Considerations When Treating Hepatitis C in a Cirrhotic Transplant Candidate

Abstract

Cure of HCV with DAA can improve liver function and allow delisting in some patients. Beyond a threshold of hepatic impairment (likely MELD score > 16 to 20), patients may experience a decline in MELD score with HCV cure without improvement in liver-related complications resulting in decreased opportunity to receive a LT. Eradicating HCV from patients who need LT regardless also deprives them of the option of receiving HCV-positive donor organs. Patients with MELD > 16 or Child-Pugh B/C may also have reduced cure rates of HCV, increased risk of hepatic decompensation, and adverse events with DAA pre-LT compared to post-LT DAA therapy. Preliminary data demonstrates increase risk of hepatocellular carcinoma (HCC) recurrence after treatment with DAA with subsequent studies raising doubts about this association. Patients with HCV cirrhosis on the LT waiting list with MELD score > 16, CTP-B/C, and HCC are best treated after LT with better response, tolerability, and the ability to receive organs from a larger donor pool that includes HCV-positive donors. Larger, prospective studies are needed to assess whether increased HCC recurrence after DAA is a true effect.

Pretransplant Hepatitis C Virus Treatment Decreases Access to High-quality Livers

“…Additionally, Daniel et al highlight the negative consequences of pre-LT HCV treatment, including potentially limiting the donor pool to HCV-negative recipients. 7 This remains a concern at many centers in the United States, as HCV-positive donor to HCV-negative recipients remains experimental and not routine at many institutions across the country. Despite the fact that we do perform HCV-positive to HCV-negative transplants, we still saw shorter waitlist times for untreated recipients at our center, suggesting that there are potentially additional advantages to deferring treatment.…”

New hope for hepatitis C virus: Summary of global epidemiologic changes and novel innovations over 20 years

“…Without curative therapies including liver transplantation, re-infection with HCV occurs in high frequency and commonly results in significant liver graft destruction, resulting in poor patient survival[ 55 ]. Approximately 80% of patients will develop allograft hepatitis within two years of liver transplantation without eradication, and 20% of those patients progress to advanced fibrosis or cirrhosis within five years of transplantation[ 56 ]. Of note, cholestatic hepatitis C, which can occur in up to 5% to 10% of patients within one year of liver transplantation, can be rapidly progressive and life-threatening[ 55 ].…”

“…The overall low burden of DDIs with widely used immunosuppressants poses no contraindication for use in the post-transplantation period[ 55 ]. The advantages of early or pre-transplantation viral eradication can include improved overall liver function, quality of life and liver-related complications, potential avoidance of the need for liver transplantation, and lower rate of post-transplantation infection recurrence[ 56 ]. However, pre-transplantation eradication can increase wait times for transplantation by limiting access to HCV-positive donor livers and through the improvement of liver function to the degree that de-prioritizes patients on organ transplantation wait lists[ 56 ].…”

<p>Assessment of Renal Function in Post-Liver Transplant HCV-Positive Patients Treated with Direct Acting Antivirals</p>

“…3,4 The treatment of HCV infection with SVR achievement has many advantages regarding risk reduction of liver decompensation and hepatocellular carcinoma, improved survival and outcomes, even in patients with severe hepatic disease. 5 Past treatment with interferon and ribavirin for recurrent liver graft infection with hepatitis C virus, despite its positive impact on survival, had several side-effects, such as low SVR (15-35%), a high discontinuation rate (up to 40%), and significant drug-drug interactions. 6 Currently, the direct-acting antivirals (DAAs) are considered the treatment of choice for HCV infection.…”

“…18 Furthermore, drug-drug interactions are a major concern regarding renal safety, when treating HCV patients in the setting of immunosuppressive drugs post-LT, while some DAAs need no dose adjustment, others require meticulous dose adjustment when given concomitantly with immunosuppressive therapy. 5 The aim of this work was to evaluate the effect of DAAs on renal function in post-liver transplant patients with chronic hepatitis C virus infection at the end and after the completion of treatment.…”