 00:44:35,406
INCLUDE THE PICTURE BECAUSE OUR

812
00:44:35,472 --> 00:44:37,875
FEARLESS LEADERS AND THERE'S

813
00:44:37,941 --> 00:44:41,412
DR. ARIAS WHO ATTENDS OUR ROUNDS

814
00:44:41,478 --> 00:44:42,679
REGULARLY AND HAS A LOT TO SAY.

815
00:44:42,746 --> 00:44:47,418
I WANT TO END WITH THIS PATIENT

816
00:44:47,484 --> 00:44:48,652
AGAIN.

817
00:44:48,719 --> 00:44:55,692
THE FIRST PATIENT TO BE SHOWN TO

818
00:44:55,759 --> 00:44:58,362
HAVE CIRRHOSIS REGRESS AND IT'S

819
00:44:58,429 --> 00:45:04,468
POSSIBLE BY THE DREAMS AND MY

820
00:45:04,535 --> 00:45:04,968
EDI

821
00:45:05,035 --> 00:45:06,370
IDEAL IS TO TAKE IT FROM THE

822
00:45:06,437 --> 00:45:07,171
PATIENT LEVEL TO THE POPULATION

823
00:45:07,237 --> 00:45:07,371
LEVEL.

824
00:45:07,438 --> 00:45:10,207
THANK YOU FOR YOUR ATTENTION.

825
00:45:10,274 --> 00:45:11,408
>> THANK YOU VERY MUCH.

826
00:45:11,475 --> 00:45:13,610
MAY I REMIND EVERYBODY, PLEASE

827
00:45:13,677 --> 00:45:20,751
TO SUBMIT THEIR QUESTIONS

828
00:45:20,818 --> 00:45:23,253
ELECTRONICALLY IF YOU'RE

829
00:45:23,320 --> 00:45:30,627
WATCHING THIS VISUALLY AND THE

830
00:45:30,694 --> 00:45:37,468
SECOND SPEAKER IS MARC GHANY TO

831
00:45:37,534 --> 00:45:44,274
TELL US ABOUT HEPATITIS E.

832
00:45:44,341 --> 00:45:46,243
>> GREAT.

833
00:45:46,310 --> 00:45:53,383
WE'RE MOVING DOWN THE HEPATITIS

834
00:45:53,450 --> 00:45:53,650
ALPHABET.

835
00:45:53,717 --> 00:45:56,220
NO LESS IMPORTANT VIRUS, I MIGHT

836
00:45:56,286 --> 00:45:56,487
ADD.

837
00:45:56,553 --> 00:46:05,129
I'LL ALSO BEGIN WITH A CASE THAT

838
00:46:05,195 --> 00:46:06,663
WILL ILLUSTRATE THE CLINICAL

839
00:46:06,730 --> 00:46:11,168
DISEASE OF THE VIRUS I'M GOING

840
00:46:11,235 --> 00:46:21,712
TO TALK ABOUT AND A 42-YEAR-OLD

841
00:46:21,778 --> 00:46:23,947
FEMALE WAS REFERRED TO US DUE TO

842
00:46:24,014 --> 00:46:25,682
A TEST WITH THE HEALTH OF HER

843
00:46:25,749 --> 00:46:29,219
LIVER AND HER PRESENTATION WAS

844
00:46:29,286 --> 00:46:32,956
100, FOUR TIMES NORMAL AND

845
00:46:33,023 --> 00:46:36,393
COMPLAINED OF MILD FATIGUE WAS

846
00:46:36,460 --> 00:46:45,169
HER ONLY SYSTEM AND HER AILITY

847
00:46:45,235 --> 00:46:47,871
PEAKED AND DEVELOPED JUANDICE

848
00:46:47,938 --> 00:46:58,315
WITH A BILIRUBIN LEVEL WAS 2500

849
00:46:58,382 --> 00:47:02,619
AND SUBSEQUENTLY TESTED POSITIVE

850
00:47:02,686 --> 00:47:06,056
FOR HEPATITIS E AND HEV AND RNA

851
00:47:06,123 --> 00:47:06,757
AND GENOTYPE 3.

852
00:47:06,823 --> 00:47:09,059
THE ONLY RISK FACTOR WE COULD

853
00:47:09,126 --> 00:47:11,628
IDENTIFY WAS A SCALPEL INJURY

854
00:47:11,695 --> 00:47:15,999
AND EXPOSURE TO PIG BLOOD AND

855
00:47:16,066 --> 00:47:25,108
DENIED FOREIGN TRAVEL OR

856
00:47:25,175 --> 00:47:33,951
INGESTION OF PORK OR GAME AND

857
00:47:34,017 --> 00:47:39,590
LEL LET ME TELL BUT HEPATITIS E

858
00:47:39,656 --> 00:47:41,491
IT'S BEEN ESTIMATED OVER 900

859
00:47:41,558 --> 00:47:45,128
BILLION PERSONS HAVE BEEN

860
00:47:45,195 --> 00:47:48,465
INFECTED TRANSLATES TO 1 IN 8

861
00:47:48,532 --> 00:47:50,067
PEOPLE ON THE PLANET AND

862
00:47:50,133 --> 00:47:55,739
ESTIMATED THERE'S ABOUT 20

863
00:47:55,806 --> 00:47:57,574
MILLION INCIDENT INFECTIONS

864
00:47:57,641 --> 00:47:59,276
RESULTING IN 70,000 DEATHS AND

865
00:47:59,343 --> 00:48:02,679
MOST DO NOT PRESENT WITH

866
00:48:02,746 --> 00:48:05,082
JUANDICE AND RESULTS WITHOUT

867
00:48:05,148 --> 00:48:06,950
LONG-TERM SEQUELAE BUT SEVERE

868
00:48:07,017 --> 00:48:10,020
CASES WITH JUANDICE CAN OCCUR

869
00:48:10,087 --> 00:48:13,457
THOSE WITH IMMUNODEFICIENCY AND

870
00:48:13,523 --> 00:48:14,758
PEOPLE IN PREEXISTING DISEASE

871
00:48:14,825 --> 00:48:19,029
AND PREGNANT WOMEN.

872
00:48:19,096 --> 00:48:22,532
INTERESTINGLY, CASES OF CHRONIC

873
00:48:22,599 --> 00:48:26,203
INFECTION HAVE BEGUN TO BE

874
00:48:26,270 --> 00:48:28,972
DESCRIBED PRIMARILY IN

875
00:48:29,039 --> 00:48:29,806
IMMUNOSUPPRESSED INDIVIDUALS AND

876
00:48:29,873 --> 00:48:32,643
TRANS PLANT RECIPIENTS.

877
00:48:32,709 --> 00:48:34,511
PATIENTS ON CANCER CHEMOTHERAPY

878
00:48:34,578 --> 00:48:41,918
AND THOSE INFECTED WITH HIV.

879
00:48:41,985 --> 00:48:44,021
SOME HISTORICAL PERSPECTIVES.

880
00:48:44,087 --> 00:48:48,458
THE VIRUS CAME ON THE MEDICAL

881
00:48:48,525 --> 00:48:51,895
RADAR IN 1978 WHEN THERE WAS A

882
00:48:51,962 --> 00:48:55,132
LARGE OUTBREAK OF JUANDICE IN

883
00:48:55,198 --> 00:48:58,402
KAS MIR, INDIA AND IT WAS

884
00:48:58,468 --> 00:49:08,912
THOUGHT TO BE ENTERICALLY

885
00:49:12,516 --> 00:49:15,585
TRANSMITTED NON-A AND NON-B

886
00:49:15,652 --> 00:49:17,220
HEPATITIS AND AFFECTED PERSONS

887
00:49:17,287 --> 00:49:21,758
OF 15 TO 45 AND A SELF-LIMITED

888
00:49:21,825 --> 00:49:23,060
HEPATITIS BUT HAD A HIGH

889
00:49:23,126 --> 00:49:25,829
MATERNAL AND FETAL MORTALITY AND

890
00:49:25,896 --> 00:49:27,731
LATER THOUGHT TO CAUSE

891
00:49:27,798 --> 00:49:30,267
EPIDEMIOLOGY AND SPORADIC CASES

892
00:49:30,334 --> 00:49:31,134
OF HEPATITIS.

893
00:49:31,201 --> 00:49:33,704
THERE WAS A SECOND OUTBREAK OF

894
00:49:33,770 --> 00:49:36,373
HEPATITIS THAT OCCURRED IN A

895
00:49:36,440 --> 00:49:37,808
RUSSIAN MILITARY CAMP IN

896
00:49:37,874 --> 00:49:40,544
AFGHANISTAN AND A CAMP DOCTOR

897
00:49:40,610 --> 00:49:43,513
TOOK IT UPON HIMSELF TO INGEST

898
00:49:43,580 --> 00:49:46,483
STOOL EXTRACTS FROM INFECTED

899
00:49:46,550 --> 00:49:49,886
PATIENTS AND FIVE WEEKS LATER HE

900
00:49:49,953 --> 00:49:51,722
DEVELOPED SEVERE ACUTE VIRUS AND

901
00:49:51,788 --> 00:49:55,058
VIRUS LIKE PARTICLES WERE

902
00:49:55,125 --> 00:49:57,394
OBSERVED FROM STOOL COLLECTED ON

903
00:49:57,461 --> 00:49:59,396
THE DAYS FOLLOWING INGESTION AND

904
00:49:59,463 --> 00:50:04,601
HIS STOOL WAS LATER USED TO

905
00:50:04,668 --> 00:50:10,407
INFECT THE CHIMPANZEE CONFIRMING

906
00:50:10,474 --> 00:50:14,211
IT WAS DUE TO A MICROORGANISM

907
00:50:14,277 --> 00:50:17,114
AND IN 1990 THERE WAS A

908
00:50:17,180 --> 00:50:19,216
PARTIALLY CLONED VIRUS AND THEN

909
00:50:19,282 --> 00:50:23,320
IT THE GENOME WAS SEQUENCED AND

910
00:50:23,387 --> 00:50:29,159
THE FIRST SEROLOGIC ASSAY WAS

911
00:50:29,226 --> 00:50:32,996
DEVELOPED AND THE TAXOLOGY HAS

912
00:50:33,063 --> 00:50:35,432
CHANGED AND IT BELONGS TO A

913
00:50:35,499 --> 00:50:42,506
SINGLE FAMILY AND THERE'S TWO

914
00:50:42,572 --> 00:50:42,806
SUBFAMILIES.

915
00:50:42,873 --> 00:50:45,942
THERE ARE FIVE GENERA AND NINE

916
00:50:46,009 --> 00:50:49,713
SUBSPECIES.

917
00:50:49,780 --> 00:50:55,719
THE MOST IMPORTANT IS THE TWO

918
00:50:55,786 --> 00:50:58,388
SPECIES NAMED AFTER THE PERSON

919
00:50:58,455 --> 00:50:59,923
WHO DISCOVERED THE VIRUS AND

920
00:50:59,990 --> 00:51:01,992
THERE'S EIGHT GENOTYPES.

921
00:51:02,058 --> 00:51:04,394
FIVE OF WHICH INFECT HUMANS.

922
00:51:04,461 --> 00:51:08,298
1 IN 2 ONLY INFECT HUMANS AND 3,

923
00:51:08,365 --> 00:51:11,001
4 AND 7 ARE THOUGHT TO BE

924
00:51:11,067 --> 00:51:15,238
ZOONOTIC INFECTIONS.

925
00:51:15,305 --> 00:51:19,776
THE HEPATITIS E VIRUS HAS A

926
00:51:19,843 --> 00:51:22,145
CAPSID COMPRISED OF 180 COPIES

927
00:51:22,212 --> 00:51:23,713
OF THE CAPSID PROTEINS AND TWO

928
00:51:23,780 --> 00:51:26,149
PRART CAL HAVE BEEN IDENTIFIED.

929
00:51:26,216 --> 00:51:29,186
ONE IS A QUASI-ENVELOPE SPECIES

930
00:51:29,252 --> 00:51:32,022
WRAPPED IN A HOST LIPID ENVELOPE

931
00:51:32,088 --> 00:51:35,325
AND NOT ENVELOPE VIRUS AND THE

932
00:51:35,392 --> 00:51:39,830
ENVELOPE VIRUS IS THOUGHT TO BE

933
00:51:39,896 --> 00:51:40,964
RESISTANT AGAINST THE VIRAL

934
00:51:41,031 --> 00:51:43,300
CAPSID PROTEIN AND MAY BE

935
00:51:43,366 --> 00:51:44,968
IMPORTANT FOR THE TROPISM AND

936
00:51:45,035 --> 00:51:46,803
THE NON-VIRAL VIRUS IS THOUGHT

937
00:51:46,870 --> 00:51:48,772
TO BE THE MORE INFECTIOUS ONE

938
00:51:48,839 --> 00:51:49,940
AND THE ONE RESPONSIBLE FOR

939
00:51:50,006 --> 00:51:54,911
TRANSMITTING THE INFECTION.

940
00:51:54,978 --> 00:51:57,314
AND THE GENOME AS SHOWN IN THE

941
00:51:57,380 --> 00:51:59,316
CARTOON IS A POSITIVE SENSE

942
00:51:59,382 --> 00:52:01,885
SINGLE STRAND RNA OF

943
00:52:01,952 --> 00:52:06,122
APPROXIMATELY 7.2 KB IN LINK AND

944
00:52:06,189 --> 00:52:16,666
THE IT THERE'S A POLY ADENY

945
00:52:21,638 --> 00:52:23,373
LATED END AND THERE'S A LARGE

946
00:52:23,440 --> 00:52:27,043
PROTEIN OF 1700 AMINO ACIDS

947
00:52:27,110 --> 00:52:31,314
IMPORTANT FOR VIRAL REPLICATION.

