1 00:00:09,041 --> 00:00:11,243 WELCOME TO THE CLINICAL CENTER GRAND ROUNDS, 2 00:00:11,243 --> 00:00:15,047 A WEEKLY SERIES OF EDUCATIONAL LECTURES FOR PHYSICIANS AND 3 00:00:15,047 --> 00:00:17,683 HEALTH CARE PROFESSIONALS BROADCAST FROM THE CLINICAL 4 00:00:17,683 --> 00:00:20,653 CENTER AT THE NATIONAL INSTITUTES OF HEALTH IN 5 00:00:20,653 --> 00:00:22,454 BETHESDA, MD. 6 00:00:22,454 --> 00:00:25,991 THE NIH CLINICAL CENTER IS THE WORLD'S LARGEST HOSPITAL TOTALLY 7 00:00:25,991 --> 00:00:29,695 DEDICATED TO INVESTIGATIONAL RESEARCH AND LEADS THE GLOBAL 8 00:00:29,695 --> 00:00:32,631 EFFORT IN TRAINING TODAY'S INVESTIGATORS AND DISCOVERING 9 00:00:32,631 --> 00:00:34,800 TOMORROW'S CURES. 10 00:00:34,800 --> 00:00:44,113 LEARN MORE BY VISITING US ONLINE AT HTTP://CLINICALCENTER.NIH.GOV 11 00:00:44,113 --> 00:00:44,513 GOOD AFTERNOON. 12 00:00:44,513 --> 00:00:48,451 WELCOME TO TODAY'S CLINICAL 13 00:00:48,451 --> 00:00:49,985 CENTER GROUND ROUNDS FEATURING 14 00:00:49,985 --> 00:00:54,356 THIS YEAR'S JOHN LAWS DECKER 15 00:00:54,356 --> 00:00:55,124 LECTURE. 16 00:00:55,124 --> 00:00:56,959 IT'S 50561. 17 00:00:56,959 --> 00:01:01,363 PLEASE TEXT THIS CODE TO JOHN 18 00:01:01,363 --> 00:01:03,332 HOPKINS. 19 00:01:03,332 --> 00:01:04,467 WE KINDLY INVITE YOU PROVIDE 20 00:01:04,467 --> 00:01:05,901 FEEDBACK BY SCANNING THE QR CODE 21 00:01:05,901 --> 00:01:06,836 ON THE CME SLIDE. 22 00:01:06,836 --> 00:01:09,238 FOR THOSE APPLYING FOR CME, YOU 23 00:01:09,238 --> 00:01:11,140 WILL RECEIVE A FEEDBACK SURVEY 24 00:01:11,140 --> 00:01:12,174 LINK VIA EMAIL. 25 00:01:12,174 --> 00:01:13,476 THE SURVEY WILL BE USED TO 26 00:01:13,476 --> 00:01:15,044 PROVIDE US IMPORTANT FEEDBACK 27 00:01:15,044 --> 00:01:17,379 ABOUT THIS PRESENTATION, ALLOWS 28 00:01:17,379 --> 00:01:19,548 YOU TO SUBMIT ANY SUGGESTIONS 29 00:01:19,548 --> 00:01:22,852 FOR FUTURE GRAND RAPIDS TOPICS. 30 00:01:22,852 --> 00:01:23,486 FOLLOWING THE PRESENTATION TODAY 31 00:01:23,486 --> 00:01:24,320 QUESTIONS FOR THE SPEAKERS WILL 32 00:01:24,320 --> 00:01:25,554 BE TAKEN FROM THE MICROPHONES IN 33 00:01:25,554 --> 00:01:26,722 THE AISLES. 34 00:01:26,722 --> 00:01:28,858 ADDIT 35 00:01:28,858 --> 00:01:35,397 ADDITIONALLY HAVE -- VIDEO 36 00:01:35,397 --> 00:01:38,033 CASTERS MAY SUBMIT QUESTIONS. 37 00:01:38,033 --> 00:01:39,969 THEY WILL BE ANSWERED IF TIME 38 00:01:39,969 --> 00:01:40,503 PERMITS. 39 00:01:40,503 --> 00:01:42,171 TODAY'S PRESENTATION IS THE 20TH 40 00:01:42,171 --> 00:01:45,174 ANNUAL JOHN LAWS DECKER MEMORIAL 41 00:01:45,174 --> 00:01:47,109 LECTURE AS PART OF OUR 42 00:01:47,109 --> 00:01:50,713 CONTEMPORARY CLINICAL MEDICINE 43 00:01:50,713 --> 00:01:51,146 SER 44 00:01:51,146 --> 00:01:51,380 SERIES. 45 00:01:51,380 --> 00:01:53,115 TODAY WE HONOR THE LEGACY OF 46 00:01:53,115 --> 00:01:55,451 DR. JOHN DECKER WHO SERVED AS 47 00:01:55,451 --> 00:01:59,488 NIH CLINICAL DIRECTOR IN 1983 TO 48 00:01:59,488 --> 00:02:00,289 1990. 49 00:02:00,289 --> 00:02:07,096 DURING DR. DECKER'S TENURE 50 00:02:07,096 --> 00:02:08,898 INCLUDES THE CLINICAL USE OF 51 00:02:08,898 --> 00:02:11,400 MAGNETIC IMAGES AND MARSHALLS OF 52 00:02:11,400 --> 00:02:13,269 RESOURCES FOR AIDS RESEARCH. 53 00:02:13,269 --> 00:02:15,037 I'M HONORED AND PLEASED TO 54 00:02:15,037 --> 00:02:16,171 WELCOME THE DECKER FAMILY TODAY 55 00:02:16,171 --> 00:02:17,439 TO INCLUDE MR. DAVID DECKER, THE 56 00:02:17,439 --> 00:02:20,142 SON OF DR. DECKER AND HIS 57 00:02:20,142 --> 00:02:21,710 GRANDSONS IAN AND TOMAS. 58 00:02:21,710 --> 00:02:21,977 WELCOME. 59 00:02:21,977 --> 00:02:24,113 THANK YOU FOR BEING HERE. 60 00:02:24,113 --> 00:02:26,515 I WOULD NOW LIKE TO TURN THE 61 00:02:26,515 --> 00:02:29,351 MICROPHONE OVER TO MR. DAVID 62 00:02:29,351 --> 00:02:32,755 CARAMEL, SENIOR HAVE THE AND 63 00:02:32,755 --> 00:02:36,926 CHIEF GROWTH AND OFFICER FOR 64 00:02:36,926 --> 00:02:39,028 REMARKS ON BEHALF. 65 00:02:39,028 --> 00:02:41,864 >> THANK YOU, DR. BURKLOW. 66 00:02:41,864 --> 00:02:42,565 WELCOME EVERYBODY. 67 00:02:42,565 --> 00:02:44,166 MY NAME IS DAVID CARAMEL. 68 00:02:44,166 --> 00:02:44,967 I'M DELIGHTED TO WELCOME YOU TO 69 00:02:44,967 --> 00:02:50,139 THIS MILESTONE JOHN LAWS DECKER 70 00:02:50,139 --> 00:02:53,008 MEMORIAL LECTURE FEATURING THE 71 00:02:53,008 --> 00:02:53,576 2024 DISTINGUISHED CLINICAL 72 00:02:53,576 --> 00:02:55,511 TEACHER AWARD, DR. DAVID KLE 73 00:02:55,511 --> 00:02:56,412 KLEIKLEI 74 00:02:56,412 --> 00:02:57,279 KLEINER. 75 00:02:57,279 --> 00:02:58,447 DR. KLEINER, WE LOOK FORWARD TO 76 00:02:58,447 --> 00:02:59,949 YOUR PRESENTATION. 77 00:02:59,949 --> 00:03:02,217 THE FNIH IS PROUD TO HAVE BEEN 78 00:03:02,217 --> 00:03:02,751 PARTNER OF THIS IMPORTANT 79 00:03:02,751 --> 00:03:06,188 LECTURE SINCE 2003 WHEN THE NIH 80 00:03:06,188 --> 00:03:08,524 BEGAN RECOGNIZING THE LATE 81 00:03:08,524 --> 00:03:09,892 CLINICAL CENTER DIRECTOR JOHN 82 00:03:09,892 --> 00:03:12,895 LAWS DECKER ANNUALLY THROUGH 83 00:03:12,895 --> 00:03:15,297 THIS CLINICAL CENTER GRAND ROUND 84 00:03:15,297 --> 00:03:17,099 LECTURE SERIES. 85 00:03:17,099 --> 00:03:18,233 AT THAT TIME THE FAMILY OF 86 00:03:18,233 --> 00:03:22,237 DR. DECKER WORKED WITH THE FNIH 87 00:03:22,237 --> 00:03:25,741 TO ESTABLISH THE E MEMORIAL 88 00:03:25,741 --> 00:03:27,943 FUND IN HONOR OF THEIR LATE 89 00:03:27,943 --> 00:03:28,243 FATHER. 90 00:03:28,243 --> 00:03:29,311 DURING HIS LIFETIME DR. DECKER 91 00:03:29,311 --> 00:03:31,113 WAS AN OUTSTANDING TEACHER WHO 92 00:03:31,113 --> 00:03:32,915 STRIVED TO CONNECT SCIENTIFIC 93 00:03:32,915 --> 00:03:33,916 COMMUNICATIONS AROUND THE WORLD 94 00:03:33,916 --> 00:03:34,416 TO ACCELERATE IMPORTANT 95 00:03:34,416 --> 00:03:34,883 RESEARCH. 96 00:03:34,883 --> 00:03:38,721 THIS IS THEIR AND OUR WAY OF 97 00:03:38,721 --> 00:03:40,289 EXTENDING HIS LEGACY. 98 00:03:40,289 --> 00:03:42,725 I ALSO WANT TO THANK THE DECKER 99 00:03:42,725 --> 00:03:47,096 FAMILY FOR YOUR GENEROSITY AND 100 00:03:47,096 --> 00:03:48,897 INSPIRED VISION IN ESTABLISHING 101 00:03:48,897 --> 00:03:50,265 THE DECKER MEMORIAL FUND. 102 00:03:50,265 --> 00:03:52,034 I'M PLEASED THAT DR. DECKER'S 103 00:03:52,034 --> 00:03:53,335 SON DAVID AND GRANDSONS IAN AND 104 00:03:53,335 --> 00:03:55,237 TOMAS ARE HERE TODAY. 105 00:03:55,237 --> 00:03:57,573 AND OTHER MEMBERS OF THE FAMILY 106 00:03:57,573 --> 00:03:59,742 ARE JOINING ONLINE, I BELIEVE. 107 00:03:59,742 --> 00:04:02,544 THE FNIH IS PROUD OF OUR LONG 108 00:04:02,544 --> 00:04:03,646 STANDING COLLABORATION WITH YOU 109 00:04:03,646 --> 00:04:04,213 AND THE CLINICAL CENTER TO 110 00:04:04,213 --> 00:04:06,015 RECOGNIZE INNOVATIVE 111 00:04:06,015 --> 00:04:07,516 ESTABLISHMENTS. 112 00:04:07,516 --> 00:04:08,417 -- ACCOMPLISHMENT. 113 00:04:08,417 --> 00:04:10,319 WE INVITE YOU TO EXPLORE THE 114 00:04:10,319 --> 00:04:12,221 MANY PARTNERSHIPS FORMED IN THE 115 00:04:12,221 --> 00:04:14,256 INNOVATIVE SCIENTIFIC THINKING 116 00:04:14,256 --> 00:04:16,291 THAT IS SUPPORTED THROUGH OUR 117 00:04:16,291 --> 00:04:16,558 PROGRAMS. 118 00:04:16,558 --> 00:04:18,160 I THINK IT'S UP THERE AS WELL. 119 00:04:18,160 --> 00:04:21,330 OUR WEBSITE IS FNIH.ORG. 120 00:04:21,330 --> 00:04:23,732 SO NOW I'LL TURN THINGS BACK TO 121 00:04:23,732 --> 00:04:24,500 DR. BURKLOW. 122 00:04:24,500 --> 00:04:25,601 THANK YOU FOR JOINING US FOR 123 00:04:25,601 --> 00:04:26,935 THIS EVENT AND PLEASE ENJOY THE 124 00:04:26,935 --> 00:04:33,642 20TH. 125 00:04:33,642 --> 00:04:35,844 >> [APPLAUSE] 126 00:04:35,844 --> 00:04:36,779 >> THANK YOU MR. CARAMEL. 127 00:04:36,779 --> 00:04:37,880 AND TO THE DECKER FAMILY, THANK 128 00:04:37,880 --> 00:04:38,280 YOU VERY MUCH. 129 00:04:38,280 --> 00:04:40,215 WE EXTEND OUR GRATITUDE FOR YOUR 130 00:04:40,215 --> 00:04:40,683 CONTINUING SUPPORT. 131 00:04:40,683 --> 00:04:43,952 EACH YEAR THE NIH CLINICAL 132 00:04:43,952 --> 00:04:46,188 FELLOWS SELECT A HIGHLY REGARDED 133 00:04:46,188 --> 00:04:47,389 MENTOR TO RECEIVE THE 134 00:04:47,389 --> 00:04:48,457 DISTINGUISHED CLINICAL TEACHER 135 00:04:48,457 --> 00:04:48,957 AWARD. 136 00:04:48,957 --> 00:04:50,859 DR. DECKER WAS AN INSPIRING 137 00:04:50,859 --> 00:04:53,929 LEADER AND MENTOR SO IT'S VERY 138 00:04:53,929 --> 00:04:55,431 APPROPRIATE THAT THE AWARDEE 139 00:04:55,431 --> 00:04:57,132 DELIVER THE ANNUAL DECKER 140 00:04:57,132 --> 00:04:58,267 MEMORIAL LECTURE. 141 00:04:58,267 --> 00:05:01,503 BEFORE INTRODUCING TODAY'S 142 00:05:01,503 --> 00:05:02,137 SPEAKER AND A 2024 DISTINGUISHED 143 00:05:02,137 --> 00:05:03,338 CLINICAL TEACHER AWARDEE I'D 144 00:05:03,338 --> 00:05:09,011 LIKE TO TURN THE PODIUM OVER WHO 145 00:05:09,011 --> 00:05:09,978 COCHAIRS THE CLINICAL COMMITTEE 146 00:05:09,978 --> 00:05:12,448 TO ANNOUNCE THE WINNER OF THE 147 00:05:12,448 --> 00:05:13,015 2025 DISTINGUISHED CLINICAL 148 00:05:13,015 --> 00:05:23,425 TEACHER AWARD. 149 00:05:23,425 --> 00:05:24,026 >> HI EVERYONE. 150 00:05:24,026 --> 00:05:26,228 I'M THE CLINICAL FELLOW 151 00:05:26,228 --> 00:05:27,563 COMMITTEE CO-CHAIR. 152 00:05:27,563 --> 00:05:30,866 WE'D LIKE TO THANK DR. BURKLOW 153 00:05:30,866 --> 00:05:33,368 FOR HIS ON GOING SUPPORT TO 154 00:05:33,368 --> 00:05:34,369 FELLOWS AND IMPORTANT FOR 155 00:05:34,369 --> 00:05:37,306 MENTORING AT NIH. 156 00:05:37,306 --> 00:05:38,841 I'M HONORED TO ANNOUNCE THE 157 00:05:38,841 --> 00:05:44,179 WINNER OF 2 -- 2025 AWARD. 158 00:05:44,179 --> 00:05:45,948 THEY SET AND ACHIEVE GOALS, 159 00:05:45,948 --> 00:05:50,152 ANTICIPATE ROADBLOCKS AND OVER 160 00:05:50,152 --> 00:05:54,089 COME OBSTACLES. 161 00:05:54,089 --> 00:05:54,623 ALL RIGHT. 162 00:05:54,623 --> 00:05:56,125 SO ALL INDIVIDUALS NOMINATED FOR 163 00:05:56,125 --> 00:05:58,727 THIS YEAR'S AWARDS DESERVE 164 00:05:58,727 --> 00:06:00,229 RECOGNITION AS OUTSTANDING 165 00:06:00,229 --> 00:06:00,662 CLINICAL MENTORS. 166 00:06:00,662 --> 00:06:02,531 I'D LIKE TO THANK ALL THE 167 00:06:02,531 --> 00:06:04,133 NOMINEES FOR THEIR COMMITMENT TO 168 00:06:04,133 --> 00:06:05,567 TRAINING CLINICAL INVESTIGATORS 169 00:06:05,567 --> 00:06:10,639 AT NIH AND THEIR OVER ALL 170 00:06:10,639 --> 00:06:10,973 CONTRIBUTION. 171 00:06:10,973 --> 00:06:12,608 EACH YEAR THE AWARD IS DECIDED 172 00:06:12,608 --> 00:06:14,576 BY THE VOTE OF FELLOWS AND 173 00:06:14,576 --> 00:06:17,212 PRESENTED TO AN INDIVIDUAL WHO 174 00:06:17,212 --> 00:06:20,682 HAS IDEALS OF TEACHER AND 175 00:06:20,682 --> 00:06:21,583 RESEARCHER. 176 00:06:21,583 --> 00:06:23,051 HERE ARE A FEW WORDS ABOUT THIS 177 00:06:23,051 --> 00:06:25,587 YEAR'S AWARDEE. 178 00:06:25,587 --> 00:06:26,588 A DEDICATED TEACHER WHO DEVOTES 179 00:06:26,588 --> 00:06:28,056 TIME AND EFFORTS TO SHOW US 180 00:06:28,056 --> 00:06:30,259 CASES AND GIVE US EXPOSURE TO 181 00:06:30,259 --> 00:06:35,264 THINGS BEYOND THE DAYS IN 182 00:06:35,264 --> 00:06:37,866 DAY-TO-DAY SESSIONS. HE HAS A 183 00:06:37,866 --> 00:06:38,700 PLACE OPEN AT 4:00 P.M. 184 00:06:38,700 --> 00:06:42,271 HE HAS AN EXTENSIVE CASE ARCHIVE 185 00:06:42,271 --> 00:06:43,839 COVERING VARIOUS SURGICAL 186 00:06:43,839 --> 00:06:45,941 SUBSPECIALTIES AND PROVIDES A 187 00:06:45,941 --> 00:06:48,343 SLIDE SHOW SESSION TO HELP US 188 00:06:48,343 --> 00:06:49,711 OUT IF IN THE FIELD. 189 00:06:49,711 --> 00:06:51,079 HE'S A WORLDWIDE KNOWN AUTHOR 190 00:06:51,079 --> 00:06:52,648 WITH GREAT IMPACT IN THE FIELD. 191 00:06:52,648 --> 00:06:55,450 HE'S CONTRIBUTED TO THE 192 00:06:55,450 --> 00:06:57,252 LITERATURE WITH LOTS OF 193 00:06:57,252 --> 00:06:58,720 INKNOWTIVE PAPERS. 194 00:06:58,720 --> 00:07:00,923 HE RECEIVED CONSULTATION CASES 195 00:07:00,923 --> 00:07:02,491 NOT ONLY AROUND THE U.S. BUT 196 00:07:02,491 --> 00:07:04,193 ALSO ALL OVER THE WORLD. 197 00:07:04,193 --> 00:07:06,595 NOT LIMITED TOO BUT INCLUDING 198 00:07:06,595 --> 00:07:08,463 COUNTRIES SUCH AS PR, VIETNAM 199 00:07:08,463 --> 00:07:10,933 AND TURKEY. 200 00:07:10,933 --> 00:07:13,435 SO PLEASE JOIN ME IN C 201 00:07:13,435 --> 00:07:23,412 CONGRATULATING OUR 2025 202 00:07:23,412 --> 00:07:25,714 DISTINGUISHED CLINICAL AWARD 203 00:07:25,714 --> 00:07:25,981 WINNER. 204 00:07:25,981 --> 00:07:28,050 >> [APPLAUSE] 205 00:07:28,050 --> 00:07:28,684 >> CONGRATULATIONS DOCTOR. 206 00:07:28,684 --> 00:07:31,153 NOW I'D LIKE TO TURN THE MIC 207 00:07:31,153 --> 00:07:33,922 BACK OVER TO DR. BURKLOW TO 208 00:07:33,922 --> 00:07:36,859 INTRODUCE DOCTOR KLEINER, OUR 209 00:07:36,859 --> 00:07:43,131 2024 WINNER. 