Steatohepatitis Grading. Bile Duct Lesions

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1 Common Problems in Hepatopathology Steatohepatitis Grading & Bile Duct Lesions Larry Burgart, MD Abbott NW Hospital, Minneapolis University of Minnesota

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3 Inflammatory Liver Disease Lawrence Burgart, M.D.

4 Approach to Liver Histology Review slide as unknown Bias is too powerful if clinical info known

5 Approach to Liver Histology Review slide as unknown Bias is too powerful if clinical info known Rules of liver pathology (Dr. Ken Batts) 1) You re a fool if you look at the history before the slides.

6 Approach to Liver Histology Review slide as unknown Bias is too powerful if clinical info known Rules of liver pathology 1) You re a fool if you look at the history before the slides. 2) You re a damned fool if you sign out the case without the clinical history.

7 Approach to Liver Histology Review slide as unknown Bias is too powerful if clinical info known Rules of liver pathology 1) You re a fool if you look at the history before the slides. 2) You re a damned fool if you sign out the case without the clinical history. Ultimately the diagnosis is histology + clinical

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9 Approach to Liver Histology Step 1: Hepatitic v. Biliary Can be complex Hepatitic - intact ducts; necroinflammatory hepatocellular damage Step 2: Acute v. Chronic -- key decision point Acute: broad DDx (not hopeless!) Chronic: manageable DDX Fibrosis

10 Algorithm for Liver Histology Chronic liver disease - short DDx Hepatitis Biliary Hepatitis B & C Primary biliary cirrhosis Autoimmune Primary sclerosing (PSC) Steatohepatitis Secondary sclerosing Hemochromatosis Autoimmune cholangitis Alpha-1 antitrypsin Idiopathic ductopenia Wilson s disease

11 Algorithm for Liver Histology Chronic liver disease - short DDx Hepatitis Biliary Hepatitis B & C Primary biliary cirrhosis Autoimmune Primary sclerosing (PSC) Steatohepatitis Secondary sclerosing Hemochromatosis Autoimmune cholangitis Alpha-1 antitrypsin Idiopathic ductopenia Wilson s disease

12 Algorithm for Liver Histology Chronic liver disease - short DDx Hepatitis Biliary Hepatitis B & C Primary biliary cirrhosis Autoimmune Primary sclerosing (PSC) Steatohepatitis Secondary sclerosing Hemochromatosis Autoimmune cholangitis Alpha-1 antitrypsin Cholestasis of sarcoidosis Wilson s disease Idiopathic ductopenia

13 Fatty Liver Disease Takes Over The World

14 Fatty Liver Disease Takes Over The World Of Hepatopathology

15 New World 1980 Dr. Jurgen Ludwig Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease.

16 New World 1980 Dr. Jurgen Ludwig Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. NASH is born

17 New World 1980 Dr. Jurgen Ludwig Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. NASH is born NAFLD follows

18 Boom in NAFLD Parallels epidemiology of obesity Obesity => insulin resistance Speculation, other factors in food supply Trans fats High fructose corn syrup Animal models

19 Clinical Importance NAFLD affects 25-40% of adult Americans 10-30% NAFLD => Progressive NASH 2-10% of overweight individuals => NASH Aging population in increasingly obese society

20 Steatosis / Steatohepatitis Distinctive histologic pattern of liver disease Multiple etiologies Alcoholic Nonalcoholic (obesity, insulin resistance) Amiodarone Usually clinically apparent Significant histologic overlap (more to come)

21 Inflammatory Liver Disease Lawrence Burgart, M.D.

22 Practical Problem: steatohepatitis? Inflammatory Liver Hepatocyte ballooning Disease Lobular inflammation Lawrence Burgart, M.D.

23 Practical Problem: steatohepatitis? Inflammatory Liver Hepatocyte ballooning Disease Lobular inflammation Lawrence Burgart, M.D.

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28 Alcohol v NASH Tends to be more active More Mallory s and neutrophils More cholestasis Relatively specific, not very sensitive: Foamy degeneration (uncommon) Sclerosing hyalin fibrosis

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36 Amiodarone

37 Portal changes vary

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39 Staging & Grading Dr. Elizabeth Brunt field leader Med school: UT Galveston St. Louis: Wash U., SLU, Wash U.

