Hepatitis C virus (HCV) infection is one of the major causes of all chronic liver disease and HCV-associated cirrhosis is one of the most common indication for orthotopic liver transplantation (OLT) among adults. Recurrence of HCV following orthotopic liver transplantation (OLT) occurs in almost every patient (1). HCV infection remains a serious problem after liver transplantation and recurrent hepatic infection is the leading cause of graft failure.

Pathogenesis: Variables that influence the progression of recurrent HCV following orthotopic liver transplantation (OLT) are incompletely understood, but donor characteristics (donor type, age), viral characteristics (genotype, viral load), the inflammatory grade of the explanted liver, and the patient’s immune status and immunosuppressive regimen may be important (2). The degree of inflammation present in the patient’s explanted liver at the time of transplantation correlate well with fibrosis progression in recurrent HCV (3). The level and type of immunosuppression following transplantation likely influence the severity of disease recurrence.

Clinical Course: The course of HCV infection accelerates after OLT and progression to cirrhosis occur in 10-20 % during the first five years time.

Diagnosis: HCV RNA levels and liver biopsy is important in establishing diagnosis. Features that are supportive of recurrent HCV are lobular activity, interface hepatitis, piecemeal necrosis, and lymphocyte predominance or lymphoid follicles

Management: Several strategies for HCV treatment in the setting of transplantation have been attempted: treatment prior to transplantation to prevent infection of the graft, immediate or peri-operative prophylaxis, early preemptive HCV therapy, and treatment of established recurrent disease. Eradication of HCV infection prior to transplantation would be the ideal approach, as patients who undergo transplantation in the absence of viremia are much less likely to have recurrent infection. However, treatment of patients with decompensated cirrhosis is difficult. Genotype 1 patients have approximately 15 percent sustained virologic response (SVR) rate with the cost of exacerbations of encephalopathy, infections and other serious adverse events (4). There is no consensus on the role of prophylactic or preemptive therapy following transplantation prior to HCV-related liver injury from recurrent infection (2). The combination of peginterferon and ribavirin treatment after OLT has been associated with the best treatment responses overal. SVR rates are approximately 25% however discontinuation to therapy is also about 25% (5). The future of direct acting antiviral agents (protease and polymerase inhibitors) is promising, and the promise of interferon-free regimens may become a reality in the next several years (6). Indications and contraindications for retransplantation remain unclear and practices vary widely among institutions.Unfortunately, the prognosis for such patients is generally poor.

References

1. Wright TL, Donegan E, Hsu HH, et al. Recurrent and acquired hepatitis C viral infection in liver transplant recipients. Gastroenterology 1992; 103:317.
2. Pessoa MG, Bzowej N, Berenguer M, et al. Evolution of hepatitis C virus quasispecies in patients with severe cholestatic hepatitis after liver transplantation. Hepatology 1999; 30:1513.
3. Ghabril M, Dickson RC, Krishna M, et al. Explanted liver inflammatory grade predicts fibrosis progression in hepatitis C recurrence. Liver Transpl 2011; 17:685.
4. Everson GT, Terrault NA, Lok AS, et al. A randomized controlled trial of pretransplant antiviral therapy to prevent recurrence of hepatitis C after liver transplantation. Hepatology 2013; 57:1752.
5. Wang CS, Ko HH, Yoshida EM, et al. Interferon-based combination anti-viral therapy for hepatitis C virus after liver transplantation: a review and quantitative analysis. Am J Transplant 2006; 6:1586.
6. Werner CR, Egetemeyr DP, Lauer UM, et al. Telaprevir-based triple therapy in liver transplant patients with hepatitis C virus: a 12-week pilot study providing safety and efficacy data. Liver Transpl 2012; 18:1464.