210 00:07:43,131 --> 00:07:46,335 >> THANK YOU DR. ZEQUAY. 211 00:07:46,335 --> 00:07:48,737 WELL DESERVED. 212 00:07:48,737 --> 00:07:50,706 SO WE SEEM TO HAVE RUN ON HERE 213 00:07:50,706 --> 00:07:51,807 IN PATHOLOGY AND TEACHING SO I 214 00:07:51,807 --> 00:07:55,544 GUESS THAT'S A GOOD THING. 215 00:07:55,544 --> 00:07:59,047 I'M NOW HONORED TO INTRODUCE 216 00:07:59,047 --> 00:08:02,217 TODAY'S TEACHER AND RECIPIENT OF 217 00:08:02,217 --> 00:08:05,754 THE 2024 DISTINGUISHED TEACHER 218 00:08:05,754 --> 00:08:05,988 AWARD. 219 00:08:05,988 --> 00:08:07,322 DR. DAVID KLEINER. 220 00:08:07,322 --> 00:08:10,025 HE EARNED HIS DEGREES AT SAINT 221 00:08:10,025 --> 00:08:11,560 OLAF COLLEGE AND UNIVERSITY OF 222 00:08:11,560 --> 00:08:13,829 CHICAGO WHERE HE EARNED HIS PHD 223 00:08:13,829 --> 00:08:15,898 IN CHEMISTRY AND MEDICAL DEGREE. 224 00:08:15,898 --> 00:08:19,101 DR. KLEINER IN TERMS OF 225 00:08:19,101 --> 00:08:26,275 RESIDENCE D -- RESIDENCY. 226 00:08:26,275 --> 00:08:28,443 AT THE NCI HE'S NOW A SENIOR 227 00:08:28,443 --> 00:08:30,145 PHYSICIAN, DIRECTOR OF 228 00:08:30,145 --> 00:08:30,879 LABORATORY INFORMATION SYSTEM 229 00:08:30,879 --> 00:08:33,115 AND CHIEF OF THE POSTMORTEM 230 00:08:33,115 --> 00:08:37,352 SECTION WITH EXPERTISE IN 231 00:08:37,352 --> 00:08:37,653 PATHOLOGY. 232 00:08:37,653 --> 00:08:38,553 HIS INTERNATIONALLY RECOGNIZED 233 00:08:38,553 --> 00:08:40,923 RESEARCH HAS FOCUSED ON CHRONIC 234 00:08:40,923 --> 00:08:43,091 LIVER DISEASE AND DRUG-INDUCED 235 00:08:43,091 --> 00:08:44,693 INJURY AND LIVER CANCER. 236 00:08:44,693 --> 00:08:47,763 WITH ATTENTION TO ASSESSING HIS 237 00:08:47,763 --> 00:08:49,031 RESPONSES TO THERAPY. 238 00:08:49,031 --> 00:08:54,069 HE IS A KEY PATHOLOGIST FOR THE 239 00:08:54,069 --> 00:08:58,941 NATIONAL INSTITUTE FOR DIABETES, 240 00:08:58,941 --> 00:09:00,409 THE NON ALCOHOLIC STEATOTIC 241 00:09:00,409 --> 00:09:03,245 HEPATITIS NETWORK, DRUG INDUCED 242 00:09:03,245 --> 00:09:05,180 LIVER NETWORK AND HEPATITIS B 243 00:09:05,180 --> 00:09:05,814 RESEARCH NETWORK. 244 00:09:05,814 --> 00:09:07,983 A RESEARCHER AND SCHOLAR HE'S 245 00:09:07,983 --> 00:09:12,187 AUTHORED OR CO-AUTHORED OVER 500 246 00:09:12,187 --> 00:09:13,488 PEER REVIEWED ARTICLES, BOOK 247 00:09:13,488 --> 00:09:16,325 CHAPTERS AND EDITORIALS WITH A 248 00:09:16,325 --> 00:09:19,861 FOCUS OF DRUG UNDEUCED LIVER 249 00:09:19,861 --> 00:09:22,864 INJURY AND HEPOTITIS. 250 00:09:22,864 --> 00:09:27,703 DR. KLEINER IS A VALUED TEACHER 251 00:09:27,703 --> 00:09:28,670 AND MENTOR WHO BRINGS HIS 252 00:09:28,670 --> 00:09:30,072 PASSION TO THE MICROSCOPE. 253 00:09:30,072 --> 00:09:31,873 INSPIRING HIS MANY CURRENT AND 254 00:09:31,873 --> 00:09:32,941 PAST FELLOWS AND RESIDENTS IN 255 00:09:32,941 --> 00:09:37,713 PATHOLOGY. 256 00:09:37,713 --> 00:09:40,248 THE TITLE OF DR. KLEINER'S 257 00:09:40,248 --> 00:09:41,216 PRESENTATION TODAY IS STEATOTIC 258 00:09:41,216 --> 00:09:42,918 LIVER DISEASE FROM FIRST 259 00:09:42,918 --> 00:09:46,154 DESCRIPTION TO FIRST DRUG 260 00:09:46,154 --> 00:09:49,224 APPROVAL THROUGH THE EYES OF THE 261 00:09:49,224 --> 00:09:49,558 PATHOLOGIST. 262 00:09:49,558 --> 00:09:52,060 PLEASE JOIN ME IN RECOGNIZING 263 00:09:52,060 --> 00:09:54,062 OUR SPEAKER AND THE WINNER OF 264 00:09:54,062 --> 00:09:56,598 THE TEACHER AWARD, DR. DAVID 265 00:09:56,598 --> 00:09:56,865 KLEINER. 266 00:09:56,865 --> 00:09:58,066 >> [APPLAUSE] 267 00:09:58,066 --> 00:10:00,035 >> THANK YOU. 268 00:10:00,035 --> 00:10:00,836 THANK YOU TOO TO THE DECKER 269 00:10:00,836 --> 00:10:02,871 FAMILY. 270 00:10:02,871 --> 00:10:05,674 I OVER LAPPED A LITTLE BIT WITH 271 00:10:05,674 --> 00:10:10,812 DR. DECKER AS -- WHEN HE WAS THE 272 00:10:10,812 --> 00:10:13,582 CLINICAL DIRECTOR OF THE 273 00:10:13,582 --> 00:10:15,450 CLINICAL CENTER BUT ONLY FOR A 274 00:10:15,450 --> 00:10:16,318 FEW YEARS AND I WAS ONLY JUNIOR 275 00:10:16,318 --> 00:10:17,219 AT THE TIME. 276 00:10:17,219 --> 00:10:18,086 SO I DON'T THINK I ACTUALLY EVER 277 00:10:18,086 --> 00:10:20,355 MET HIM. 278 00:10:20,355 --> 00:10:23,191 SO ON WE GO. 279 00:10:23,191 --> 00:10:25,727 SO I HAVE FINANCIAL CONFLICTS OF 280 00:10:25,727 --> 00:10:27,062 INTEREST RELEVANT TO THIS 281 00:10:27,062 --> 00:10:28,196 PRESENTATION, WHICH I'M SURE 282 00:10:28,196 --> 00:10:28,930 MANY IN THE AUDIENCE CAN ALSO 283 00:10:28,930 --> 00:10:32,234 SAY. 284 00:10:32,234 --> 00:10:33,268 SO THIS IS AN EDUCATIONAL TALK. 285 00:10:33,268 --> 00:10:35,337 SO THERE ARE SOME OBJECTIVES. 286 00:10:35,337 --> 00:10:38,373 THERE WILL NOT BE A QUIZ. 287 00:10:38,373 --> 00:10:41,676 SO I'M GOING TO REVIEW THE 288 00:10:41,676 --> 00:10:42,377 PATHOLOGY OF THIS STEATOTIC 289 00:10:42,377 --> 00:10:43,311 LIVER DISEASE AND THE SCORING 290 00:10:43,311 --> 00:10:45,013 SYSTEM THAT WE DEVELOPED FOR USE 291 00:10:45,013 --> 00:10:48,116 AND RESEARCH AND CLINICAL 292 00:10:48,116 --> 00:10:48,383 TRIALS. 293 00:10:48,383 --> 00:10:50,018 ESPECIALLY HIGHLIGHT SOME OF THE 294 00:10:50,018 --> 00:10:52,421 CONTRIBUTIONS OF THE NETWORK 295 00:10:52,421 --> 00:10:53,688 THAT I BELONG IN -- BELONG TO 296 00:10:53,688 --> 00:10:57,392 AND THAT THE NIDDK SPONSORED. 297 00:10:57,392 --> 00:10:58,560 AND A LITTLE BIT ABOUT THE 298 00:10:58,560 --> 00:11:01,096 HISTORY WHICH SPANS 45 YEARS OF 299 00:11:01,096 --> 00:11:01,296 TIME. 300 00:11:01,296 --> 00:11:03,398 I'VE GOT ABOUT THAT MANY MINUTES 301 00:11:03,398 --> 00:11:06,068 SO I CAN ONLY HIT THE 302 00:11:06,068 --> 00:11:07,536 HIGHLIGHTS. 303 00:11:07,536 --> 00:11:09,371 I DO WANT TO TAKE ONE SLIDE TO 304 00:11:09,371 --> 00:11:13,442 EXPLAIN A NEW NOMENCLATURE THAT 305 00:11:13,442 --> 00:11:15,844 WAS INTRODUCED IN 2023. 306 00:11:15,844 --> 00:11:18,780 WE HAVE CHANGED THE NAME OF THIS 307 00:11:18,780 --> 00:11:19,981 DISEASE BUT MOST OF THE PAPERS 308 00:11:19,981 --> 00:11:22,717 AND THINGS THAT I WILL REVIEW 309 00:11:22,717 --> 00:11:25,253 REFER TO THE OLD NAME, SO NOW 310 00:11:25,253 --> 00:11:29,691 THIS DISEASE IS CALLED METABOLIC 311 00:11:29,691 --> 00:11:30,392 DYSFUNC 312 00:11:30,392 --> 00:11:32,961 DYSFUNCTION STEATOTIC LIVER 313 00:11:32,961 --> 00:11:33,862 DISEASE. 314 00:11:33,862 --> 00:11:37,833 USED TO BE CALLED NON ALCOHOLIC 315 00:11:37,833 --> 00:11:41,436 LIVER DISEASE. 316 00:11:41,436 --> 00:11:44,272 THE STEATOHEPATITIS VERSUS NON 317 00:11:44,272 --> 00:11:46,074 ALCOHOLIC STEATOHEPATITIS. 318 00:11:46,074 --> 00:11:47,409 THE ABBREVIATIONS ARE AT THE 319 00:11:47,409 --> 00:11:49,077 BOTTOM THERE AND NASH OR MASH. 320 00:11:49,077 --> 00:11:56,718 I WILL MOSTLY USE THE NAFLD AND 321 00:11:56,718 --> 00:11:57,886 NASH FOR THIS TALK. 322 00:11:57,886 --> 00:12:01,389 WHY IS THIS SO IMPORTANT? 323 00:12:01,389 --> 00:12:02,958 I THINK IT'S IMPORTANT WHEREVER 324 00:12:02,958 --> 00:12:05,260 WE STUDY DISEASE TO UNDERSTAND 325 00:12:05,260 --> 00:12:06,061 WHY A DISEASE IS PARTICULARLY 326 00:12:06,061 --> 00:12:06,361 IMPORTANT. 327 00:12:06,361 --> 00:12:09,831 AND I THINK THIS MAP SHOWS THE 328 00:12:09,831 --> 00:12:15,003 SIGNIFICANCE OF THIS DISEASE. 329 00:12:15,003 --> 00:12:18,840 THIS IS AN INCIDENTS MAP 330 00:12:18,840 --> 00:12:22,210 COVERING MOST OF THE RWORLD. 331 00:12:22,210 --> 00:12:23,612 NOT SURE WHY THEY LEFT OUT PARTS 332 00:12:23,612 --> 00:12:25,647 OF THE WORLD BECAUSE IT'S BEEN 333 00:12:25,647 --> 00:12:27,616 COVERED BY AUTHORS IN PREVIOUS 334 00:12:27,616 --> 00:12:27,849 PAPERS. 335 00:12:27,849 --> 00:12:28,850 WHAT YOU CAN SEE A NEARLY A 336 00:12:28,850 --> 00:12:32,587 THIRD OF PEOPLE IN THE WORLD ARE 337 00:12:32,587 --> 00:12:33,321 AFFECTED BY STEATOTIC LIVER 338 00:12:33,321 --> 00:12:34,356 DISEASE. 339 00:12:34,356 --> 00:12:35,624 IT'S A STAGGERING, REALLY 340 00:12:35,624 --> 00:12:38,026 STAGGERING NUMBER. 341 00:12:38,026 --> 00:12:40,795 IT'S RELATIVELY EVENLY 342 00:12:40,795 --> 00:12:42,831 DISTRIBUTED WITH SOME HIGH 343 00:12:42,831 --> 00:12:45,367 POINTS, LATIN AMERICA 344 00:12:45,367 --> 00:12:46,034 PARTICULARLY AFFECTED. 345 00:12:46,034 --> 00:12:50,138 IT'S NOT SHOWN ON THIS BUT SUB 346 00:12:50,138 --> 00:12:53,041 SAHARAN AFRICA HAS A LOWER 347 00:12:53,041 --> 00:12:53,308 INCIDENT. 348 00:12:53,308 --> 00:12:55,310 IT'S ABOUT 15%. 349 00:12:55,310 --> 00:12:55,944 BUT EVERYWHERE ELSE IT'S ABOUT 350 00:12:55,944 --> 00:12:58,813 30%. 351 00:12:58,813 --> 00:13:02,017 MORE SIGNIFICANTLY IS THAT THE 352 00:13:02,017 --> 00:13:04,019 CRITICAL PART OF THIS DISEASE 353 00:13:04,019 --> 00:13:09,824 WHERE IT BECOMES FIBROTIC AND 354 00:13:09,824 --> 00:13:10,559 PROGRESSES THE STEATOTIC IS A 355 00:13:10,559 --> 00:13:11,092 SIXTH OF THOSE. 356 00:13:11,092 --> 00:13:13,128 YOU CAN SEE THOSE NUMBERS UP ON 357 00:13:13,128 --> 00:13:17,566 THE PANEL OVER HERE ON THE 358 00:13:17,566 --> 00:13:17,799 RIGHT. 359 00:13:17,799 --> 00:13:24,906 THE NASH PREF -- PREVALENCE 360 00:13:24,906 --> 00:13:26,141 NUMBERS. 361 00:13:26,141 --> 00:13:30,712 THEY VARY FROM 4.5% TO 7% OF THE 362 00:13:30,712 --> 00:13:31,246 POPULATION. 363 00:13:31,246 --> 00:13:34,082 DOWN BELOW WE SEE THE END 364 00:13:34,082 --> 00:13:37,519 EFFECTS OF THOSE. 365 00:13:37,519 --> 00:13:40,655 MORTALITY, CARDIAC SPECIFIC 366 00:13:40,655 --> 00:13:43,825 MORTALITY OF FATTY LIVER DISEASE 367 00:13:43,825 --> 00:13:45,227 IS 4 PER THOUSAND. 368 00:13:45,227 --> 00:13:47,262 SO .4%. 369 00:13:47,262 --> 00:13:49,731 CANCERS ARE ALSO RELATED TO THIS 370 00:13:49,731 --> 00:13:55,503 DISEASE AT ABOUT .3% OF 371 00:13:55,503 --> 00:13:56,304 PATIENTS. 372 00:13:56,304 --> 00:13:59,708 AND LIVER SPECIFIC DEATH IS 373 00:13:59,708 --> 00:14:02,010 SLIGHT DLY -- WELL, 1 TO 2%. TS 374 00:14:02,010 --> 00:14:04,179 IS A REALLY IMPACTFUL DISEASE 375 00:14:04,179 --> 00:14:05,614 AND ONE THAT WE NEED TO PAY 376 00:14:05,614 --> 00:14:07,182 QUITE A BIT OF ATTENTION TO IT. 377 00:14:07,182 --> 00:14:08,683 THIS SHOWS THE TIME COURSE 378 00:14:08,683 --> 00:14:10,051 THOUGH DESPITE THE FACT THAT A 379 00:14:10,051 --> 00:14:11,486 THIRD OF THE POPULATION OF THE 380 00:14:11,486 --> 00:14:13,154 WORLD IS AFFECTED. 381 00:14:13,154 --> 00:14:16,958 THIS IS A VERY SLOW DISEASE. 382 00:14:16,958 --> 00:14:20,028 SO IF YOU START WITH 100 383 00:14:20,028 --> 00:14:22,697 PATIENTS WITH NAFLD, OVER THE 384 00:14:22,697 --> 00:14:27,035 COURSE OF 20 TO 30 TO 40, 50 385 00:14:27,035 --> 00:14:30,038 YEARS ONLY 5 OF THOSE PATIENTS 386 00:14:30,038 --> 00:14:30,672 WILL DEVELOP CIRRHOSIS WHICH IS 387 00:14:30,672 --> 00:14:34,009 REALLY THE STAGE THAT WE WORRY 388 00:14:34,009 --> 00:14:34,276 ABOUT. 389 00:14:34,276 --> 00:14:36,978 A COUPLE OF THOSE WILL 390 00:14:36,978 --> 00:14:39,447 DECOMPENSATE AND THEN WE MIGHT 391 00:14:39,447 --> 00:14:41,082 END UP WITH LIVER 392 00:14:41,082 --> 00:14:42,284 TRANSPLANTATION OR DEATH RELATED 393 00:14:42,284 --> 00:14:44,419 TO CIRRHOSIS. 394 00:14:44,419 --> 00:14:46,755 THEN MOST OF THESE PATIENTS WILL 395 00:14:46,755 --> 00:14:50,492 NEVER DEVELOP THAT AND THEY WILL 396 00:14:50,492 --> 00:14:51,559 DIE WITH THE DISEASE RATHER THAN 397 00:14:51,559 --> 00:14:52,494 FROM IT. 398 00:14:52,494 --> 00:14:54,296 AND IT'S IMPORTANT FOR US TO TRY 399 00:14:54,296 --> 00:14:56,531 AND UNDERSTAND THE NATURAL 400 00:14:56,531 --> 00:14:57,866 HISTORY OF THE DISEASE SO WE CAN 401 00:14:57,866 --> 00:15:01,703 FOCUS ON THE PEOPLE WHO ARE 402 00:15:01,703 --> 00:15:02,203 REALLY GOING TO SUFFER. 403 00:15:02,203 --> 00:15:03,538 SO I'M A PATHOLOGIST. 404 00:15:03,538 --> 00:15:04,105 WE'RE GOING TO TALK ABOUT 405 00:15:04,105 --> 00:15:04,406 PATHOLOGY. 406 00:15:04,406 --> 00:15:07,375 TO UNDERSTAND ABNORMAL, YOU 407 00:15:07,375 --> 00:15:09,477 FIRST HAVE TO UNDERSTAND NORMAL. 408 00:15:09,477 --> 00:15:11,680 SO NORMAL ADULT LIVER, I SWIPED 409 00:15:11,680 --> 00:15:14,082 THE PICTURE FROM THE NIDDK 410 00:15:14,082 --> 00:15:16,384 WEBSITE, IT'S ABOUT 3 TO 4 411 00:15:16,384 --> 00:15:16,885 POUNDS, RIGHT. 412 00:15:16,885 --> 00:15:18,653 ABOUT 2% OF YOUR BODY WEIGHT. 413 00:15:18,653 --> 00:15:20,855 THAT'S NORMAL. 414 00:15:20,855 --> 00:15:21,856 YOU CAN SEE OVER ON THE GRAPH ON 415 00:15:21,856 --> 00:15:26,561 THE SIDE THAT IT STARTS OUT 416 00:15:26,561 --> 00:15:30,231 PRETTY SMALL, ABOUT 70 GRAMS, A 417 00:15:30,231 --> 00:15:31,700 FEW OUNCES. 