Inflexion of the curve: Hepatitis C's waning role in liver transplantation

Five years after the introduction of sofosbuvir, the management of hepatitis C virus (HCV) infection in patients with advanced liver disease has rapidly evolved. HCV has now been displaced from its role as the single commonest indication for liver transplantation (LT) by nonalcoholic fatty liver disease. Although this undoubtedly to a large extent reflects the latter’s rising prevalence, other factors are clearly involved namely effective and well-tolerated therapy for HCV. Sustained virological response rates in well-compensated cirrhotics are now not appreciably lower than for noncirrhotics. Extension of direct-acting antiviral (DAA) therapy to patients with advanced enough cirrhosis to prompt listing for transplant is increasingly being reported with a subsequent modest reduction in Model for End-Stage Liver Disease (MELD) scores following viral clearance. In the current issue, Kwong and colleagues address the impact of DA therapy on wait-list mortality in patients listed for LT for HCV-related liver disease as well as its effect on the MELD score. Using data from Organ Procurement and Transplantation Network (OPTN) from 2004 onward, they divided potential recipients listed for LT into 3 cohorts by date of listing with the most recent cohort including transplant candidates from January 2014 onward. The primary outcome was death on the waiting list and the secondary rate of change in MELD score. In the most recent cohort of liver transplant candidates with HCV, there was a 21% lower risk of death compared with the cohort before. This reduction in risk of death was not observed in non-HCV–infected listed patients. Furthermore, the rate of increase in MELD in listed patients diminished only in the most recent HCV group. Although the OPTN database does not capture information about HCV therapy, it lends support to a growing consensus that advanced HCV-related liver disease is diminishing in the United States. Flemming and colleagues had recently reported that the number of LT candidates listed for HCV-related liver disease had declined by 32% in the DA era through the end of 2015. Belli and colleagues in a multicenter study described delisting for LT in HCV patients without a complicating hepatocellular carcinoma (HCC) following successful DAA therapy. Of 103 LT HCVinfected LT candidates, delisting occurred in 34 due to an improvement in hepatocellular function with a decline in median MELD of 3.4. Delisting was more likely with a lower MELD score (< 16) at time of listing and improvement in serum albumin with antiviral therapy. These trends mirror an earlier experience in LT following the introduction of effective oral therapies for hepatitis B with a corresponding decrease in transplant listing for decompensated cirrhosis and ability to salvage listed patients with suppression of HBV replication. These and similar data attest to the rapidly changing management of HCV in patients especially as DAA therapy has become feasible even in the face of advanced cirrhosis. An unresolved issue is at what point is antiviral therapy no longer appropriate in decompensated cirrhosis. Using a Markov model, Chhatwal and colleagues incorporated data from trials of DAA in advanced cirrhosis as well as from UNOS to suggest HCV therapy should be considered up to a MELD of between 23 and 27. Factors predicting likelihood of improvement with antiviral therapy in cirrhosis appear to include factors not captured by the MELD score such as serum albumin. For HCV-infected patients an additional strategy to reduce wait-list mortality is use of organs from donors, which however is only feasible if HCV infection has not been eradicated in the recipient. In Kwong’s analysis, organs from HCV-positive donors increased to Abbreviations: DAA, direct-acting antiviral; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; LT, liver transplantation; MELD, Model for End-Stage Liver Disease; OPTN, Organ Procurement and Transplantation Network.