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  • Basic patterns of liver damage what information can a liver biopsy

    provide and what clinical information

    does the pathologist need?

    Rob Goldin

  • Fatty liver disease

    Is there fatty change ?

    Is there a fatty liver hepatitis?

    What is the cause of the fatty liver disease?

    Clinical Liver Disease Volume 2, April 2013, Pages 6467


    Clinical Liver Disease Volume 1, September 2012, Pages 108111


  • Types of fatty change:Large droplet

    mesovesicular fatty change

  • Causes of large droplet fatty change

    Obesity and Diabetes Mellitus

    Protein-calorie malnutrition


    Drugs and toxins (e.g. alcohol, corticosteroids)

    Metabolic disorders ( e.g. Wilsons Disease)

    Infections ( e.g. hepatitis C)

  • Types of fatty change:Small droplet

  • Causes of small droplet fatty change


    Fatty liver of pregnancy

    Drugs (e.g. nucleoside analogues)

    Toxins (e.g. Jamaican vomiting disease)

    Inborn errors of metabolism (e.g. urea cycle disorders).

    Reyes syndrome

    Infections (e.g. Hepatitis A)

  • Fatty liver disease: More than just fat

    Is there fibrosis?

    Is there a fatty liver hepatitis?

    Ballooning and inflammation

  • (B) Normal hepatocytes,


    grade 0. Cytoplasm is pink and

    granular and liver cells have

    sharp angles.

    (C) Ballooning, grade 1.

    Hepatocytes have rounded

    contours with clear reticular

    cytoplasm. Size is quite similar

    to that of normal hepatocytes.

    (D) Ballooning, grade 2.

    Cells are rounded with clear

    cytoplasm and twice as large as

    normal hepatocytes.

    Recognising ballooning

    Hepatology Volume 56, November 2012 Pages 17511759

  • Nuclear vacuolation

  • Causes of nuclear vacuolation


    Insulin resistance

    Wilsons disease

    Glycogen storage disease

  • Gastroenterology, Volume 146,

    Issue 5, 2014, 1231 - 1239

    A Histologic Scoring System for

    Prognosis of Patients With

    Alcoholic Hepatitis

  • Histologic features independently associated with 90-day survival included in the Histologic AHHS. ( A C ) Degree of fibrosis

    (Masson trichrome staining): portal fibrosis, expansive areas of liver fibrosis, and cirrhosis, respectively. H&E s...

  • Histologic features independently associated with 90-day survival included in the Histologic AHHS. ( A ) Hepatocellular and

    canalicular bilirubinostasis ( arrow ). ( B ) Ductular bilirubinostasis ( arrow ). ( C ) Megamitochondria ( arrows ). ( D and E) Mild and

    severe PMN infiltration, respectively (arrow). H&E stain.

  • Gastroenterology, Volume 146, Issue 5, 2014, 1231 - 1239


    Stage of fibrosis

    No fibrosis or portal fibrosis 0

    Expansive fibrosis 0

    Bridging fibrosis or cirrhosis +3


    No 0

    Hepatocellular only 0

    Canalicular or ductular +1

    Canalicular or ductular plus hepatocellular +2

    PMN infiltration

    No/Mild +2

    Severe 0


    No megamitochondria +2

    Megamitochondria 0

    The AHHS categories are as follows: mild, 03; intermediate, 45; severe, 69.

    AHHS for Prognostic Stratification of AH

  • Chronic viral hepatitis

    Assess disease severity:

    Grade (necro-inflammation)

    Stage (fibrosis)

    ? Score (using modified Histological Activity Index / METAVIR)

    Assess disease progression or response to treatment

    Modern Pathology 2007; 20: S3

  • Chronic viral hepatitis

    Hepatitis related changes:

    HBV: Ground glass cells

    HCV: Lymphoid follicles, hepatitic bile duct damage, fatty change

    HDV: Increased lobular activity

    Large cell changeClinical Liver Disease Volume 1, April 2012 , Pages 3235


    Clinical Liver Disease Volume 2, February 2013, Pages 4951


  • HBV: Ground glass hepatocytes


  • HCV: Lymphoid aggregate/follicle

  • HCV: Hepatitic bile duct damage

  • HCV genotype 3: Fatty change

  • HDV

  • Something else going on

    Drug reaction

    Another virus

    Fatty liver disease

    fatty liver hepatitis in 5% of liver biopsies of patients with chronic liver disease

    Mod Pathol 2003; 16: 49

    Iron overload

    In patients with HCV:

    stainable iron in 16%,

    grade 2 and 3 (out of 4) iron in 7%.