418 00:15:31,700 --> 00:15:35,236 THEN AS YOU GROW UP THROUGH 419 00:15:35,236 --> 00:15:37,505 PUBERTY IT ATTAINS NEARLY ADULT 420 00:15:37,505 --> 00:15:38,273 SIZE BY THE TIME YOU'RE A 421 00:15:38,273 --> 00:15:39,774 TEENAGER. 422 00:15:39,774 --> 00:15:47,082 BUT WE'RE GOING TO DEAL WITH THE 423 00:15:47,082 --> 00:15:50,018 MIC 424 00:15:50,018 --> 00:15:50,485 MICROSCOPIC. 425 00:15:50,485 --> 00:15:53,388 YOU SEE A PHOTO MICRO GRAPH OF A 426 00:15:53,388 --> 00:15:54,556 NORMAL LIVER. 427 00:15:54,556 --> 00:15:56,124 I EXPECT MANY IN THE AUDIENCE 428 00:15:56,124 --> 00:16:01,763 HAVE NOT LOOKED AT HISTOLOGY 429 00:16:01,763 --> 00:16:03,098 SINCE MEDICAL SCHOOL OR NEVER 430 00:16:03,098 --> 00:16:03,498 ENCOUNTERED IT. 431 00:16:03,498 --> 00:16:06,701 SO A BRIEF REVIEW. 432 00:16:06,701 --> 00:16:09,671 THIS IS A STAIN. 433 00:16:09,671 --> 00:16:12,507 THE PURPLE CIRCLES ARE ALL CELL 434 00:16:12,507 --> 00:16:14,943 NUCLEI. 435 00:16:14,943 --> 00:16:20,949 THEN THE PINK IS THE PSYDOPLASM. 436 00:16:20,949 --> 00:16:21,616 YOU CAN SEE THE EDGE. 437 00:16:21,616 --> 00:16:26,988 THAT'S THE CELL BOARD PER -- 438 00:16:26,988 --> 00:16:27,322 BORDER. 439 00:16:27,322 --> 00:16:28,790 SO THIS SHOWS THE NORMAL 440 00:16:28,790 --> 00:16:30,058 ARCHITECTURE OF THE LIVER WHICH 441 00:16:30,058 --> 00:16:30,925 IS SIMPLE. 442 00:16:30,925 --> 00:16:34,295 BLOOD FLOWS IN THROUGH TWO 443 00:16:34,295 --> 00:16:36,231 VESSELS, THE PORTAL VEIN WHICH 444 00:16:36,231 --> 00:16:38,066 COMES FROM THE GUT AND THE 445 00:16:38,066 --> 00:16:38,933 ARTERI 446 00:16:38,933 --> 00:16:40,402 ARTERIES, I'LL SHOW YOU A 447 00:16:40,402 --> 00:16:42,237 PICTURE IN A MINUTE FLOW THROUGH 448 00:16:42,237 --> 00:16:44,572 THE SITES TO THE CENTRAL VEIN. 449 00:16:44,572 --> 00:16:47,876 SO THE BLOOD COMES IN, GETS 450 00:16:47,876 --> 00:16:49,711 FILTERED, PROCESSED AND THEN OUT 451 00:16:49,711 --> 00:16:51,446 REPACKAGED AND COMES OUT OF THE 452 00:16:51,446 --> 00:16:52,113 LIVER OVER THERE. 453 00:16:52,113 --> 00:16:54,716 I'M OBVIOUSLY OVER SIMPLIFYING A 454 00:16:54,716 --> 00:16:55,049 LOT. 455 00:16:55,049 --> 00:16:56,551 THEN BILE DRAINS OUT OF THE 456 00:16:56,551 --> 00:16:57,285 LIVER THROUGH THE BILE DUCT 457 00:16:57,285 --> 00:16:59,354 WHICH IS OVER IN THE PORTAL 458 00:16:59,354 --> 00:16:59,554 AREA. 459 00:16:59,554 --> 00:17:01,923 SO HERE'S A BIGGER PICTURE. 460 00:17:01,923 --> 00:17:02,791 SO WE SEE CENTRAL VEIN OVER HERE 461 00:17:02,791 --> 00:17:05,693 ON THE LEFT. 462 00:17:05,693 --> 00:17:08,963 VERY WELL DEFINED, FEW RED BLOOD 463 00:17:08,963 --> 00:17:12,667 CELLS IN THE MIDDLE AND THEN 464 00:17:12,667 --> 00:17:13,568 PATASITES ALL AROUND. 465 00:17:13,568 --> 00:17:15,370 AND THEN THE LARGE PORTAL AREA, 466 00:17:15,370 --> 00:17:16,738 THE LARGE PORTAL VEIN AND A 467 00:17:16,738 --> 00:17:18,273 COUPLE OF ARTERIES AND BILE DUCT 468 00:17:18,273 --> 00:17:18,873 UP TO THE UPPER RIGHT. 469 00:17:18,873 --> 00:17:20,542 OKAY. 470 00:17:20,542 --> 00:17:23,845 THE OTHER STAIN THAT I'M GOING 471 00:17:23,845 --> 00:17:27,015 TO SHOW YOU IS A MASAN STAIN, 472 00:17:27,015 --> 00:17:31,886 WHICH IS A STAIN WE USE TO 473 00:17:31,886 --> 00:17:34,522 HIGHLIGHT COLOGIN. 474 00:17:34,522 --> 00:17:34,889 THIS IS NORMAL. 475 00:17:34,889 --> 00:17:39,828 THE BLUE IS THE COLLAGEN. 476 00:17:39,828 --> 00:17:41,229 YOU CAN SEE IT IN THE PORTAL 477 00:17:41,229 --> 00:17:42,730 AREA QUITE NICELY. 478 00:17:42,730 --> 00:17:43,465 I DON'T HAVE A CENTRAL VEIN OR 479 00:17:43,465 --> 00:17:45,633 THERE MIGHT BE ONE DOWN HERE IN 480 00:17:45,633 --> 00:17:47,702 THE FAR LEFT CORNER BUT THERE'S 481 00:17:47,702 --> 00:17:52,640 JUST A THIN RIM OF COLLAGEN 482 00:17:52,640 --> 00:17:53,141 AROUND THAT VEIN. 483 00:17:53,141 --> 00:17:54,976 NOW YOU'RE FULLY ACQUAINTED WITH 484 00:17:54,976 --> 00:17:56,311 THE PATHOLOGY OF THE LIVER, OR 485 00:17:56,311 --> 00:17:56,978 THE NORMAL. 486 00:17:56,978 --> 00:17:59,180 SO WE ARE GOING TO TALK ABOUT 487 00:17:59,180 --> 00:17:59,481 PATHOLOGY. 488 00:17:59,481 --> 00:18:01,049 THERE'S FOUR STAGES OF STEATOTIC 489 00:18:01,049 --> 00:18:01,716 LIVER DISEASE WHICH IS IMPORTANT 490 00:18:01,716 --> 00:18:02,383 FOR UNDERSTANDING WHAT IS GOING 491 00:18:02,383 --> 00:18:06,020 ON HERE. 492 00:18:06,020 --> 00:18:10,892 THERE'S THE FAT, THE STEATOSIS, 493 00:18:10,892 --> 00:18:12,327 WHICH IS INSIDE. 494 00:18:12,327 --> 00:18:14,395 THERE'S INFLAMMATION, THE 495 00:18:14,395 --> 00:18:15,063 HEPATITIS COMPONENT OF THIS 496 00:18:15,063 --> 00:18:15,530 DISEASE. 497 00:18:15,530 --> 00:18:21,035 SO CLUSTERS OF INFLAMMATORY 498 00:18:21,035 --> 00:18:23,004 CELLS IN THE PORTAL. 499 00:18:23,004 --> 00:18:25,106 AND THEN THE BALLOONING INJURY 500 00:18:25,106 --> 00:18:26,307 WHICH IS IMPORTANT TO, IT IS A 501 00:18:26,307 --> 00:18:29,344 SWELLING DUE TO INJURY TO THE 502 00:18:29,344 --> 00:18:32,313 ORGAN AND THE MEMBRANES OF THE 503 00:18:32,313 --> 00:18:32,814 SITE. 504 00:18:32,814 --> 00:18:34,616 AND THEN FIBROSIS, WHICH IS THE 505 00:18:34,616 --> 00:18:34,883 SCARRING. 506 00:18:34,883 --> 00:18:37,418 SO I'LL SHOW YOU ALL THESE 507 00:18:37,418 --> 00:18:37,652 THINGS. 508 00:18:37,652 --> 00:18:39,988 SO THIS IS WHAT STEATOSIS LOOKS 509 00:18:39,988 --> 00:18:40,255 LIKE. 510 00:18:40,255 --> 00:18:43,424 THE LIPID IN THE CELLS DISSOLVED 511 00:18:43,424 --> 00:18:44,726 OUT WHEN WE PROCESS THE CELLS TO 512 00:18:44,726 --> 00:18:46,561 LOOK AT THEM UNDER THE 513 00:18:46,561 --> 00:18:46,861 MICROSCOPE. 514 00:18:46,861 --> 00:18:49,330 IT LOOKS LIKE THESE EMPTY HOLES. 515 00:18:49,330 --> 00:18:51,733 THOSE ARE NORMALLY LIPID FILLED 516 00:18:51,733 --> 00:18:56,504 AND WITHIN THE PATASITES. 517 00:18:56,504 --> 00:18:58,172 YOU CAN BARELY SEE THE PLASM 518 00:18:58,172 --> 00:19:00,208 BECAUSE THE FAT IS TAKING UP SO 519 00:19:00,208 --> 00:19:02,210 MUCH ROOM. 520 00:19:02,210 --> 00:19:03,545 IT CAN LOOK ALMOST LIKE TISSUE 521 00:19:03,545 --> 00:19:08,049 THAT YOU MIGHT FIND IN THE 522 00:19:08,049 --> 00:19:09,083 ABDOMEN OR UNDERNEATH THE SKIN. 523 00:19:09,083 --> 00:19:12,153 IT USUALLY NEVER GETS THAT BAD 524 00:19:12,153 --> 00:19:13,354 BUT IT CAN. 525 00:19:13,354 --> 00:19:15,156 THEY CAN BE DIFFERENT SIZES. 526 00:19:15,156 --> 00:19:19,694 YOU CAN HAVE BIG VACULES OR 527 00:19:19,694 --> 00:19:22,096 LITTLE BUT THEY ARE ALL LIPID. 528 00:19:22,096 --> 00:19:24,566 WE HAVE THE INFLAMMATION. 529 00:19:24,566 --> 00:19:29,437 ON THE LEFT PANEL YOU SEE 530 00:19:29,437 --> 00:19:29,904 LOBULAR INFLAMMATION. 531 00:19:29,904 --> 00:19:32,040 THEY POINT TO LITTLE CLUSTERS OF 532 00:19:32,040 --> 00:19:35,209 INFLAMMATORY CELLS. 533 00:19:39,547 --> 00:19:40,715 YOU SEE LITTLE INCLUDCLUSTER HE 534 00:19:40,715 --> 00:19:41,082 HERE. 535 00:19:41,082 --> 00:19:42,483 THEY ARE THE MOST COMMON 536 00:19:42,483 --> 00:19:44,319 INFLAMMATORY CELLS. 537 00:19:44,319 --> 00:19:45,253 ON THE RIGHT YOU CAN SEE A 538 00:19:45,253 --> 00:19:46,654 PORTAL AREA AND ALL THE CELLS 539 00:19:46,654 --> 00:19:48,957 INSIDE THE PORTAL AREA ARE ALL 540 00:19:48,957 --> 00:19:50,058 MOSTLY INFLAMMATORY CELLS. 541 00:19:50,058 --> 00:19:53,061 SO YOU CAN HAVE PORTAL 542 00:19:53,061 --> 00:19:56,898 INFLAMMATION OR LOBULAR 543 00:19:56,898 --> 00:19:57,231 INFLAMMATION. 544 00:19:57,231 --> 00:20:02,070 THE BALLOONS G. 545 00:20:02,070 --> 00:20:05,406 THE YELLOW INDICATING BALLOON 546 00:20:05,406 --> 00:20:05,640 CELLS. 547 00:20:05,640 --> 00:20:13,147 IT'S ALL MESSED UP. IT'S CLUMPY 548 00:20:13,147 --> 00:20:14,315 AND STRANDY. 549 00:20:14,315 --> 00:20:18,052 I HAVE THE BLUE AREA UP ABOVE 550 00:20:18,052 --> 00:20:19,921 THAT POINTS TO THIS BIG CELL 551 00:20:19,921 --> 00:20:23,891 WHICH IS THE MALLOY-DENK BODY. 552 00:20:23,891 --> 00:20:26,060 THESE ARE CLUMPS OF PROTEINS 553 00:20:26,060 --> 00:20:28,262 WHICH ARE AN IMPORTANT 554 00:20:28,262 --> 00:20:29,564 CHARACTERISTIC OF THESE 555 00:20:29,564 --> 00:20:30,932 BALLOONED SITES AND THEY HELP US 556 00:20:30,932 --> 00:20:31,299 IDENTIFY THEM. 557 00:20:31,299 --> 00:20:33,234 OKAY. 558 00:20:33,234 --> 00:20:39,007 SO NOW COMPARING THE NORMAL 559 00:20:39,007 --> 00:20:41,843 AGAINST THE OTHER. 560 00:20:41,843 --> 00:20:42,644 THIS IS ALL HAPPENING ALL AT 561 00:20:42,644 --> 00:20:45,179 ONCE HERE ON THE RIGHT. 562 00:20:45,179 --> 00:20:46,881 YOU CAN SEE THE FAT AND YOU SEE 563 00:20:46,881 --> 00:20:48,883 THE BALLOONING AND THE 564 00:20:48,883 --> 00:20:50,084 INFLAMMATION AND IT'S ALL MIXED 565 00:20:50,084 --> 00:20:50,385 TOGETHER. 566 00:20:50,385 --> 00:20:53,955 AND THEN COMPARED TO WHAT THE 567 00:20:53,955 --> 00:20:55,456 PANEL ON THE LEFT, WHICH IS ALL 568 00:20:55,456 --> 00:20:55,690 NORMAL. 569 00:20:55,690 --> 00:20:59,394 SO QUITE A LOT IS HAPPENING IN 570 00:20:59,394 --> 00:21:01,729 THESE LIVER BIOPSIES. 571 00:21:01,729 --> 00:21:07,435 AND THERE'S ALSO A LOT OF 572 00:21:07,435 --> 00:21:07,702 FIBROSIS. 573 00:21:07,702 --> 00:21:09,170 THE NORMAL IS ON THE LEFT. 574 00:21:09,170 --> 00:21:09,971 NORMAL PORTAL AREA. 575 00:21:09,971 --> 00:21:11,205 SEE ALL OF THIS STRANDING IN 576 00:21:11,205 --> 00:21:12,874 BETWEEN THE CELLS? 577 00:21:12,874 --> 00:21:14,776 MAKING THESE CONNECTIONS. 578 00:21:14,776 --> 00:21:15,410 CUTTING THE CELLS OFF FROM ONE 579 00:21:15,410 --> 00:21:18,046 ANOTHER. 580 00:21:18,046 --> 00:21:20,782 THIS IS THE FIBROSIS THAT 581 00:21:20,782 --> 00:21:21,783 HAPPENS IN STEATOHEPATITIS. 582 00:21:21,783 --> 00:21:30,191 IT FORMS THESE NETWORKS OF CO 583 00:21:30,191 --> 00:21:32,593 COLLAGEN THROUGH THE CELLS AND 584 00:21:32,593 --> 00:21:36,297 THEY DROP OUT AND STEATOSIS. 585 00:21:36,297 --> 00:21:38,166 A LITTLE BIT OF HISTORY. 586 00:21:38,166 --> 00:21:43,271 BACK IN 1980 WE HAVE A LANDMARK 587 00:21:43,271 --> 00:21:49,577 PAPER FROM THE MAYO CLINIC. 588 00:21:49,577 --> 00:21:51,446 LUDWIG PUBLISHED A PAPER, NOT 589 00:21:51,446 --> 00:21:54,082 TOPLINE JOURNAL BY THE ONE BUT 590 00:21:54,082 --> 00:21:55,483 ONE THAT PRODUCED REALLY 591 00:21:55,483 --> 00:21:58,886 RESPECTABLE PAPERS THAT 592 00:21:58,886 --> 00:21:59,654 DESCRIBED THIS PATHOLOGY. 593 00:21:59,654 --> 00:22:03,224 NOW THIS PATHOLOGY HAD BEEN 594 00:22:03,224 --> 00:22:04,292 DESCRIBED BEFORE BUT HIS 595 00:22:04,292 --> 00:22:05,359 CONTRIBUTION, ONE OF HIS MAIN 596 00:22:05,359 --> 00:22:08,730 CONTRIBUTIONS WAS TO GIVE IT A 597 00:22:08,730 --> 00:22:09,130 NAME. 598 00:22:09,130 --> 00:22:10,932 ANYONE, ANY PERSON WHO HAS AN 599 00:22:10,932 --> 00:22:12,100 ILLNESS THAT DOES NOT HAVE A 600 00:22:12,100 --> 00:22:15,436 NAME WILL TELL YOU HOW IMPORTANT 601 00:22:15,436 --> 00:22:17,472 A NAME IS FOR TREATING A DISEASE 602 00:22:17,472 --> 00:22:18,039 AND SOLVING THE PROBLEM. 603 00:22:18,039 --> 00:22:22,043 SO HE CALLED IT STEATOHEPATITIS. 604 00:22:22,043 --> 00:22:23,111 IN PARTICULAR THIS PATHOLOGY IS 605 00:22:23,111 --> 00:22:25,146 VERY SIMILAR TO WHAT YOU SEE IN 606 00:22:25,146 --> 00:22:27,615 ALCOHOLIC HEPATITIS, HE CALLED 607 00:22:27,615 --> 00:22:29,784 IT NON ALCOHOLIC 608 00:22:29,784 --> 00:22:30,184 STEATOHEPATITIS. 609 00:22:30,184 --> 00:22:31,919 THAT'S WHERE OUR STORY BEGINS. 610 00:22:31,919 --> 00:22:32,920 NOW MY PART IN THIS STORY REALLY 611 00:22:32,920 --> 00:22:36,357 DOESN'T PICK UP UNTIL 18 YEARS 612 00:22:36,357 --> 00:22:38,025 LATER WHEN THE NIDDK CONVENED A 613 00:22:38,025 --> 00:22:42,563 WORKSHOP ON NON ALCOHOLIC 614 00:22:42,563 --> 00:22:43,131 STEATOHEPATITIS IN 1998. 615 00:22:43,131 --> 00:22:46,067 THESE WERE MOST OF THE SPEAKERS. 616 00:22:46,067 --> 00:22:50,004 SO I'M IN THERE SOMEWHERE. 617 00:22:50,004 --> 00:22:51,339 I HAD MORE HAIR THEN. 618 00:22:51,339 --> 00:22:53,341 I WAS TASKED WITH GATHERING THE 619 00:22:53,341 --> 00:22:53,674 PATHOLOGISTS. 620 00:22:53,674 --> 00:22:56,077 SO AROUND ME ARE THE 621 00:22:56,077 --> 00:22:56,711 PATHOLOGISTS WHO HAD PUBLISHED 622 00:22:56,711 --> 00:23:01,849 ON THIS TOPIC BEFORE. 623 00:23:01,849 --> 00:23:05,853 SEVERAL OF WHOM BECAME MY 624 00:23:05,853 --> 00:23:06,187 MENTORS. 625 00:23:06,187 --> 00:23:09,423 ONE OF WHOM, DR. ELIZABETH 626 00:23:09,423 --> 00:23:11,092 BRUNT, WHO IS STANDING HERE, 627 00:23:11,092 --> 00:23:12,794 BECAME A CLOSE COLLEAGUE FOR 628 00:23:12,794 --> 00:23:13,928 MANY SUBSEQUENT YEARS. 629 00:23:13,928 --> 00:23:16,397 THEN EVERYBODY ELSE ON HERE IS 630 00:23:16,397 --> 00:23:20,601 PRETTY MUCH A HEPATOLOGIST. 