Acute Submassive Hepatic Necrosis Due to Methyldopa

Abstract

Acute submassive hepatic necrosis in a patient who had received methyldopa for 10 weeks is described. The liver lesion was associated with a positive lupus erythematosus preparation, a positive direct Coombs test, and transient portal hypertension. Causal relation between methyldopa and the hepatic necrosis was established by an unequivocal response of transaminase activity to readministration of the drug. The most striking histological feature during the acute phase of the disease was extensive necrosis of liver cells in the periportal areas. The initial illness improved rapidly, and the patient has since remained asymptomatic. However, the following subsequent observations suggest that hepatic necrosis due to methyldopa may have initiated chronic liver disease: (1) the left lobe of the liver became persistently enlarged and firm after recovery from the acute liver injury; (2) liver scans 6 and 9 months after the acute episode revealed generalized mottling and a hypertrophied left lobe; (3) the liver tests did not return to normal for a period of 9 months; and (4) follow-up liver biopsies revealed broadened periportal fibrosis at 6 months and collapsed stroma at 10 months after the acute submassive necrosis, although there was insignificant inflammatory activity at the time of the biopsy.