Drug Induced Liver Disease (Hepatotoxicity)-Chapter 11-HISTOLOGICAL PATTERN IN DRUG-INDUCED LIVER DISEASE Part-3

Figure.11.5:-Minocycline-induced autoimmune hepatitis. Marked necroinflammatory activity with numerous plasma cells.

Figure.11.6:- Methotrexate toxicity. Prominent macrovesicular steatosis and periportal fibrosis.

Figure.11.7:- Anabolic-steroid-induced pure cholestasis. Prominent bile plugs are present in hepatocytes and canaliculi without inflammation or hepatocellular damage.

Figure.11.8:- Erythromycin-related cholestatic hepatitis. Features similar to acute hepatitis are present, as well as bile plugs in hepatocytes and canaliculi.

Differential diagnosis

          Drug-induced cholestatic injury can be histologically indistinguishable from obstructive biliary disease. While the latter typically results in portal tract oedema and ductular reaction with inflammation, cholestasis may be the only significant feature in early stages. Drug-induced cholestatic hepatitis also needs to be distinguished from autoimmune hepatitis and acute viral hepatitis.

         Chronic biliary diseases such as primary biliary cirrhosis and primary sclerosing cholangitis do not show cholestasis on biopsy early in the course of the disease; serological tests such as antimitochondrial antibodies and cholangiography, respectively, can more definitely rule out these diagnoses.

Chronic cholestasis and ductopenia

         Cholestatic symptoms and biochemical findings usually resolve with cessation of the offending drug but may persist in some instances. Drugs causing prolonged cholestasis (defined as greater than 3 months in duration) and ductopenia include antibiotics such as amoxicillin–clavulanic acid and flucloxacillin, antifungals such as terbinafine and, rarely, oral contraceptives. Amiodarone can also cause prolonged disease.

Vanishing bile duct syndrome

         Cholestasis with variable degree of inflammation, bile duct injury and hepatocellular damage is seen early in the course of the disease (fig 9). If the disease persists for a few months or beyond, loss of bile ducts and overt ductopenia may be observed, termed “vanishing bile duct syndrome”. Persistent inflammation and bile ductular reaction also may be present. Rare cases can progress to cirrhosis. Vanishing bile duct syndrome can be triggered by anticonvulsants such as carbamazepine and zonisamide, antipsychotics such as chlorpromazine  and sulpiride, NSAIDs such as ibuprofen  and tenoxicam, and antibiotics such as amoxicillin, flucloxacillin, clindamycin and trimethoprim-sulfamethoxazole. 

Figure.11.9:- Prolonged cholestasis. Persistence of canalicular bile plugs accompanied by feathery degeneration of periportal hepatocytes (cholate stasis).

Figure.11.10:- Fibrin-ring granulomas. Fat vacuole surrounded by a ring of fibrin deposition and epithelioid cells.

Figure.11.11:- Microvesicular steatosis. Numerous small lipid droplets are present throughout the hepatocytic cytoplasm.

Figure.11.12:- Amiodarone steatohepatitis. Marked hepatocyte ballooning, numerous Mallory hyaline and minimal steatosis.