631 00:23:20,601 --> 00:23:23,371 YOU CAN SEE THE BALANCE HERE. 632 00:23:23,371 --> 00:23:26,707 ONE PATHOLOGIST AND ONE 633 00:23:26,707 --> 00:23:27,041 HEPATOLIGIST. 634 00:23:27,041 --> 00:23:31,445 THIS WAS A LITTLE BIT MORE 635 00:23:31,445 --> 00:23:31,712 BALANCED. 636 00:23:31,712 --> 00:23:36,217 FROM THAT WORKSHOP GREW THE NASH 637 00:23:36,217 --> 00:23:37,084 NETWORK. THIS IS THE TIMELINE. 638 00:23:37,084 --> 00:23:38,386 IT'S STILL GOING ON TODAY 639 00:23:38,386 --> 00:23:39,821 ALTHOUGH WE'RE CLOSING OUT THE 640 00:23:39,821 --> 00:23:40,688 NETWORK. 641 00:23:40,688 --> 00:23:41,789 WE'VE KIND OF ACCOMPLISHED MOST 642 00:23:41,789 --> 00:23:42,657 OF OUR GOALS. 643 00:23:42,657 --> 00:23:44,358 YOU CAN SEE THAT WE'VE DONE 644 00:23:44,358 --> 00:23:45,560 QUITE A LOT. 645 00:23:45,560 --> 00:23:49,330 SO FUNDING STARTED AROUND HERE. 646 00:23:49,330 --> 00:23:51,532 WE'VE DONE FIVE CLINICAL TRIALS 647 00:23:51,532 --> 00:23:54,702 AND WE'RE FINISHING A SIXTH NOW. 648 00:23:54,702 --> 00:23:57,772 WE DID A HUGE NATURAL HISTORY 649 00:23:57,772 --> 00:23:58,005 STUDY. 650 00:23:58,005 --> 00:24:01,676 AS ONE OF THE CO-LEADERS OF THE 651 00:24:01,676 --> 00:24:02,443 PATHOLOGY COMMITTEE, WE 652 00:24:02,443 --> 00:24:03,878 REGULARLY REVIEWED THE CASES 653 00:24:03,878 --> 00:24:05,279 THAT CAME INTO THE NETWORK. 654 00:24:05,279 --> 00:24:07,515 SO AS OF THE END OF LAST YEAR 655 00:24:07,515 --> 00:24:10,651 WE'D ACTUALLY REVIEWED ALMOST 656 00:24:10,651 --> 00:24:12,486 7,000 BIOPSIES AND SCORED THEM 657 00:24:12,486 --> 00:24:13,387 AS I WILL DESCRIBE. 658 00:24:13,387 --> 00:24:16,824 SO WE'VE DONE QUITE A LOT. 659 00:24:16,824 --> 00:24:19,393 SO WHEN THIS NETWORK FORMED THEY 660 00:24:19,393 --> 00:24:21,429 FORMED A PATHOLOGY COMMITTEE, IT 661 00:24:21,429 --> 00:24:22,797 WAS ONE PATHOLOGIST FROM EACH OF 662 00:24:22,797 --> 00:24:24,899 THE CLINICAL CENTERS AND THEN 663 00:24:24,899 --> 00:24:25,099 ME. 664 00:24:25,099 --> 00:24:26,234 AND OUR FIRST GOAL WAS TO CREATE 665 00:24:26,234 --> 00:24:28,669 A SCORING SYSTEM THAT COULD BE 666 00:24:28,669 --> 00:24:30,071 USED TO TRACK THE PATHOLOGY IN 667 00:24:30,071 --> 00:24:31,505 THESE PATIENTS. 668 00:24:31,505 --> 00:24:32,273 THAT'S REALLY IMPORTANT BECAUSE 669 00:24:32,273 --> 00:24:35,076 WE DIDN'T HAVE IMAGE ANALYSIS 670 00:24:35,076 --> 00:24:35,409 BACK THEN. 671 00:24:35,409 --> 00:24:36,277 AT LEAST NOT IN ANY WAY THAT WE 672 00:24:36,277 --> 00:24:37,311 COULD USE. 673 00:24:37,311 --> 00:24:39,914 AND SO WE NEEDED TO TAKE THE 674 00:24:39,914 --> 00:24:41,816 IMAGING OR THE PICTURES THAT I 675 00:24:41,816 --> 00:24:43,417 SHOWED YOU AND TURN THEM INTO 676 00:24:43,417 --> 00:24:44,252 NUMBERS SO WE COULD PUT THEM 677 00:24:44,252 --> 00:24:46,053 INTO A DATABASE AND ANALYZE 678 00:24:46,053 --> 00:24:46,287 THEM. 679 00:24:46,287 --> 00:24:48,222 SO THAT WAS OUR JOB. 680 00:24:48,222 --> 00:24:49,423 AND SO WE GATHERED. 681 00:24:49,423 --> 00:24:52,593 THIS WAS THE FIRST CENTRAL 682 00:24:52,593 --> 00:24:53,427 PATHOLOGY MEETING ACTUALLY TO DO 683 00:24:53,427 --> 00:24:54,528 -- TO LOOK AT CASES. 684 00:24:54,528 --> 00:24:55,897 BUT WE HAD MET BEFORE AND IT WAS 685 00:24:55,897 --> 00:24:57,798 PRETTY MUCH THE SAME GROUP. 686 00:24:57,798 --> 00:24:59,267 SO, AGAIN, YOU SEE BETH BRUNT 687 00:24:59,267 --> 00:25:00,835 HERE IN THE MIDDLE. 688 00:25:00,835 --> 00:25:02,837 MOST OF THESE PEOPLE ARE THE 689 00:25:02,837 --> 00:25:03,838 PATHOLOGISTS THAT FORMED THE 690 00:25:03,838 --> 00:25:06,173 CORE OF THAT FIRST GROUP. 691 00:25:06,173 --> 00:25:08,542 THEN WE HAVE STATISTICAL HELP 692 00:25:08,542 --> 00:25:09,944 FROM OUR DATA COORDINATION 693 00:25:09,944 --> 00:25:16,684 CENTER AT JOHN HOPKINS AND JOHN 694 00:25:16,684 --> 00:25:19,553 HOPKINS PI WHO PLAYED A BIG PART 695 00:25:19,553 --> 00:25:25,326 AS ONE OF THE LEAD HEPATOLOGISTS 696 00:25:25,326 --> 00:25:26,360 IN THE NETWORK. 697 00:25:26,360 --> 00:25:27,428 WE WROTE THIS PAPER. 698 00:25:27,428 --> 00:25:28,496 WE MET HERE IN THE BASEMENT 699 00:25:28,496 --> 00:25:29,730 ACTUALLY ON THE OTHER SIDE OF 700 00:25:29,730 --> 00:25:33,401 THIS WALL TO TALK ABOUT WHAT 701 00:25:33,401 --> 00:25:35,136 COULD WE LOOK AT IN THESE -- 702 00:25:35,136 --> 00:25:36,804 WHAT DID WE THINK WE COULD 703 00:25:36,804 --> 00:25:37,171 RECORD. 704 00:25:37,171 --> 00:25:39,640 I ASKED ALL OF THE PARTICIPANTS 705 00:25:39,640 --> 00:25:40,241 TO CONTRIBUTE THREE CASES AT 706 00:25:40,241 --> 00:25:42,176 LEAST. 707 00:25:42,176 --> 00:25:44,612 ONE THAT THEY THOUGHT WAS 708 00:25:44,612 --> 00:25:47,081 DEFINITELY STEATOHEPATITIS, ONE 709 00:25:47,081 --> 00:25:48,749 THAT WAS NOT, NO ONE WOULD AGREE 710 00:25:48,749 --> 00:25:49,517 THAT IT WAS AND THEN SOMETHING 711 00:25:49,517 --> 00:25:51,018 IN BETWEEN. 712 00:25:51,018 --> 00:25:54,655 SO WE REVIEWED THE CASES AT A 713 00:25:54,655 --> 00:25:58,259 MULTI-HEAD MICROSCOPE, KICAME U 714 00:25:58,259 --> 00:26:00,161 WITH A SCORING SYSTEM, 715 00:26:00,161 --> 00:26:02,063 CIRCULATED THE CASES TWICE TO DO 716 00:26:02,063 --> 00:26:04,565 THE OBSERVER VARIABILITY STUDIES 717 00:26:04,565 --> 00:26:06,467 AND THEN PUBLISHED. 718 00:26:06,467 --> 00:26:10,204 SO IT'S BASICALLY A METHODS 719 00:26:10,204 --> 00:26:10,438 PAPER. 720 00:26:10,438 --> 00:26:12,206 IT KIND OF EXPLODED ON US. 721 00:26:12,206 --> 00:26:13,841 IT WAS PICKED UP BY A LOT OF 722 00:26:13,841 --> 00:26:17,411 OTHER PEOPLE WHO FOUND IT VERY 723 00:26:17,411 --> 00:26:17,678 USEFUL. 724 00:26:17,678 --> 00:26:20,147 SO THAT WAS WONDERFUL, THAT WAS 725 00:26:20,147 --> 00:26:20,648 PART OF OUR GOAL. 726 00:26:20,648 --> 00:26:22,583 WE ALSO USED IT FOR THE NETWORK. 727 00:26:22,583 --> 00:26:23,551 THIS IS THE SCORING SYSTEM. 728 00:26:23,551 --> 00:26:27,521 I AM NOT GOING TO GO THROUGH 729 00:26:27,521 --> 00:26:27,755 THIS. 730 00:26:27,755 --> 00:26:31,158 SO BE THANKFUL FOR THAT. 731 00:26:31,158 --> 00:26:32,393 THE THINGS IN ORANGE WERE THE 732 00:26:32,393 --> 00:26:35,229 THINGS THAT WE STARTED OUT WITH. 733 00:26:35,229 --> 00:26:36,630 EVERYTHING ELSE IN WHITE WE 734 00:26:36,630 --> 00:26:36,998 ADDED LATER ON. 735 00:26:36,998 --> 00:26:39,200 SOME OF THE THINGS DROPPED OUT 736 00:26:39,200 --> 00:26:39,700 WITH TIME. 737 00:26:39,700 --> 00:26:42,203 AS I SAY, I'M NOT GOING TO GO 738 00:26:42,203 --> 00:26:43,304 THROUGH WITH IT BUT I AM GOING 739 00:26:43,304 --> 00:26:44,972 TO TELL YOU ABOUT THE THREE OR 740 00:26:44,972 --> 00:26:48,242 FOUR MOST IMPORTANT THINGS. 741 00:26:48,242 --> 00:26:52,580 SO WE CAME UP WITH SOME CORE 742 00:26:52,580 --> 00:26:53,414 ELEMENTS. THESE CAME OUT OF 743 00:26:53,414 --> 00:26:54,348 STATISTICAL ANALYSIS THAT WE DID 744 00:26:54,348 --> 00:26:57,985 THAT ULTIMATELY TURNED INTO A 745 00:26:57,985 --> 00:26:58,552 COMPOSITE SCORE. 746 00:26:58,552 --> 00:27:00,955 BUT WHAT WE -- WHAT TURNED OUT 747 00:27:00,955 --> 00:27:02,923 TO BE MOST IMPORTANT WAS A 748 00:27:02,923 --> 00:27:04,792 MEASURE OF STEATOSIS, WHICH IS A 749 00:27:04,792 --> 00:27:05,993 VERY SIMPLE LOW POWER 750 00:27:05,993 --> 00:27:07,194 EXAMINATION OF THE BIOPSY AND 751 00:27:07,194 --> 00:27:10,231 HOW MUCH THE LIVER SEEMED TO BE 752 00:27:10,231 --> 00:27:12,633 INVOLVED BY THE FAT. 753 00:27:12,633 --> 00:27:13,934 LOBULAR INFLAMMATION. 754 00:27:13,934 --> 00:27:15,302 AGAIN, WE WERE FOCUSING ON THESE 755 00:27:15,302 --> 00:27:17,204 LITTLE SITES OF INFLAMMATION AND 756 00:27:17,204 --> 00:27:21,142 COUNTING THEM, ESTIMATING THEM 757 00:27:21,142 --> 00:27:22,343 REALLY, IN A 20X FIELD. 758 00:27:22,343 --> 00:27:26,047 SO IN THE MICROSCOPE A 759 00:27:26,047 --> 00:27:27,915 PARTICULAR OBJECTIVE TO SEE HOW 760 00:27:27,915 --> 00:27:29,650 MANY AVERAGED ACROSS THE WHILE 761 00:27:29,650 --> 00:27:29,917 BIOPSY. 762 00:27:29,917 --> 00:27:31,452 AND THEN THE BALLOONING WHETHER 763 00:27:31,452 --> 00:27:33,054 WE DIDN'T SEE ANY OR WHERE WE 764 00:27:33,054 --> 00:27:34,455 FOUND THEM EASILY AND THEY WERE 765 00:27:34,455 --> 00:27:36,624 BIG OR WHERE THERE WERE ONLY A 766 00:27:36,624 --> 00:27:39,060 FEW OR THEY WERE HARD TO FIND. 767 00:27:39,060 --> 00:27:42,630 SO VERY SIMPLE SCORE. 768 00:27:42,630 --> 00:27:45,166 WE ALSO SCORED THE FIBROSIS OR 769 00:27:45,166 --> 00:27:46,834 STAGED THE FIBROSIS. 770 00:27:46,834 --> 00:27:50,371 EVERYTHING FROM NO FIBROSIS UP 771 00:27:50,371 --> 00:27:51,705 TO CIRRHOSIS WHICH WAS A STAGE 772 00:27:51,705 --> 00:27:52,640 FOUR. 773 00:27:52,640 --> 00:27:55,609 YOU CAN SEE A LITTLE BIT OF 774 00:27:55,609 --> 00:27:57,778 EARLY FIBROSIS IN THE TOP PHOTO 775 00:27:57,778 --> 00:28:00,448 AND A MORE EXTENSIVE ONE LIKE 776 00:28:00,448 --> 00:28:02,583 THE ONE I SHOWED BEFORE. THIS 777 00:28:02,583 --> 00:28:08,122 IS CIRRHOSIS DOWN AT THE BOTTOM 778 00:28:08,122 --> 00:28:12,760 WHERE YOU CAN SEE BIG BANDS OF 779 00:28:12,760 --> 00:28:13,928 COLLAGEN AT THE BOTTOM. 780 00:28:13,928 --> 00:28:16,464 WE GOT DONE, PRESENTED TO THE 781 00:28:16,464 --> 00:28:16,764 COMMITTEE. 782 00:28:16,764 --> 00:28:19,800 THE STATISTICIAN SAID THIS IS 783 00:28:19,800 --> 00:28:21,135 WONDERFUL BUT WE CAN'T USE A 784 00:28:21,135 --> 00:28:21,735 SINGLE SCORE TO DETERMINE 785 00:28:21,735 --> 00:28:22,937 WHETHER OR NOT SOMEBODY IS 786 00:28:22,937 --> 00:28:23,804 CHANGING THEIR DISEASE OR 787 00:28:23,804 --> 00:28:24,405 RESPONDING TO TREATMENT OR 788 00:28:24,405 --> 00:28:24,672 WHATEVER. 789 00:28:24,672 --> 00:28:27,341 SO WE HAD TO COME UP WITH A 790 00:28:27,341 --> 00:28:27,942 COMPOS 791 00:28:27,942 --> 00:28:28,242 COMPOSITE. 792 00:28:28,242 --> 00:28:30,044 MY RESPONSE TO THIS WAS SORT OF 793 00:28:30,044 --> 00:28:31,645 AS YOU SEE THE BOWLS OF FRUIT 794 00:28:31,645 --> 00:28:33,814 THERE, YOU HAVE LOTS OF 795 00:28:33,814 --> 00:28:35,082 DIFFERENT FRUIT IN THE FIRST 796 00:28:35,082 --> 00:28:37,718 BOWL AND OTHER KINDS OF FRUIT IN 797 00:28:37,718 --> 00:28:38,719 THE SECOND BOWL. 798 00:28:38,719 --> 00:28:40,588 HAS THE SECOND BOWL IMPROVED OR 799 00:28:40,588 --> 00:28:43,657 REGRESSED? 800 00:28:43,657 --> 00:28:48,062 WELL, YOU HAVE BAA -- BANANAS IN 801 00:28:48,062 --> 00:28:48,963 THE SECOND BUT NOT THE FIRST. 802 00:28:48,963 --> 00:28:52,566 THE GRAPES ARE DONE. 803 00:28:52,566 --> 00:28:53,334 IF -- ARE GONE. 804 00:28:53,334 --> 00:28:54,969 IF THE GRAPES ARE THE PROBLEM 805 00:28:54,969 --> 00:28:57,538 THINGS ARE BETTER NOW. 806 00:28:57,538 --> 00:28:59,073 THAT IS THE WAY I FELT ABOUT IT 807 00:28:59,073 --> 00:29:00,374 BUT I WAS OVERRULED AND IT'S 808 00:29:00,374 --> 00:29:01,809 PROBABLY JUST AS WELL. 809 00:29:01,809 --> 00:29:03,043 WHAT WE DID WAS DID A 810 00:29:03,043 --> 00:29:04,545 STATISTICAL ANALYSIS ON ALL OF 811 00:29:04,545 --> 00:29:06,046 THESE FEATURES THAT WE LOOKED 812 00:29:06,046 --> 00:29:06,280 AT. 813 00:29:06,280 --> 00:29:07,982 WE SAW WHAT WAS MOST RELATED TO 814 00:29:07,982 --> 00:29:08,949 WHAT WE THOUGHT WAS 815 00:29:08,949 --> 00:29:09,750 STEATOHEPATITIS. 816 00:29:09,750 --> 00:29:13,721 WE CAME UP WITH FOUR THINGS, 817 00:29:13,721 --> 00:29:23,397 STEATOSIS, LOBULAR, INFLAMM 818 00:29:23,397 --> 00:29:23,731 INFLAMMATION. 819 00:29:23,731 --> 00:29:29,303 THESE WERE RELATED TO THE 820 00:29:29,303 --> 00:29:29,837 SEVER 821 00:29:29,837 --> 00:29:30,104 SEVERITY. 822 00:29:30,104 --> 00:29:31,906 YOU CAN SEE THE PERCENTAGE OF 823 00:29:31,906 --> 00:29:42,449 CASES THAT WE CALLED DEFT NIT -- 824 00:29:43,250 --> 00:29:44,618 DEFINITE STEATOHEPATITIS GOING 825 00:29:44,618 --> 00:29:44,785 UP. 826 00:29:44,785 --> 00:29:46,754 SO WE CREATED THIS SCORE, THIS 827 00:29:46,754 --> 00:29:47,488 ACTIVITY SCORE WHICH WAS -- WE 828 00:29:47,488 --> 00:29:50,391 JUST ADDED THESE THINGS 829 00:29:50,391 --> 00:29:50,658 TOGETHER. 830 00:29:50,658 --> 00:29:53,060 SO INSTEAD OF GRAPES AND BANANAS 831 00:29:53,060 --> 00:29:56,630 AND APPLES, WE HAVE FRUIT, 832 00:29:56,630 --> 00:30:00,134 STEATOSIS PLUS LOBULAR 833 00:30:00,134 --> 00:30:01,368 INFLAMMATION BLUE BALLOONING 834 00:30:01,368 --> 00:30:02,903 SCORE WENT FROM 0 TO 8. 835 00:30:02,903 --> 00:30:04,104 NOW THE STATISTICIANS WERE 836 00:30:04,104 --> 00:30:05,873 HAPPY, THEY COULD SEE A CHANGE 837 00:30:05,873 --> 00:30:06,874 OVER AN 8-POINT SCALE. 838 00:30:06,874 --> 00:30:08,709 OVER ON THE RIGHT IS A GRAPH 839 00:30:08,709 --> 00:30:09,343 SHOWING HOW THE SCORE TRANSLATED 840 00:30:09,343 --> 00:30:12,479 INTO WHAT WE -- WHAT OUR 841 00:30:12,479 --> 00:30:14,048 DIAGNOSIS WAS. 842 00:30:14,048 --> 00:30:17,551 SO HIGH SCORE THINGS ALMOST 843 00:30:17,551 --> 00:30:18,185 ALWAYS GOT CALLED STEATOTIC OR 844 00:30:18,185 --> 00:30:26,794 STEATOHEPATITIS -- CALLED 845 00:30:26,794 --> 00:30:27,194 STEATOHEPATITIS. 