In the United States, an estimated 2.7 to 3.9 million people have chronic hepatitis C virus (HCV) infection.1 In 2014, 0.7 acute HCV cases per 100,000 population were reported to the Centers for Disease Control and Prevention, representing an increase from 2010 to 2012, and many more cases go undiagnosed or unreported.1 According to the Centers for Disease Control and Prevention, HCV infection has reached epidemic levels in most states, with rural communities and younger persons (<40 years) disproportionately affected.2 Most patients (75%-85%) remain chronically infected with HCV, often unaware of their infection because they are asymptomatic or only have vague, transient symptoms.1 When HCV infection remains unrecognized and untreated, it is associated with numerous complications, including an increased risk for chronic liver disease, cirrhosis, and liver cancer, which might necessitate liver transplantation.
Historically, many HCV recipients undergoing liver transplantation remained infected at the time of transplantation.3,4 Detectable viremia before liver transplantation has been associated with adverse outcomes, including HCV recurrence in the new graft, negatively affecting survival.3,4 For decades, a combination of pegylated interferon and ribavirin was the only antiviral treatment available, but it was rarely effective, particularly in patients with more advanced graft hepatitis, and was also poorly tolerated.3,4 However, many safe and effective direct-acting antiviral (DAA) therapies have since come to the market, revolutionizing HCV treatment, including for patients requiring liver transplantation. This has led several liver transplantation societies, including the European Liver and Intestine Transplant Association and the International Liver Transplantation Society, to release consensus statements about the use of DAAs in HCV-positive liver transplant candidates and recipients.3-5
Infectious Disease Advisor had the opportunity to discuss the use of DAAs in the management of HCV in the liver transplantation setting with Leslie B. Lilly, MD, FRCPC, medical director, GI Transplantation, and assistant professor of medicine, Toronto General Hospital, Ontario, Canada. Dr Lilly was part of the working group that developed the International Liver Transplantation Society consensus statements.
Infectious Disease Advisor: What is your perspective on using antiviral therapy to treat HCV in a candidate for liver transplant? Are there any benefits or risks?
Leslie B. Lilly, MD, FRCPC: In general, patients infected with hepatitis C should be treated early enough in their disease course that progression to cirrhosis, liver failure, and liver cancer can be avoided. Patients with cirrhosis who show no signs of liver failure or who have mild signs may benefit from treatment and avoid liver transplantation. Patients referred and listed with very advanced disease are less likely to benefit, and treatment should be deferred until after transplantation. Where the line is drawn is still debated, and it is important that the treating physician is in communication with the transplant program as that decision is made.
Infectious Disease Advisor: HCV is a leading cause of hepatocellular carcinoma, and many patients waitlisted for liver transplant have HCV cirrhosis and hepatocellular carcinoma. What regimen do you prefer for treating these patients before transplant?
Dr Lilly: There is some controversy about when patients should be treated; ideally, before the development of cancer, of course. However, some research has suggested that treating early after cancer treatment with ablation treatment might increase the risk for disease recurrence. Until that is clarified, our program endorses treatment of HCV in patients with cirrhosis awaiting transplant. In some cases, a virological cure might improve liver function enough to allow more aggressive cancer treatments, thereby increasing the likelihood that the patient will make it to transplant and remain cancer free afterward. The choice of treatments is determined by genotype, treatment history, and renal function.
Infectious Disease Advisor: What are some considerations when using a DAA to treat a waitlisted patient who has decompensated cirrhosis without hepatocellular carcinoma?
Dr Lilly: Patients with advanced disease are unlikely to improve enough to avoid a transplant, yet may improve enough that transplantation becomes unlikely, as they will be further from the top of the waiting list. As mentioned, the decision of timing of treatment is best made in conjunction with the transplant physicians.
Infectious Disease Advisor: Are there any HCV-infected patients with decompensated cirrhosis for whom you would recommend against antiviral therapy before a liver transplant?
Dr Lilly: Patients with advanced disease ([Model for End-Stage Liver Disease] scores >19 or so) or those who have already received DAAs and have relapsed and have few or no retreatment options.