948
00:52:31,381 --> 00:52:40,390
RF2 AND 3 COME FROM AN RNA AND

949
00:52:40,457 --> 00:52:43,126
THERE'S A SHELL, MIDDLE AND

950
00:52:43,193 --> 00:52:45,695
PROTRUDING DOMAIN AND THOUGHT TO

951
00:52:45,762 --> 00:52:48,532
BE A SITE FOR A NEUTRALIZING

952
00:52:48,598 --> 00:52:51,668
ANTIBODY OR 3 SEEMS TO BE

953
00:52:51,735 --> 00:52:56,339
IMPORTANT FOR VIRAL ASSEMBLY AND

954
00:52:56,406 --> 00:52:59,476
SECRETION OF THE VIRUS AND THE

955
00:52:59,543 --> 00:53:02,045
FOURTH IDENTIFIED IN GEOTYPE 1

956
00:53:02,112 --> 00:53:03,313
INFECTION AND A REPLICATION

957
00:53:03,380 --> 00:53:06,049
ENHANCER MAY BE RELEVANT FOR THE

958
00:53:06,116 --> 00:53:10,287
DISEASE MEDIATED OR CAUSED BY

959
00:53:10,353 --> 00:53:12,822
HEPATITIS E VIRUS TYPE 1.

960
00:53:12,889 --> 00:53:14,257
SO HOW DOES THE VIRUS REPLICATE?

961
00:53:14,324 --> 00:53:17,093
THAT IS SHOWN IN THE CARTOON.

962
00:53:17,160 --> 00:53:20,397
THE VIRUS CAUSES AND INFECTS

963
00:53:20,463 --> 00:53:31,107
REPLICATES WITHIN HE PAPATOCYTE

964
00:53:31,174 --> 00:53:33,076
AND INTERACTED WITH ANOTHER

965
00:53:33,143 --> 00:53:35,512
SURFACE RECEPTOR AND THROUGH A

966
00:53:35,579 --> 00:53:45,889
MEDIATED PROCESS.

967
00:53:48,725 --> 00:53:52,329
AND ENCODES THE ORF1 PROTEIN FOR

968
00:53:52,395 --> 00:53:59,235
A SUB GENOMIC NEGATIVE STRAND

969
00:53:59,302 --> 00:54:06,343
RNA WHICH SERVES AS A TEMPLATE

970
00:54:06,409 --> 00:54:07,877
FOR TRANSCRIPTION AND

971
00:54:07,944 --> 00:54:12,148
TRANSLATION OF THE OTHER TWO

972
00:54:12,215 --> 00:54:15,318
PROTEINS THE ORF2 AND 3 AND THE

973
00:54:15,385 --> 00:54:18,855
CAPSID PROTEINS SHOWN BY THE

974
00:54:18,922 --> 00:54:23,793
LIGHT BLUE TRIANGLES GOES TO THE

975
00:54:23,860 --> 00:54:27,063
RETICULUM WHERE VIRAL ASSEMBLY

976
00:54:27,130 --> 00:54:29,466
HAPPENS WITH THE POSITIVE SENSE

977
00:54:29,532 --> 00:54:29,799
RNA STRAND.

978
00:54:29,866 --> 00:54:38,208
THIS WORKS ITS WAY THROUGH THE

979
00:54:38,274 --> 00:54:39,042
SECRETORY PROCESS OF THE CELL

980
00:54:39,109 --> 00:54:43,680
AND REQUIRES THE ORF3 PROTEIN

981
00:54:43,747 --> 00:54:46,683
FOR THIS PURPOSE AND BECOMES AN

982
00:54:46,750 --> 00:54:51,421
ENVELOPE WITH HOST LIPIDS AND

983
00:54:51,488 --> 00:54:54,124
SECRETED THROUGH AN EXOSOMAL

984
00:54:54,190 --> 00:54:57,360
PATHWAY AND IT CONTAINS HOST

985
00:54:57,427 --> 00:54:58,662
LIPIDS AS WELL AS OPEN READING

986
00:54:58,728 --> 00:55:00,897
FRAME THREE.

987
00:55:00,964 --> 00:55:06,302
AND IT'S THEN SECRETED INTO

988
00:55:06,369 --> 00:55:09,339
WHERE THE BILE REMOVES THE HOST

989
00:55:09,406 --> 00:55:14,711
LIPIDS AND THE NON-ENVELOPE

990
00:55:14,778 --> 00:55:17,981
VIRUS GOES DOWN THE

991
00:55:18,048 --> 00:55:20,116
GASTROINTESTINAL TRACT AND

992
00:55:20,183 --> 00:55:25,255
SECRETED IN STOOL AND COMPLETES

993
00:55:25,321 --> 00:55:28,091
ITS LIFE CYCLE AND 4 HAS BEEN

994
00:55:28,158 --> 00:55:31,361
IDENTIFIED AS A HYPERENDEMIC,

995
00:55:31,428 --> 00:55:40,970
DISTINCTIVE AND SPORE -- SPO

996
00:55:41,037 --> 00:55:45,175
SPORATIC AND THERE'S ASIA AND

997
00:55:45,241 --> 00:55:48,745
MEXICO AND ENDEMIC REGIONS SHOW

998
00:55:48,812 --> 00:55:53,383
CHINA, PARTS OF JAPAN AND THE

999
00:55:53,450 --> 00:55:56,820
MIDDLE EAST AND ENDEMIC REGIONS

1000
00:55:56,886 --> 00:56:00,957
ARE ASSOCIATED WITH LARGE WATER

1001
00:56:01,024 --> 00:56:05,962
BORN OUTBREAKS TYPICALLY DUE TO

1002
00:56:06,029 --> 00:56:08,465
HEPATITIS GENOTYPE 1 AND 2.

1003
00:56:08,531 --> 00:56:09,733
THERE'S A DISTINCT ZONE SHOWN IN

1004
00:56:09,799 --> 00:56:11,034
GREEN AND IT'S DIFFERENT FROM

1005
00:56:11,101 --> 00:56:13,737
OTHER REGIONS OF THE WORLD AND

1006
00:56:13,803 --> 00:56:17,140
DUE TO INFECTION WITH A SUBTYPE

1007
00:56:17,207 --> 00:56:19,175
OF GENOTYPE 1 AND THEN FOR THE

1008
00:56:19,242 --> 00:56:22,979
REST OF THE WORLD WHICH IS

1009
00:56:23,046 --> 00:56:26,416
ESSENTIALLY MOSTLY DEVELOPED

1010
00:56:26,483 --> 00:56:28,651
REGIONS BUT ALSO SOME EMERGING

1011
00:56:28,718 --> 00:56:34,491
COUNTRIES DUE TO SPORADIC OR

1012
00:56:34,557 --> 00:56:38,361
LOCALLY ACQUIRED HEPATITIS E

1013
00:56:38,428 --> 00:56:40,330
ASSOCIATED WITH INFECTION AND

1014
00:56:40,396 --> 00:56:42,766
JUNO TYPE 3 AND 4 WE'LL TALK

1015
00:56:42,832 --> 00:56:44,033
ABOUT FURTHER IN THE TALK.

1016
00:56:44,100 --> 00:56:46,436
IT'S BEEN DIFFICULT TO DETERMINE

1017
00:56:46,503 --> 00:56:49,973
THE TRUE PREVALENCE OF HEPATITIS

1018
00:56:50,039 --> 00:56:55,545
E GLOBALLY BECAUSE OF THE

1019
00:56:55,612 --> 00:56:58,214
SPECIFICITY OF THE ASSAYS AND

1020
00:56:58,281 --> 00:56:59,682
PAUCITY FROM THE AMERICAS AND

1021
00:56:59,749 --> 00:57:01,818
THIS IS DATA FROM META-ANALYSIS

1022
00:57:01,885 --> 00:57:04,354
SHOWING THE PREVALENCE BASED ON

1023
00:57:04,420 --> 00:57:10,493
IGG, IGM AND HEV RNA AND THE

1024
00:57:10,560 --> 00:57:21,104
HIGHEST PREVALENCE IS IN AFRICA.

1025
00:57:22,472 --> 00:57:24,741
THE HIGHEST PREVALENCE IS IN

1026
00:57:24,808 --> 00:57:29,846
AFRICA AND ASIA FOLLOWED BY

1027
00:57:29,913 --> 00:57:34,684
SOUTH AMERICA AND OCEANA AND THE

1028
00:57:34,751 --> 00:57:37,120
PREVALENCE OF HEV RNA VERY LOW

1029
00:57:37,187 --> 00:57:40,323
BUT WE SHOULD INTERPRET SOME

1030
00:57:40,390 --> 00:57:41,791
DATA WITH CAUTION BECAUSE OF THE

1031
00:57:41,858 --> 00:57:43,059
PAUCITY OF DATA PARTICULARLY

1032
00:57:43,126 --> 00:57:45,995
FROM AFRICA AND THE AMERICAS.

1033
00:57:46,062 --> 00:57:48,865
THIS SLIDE SHOWS THE GLOBAL

1034
00:57:48,932 --> 00:57:50,300
DISTRIBUTION OF THE FOUR MAJOR

1035
00:57:50,366 --> 00:57:53,837
PHENOTYPES THAT INFECT HUMANS, 1

1036
00:57:53,903 --> 00:57:55,405
THROUGH 4.

1037
00:57:55,471 --> 00:58:00,643
1 IN RED AND 2 IN BLUE AND 3 IN

1038
00:58:00,710 --> 00:58:02,378
YELLOW AND 4 IN BROWN.

1039
00:58:02,445 --> 00:58:04,681
YOU SEE THE GLOBAL DISTRIBUTION

1040
00:58:04,747 --> 00:58:07,951
OF THE GENOTYPES ESSENTIALLY

1041
00:58:08,017 --> 00:58:11,521
MIRRORS OF THAT THE DIFFERENT

1042
00:58:11,588 --> 00:58:14,457
ZONALITY OF HEPATITIS D ON THE

1043
00:58:14,524 --> 00:58:15,892
PREACHES SLIDE.

1044
00:58:15,959 --> 00:58:20,563
SO HEPATITIS GEOTYPES 1 AND 2

1045
00:58:20,630 --> 00:58:25,101
ARE ASSOCIATED WITH LARGE

1046
00:58:25,168 --> 00:58:27,871
WATERBORNE OUTBREAKS IN THE

1047
00:58:27,937 --> 00:58:29,272
REGIONS SHOWN HERE AND GENOTYPE

1048
00:58:29,339 --> 00:58:33,142
3 IS ASSOCIATED WITH LOCALLY

1049
00:58:33,209 --> 00:58:35,645
ACQUIRED HEPATITIS E.

1050
00:58:35,712 --> 00:58:41,117
AND GENOTYPE 4 IS SEEN IN CHINA

1051
00:58:41,184 --> 00:58:45,054
AND JAPAN.

1052
00:58:45,121 --> 00:58:46,890
TRANSMISSION AND HYPER ENDEMIC

1053
00:58:46,956 --> 00:58:49,993
AND ENDEMIC REGIONS IS THROUGH

1054
00:58:50,059 --> 00:58:52,161
THE FECAL-ORAL ROUTE AND WATER

1055
00:58:52,228 --> 00:58:54,030
AND PERSON TO PERSON

1056
00:58:54,097 --> 00:58:55,565
TRANSMISSION NOT THE COMMON

1057
00:58:55,632 --> 00:58:56,566
ROUTE OF TRANSMISSION.

1058
00:58:56,633 --> 00:59:05,241
BY TRANSMISSION OF SPORADIC OR

1059
00:59:05,308 --> 00:59:07,510
HEPATITIS B IS THOUGHT TO BE

1060
00:59:07,577 --> 00:59:09,946
ZOONOTIC AND TRANSMISSION IS

1061
00:59:10,013 --> 00:59:11,381
PRIMARILY THROUGH DIRECT CONTACT

1062
00:59:11,447 --> 00:59:14,050
WITH AN INFECTED ANIMAL SUCH AS

1063
00:59:14,117 --> 00:59:15,585
A PERSON WITH OCCUPATIONAL

1064
00:59:15,652 --> 00:59:20,623
EXPOSURE SUCH AS VETS, FARMERS,

1065
00:59:20,690 --> 00:59:25,128
FARM WORKERS AND INDIRECT

1066
00:59:25,194 --> 00:59:29,299
EXPOSURE TO ANIMAL FECES FROM

1067
00:59:29,365 --> 00:59:30,400
CONTAMINATED WATER AND THE OTHER

1068
00:59:30,466 --> 00:59:34,270
IS THROUGH CONSUMPTION MUCH

1069
00:59:34,337 --> 00:59:37,974
INFECTED MEAT IMPROPERLY

1070
00:59:38,041 --> 00:59:41,511
PREPARED AND MEAT FROM PIGS,

1071
00:59:41,577 --> 00:59:46,082
WILD BORE OR DEER AND THERE'S

1072
00:59:46,149 --> 00:59:48,084
BLOOD TRANSMISSION THROUGH BLOOD

1073
00:59:48,151 --> 00:59:50,820
PRODUCTS FROM MOTHER TO INFANT

1074
00:59:50,887 --> 00:59:55,858
OR VERTICAL TRANSMISSION AND

1075
00:59:55,925 --> 00:59:57,694
THROUGH OCCUPATIONAL EXPOSURE.