    J Gastroenterol Hepatol 2005; 20: 243

  • Large cell change (or is it dysplasia?)

  • Iron overload

    What is the pattern if iron overload?

    Grade the degree of iron overload

    Assess fibrosis

    ? Send tissue for biochemical iron measurement

    Mod Pathol 2007; 20: S31S39.

  • What is the pattern of iron overload?

    Parenchymal Macrophage

  • Patterns of iron overload

    Parenchymal overload

    gut derived iron.

    Macrophage iron

    transfusion derived iron


  • Mixed pattern of iron overload:Sickle cell anaemia Ferroportin deficiency

  • Autoimmune hepatitis

    Help in making the diagnosis

    Help in assessing the response to treatment

    Clinical Liver Disease Volume 3, February 2014, Pages 3841


  • Simplified histological criteria for the diagnosis of AIH


    1. Interface hepatitis

    2. lymphocytic / lympho-plasmacytic infiltrates in portal tracts and extending into the lobule

    3. rosetting of liver cells

    Compatible" a chronic hepatitis with lymphocytic infiltration without all the above features

    Atypical" for AIH when showing signs of another diagnosis.

  • Autoimmune Hepatitis

  • The Overlap Syndromes of Autoimmune Hepatitis

    Clinical Liver Disease Volume 3, January 2014, Pages 25


  • Drug reaction

    Any kind of liver disease can be caused by a drug

    Histological features suggesting a drug reaction:

    Eosinophils, plasma cells, granulomas, sharply demarcated necrosis, cholestatic hepatitis

    Clinical Liver Disease Volume 4, Issue 1, July 2014, Pages 1216


  • Injury Patterns of Selected Drugs in Common Use

    Drug Pattern of Injury

    Paracetamol Zone 3 necrosis (with little additional inflammation)

    Amiodarone Steatohepatitis-like, with numerous Mallory-Denk bodies

    and fibrosis

    Amoxicillin-clavulanate Cholestatic hepatitis (with prominent duct injury)

    Anabolic steroids Acute cholestasis to cholestatic hepatitis with little duct


    Azithromycin Variable: Hepatitis with or without cholestasis

    Diclofenac Zone 3 necrosis with lymphocytic inflammation

    Isoniazid Acute or chronic hepatitis

    Methotrexate Steatosis and fibrosis, sometimes steatohepatitis-like

    Minocycline Acute or chronic hepatitis

    Nitrofurantoin Acute or chronic hepatitis

    Oxaliplatin Hepatoportal sclerosis, sinusoidal dilation, nodular

    regenerative hyperplasia

  • Drug reaction

  • Drug reaction

  • Drug reaction

  • Histological predictors of severity in drug-induced liver disease.

    More severe disease associated with: 1. necrosis2. fibrosis stage3. microvesicular steatosis4. cholangiolar cholestasis 5. bile duct damage

    Milder disease associated with: 1. granulomas2. increased eosinophils


  • Biliary tract disease

  • Biliary tract disease: Orcein stain

  • Biliary tract disease: CK7

  • Causes of Disappearing Bile Ducts

    PBC* (and its variants)

    PSC (and its variants)

    Drugs and Toxins

    Chronic transplant rejection

    Graft Vs. Host

    Hodgkins Disease, Histiocytosis X


    Paucity of interlobular bile ducts



  • Primary Biliary Cholangitits

    = the name for Primary Biliary Cirrhosis

  • Vascular Disease:Non-cirrhotic portal hypertension

  • Vascular Disease:Non-cirrhotic portal hypertension

  • Causes of Nodular Regenerative Hyperplasia

    Connective tissue disorders

    Myeloproliferative disorders

    Chronic vascular congestion

    Drugs e.g. steroids, anticancer drugs, anticonvulsants, immunosuppressive agents

    Clinical Liver Disease, Volume 6, October 2015, Pages 103106 (

  • Discrepancy rates in liver biopsy reporting

    fibrosis staging

    recognising and interpreting bile duct disorders

    misdiagnoses of autoimmune hepatitis

    J Clin Pathol 2014;67:825-827

    Histopathology. 2016 Jan 30. doi: 10.1111/his.12940

  • What clinical in