Contributed by John R. Lake, MD
A rare, severe form of viral hepatitis, cholestatic hepatitis C virus (HCV) affects a minority of HCV-infected patients after liver transplantation. The disease is characterized by ballooning of hepatocytes, an absence of inflammation, and cholangiolar proliferation without bile duct obstruction. Levels of serum HCV-ribonucleic acid (HCV-RNA) in these patients are typically very high, and prognosis has historically been quite poor, with rapid deterioration and death occurring despite liver retransplant.1 Here we describe a middle-aged man with cholestatic HCV diagnosed 9 months post-transplant and his successful treatment using directacting antiviral (DAA) therapy in a clinical trial setting.
A 54-year-old male presented to the Liver Clinic with jaundice 9 months post-transplant. His blood work showed a very high HCV RNA load of 7.3 log IU/mL, as well as markedly elevated levels of liver enzymes ALT and AST. A liver biopsy revealed cholestatic HCV infection.
The patient chose to enroll in a clinical trial of a thirdgeneration DAA combination therapy. He received ledipasvir, sofosbuvir, and ribavirin for 24 weeks. After 4 weeks of treatment, the patient’s HCV RNA load became undetectable, and the concentrations of ALT and AST decreased. After 8 weeks, the patient’s HCV RNA load remained undetectable, and his liver enzymes and bilirubin were within normal limits. At 12-weeks post-treatment, the patient remained well, and his blood work remained normal. He returned to work and all typical daily activities. At 2 years after treatment, he is well with normal liver tests.
All patients with detectable HCV viremia at the time of transplant experience a recurrence of infection within hours of transplantation and, generally, recurrence of disease.2
Although cholestatic HCV infection is very aggressive, recent data indicate that certain all-oral combination DAAs can be highly effective in this setting, achieving sustained virologic response rates of over 95%.3, 4 To achieve these response rates, DAAs should be given early on, when recurrence of hepatitis is first detected post-transplant. DAAs have less benefit when administered late, and patients treated well after the infection’s first re-appearance may still succumb, due to their poor general condition and high susceptibility to infections.5
1. Dumortier J, Boillot O, Scoazec JY. Natural history, treatment and prevention of hepatitis C recurrence after liver transplantation: past, present and future. World J Gastroenterol. 2014;20:11069-11079.
2. McCaughan GW, Zekry A. Pathogenesis of hepatitis C virus recurrence in the liver allograft. Liver Transpl. 2002;8:S7-S13.
3. Leroy V, Dumortier J, Coilly A, et al. Efficacy of sofosbuvir and daclatasvir in patients with fibrosing cholestatic hepatitis c after liver transplantation. Clin Gastroenterol Hepatol. 2015;13:1993-2001.e2.
4. Charlton M, Everson GT, Flamm SL, et al. Ledipasvir and sofosbuvir plus ribavirin for treatment of hcv infection in patients with advanced liver disease. Gastroenterology. 2015;149:649-659.
5. Pellicelli AM, et al. Sofosbuvir plus daclatasvir for post-transplant recurrent hepatitis C: potent antiviral activity but no clinical benefit if treatment is given late. Dig Liver Dis. 2014;46:923-927.
New direct-acting antivirals show promise in the treatment of recurring hepatitis C infections. A leading cause of liver failure and transplant, HCV recurs in 80% of transplant patients with the disease.Continue reading