1076
00:59:57,760 --> 00:59:59,529
AS MENTIONED ALSO WITH ENDEMIC

1077
00:59:59,595 --> 01:00:00,330
FORMS FROM PERSON TO PERSON IS

1078
01:00:00,396 --> 01:00:07,503
NOT COMMON.

1079
01:00:07,570 --> 01:00:11,107
THIS SHOWS THE COURSE OF ACUTE

1080
01:00:11,174 --> 01:00:14,110
HEPATITIS E AND THE MAJORITY OF

1081
01:00:14,177 --> 01:00:15,945
CASES HEPATITIS E PRESENTS AS A

1082
01:00:16,012 --> 01:00:18,414
SYMPTOMATIC INFECTION AND NOT

1083
01:00:18,481 --> 01:00:21,751
RECOGNIZED BUT IN 30% OF

1084
01:00:21,818 --> 01:00:23,586
PATIENTS THE CLASSIC

1085
01:00:23,653 --> 01:00:28,891
PRESENTATION ENSUES AND THERE'S

1086
01:00:28,958 --> 01:00:37,100
A PRODROMAL AND CONVALESCENT

1087
01:00:37,166 --> 01:00:39,369
PHASE HAS BEEN IDENTIFIED AND

1088
01:00:39,435 --> 01:00:42,105
ONE LASTED BY TWO TO SIX WEEKS

1089
01:00:42,171 --> 01:00:45,108
CHARACTERIZED BY NON SPECIFIC

1090
01:00:45,174 --> 01:00:50,213
SYMPTOMS SUCH AS MALAISE AND

1091
01:00:50,279 --> 01:00:53,349
THERE'S ENTERIC PHASE WHERE

1092
01:00:53,416 --> 01:00:54,717
JUANDICE IS PRESENT AND DARK

1093
01:00:54,784 --> 01:00:56,586
URINE AND CAN LAST FROM A COUPLE

1094
01:00:56,652 --> 01:00:58,021
DAYS TO SEVERAL WEEKS AND

1095
01:00:58,087 --> 01:00:59,856
FOLLOWED BY THE CONVALESCENT

1096
01:00:59,922 --> 01:01:03,726
PHASE WHERE RECOVERY ENSUES IN

1097
01:01:03,793 --> 01:01:09,098
ALMOST ALL CASES AND ALT LEVELS

1098
01:01:09,165 --> 01:01:13,069
RETURN TO NORMAL AND JUANDICE

1099
01:01:13,136 --> 01:01:13,503
RESOLVES.

1100
01:01:13,569 --> 01:01:15,772
LOOKING AT THE SEROLOGIC

1101
01:01:15,838 --> 01:01:19,776
PROFILE, IGM IS DETECTED IN

1102
01:01:19,842 --> 01:01:21,511
ALMOST EVERYONE AT THE TIME OF

1103
01:01:21,577 --> 01:01:23,446
PRESENTATION OF JUANDICE AND CAN

1104
01:01:23,513 --> 01:01:26,649
BE RELIABLY DETECTED IN MOST

1105
01:01:26,716 --> 01:01:27,316
INDIVIDUALS WITHIN TWO WEEKS OF

1106
01:01:27,383 --> 01:01:30,186
INFECTION.

1107
01:01:30,253 --> 01:01:33,122
IT RAPIDLY RISES AND REMAINS

1108
01:01:33,189 --> 01:01:37,393
DETECTABLE UP TO FIVE MONTHS.

1109
01:01:37,460 --> 01:01:39,529
IGG ANTIBODY FOLLOWS CLOSELY THE

1110
01:01:39,595 --> 01:01:41,964
COURSE OF IGM BUT REMAINS

1111
01:01:42,031 --> 01:01:45,068
ELEVATED UP TO 14 YEARS AND IS A

1112
01:01:45,134 --> 01:01:45,701
MARKER OF PRIOR EXPOSURE TO THE

1113
01:01:45,768 --> 01:01:50,606
VIRUS.

1114
01:01:50,673 --> 01:01:52,775
HEPATITIS E VIRUS RNA AND VIRUS

1115
01:01:52,842 --> 01:01:56,512
DETECT IN STOOL CAN BE DETECTED

1116
01:01:56,579 --> 01:02:01,350
DURING THE INCUBATION OF

1117
01:02:01,417 --> 01:02:03,286
PRODOMAL PHASE AND REMAINS

1118
01:02:03,352 --> 01:02:05,154
POSITIVE FOUR TO SIX WEEKS

1119
01:02:05,221 --> 01:02:05,755
RESPECTIVELY FOR EACH OF THE

1120
01:02:05,822 --> 01:02:16,199
DIFFERENT PARAMETERS.

1121
01:02:17,233 --> 01:02:19,368
THERE'S DIAGNOSIS FIRST THE

1122
01:02:19,435 --> 01:02:21,637
INDEX OF SUSPICION AND THE FIRST

1123
01:02:21,704 --> 01:02:25,775
TEST SHOULD BE FOR ANTI-HIV AGM

1124
01:02:25,842 --> 01:02:28,010
AND IF POSITIVE IT SHOWS RECENT

1125
01:02:28,077 --> 01:02:29,679
OR ACTIVE INFECTION BUT SHOULD

1126
01:02:29,745 --> 01:02:35,151
BE CONFIRMED BY TESTING FOR

1127
01:02:35,218 --> 01:02:35,551
HEPATITIS E RNA.

1128
01:02:35,618 --> 01:02:38,721
IF BOTH ARE POSITIVE THIS

1129
01:02:38,788 --> 01:02:41,624
INDICATES RECENT AND ACTIVE

1130
01:02:41,691 --> 01:02:42,225
INFECTION.

1131
01:02:42,291 --> 01:02:43,860
NOW, IF IMMUNOCOMPROMISED

1132
01:02:43,926 --> 01:02:47,230
INDIVIDUALS TESTING SHOULD BEGIN

1133
01:02:47,296 --> 01:02:54,770
WITH ANTI-HIV IGM BUT A MAJORITY

1134
01:02:54,837 --> 01:02:57,974
MAY BE NEGATIVE AND IT SHOULD BE

1135
01:02:58,040 --> 01:03:04,413
MANDATORY TO TEST FOR IGV RNA

1136
01:03:04,480 --> 01:03:06,449
AND IF PRESENT INDICATES RECENT

1137
01:03:06,516 --> 01:03:06,849
INFECTION.

1138
01:03:06,916 --> 01:03:10,153
IN THE PAST THE AVAILABILITY OF

1139
01:03:10,219 --> 01:03:10,887
TESTING FOR THE RNA WAS

1140
01:03:10,953 --> 01:03:11,821
DIFFICULT TO COME ABOUT.

1141
01:03:11,888 --> 01:03:14,257
THIS HAS NOW CHANGED AND THESE

1142
01:03:14,323 --> 01:03:16,125
TESTS ARE AVAILABLE AT MOST

1143
01:03:16,192 --> 01:03:17,927
COMMERCIAL LABORATORIES.

1144
01:03:17,994 --> 01:03:24,333
HERE AT THE NIH PATRICIA'S

1145
01:03:24,400 --> 01:03:28,471
FOSSI'S LAB STILL TESTS FOR IT

1146
01:03:28,538 --> 01:03:32,341
AND WHEN SHOULD ONE TEST FOR

1147
01:03:32,408 --> 01:03:33,876
HEPATITIS E VIRUS RNA IN

1148
01:03:33,943 --> 01:03:35,278
SITUATIONS WHERE PATIENTS HAVE A

1149
01:03:35,344 --> 01:03:38,281
POOR IGM RESPONSE IT'S

1150
01:03:38,347 --> 01:03:43,119
RECOMMENDED TO ORDER AN HEV00

1151
01:03:43,186 --> 01:03:45,121
AND MANDATORY FOR CHRONIC

1152
01:03:45,188 --> 01:03:47,657
INFECTION AND PRIOR TO JORG

1153
01:03:47,723 --> 01:03:49,926
ORRINGAN TRANSPLANTATION.

1154
01:03:49,992 --> 01:03:51,427
AND NEEDED FOR BLOOD TRANSFUSION

1155
01:03:51,494 --> 01:03:52,929
AND I'LL GET TO THIS LATER IN

1156
01:03:52,995 --> 01:03:53,629
THE TALK.

1157
01:03:53,696 --> 01:03:55,231
OF COURSE TO EVALUATE THE

1158
01:03:55,298 --> 01:03:57,099
RESPONSE TO ANTI-VIRAL DRUG

1159
01:03:57,166 --> 01:04:00,203
THERAPY.

1160
01:04:00,269 --> 01:04:04,440
NOW, I WANTED TO SAY A FEW WORDS

1161
01:04:04,507 --> 01:04:07,877
ABOUT DIAGNOSTIC TEST FOR

1162
01:04:07,944 --> 01:04:08,544
HEPATITIS E BECAUSE THERE ARE A

1163
01:04:08,611 --> 01:04:10,780
LOT OF ISSUES CURRENTLY WITH THE

1164
01:04:10,846 --> 01:04:13,182
CURRENT ASSAYS.

1165
01:04:13,249 --> 01:04:17,386
MOST THE DIAGNOSTIC ASSAYS RIGHT

1166
01:04:17,453 --> 01:04:25,428
NOW RELY ON RECOMBINANT ASSAYS

1167
01:04:25,494 --> 01:04:27,630
AND THEY'RE HIGHLY VARIABLE.

1168
01:04:27,697 --> 01:04:28,764
THIS LEADS TO A LOT OF

1169
01:04:28,831 --> 01:04:30,099
CONSTERNATION WITH BEING ABLE TO

1170
01:04:30,166 --> 01:04:34,070
DETERMINE WHAT THE TRUE

1171
01:04:34,136 --> 01:04:35,338
PREVALENCE OF HEPATITIS E IS

1172
01:04:35,404 --> 01:04:37,740
GLOBALLY AND THIS WAS

1173
01:04:37,807 --> 01:04:40,209
ILLUSTRATED IN THE STUDY BY

1174
01:04:40,276 --> 01:04:44,447
DR. PURCELL WHERE THEY TESTED A

1175
01:04:44,513 --> 01:04:47,016
PANEL FOR HEPATITIS E USING 12

1176
01:04:47,083 --> 01:04:50,286
ASSAYS AND YOU CAN SEE AMONG

1177
01:04:50,353 --> 01:04:53,122
PRIOR REACTIVE TEST SAMPLES BY

1178
01:04:53,189 --> 01:04:56,926
TWO OR MORE TESTS, YOU CAN SEE A

1179
01:04:56,993 --> 01:04:58,361
WIDE VARIATION IN POSITIVITY

1180
01:04:58,427 --> 01:05:04,700
THERE FROM A LOW OF 6% TO A HIGH

1181
01:05:04,767 --> 01:05:07,603
OF 100% AND YOU CAN SEE THE

1182
01:05:07,670 --> 01:05:09,605
NUMBER THAT TESTED POSITIVE

1183
01:05:09,672 --> 01:05:13,542
RANGE FROM 4 TO 71% AND AMONG 39

1184
01:05:13,609 --> 01:05:14,877
SAMPLES PREVIOUSLY TESTED

1185
01:05:14,944 --> 01:05:18,447
NEGATIVE BY TWO OR MORE ASSAYS,

1186
01:05:18,514 --> 01:05:20,683
THE DETECTION RATE RANGED FROM 0

1187
01:05:20,750 --> 01:05:21,517
TO 31%.

1188
01:05:21,584 --> 01:05:25,821
SO THE OVER ALL CONCORDANCE

1189
01:05:25,888 --> 01:05:29,091
RANGED FROM 49 TO 94%.

1190
01:05:29,158 --> 01:05:33,663
THIS HIGHLIGHTS THE ISSUE WITH

1191
01:05:33,729 --> 01:05:36,299
THE CURRENT DIAGNOSTIC ASSAYS.

1192
01:05:36,365 --> 01:05:40,736
THIS PARTICULARLY RELEVANT IN

1193
01:05:40,803 --> 01:05:41,671
LOW ENDEMIC REGIONS.

1194
01:05:41,737 --> 01:05:43,306
I WANTED TO BRING THIS TO YOUR

1195
01:05:43,372 --> 01:05:45,174
ATTENTION AND WORD OF CAUTION

1196
01:05:45,241 --> 01:05:48,110
HOW WE INTERPRET THE RESULTS OF

1197
01:05:48,177 --> 01:05:49,545
PREVALENCE STUDIES FROM LOW

1198
01:05:49,612 --> 01:05:49,912
ENDEMIC AREAS.

1199
01:05:49,979 --> 01:05:53,816
IT'S ALL OVER THE MAP.

1200
01:05:53,883 --> 01:05:56,552
SO, I WANT TO TURN TO THE

1201
01:05:56,619 --> 01:05:58,487
CLINICAL FEATURES OF HEPATITIS E

1202
01:05:58,554 --> 01:06:02,325
AND THIS SHOWS THE COMPARISON OF

1203
01:06:02,391 --> 01:06:06,495
CLINICAL AND EPIDEMIOLOGIC FEE

1204
01:06:06,562 --> 01:06:10,032
TIRES OF HEPATITIS E AND THEY'RE

1205
01:06:10,099 --> 01:06:12,168
QUITE DISTINCTIVE AND DIFFERENT

1206
01:06:12,234 --> 01:06:20,843
AND FROM OTHER FORMS OF VIRAL

1207
01:06:20,910 --> 01:06:21,110
HEPATITIS.

