Basic patterns of liver damage what information can a liver biopsy provide and what clinical information does the pathologist need? Rob Goldin r.goldin@imperial.ac.uk
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 64 67 (http://onlinelibrary.wiley.com/doi/10.1002/cld.172/full) Clinical Liver Disease Volume 1, September 2012, Pages 108 111 (http://onlinelibrary.wiley.com/doi/10.1002/cld.31/full)
Types of fatty change: Large droplet mesovesicular fatty change
Causes of large droplet fatty change Obesity and Diabetes Mellitus Protein-calorie malnutrition TPN Drugs and toxins (e.g. alcohol, corticosteroids) Metabolic disorders ( e.g. Wilson s Disease) Infections ( e.g. hepatitis C)
Types of fatty change: Small droplet
Causes of small droplet fatty Alcohol 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). Reye s syndrome Infections (e.g. Hepatitis A)
Is there fibrosis? Fatty liver disease: More than just fat Is there a fatty liver hepatitis? Ballooning and inflammation
Recognising ballooning (B) Normal hepatocytes, ballooning, 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. Hepatology Volume 56, November 2012 Pages 1751 1759
Nuclear vacuolation
Causes of nuclear vacuolation Physiological Insulin resistance Wilson s disease Glycogen storage disease
A Histologic Scoring System for Prognosis of Patients With Alcoholic Hepatitis Gastroenterology, Volume 146, Issue 5, 2014, 1231-1239
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.
AHHS for Prognostic Stratification of AH Points Stage of fibrosis No fibrosis or portal fibrosis 0 Expansive fibrosis 0 Bridging fibrosis or cirrhosis +3 Bilirubinostasis No 0 Hepatocellular only 0 Canalicular or ductular +1 Canalicular or ductular plus hepatocellular +2 PMN infiltration No/Mild +2 Severe 0 Megamitochondria No megamitochondria +2 Megamitochondria 0 The AHHS categories are as follows: mild, 0 3; intermediate, 4 5; severe, 6 9. Gastroenterology, Volume 146, Issue 5, 2014, 1231-1239
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 change Clinical Liver Disease Volume 1, April 2012, Pages 32 35 (http://onlinelibrary.wiley.com/doi/10.1002/cld.30/full) Clinical Liver Disease Volume 2, February 2013, Pages 49 51 (http://onlinelibrary.wiley.com/doi/10.1002/cld.139/full)
HBV: Ground glass hepatocytes Orcein
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 Iron overload In patients with HCV: Mod Pathol 2003; 16: 49 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: S31 S39.
What is the pattern of iron overload? Parenchymal Macrophage
Patterns of iron overload Parenchymal overload gut derived iron. Macrophage iron transfusion derived iron Mixed
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 38 41 (http://onlinelibrary.wiley.com/doi/10.1002/cld.321/full)
Simplified histological criteria for Typical 1. Interface hepatitis the diagnosis of AIH 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 2 5 (http://onlinelibrary.wiley.com/doi/10.1002/cld.294/full)
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 12 16 (http://onlinelibrary.wiley.com/doi/10.1002/cld.371/full)
Injury Patterns of Selected Drugs in Common Use Drug Paracetamol Amiodarone and fibrosis Amoxicillin-clavulanate Anabolic steroids Azithromycin Diclofenac Isoniazid Methotrexate Minocycline Nitrofurantoin Oxaliplatin Pattern of Injury Zone 3 necrosis (with little additional inflammation) Steatohepatitis-like, with numerous Mallory-Denk bodies Cholestatic hepatitis (with prominent duct injury) Acute cholestasis to cholestatic hepatitis with little duct injury Variable: Hepatitis with or without cholestasis Zone 3 necrosis with lymphocytic inflammation Acute or chronic hepatitis Steatosis and fibrosis, sometimes steatohepatitis-like Acute or chronic hepatitis Acute or chronic hepatitis 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. necrosis 2. fibrosis stage 3. microvesicular steatosis 4. cholangiolar cholestasis 5. bile duct damage Milder disease associated with: 1. granulomas 2. increased eosinophils
http://livertox.nih.gov/
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 Hodgkin s Disease, Histiocytosis X Sarcoid Paucity of interlobular bile ducts HIV Idiopathic
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 103 106 (http://onlinelibrary.wiley.com/doi/10.1002/cld.505/full)
Discrepancy rates in liver biopsy fibrosis staging reporting 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 information does the pathologist need? A decent clinical history!
Clinical information Look at the biopsy and write the description without knowing any clinical information Only write the conclusion when you have the information
Example of not very useful clinical information Liver biopsy Abnormal LFTs Complex medical history
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