Definition/General
Introduction:
Hepatitis represents inflammatory liver disease with various etiologies
FNAC is rarely performed due to bleeding risk and limited diagnostic value
When performed, shows inflammatory infiltrate with hepatocyte injury
It includes viral, autoimmune, drug-induced, and toxic hepatitis.
Origin:
Results from direct hepatocyte injury or immune-mediated damage
Viral hepatitis: direct cytopathic effect or immune response
Autoimmune hepatitis: molecular mimicry mechanism
Drug-induced hepatitis: toxic metabolites or hypersensitivity
Alcohol-induced: oxidative stress and inflammation.
Classification:
Etiology-based: Viral hepatitis (HAV, HBV, HCV, HDV, HEV)
Autoimmune hepatitis (Type 1, 2)
Drug-induced liver injury (DILI)
Alcoholic hepatitis
Non-alcoholic steatohepatitis (NASH)
Toxic hepatitis
Time-based: Acute (<6 months) vs Chronic (>6 months).
Epidemiology:
Leading cause of liver disease globally
Viral hepatitis B/C major burden in developing countries
Autoimmune hepatitis: female predominance
Drug-induced hepatitis: increasing incidence
Alcoholic hepatitis: male predominance
Indian subcontinent: high prevalence of viral hepatitis B/C.
Clinical Features
Presentation:
Acute hepatitis: jaundice, fatigue, abdominal pain
Chronic hepatitis: may be asymptomatic
Fulminant hepatitis: encephalopathy, coagulopathy
Autoimmune hepatitis: extrahepatic manifestations
Drug-induced: temporal relationship with medication
Alcoholic hepatitis: fever, tender hepatomegaly.
Symptoms:
Constitutional symptoms: fatigue, malaise, anorexia
Gastrointestinal: nausea, vomiting, abdominal pain
Jaundice: icterus, dark urine, pale stools
Pruritus (cholestatic pattern)
Arthralgia (viral, autoimmune)
Rash (drug hypersensitivity)
Fever variable.
Risk Factors:
Viral exposure: unprotected sex, IV drug use, transfusions
Medications: acetaminophen, antibiotics, NSAIDs
Alcohol consumption
Autoimmune diseases
Family history (autoimmune, viral)
Occupational exposure
Travel to endemic areas.
Screening:
Liver function tests: elevated ALT, AST, bilirubin
Viral markers: HBsAg, anti-HCV, HAV IgM
Autoimmune markers: ANA, ASMA, anti-LKM
Drug levels if applicable
Imaging: hepatomegaly, ascites
Coagulation studies: PT/INR.
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Gross Description
Appearance:
FNAC shows mixed inflammatory infiltrate
Hepatocytes with degenerative changes
Lymphocytes and plasma cells predominant
Neutrophils in acute cases
Necrotic debris variable
Bile pigment in cholestatic cases
Background may be hemorrhagic.
Characteristics:
Inflammatory cell predominance
Hepatocytes: swelling, ballooning, necrosis
Portal inflammation: lymphocytes, plasma cells
Lobular inflammation: spotty necrosis
Interface hepatitis: piecemeal necrosis
Eosinophils in drug-induced cases
Pigment-laden macrophages.
Size Location:
Diffuse liver involvement typical
Portal tract expansion in chronic cases
Lobular disarray in acute hepatitis
Interface changes at portal-parenchymal junction
Panlobular involvement in severe cases
Bridging necrosis in fulminant hepatitis.
Multifocality:
Diffuse hepatic inflammation
Portal tract involvement
Lobular inflammatory foci
Interface hepatitis zones
Bridging inflammation in severe cases
Extrahepatic manifestations: lymphadenopathy, splenomegaly.
Microscopic Description
Histological Features:
Portal inflammation: lymphocytes, plasma cells, eosinophils
Interface hepatitis: piecemeal necrosis
Lobular inflammation: spotty necrosis, Councilman bodies
Hepatocyte changes: ballooning, steatosis
Cholestasis variable
Fibrosis in chronic cases.
Cellular Characteristics:
Inflammatory cells: lymphocytes (predominant), plasma cells, eosinophils
Hepatocytes: swelling, acidophilia, necrosis
Councilman bodies (apoptotic hepatocytes)
Mallory bodies (alcoholic hepatitis)
Kupffer cell hyperplasia
Ground glass cells (HBV).
Architectural Patterns:
Portal expansion by inflammatory infiltrate
Interface hepatitis: portal-parenchymal boundary disruption
Lobular disarray: loss of normal architecture
Bridging necrosis: portal-portal, portal-central
Cholestatic pattern: bile plugs, ductular reaction.