1208
01:06:21,177 --> 01:06:23,646
ONE CAN DESCRIBE THEM AS TWO

1209
01:06:23,713 --> 01:06:24,246
DIFFERENT DISEASES.

1210
01:06:24,313 --> 01:06:27,817
THE DISTRIBUTION IS PRIMARILY

1211
01:06:27,883 --> 01:06:33,923
THOSE 15 TO 40 YEARS OLD WHERE

1212
01:06:33,989 --> 01:06:44,300
LOCALLY ACQUIRED AUTOCHTHONOUS

1213
01:06:44,367 --> 01:06:46,035
IS IN DIFFERENT FORM AND THERE'S

1214
01:06:46,102 --> 01:06:51,640
MALE DOMINANCE IN LOCALLY

1215
01:06:51,707 --> 01:06:59,548
ACQUIRED HAEMENT

1216
01:07:03,753 --> 01:07:06,222
AND THE SEASONALITY WITH THE

1217
01:07:06,288 --> 01:07:07,790
FORMS AND LOC ALY

1218
01:07:10,726 --> 01:07:12,628
-- LOCALLY ACQUIRED HEPATITIS E

1219
01:07:12,695 --> 01:07:18,200
AND THE ONLY RESERVOIR IS HUMAN

1220
01:07:18,267 --> 01:07:28,811
WHERE AUTOCHTHONOUS HEPATITIS E

1221
01:07:40,890 --> 01:07:45,094
THERE'S A PREVALENCE THROUGHOUT

1222
01:07:45,161 --> 01:07:47,296
LIFE AND AUTOCHTHONOUS HEPATITIS

1223
01:07:47,363 --> 01:07:49,098
E MY PRESENT WITH NEUROLOGICAL

1224
01:07:49,165 --> 01:07:51,567
COMPLICATIONS.

1225
01:07:51,634 --> 01:07:55,137
SO THE CLINICAL PRESENTATION OF

1226
01:07:55,204 --> 01:07:59,542
LOCALLY ACQUIRED AUTOCHTHONOUS

1227
01:07:59,608 --> 01:08:01,143
HEPATITIS E IS SHOWN HERE AND

1228
01:08:01,210 --> 01:08:03,412
FOR MOST IT'S AN ASYMPTOMATIC

1229
01:08:03,479 --> 01:08:07,550
INFECTION AND A SMALLER

1230
01:08:07,616 --> 01:08:08,918
PROPORTION PRESENT WITH

1231
01:08:08,984 --> 01:08:09,819
INFECTION THAT GOES UNRECOGNIZED

1232
01:08:09,885 --> 01:08:13,022
AND A SMALL PROPORTION OF

1233
01:08:13,088 --> 01:08:16,659
PATIENTS PRESENT WITH

1234
01:08:16,725 --> 01:08:17,927
SYMPTOMATIC CLASSIC HEPATITIS

1235
01:08:17,993 --> 01:08:18,994
WITH JUANDICE.

1236
01:08:19,061 --> 01:08:24,300
I WANTED TO HIGHLIGHT ONE NEEDS

1237
01:08:24,366 --> 01:08:29,872
TO HAVE A HIGH SUSPICION FOR

1238
01:08:29,939 --> 01:08:32,107
HEPATITIS E BECAUSE THERE'S A

1239
01:08:32,174 --> 01:08:34,276
VARIABLE PRESENTATION THAT

1240
01:08:34,343 --> 01:08:35,544
INCLUDES ACUTE HEPATITIS AND

1241
01:08:35,611 --> 01:08:37,980
ACUTE AND CHRONIC LIVER FAILURE

1242
01:08:38,047 --> 01:08:41,617
MAY PRESENT AS A DRUG INDUCED

1243
01:08:41,684 --> 01:08:42,251
LIVER INJURY WITH SYMPTOMS

1244
01:08:42,318 --> 01:08:44,653
WITHOUT LIVER FEATURES AND THEN

1245
01:08:44,720 --> 01:08:46,355
AS MISCELLANEOUS SYNDROME

1246
01:08:46,422 --> 01:08:49,158
INCLUDING THAT OF A GLOBULAR

1247
01:08:49,225 --> 01:08:49,859
NEPHRITIS.

1248
01:08:49,925 --> 01:08:53,195
YOU HAVE TO HAVE YOUR CLINICAL

1249
01:08:53,262 --> 01:08:59,668
CLINICIAN HAT ON TO SOMETIMES

1250
01:08:59,735 --> 01:09:00,302
DIAGNOSE HEPATITIS E AND THIS

1251
01:09:00,369 --> 01:09:01,837
WILL BE IN SEVERAL STUDIES I'LL

1252
01:09:01,904 --> 01:09:06,942
SHARE NOW.

1253
01:09:07,009 --> 01:09:10,946
ONE STUDY SHOWED THE LIVER

1254
01:09:11,013 --> 01:09:13,082
FAILURE ASSOCIATED WITH HIGH

1255
01:09:13,148 --> 01:09:14,350
MORTALITY AND THIS WAS CONDUCTED

1256
01:09:14,416 --> 01:09:24,894
IN INDIA LOOKING AT 107 CIR

1257
01:09:30,165 --> 01:09:34,603
OTICS SUGGESTING IT MAY BE

1258
01:09:34,670 --> 01:09:35,571
PREDISPOSED TO ACQUIRING

1259
01:09:35,638 --> 01:09:46,115
HEPATITIS E VIRUS INFECTION.

1260
01:09:52,721 --> 01:09:55,991
AND GROUP 3 WAS CIR OTIC WITH A

1261
01:09:56,058 --> 01:09:58,727
STABLE DISEASE AND LOOKING AT

1262
01:09:58,794 --> 01:10:04,199
THE GREEN LINE THEY HAVE RAPID

1263
01:10:04,266 --> 01:10:11,707
DECOMPOSITION ANDRHOTIC WITH A

1264
01:10:11,774 --> 01:10:12,308
STABLE DISEASE AND LOOKING AT

1265
01:10:12,374 --> 01:10:12,942
THE GREEN LINE THEY HAVE RAPID

1266
01:10:13,008 --> 01:10:15,511
DECOMPOSITION AND IN COMPARISON

1267
01:10:15,578 --> 01:10:19,615
THOSE WITH CIRRHOSIS WITHOUT

1268
01:10:19,682 --> 01:10:21,450
DECOMPENSATION VIRAL RNA WAS

1269
01:10:21,517 --> 01:10:23,319
PRESENT IN ONLY 10% AND THEIR

1270
01:10:23,385 --> 01:10:25,321
SURVIVAL WAS MORE THAN 90% AT

1271
01:10:25,387 --> 01:10:26,689
ONE YEAR.

1272
01:10:26,755 --> 01:10:29,525
IN CONTRAST, HEPATITIS D IS

1273
01:10:29,592 --> 01:10:31,994
RARELY ASSOCIATED WITH ACUTE AND

1274
01:10:32,061 --> 01:10:33,095
CHRONIC LIVER FAILURE IN THE

1275
01:10:33,162 --> 01:10:34,897
U.S. AND THIS IS DATA FROM THE

1276
01:10:34,964 --> 01:10:39,835
LIVER UNIT CONDUCTED BY ONE OF

1277
01:10:39,902 --> 01:10:42,538
THE FELLOWS AND THEY LOOKED AT

1278
01:10:42,605 --> 01:10:47,977
PATIENTS WHO HAD PARTICIPATED IN

1279
01:10:48,043 --> 01:10:58,554
THE TRIAL LOOKING AT LOW DOSE

1280
01:11:02,257 --> 01:11:05,728
PEGINTERFERON AND TREATED FOR

1281
01:11:05,794 --> 01:11:06,695
FOUR YEARS.

1282
01:11:06,762 --> 01:11:09,565
THERE WERE 314 PATIENTS WHO

1283
01:11:09,632 --> 01:11:14,203
EXPERIENCED HEPATIC

1284
01:11:14,269 --> 01:11:17,773
DECOMPENSATION AND 89 PATIENTS

1285
01:11:17,840 --> 01:11:22,878
WEREFIDE WITH RAPID

1286
01:11:22,945 --> 01:11:26,649
DECOMPENSATION WITHIN 24 WEEK

1287
01:11:26,715 --> 01:11:27,783
PERIOD AND IDENTIFIED 267

1288
01:11:27,850 --> 01:11:28,851
CONTROLS WITHOUT DECOMPENSATION

1289
01:11:28,917 --> 01:11:33,122
AND THEY WERE ALL TESTED FOR

1290
01:11:33,188 --> 01:11:34,123
HEPATITIS E.

1291
01:11:34,189 --> 01:11:36,525
I GG, IGM AND RNA.

1292
01:11:36,592 --> 01:11:42,398
YOU CAN SEE THE PREVALENCE OF

1293
01:11:42,464 --> 01:11:44,366
IGG WAS SIMILAR BETWEEN CASES

1294
01:11:44,433 --> 01:11:45,668
AND CONTROLS SIMILAR TO THE

1295
01:11:45,734 --> 01:11:46,235
PREVALENCE OF THE

1296
01:11:46,301 --> 01:11:47,503
U.S. POPULATION AT THE TIME THE

1297
01:11:47,569 --> 01:11:49,905
STUDY WAS CONDUCTED.

1298
01:11:49,972 --> 01:11:52,608
AND THE PREVALENCE OF IGM WAS

1299
01:11:52,675 --> 01:11:55,210
BETWEEN CASES OF CONTROLS AND NO

1300
01:11:55,277 --> 01:11:58,747
PATIENTS HAVE HIV RNA

1301
01:11:58,814 --> 01:12:01,283
HIGHLIGHTING AT LEAST IN

1302
01:12:01,350 --> 01:12:02,451
NON-ENDEMIC AREA IT'S NOT A

1303
01:12:02,518 --> 01:12:04,753
CAUSE OF ACUTE AND CHRONIC LIVER

1304
01:12:04,820 --> 01:12:05,788
FAILURE AND ANOTHER STUD AGREE

1305
01:12:05,854 --> 01:12:07,222
FROM THE U.S.

1306
01:12:07,289 --> 01:12:12,561
THIS ONE FROM THE ACUTE LIVER

1307
01:12:12,628 --> 01:12:15,731
INJURY CONSORTIUM ANOTHER LARGE

1308
01:12:15,798 --> 01:12:19,368
NIH CONSORTIUM OF OVER 600

1309
01:12:19,435 --> 01:12:24,506
PATIENTS WERE EFFTESTED WITH AC

1310
01:12:24,573 --> 01:12:27,643
LIVER FAILURE AND ONLY 10%

1311
01:12:27,710 --> 01:12:36,085
TESTED POSITIVE FOR IGG AND ONE

1312
01:12:36,151 --> 01:12:38,787
WAS FOUND TO BE RNA POSITIVE AND

1313
01:12:38,854 --> 01:12:40,589
IDENTIFIED AS HAVING GENOTYPE 3

1314
01:12:40,656 --> 01:12:47,162
INFECTION AND ONE HAD DETECT AND

1315
01:12:47,229 --> 01:12:50,999
HEPATITIS E ANTIGEN HIGHLIGHTING

1316
01:12:51,066 --> 01:12:54,203
IT'S NOT A MAJOR CAUSE OF ACUTE

1317
01:12:54,269 --> 01:12:58,340
LIVER FAILURE COMPARED TO THE

1318
01:12:58,407 --> 01:13:01,577
DATA FROM EPIDEMIC AREAS.

1319
01:13:01,643 --> 01:13:04,713
HEPATITIS E MAY MASQUERADE AS A

1320
01:13:04,780 --> 01:13:05,547
DRUG-INDUCED LIVER INJURY.

1321
01:13:05,614 --> 01:13:08,183
THIS IS DATA FROM A LARGE NIH

1322
01:13:08,250 --> 01:13:11,687
FUNDED NETWORK LOOKING AT OVER

1323
01:13:11,754 --> 01:13:22,231
300 PATIENTS AND DILI AND ONLY A

1324
01:13:22,297 --> 01:13:28,303
MINORITY WERE IGM POSITIVE AND

1325
01:13:28,370 --> 01:13:30,672
ONLY FOUR WERE RNA POSITIVE AND

1326
01:13:30,739 --> 01:13:33,942
THEY REASSESSED AND IT WAS

1327
01:13:34,009 --> 01:13:38,614
EVIDENT SEVEN OF THESE HEPATITIS

1328
01:13:38,680 --> 01:13:40,749
E WAS LIKELY THE CAUSE AND THE

1329
01:13:40,816 --> 01:13:42,317
CASES WERE MISDIAGNOSED AND THE

1330
01:13:42,384 --> 01:13:48,223
OTHER TWO WERE LIKELY TO HAVE

1331
01:13:48,290 --> 01:13:49,792
HEPATITIS E AND NOT A

1332
01:13:49,858 --> 01:13:57,466
DRUG-INDUCED LIVER INJURY AND IT

1333
01:13:57,533 --> 01:13:59,601
CAN PRESENT WITH AN INITIAL

1334
01:13:59,668 --> 01:14:00,602
PRESENTATION THOUGH A LOT OF THE

1335
01:14:00,669 --> 01:14:02,204
DATA COMES FROM SINGLE CASE

1336
01:14:02,271 --> 01:14:04,239
REPORTS OR SMALL CASE SERIES SO

1337
01:14:04,306 --> 01:14:06,575
IT'S BEEN DIFFICULT TO ESTABLISH

1338
01:14:06,642 --> 01:14:07,042
A CAUSALITY.

