Academe Learn
CBME Curriculum Preview

Page 24 of 32

PA24.9 | Liver Disease & Tumour Morphology — Practical — SDL Guide (Part 2)

Chronic Hepatitis

Four-panel medical diagram showing chronic hepatitis histology with expanded portal inflammation, interface hepatitis, fibrosis progression, ground-glass hepatocytes, and HBV versus HCV microscopic clues.

Chronic Hepatitis: Histological Hallmarks

Panel A: Expanded portal tract, dense lymphocytic infiltrate, plasma cells, limiting plate, interface hepatitis zone, periportal hepatocyte injury, early periportal fibrosis. Panel B: F0 no fibrosis, F1-F2 portal fibrosis, F3 bridging fibrosis, F4 cirrhosis, portal-to-portal bridge, portal-to-central bridge, regenerative nodule. Panel C: Ground-glass hepatocytes, pale finely granular cytoplasm, HBsAg in smooth endoplasmic reticulum, orcein/Victoria blue positive staining. Panel D: HBV clue: ground-glass hepatocytes; HCV clues: portal lymphoid follicle, fatty change, bile duct damage.

Chronic hepatitis is defined as hepatic inflammation persisting beyond 6 months. The histological hallmarks differ from acute hepatitis:

Portal inflammation — Dense lymphocytic (± plasma cell) infiltrate expanding and filling portal tracts. The degree of portal inflammation correlates with disease activity.

Interface hepatitis (formerly piecemeal necrosis) — Lymphocytes spill beyond the portal limiting plate to destroy periportal hepatocytes. This is the active front of immune damage and is the key marker of histological activity.

Fibrosis — Begins as portal fibrosis, extends as bridging fibrosis (portal-to-portal or portal-to-central bridging), and ultimately becomes cirrhosis. Staged 0-4 (Metavir) or 0-6 (Ishak).

Ground-glass hepatocytes — Pale, finely granular cytoplasm due to smooth-ER proliferation filled with HBsAg. Seen in chronic HBV infection. On special stains: positive with orcein or Victoria blue (HBsAg).

HCV tends to cause: lymphoid follicles in portal tracts, fatty change (especially genotype 3), and bile duct damage — a useful discriminator from HBV.

H&E-style educational diagram of chronic hepatitis showing an expanded portal tract with dense lymphocytic inflammation, interface hepatitis across the limiting plate, and early periportal fibrosis.

Chronic Hepatitis: Portal Inflammation and Interface Hepatitis

Panel A: Main H&E 20x field showing expanded portal tract, dense lymphocytic infiltrate, limiting plate, interface hepatitis zone, periportal hepatocytes, and early periportal fibrosis.. Panel B: Magnified portal-parenchymal junction showing lymphocytes breaching the limiting plate and damaging periportal hepatocytes.. Panel C: Simplified color-coded schematic showing portal tract, lymphocytic inflammation, dashed limiting plate, highlighted interface hepatitis zone, and periportal fibrosis..

CLINICAL PEARL

The Metavir score combines two numbers: A (activity, 0-3) and F (fibrosis, 0-4). A2F3 means moderate activity with severe fibrosis — almost bridging cirrhosis. When you read a biopsy report with these numbers, the A reflects how inflamed the liver is right now (and therefore how urgently antiviral treatment is needed), while F reflects cumulative structural damage. Activity can improve on treatment; fibrosis beyond F3 is largely irreversible.

Alcoholic Hepatitis

Four-panel diagram of alcoholic hepatitis showing Mallory-Denk bodies, neutrophilic satellitosis, steatosis, and zone 3 chicken-wire fibrosis around the central vein.

Alcoholic Hepatitis: Key Histological Features

Panel A: Core liver biopsy view showing central vein zone 3, sinusoids, ballooned hepatocytes, Mallory-Denk bodies, neutrophilic satellitosis, and macrovesicular steatosis.. Panel B: Magnified ballooned hepatocyte showing rope-like eosinophilic Mallory-Denk bodies composed of ubiquitinated cytokeratin 8/18 intermediate filaments.. Panel C: Comparison of alcoholic hepatitis with neutrophil-dominant satellitosis versus viral hepatitis with lymphocyte-dominant inflammation.. Panel D: Trichrome-style lobule showing zone 3 perivenular chicken-wire pericellular fibrosis radiating from the central vein toward portal tracts..

Alcoholic hepatitis (AH) is a histologically distinct pattern of alcohol-related liver injury, different from simple steatosis. The four key features:

  1. Mallory-Denk bodies (formerly Mallory hyaline) — Irregular, rope-like, deeply eosinophilic cytoplasmic inclusions within ballooned hepatocytes. Composed of ubiquitinated, misfolded intermediate filaments (cytokeratin 8/18). Not pathognomonic of AH alone (also seen in PBC, Wilson, NASH) but are the most visually striking feature.
  1. Neutrophilic satellitosis — Neutrophils clustering around Mallory-containing hepatocytes. This neutrophil-dominant inflammation distinguishes AH from viral hepatitis (which is lymphocyte-dominant).
  1. Perivenular fibrosis ("chicken-wire" fibrosis) — Fibrosis radiating from zone 3 (central vein) outward along the sinusoids, giving a pericellular chicken-wire pattern on trichrome stain. A direct alcohol toxic effect; zone 3 is most vulnerable due to lowest oxygen tension.
  1. Steatosis coexisting in background hepatocytes.

