Successful Treatment of Fibrosing Cholestatic Hepatitis C With Sofosbuvir and Simeprevir

Abstract

Case Report: A 62-year-old female with HCV (GT 1a, nonresponder to pegylated interferon-alfa [PEG] and ribavirin [RBV]) who had been doing well on tacrolimus and mycophenolate presented with jaundice 3 years after liver transplantation (LT). Labs were significant for AST 391 u/L, ALT 324 u/L, AP 184 u/L, TB 1.3 mg/dL, and DB 0.4 mg/dL. An ultrasound showed a patent portal vein and hepatic artery. A liver biopsy showed moderate acute cellular rejection (ACR), also with cholestasis and portal fibrosis. The patient was treated with 3 doses of methylprednisolone 500 mg IV followed by a prednisone taper. Repeat liver biopsies 12 and 26 days later were interpreted as resolving ACR, but still showed moderate cholestasis, raising concern for fibrosing cholestatic HCV (FCH). Labs showed AST 193, ALT 334, AP 334, GGT 1054 u/L, TB 19.7, DB 11.4, HCV RNA 4,009,783 IU/mL. PCR for CMV and EBV was negative. When the patient’s labs worsened with a TB of 39.1 and HCV RNA 1,076,167 IU/mL after a second course of methylprednisolone, a fourth liver biopsy done 7 weeks after initial presentation revealed marked cholestasis, numerous damaged bile ducts, mixed inflammation, and stage 2 fibrosis. FCH could not be ruled out histologically, and clinical suspicion was high, thus treatment was begun with a combination of sofosbuvir (SOF), simeprevir (SIM), and RBV. The patient’s liver tests markedly improved and after 6 weeks; her HCV RNA level was undetectable. RBV was discontinued at week 6 due to anemia. The patient is doing well at week 16 with normalization of her labs (Figure 1), with a plan to complete a 24-week course of SOF/SIM.Figure 1Discussion: FCH is an aggressive form of HCV that can occur in up to 14% of patients transplanted for HCV, and can lead to graft loss and death. Differentiating FCH from ACR can be challenging, and can lead to a delay in diagnosis. Treatment of presumptive ACR with high-dose steroids can exacerbate FCH. With the advent of safer and more effective HCV regimens, the histologic criteria for FCH may need to be broadened in order to identify patients who may benefit from earlier HCV treatment.