1339
01:14:07,109 --> 01:14:10,078
HOWEVER, FOR THE NEUROLOGICAL

1340
01:14:10,145 --> 01:14:10,746
COMPLICATIONS, THEY'RE MUCH

1341
01:14:10,813 --> 01:14:14,249
LARGER SERIES AND A GREATER

1342
01:14:14,316 --> 01:14:16,919
BURDEN OF DATA WHICH DOES

1343
01:14:16,985 --> 01:14:21,089
SUGGEST THERE MIGHT BE A

1344
01:14:21,156 --> 01:14:31,600
CAUSALITY AS LISTED THERE.

1345
01:14:35,737 --> 01:14:37,906
I WANTED TO TALK ABOUT PREGNANCY

1346
01:14:37,973 --> 01:14:40,142
WHERE IT CAN REACH AS HIGH AS

1347
01:14:40,209 --> 01:14:40,309
33%.

1348
01:14:40,375 --> 01:14:42,010
THERE'S A HIGHER RATE OF ACUTE

1349
01:14:42,077 --> 01:14:44,279
LIVER FAILURE IN PREGNANT WOMEN

1350
01:14:44,346 --> 01:14:51,653
AND THE MECHANISMS AREN'T CLEAR.

1351
01:14:51,720 --> 01:14:54,623
CLINICAL AND ANIMAL DATA TO

1352
01:14:54,690 --> 01:14:57,092
SUGGEST HEPATITIS E CAN INFECT

1353
01:14:57,159 --> 01:14:58,527
THE PLACENTA AND CAUSE INJURY

1354
01:14:58,594 --> 01:15:03,599
INCLUDING FIBROSIS AND FIBROSIS

1355
01:15:03,665 --> 01:15:05,167
OF THE CORD AND THERE'S EVIDENCE

1356
01:15:05,234 --> 01:15:09,104
OF VERTICAL TRANSMISSION TO THE

1357
01:15:09,171 --> 01:15:12,474
FETUS WHICH CAN CAUSE SEVERE

1358
01:15:12,541 --> 01:15:15,277
NEONATAL HEPATITIS AND THE

1359
01:15:15,344 --> 01:15:18,547
IMMUNE DYSFUNCTION DURING

1360
01:15:18,614 --> 01:15:19,281
PREGNANCY CAN LEAD TO HIGHER

1361
01:15:19,348 --> 01:15:21,950
VIRAL REPLICATION AND LEAD TO

1362
01:15:22,017 --> 01:15:22,951
WORSE OUTCOMES.

1363
01:15:23,018 --> 01:15:24,553
THE TRUE CAUSE FOR THE WORSE

1364
01:15:24,620 --> 01:15:25,187
DISEASE IN PREGNANT WOMEN NOT

1365
01:15:25,254 --> 01:15:26,488
CLEAR.

1366
01:15:26,555 --> 01:15:29,291
AND THIS IS AN AREA OF ACTIVE

1367
01:15:29,358 --> 01:15:32,961
RESEARCH.

1368
01:15:33,028 --> 01:15:35,931
FOLLOWING THE DISCOVERY IT WAS

1369
01:15:35,998 --> 01:15:37,399
LONG THOUGHT OR BELIEVED

1370
01:15:37,466 --> 01:15:41,703
HEPATITIS E WAS A SELF-LIMITING

1371
01:15:41,770 --> 01:15:43,272
HEPATITIS SIMILAR TO HEPATITIS A

1372
01:15:43,338 --> 01:15:45,607
AND IN THE LATE 1980s, CASE

1373
01:15:45,674 --> 01:15:51,546
REPORTS BEGAN TO EMERGE OF VIRUS

1374
01:15:51,613 --> 01:15:53,415
RNA IN DELIVER TRANSPLANT

1375
01:15:53,482 --> 01:15:57,920
RECIPIENTS AND IT'S NOW WELL

1376
01:15:57,986 --> 01:15:59,054
DOCUMENTED HEPATITIS E CAN CAUSE

1377
01:15:59,121 --> 01:16:02,925
A CHRONIC INFECTION BUT OCCURS

1378
01:16:02,991 --> 01:16:05,093
ALMOST EXCLUSIVELY AMONG

1379
01:16:05,160 --> 01:16:06,361
IMMUNOCOMPROMISED PERSONS AND

1380
01:16:06,428 --> 01:16:09,865
SOLID ORGAN TRANSPLANT

1381
01:16:09,932 --> 01:16:10,999
RECIPIENTS, PATIENTS RECEIVING

1382
01:16:11,066 --> 01:16:12,567
CANCER THERAPY AND HIV INFECTED

1383
01:16:12,634 --> 01:16:13,001
PERSONS.

1384
01:16:13,068 --> 01:16:16,438
THE PREVALENCE IS 1 TO 2% AND

1385
01:16:16,505 --> 01:16:18,273
ONLY BEEN REPORTED WITH GENOTYPE

1386
01:16:18,340 --> 01:16:19,141
3 INFECTION.

1387
01:16:19,207 --> 01:16:21,276
ABOUT 10% OF PATIENTS CAN

1388
01:16:21,343 --> 01:16:23,412
PROGRESS TO CIRRHOSIS AND THE

1389
01:16:23,478 --> 01:16:24,313
SOURCE OF INFECTION IS OFTEN

1390
01:16:24,379 --> 01:16:29,084
UNKNOWN.

1391
01:16:29,151 --> 01:16:30,652
SHOWN HERE IS THE PREVALENCE OF

1392
01:16:30,719 --> 01:16:32,688
HEPATITIS E IN THE SOLID ORGAN

1393
01:16:32,754 --> 01:16:33,755
TRANSPLANT POPULATION.

1394
01:16:33,822 --> 01:16:36,959
IT'S ESTIMATED USING IGG IT'S

1395
01:16:37,025 --> 01:16:39,594
ABOUT 20% AND THAT'S SIMILAR TO

1396
01:16:39,661 --> 01:16:40,095
THE GENERAL POPULATION.

1397
01:16:40,162 --> 01:16:42,331
AND IT VARIES BY THE

1398
01:16:42,397 --> 01:16:44,166
TRANSPLANTED ORGAN BEING HIGHEST

1399
01:16:44,232 --> 01:16:46,201
IN LIVER FOLLOWED BY KIDNEY,

1400
01:16:46,268 --> 01:16:47,903
HEART AND LUNG AND THE RATE OF

1401
01:16:47,970 --> 01:16:51,106
CHRONIC INFECTION IS LOW.

1402
01:16:51,173 --> 01:16:55,577
IT'S ABOUT .5% TO 1.5% AND

1403
01:16:55,644 --> 01:16:58,947
IMPORTANT TO RECOGNIZE

1404
01:16:59,014 --> 01:17:02,651
RE-INFECTION MAY RE-OCCUR.

1405
01:17:02,718 --> 01:17:03,685
CO-INFECTION WITH HEPATITIS E

1406
01:17:03,752 --> 01:17:08,890
HAS BEEN DESCRIBED NOW.

1407
01:17:08,957 --> 01:17:11,493
FIRST CASE REPORT WAS PUBLISHED

1408
01:17:11,560 --> 01:17:13,095
IN THE NEW ENGLAND JOURNAL AND

1409
01:17:13,161 --> 01:17:17,666
THE INCIDENTS IN THE POPULATION

1410
01:17:17,733 --> 01:17:22,037
IS LOW FROM 0 TO 9% AND RELATED

1411
01:17:22,104 --> 01:17:25,273
TO GENOTYPE 3 INFECTION.

1412
01:17:25,340 --> 01:17:29,511
A LOW CD4 COUNT IS THE ONLY RISK

1413
01:17:29,578 --> 01:17:30,746
FACTOR IDENTIFIED IN THIS

1414
01:17:30,812 --> 01:17:33,382
POPULATION AND ONE CASE REPORT

1415
01:17:33,448 --> 01:17:38,520
WITH PROGRESSION WITH CIRRHOSIS.

1416
01:17:38,587 --> 01:17:41,690
THIS SHOWS A CARTOON WHICH IS A

1417
01:17:41,757 --> 01:17:45,494
MANAGEMENT ALGORITHM FOR

1418
01:17:45,560 --> 01:17:46,361
PATIENTS WITH CHRONIC HEPATITIS

1419
01:17:46,428 --> 01:17:47,429
E INFECTION.

1420
01:17:47,496 --> 01:17:50,465
AS I MENTIONED IN THE VAST

1421
01:17:50,532 --> 01:17:55,137
MAJORITY OF INDIVIDUALS WITH

1422
01:17:55,203 --> 01:17:56,304
ACUTE HEPATITIS E THERE'S GOING

1423
01:17:56,371 --> 01:17:58,974
TO BE SPONTANEOUS RESOLUTION

1424
01:17:59,041 --> 01:18:01,376
WITH CLEARANCE OF THE VIRAL RNA.

1425
01:18:01,443 --> 01:18:02,611
HOWEVER, THERE'S A SMALL

1426
01:18:02,677 --> 01:18:04,646
PERCENTAGE OF PATIENTS WHERE THE

1427
01:18:04,713 --> 01:18:06,381
RNA WILL PERSIST BEYOND SIX

1428
01:18:06,448 --> 01:18:07,916
MONTHS AND THIS IS THE

1429
01:18:07,983 --> 01:18:13,088
DEFINITION OF CHRONIC INFECTION.

1430
01:18:13,155 --> 01:18:21,096
THE FIRST IS APPROACH IF

1431
01:18:21,163 --> 01:18:28,336
RECEIVING IMMUNOEXPRESSIVE  --

1432
01:18:28,403 --> 01:18:36,645
IMMUNOSUPPRESSIVE CASES AND CAN

1433
01:18:36,711 --> 01:18:40,215
CLEAR AND IF NOT MEDICATION

1434
01:18:40,282 --> 01:18:42,884
LEADING TO VIRAL CLEARANCE FOR

1435
01:18:42,951 --> 01:18:44,086
THREE-QUARTERS OF PATIENTS AND

1436
01:18:44,152 --> 01:18:47,322
THE REGIMENT IS EMPIRICAL AND WE

1437
01:18:47,389 --> 01:18:50,992
DON'T KNOW WHAT THE OPTIMAL DOSE

1438
01:18:51,059 --> 01:18:55,997
IS FOR TREATING HEPATITIS E JUST

1439
01:18:56,064 --> 01:18:57,532
BECAUSE THE CHRONIC INFECTION IS

1440
01:18:57,599 --> 01:18:58,733
SO RARE IT'S DIFFICULT TO DO

1441
01:18:58,800 --> 01:19:00,969
LARGE CONTROLLED STUDIES.

1442
01:19:01,036 --> 01:19:03,371
IF THE VIRUS PERSISTS AFTER.

1443
01:19:03,438 --> 01:19:08,076
THERE'S TWO OPTIONS, ONE TO

1444
01:19:08,143 --> 01:19:09,811
CONTINUE WITH THE MEDICATION FOR

1445
01:19:09,878 --> 01:19:12,080
AN ADDITIONAL TWO MONTHS OR FOR

1446
01:19:12,147 --> 01:19:16,351
LIVER TRANSPLANT RECIPIENTS TO

1447
01:19:16,418 --> 01:19:18,620
RECOMMEND PEGINTERFERON AND IT'S

1448
01:19:18,687 --> 01:19:21,790
EFFECTIVE IN 34% OF PATIENTS.

1449
01:19:21,857 --> 01:19:23,792
PEGINTERFERON IS CONTRAINDICATED

1450
01:19:23,859 --> 01:19:26,528
IN OTHER TRANSPLANT RECIPIENTS

1451
01:19:26,595 --> 01:19:29,097
BECAUSE OF HIGH RISK OF ORGAN

1452
01:19:29,164 --> 01:19:35,937
REJECTION.

1453
01:19:36,004 --> 01:19:46,381
WHAT ABOUT PREVENTION.

1454
01:19:47,816 --> 01:19:55,390
FOR AUTOCHTHONOUS HEPATITIS

1455
01:19:55,457 --> 01:20:01,730
ISOLATION OF ANIMALS AND

1456
01:20:01,796 --> 01:20:03,965
MONITORING WASTE RUNOFF BUT NOT

1457
01:20:04,032 --> 01:20:04,733
WIDELY ADOPTED AND FOR

1458
01:20:04,799 --> 01:20:06,535
INDIVIDUALS THE ONE SINGLE THING

1459
01:20:06,601 --> 01:20:11,072
YOU CAN DO TO TRY TO PREVENT

1460
01:20:11,139 --> 01:20:13,975
HEPATITIS E INFECTION IS AVOID

1461
01:20:14,042 --> 01:20:19,881
CONSUMPTION OF UNDER COOKED MEAT

1462
01:20:19,948 --> 01:20:21,716
PARTICULARLY PORK OR GAME AND IT

1463
01:20:21,783 --> 01:20:25,620
SHOULD BE HEATED TO 160 DEGREES

1464
01:20:25,687 --> 01:20:28,657
FOR AT LATEST 20 MINUTES BEFORE

1465
01:20:28,723 --> 01:20:32,827
CONSUMPTION AND ONE SHOULD AVOID

1466
01:20:32,894 --> 01:20:38,200
CONSUMPTION OF RAW SHELLFISH

1467
01:20:38,266 --> 01:20:41,102
ESPECIALLY IF IMMUNOCOMPROMISED

1468
01:20:41,169 --> 01:20:43,972
AND THIS HAS BEEN IMPLEMENTED IN

1469
01:20:44,039 --> 01:20:47,976
A FEW WESTERN COUNTRIES.

