CHAPTER 95
Liver biopsy and histopathological diagnosis

Sugantha Govindarajan

USC Keck School of Medicine, Los Angeles, CA, USA

Evaluation of liver biopsy requires that the pathologist recognize the architecture and identify the pathological changes, and correlate the changes with clinical and laboratory data (Figures 95.1–95.99). Although some histological diagnosis can be made without the help of the clinical or laboratory data, most meaningful information is obtained with a proper clinical–pathological correlation.

Special stains, such as Masson trichrome, demonstrate fibrosis or cirrhosis of the liver, an indication of a chronic process. Other routine stains include stains for iron, reticulin, and diastase‐resistant periodic acid–Schiff‐positive material. Granulomas of the liver require special stains for the etiological agent, such as acid‐fast organisms and fungi. Shikata or orcein stain identifies hepatitis B surface antigen as well as copper‐binding protein, metallothionein. Immunoperoxidase stains detect viral and nonviral protein in the biopsy material using specific antibodies directed against the proteins.

Routine hematoxylin and eosin‐stained sections are the most valuable tools in the diagnosis. Well‐embedded (3 μm) sections with good H&E stain will provide great cellular details of hepatocytes, such as inclusions in the cytoplasm or the nuclei, as well as features such as fat, cholestasis, or dysplasia.

Initial assessment of the architecture is followed by a closer review of the portal tract or the fibrous septa if cirrhosis is present. Elements to be examined are the bile ducts, epithelial abnormalities or their absence or proliferation, cellular types of the inflammatory infiltrates, and the infiltrates’ involvement of the bile ducts, the parenchymal limiting plate, or the vessels (vasculitis). The portal tracts or the fibrous septa should also be examined under polarized light for foreign material in the macrophages, which is usually seen in patients with a history of intravenous drug addiction.

The parenchyma is examined for cord sinusoidal pattern; normal one‐cell thickness is altered in hepatocellular carcinoma to 3–4 or more cells that thicken the trabeculae. Parenchymal cytoplasmic inclusions such as Mallory bodies, mega‐mitochondria, and α_l‐antitrypsin, or ground‐glass cytoplasmic appearance are identified under higher magnifications in the review process. Areas of hepatocytolysis often appear as focal punched‐out or spotty necrosis with an accumulation of Kupffer cells and lymphocytes, or as large areas of collapsed reticulin with loss of hepatocytes. Hepatocytolysis is often localized in the perivenular zones. Individual cell necrosis is seen as acidophil bodies or apoptotic cells.

Attention also should be paid to the sinusoidal lining cells, Ito cells, and the space of Disse. In alcoholic liver disease, there is collagen deposition of the sinusoidal space, which stands out on Masson trichrome stain. Amyloid is also seen in this space, either as reticular or globular type, and is demonstrated by Congo red stain.

In addition to histology to confirm the clinical diagnosis, liver biopsy has become a very important prognostic tool to assess the responses to treatment of chronic viral hepatitis B and C. The Histology Activity Index (HAI) is measured using several standardized methods on pretreatment and 1–2‐year follow‐up biopsies. This quantitative measurement of necroinflammation and fibrosis by either Knodell or Ishak scoring (Table 95.1) has been applied to many long‐term therapeutic protocols. Standardization of scoring has been helpful in studies that compare different treatment modalities. Its application for individual cases also helps the clinician with patient follow‐up and monitoring of other serological viral markers.

Liver biopsies are also extremely valuable in post‐liver transplant settings. Standard protocols of liver biopsies help confirm clinical diagnoses from rejection to opportunistic infections. Post‐liver transplantation management of patients is largely dependent on the liver biopsy interpretations in conjunction with other laboratory studies.

With proper indications and carefully chosen technique, a needle biopsy of the liver is an invaluable tool. Most often, the biopsy provides the final diagnosis when the pathology interpretation is made using the combined expertise of the pathologist and the hepatologist.