846 00:30:27,194 --> 00:30:28,229 IT'S THE HUMP IN THE MIDDLE 847 00:30:28,229 --> 00:30:30,064 WHERE WE CALLED IT BORDERLINE OR 848 00:30:30,064 --> 00:30:30,364 SUSPICIOUS. 849 00:30:30,364 --> 00:30:32,333 IT HAD ALL OF THE FEATURES BUT 850 00:30:32,333 --> 00:30:33,367 NOT ALL OF THE FEATURES. 851 00:30:33,367 --> 00:30:35,035 SO THOSE WERE KIND OF IN THE 852 00:30:35,035 --> 00:30:35,269 MIDDLE. 853 00:30:35,269 --> 00:30:38,639 WE DID NOT ADD THE FIBROSIS 854 00:30:38,639 --> 00:30:40,174 BECAUSE IT'S MORE OF AN OUTCOME. 855 00:30:40,174 --> 00:30:43,177 WE FELT THAT THE ACTIVITY WAS 856 00:30:43,177 --> 00:30:44,945 CREATING THE FIBROSIS. 857 00:30:44,945 --> 00:30:46,680 WE DIDN'T WANT TO MIX IT ALL 858 00:30:46,680 --> 00:30:47,047 TOGETHER. 859 00:30:47,047 --> 00:30:48,349 WE DID WANT TO KNOW WHAT ALL OF 860 00:30:48,349 --> 00:30:48,849 THIS MEANT. 861 00:30:48,849 --> 00:30:52,453 SO A COUPLE OF YEARS LATER, SO 862 00:30:52,453 --> 00:30:54,622 NOW 2011, WE PUBLISHED A PAPER 863 00:30:54,622 --> 00:30:56,290 LOOKING AT ALL OF THE BIOPSIES 864 00:30:56,290 --> 00:30:58,392 THAT WE HAD SCORED THUS FAR, AT 865 00:30:58,392 --> 00:30:59,493 LEAST IN ADULTS. 866 00:30:59,493 --> 00:31:02,663 YOU CAN SEE THE GRAPH, WHICH 867 00:31:02,663 --> 00:31:03,664 LOOKS VERY SIMILAR TO THE 868 00:31:03,664 --> 00:31:05,432 PREVIOUS ONE NOW LOOKS CLEANER. 869 00:31:05,432 --> 00:31:06,400 WE DON'T HAVE SO MUCH NOISE DOWN 870 00:31:06,400 --> 00:31:07,701 HERE OR UP HERE. 871 00:31:07,701 --> 00:31:10,638 EVERYTHING, YOU KNOW, GOES TO 872 00:31:10,638 --> 00:31:11,038 STEATOHEPATITIS. 873 00:31:11,038 --> 00:31:12,306 WE STILL HAVE THIS HUMP IN THE 874 00:31:12,306 --> 00:31:13,540 MIDDLE OF THESE BORDERLINE 875 00:31:13,540 --> 00:31:15,409 CASES. 876 00:31:15,409 --> 00:31:18,112 BUT WHAT WE FOUND WAS THAT THE 877 00:31:18,112 --> 00:31:20,381 SCORE THAT WE CREATED WAS MORE 878 00:31:20,381 --> 00:31:21,882 ASSOCIATED WITH ALT. 879 00:31:21,882 --> 00:31:24,118 YOU CAN SEE THAT UP ABOVE. 880 00:31:24,118 --> 00:31:25,653 SO WE DIVIDE THE SCORES INTO A 881 00:31:25,653 --> 00:31:28,422 SCORE OF 5 OR GREATER VERSUS 4 882 00:31:28,422 --> 00:31:30,791 OR LESS VERSUS THE DIAGNOSIS 883 00:31:30,791 --> 00:31:31,392 THAT WE GAVE IT. 884 00:31:31,392 --> 00:31:33,027 AND THE SCORE WHEN WE PUT BOTH 885 00:31:33,027 --> 00:31:35,162 IN THE MODEL, THE SCORE COMES 886 00:31:35,162 --> 00:31:37,131 OUT TO BE MORE SIGNIFICANT AND 887 00:31:37,131 --> 00:31:40,868 HAVE A HIGHER ODDS RATIO OF, YOU 888 00:31:40,868 --> 00:31:41,935 KNOW, DETERMINING WHICH HAS THE 889 00:31:41,935 --> 00:31:44,171 HIGHER ALT. 890 00:31:44,171 --> 00:31:46,473 AND THEN WHEN YOU LOOK AT 891 00:31:46,473 --> 00:31:49,176 DIABETES AS A DIAGNOSIS, SO THE 892 00:31:49,176 --> 00:31:51,445 DIABETICS IN OUR POPULATION, THE 893 00:31:51,445 --> 00:31:53,213 SCORE DIDN'T MATTER SO MUCH. 894 00:31:53,213 --> 00:31:54,948 IT WAS NOT EVEN STATISTICALLY 895 00:31:54,948 --> 00:31:55,282 SIGNIFICANT. 896 00:31:55,282 --> 00:31:56,917 BUT THE DIAGNOSIS WAS. 897 00:31:56,917 --> 00:31:59,520 SO WE WERE SEEING THINGS IN THE 898 00:31:59,520 --> 00:32:01,488 BIOPSY THAT WENT BEYOND THE 899 00:32:01,488 --> 00:32:01,722 SCORE. 900 00:32:01,722 --> 00:32:04,658 SO WE COULD HAVE MILD CASES, 901 00:32:04,658 --> 00:32:05,693 WHICH WERE STILL STEATOHEPATITIS 902 00:32:05,693 --> 00:32:07,695 AND HIGH SCORE CASES THAT WERE 903 00:32:07,695 --> 00:32:12,099 NOT. 904 00:32:12,099 --> 00:32:13,734 SO THAT'S WHY THE SCORE WAS A 905 00:32:13,734 --> 00:32:14,668 LITTLE BIT DIFFERENT FROM THE 906 00:32:14,668 --> 00:32:14,968 DIAGNOSIS. 907 00:32:14,968 --> 00:32:21,909 SO WE MAINTAINED THAT DIFFERENCE 908 00:32:21,909 --> 00:32:22,976 ALL THE WAY THING. 909 00:32:22,976 --> 00:32:25,846 THE IMPORTANT THING WAS TO USE 910 00:32:25,846 --> 00:32:26,947 THIS SCORING SYSTEM IN CLINICAL 911 00:32:26,947 --> 00:32:30,017 TRIALS AND STUDY DISEASE 912 00:32:30,017 --> 00:32:30,351 PROGRESSION. 913 00:32:30,351 --> 00:32:30,918 WHOOPS. 914 00:32:30,918 --> 00:32:34,755 SO THE NASH CRN DID SIX CLINICAL 915 00:32:34,755 --> 00:32:34,988 TRIALS. 916 00:32:34,988 --> 00:32:36,090 YOU CAN SEE THEY ARE ALL 917 00:32:36,090 --> 00:32:36,523 ABBREVIATIONS HERE. 918 00:32:36,523 --> 00:32:40,461 WE DID TWO IN ADULTS AND TWO IN 919 00:32:40,461 --> 00:32:42,596 CHILDREN THAT HAD PRE AND POST 920 00:32:42,596 --> 00:32:46,867 TREATMENT BIOPSIES SO YOU COULD 921 00:32:46,867 --> 00:32:49,903 SEE WHAT WAS HAPPENING TO THESE 922 00:32:49,903 --> 00:32:50,204 PATIENTS. 923 00:32:50,204 --> 00:32:51,572 WE HAD ANOTHER PEDIATRIC STUDY 924 00:32:51,572 --> 00:32:54,608 THAT HAD A STUDY ENTRY BIOPSY 925 00:32:54,608 --> 00:32:59,747 ONLY AND THEN MOST RECENTLY OR 926 00:32:59,747 --> 00:33:01,482 ON GOING STUDY ONLY HAS A ENTRY 927 00:33:01,482 --> 00:33:02,316 BIOPSY AND ACTUALLY THAT WAS 928 00:33:02,316 --> 00:33:03,517 MADE OPTIONAL AFTER WE STARTED 929 00:33:03,517 --> 00:33:05,486 ENROLLING. 930 00:33:05,486 --> 00:33:06,720 I AM ONLY GOING TO TALK ABOUT 931 00:33:06,720 --> 00:33:07,254 ONE OF THESE. 932 00:33:07,254 --> 00:33:09,890 I'M GOING TO TALK ABOUT THE 933 00:33:09,890 --> 00:33:10,958 FLINT TRIAL, WHICH WAS THE 934 00:33:10,958 --> 00:33:12,126 SECOND ADULT TRIAL WE DID. IT'S 935 00:33:12,126 --> 00:33:14,561 A SIMPLER TRIAL. 936 00:33:14,561 --> 00:33:24,972 THIS WAS TO TEST THE DRUG 937 00:33:24,972 --> 00:33:25,305 OBETICHOLIC. 938 00:33:25,305 --> 00:33:26,673 IT WAS ONLY ADULTS. 939 00:33:26,673 --> 00:33:31,278 THEY HAD TO HAVE STEATOHEPATITIS 940 00:33:31,278 --> 00:33:32,112 AND BIOPSY OR THAT DIAGNOSIS HAD 941 00:33:32,112 --> 00:33:33,947 TO BE THERE AND THE SCORE HAD TO 942 00:33:33,947 --> 00:33:35,082 BE FOUR OR GREATER. 943 00:33:35,082 --> 00:33:38,986 SO WHAT WE WERE TRYING TO DO WAS 944 00:33:38,986 --> 00:33:41,288 GET THE MORE SEVERE DISEASE 945 00:33:41,288 --> 00:33:42,723 PATIENTS TO SEE CHANGE. 946 00:33:42,723 --> 00:33:44,658 THEY COULDN'T HAVE CIRRHOSIS SO 947 00:33:44,658 --> 00:33:45,726 THAT WAS AN EXCLUSION. 948 00:33:45,726 --> 00:33:47,060 YOU CAN SEE THE OTHER DETAILS. 949 00:33:47,060 --> 00:33:51,532 IF -- THE BIOPSY HAD TO BE DONE 950 00:33:51,532 --> 00:33:52,866 AT LEAST THREE MONTHS, NO LONGER 951 00:33:52,866 --> 00:33:53,400 THAN THREE MONTHS BEFORE 952 00:33:53,400 --> 00:33:55,436 TREATMENT AND THEN A SECOND 953 00:33:55,436 --> 00:33:57,471 BIOPSY AFTER 72 WEEKS OF 954 00:33:57,471 --> 00:33:57,838 TREATMENT. 955 00:33:57,838 --> 00:34:00,007 AND THE PRIMARY ENDPOINT, THE 956 00:34:00,007 --> 00:34:03,710 MAIN POINT WAS TO SHOW 957 00:34:03,710 --> 00:34:04,511 HISTOLOGIC IMPROVEMENT. 958 00:34:04,511 --> 00:34:07,014 THE SCORE HAD TO DROP BY TWO 959 00:34:07,014 --> 00:34:09,116 POINTS AND THE FIBROSIS COULDN'T 960 00:34:09,116 --> 00:34:09,483 BE COURSE. 961 00:34:09,483 --> 00:34:12,419 SO THIS IS THE SCHEMATIC OF THE 962 00:34:12,419 --> 00:34:13,153 STUDY DESIGN. 963 00:34:13,153 --> 00:34:17,791 SO PATIENTS GET ENROLLED, GOT A 964 00:34:17,791 --> 00:34:19,059 LIVER BIOPSY, RANDOMIZED TO ONE 965 00:34:19,059 --> 00:34:20,194 OF THESE TWO THERAPIES AND THEN 966 00:34:20,194 --> 00:34:22,629 TREATED FOR 72 WEEKS AND CAME 967 00:34:22,629 --> 00:34:24,598 OUT THE OTHER END, GOT ANOTHER 968 00:34:24,598 --> 00:34:26,099 BIOPSY AND FOLLOWED FOR ANOTHER 969 00:34:26,099 --> 00:34:30,270 24 WEEKS. 970 00:34:30,270 --> 00:34:33,974 THIS IS THE DIAGRAM THAT SHOWED 971 00:34:33,974 --> 00:34:35,609 YOU HOW THE PATIENTS FLOWED IN 972 00:34:35,609 --> 00:34:35,876 NUMBERS. 973 00:34:35,876 --> 00:34:37,444 IT WAS A LITTLE COMPLICATED 974 00:34:37,444 --> 00:34:40,147 BECAUSE WE HAD SORT OF AN EARLY 975 00:34:40,147 --> 00:34:40,380 STOP. 976 00:34:40,380 --> 00:34:42,583 SO OUT OF THE 345 PATIENTS THAT 977 00:34:42,583 --> 00:34:45,819 WERE ASSESSED, 62 WERE 978 00:34:45,819 --> 00:34:46,520 INELIGIBLE FOR ONE REASON OR 979 00:34:46,520 --> 00:34:47,721 ANOTHER. 980 00:34:47,721 --> 00:34:54,261 SO WE RANDOMIZED. 981 00:34:54,261 --> 00:34:57,598 ABOUT HALF EACH AND PLACEBO. 982 00:34:57,598 --> 00:34:59,466 SOME PATIENTS DIDN'T GET A BUY 983 00:34:59,466 --> 00:35:02,569 OLE -- BIOPSY IN THE END AND 984 00:35:02,569 --> 00:35:05,072 ASSUMED TO NOT HAVE IMPROVED. 985 00:35:05,072 --> 00:35:06,340 THEN THE DATA SAFETY AND 986 00:35:06,340 --> 00:35:07,207 MONITORING BOARD ACTUALLY 987 00:35:07,207 --> 00:35:09,910 DETERMINED THAT WE HAD REACHED 988 00:35:09,910 --> 00:35:11,011 AN ENDPOINT BEFORE EVERYONE HAD 989 00:35:11,011 --> 00:35:14,081 GONE THROUGH THE TRIAL SO WE 990 00:35:14,081 --> 00:35:18,852 DIDN'T DO THE LAST 64 BIOPSIES. 991 00:35:18,852 --> 00:35:21,922 IN TEND WE HAD 192 BIOPSIES ON 992 00:35:21,922 --> 00:35:24,424 ONE SIDE, 98 ON THE OTHER. 993 00:35:24,424 --> 00:35:27,261 WE INCLUDED THESE EXTRAS AND NOT 994 00:35:27,261 --> 00:35:27,528 IMPROVED. 995 00:35:27,528 --> 00:35:28,529 SO HOW DID WE DO? 996 00:35:28,529 --> 00:35:29,696 WE HIT OUR ENDPOINT. 997 00:35:29,696 --> 00:35:30,631 SO THERE WAS AN IMPROVEMENT IN 998 00:35:30,631 --> 00:35:34,101 THE SCORE OF GREATER THAN 2 999 00:35:34,101 --> 00:35:34,334 POINTS. 1000 00:35:34,334 --> 00:35:38,071 YOU CAN SEE DOWN HERE 21% OF THE 1001 00:35:38,071 --> 00:35:43,810 PATIENTS ON PLACEBO AND 46% OF 1002 00:35:43,810 --> 00:35:45,846 THE PATIENTS WHO GOT TREATED. 1003 00:35:45,846 --> 00:35:48,649 THAT WAS HIGHLY STA 1004 00:35:48,649 --> 00:35:49,883 STATISTICALLY SIGNIFICANT. 1005 00:35:49,883 --> 00:35:51,752 THAT WAS A PERSISTENT FINDING. 1006 00:35:51,752 --> 00:35:53,820 10 TO 20% OF PATIENTS GET BETTER 1007 00:35:53,820 --> 00:35:54,688 ON THEIR OWN. 1008 00:35:54,688 --> 00:35:57,224 THAT HAS TO DO WITH A 1009 00:35:57,224 --> 00:35:58,158 COMPLICATED NATURAL HISTORY OF 1010 00:35:58,158 --> 00:35:59,326 THIS DISEASE AND SOME OTHER 1011 00:35:59,326 --> 00:35:59,593 FACTORS. 1012 00:35:59,593 --> 00:36:02,963 BUT IT DOES SEEM TO BE A REAL 1013 00:36:02,963 --> 00:36:05,399 PHENOMENON. 1014 00:36:05,399 --> 00:36:05,933 MAKES EVERYTHING HARDER. 1015 00:36:05,933 --> 00:36:07,734 AND WHEN YOU LOOKED AT THE 1016 00:36:07,734 --> 00:36:08,936 INDIVIDUAL COMPONENTS, SO NOT 1017 00:36:08,936 --> 00:36:10,571 ONLY THE COMPOSITE SCORE BUT ALL 1018 00:36:10,571 --> 00:36:12,539 THESE INDIVIDUAL FEATURES, WE 1019 00:36:12,539 --> 00:36:16,843 ALSO SHOWED IMPROVEMENT . 1020 00:36:16,843 --> 00:36:19,947 SO THE STEATOSIS GOT BETTER, 1021 00:36:19,947 --> 00:36:23,050 INFLAMMATION GOT BETTER, 1022 00:36:23,050 --> 00:36:23,784 BALLOONING GOT BETTER. 1023 00:36:23,784 --> 00:36:25,519 YOU CAN SEE THE PATIENTS 1024 00:36:25,519 --> 00:36:26,553 IMPROVED. 1025 00:36:26,553 --> 00:36:29,256 DOWN BELOW IS THE SCORE. 1026 00:36:29,256 --> 00:36:31,925 ON STEATOSIS ON AVERAGE DROPPED 1027 00:36:31,925 --> 00:36:37,764 .8 POINTS COMPARED TO .4 OF 1028 00:36:37,764 --> 00:36:38,498 PLACEBO ACROSS THE BOTTOM THERE. 1029 00:36:38,498 --> 00:36:40,567 FIBROSIS ALSO IMPROVED. SO THAT 1030 00:36:40,567 --> 00:36:42,603 WAS REALLY A BIG BONUS. 1031 00:36:42,603 --> 00:36:45,639 SO WE HAD 35% OF PATIENTS 1032 00:36:45,639 --> 00:36:48,675 IMPROVING ON DRUG AND 19% ON 1033 00:36:48,675 --> 00:36:49,142 PLACEBO AND THAT WAS 1034 00:36:49,142 --> 00:36:51,278 SIGNIFICANT. 1035 00:36:51,278 --> 00:36:54,081 ONE THING THAT WE DIDN'T SEE IS 1036 00:36:54,081 --> 00:36:58,085 THAT PATIENTS DIDN'T RESOLVE 1037 00:36:58,085 --> 00:37:00,954 THEIR STEATOHEPATITIS. 1038 00:37:00,954 --> 00:37:02,155 SO WE COULD STILL DETECT THAT 1039 00:37:02,155 --> 00:37:02,990 THIS WAS THERE AT THE SECOND 1040 00:37:02,990 --> 00:37:05,392 BIOPSY IN MOST OF THE PATIENTS 1041 00:37:05,392 --> 00:37:08,428 WHICH TO ME TELLS ME THAT WE'RE 1042 00:37:08,428 --> 00:37:10,530 DAMPENING THE ACTIVITY OF THE 1043 00:37:10,530 --> 00:37:13,934 DISEASE BUT NOT MAKING IT GO 1044 00:37:13,934 --> 00:37:14,301 AWAY COMPLETE. 1045 00:37:14,301 --> 00:37:16,269 IT WAS HAVING ENOUGH AN EFFECT 1046 00:37:16,269 --> 00:37:20,807 THAT WE WERE SEEING FIBROSIS 1047 00:37:20,807 --> 00:37:21,508 IMPROVE 1048 00:37:21,508 --> 00:37:21,842 IMPROVEMENT. 