Severe AH: Mortem de Brouwer lobular inflammation, bridging necrosis, and cholestasis (bile plugs) can develop.

The combination of steatosis + Mallory-Denk bodies + neutrophilic inflammation + zone-3 perivenular fibrosis defines alcoholic steatohepatitis (ASH) — analogous to NASH but aetiologically distinct.

SELF-CHECK

A liver biopsy from a 45-year-old chronic alcohol user shows ballooned hepatocytes containing rope-like eosinophilic cytoplasmic inclusions, with neutrophils clustering around these cells and pericellular fibrosis in zone 3. What are the inclusions?

A. Ground-glass inclusions of HBsAg

B. Mallory-Denk bodies (ubiquitinated cytokeratin aggregates)

C. Councilman bodies (apoptotic hepatocyte remnants)

D. Lipofuscin granules

Reveal Answer

Answer: B. Mallory-Denk bodies (ubiquitinated cytokeratin aggregates)

Rope-like eosinophilic cytoplasmic inclusions in ballooned hepatocytes surrounded by neutrophils in a chronic alcohol user = Mallory-Denk bodies. They are aggregates of ubiquitinated cytokeratin 8/18. Ground-glass inclusions (option A) are smooth, pale, and peri-nuclear, associated with HBV. Councilman bodies (option C) are extruded, rounded, cell-death remnants — not intracytoplasmic inclusions. Lipofuscin is brown, fine-granular, and accumulates with age — not rope-like.

Cirrhosis — Gross and Microscopic

Four-panel medical diagram comparing gross and microscopic cirrhosis with normal liver architecture, fibrous septa, regenerative nodules, reticulin collapse, and complications.

Cirrhosis: Gross and Microscopic Features

Panel A: Shrunken firm liver, nodular capsular surface, micronodular cirrhosis <3 mm, macronodular cirrhosis >3 mm, mixed nodularity. Panel B: Normal hepatic lobule, central vein, portal tract, hepatic plates, intact reticulin framework, preserved lobular landmarks. Panel C: Regenerative nodules, blue fibrous septa on Masson trichrome, incorporated portal tracts, absent or eccentric central vein, lost lobular architecture. Panel D: Collapsed reticulin network, cholestasis, large-cell dysplasia, small-cell dysplasia, early HCC focus arising within nodular cirrhotic background.

Cirrhosis is the end-stage of chronic liver disease, defined by two co-occurring features: extensive fibrosis and regenerative nodule formation. Both must be present; fibrosis alone (even bridging) is not cirrhosis.

Gross appearance:
- Micronodular cirrhosis (nodules <3 mm, uniform): alcohol-related, haemochromatosis.
- Macronodular cirrhosis (nodules >3 mm, variable): viral hepatitis (HBV, HCV).
- Mixed patterns exist. Liver is shrunken (end-stage), firm, and has a nodular capsular surface.

Microscopic:
- Regenerative nodules — clusters of hepatocytes with internal blood supply (hepatic arterioles) but no organised central vein → lobular landmarks are lost.
- Fibrous septa — stain blue on Masson trichrome, providing the scaffold around nodules.
- Reticulin stain: collapse of the normal reticulin network within nodules marks loss of liver plate architecture. Intact reticulin = preserved architecture (reactive nodule or partial collapse).
- Portal tracts can be incorporated into septa and become unidentifiable.

Key distinction: in cirrhosis the central vein is absent or eccentric within nodules — this is the single best histological clue that you are looking at a regenerative nodule rather than normal parenchyma.

Complications visible histologically: cholestasis, hepatocyte dysplasia (large-cell and small-cell), and frank HCC arising within nodular background.

SELF-CHECK

On a trichrome-stained liver section, you see irregular blue-staining bands completely surrounding groups of hepatocytes. The central vein is absent within the hepatocyte clusters. What is the diagnosis?

A. Bridging fibrosis (F3) without cirrhosis

B. Massive hepatic necrosis

C. Cirrhosis with regenerative nodules

D. Hepatic amyloidosis

Reveal Answer

Answer: C. Cirrhosis with regenerative nodules

Blue fibrous bands (trichrome) completely surrounding hepatocyte clusters that lack a central vein = cirrhosis with regenerative nodules. The absence of the central vein within nodules is the key differentiator from bridging fibrosis (F3), where the lobular landmarks — though bridged — can still be partially identified. Massive necrosis shows collapse and dropout, not nodule formation. Amyloid deposits in a homogeneous pattern in sinusoidal walls, not as complete nodule-surrounding septa.