Liver Histology: Diagnostic and Prognostic Features

Abstract

When patients with suspected drug-induced liver injury (DILI) undergo liver biopsy, the pathologist can provide a wealth of information on the morphologic changes. The most common histologic patterns of DILI include mimics of acute and chronic hepatitis as well as acute cholestasis, chronic cholestasis, and a mixed pattern that combines hepatitis with cholestasis. The pattern may suggest etiologies of injury or correlate with reported patterns of injury for specific agents. Biopsy may exonerate or indict particular drugs as causal agents of injury and provide specific information on severity of injury and specific types of changes related to various outcomes.

Keywords: Acute hepatitis; Cholestatic hepatitis; Hepatic necrosis; Hepatotoxicity; Nodular regenerative hyperplasia.

Fig. 1.

Necroinflammatory patterns. (A, B) Acute hepatitis due to azithromycin. There were irregular, nonzonal regions of necrosis (arrows [A]) whereas numerous apoptotic hepatocytes and foci of lobular inflammation were seen near central veins (B). (C) Zone 3 necrosis due to acetaminophen. A mild mononuclear infiltrate is present in the necrotic zone. (D) Chronic hepatitis-like portal inflammation due to atorvastatin. (A) Hematoxylin-Eosin, original magnification ×200; (B) Hematoxylin-Eosin, original magnification ×400; (C) Hematoxylin-Eosin, original magnification ×100; and (D) Hematoxylin-Eosin, original magnification × 200.

Fig. 2.

Cholestatic patterns. (A) Acute cholestasis due to an anabolic steroid. Canalicular bile plugs in zone 3 (arrows) are present but there is minimal inflammation. (B) Bile duct injury (arrow) due to amoxicillin-clavulanate. Cholestasis (not pictured) was seen in zone 3. (C, D) Chronic cholestasis and bile duct loss due to gabapentin. The portal areas show no ducts, as confirmed by staining for keratin 7 (D). (A) Hematoxylin-Eosin, original magnification ×400; (B) Hematoxylin-Eosin, original magnification ×400; (C) Hematoxylin-Eosin, original magnification ×400; and (D) Keratin 7 immunohistochemistery, original magification ×200).

Fig. 3.

Steatohepatitis due to methotrexate. (A) Ballooning injury with Mallory-Denk bodies (arrows). (B) Extensive perisinusoidal fibrosis seen in a reticulin stain. (A) Hematoxylin-Eosin, original magnification ×400 and (B) Reticulin, original magnification ×200.

Fig. 4.

Vascular injury patterns. (A-C) NRH and hepatoportal sclerosis due to oxaliplatin. A low-magnification overview shows areas of vascular congestion outlining nodules (A). The Masson trichrome stain showed that most of the small portal areas lacked a vein (B). Reticulin staining shows the characteristic nodular regeneration (C). (D) Veno-occlusive changes after hematopoietic stem cell transplantation. A small vein shows nearly complete occlusion by loose collagen and cells. (A) Hematoxylin-Eosin, original magnification ×40; (B) Masson trichrome, original magnification ×200; (C) Reticulin, original magnification ×100; (D) Masson trichrome, original magnification ×400.

Fig. 5.

Resolving injury due to nitrofurantoin. A biopsy performed during the resolving phase of DILI shows minimal changes, seen as clusters of pigmented macrophages highlighted by a PAS stain with diastase digestion (Periodic acid-Schiff with diastase, original magnification ×400).