Pre and Post Transplant Management of Hepatitis C

Pre and Post Transplant Management of Hepatitis C

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Introduction

Hepatitis C Virus (HCV) is a common cause of liver failure and cancer that necessitates liver transplantation (LT). HCV infection was rarely treated successfully before or after transplantation prior to the availability of specific direct-acting antiviral (DAA) drugs.

The use of interferon-free DAA therapy has changed the management of patients post-LT and those on the transplant waiting list in the last two years. In most patients, DAA treatment after LT will eradicate infection and normalize liver function tests. DAA treatment of patients with liver disease who are awaiting LT prevents inammation and improves liver function in the patients. Majority will still need a transplant, but some may improve enough and rapidly enough to be taken off the LT waiting list.

Historically, two principal strategies have existed to treat HCV:

(1) pre–liver transplant for those who have well-compensated cirrhosis and can tolerate 48 or 72 weeks of interferon-based therapy.

(2) post-liver transplant, either pre-emptive treatment or treatment following evidence of histological recurrence.

HCV Treatment in Pre–Liver Transplant

Interferon-based therapy should be avoided in people who have cirrhosis because there is a chance of hepatic decompensation and infections. For genotype 1 patients with compensated cirrhosis, HCV treatment with interferon-free regimens containing at least two DAAs is recommended. 

In patients with advanced fibrosis, daclatasvir and sofosbuvir with or without ribavirin for 12 weeks resulted in 100 percent SVR in those with HCV genotypes 1, 2, and 3 . A novel technique of offering an aviremic patient abbreviated HCV therapy with DAA and LT has been shown to prevent recurrent HCV in the allograft by 64%. Another agent under investigation is hepatitis C immunoglobulin (HCIG), which, if given in aviremic or low viremic (100 IU/ mL) patients during the peritransplant phase, could prevent allograft recurrence.

According to AASLD, HCV treatment with sofosbuvir-ledipasvir did not improve hepatic activity or disease severity index. As a result, HCV management with newer DAAs may be considered after LT in a subset of patients with decompensated cirrhosis.

HCV treatment in post-liver transplant

The incidence of HCV recurrence after LT is very variable, ranging from a normal mild elevation of serum aminotransferases to an infrequent occurrence of 2% – 5% of cholestatic hepatitis leading to graft failure within one year after LT. Early posttransplantation treatment applies to the first 2-6 weeks after transplantation when reinfection has already set in but no symptoms of hepatocyte damage have yet emerged. Interferon monotherapy has an SVR rate of 0%–11%, pegylated interferon has an SVR rate of 8%, and interferon in combination with ribavirin has an SVR rate of 18%–33%.  Because of comorbidities and a low tolerance for side effects, maintaining antiviral therapy at this stage of transplantation is difficult.Achieving SVR improves graft survival, graft fibrosis regression, and long-term survival. 

In the post-LT environment, pegylated interferon with ribavirin has been linked to poor tolerability and, more importantly, poor SVR. SVR values for pegylated interferon monotherapy are 18%, regular interferon plus ribavirin is 22%, and pegylated interferon plus ribavirin is 28%. With the approval of simeprevir, an NS3/4A PI, and sofosbuvir, a pan-genotypic NS5B nucleotide analogue, interferon-free HCV treatment has become a viable alternative with significantly improved efficacy and ease of use following LT. 

The AASLD and the Infectious Diseases Society of America provided guidelines for the use of sofosbuvir plus simeprevir with or without ribavirin for 12 to 24 weeks, based on the risks of interferon in LT patients. Recent data on the use of sofosbuvir plus simeprevir in post-LT situations for genotype 1 HCV patients showed overall SVR rates of 91% to 92% after just 12 weeks of care, independent of the use of ribavirin.

Table 1. AASLD/IDSA guidelines for management of post-transplant HCV

Conclusion

We are living in a time when HCV treatment methods are rapidly changing, and we are making substantial progress in both pre and post-LT HCV management. Despite the optimism and success in the treatment of HCV, none of the above regimens are FDA-approved for use after LT and are still considered off-label at this time. With ever-increasing pressure, one or more regimens are expected to be accepted by the FDA in the near future.

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