Enterprise Interest Nothing to declare

Transcription

1 Enterprise Interest Nothing to declare

2 29 th European Congress of Pathology, Amsterdam, Sept 2 nd -6 th, 2017 What s new in alcohol-mediated liver injury? Carolin Lackner Institute of Pathology Medical University of Graz Austria

3 Burden of disease due to alcohol misuse Alcohol accounts for 6.5 % of all deaths (men:11%, women: 1.8%) o 50% of all deaths from cirrhosis 11.6% of all disability-adjusted life years (men: 17.3 %, women: 4.4%) ~50% of all liver transplantations in Europe Alcohol-related mortality is disproportionally high in young European males (25%) and females (10%) Rehm J, Lancet 2009 WHO Global Status Report on Alcohol and Health 2014

4 Disparities between research & burden in liver diseases 6.7 Attention-to-Burden Index, ABI Ndugga N, BMJ Open 2017

5 Normal liver Types of alcoholic liver disease Steatosis Fibrosis Decompensation: 20-40% Clin AH 28d mortality: 35% Cirrhosis 80-90% HCC 20-40% Alcoholic hepatitis 8-20% 8-20% Bataller R, Semin Liver Dis 2015

6 Clinical presentation of ALD Severely ill Jaundiced Cirrhotic Decompensated Early/compensated No/mild symptoms Low 30d survival rate High 30d survival rate

7 Histology in the management of decompensated ALD Prognosis assessment MDF/MELD/ABIC/GAHS SHORT-TERM mortality risk HIGH LOW Steroids indicated: Liver biopsy Standard care Diagnosis/exclusion of AH Prognosis, early detection of infection/aclf Response to steroids

8 Histological diagnosis of AH

9 Alcoholic hepatitis Steatosis Ballooning Lobular inflammation

10 Fibrosis progression in ALD Stage CAB

11 Histological definitions of alcoholic hepatitis Fibrosis Lob inflam PMC Lob.Inflam mononucl & PMC Mallory- Denk bodies Necrosis Ballooning Steatosis International Group Lancet 1981 MacSween RMN Semin Liver Dis 1986 Periven. Lefkowitch J Clin Liver Dis 2005 Brunt B MacSweens Pathology of the Liver

12 Histological confirmation of clinical AH Reference Altamirano J Gastroenterology 2014 Spahr L BMC Gastroenterol 2011 Clinical AH n AH on histology n (%) (67) (91) Dominguez A Am J Gastroenterol 2008 Mookerjee R/Lackner C J Hep 2011 Bissonnette J Hepatology (88) (50) 83 / (55) / 48 (71)

13 Histological diagnoses in patients with clinical AH Bissonnette J, Hepatology 2017 Cohort n AH on histology Test Validation Histological diagnosies in patients without AH on histology Alc cirrhosis : 35 Steatosis + fibrosis: 1 Susp. BSEP mutation: 1 Viral/drug induced chronic hepatitis: 1 Alc cirrhosis/fibrosis: 14 Alc foamy degeneration: 2 Hypoxic hepatitis: 3 Infectious mononucleosis: 1

14 Histological factors associated with infection & prediction of short-term mortality

15 Cholestasis Ductular CH Canalicular CH

16 Predictors of short-term outcome in ALD Author Reference n Diagnosis Follow up Outcome Infection Katoonizadeh A/ Laleman W, Gut ACLF 48 hr Age, SIRS Ductular CH, MDB SIRS Ductular CH Spahr L, BMC Gastroent Clin AH, No sepsis 90 d Age, MDF Canalicular CH Mookerjee R/Lackner C, J Hep Decomp ALD +/-SIRS 28 d SIRS AH grade SIRS neg pat. Canalicular CH Altamirano J, Gastroenterol Clin&hist AH 90 d Fibrosis Megamitochondria CH, PMN Canalicular/ Ductular CH

17 Altamirano J, Gastroenterology 2014 ALCOHOLIC HEPATITIS HISTOLOGIC SCORE: AHHS

18 Role of histology in the management of early/compensated ALD? Asymptomatic or oligosymptomatic Frequently overlooked condition Poorly characterized Utility of long-term mortality predictors Frequent In Austria: Guide intervention (abstinence councelling) people to prevent at risk? fibrosis progression, decompensation & complications

19 Decompensation PREVENTABLE!! Early/compensated ALD

20 Predictors of long-term outcome in ALD Author Reference Pessione F Liver Int 2003 Cortez-Pinto H Dig Dis Sci 2003 n Patients Follow up 122 Cirrhosis 5 yr 82 Clinical AH 12 yr Prognostic factors Age, CPS,GI-bleeding, HBV, HCV, smoking, alcohol abuse AH Mallory-Denk bodies Septal fibrosis / cirrhosis Elphick DA Am J Gastroenterol Biopsy within 1 mt of decomp 2 yr CPS, MDF Masson S Liver Int Septal fibrosis & Cirrhosis 15 yr Alcohol abuse, smoking, age Bilirubin

21 Predictors of long-term mortality in ALD Early/compensated (n=60) Decompensated (n=132) Fibrosis stage F Pericell fibrosis Sex Bilirubin INR 52% of cases P Present Female p <0.001 <0.001 Variables entered Fibrosis stage, ductular reaction, ASH abstinence, INR, albumin, platelet count Variables entered Pericellular fibrosis, canalicular cholestasis, ductular cholestasis, ASH, abstinence, sex, bilirubin, INR, albumin, leukocyte count, platelet count, sodium Lackner C, Spindelboeck W, J Hep 2017

22 What s new in alcoholic liver disease? Conclusion Histology is an important guide in the management of ALD Decompensated Histological confirmation of clinical AH selects patients for steroid treatment Ductular/canalicular cholestasis are evolving early markers of infection and sepsis Early/compensated Massively understudied but very frequent liver disease High prevalence of stage 3 & 4 fibrosis (apprx. 50%) Histological fibrosis stage may be the most important independent factor for prediction of long-term outcome Early diagnosis is pivotal to prevent disease progression