1470
01:20:48,043 --> 01:20:49,444
THE PREVALENCE OF HEPATITIS E

1471
01:20:49,511 --> 01:20:53,882
RNA RANGES THERE 1 TO 4,000

1472
01:20:53,949 --> 01:20:56,484
DONORS AND 11 EUROPEAN COUNTRIES

1473
01:20:56,551 --> 01:20:58,720
RECOMMEND MINI POOL SCREENING

1474
01:20:58,787 --> 01:21:02,324
FOR HEPATITIS E.

1475
01:21:02,390 --> 01:21:02,657
HO

1476
01:21:02,724 --> 01:21:03,992
HOWEVER, THIS IS NOT YET ADOPTED

1477
01:21:04,059 --> 01:21:04,526
IN THE UNITED STATES.

1478
01:21:04,593 --> 01:21:12,267
ONE STUDY CONDUCTED HERE AT THE

1479
01:21:12,334 --> 01:21:18,773
NIH HARVEY ALTER SCREENED FOR

1480
01:21:18,840 --> 01:21:19,941
HEPATITIS E AND FOUND A

1481
01:21:20,008 --> 01:21:22,210
PREVALENCE OF 22% CORRESPONDING

1482
01:21:22,277 --> 01:21:25,313
TO THE PREVALENCE OF HEPATITIS E

1483
01:21:25,380 --> 01:21:26,214
IN THE GENERAL U.S. POPULATION

1484
01:21:26,281 --> 01:21:29,084
AT THE TIME AND NONE WERE FOUND

1485
01:21:29,150 --> 01:21:32,420
TO BE HEPATITIS E RNA BUT

1486
01:21:32,487 --> 01:21:35,190
THERE'S DEBATE GOING ON WHETHER

1487
01:21:35,257 --> 01:21:39,127
THE U.S. SHOULD ADOPT SCREENING

1488
01:21:39,194 --> 01:21:40,729
FOR HEPATITIS E BUT PART OF THE

1489
01:21:40,795 --> 01:21:43,365
REASON IT HASN'T YET IS BECAUSE

1490
01:21:43,431 --> 01:21:46,268
OF THE PRESUMED LOW PREVALENCE

1491
01:21:46,334 --> 01:21:50,939
OF HEPATITIS E IN THE U.S.

1492
01:21:51,006 --> 01:21:54,776
FOR EPIDEMIC HEPATITIS E TO

1493
01:21:54,843 --> 01:21:57,212
IMPROVE SANITATION AND AVOID

1494
01:21:57,279 --> 01:21:59,714
CONTAMINATED WATER WE NOW HAVE A

1495
01:21:59,781 --> 01:22:01,016
SAFE VACCINE AVAILABLE.

1496
01:22:01,082 --> 01:22:03,585
THERE'S THREE RECOMBINANT

1497
01:22:03,652 --> 01:22:06,721
HEPATITIS E VACCINES DEVELOPED.

1498
01:22:06,788 --> 01:22:11,726
ALL DERIVED FROM THE PROTEIN AND

1499
01:22:11,793 --> 01:22:14,229
CLINICAL EFFICACY HAS BEEN

1500
01:22:14,296 --> 01:22:15,930
DEMONSTRATED WITH ALL THREE

1501
01:22:15,997 --> 01:22:16,197
PRODUCTS.

1502
01:22:16,264 --> 01:22:19,567
THE FIRST WAS CO-JOINTLY

1503
01:22:19,634 --> 01:22:30,178
DEVELOPED BY GLAXOSMITHKLINE AND

1504
01:22:35,150 --> 01:22:36,618
NIAID AND THE VACCINE DOESN'T GO

1505
01:22:36,685 --> 01:22:38,019
FURTHER BECAUSE OF ECONOMIC

1506
01:22:38,086 --> 01:22:40,822
CONSIDERATIONS AND ANOTHER WAS A

1507
01:22:40,889 --> 01:22:42,157
VACCINE DEVELOPED IN CHINA AND

1508
01:22:42,223 --> 01:22:45,827
DEMONSTRATED EFFICACY IN A PHASE

1509
01:22:45,894 --> 01:22:48,096
1 TRIAL BUT DIDN'T MOVE FORWARD

1510
01:22:48,163 --> 01:22:52,667
BECAUSE OF ECONOMIC

1511
01:22:52,734 --> 01:22:54,903
CONSIDERATIONS AND THE THIRD

1512
01:22:54,969 --> 01:22:58,473
VACCINE HEV-239 WAS DEMONSTRATE

1513
01:22:58,540 --> 01:23:01,076
AND CURRENTLY LICENSED IN CHINA

1514
01:23:01,142 --> 01:23:03,144
AND PAKISTAN.

1515
01:23:03,211 --> 01:23:04,612
THIS IS A DATA FROM THE

1516
01:23:04,679 --> 01:23:09,250
RANDOMIZED TRIAL THAT LED TO THE

1517
01:23:09,317 --> 01:23:10,485
APPROVAL OF THIS VACCINE THE

1518
01:23:10,552 --> 01:23:15,390
VACCINE WAS TESTED IN OVER 100

1519
01:23:15,457 --> 01:23:19,227
ADULTS AND PATIENT RANDOMIZED TO

1520
01:23:19,294 --> 01:23:23,732
RECEIVE THE MEDICATION OR

1521
01:23:23,798 --> 01:23:25,667
PLACEBO AND HEPATITIS B VIRUS

1522
01:23:25,734 --> 01:23:29,738
AND THE PRIMARY END POINT WAS

1523
01:23:29,804 --> 01:23:31,773
AFTER THE LAST DOSE OF THE

1524
01:23:31,840 --> 01:23:36,945
VACCINE IN THE PROTOCOL

1525
01:23:37,011 --> 01:23:43,284
ANALYSIS, 15 CASES OF HEPATITIS

1526
01:23:43,351 --> 01:23:46,388
C OCCURRED AND THE INTENTION TO

1527
01:23:46,454 --> 01:23:49,124
TREAT ANALYSIS THERE WERE 22

1528
01:23:49,190 --> 01:23:52,494
CASES AND 21 OCCURRED IN THE

1529
01:23:52,560 --> 01:23:53,995
PLACEBO GROUP COMPARED TO ONE IN

1530
01:23:54,062 --> 01:23:57,098
THE VACCINE GROUP FOR A VACCINE

1531
01:23:57,165 --> 01:24:03,037
EFFICACY OF 95%.

1532
01:24:03,104 --> 01:24:05,607
THIS FOLLOW UP WAS EXTENDED FOR

1533
01:24:05,673 --> 01:24:07,609
4.5 YEARS AND 60 CASES OF

1534
01:24:07,675 --> 01:24:09,711
HEPATITIS E WERE IDENTIFIED.

1535
01:24:09,778 --> 01:24:10,912
SEVEN IN THE VACCINE GROUP AND

1536
01:24:10,979 --> 01:24:14,449
53 IN THE CONTROL GROUP FOR AN

1537
01:24:14,516 --> 01:24:17,519
OVER ALL VACCINE EFFICACY OF 87%

1538
01:24:17,585 --> 01:24:21,656
OVER THE 4.5 YEAR FOLLOW UP.

1539
01:24:21,723 --> 01:24:24,092
AND 87% OF THOSE WHO RECEIVED

1540
01:24:24,159 --> 01:24:26,227
THREE DOSES OF THE VACCINE

1541
01:24:26,294 --> 01:24:28,229
MAINTAINED ANTIBODY UP TO 4.5

1542
01:24:28,296 --> 01:24:29,197
YEARS LATER INDICATING THE

1543
01:24:29,264 --> 01:24:36,438
VACCINE IS VERY DURABLE.

1544
01:24:36,504 --> 01:24:41,709
ONE WOULD ASK WHY ISN'T THE

1545
01:24:41,776 --> 01:24:44,112
VACCINE BEING USE MORE

1546
01:24:44,179 --> 01:24:44,446
WIDESPREAD.

1547
01:24:44,512 --> 01:24:46,047
THERE'S A NUMBER OF BARRIERS TO

1548
01:24:46,114 --> 01:24:47,115
VACCINE USE.

1549
01:24:47,182 --> 01:24:50,084
FIRST IS THE LIMITED AWARENESS

1550
01:24:50,151 --> 01:24:52,554
REGARDING HEPATITIS E AND THE

1551
01:24:52,620 --> 01:24:54,088
AVAILABLE VACCINE AMONG

1552
01:24:54,155 --> 01:24:55,690
REGULATORS, POLICY MAKERS AND

1553
01:24:55,757 --> 01:24:57,559
COMMUNITIES THAT ARE PRONE TO

1554
01:24:57,625 --> 01:25:01,696
LARGE OUTBREAKS.

1555
01:25:01,763 --> 01:25:03,398
THERE'S ALSO LIMITED DATA ON

1556
01:25:03,465 --> 01:25:08,470
VACCINE EFFICACY ONLY ONE STUDY

1557
01:25:08,536 --> 01:25:13,107
FROM AN OUTBREAK DATA AND

1558
01:25:13,174 --> 01:25:14,876
THERE'S LIMITED INFORMATION ON

1559
01:25:14,943 --> 01:25:17,712
PREGNANT WOMEN AND YOUNGER AGE

1560
01:25:17,779 --> 01:25:19,280
GROUPS AND THE LAST THREE

1561
01:25:19,347 --> 01:25:21,416
FACTORS HAVE BEEN THE MAJOR

1562
01:25:21,483 --> 01:25:24,686
REASONS W.H.O. HASN'T BEEN A

1563
01:25:24,752 --> 01:25:26,387
GREATER PROPONENT OF

1564
01:25:26,454 --> 01:25:27,789
RECOMMENDING MORE WIDESPREAD USE

1565
01:25:27,856 --> 01:25:30,058
OF THE VACCINE AND THERE'S

1566
01:25:30,124 --> 01:25:31,359
UNCERTAINTY ABOUT THE VACCINE

1567
01:25:31,426 --> 01:25:32,327
SUPPLY.

1568
01:25:32,393 --> 01:25:37,732
TO SUMMARIZE FOR YOU IN RESOURCE

1569
01:25:37,799 --> 01:25:40,768
LIMITED AREAS HEPATITIS E IS

1570
01:25:40,835 --> 01:25:43,471
PRIMARILY WATERBORNE WITH

1571
01:25:43,538 --> 01:25:46,441
HEPATITIS RELATED TO INFECTION

1572
01:25:46,508 --> 01:25:49,544
WITH PHENOTYPES 1 AND 2 AND IN

1573
01:25:49,611 --> 01:25:50,845
HIGH INCOME COUNTRIES IT'S

1574
01:25:50,912 --> 01:25:52,447
CONSIDERED A ZOONOTIC INFECTION

1575
01:25:52,514 --> 01:25:55,550
CAUSING ACUTE AND CHRONIC

1576
01:25:55,617 --> 01:25:57,385
INFECTION AND CHRONIC INFECTION

1577
01:25:57,452 --> 01:26:00,655
IS ONLY ASSOCIATED WITH GENOTYPE

1578
01:26:00,722 --> 01:26:02,657
3 NEVER 1 OR 2.

1579
01:26:02,724 --> 01:26:04,926
AND A WANTED TO HIGHLIGHT A FEW

1580
01:26:04,993 --> 01:26:09,998
UNRESOLVED ISSUES I THINK ARE

1581
01:26:10,064 --> 01:26:15,904
AREAS FOR FURTHER INVESTIGATION

1582
01:26:15,970 --> 01:26:17,405
WE DON'T KNOW HOW TO EXPLAIN THE

1583
01:26:17,472 --> 01:26:20,942
HIGH MORTALITY IN PREGNANT WOMEN

1584
01:26:21,009 --> 01:26:24,212
OR WHAT ACCOUNTS FOR THE

1585
01:26:24,279 --> 01:26:28,216
MANIFESTATIONS OF GENOTYPE 3 AND

1586
01:26:28,283 --> 01:26:30,685
DON'T KNOW THE OPTIMAL THERAPY

1587
01:26:30,752 --> 01:26:33,121
AND MORE EFFECTIVE THERAPIES

1588
01:26:33,187 --> 01:26:35,189
WOULD BE DESIRABLE.

1589
01:26:35,256 --> 01:26:36,491
THERE'S DEBATE GOING ON WHETHER

1590
01:26:36,558 --> 01:26:39,727
THE BLOOD SUPPLY SHOULD BE

1591
01:26:39,794 --> 01:26:40,028
SCREENED.

1592
01:26:40,094 --> 01:26:42,764
AND THIS PARTLY RELATED TO WHAT

1593
01:26:42,830 --> 01:26:44,165
THE PREVALENCE IS IN YOUR

1594
01:26:44,232 --> 01:26:46,734
PARTICULAR REGION.