1049 00:37:21,842 --> 00:37:24,611 SO IT IMPROVED THE FEATURES OF 1050 00:37:24,611 --> 00:37:26,780 NASH INCLUDING FIBROSIS. IT WAS 1051 00:37:26,780 --> 00:37:28,081 ASSOCIATED WITH SOME SIDE 1052 00:37:28,081 --> 00:37:31,051 EFFECTS THAT WAS SEVERE IN SOME 1053 00:37:31,051 --> 00:37:31,351 PATIENTS. 1054 00:37:31,351 --> 00:37:34,087 IT DID CAUSE AN ELEVATED TOTAL 1055 00:37:34,087 --> 00:37:37,924 AND LDL CHOLESTEROL BUT 1056 00:37:37,924 --> 00:37:39,559 DECREASED HDL CHOLESTEROL. 1057 00:37:39,559 --> 00:37:40,360 THAT WAS PLANNED FOR FUTURE 1058 00:37:40,360 --> 00:37:43,230 CLINICAL TRIALS TO LOOK AT THAT 1059 00:37:43,230 --> 00:37:44,698 MORE CAREFULLY. 1060 00:37:44,698 --> 00:37:47,401 BUT THIS TRIAL, WHEN THIS TRIAL 1061 00:37:47,401 --> 00:37:49,002 SORT OF WENT PUBLIC, THIS IS 1062 00:37:49,002 --> 00:37:50,971 WHEN THE PHARMACEUTICAL 1063 00:37:50,971 --> 00:37:52,172 COMPANIES REALLY GOT INTERESTED 1064 00:37:52,172 --> 00:37:54,274 AND SORT OF DATES FROM THIS 1065 00:37:54,274 --> 00:37:54,474 TIME. 1066 00:37:54,474 --> 00:37:56,777 AFTER THAT THERE WERE LOTS OF 1067 00:37:56,777 --> 00:37:58,412 CLINICAL TRIALS. 1068 00:37:58,412 --> 00:38:03,150 MOST OF WHICH USED HISTOLOGIC 1069 00:38:03,150 --> 00:38:04,051 ENDPOINTS AND THIS SCORING 1070 00:38:04,051 --> 00:38:07,554 SYSTEM TO EVALUATE THE CHANGES. 1071 00:38:07,554 --> 00:38:09,423 THE OTHER STUDY I WANT TO POINT 1072 00:38:09,423 --> 00:38:10,757 OUT HERE IS IN LONGITUDINAL 1073 00:38:10,757 --> 00:38:11,425 STUDY WE DID. 1074 00:38:11,425 --> 00:38:13,093 WE HAD A LOT OF PATIENTS 1075 00:38:13,093 --> 00:38:17,564 ENROLLED, A LOT OF PATIENTS WITH 1076 00:38:17,564 --> 00:38:18,432 PAIRED BIOPSIES WHO HAD NOT BEEN 1077 00:38:18,432 --> 00:38:18,965 TREATED IN BETWEEN. 1078 00:38:18,965 --> 00:38:21,101 SO WE GATHERED ALL THOSE 1079 00:38:21,101 --> 00:38:22,669 BIOPSIES TOGETHER AND ANALYZED 1080 00:38:22,669 --> 00:38:22,869 THEM. 1081 00:38:22,869 --> 00:38:24,137 EVERYONE WHO HAD A BIOPSY AT 1082 00:38:24,137 --> 00:38:26,006 LEAST A YEAR APART AND THAT WERE 1083 00:38:26,006 --> 00:38:28,075 NOT TREATED IN A CLINICAL TRIAL 1084 00:38:28,075 --> 00:38:31,044 IN BETWEEN. 1085 00:38:31,044 --> 00:38:33,647 SO AGAIN A COMPLICATED CONSORT 1086 00:38:33,647 --> 00:38:33,914 DIAGRAM. 1087 00:38:33,914 --> 00:38:39,686 THE MOST SPOIMPORTANT THING AT 1088 00:38:39,686 --> 00:38:43,056 END AFTER ELIMINATING EVERYTHING 1089 00:38:43,056 --> 00:38:44,391 THAT WOULDN'T FIT OUR 1090 00:38:44,391 --> 00:38:46,860 DEFINITIONS WE HAD DATA ON 464 1091 00:38:46,860 --> 00:38:48,695 PATIENTS AND CLINICAL DATA TO GO 1092 00:38:48,695 --> 00:38:50,097 WITH THAT ON 219. 1093 00:38:50,097 --> 00:38:51,465 SOME BIOPSIES WERE WAY BEFORE 1094 00:38:51,465 --> 00:38:52,299 THE NETWORK STARTED SO THEY 1095 00:38:52,299 --> 00:38:56,703 DIDN'T HAVE CLINICAL DATA. 1096 00:38:56,703 --> 00:38:58,205 SO WHAT DID WE FIND. 1097 00:38:58,205 --> 00:38:59,339 SO THERE WERE A LOT OF FINDINGS 1098 00:38:59,339 --> 00:39:01,908 IN THIS STUDY BUT I'M GOING TO 1099 00:39:01,908 --> 00:39:05,679 FOCUS ON THE HISTOLOGIC ONES. 1100 00:39:05,679 --> 00:39:11,785 IF YOU JUST LOOK AT THE 1101 00:39:11,785 --> 00:39:13,186 HISTOLOGY YOU CAN SEE BASELINE 1102 00:39:13,186 --> 00:39:14,488 AND CHANGES OVER TIME IN BETWEEN 1103 00:39:14,488 --> 00:39:15,188 THE TWO BIOPSIES. 1104 00:39:15,188 --> 00:39:17,224 THE THINGS THAT CAME OUT AS 1105 00:39:17,224 --> 00:39:18,458 SIGNIFICANT WERE BASELINE 1106 00:39:18,458 --> 00:39:20,560 BALLOONING AND PORTAL 1107 00:39:20,560 --> 00:39:22,095 INFORMATION AND CHANGES IN 1108 00:39:22,095 --> 00:39:23,497 CHANGING AND PORTAL 1109 00:39:23,497 --> 00:39:23,930 INFLAMMATION. 1110 00:39:23,930 --> 00:39:28,101 MOST OF THESE THINGS WERE 1111 00:39:28,101 --> 00:39:30,137 SIGNIFICANT EXCEPT LOBULAR 1112 00:39:30,137 --> 00:39:31,004 INFLAMMATION ODDLY ENOUGH DIDN'T 1113 00:39:31,004 --> 00:39:32,706 COME OUT AS A SIGNIFICANT 1114 00:39:32,706 --> 00:39:37,043 FINDING IN THIS ANALYSIS. 1115 00:39:37,043 --> 00:39:39,980 BUT WE COULD SAY IF YOU KNOW 1116 00:39:39,980 --> 00:39:42,616 WHERE THE BASELINE IS WHICH 1117 00:39:42,616 --> 00:39:45,919 PATIENTS ARE LIKELY TO DO WORSE 1118 00:39:45,919 --> 00:39:47,087 OVER THE NEXT FEW YEARS. 1119 00:39:47,087 --> 00:39:48,889 IF YOU KNOW THEN SOME CLINICAL 1120 00:39:48,889 --> 00:39:50,490 THINGS ABOUT THOSE PATIENTS, YOU 1121 00:39:50,490 --> 00:39:52,392 COULD SAY, YOU KNOW, WHO WAS 1122 00:39:52,392 --> 00:39:55,328 REALLY GETTING BETTER OR WORSE. 1123 00:39:55,328 --> 00:39:57,631 WE ALSO USED THE COMPOSITE 1124 00:39:57,631 --> 00:40:00,100 SCORE, WHICH DIDN'T HAVE SO MUCH 1125 00:40:00,100 --> 00:40:03,036 SIGNIFICANCE ON REGRESSION. 1126 00:40:03,036 --> 00:40:05,605 I THINK PARTLY BECAUSE IT WAS 1127 00:40:05,605 --> 00:40:09,643 THE MALLORY-DANK BODY IS A GOOD 1128 00:40:09,643 --> 00:40:10,610 SURROGATE FOR BALLOONING AND 1129 00:40:10,610 --> 00:40:11,845 DECREASED THE IMPORTANCE OF THE 1130 00:40:11,845 --> 00:40:14,314 OTHER CHANGES IN THE NASH. 1131 00:40:14,314 --> 00:40:15,549 PROGRESSION, IT DID MAKE A 1132 00:40:15,549 --> 00:40:16,850 DIFFERENCE AT BASELINE. 1133 00:40:16,850 --> 00:40:17,717 AND THEN CHANGES WERE 1134 00:40:17,717 --> 00:40:19,219 SIGNIFICANT. 1135 00:40:19,219 --> 00:40:23,957 SO ACTIVITY UP, ACTIVITY DOWN, 1136 00:40:23,957 --> 00:40:25,926 FIBROSIS EITHER IMPROVES OR 1137 00:40:25,926 --> 00:40:26,226 WORSENS. 1138 00:40:26,226 --> 00:40:28,495 IT'S TRUE WITH THE DIAGNOSIS 1139 00:40:28,495 --> 00:40:28,695 TOO. 1140 00:40:28,695 --> 00:40:29,930 THIS IS KIND OF A COMPLICATED 1141 00:40:29,930 --> 00:40:30,297 GRAPH. 1142 00:40:30,297 --> 00:40:33,333 BUT WHAT I WANT YOU TO FOCUS ON, 1143 00:40:33,333 --> 00:40:34,801 SO THE STAGES ARE DOWN HERE. 1144 00:40:34,801 --> 00:40:36,937 SO CIRRHOSIS IS AT THE RIGHT. 1145 00:40:36,937 --> 00:40:38,805 NO FIBROSIS IS AT THE LEFT. 1146 00:40:38,805 --> 00:40:42,309 SO BLUE OR DARK PURPLE I GUESS 1147 00:40:42,309 --> 00:40:42,609 IS GOOD. 1148 00:40:42,609 --> 00:40:43,376 AND RED IS BAD. 1149 00:40:43,376 --> 00:40:44,978 THEY ARE ALL STACKED UP NICELY, 1150 00:40:44,978 --> 00:40:47,480 RIGHT. 1151 00:40:47,480 --> 00:40:53,653 SO IF YOUR DIAGNOSIS GETS WORSE, 1152 00:40:53,653 --> 00:40:56,623 FROM FATTY LIVER DISEASE TO 1153 00:40:56,623 --> 00:40:57,958 NASH, THIS BLUE BAR GOES ALMOST 1154 00:40:57,958 --> 00:40:59,326 TO NOTHING. 1155 00:40:59,326 --> 00:41:01,228 MEANS THAT EVERYBODY GETS 1156 00:41:01,228 --> 00:41:04,431 FIBROSIS AFTER ABOUT FOUR YEARS. 1157 00:41:04,431 --> 00:41:06,867 THAT SOME PATIENTS GET -- MOVE 1158 00:41:06,867 --> 00:41:08,435 INTO ADVANCED FIBROSIS. 1159 00:41:08,435 --> 00:41:10,237 IN IN MIDDLE CATEGORY HAVING 1160 00:41:10,237 --> 00:41:12,272 BORDERLINE FEATURES INTO 1161 00:41:12,272 --> 00:41:14,207 STEATOHEPATITIS, THERE ARE A LOT 1162 00:41:14,207 --> 00:41:15,575 OF PEOPLE THAT DEVELOP 1163 00:41:15,575 --> 00:41:15,876 CIRRHOSIS. 1164 00:41:15,876 --> 00:41:18,578 IF YOU JUST GO FROM FATTY LIVER 1165 00:41:18,578 --> 00:41:20,447 TO A BORDERLINE DIAGNOSIS, EVEN 1166 00:41:20,447 --> 00:41:23,717 THEY GET WORSE. 1167 00:41:23,717 --> 00:41:25,619 SO THERE'S PROGRESSION WHEN THE 1168 00:41:25,619 --> 00:41:27,354 DISEASE GETS WORSE THE FIBROSIS 1169 00:41:27,354 --> 00:41:28,188 GETS WORSE. 1170 00:41:28,188 --> 00:41:30,190 THAT MAKES SENSE. 1171 00:41:30,190 --> 00:41:32,158 BUT THIS WAS REALLY THE FIRST 1172 00:41:32,158 --> 00:41:33,860 LONGITUDINAL BIOPSY-BASED STUDY 1173 00:41:33,860 --> 00:41:35,428 TO SHOW THAT. 1174 00:41:35,428 --> 00:41:37,430 AND THEN THIS IS THE FINAL GRAPH 1175 00:41:37,430 --> 00:41:41,368 I'M GOING TO SHOW ON THIS. 1176 00:41:41,368 --> 00:41:42,636 DISEASE ACTIVITY IN STAGE RUN IN 1177 00:41:42,636 --> 00:41:42,903 PARALLEL. 1178 00:41:42,903 --> 00:41:44,905 SO THE CHANGE IN THE NASH SCORE, 1179 00:41:44,905 --> 00:41:47,707 WHATEVER CONTRIBUTES TO THAT 1180 00:41:47,707 --> 00:41:49,976 CHANGE RUNS MORE OR LESS IN LINE 1181 00:41:49,976 --> 00:41:53,413 WITH THE CHANGE IN THE STAGE. 1182 00:41:53,413 --> 00:41:53,980 SO STAGE IMPROVEMENT, NASH 1183 00:41:53,980 --> 00:41:56,883 IMPROVEMENT GO TOGETHER. 1184 00:41:56,883 --> 00:41:59,519 SO THIS WAS THE LARGEST PAIRED 1185 00:41:59,519 --> 00:42:01,087 BIOPSY STUDY. 1186 00:42:01,087 --> 00:42:02,856 IT'S STILL THE LARGEST PAIRED 1187 00:42:02,856 --> 00:42:04,891 BIOPSY STUDY. 1188 00:42:04,891 --> 00:42:07,527 I WENT THROUGH MOST OF THESE 1189 00:42:07,527 --> 00:42:07,894 OBSERVATIONS. 1190 00:42:07,894 --> 00:42:10,330 SO I'M GOING TO GO ON. 1191 00:42:10,330 --> 00:42:13,099 SO WE'VE HAD A COUPLE OF STUDIES 1192 00:42:13,099 --> 00:42:16,069 THAT HAVE COME OUT OF THIS THAT 1193 00:42:16,069 --> 00:42:18,305 HAVE RELATED TO FINDINGS OUTSIDE 1194 00:42:18,305 --> 00:42:21,341 PURELY THE AREA OF PATHOLOGY. 1195 00:42:21,341 --> 00:42:22,809 THIS WAS A GENOME WIDE 1196 00:42:22,809 --> 00:42:25,145 ASSOCIATION STUDY USING IMAGING 1197 00:42:25,145 --> 00:42:26,680 ON PATIENTS WHO WERE ENROLLED IN 1198 00:42:26,680 --> 00:42:28,048 THE DALLAS HEART STUDY. 1199 00:42:28,048 --> 00:42:29,482 THIS WAS NOT A BIOPSY STUDY. 1200 00:42:29,482 --> 00:42:31,918 THIS WAS A STUDY BASED ON MRI 1201 00:42:31,918 --> 00:42:36,122 IMAGING OF FAT. 1202 00:42:36,122 --> 00:42:45,065 THEY FOUND A POLYMORPHISM IN THE 1203 00:42:45,065 --> 00:42:48,335 DNA NEAR THIS GENE PNPLA3. 1204 00:42:48,335 --> 00:42:49,602 SO YOU CAN SEE THAT THAT LITTLE 1205 00:42:49,602 --> 00:42:54,774 DOT OUT ON THE END RIGHT HERE, 1206 00:42:54,774 --> 00:42:57,444 THAT'S THE ONLY SIGNIFICANT 1207 00:42:57,444 --> 00:42:58,311 POLYMORPHISM THEY FOUND ACROSS 1208 00:42:58,311 --> 00:42:59,879 THE WHOLE GENOME. THIS WAS THE 1209 00:42:59,879 --> 00:43:03,984 VERY FIRST STUDY OR ONE OF THE 1210 00:43:03,984 --> 00:43:06,086 FIRST AND MOST IMPORTANT 1211 00:43:06,086 --> 00:43:06,353 STUDIES. 1212 00:43:06,353 --> 00:43:07,020 SHORTLY AFTER THAT WE PUBLISHED 1213 00:43:07,020 --> 00:43:10,457 TWO -- THERE WERE TWO BIOPSY 1214 00:43:10,457 --> 00:43:13,259 STUDIES THAT CAME OUT OF THE 1215 00:43:13,259 --> 00:43:13,526 NETWORK. 1216 00:43:13,526 --> 00:43:14,928 BOTH CONFIRMING THIS AND 1217 00:43:14,928 --> 00:43:18,832 EXTENDING THOSE OBSERVATIONS NOW 1218 00:43:18,832 --> 00:43:21,101 INCLUDING HISTOLOGY. 1219 00:43:21,101 --> 00:43:22,802 I'M GOING TO TALK ABOUT THE ONE 1220 00:43:22,802 --> 00:43:27,173 DONE OUT OF THE NIH. 1221 00:43:27,173 --> 00:43:29,943 RAKMAN WAS THE PI ON THIS 1222 00:43:29,943 --> 00:43:30,243 PORTFOLIO. 1223 00:43:30,243 --> 00:43:32,345 WE LOOKED AT THIS, CONFIRMED IT 1224 00:43:32,345 --> 00:43:35,982 WAS PRESENT AND SPECIFICALLY THE 1225 00:43:35,982 --> 00:43:38,618 C TO G DIFFERENCE AT THIS POINT 1226 00:43:38,618 --> 00:43:42,722 IN THE GENOME AND THAT ACTUALLY 1227 00:43:42,722 --> 00:43:44,824 CORRESPONDED TO TO A CHANGE IN 1228 00:43:44,824 --> 00:43:47,727 THE AMINO ACID SEQUENCE OF THIS 1229 00:43:47,727 --> 00:43:49,095 PROT 1230 00:43:49,095 --> 00:43:49,362 PROTEIN. 1231 00:43:49,362 --> 00:43:51,564 WHEN YOU HAD TWO OF THEM WERE 1232 00:43:51,564 --> 00:43:56,336 MORE LIKELY TO HAVE STEATOSIS OR 1233 00:43:56,336 --> 00:43:58,071 MALLORY BODIES. 1234 00:43:58,071 --> 00:43:59,739 SORRY AND INFLAMMATION. 1235 00:43:59,739 --> 00:44:02,075 THOSE THREE IMPORTANT THINGS, 1236 00:44:02,075 --> 00:44:07,680 AGAIN MALLORY BODIES BEING A 1237 00:44:07,680 --> 00:44:09,315 SURROGATE FOR BALLOONING ALL 1238 00:44:09,315 --> 00:44:14,888 WENT UP IN PATIENTS WITH G 1239 00:44:14,888 --> 00:44:15,255 ALLEL. 1240 00:44:15,255 --> 00:44:16,990 ALL FLEE OF THOSE WERE 1241 00:44:16,990 --> 00:44:17,290 IMPORTANT. 1242 00:44:17,290 --> 00:44:20,427 THE GRAPH ON THE RIGHT SHOWS THE 1243 00:44:20,427 --> 00:44:21,961 PEDIATRIC POPULATION, WHAT AGE 1244 00:44:21,961 --> 00:44:22,996 AT FIRST BIOPSY, WHICH IS KIND 1245 00:44:22,996 --> 00:44:25,265 OF A SURROGATE FOR WHEN PEOPLE 1246 00:44:25,265 --> 00:44:28,068 PICKED UP THE DISEASE. 1247 00:44:28,068 --> 00:44:31,237 IF YOU WERE UNDER 9 AND GOT A 1248 00:44:31,237 --> 00:44:33,540 BIOPSY YOU WERE ABOUT 90% LIKELY 1249 00:44:33,540 --> 00:44:38,078 TO HAVE THIS G ALLEL. 1250 00:44:38,078 --> 00:44:38,745 SO PRETTY IMPORTANT MARKER. 1251 00:44:38,745 --> 00:44:40,647 WE'VE ALSO LOOKED AT 1252 00:44:40,647 --> 00:44:43,349 TRANSCRIPTOMICS. 1253 00:44:43,349 --> 00:44:47,120 THERE'S ARUN'S NAME AND MELISSA 1254 00:44:47,120 --> 00:44:48,655 CANTOS WAS A PATHOLOGIST WITH 1255 00:44:48,655 --> 00:44:50,924 THE NASH CRN. 1256 00:44:50,924 --> 00:44:52,926 SO SHE DID ALL THE SCORING FROM 1257 00:44:52,926 --> 00:44:53,259 THIS STUDY. 