Fibrosing cholestatic (FCH) hepatitis C is characterized by high HCV load causing direct hepatotoxicity, progressive hepatic failure and death. The standard treatment of choice, based on interferon plus ribavirine, is risky in kidney transplant recipients, being associated with steroid-resistant acute rejection and graft loss. Recently, sofosbuvir, a novel oral nucleotide NS5B polymerase inhibitor, has been successfully employed for the treatment of chronic HCV infection in phase III randomized clinical trials. However, there are no published reports documenting the use of sofosbuvir for the treatment of FCH hepatitis C in kidney transplant recipients. Herein, we describe a case of an HCV-HIV positive patient who developed a fibrosing cholestatic hepatitis C after kidney transplantation treated with sofosbuvir.
A 47-year-old man was admitted because of a progressive deterioration of liver functions tests. He had received a kidney transplant 40 days earlier under standard immunosuppressive therapy (basiliximab induction, maintenance with cyclosporine (Cya) [average blood trough levels 150, ng/mL], MMF [1g/bid], and methylprednisolone (MP) [4mg/day]). The post-operative period was uneventful, and graft function was stable (serum creatinine 1.7mg/dL). His medical history was significant for chronic HCV infection not responsive to the interferon based therapy but with no signs of progressive chronic liver disease, HIV infection on antiretroviral treatment with undetectable viremia since 6 years, and ESRD due to HIV collapsing FSGS 11 years earlier. At the time of transplantation, HCV-RNA levels were 265.400 IU/mL. Total serum bilirubin levels, which were 3.8 mg/dl at the time of admission, increased up to 5.8 mg/dl over the following 2 weeks.
Serum gamma-GT and ALT peaked at 461 IU/L and 577 IU/L respectively (day 6 from admission). HCV viremia increased up to 69.326.200 IU/mL, whereas HIV-RNA remained undetectable. Liver biopsy (day 1 from admission) showed FCH with intracellular viral inclusions. MMF treatment was withdrawn and cyclosporine dose was halved.
Despite a plateauing of the liver function tests, HCV-RNA viral load did not decline significantly. Two months after admission, we started treatment with sofosbuvir (compassionate use) plus rivabirin. After four weeks of therapy HCV RNA became undetectable and all the liver function tests returned to the normal range (Figure) The patient did not develop treatment side effects a part from anemia requiring Epoetin 40000/IU per week. Three months from admission, the patient underwent a renal graft biopsy that did not show signs of rejection. Cyclosporine dosage was increased to reach to standard blood levels, but MMF was not resumed. After 24 weeks of therapy sofosbuvir and ribavir were withdrawn and MMF was reintroduced (500 mg/bid). At last follow up (12 months from admission), there was no detectable HCV and HIV, liver function tests were normal and renal function was stable (creatinine 1,7 mg/dL).
The present case shows that IFN free sofosbuvir based therapy may be a safe and effective approach for treatmentof fibrosing cholestatic hepatitis C in kidney transplant recipients.