1595
01:26:46,801 --> 01:26:48,603
WE NEED BETTER DIAGNOSTIC TESTS

1596
01:26:48,670 --> 01:26:51,139
AS HIGHLIGHTED AND NEEDS TO BE

1597
01:26:51,205 --> 01:26:53,241
MORE STUDIES OF VACCINE EFFICACY

1598
01:26:53,308 --> 01:26:55,143
IN OTHER REGIONS AND OTHER

1599
01:26:55,209 --> 01:26:56,277
POPULATIONS AN TO DETERMINE

1600
01:26:56,344 --> 01:26:58,513
WHETHER THERE'S CROSS-PROTECTION

1601
01:26:58,580 --> 01:26:59,514
BETWEEN THE VACCINE OR

1602
01:26:59,581 --> 01:26:59,814
GENOTYPES.

1603
01:26:59,881 --> 01:27:01,249
SO I THINK I'LL STOP IT THERE

1604
01:27:01,316 --> 01:27:03,217
AND HAPPY TO TAKE ANY QUESTIONS.

1605
01:27:03,284 --> 01:27:03,785
THANK YOU SO MUCH FOR YOUR

1606
01:27:03,851 --> 01:27:11,593
ATTENTION.

1607
01:27:11,659 --> 01:27:14,462
>> THANK YOU VERY MUCH.

1608
01:27:14,529 --> 01:27:19,601
THERE'S A MICROPHONE IN THE

1609
01:27:19,667 --> 01:27:29,877
AISLE THERE.

1610
01:27:58,373 --> 01:27:59,707
BASED ON YOUR RESEARCH WHAT

1611
01:27:59,774 --> 01:28:00,608
GUIDELINES WOULD YOU RECOMMEND

1612
01:28:00,675 --> 01:28:01,709
FOR THE GENERAL PUBLIC FOR

1613
01:28:01,776 --> 01:28:06,648
TESTING AND VACCINATION?

1614
01:28:06,714 --> 01:28:09,484
>> I THINK IT'S RELATIVELY

1615
01:28:09,550 --> 01:28:09,851
STRAIGHTFORWARD.

1616
01:28:09,917 --> 01:28:12,353
TO REPEAT THE QUESTION, WHAT GID

1617
01:28:12,420 --> 01:28:14,055
LINES WOULD BE RECOMMENDED IF

1618
01:28:14,122 --> 01:28:18,292
THE CURRENT GUIDELINES ARE

1619
01:28:18,359 --> 01:28:18,660
SUBOPTIMAL.

1620
01:28:18,726 --> 01:28:20,428
EVERYONE IN HEPATITIS B SHOULD

1621
01:28:20,495 --> 01:28:25,099
BE CHECKED FOR HEPATITIS E ONCE

1622
01:28:25,166 --> 01:28:26,000
AND VACCINATION HEPATITIS B

1623
01:28:26,067 --> 01:28:29,103
SHOULD BE UNIVERSAL.

1624
01:28:29,170 --> 01:28:38,212
VERY EASY.

1625
01:28:38,279 --> 01:28:42,316
>> IT'S ALSO BEEN ASKED WHETHER

1626
01:28:42,383 --> 01:28:47,455
SAMPLES OF THE BLOOD BANK FROM

1627
01:28:47,522 --> 01:28:50,625
YEARS GONE BY HAVE BEEN TESTED

1628
01:28:50,692 --> 01:28:56,130
TO GIVE SOME CLUE AS TO HOW LONG

1629
01:28:56,197 --> 01:28:58,599
THEY'VE BEEN IN THE CIRCULATION

1630
01:28:58,666 --> 01:29:03,905
AND NOT PREVIOUSLY RECOGNIZED.

1631
01:29:03,971 --> 01:29:07,809
DO YOU WANT TO COMMENT?

1632
01:29:07,875 --> 01:29:11,079
>> I MENTIONED HOW HARVEY ALTER

1633
01:29:11,145 --> 01:29:13,081
LOOKED AT 1,000 BLOOD DONOR

1634
01:29:13,147 --> 01:29:17,085
SAMPLES AND THE PREVALENCE OF

1635
01:29:17,151 --> 01:29:23,591
ANTIBODY TO HEPATITIS B, IGG WAS

1636
01:29:23,658 --> 01:29:27,595
20% BUT NONE WERE FOUND TO BE

1637
01:29:27,662 --> 01:29:31,099
HEPATITIS B RNA AND THAT FIGURE

1638
01:29:31,165 --> 01:29:33,534
RESEMBLES THE PREVALENCE IN THE

1639
01:29:33,601 --> 01:29:35,236
U.S. GENERAL POPULATION BASED ON

1640
01:29:35,303 --> 01:29:37,071
THE NHANES STUDY DONE IN 2010

1641
01:29:37,138 --> 01:29:44,946
AROUND THE SAME TIME.

1642
01:29:45,012 --> 01:29:47,615
>> TO ADDRESS THE HEPATITIS B IN

1643
01:29:47,682 --> 01:29:49,917
TERMS OF SUBTEXT, HOW LONG HAS

1644
01:29:49,984 --> 01:29:51,753
IT BEEN IN CIRCULATION?

1645
01:29:51,819 --> 01:29:52,520
IT'S INTERESTING.

1646
01:29:52,587 --> 01:29:56,424
IF YOU'RE GOING TO ISOLATED

1647
01:29:56,491 --> 01:29:58,326
POPULATIONS IN THE AMAZON AND

1648
01:29:58,392 --> 01:30:00,428
GLOBALLY, POPULATIONS THAT HAVE

1649
01:30:00,495 --> 01:30:02,463
HAD NO CONTACT FOR THOUSANDS OF

1650
01:30:02,530 --> 01:30:05,767
YEARS WITH OTHER POPULATIONS,

1651
01:30:05,833 --> 01:30:11,372
YOU FIND HEPATITIS B AND D.

1652
01:30:11,439 --> 01:30:12,940
SO HEPATITIS B HAS BEEN AROUND

1653
01:30:13,007 --> 01:30:14,776
AS LONG AS HUMANS HAVE AND

1654
01:30:14,842 --> 01:30:17,311
HEPATITIS D GOES BACK PRETTY

1655
01:30:17,378 --> 01:30:23,885
FAR.

1656
01:30:23,951 --> 01:30:26,621
>> WHAT DO WE KNOW ABOUT

1657
01:30:26,687 --> 01:30:27,455
RETENTION RATES --

1658
01:30:27,522 --> 01:30:30,324
>> WELL, I WANTED TO ASK A

1659
01:30:30,391 --> 01:30:33,127
COUPLE QUESTIONS.

1660
01:30:33,194 --> 01:30:35,596
FIRST, TO BOTH PRESENTERS, WHAT

1661
01:30:35,663 --> 01:30:40,768
IS YOUR SPECULATION WITH REGARD

1662
01:30:40,835 --> 01:30:43,971
TO ARE THERE OTHER ISSUES NOW

1663
01:30:44,038 --> 01:30:46,207
GONE TO BE DISCOVERED AND WE'VE

1664
01:30:46,274 --> 01:30:47,208
GONE THROUGH FIVE LETTERS OF THE

1665
01:30:47,275 --> 01:30:48,810
ALPHABET AND THE SIXTH IS

1666
01:30:48,876 --> 01:30:59,420
PERHAPS BECKONING FOR DISCOVERY.

1667
01:31:04,425 --> 01:31:08,830
AND WHAT HAPPENED TO BERIANI WHO

1668
01:31:08,896 --> 01:31:13,100
DEMONSTRATE THE LIKELY

1669
01:31:13,167 --> 01:31:14,802
INFECTIOUS AGENT FOR HEPATITIS

1670
01:31:14,869 --> 01:31:14,936
D.

1671
01:31:15,002 --> 01:31:17,071
I HOPE HE SURVIVED.

1672
01:31:17,138 --> 01:31:21,108
>> HE SURVIVED.

1673
01:31:21,175 --> 01:31:24,879
HE WAS ACTUALLY QUITE SICK BUT

1674
01:31:24,946 --> 01:31:35,456
HAD A SELF-LIMITING HEPATITIS.

1675
01:31:36,123 --> 01:31:37,725
>> HE LOVED TELLING THE STORY

1676
01:31:37,792 --> 01:31:40,661
AND ONE OF THE THINGS HE TOLD US

1677
01:31:40,728 --> 01:31:42,230
WAS HE CHOSE CHOCOLATE ICE CREAM

1678
01:31:42,296 --> 01:31:45,700
SO HE WOULDN'T HAVE TO SEE WHAT

1679
01:31:45,766 --> 01:31:47,535
HE WAS EATING AND HE WAS --

1680
01:31:47,602 --> 01:31:51,072
THERE WERE AMUSING THINGS ABOUT

1681
01:31:51,138 --> 01:31:51,339
HIM.

1682
01:31:51,405 --> 01:31:53,608
FOR MANY REASONS HE WAS A HUGE

1683
01:31:53,674 --> 01:31:57,378
GUY WITH A LOT OF CHARISMA AND

1684
01:31:57,445 --> 01:31:58,746
PERSONALITY.

1685
01:31:58,813 --> 01:32:00,047
DO YOU WANT IT TAKE THE NEXT

1686
01:32:00,114 --> 01:32:04,518
QUESTION?

1687
01:32:04,585 --> 01:32:13,394
>> THE FIRST QUESTION WAS WERE

1688
01:32:13,461 --> 01:32:15,663
THERE OTHER VIRUSES WAITING TO

1689
01:32:15,730 --> 01:32:18,165
BE DISCOVERED AND THERE IS

1690
01:32:18,232 --> 01:32:23,504
HEPATITIS G AND NONE

1691
01:32:23,571 --> 01:32:24,906
CONVINCINGLY SHOWN TO BE RELATED

1692
01:32:24,972 --> 01:32:27,441
TO TRANSFUSION RELATED

1693
01:32:27,508 --> 01:32:28,009
HEPATITIS.

1694
01:32:28,075 --> 01:32:29,076
THEY JUST OCCUR IN THE

1695
01:32:29,143 --> 01:32:32,046
POPULATION BUT PROBABLY DON'T

1696
01:32:32,113 --> 01:32:35,850
CAUSE ANY DISEASE.

1697
01:32:35,917 --> 01:32:40,154
AS A TESTAMENT THE TRANSFUSION

1698
01:32:40,221 --> 01:32:42,256
OF HEPATITIS IS EXCEEDINGLY RARE

1699
01:32:42,323 --> 01:32:45,092
AND IF THERE'S VIRUSES TO BE

1700
01:32:45,159 --> 01:32:46,694
IDENTIFIED THEY WON'T BE A

1701
01:32:46,761 --> 01:32:47,962
SIGNIFICANT COURSE FOR

1702
01:32:48,029 --> 01:32:50,364
TRANSFUSION RELATED HEPATITIS.

1703
01:32:50,431 --> 01:32:53,734
MAYBE THEO WANTS TO ADD.

1704
01:32:53,801 --> 01:32:56,604
>> THERE WAS HEPATITIS F BUT IT

1705
01:32:56,671 --> 01:32:58,606
TURNED OUT NOT TO BE TRUE.

1706
01:32:58,673 --> 01:33:00,875
>> THAT WAS GOING TO BE MY NEXT

1707
01:33:00,942 --> 01:33:01,142
QUESTION.

1708
01:33:01,208 --> 01:33:03,311
>> IT'S BY THE FRENCH AND TURNED

1709
01:33:03,377 --> 01:33:09,016
OUT NOT TO BE THE CASE AND THE

1710
01:33:09,083 --> 01:33:11,018
VARIOUS WAS TRANSMITTED FROM

1711
01:33:11,085 --> 01:33:14,121
GENERAL SURGEON BUT IT WAS A

1712
01:33:14,188 --> 01:33:20,294
PRIMATE VIRUS GBV.

1713
01:33:20,361 --> 01:33:23,764
I AGREE WITH MARC BUT THERE'S

1714
01:33:23,831 --> 01:33:25,533
ONE PIECE OF DATA WHICH LOOKED

1715
01:33:25,599 --> 01:33:31,339
AT AN OUTBREAK ON AN ISLAND OFF

1716
01:33:31,405 --> 01:33:34,175
THE COAST OF INDIA COULD NOT

1717
01:33:34,241 --> 01:33:37,979
IDENTIFY THE NON-HEPATITIS VIRUS

1718
01:33:38,045 --> 01:33:41,015
AND SEEMED TO SPREAD CONSISTENT

1719
01:33:41,082 --> 01:33:42,450
WITH THE HEPATITIS VIRUS AND

1720
01:33:42,516 --> 01:33:44,652
MAYBE SOME ARE LOOKING TO BE

1721
01:33:44,719 --> 01:33:45,119
DISCOVERED.

1722
01:33:45,186 --> 01:33:48,155
>> MAYBE SOMEONE IN THE FUTURE.

1723
01:33:48,222 --> 01:33:49,256
OR THE ROOM.

1724
01:33:49,323 --> 01:33:51,926
YOU SAID THE F WAS FROM A FRENCH

1725
01:33:51,993 --> 01:33:53,928
INVESTIGATOR AND THE G A GERMAN.

1726
01:33:53,995 --> 01:33:57,098
>> YES.

1727
01:33:57,164 --> 01:34:07,541
>> THAT'S INTERESTING.

1728
01:34:13,948 --> 01:34:16,083
>> WE STILL DON'T KNOW THE CAUSE

1729
01:34:16,150 --> 01:34:17,451
OF HEPATITIS.

