Alcoholic Hepatitis. Alexander Kuo, M.D. Associate Professor of Medicine Director, Hepatology and Liver Transplantation UC San Diego

Transcription

1 Alcoholic Hepatitis Alexander Kuo, M.D. Associate Professor of Medicine Director, Hepatology and Liver Transplantation UC San Diego

2 None Disclosures

3 Learning Objectives Spectrum of alcoholic liver disease Definition of acute alcoholic hepatitis Clinical presentation and treatment of AH Future therapeutic targets for AH Liver transplant for AH

4 Alcohol Use in the United States In 2013, 86.8% of people 18 or over reported alcohol use at some point in their lifetime 70.7% reported they drank in the last year 56.4% reported they drank in the last month Substance Abuse and Mental Health Services Administration (SAMHSA) National Survey on Drug Use and Health (NSDUH)

5 Drinking Levels Moderate alcohol use 1 drink per day for women 2 drinks per day for men Binge drinking 5 or more drinks in one occasion at least 1 time in the last month Heavy drinking 5 or more drinks in one occasion at least 5 days in the last month

6 Alcohol Use Disorder (AUD) DSM-4 Alcohol abuse Alcohol dependence DSM-5 (May 2013) Alcohol Abuse Disorder (AUD) Mild (2-3 symptoms) Moderate (4-5 symptoms) Severe (6 or more symptoms)

7 Alcohol Use Disorder (AUD) 7.2% of people 18 and older had an AUD in 2012 = 17 million adults 11.2 million men 5.7 million women 855,00 adolescents (age 12-17) had an AUD in ,000 alcohol related deaths annually 31% of all driving fatalities involve alcohol (10,076 deaths in 2013) Substance Abuse and Mental Health Services Administration (SAMHSA) National Survey on Drug Use and Health (NSDUH)

8 Indications for liver transplantation in the U.S.

9 Spectrum of Alcoholic Liver Disease Orman et al. J Gastro Hep 2013.

10 Alcoholic Hepatitis Liver inflammation caused by excessive alcohol intake Diagnosed with liver biopsy showing ballooned hepatocytes, Mallory hyaline, lobular inflammation, and peri-sinusoidal fibrosis Mild clinical presentation elevation in aminotransferases that normalizes with sobriety Severe clinical presentation Jaundice Ascites Encephalopathy Coagulopathy 30-day mortality 30-50%

11 Case 40 year old woman is admitted with new onset jaundice, abdominal distention, and lower extremity edema Labs show bilirubin 28, PT 22, INR 2.7, AST 250, ALT 70, WBC 12, Creatinine 1.0 MELD score 30 Discriminant Function score of 72 (>32 is severe) DF=4.6 x(pt-lab control PT) +bilirubin I only drink 2-3 glasses of wine a night.

12 What is one drink? = 12 grams etoh

13 Case Perform diagnostic paracentesis which rules out infection (spontaneous bacterial peritonitis) UA, urine CXR, blood cx, and CXR all negative for infection Transjugular liver biopsy performed

14 Case Dietician is consulted. Tube feeds are started. Prednisolone 40 mg daily started HD #7 the bilirubin remains 28 Creatinine begins to rise, pentoxifylline 400 mg tid started to reduce the chance for hepatorenal syndrome HD #10 creatinine 2.5, urine output falls to <600 cc daily HD #12 creatinine 3.9, anuric, SOB from large ascites, pleural effusion, and mild pulmonary edema Renal consulted for dialysis but renal feels HD would be futile Pleur-X catheter placed, patient discharged to hospice and dies 2 days after discharge

15 What else could we have done?

16 Current Therapies for Alcoholic Hepatitis Prednisolone 40 mg daily x28 days Pentoxifylline 400 mg tid x28 days IV NAC x7 days + steroids

17 STOPAH Trial 1103 pts with severe AH randomized to prednisolone, pentoxifylline, both or neither Thursz et al. NEJM April 2015.

18 N-acetylcystine+steroids vs Steroids for AH 174 pts with severe AH randomized to NAC +prednisolone vs prednisolone only Nguyen-Khac et al. NEJM Nov 2011.

19 Gzabo. Gastro 2015.

20 Gzabo. Gastro 2015.

21 Alcohol Liver Injury Wheeler. Alcohol Red Health 2003.

22 Possible Future Therapeutic Targets Alter the gut microbiome Probiotics Fecal transplantation? Decrease gut permeability Zinc therapy Upregulate tight junctions Decrease LPS-induced inflammation Anti-LPS antibodies TLR4 antagonists

23 Role for Liver Transplantation in AH In pts with severe alcoholic hepatitis (DF>32) with no response to steroids, 6 month mortality is ~70% 6 month sobriety is a poor predictor for alcohol recidivism Better predictors are social support and psychiatric comorbidities Pts with alcoholic hepatitis have not been widely considered for transplant due to lack of >6 months sobriety despite liver transplant being a established therapy Possible barriers to wider use of LT include fear of recidivism, donor organ shortage, social/ethical considerations Louvet et al. Hepatology 2007.

24 Liver Transplant for Alcoholic Hepatitis 7 centers in France performed early LT for pts with severe AH Severe AH (DF>32) with non-response to steroids First decompensating event Good support Pts agree to lifelong alcohol abstinence All team members (hepatogists, nurses, surgeons, SW, psychologist, residents, fellow) had to agree to list Mathurin et al. NEJM 2011.

25 Liver Transplant for Alcoholic Hepatitis 26 pts transplanted for AH Represented 2.9% of all transplant performed between at these 7 centers 1 year survival in LT recipients vs controls with AH was 77% vs 23% 3 pts resumed drinking 1 at 720 day 1 at 750 days 1 at 1140 days Mathurin et al. NEJM 2011.

26 Survey of Liver Transplant Programs in U.S. 45 of 110 liver transplant centers responded to a survey ed to program directors 12 of 45 centers (27%) reported listing pts with alcoholic hepatitis Of 3,290 transplants performed, 45 were done for AH (1.37%) 6 month, 1 year and 5 year survival was 93%, 93%, and 87% Alcohol recidivism rate was 17% (compared to 15-20% for pts transplanted for alcoholic cirrhosis) Hasanin et al. Liver Transpl Jul 2015.

27 Summary Alcoholic hepatitis is an acute presentation of alcoholic liver disease In pts with severe AH (DF>32) who do not respond to steroids, 6 month mortality is ~70% Treatment options focus on nutrition and steroids Liver transplant is an effective treatment for severe AH Currently offered in <30% of transplant programs in the U.S. Outcomes are outstanding Alcohol recidivism rates are no different compared to pts transplanted for alcoholic cirrhosis Future therapies for AH may include altering the gut microbiome and preventing leaky gut

28 Thank you!