40 Staging Five stages of fibrosis (0-4) 1 zone 3 perisinusoidal fibrosis 2 zone 3 and periportal 3 septal fibrosis without nodules Central-central, central-portal, etc 4 cirrhosis, micronodular

41 Inflammatory Liver Disease Lawrence Burgart, M.D.

42 Inflammatory Liver Disease Lawrence Burgart, M.D.

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44 Grading NASH 3 degrees necroinflammatory activity (1-3) Grade Steatosis Ballooning Inflammation 1- Mild 1-2+ (<66%) Minimal Lobular: Mod 2-3+ (>33%, <66%) Moderate Lobular: Marked 3+ Marked Lobular: 3+

45 Inflammatory Liver Disease Lawrence Burgart, M.D.

46 Inflammatory Liver Disease Lawrence Burgart, M.D.

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48 Inflammatory Liver Disease Lawrence Burgart, M.D.

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56 Steatohepatitis Clinical Help ANA + in a significant minority of NASH Steatohepatitis NOT pattern of autoimmune

57 Steatohepatitis Clinical Help ANA + in a significant minority of NASH Steatohepatitis NOT pattern of autoimmune Alcoholic steatohepatitis, AST > ALT >1 sensitive, not specific (high stage NASH) >2 specific, not sensitive

58 Steatohepatitis Clinical Help ANA + in a significant minority of NASH Alcoholic steatohepatitis, AST > ALT Hepatitis C evaluate for steatohepatitis using same morphologic criteria and provide estimate of relative influence

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60 Biliary Disease Differentiate biliary from hepatitis Ductocentric inflammation / fibrosis Cholate stasis, zone 1 hepatocytes Hepatocyte capture Subclassify Large duct v small duct CPC

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63 Cholate stasis

64 Inflammatory Liver Disease Lawrence Burgart, M.D.

65 Inflammatory Liver Disease Lawrence Burgart, M.D. Rhodanine

66 Later stages cholate stasis

67 Hepatocyte capture

68 Inflammatory Liver Disease Lawrence Burgart, M.D.

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70 Biliary Disease Differentiate biliary from hepatitis Ductocentric inflammation / fibrosis Cholate stasis, zone 1 hepatocytes Hepatocyte capture Subclassify Large duct v small duct CPC

71 Biliary Disease Clinical Differentiation Primary sclerosing cholangitis (large duct) Positive cholangiogram (ERCP), exclude secondary history Small duct PSC Idiopathic inflammatory bowel disease, usually CUC Primary biliary cirrhosis family AMA+ ---> PBC (90%) ANA+ (ASmA+) ---> Autoimmune cholangiopathy (9%) Negative serology ---> AMA- PBC (1%); woman >40yo

72 Primary Sclerosing Cholangitis Strong IIBD association 70% have CUC 5% of CUC patients have PSC Chief complaints are pruritus, fatigue, and eventually cirrhosis-related complaints Cholestatic enzyme picture URSO, transplantation

73 Ductular proliferation Large duct disease

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75 Primary Biliary Cirrhosis 90% disease Women (always >35) AMA positive If AMA neg, ANA &/or ASmA positive Autoimmune cholaniopathy poor term ANA / ASmA positive, AMA negative Behaves just like PBC, NO to steroids

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78 Biliary Disease Clinical Differentiation Primary sclerosing cholangitis (large duct) Positive cholangiogram (ERCP), exclude secondary history Small duct PSC Idiopathic inflammatory bowel disease, usually CUC Primary biliary cirrhosis family AMA+ ---> PBC (90%) ANA+ (ASmA+) ---> Autoimmune cholangiopathy (9%) Negative serology ---> AMA- PBC (1%); woman >40yo

79 Overlapping Biliary Disease Autoimmune Hepatitis ~11% PBC, 4% PSC cases have overlap AIH Foils include overcalls and undercalls In biliary cases, interface inflamm overcalled AIH AIH with prominent activity can mask biliary ds CPC important, ALT > 300; ALP abnormal

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