1730
01:34:17,518 --> 01:34:20,388
>> THERE WAS AN OUTBREAK OF

1731
01:34:20,454 --> 01:34:21,822
HEPATITIS TWO YEARS AGO THAT

1732
01:34:21,889 --> 01:34:22,990
OCCURRED PRIMARILY IN CHILDREN

1733
01:34:23,057 --> 01:34:25,860
AND THERE WERE TWO CHARGE

1734
01:34:25,926 --> 01:34:27,395
COHORTS DESCRIBED.

1735
01:34:27,461 --> 01:34:28,429
BOTH FROM BIRMINGHAM, ALABAMA

1736
01:34:28,496 --> 01:34:38,706
AND ENGLAND.

1737
01:34:55,623 --> 01:34:57,358
THERE ARE MORE CASES BEING

1738
01:34:57,425 --> 01:34:58,059
IDENTIFIED.

1739
01:34:58,125 --> 01:35:06,200
WE HAVE A QUESTION WITH OTHER

1740
01:35:06,267 --> 01:35:08,803
HEPATOVIRUSES HAVE THE CAPACITY

1741
01:35:08,869 --> 01:35:19,246
TO ACCEPT HEPATITIS D.

1742
01:35:24,552 --> 01:35:27,321
>> ARE THERE OTHER VIRUSES THAT

1743
01:35:27,388 --> 01:35:29,924
CAN TRANSMIT HEPATITIS D.

1744
01:35:29,990 --> 01:35:31,659
IT DOESN'T SEEM TO BE THE CASE

1745
01:35:31,725 --> 01:35:36,263
AND THERE IS A CASE LOOKING AT

1746
01:35:36,330 --> 01:35:46,407
SC

1747
01:35:46,674 --> 01:35:46,974
SCHOGREN'S SYNDROME.

1748
01:35:47,041 --> 01:35:47,741
>> WE HAVE A QUESTION AS TO WHAT

1749
01:35:47,808 --> 01:35:50,344
DO WE KNOW ABOUT THE MUTATION

1750
01:35:50,411 --> 01:35:58,786
RATE OF THESE VIRUSES?

1751
01:35:58,853 --> 01:36:01,822
>> IT HAS A ROD-LIKE STRUCTURE.

1752
01:36:01,889 --> 01:36:05,826
IT'S ALMOST LIKE A DNA MOLECULE

1753
01:36:05,893 --> 01:36:08,896
THOUGH IT'S RNA AND THERE'S

1754
01:36:08,963 --> 01:36:10,564
EXTENSIVE BASE PAIRING AND IF

1755
01:36:10,631 --> 01:36:12,633
THERE IS ONE THAT NEEDS TO BE

1756
01:36:12,700 --> 01:36:15,870
COMPENSATED ON THE OTHER SIDE,

1757
01:36:15,936 --> 01:36:17,037
THERE ARE DIFFERENT GENOTYPES

1758
01:36:17,104 --> 01:36:19,173
AND IT'S AN RNA VIRUS AND IT'S

1759
01:36:19,240 --> 01:36:21,275
VERY LIMITED.

1760
01:36:21,342 --> 01:36:23,377
IT'S NOTHING LIKE HEPATITIS C.

1761
01:36:23,444 --> 01:36:26,113
>> SAME FOR HEPATITIS C AS AN

1762
01:36:26,180 --> 01:36:29,083
RNA VIRUS ONE WOULD EXPECT

1763
01:36:29,150 --> 01:36:31,652
DIFFERENT MUTATIONS ARE PRODUCED

1764
01:36:31,719 --> 01:36:35,623
DURING REPLICATION AND THERE ARE

1765
01:36:35,689 --> 01:36:37,758
SPECIES BUT THERE'S ESSENTIALLY

1766
01:36:37,825 --> 01:36:39,627
FOUR MAJOR GENOTYPES, 1 THROUGH

1767
01:36:39,693 --> 01:36:39,894
4.

1768
01:36:39,960 --> 01:36:42,062
I'M NOT AWARE OF ANY NEW

1769
01:36:42,129 --> 01:36:45,065
EMERGING GENOTYPES THAT HAVE

1770
01:36:45,132 --> 01:36:46,066
BEEN IDENTIFIED.

1771
01:36:46,133 --> 01:36:47,468
OR DIFFERENT DISEASES CAUSED BY

1772
01:36:47,535 --> 01:36:57,778
SUB VARIANTS.

1773
01:37:03,217 --> 01:37:06,787
>> IS THERE A MODE OF ENTRY INTO

1774
01:37:06,854 --> 01:37:10,457
THOSE CELLS SIMILAR TO THE

1775
01:37:10,524 --> 01:37:10,958
TRANSPORTER?

1776
01:37:11,025 --> 01:37:12,193
IS THAT KNOWN?

1777
01:37:12,259 --> 01:37:15,196
>> YOU'RE ASKING ABOUT HEPATITIS

1778
01:37:15,262 --> 01:37:20,601
B ENTERING GROUND SQUIRRELS OR

1779
01:37:20,668 --> 01:37:21,068
HERONS?

1780
01:37:21,135 --> 01:37:23,204
IT'S THE BILE SALT TO ACID

1781
01:37:23,270 --> 01:37:27,474
TRANSPORTER AND YOU'RE THE BILE

1782
01:37:27,541 --> 01:37:29,710
EXPERT, DR. ARIAS IS, FOR THOSE

1783
01:37:29,777 --> 01:37:33,781
WHO DON'T KNOW AMONGST OTHER

1784
01:37:33,847 --> 01:37:36,383
THINGS AND THEY FOUND FANTASTIC

1785
01:37:36,450 --> 01:37:37,685
STUDIES FROM THE SAN DIEGO ZOO

1786
01:37:37,751 --> 01:37:42,756
LOOKING AT BILE IN MULTIPLE

1787
01:37:42,823 --> 01:37:46,026
SPECIES SO, YES.

1788
01:37:46,093 --> 01:37:46,660
>> AND FOR HEPATITIS E IS THAT

1789
01:37:46,727 --> 01:37:51,865
SIMILAR?

1790
01:37:51,932 --> 01:37:53,734
>> WE DON'T YET WHAT THE

1791
01:37:53,801 --> 01:37:56,103
RECEPTOR IS FOR HEPATITIS E.

1792
01:37:56,170 --> 01:38:03,811
THAT'S YET TO BE IDENTIFIED.

1793
01:38:03,877 --> 01:38:05,412
ONE THING I'D MENTION TO

1794
01:38:05,479 --> 01:38:08,382
COMPLEMENT THEO'S ANSWER IS THE

1795
01:38:08,449 --> 01:38:13,087
TRANSPORTING POLY PEPTIDE IS

1796
01:38:13,153 --> 01:38:15,055
RESPONSIBLE FOR THE TROPISM OF

1797
01:38:15,122 --> 01:38:20,094
HEPATITIS B THAT'S WHY IT'S ONLY

1798
01:38:20,160 --> 01:38:25,099
SIGN APES AND HUMANS.

1799
01:38:25,165 --> 01:38:28,102
>> WE HAVE A QUESTION WHETHER --

1800
01:38:28,168 --> 01:38:29,536
>> NOT THE HUMAN VIRUS.

1801
01:38:29,603 --> 01:38:31,505
>> YES, SORRY.

1802
01:38:31,572 --> 01:38:33,974
>> ARE EITHER OF THESE VIRUSES

1803
01:38:34,041 --> 01:38:42,516
SECRETED IN HUMAN MILK?

1804
01:38:42,583 --> 01:38:46,186
>> I'M NOT AWARE OF HEPATITIS E

1805
01:38:46,253 --> 01:38:49,023
BEING SECRETED IN HUMAN MILK.

1806
01:38:49,089 --> 01:38:50,791
THERE WAS A PAPER PUBLISHED LAST

1807
01:38:50,858 --> 01:38:55,296
YEAR SAYING IT'S SECRETED IN

1808
01:38:55,362 --> 01:38:56,730
URINE AND URINE MAY BE

1809
01:38:56,797 --> 01:38:58,565
CONCENTRATED THERE SO DETECTION

1810
01:38:58,632 --> 01:39:00,901
RATES MAY BE HIGHER IN URINE

1811
01:39:00,968 --> 01:39:03,137
THAN IN STOOL OR SERUM BUT I'M

1812
01:39:03,203 --> 01:39:05,706
NOT AWARE OF STUDIES LOOKING AT

1813
01:39:05,773 --> 01:39:12,646
WHETHER IT'S TRANSMITTED IN MOO

1814
01:39:12,713 --> 01:39:15,482
-- MATERNAL MILK.

1815
01:39:15,549 --> 01:39:16,784
>> IT'S NOT THOUGHT TO BE

1816
01:39:16,850 --> 01:39:19,320
SIGNIFICANT AND INFANTS ARE

1817
01:39:19,386 --> 01:39:21,422
SCREENED AND VACCINATED IN THE

1818
01:39:21,488 --> 01:39:31,231
WEST.

1819
01:39:31,298 --> 01:39:34,535
>> THIS IS THE LAST QUESTION AND

1820
01:39:34,601 --> 01:39:43,644
WHAT THE QUESTIONER IS ASKING IS

1821
01:39:43,711 --> 01:39:45,813
BOTH HEPATITIS D AND E WERE

1822
01:39:45,879 --> 01:39:49,083
BASICALLY DISCOVERED BECAUSE OF

1823
01:39:49,149 --> 01:39:52,353
PATIENTS WHO WERE SICK WITH

1824
01:39:52,419 --> 01:39:55,622
HEPATITIS AND IN THE CASE OF E,

1825
01:39:55,689 --> 01:39:57,324
DID NOT HAVE ANY OF THE KNOWN

1826
01:39:57,391 --> 01:40:00,427
VIRUSES AT THE TIME SO THE

1827
01:40:00,494 --> 01:40:02,763
QUESTIONER IS ASKING WHETHER IT

1828
01:40:02,830 --> 01:40:07,434
IS LIKELY THAT THERE ARE OTHER

1829
01:40:07,501 --> 01:40:18,045
HEPATITIS VIRUSES OUT THERE AND

1830
01:40:21,348 --> 01:40:25,552
ARE THERE WAYS OF ANTICIPATING

1831
01:40:25,619 --> 01:40:30,858
THE PRESENCE AND IF THEY'RE

1832
01:40:30,924 --> 01:40:32,693
CAPABLE OF CAUSING DISEASE.

1833
01:40:32,760 --> 01:40:36,597
ARE THERE EFFORTS TO ANTICIPATE

1834
01:40:36,663 --> 01:40:40,300
THE POSSIBILITY OF ADDITIONAL

1835
01:40:40,367 --> 01:40:46,640
INFECTIOUS HEPATITIS VIRUSS?

1836
01:40:46,707 --> 01:40:49,076
-- VIRUSES?

1837
01:40:49,143 --> 01:40:51,345
>> WE THOUGHT FOR A LONG TIME WE

1838
01:40:51,412 --> 01:40:52,780
WERE DONE AND THEN COVID CAME

1839
01:40:52,846 --> 01:40:54,381
ALONG AND TAUGHT US THERE ARE

1840
01:40:54,448 --> 01:40:57,618
OTHER VIRUSES IN OTHER PLACES.

1841
01:40:57,684 --> 01:41:02,122
SO HIV IS A SIMILAR STORY.

1842
01:41:02,189 --> 01:41:04,158
SO, I THINK WITH THE WAY THINGS

1843
01:41:04,224 --> 01:41:07,561
ARE RIGHT NOW AS WE SAID

1844
01:41:07,628 --> 01:41:11,098
PREVIOUSLY THERE'S NO OTHER

1845
01:41:11,165 --> 01:41:12,966
PREVIOUS FECAL OR TRANSFUSION

1846
01:41:13,033 --> 01:41:14,535
TRANSMITTED VIRUS BUT THE

1847
01:41:14,601 --> 01:41:16,503
EXHILARATING THING ABOUT

1848
01:41:16,570 --> 01:41:17,137
MEDICINE IS THERE'S ALWAYS

1849
01:41:17,204 --> 01:41:21,074
SOMETHING NEW TO BE LEARNED.

1850
01:41:21,141 --> 01:41:24,044
>> WELL, WE HAVE NO FURTHER

1851
01:41:24,111 --> 01:41:27,448
QUESTIONS SO I WANT TO ON BEHALF

1852
01:41:27,514 --> 01:41:29,616
OF EVERYONE HERE AND THE AT THE

1853
01:41:29,683 --> 01:41:33,086
NIH WHO ARE WATCHING ONLINE AND

1854
01:41:33,153 --> 01:41:37,090
AROUND THE WORLD WANT TO THANK

1855
01:41:37,157 --> 01:41:40,561
YOU BOTH FOR BRINGING TO OUR

1856
01:41:40,627 --> 01:41:43,130
ATTENTION THESE EXTRAORDINARY

1857
01:41:43,197 --> 01:41:44,798
DEVELOPMENTS WHICH I DON'T THINK

1858
01:41:44,865 --> 01:41:46,567
WERE WIDELY KNOWN AMONGST THE

1859
01:41:46,633 --> 01:41:51,638
GENERAL MEDICAL PUBLIC AND

1860
01:41:51,705 --> 01:41:54,508
PERHAPS AMONGST OUR STUDENTS SO

1861
01:41:54,575 --> 01:41:55,709
THANK YOU VERY MUCH FOR VERY

1862
01:41:55,776 --> 01:41:57,044
EXQUISITE

1863
01:41:57,110
PRESENTATIONS