Grading Criteria:
Activity grading (A0-A3): minimal to severe
Portal inflammation (0-4 scale)
Interface hepatitis (0-4 scale)
Lobular necrosis (0-4 scale)
Fibrosis staging (F0-F4)
Modified HAI score (Histology Activity Index).
Immunohistochemistry
Positive Markers:
CD3 (T-lymphocytes)
CD20 (B-lymphocytes)
CD68 (macrophages, Kupffer cells)
CK7 (ductular reaction)
Hepatocyte marker (residual hepatocytes)
Smooth muscle actin (stellate cells)
HBsAg, HBcAg (viral hepatitis B).
Negative Markers:
Markers depend on differential diagnosis
CD34 (loss in chronic cases)
Reticulin (architectural collapse)
Iron stain (exclude hemochromatosis)
Copper stain (exclude Wilson disease)
α1-antitrypsin (exclude deficiency).
Diagnostic Utility:
Limited utility in FNAC
Inflammatory cell typing
Viral antigen detection (HBV)
Exclude malignancy
Assess ductular reaction
Stellate cell activation
Histology preferred for grading and staging.
Molecular Subtypes:
Viral genotypes: HBV (A-J), HCV (1-6)
Autoimmune subtypes: Type 1 (ANA+), Type 2 (anti-LKM+)
Drug-induced patterns: hepatocellular, cholestatic, mixed
Genetic polymorphisms: drug metabolism
HLA associations: autoimmune hepatitis.
Molecular/Genetic
Genetic Mutations:
Viral mutations: drug resistance, immune escape
HLA polymorphisms: autoimmune susceptibility
Drug metabolism genes: CYP450 variants
Immune response genes: cytokine polymorphisms
Hepatocyte injury genes: oxidative stress pathways.
Molecular Markers:
Viral markers: HBV DNA, HCV RNA levels
Inflammatory cytokines: TNF-α, IL-6, IFN-γ
Apoptosis markers: caspase activation
Oxidative stress markers
Fibrosis markers: TGF-β, PDGF
Regeneration markers: hepatocyte growth factor.
Prognostic Significance:
Viral load: treatment response predictor
Genotype: treatment duration
Autoimmune markers: relapse risk
Histologic grade/stage: progression risk
Age and gender: outcome predictors
Comorbidities: diabetes, obesity.
Therapeutic Targets:
Antiviral therapy: nucleos(t)ide analogues, direct-acting antivirals
Immunosuppression: corticosteroids, azathioprine
Anti-fibrotic agents (experimental)
Hepatoprotective agents
Vaccination (HAV, HBV prevention)
Lifestyle modification.
Differential Diagnosis
Similar Entities:
Acute vs chronic hepatitis
Viral vs autoimmune hepatitis
Drug-induced liver injury
Alcoholic hepatitis vs NASH
Primary biliary cholangitis
Primary sclerosing cholangitis
Wilson disease
Hemochromatosis.
Distinguishing Features:
Viral hepatitis: specific serologic markers
Autoimmune: autoantibodies, female predominance
Drug-induced: temporal relationship, eosinophils
Alcoholic: AST>ALT, Mallory bodies
PBC: AMA positive, cholestatic
PSC: cholangiographic changes.
Diagnostic Challenges:
Acute vs chronic determination
Etiology identification from cytology
Activity assessment
Overlap syndromes
Drug-induced vs viral hepatitis
Autoimmune vs viral hepatitis
Histology essential for definitive diagnosis.
Rare Variants:
Granulomatous hepatitis
Eosinophilic hepatitis
Giant cell hepatitis
Plasma cell hepatitis
Interface hepatitis patterns
Cholestatic hepatitis
Fulminant hepatitis.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Clinical Information
Patient with [clinical presentation], risk factors: [exposures/medications]
Specimen Adequacy
Adequate with inflammatory infiltrate and hepatocytes
Inflammatory Pattern
Shows [lymphocytes, plasma cells, neutrophils/eosinophils]
Hepatocyte Changes
Hepatocytes show [ballooning, necrosis, degenerative changes]
Background
Background shows [necrotic debris, bile pigment, blood]
Differential Diagnosis
Differential includes [viral, autoimmune, drug-induced, toxic hepatitis]
Final Cytological Diagnosis
Inflammatory liver disease consistent with hepatitis
Recommendations
Recommend [serologic studies, tissue biopsy, clinical correlation]