1258 00:44:53,259 --> 00:44:55,128 THEY WEREN'T BIOPSIES OUT OF THE 1259 00:44:55,128 --> 00:44:55,462 NETWORK. 1260 00:44:55,462 --> 00:44:59,599 THEY RELATED HISTOLOGIC TO GENE 1261 00:44:59,599 --> 00:45:01,267 CHANGES AND LOOKED AT A WHOLE 1262 00:45:01,267 --> 00:45:03,036 BUNCH OF GENE PATHWAYS. 1263 00:45:03,036 --> 00:45:04,637 YOU CAN SEE WHEN YOU PLOT THESE 1264 00:45:04,637 --> 00:45:07,640 GENE PATHWAYS THE SUMMARY SCORES 1265 00:45:07,640 --> 00:45:11,611 AGAINST THE NASH NAS OR FIBROSIS 1266 00:45:11,611 --> 00:45:12,912 STAGE YOU CAN FIND GENE PATHWAYS 1267 00:45:12,912 --> 00:45:15,582 THAT BECOME MORE ACTIVATED OR 1268 00:45:15,582 --> 00:45:16,783 REPRESSED AS THE SCORE GOES UP 1269 00:45:16,783 --> 00:45:18,318 OR DOWN. 1270 00:45:18,318 --> 00:45:20,420 SO THIS IS A REALLY SIGNIFICANT 1271 00:45:20,420 --> 00:45:22,088 FINDING THAT WE COULD SEE ALL OF 1272 00:45:22,088 --> 00:45:23,490 THESE GENETIC CHANGES, 1273 00:45:23,490 --> 00:45:24,491 TRANSCRIPTIONAL CHANGES THAT 1274 00:45:24,491 --> 00:45:27,760 RELATED DIRECTLY TO HISTOLOGY. 1275 00:45:27,760 --> 00:45:30,063 THEY CAME UP WITH MASTER SCORES 1276 00:45:30,063 --> 00:45:31,865 THAT ALLOWED THEM TO SORT OF 1277 00:45:31,865 --> 00:45:32,499 GAUGE ACTIVITY OR FIBROSIS JUST 1278 00:45:32,499 --> 00:45:34,868 BASED ON THE TRANSCRIPTION 1279 00:45:34,868 --> 00:45:39,539 PROFILE. 1280 00:45:39,539 --> 00:45:41,107 HOW ARE WE DOING? 1281 00:45:41,107 --> 00:45:42,575 I THINK WE'RE GOOD. 1282 00:45:42,575 --> 00:45:46,079 SO CLINICAL TRIALS FOR 1283 00:45:46,079 --> 00:45:46,479 STEATOHEPATITIS. 1284 00:45:46,479 --> 00:45:47,514 I MENTIONED THERE WAS THIS 1285 00:45:47,514 --> 00:45:49,349 EXPLOSION OF CLINICAL TRIALS. 1286 00:45:49,349 --> 00:45:50,783 NOW A LOT OF PHASE THREE TRIALS 1287 00:45:50,783 --> 00:45:53,953 ARE ONGOING. 1288 00:45:53,953 --> 00:45:56,422 IN THIS REVIEW ARTICLE, WHICH 1289 00:45:56,422 --> 00:45:57,690 WAS JUST WRITTEN LAST YEAR, THEY 1290 00:45:57,690 --> 00:46:02,362 HIGHLIGHTED FOUR DRUGS IN PHASE 1291 00:46:02,362 --> 00:46:08,902 THREE CLINICAL TRIALS, . 1292 00:46:08,902 --> 00:46:11,404 THE SECOND ONE IN THE IS SECOND 1293 00:46:11,404 --> 00:46:15,341 COLUMN HERE DLSH -- THERE'S MY 1294 00:46:15,341 --> 00:46:15,608 POINTER. 1295 00:46:15,608 --> 00:46:17,010 AND TWO OTHER DRUGS. 1296 00:46:17,010 --> 00:46:18,845 THE LAST TWO DRUGS WE'RE STILL 1297 00:46:18,845 --> 00:46:19,846 WAITING FOR THOSE TRIALS TO 1298 00:46:19,846 --> 00:46:21,548 FINISH, AT LEAST AT THE TIME OF 1299 00:46:21,548 --> 00:46:22,782 THIS WRITING. 1300 00:46:22,782 --> 00:46:25,952 WHAT I'M GOING TO SHOW YOU IS 1301 00:46:25,952 --> 00:46:28,855 THE DATA FROM ONE OF THE PAPERS. 1302 00:46:28,855 --> 00:46:30,957 THIS WAS JUST PUBLISHED IN THE 1303 00:46:30,957 --> 00:46:31,991 NEW ENGLAND JOURNAL. 1304 00:46:31,991 --> 00:46:34,227 AGAIN I WAS CIRCLE THE 1305 00:46:34,227 --> 00:46:34,827 PATHOLOGISTS WHO ARE TWO AND 1306 00:46:34,827 --> 00:46:35,929 THREE ON THIS PAPER. 1307 00:46:35,929 --> 00:46:38,031 THE SECOND PAPER -- OR SECOND -- 1308 00:46:38,031 --> 00:46:40,166 THIRD AUTHOR, I'M SORRY, IS 1309 00:46:40,166 --> 00:46:41,968 CINDY GUY. SHE'S ALSO A 1310 00:46:41,968 --> 00:46:44,270 PATHOLOGIST IN THE NASH CRN. 1311 00:46:44,270 --> 00:46:47,273 AND PIER BEDOSA IS ONE OF MY 1312 00:46:47,273 --> 00:46:49,642 COLLEAGUES IN FRANCE WHO IS A 1313 00:46:49,642 --> 00:46:52,779 LEADER IN THIS FIELD, ALSO A 1314 00:46:52,779 --> 00:46:53,112 PATHOLOGIST. 1315 00:46:53,112 --> 00:47:00,720 SO THE HISTOLOGIC ENTRY CRITERIA 1316 00:47:00,720 --> 00:47:04,524 WAS THE SAME AS BEFORE, 1317 00:47:04,524 --> 00:47:08,127 STEATOHEPATITIS AND WASN'T 1318 00:47:08,127 --> 00:47:08,428 CIRRHOSIS. 1319 00:47:08,428 --> 00:47:15,235 AND THE HISTOLOGIC END POINT WAS 1320 00:47:15,235 --> 00:47:15,802 RESOLUTION OF THIS -- THAT 1321 00:47:15,802 --> 00:47:22,242 SHOULD BE WITHOUT FIBROSIS 1322 00:47:22,242 --> 00:47:22,542 WORSENING. 1323 00:47:22,542 --> 00:47:23,009 OH WELL. 1324 00:47:23,009 --> 00:47:25,545 OR IMPROVEMENT OF THE FIBROSIS 1325 00:47:25,545 --> 00:47:27,013 WITHOUT WORSENING OF THE SCORE. 1326 00:47:27,013 --> 00:47:30,717 AND THEY HIT THE TARGETS. 1327 00:47:30,717 --> 00:47:35,121 SO IT SHOWED A 30% RESPONSE RATE 1328 00:47:35,121 --> 00:47:37,257 IN TERMS OF NASH RESOLUTION WITH 1329 00:47:37,257 --> 00:47:39,592 NO WORSENING COMPARED TO 10% OF 1330 00:47:39,592 --> 00:47:40,660 THE PLACEBO PATIENTS. 1331 00:47:40,660 --> 00:47:43,696 ON THE FLIP SIDE OF THAT, 1332 00:47:43,696 --> 00:47:44,397 FIBROSIS IMPROVEMENT WITH NO 1333 00:47:44,397 --> 00:47:50,270 WORSENING OF THE NAFLD SCORE. 1334 00:47:50,270 --> 00:47:51,571 AGAIN A QUARTER OF THE PATIENTS 1335 00:47:51,571 --> 00:47:54,507 WITH 15% IN THE PLACEBO GROUP. 1336 00:47:54,507 --> 00:47:55,341 THERE WAS ANOTHER ENDPOINT THAT 1337 00:47:55,341 --> 00:47:58,511 THEY HIGHLIGHTED WHICH WAS DROP 1338 00:47:58,511 --> 00:48:00,546 IN THE NLDL CHOLESTEROL. 1339 00:48:00,546 --> 00:48:02,248 THEY ALSO HIGHLIGHTED A BUNCH OF 1340 00:48:02,248 --> 00:48:05,018 ADDITIONAL ENDPOINTS THAT WERE 1341 00:48:05,018 --> 00:48:10,923 ALL HISTOLOGIC THEY HIT AS WELL. 1342 00:48:10,923 --> 00:48:13,059 THESE WERE THE FIRST TWO. 1343 00:48:13,059 --> 00:48:14,127 TWO POINT IMPROVEMENT. 1344 00:48:14,127 --> 00:48:17,130 THEY HIT THAT MARK. 1345 00:48:17,130 --> 00:48:20,466 AND ANOTHER SIMILAR ONE, AGAIN, 1346 00:48:20,466 --> 00:48:24,070 A LITTLE BIT MORE STRINGENT, HIT 1347 00:48:24,070 --> 00:48:24,637 THAT MARK. 1348 00:48:24,637 --> 00:48:26,005 IMPROVEMENT OF EACH COMPONENT OF 1349 00:48:26,005 --> 00:48:28,908 THE SCORE, HIT THAT MARK. 1350 00:48:28,908 --> 00:48:32,312 IMPROVEMENT OF THE FIBROSIS BY 1351 00:48:32,312 --> 00:48:33,846 TWO STAGES, THAT WAS ALSO 1352 00:48:33,846 --> 00:48:34,547 SIGNIFICANT. 1353 00:48:34,547 --> 00:48:36,582 AND THEN NASH RESOLUTION AND 1354 00:48:36,582 --> 00:48:37,250 FIBROSIS IMPROVEMENT AND THEY 1355 00:48:37,250 --> 00:48:39,152 HIT THAT MARK. 1356 00:48:39,152 --> 00:48:42,789 SO EVERY SINGLE HISTOLOGIC 1357 00:48:42,789 --> 00:48:44,057 ENDPOINT THEY IDENTIFIED THIS 1358 00:48:44,057 --> 00:48:46,059 DRUG HIT. 1359 00:48:46,059 --> 00:48:50,496 SO IT'S VERY, VERY ENCOURAGENCO 1360 00:48:50,496 --> 00:48:51,064 THE FDA ALSO FOUND THIS 1361 00:48:51,064 --> 00:48:53,866 ENCOURAGING SO THEY APPROVED 1362 00:48:53,866 --> 00:48:55,668 THIS AS THE FIRST DRUG TREATMENT 1363 00:48:55,668 --> 00:48:58,071 FOR PATIENTS WITH LIVER SCARRING 1364 00:48:58,071 --> 00:48:59,572 DUE TO FATTY LIVER DISEASE. 1365 00:48:59,572 --> 00:49:01,941 SO THIS IS THE ANNOUNCEMENT OFF 1366 00:49:01,941 --> 00:49:05,712 THE FDA WEBSITE. 1367 00:49:05,712 --> 00:49:10,483 SO THIS IS THE SUMMARY. 1368 00:49:10,483 --> 00:49:13,786 SO 21 YEARS NASH CRN PATHOLOGY 1369 00:49:13,786 --> 00:49:16,789 COMMITTEE CONTRIBUTED TO THE 1370 00:49:16,789 --> 00:49:17,457 GREATER UNDERSTANDING OF THIS 1371 00:49:17,457 --> 00:49:18,825 DISEASE. THERE'S A LOT OF STUFF 1372 00:49:18,825 --> 00:49:20,626 OBVIOUSLY I DIDN'T HIGHLIGHT. 1373 00:49:20,626 --> 00:49:23,196 WE PUBLISHED 17 1374 00:49:23,196 --> 00:49:25,465 PATHOLOGY-FOCUSED PAPERS AND WE 1375 00:49:25,465 --> 00:49:28,067 MADE FUNDAMENTAL CONTRIBUTIONS 1376 00:49:28,067 --> 00:49:30,069 TO 136 OTHER. 1377 00:49:30,069 --> 00:49:31,971 MOST OF THE OTHER 136 NASH CRN 1378 00:49:31,971 --> 00:49:33,373 PAPERS INCLUDING THE FOUR 1379 00:49:33,373 --> 00:49:37,443 CLINICAL TRIALS, GENETIC 1380 00:49:37,443 --> 00:49:38,378 TRANSCRIPTOMIC STUDIES WHICH I 1381 00:49:38,378 --> 00:49:40,813 DIDN'T HAVE TIME TO COVER. 1382 00:49:40,813 --> 00:49:43,416 NON INVASIVE IMAGING AND 1383 00:49:43,416 --> 00:49:43,916 BIOMARKER STUDIES. 1384 00:49:43,916 --> 00:49:44,917 SOME OF WHICH ARE STILL GOING 1385 00:49:44,917 --> 00:49:46,185 ON. 1386 00:49:46,185 --> 00:49:49,655 AND WE ESTABLISHED THIS 1387 00:49:49,655 --> 00:49:50,957 EVALUATION METHOD FOR THE LIVER 1388 00:49:50,957 --> 00:49:52,658 BIOPSY THAT'S BEEN USED IN 1389 00:49:52,658 --> 00:49:54,761 LITERALLY HUNDREDS OF STUDIES 1390 00:49:54,761 --> 00:49:55,595 OUTSIDE THE NETWORK INCLUDING 1391 00:49:55,595 --> 00:49:58,998 THE STUDY THAT LED TO THE FIRST 1392 00:49:58,998 --> 00:50:02,602 FDA APPROVAL AS A TREATMENT FOR 1393 00:50:02,602 --> 00:50:02,835 MASH. 1394 00:50:02,835 --> 00:50:05,905 SO WHAT I HOPE YOU'VE LEARNED. 1395 00:50:05,905 --> 00:50:07,740 STEATOHEPATITIS, I COVERED THE 1396 00:50:07,740 --> 00:50:08,474 PATHOLOGY. 1397 00:50:08,474 --> 00:50:14,447 IT HAS A LOT OF DIFFERENT MICRO 1398 00:50:14,447 --> 00:50:14,781 SD 1399 00:50:14,781 --> 00:50:15,415 MICROSCOPIC CHANGES WHICH ARE 1400 00:50:15,415 --> 00:50:16,115 IMPORTANT. 1401 00:50:16,115 --> 00:50:18,217 WE CAN SCORE THOSE CHANGING 1402 00:50:18,217 --> 00:50:24,223 LOOKING AT THE SLIDES UNDER THE 1403 00:50:24,223 --> 00:50:30,430 MICROSCOPE WE CAN CORRELATE WITH 1404 00:50:30,430 --> 00:50:30,863 GEN 1405 00:50:30,863 --> 00:50:31,564 GENOMESTUDIES. IT'S BEEN USED 1406 00:50:31,564 --> 00:50:32,565 TO GAIN ACCELERATED APPROVAL FOR 1407 00:50:32,565 --> 00:50:34,200 ONE DRUG SO FAR AND I GUARANTEE 1408 00:50:34,200 --> 00:50:39,539 YOU THAT THERE WILL BE OTHERS. 1409 00:50:39,539 --> 00:50:41,974 SO LOTS OF PEOPLE TO THANK. 1410 00:50:41,974 --> 00:50:44,177 THESE ARE THE NASH CRN 1411 00:50:44,177 --> 00:50:45,077 PATHOLOGISTS SINCE WE STARTED 1412 00:50:45,077 --> 00:50:45,645 THE COMMITTEE. 1413 00:50:45,645 --> 00:50:47,847 YOU CAN SEE THERE'S BEEN SOME 1414 00:50:47,847 --> 00:50:49,215 CHANGE IN PERSONNEL AS PEOPLE 1415 00:50:49,215 --> 00:50:50,583 MOVED OUT OF ACADEMIC CENTERS 1416 00:50:50,583 --> 00:50:52,452 INTO OTHER PLACES. 1417 00:50:52,452 --> 00:50:54,454 I'VE HIGHLIGHTED TWO PEOPLE THAT 1418 00:50:54,454 --> 00:50:56,722 I REALLY COULD NOT HAVE DONE 1419 00:50:56,722 --> 00:50:58,491 THIS WITHOUT. 1420 00:50:58,491 --> 00:51:02,662 ONE IS ELIZABETH BRUNT, WHO WAS 1421 00:51:02,662 --> 00:51:04,497 MY STALLWARD CO-CHAIR FOR MANY 1422 00:51:04,497 --> 00:51:05,298 YEARS. 1423 00:51:05,298 --> 00:51:06,132 AND THEN CYNTHIA BAILEY WHO TOOK 1424 00:51:06,132 --> 00:51:11,370 OVER AFTER BETH RETIRED. 1425 00:51:11,370 --> 00:51:13,539 SO 73 MEETINGS. 1426 00:51:13,539 --> 00:51:17,210 ALMOST 7,000 CASES PLUS EXTRAS 1427 00:51:17,210 --> 00:51:19,111 ADDED TO THAT. 1428 00:51:19,111 --> 00:51:19,979 WE LOOKED AT CASES FROM ADULTS 1429 00:51:19,979 --> 00:51:25,251 AND CHILDREN WITH THE LARGEST 1430 00:51:25,251 --> 00:51:27,587 PEDIATRIC BIOPSY COHORT PROBABLY 1431 00:51:27,587 --> 00:51:29,021 IN THE WORLD IN THIS STUDY. 1432 00:51:29,021 --> 00:51:30,990 I DIDN'T COVER ANY OF THAT. 1433 00:51:30,990 --> 00:51:33,526 SO WE'VE ESTABLISHED -- IS 1434 00:51:33,526 --> 00:51:34,861 WE'VE ACCOMPLISHED QUITE A LOT. 1435 00:51:34,861 --> 00:51:37,063 AND THEN THE NATIONAL CLINICAL 1436 00:51:37,063 --> 00:51:37,864 RESEARCH NETWORK INVESTIGATORS 1437 00:51:37,864 --> 00:51:41,367 ARE ON THE LEFT HERE. 1438 00:51:41,367 --> 00:51:45,071 AND THE CURRENT MEMBERS OF THE 1439 00:51:45,071 --> 00:51:46,906 PATHOLOGY GROUP, THE DCC, COULD 1440 00:51:46,906 --> 00:51:47,907 NOT HAVE DONE ANY OF THIS WORK 1441 00:51:47,907 --> 00:51:53,613 WITHOUT OUR STATISTICIANS, JIM 1442 00:51:53,613 --> 00:51:55,081 AND ESPECIALLY PAT WILSON WHO 1443 00:51:55,081 --> 00:51:58,417 WERE AT EVERY SINGLE ONE OF OUR 1444 00:51:58,417 --> 00:51:59,452 SCORING MEETINGS. 1445 00:51:59,452 --> 00:52:01,621 AND THEN THE PROJECT SCIENTIST 1446 00:52:01,621 --> 00:52:05,258 FROM THE NIDDK. 1447 00:52:05,258 --> 00:52:06,425 I MENTIONED THE PATHOLOGISTS. 1448 00:52:06,425 --> 00:52:10,596 A LOT OF PATIENTS, GOT A LOT OF 1449 00:52:10,596 --> 00:52:10,863 BIOPSIES. 1450 00:52:10,863 --> 00:52:12,598 SO THANK YOU. 1451 00:52:12,598 --> 00:52:22,842 >> [APPLAUSE] 1452 00:52:23,075 --> 00:52:24,877 >> I WILL STAY HERE. 1453 00:52:24,877 --> 00:52:26,946 I CAN'T RUN AWAY. 1454 00:52:26,946 --> 00:52:28,281 UP THE STAIRS. 1455 00:52:28,281 --> 00:52:29,582 >> CAN YOU LOCK THE DOORS. 1456 00:52:29,582 --> 00:52:32,251 I JUST WANT TO SAY THANK YOU 1457 00:52:32,251 --> 00:52:34,954 AGAIN FOR SHARING WITH US YOUR 1458 00:52:34,954 --> 00:52:35,555 EXPERT 1459 00:52:35,555 --> 00:52:36,222 EXPERTISE. IT'S CLEAR TO ALL OF 1460 00:52:36,222 --> 00:52:38,357 US WHY YOU'VE BEEN SELECTED AS A 1461 00:52:38,357 --> 00:52:39,525 MASTER EDUCATOR. 