Autoimmune Hepatitis in Association With Sofosbuvir

Sofosbuvir in combination with ribavirin was approved by the Food and Drug Administration as a treatment option for hepatitis C (HepC) in 2013. We describe a case of autoimmune hepatitis triggered in a patient on therapy with sofosbuvir and ribavirin. A 65-year-old woman with a medical history of diabetes mellitus, hypertension, and HepC (genotype 2) underwent pretreatment liver biopsy in May 2012, which demonstrated mild chronic active hepatitis with focal piece-meal necrosis and mild stage 1 periportal fibrosis with no increased iron deposition. No features of autoimmune hepatitis were seen on biopsy. The patient was administered 400 milligrams (mg) sofosbuvir and weight-based 1000 mg ribavirin for a planned duration of 12 weeks. Liver function tests (LFTs) initially improved on therapy; however, 3 weeks after the treatment initiation, the patient started complaining of weakness and fatigue. Repeat tests revealed elevated LFTs. Autoimmune titers were positive for antinuclear antibody, anti-smooth muscle antibody with elevated immunoglobulin (IgG), and serum gamma globulin levels. Repeat liver biopsy in June 2014 showed markedly distorted architecture secondary to formation of nodules completely enclosed by fibrous septa and areas of confluent necrosis with mild to moderate chronic inflammation consisting mainly of lymphocytes and plasma cells along with moderate to severe interface hepatitis. Ballooning degeneration of hepatocytes, with rosette formation possibly associated with regenerative activity was seen, consistent with superimposed autoimmune hepatitis. Based on laboratory and biopsy findings, diagnosis of drug-induced autoimmune hepatitis was made, and the treatment for HepC with sofosbuvir and ribavirin was discontinued. The patient was subsequently administered prednisolone with improvement in LFTs. We describe a patient with autoimmune hepatitis after initiation of sofosbuvir and ribavirin. To our knowledge, this complication has never been reported before in association with sofosbuvir. The most frequent adverse events noticed with this combination regimen have been headache, anemia, fatigue, and nausea.