Management of Hepatitis C Before and After Liver Transplantation in the Era of Rapidly Evolving Therapeutic Advances

Abstract

Management of hepatitis C (HCV) in liver transplantation (LT) population presents unique challenges. Suboptimal graft survival in HCV+ LT recipients is attributable to universal HCV recurrence following LT. Although eradication of HCV prior to LT is ideal for the prevention of HCV recurrence it is often limited by adverse events, particularly in patients with advanced cirrhosis. Antiviral therapy in LT candidates needs careful monitoring, and prophylaxis with HCV antibodies is ineffective. Early antiviral therapy after LT has been investigated, but no clear benefit has been demonstrated. Protocol liver biopsy is generally recommended in HCV+ LT recipients, and antiviral therapy can be considered in those with severe/ progressive HCV recurrence. Sustained virological response (SVR) can be achieved in approximately 30% of LT recipients with pegylated interferon/ribavirin (PEG-IFN/RBV) with survival benefit, but adverse effects are common. Favorable patient characteristics for response to therapy include non-1 genotype, previously untreated, low baseline HCV-RNA, and donor IL28B genotype CC. Direct acting antiviral (DAA)-based triple therapy is associated with higher rates of SVR, but with similar or slightly higher rates of side effects, and immunosuppressive regimens need to be closely monitored and adjusted during the treatment period. Notably, the safety and efficacy of HCV treatment are very likely to improve with newer generation DAA. The benefit of immunosuppressive strategy on the natural history HCV recurrence has not been well elucidated. Based upon available evidence, cyclosporine A (CSA), mycophenolate mofetil (MMF), and sirolimus appear to have a neutral or small beneficial impact on HCV recurrence. Donor interleukin 28 B (IL28B) polymorphisms appear to impact the course and treatment outcomes in recurrent HCV. Retransplantation should be considered for patients with reasonable survival probability.

Optimal timing of hepatitis C treatment for patients on the liver transplant waiting list

“…(2) In patients who develop decompensated cirrhosis, the risk of death in the following year is approximately 15%-20%, and LT generally remains the only life-saving option. (3) However, reinfection with HCV after transplantation occurs virtually universally; allograft hepatitis C can be rapidly progressive, and retransplantation is the only therapeutic option for long-term survival in patients who advance to end-stage liver disease after LT. (4,5) Until recently, the management of HCV in patients with decompensated cirrhosis and those who underwent LT was challenging because of low efficacy and tolerance of interferon-based therapies. (5) However, the availability of oral DAAs has altered the treatment paradigm for both pre-LT and post-LT patients.…”

“…Despite recent advances in HCV treatments, the burden on the transplant waiting list is projected to remain substantial even in the era of oral direct‐acting antivirals (DAAs) . In patients who develop decompensated cirrhosis, the risk of death in the following year is approximately 15%‐20%, and LT generally remains the only life‐saving option . However, reinfection with HCV after transplantation occurs virtually universally; allograft hepatitis C can be rapidly progressive, and retransplantation is the only therapeutic option for long‐term survival in patients who advance to end‐stage liver disease after LT …”

Direct-acting agents for hepatitis C virus before and after liver transplantation

“…Drug-to-drug interactions between most of recently devised new generation DAAs and immunosuppressive drugs is not a significant issue (44). The trough levels of immunosuppressive drugs, however, should be closely monitored.…”

Potential Liver Transplant Recipients with Hepatitis C: Should They Be Treated Before or After Transplantation?

“…SMV as well as fixed-dose combination of grazoprevir (GRZ)/ elbasvir (EBV) is not recommended in CTP stage B and C cirrhosis. 89,90 When earlier generation DAAs such as boceprevir and telaprevir were used, there was genuine concern for drug interactions with immunosuppressive agents used after LT. 91 With currently used DAAs such as SOF, LDV and DCV, there is no need to adjust the dose of tacrolimus (TAC) or cyclosporine A (CSA) when given simultaneously. 88,92 However, same rule does not apply to all DAAs.…”