1462 00:52:39,525 --> 00:52:41,494 AS A PEDIATRIC CARDIOLOGIST I 1463 00:52:41,494 --> 00:52:41,727 STOOD. 1464 00:52:41,727 --> 00:52:44,063 THANK YOU. 1465 00:52:44,063 --> 00:52:47,667 THANK YOU FOR YOUR IMPACT ON THE 1466 00:52:47,667 --> 00:52:48,968 WHOLE DISCIPLINE OF 1467 00:52:48,968 --> 00:52:49,635 STEATOHEPATITIS. 1468 00:52:49,635 --> 00:52:50,102 APPRECIATE IT. 1469 00:52:50,102 --> 00:52:50,836 THANK YOU VERY MUCH AND 1470 00:52:50,836 --> 00:52:51,237 CONGRATULATIONS. 1471 00:52:51,237 --> 00:52:52,305 >> THANK YOU. 1472 00:52:52,305 --> 00:52:55,141 >> [APPLAUSE] 1473 00:52:55,141 --> 00:52:57,143 >> OF COURSE THE ONLY PERSON 1474 00:52:57,143 --> 00:53:01,414 CRINGING IS [INAUDIBLE] 1475 00:53:01,414 --> 00:53:02,315 >> YOUR TURN NEXT YEAR. 1476 00:53:02,315 --> 00:53:05,217 >> I HAVE A QUESTION THAT CAME 1477 00:53:05,217 --> 00:53:07,386 IN WITHIN THE COMMUNITY. 1478 00:53:07,386 --> 00:53:08,287 EXCELLENT TALK. 1479 00:53:08,287 --> 00:53:10,089 WERE YOU ABLE TO FIND ANY 1480 00:53:10,089 --> 00:53:11,657 EVIDENCE OF HEPATITIS VIRUS? 1481 00:53:11,657 --> 00:53:13,559 >> SO ALL OF THE PATIENTS IN 1482 00:53:13,559 --> 00:53:15,728 THE NETWORK WERE EXCLUDED IF 1483 00:53:15,728 --> 00:53:18,531 THEY HAD A CO-INFECTION WITH ONE 1484 00:53:18,531 --> 00:53:20,366 OF THE HEPATITIS VIRUSES. 1485 00:53:20,366 --> 00:53:22,668 INTERESTINGLY IN REVIEWING THE 1486 00:53:22,668 --> 00:53:26,539 BIOPSIES OF COURSE WE FIND OTHER 1487 00:53:26,539 --> 00:53:26,906 THINGS. 1488 00:53:26,906 --> 00:53:34,981 WE FINED FI-- WE FIND THINGS. 1489 00:53:34,981 --> 00:53:36,549 WE SAID ONE THIS IS NOT 1490 00:53:36,549 --> 00:53:37,083 STEATOHEPATITIS, THIS IS 1491 00:53:37,083 --> 00:53:37,583 HEPATITIS C. 1492 00:53:37,583 --> 00:53:40,553 WE SENT A MESSAGE BACK TO THE 1493 00:53:40,553 --> 00:53:40,786 CLINIC. 1494 00:53:40,786 --> 00:53:42,221 SURE ENOUGH THE PATIENT HAD BEEN 1495 00:53:42,221 --> 00:53:45,291 TESTED AND NEGATIVE FOR HEN -- 1496 00:53:45,291 --> 00:53:49,261 FOR HEP-C WHEN THEY ENTERED THE 1497 00:53:49,261 --> 00:53:51,263 STUDY AND WERE NOW INFECTED AND 1498 00:53:51,263 --> 00:53:51,530 POSITIVE. 1499 00:53:51,530 --> 00:53:53,499 SO WE DID HAVE THAT. 1500 00:53:53,499 --> 00:53:55,368 OTHERWISE THE PATIENTS WERE ALL 1501 00:53:55,368 --> 00:53:57,336 NEGATIVE. 1502 00:53:57,336 --> 00:53:58,471 >> DAVID, THANK YOU VERY MUCH. 1503 00:53:58,471 --> 00:54:01,507 INTERESTING TALK. 1504 00:54:01,507 --> 00:54:02,241 ELAINE JAFFEE. 1505 00:54:02,241 --> 00:54:02,842 >> I RECOGNIZE YOU. 1506 00:54:02,842 --> 00:54:03,309 >> YOU RECOGNIZE ME. 1507 00:54:03,309 --> 00:54:05,077 OKAY. 1508 00:54:05,077 --> 00:54:07,980 SO IS THIS A NEW DISEASE? 1509 00:54:07,980 --> 00:54:09,515 BECAUSE I DON'T REMEMBER HEARING 1510 00:54:09,515 --> 00:54:13,319 ABOUT THIS DISEASE WHEN I WAS A 1511 00:54:13,319 --> 00:54:16,088 RESIDENT UPTEEN YEAR AGO. 1512 00:54:16,088 --> 00:54:18,057 >> SO IT IS AND IT ISN'T. 1513 00:54:18,057 --> 00:54:21,060 SO IF YOU ACTUALLY GO BACK INTO 1514 00:54:21,060 --> 00:54:22,862 THE LITERATURE PRECEDING 1980 I 1515 00:54:22,862 --> 00:54:27,133 FOUND DESCRIPTIONS OF PATHOLOGY 1516 00:54:27,133 --> 00:54:29,268 IN DIABETES THAT DESCRIBED THIS 1517 00:54:29,268 --> 00:54:29,568 PATHOLOGY. 1518 00:54:29,568 --> 00:54:30,603 THEY JUST DIDN'T KNOW WHAT TO 1519 00:54:30,603 --> 00:54:31,704 CALL IT OR THEY DIDN'T HAVE A 1520 00:54:31,704 --> 00:54:33,272 NAME FOR IT. 1521 00:54:33,272 --> 00:54:35,541 WHICH IS WHY I POINTED OUT THE 1522 00:54:35,541 --> 00:54:38,911 IMPORTANCE OF NAMING SOMETHING. 1523 00:54:38,911 --> 00:54:40,379 BUT YOU'RE RIGHT. 1524 00:54:40,379 --> 00:54:42,081 THERE WAS NOT MUCH OUT THERE 1525 00:54:42,081 --> 00:54:47,119 UNTIL THIS WORKSHOP. 1526 00:54:47,119 --> 00:54:48,621 SO WHEN I DID -- I DID A 1527 00:54:48,621 --> 00:54:50,356 LITERATURE REVIEW BEFORE THE 1528 00:54:50,356 --> 00:54:51,891 WORKSHOP THAT I WENT OVER WITH 1529 00:54:51,891 --> 00:54:52,291 THE PATHOLOGISTS. 1530 00:54:52,291 --> 00:54:54,660 THERE WERE MAYBE 10 PAPERS OUT 1531 00:54:54,660 --> 00:54:56,562 THERE ON THE PATHOLOGY OF FATTY 1532 00:54:56,562 --> 00:54:59,765 LIVER DISEASE. 1533 00:54:59,765 --> 00:55:02,334 THAT CAME AFTER THAT SEMINAL 1534 00:55:02,334 --> 00:55:04,770 PAPER. 1535 00:55:04,770 --> 00:55:05,638 THERE WERE DESCRIPTIONS OF FATTY 1536 00:55:05,638 --> 00:55:06,605 LIVER BEFORE THAT. 1537 00:55:06,605 --> 00:55:08,941 SOME FAIRLY LARGE COHORT STUDIES 1538 00:55:08,941 --> 00:55:09,775 BUT THERE WAS ACTUALLY AN 1539 00:55:09,775 --> 00:55:11,277 ARGUMENT IN THE LITERATURES 1540 00:55:11,277 --> 00:55:12,445 WHETHER THIS WAS SIGNIFICANT OR 1541 00:55:12,445 --> 00:55:17,583 NOT OR WHETHER IT WAS NORMAL. 1542 00:55:17,583 --> 00:55:18,551 WE NOW KNOW THAT THAT'S NOT 1543 00:55:18,551 --> 00:55:18,951 TRUE. 1544 00:55:18,951 --> 00:55:19,985 THERE WAS A LOT OF DISBELIEF 1545 00:55:19,985 --> 00:55:21,153 THAT FAT IN THE LIVER HAD ANY 1546 00:55:21,153 --> 00:55:22,955 SIGNIFICANCE AT ALL. 1547 00:55:22,955 --> 00:55:32,998 >> BUT I MEAN YOU DESCRIBE -- 1548 00:55:32,998 --> 00:55:34,233 DESCRIBING HIGH INCIDENTS. 1549 00:55:34,233 --> 00:55:37,069 >> BECAUSE WE'RE GETTING BIGGER 1550 00:55:37,069 --> 00:55:38,471 AND DIABETIC. 1551 00:55:38,471 --> 00:55:40,740 >> IS THIS ASSOCIATED WITH 1552 00:55:40,740 --> 00:55:43,743 CHANGES IN LIFESTYLE? 1553 00:55:43,743 --> 00:55:46,145 >> PEOPLE HAVE CORRELATED TO 1554 00:55:46,145 --> 00:55:55,154 THE EPIDEMIC OF DIABETES. IT'S 1555 00:55:55,154 --> 00:55:59,925 MAINLY AN ASYMPTOMATIC UNTIL YOU 1556 00:55:59,925 --> 00:56:04,063 GET TO ADMINISTRATIVE LEAVE -- 1557 00:56:04,063 --> 00:56:05,197 TO ADVANCED LIVER DISEASE AND 1558 00:56:05,197 --> 00:56:06,465 HAVE PROBLEMS WITH CIRRHOSIS. 1559 00:56:06,465 --> 00:56:09,268 IT CAN FLY UNDER THE RADAR. 1560 00:56:09,268 --> 00:56:11,570 THE ENZYMES ARE NOT THAT 1561 00:56:11,570 --> 00:56:11,871 ELEVATED. 1562 00:56:11,871 --> 00:56:13,839 PHYSICIANS NOT AWARE OF THIS 1563 00:56:13,839 --> 00:56:15,174 DISEASE WILL SAY WE SEE THIS, WE 1564 00:56:15,174 --> 00:56:17,476 SEE A LITTLE BIT OF AN ALT 1565 00:56:17,476 --> 00:56:18,177 ELEVATION, DOESN'T MEAN 1566 00:56:18,177 --> 00:56:18,477 ANYTHING. 1567 00:56:18,477 --> 00:56:20,546 BUT, YOU KNOW, I THINK AS WE 1568 00:56:20,546 --> 00:56:22,081 BECOME MORE AND MORE AWARE OF 1569 00:56:22,081 --> 00:56:23,349 THE DISEASE AND IT'S POTENTIAL 1570 00:56:23,349 --> 00:56:25,518 CONSEQUENCES, YOU KNOW, PEOPLE 1571 00:56:25,518 --> 00:56:28,521 ARE LOOKING MORE, THERE ARE MORE 1572 00:56:28,521 --> 00:56:30,356 GUIDELINES OUT THERE, WHICH 1573 00:56:30,356 --> 00:56:31,891 DIDN'T EXIST 40 YEARS AGO. 1574 00:56:31,891 --> 00:56:37,930 >> THANK YOU. 1575 00:56:37,930 --> 00:56:39,632 >> I HAVE A QUESTION. 1576 00:56:39,632 --> 00:56:40,766 >> OKAY. 1577 00:56:40,766 --> 00:56:42,434 I'VE STUNNED EVERYONE. 1578 00:56:42,434 --> 00:56:43,969 >> WE HAVE ONE MORE. 1579 00:56:43,969 --> 00:56:46,338 >> OH. 1580 00:56:46,338 --> 00:56:48,541 >> YOU OBVIOUSLY RECOGNIZE ME 1581 00:56:48,541 --> 00:56:48,808 AS WELL. 1582 00:56:48,808 --> 00:56:50,442 SO YOU'VE GOT A REALLY HIGH 1583 00:56:50,442 --> 00:56:54,647 RESPONSE RATE IN YOUR PLACEBO 1584 00:56:54,647 --> 00:56:56,415 GROUPS IN THE CLINICAL TRIALS. 1585 00:56:56,415 --> 00:56:57,016 >> YEAH. 1586 00:56:57,016 --> 00:56:57,650 >> DO YOU THINK THIS IS DRIVEN 1587 00:56:57,650 --> 00:57:01,287 BY LIFESTYLE HABIT AS WELL? 1588 00:57:01,287 --> 00:57:04,957 >> SO I DIDN'T GO INTO IT IN 1589 00:57:04,957 --> 00:57:08,360 THAT LONGITUDINAL STUDY. 1590 00:57:08,360 --> 00:57:09,895 MORE PATIENTS GOT BETTER OVER 1591 00:57:09,895 --> 00:57:11,096 TIME THAN GOT WORSE. 1592 00:57:11,096 --> 00:57:12,431 MY THOUGHT -- AND THIS WAS NOT 1593 00:57:12,431 --> 00:57:14,967 JUST HISTOLOGIC NOISE. 1594 00:57:14,967 --> 00:57:16,702 SO THERE'S NOISE, I LOOK AT THE 1595 00:57:16,702 --> 00:57:17,870 SLIDE ONE DAY AND THINK IT'S 1596 00:57:17,870 --> 00:57:19,205 THERE, I LOOK AT IT ANOTHER DAY 1597 00:57:19,205 --> 00:57:20,172 AND THINK IT'S DIFFERENT. 1598 00:57:20,172 --> 00:57:21,941 THE SCORING ESPECIALLY CAN VARY 1599 00:57:21,941 --> 00:57:22,575 A LITTLE. 1600 00:57:22,575 --> 00:57:23,475 IT'S NOT JUST THAT. 1601 00:57:23,475 --> 00:57:25,110 BECAUSE OTHER THINGS CHANGE IN 1602 00:57:25,110 --> 00:57:26,212 THESE PATIENTS. 1603 00:57:26,212 --> 00:57:27,713 THEY LOSE WEIGHT, THEIR ENZYMES 1604 00:57:27,713 --> 00:57:27,947 CHANGE. 1605 00:57:27,947 --> 00:57:30,816 SO OTHER THINGS ARE CHANGING. 1606 00:57:30,816 --> 00:57:32,785 SO IT'S NOT ALL IN DAVE 1607 00:57:32,785 --> 00:57:34,720 KLEINER'S IMAGINATION. 1608 00:57:34,720 --> 00:57:38,924 BUT I THINK THAT TAKING GOOD 1609 00:57:38,924 --> 00:57:42,061 CARE OF PEOPLE, SEEING YOUR 1610 00:57:42,061 --> 00:57:43,128 PHYSICIAN ANNUALLY, GETTING THAT 1611 00:57:43,128 --> 00:57:45,965 ADVICE TO WATCH YOUR DIET, TO 1612 00:57:45,965 --> 00:57:48,300 LOSE WEIGHT, TO TAKE CARE OF 1613 00:57:48,300 --> 00:57:49,435 YOUR DIABETES, TO DEAL WITH 1614 00:57:49,435 --> 00:57:52,838 THOSE KIND OF PROBLEMS ACTUALLY 1615 00:57:52,838 --> 00:57:55,674 WORKS FOR SOME PERCENTAGE OF 1616 00:57:55,674 --> 00:57:55,975 PATIENTS. 1617 00:57:55,975 --> 00:57:57,042 SO THEY LOSE A LITTLE WEIGHT AND 1618 00:57:57,042 --> 00:57:58,143 THAT'S ENOUGH. 1619 00:57:58,143 --> 00:58:01,380 WHEN WE LOOKED AT WEIGHT CHANGES 1620 00:58:01,380 --> 00:58:02,781 RELATED TO THESE THINGS, YOU 1621 00:58:02,781 --> 00:58:04,016 DON'T HAVE TO LOSE MUCH WEIGHT. 1622 00:58:04,016 --> 00:58:06,252 ABOUT 10 POUNDS. 1623 00:58:06,252 --> 00:58:11,991 YOU'LL SEE CHANGES 1624 00:58:11,991 --> 00:58:12,358 HISTOLOGICALLY. 1625 00:58:12,358 --> 00:58:15,194 IT DOESN'T TAKE MUCH TO AFFECT 1626 00:58:15,194 --> 00:58:15,394 THAT. 1627 00:58:15,394 --> 00:58:17,429 SO WE DO SEE A SIGNIFICANT 10, 1628 00:58:17,429 --> 00:58:20,432 15% OF PATIENTS WHO GET BETTER 1629 00:58:20,432 --> 00:58:21,100 OVER THE COURSE OF THE CLINICAL 1630 00:58:21,100 --> 00:58:26,872 TRIAL. 1631 00:58:26,872 --> 00:58:29,174 >> JAY IS GOING TO ASK ME I'M 1632 00:58:29,174 --> 00:58:29,408 AFRAID. 1633 00:58:29,408 --> 00:58:32,711 >> JAY FROM CLINICAL CENTER. 1634 00:58:32,711 --> 00:58:34,280 ACTUALLY EVEN BEFORE THE 1635 00:58:34,280 --> 00:58:40,886 DISCOVERY OF HEPATITIS C AT THE 1636 00:58:40,886 --> 00:58:41,987 CLINICAL CENTER HARVEY ALTER 1637 00:58:41,987 --> 00:58:43,589 INTRODUCED ALT SCREENING OF 1638 00:58:43,589 --> 00:58:47,092 BLOOD DONORS AND WOULD EXCLUDE 1639 00:58:47,092 --> 00:58:50,162 SOMEONE WITH AN ELEVATED ALT. 1640 00:58:50,162 --> 00:58:54,033 WE DID BIOPSIES ON SEVERAL OF 1641 00:58:54,033 --> 00:58:54,266 THESE. 1642 00:58:54,266 --> 00:58:56,268 THE MOST COMMON DIAGNOSIS WAS 1643 00:58:56,268 --> 00:58:58,637 NOT CHRONIC HEPATITIS, IT WAS 1644 00:58:58,637 --> 00:58:59,872 FATTY LIVER DISEASE. 1645 00:58:59,872 --> 00:59:01,473 YES, THIS WAS KNOWN BUT IT 1646 00:59:01,473 --> 00:59:03,642 DIDN'T HAVE A NAME UNTIL THIS 1647 00:59:03,642 --> 00:59:08,681 GREAT PAPER BY LUDWIG THAT 1648 00:59:08,681 --> 00:59:09,148 SHOWED IT. 1649 00:59:09,148 --> 00:59:11,483 AS ALSO POINTED OUT IF YOU LOOK 1650 00:59:11,483 --> 00:59:13,419 AT THE PLACEBO GROUP THAT 1651 00:59:13,419 --> 00:59:14,987 IMPROVED, THEY LOST WEIGHT. 1652 00:59:14,987 --> 00:59:16,555 AS DAVID SAID IT'S NOT MUCH 1653 00:59:16,555 --> 00:59:16,789 WEIGHT. 1654 00:59:16,789 --> 00:59:19,158 WE HAD TROUBLE PUBLISHING THE 1655 00:59:19,158 --> 00:59:21,894 PAPER BECAUSE ALL THE OBESITY 1656 00:59:21,894 --> 00:59:22,795 EXPERTS SAID THAT'S NOT ENOUGH 1657 00:59:22,795 --> 00:59:24,430 WEIGHT LOSS TO ACCOUNT FOR 1658 00:59:24,430 --> 00:59:24,697 ANYTHING. 1659 00:59:24,697 --> 00:59:27,499 BUT WITH THIS LITTLE WEIGHT LOSS 1660 00:59:27,499 --> 00:59:28,500 IS HELPFUL. 1661 00:59:28,500 --> 00:59:29,969 AT LEAST FOR THOSE WHO AREN'T 1662 00:59:29,969 --> 00:59:33,973 TOO OVER WEIGHT. 1663 00:59:33,973 --> 00:59:35,507 >> THANK YOU. 1664 00:59:35,507 --> 00:59:38,444 DOCTOR KLEINER, THANK YOU AGAIN. 1665 00:59:38,444 --> 00:59:38,911 CONGRATULATIONS. 1666 00:59:38,911 --> 00:59:41,413 >> THANK YOU. 1667 00:59:41,413 --> 00:59:43,349 >> THE DECKER FAMILY INVITING 1668 00:59:43,349 --> 00:59:45,351 GUESTS UP TO THE MEDICAL BOARD 1669 00:59:45,351 --> 00:59:46,852 ROOM SO WE WILL SEE YOU THERE 1670 00:59:46,852 --> 00:59:47,186 MOMENTARILY. 1671 00:59:47,186 --> 00:59:57,463 >> THANK YOU.