Direct-acting antivirals reduce the need for liver transplantation in HCV-HCC patients

Compared to patients without hepatitis C virus (HCV) infection, those with HCV are associated with a 15 to 20-fold increase in risk of developing hepatocellular carcinoma (HCC) as well as being the most common reason for liver transplantation in Europe and the United States (US).1,2 Prior to 2011, HCV patients were treated with a combination of immune-boosting agent, pegylated interferon (IFN)-alfa, and ribavirin.1 Unfortunately, the combination was not well-tolerated and had poor cure rates.1 In 2011, first generation direct-acting antiviral (DAA) agents were approved and, in 2014, more potent and better tolerated DAAs also became available.1 Since then, most treated patients can achieve sustained virologic response that results in improvements in hepatic function with a majority achieving model for end-stage liver disease (MELD) scores below 20 within months of treatment completion.1 With the advent of DAAs, many patients with compensated cirrhosis no longer progress to decompensated cirrhosis (DC) and can successfully avoid liver transplantation (LT).1

On the other hand, chronic hepatitis B virus (HBV) infection is also associated with a 5 to 100-fold increase in the risk of developing HCC when compared to healthy patients.2 Historically, LT outcomes for HBV-related HCC have been significantly better than patients having HCV-HCC. To investigate the benefit of DAAs for HCV management, Dr. Parissa Tabrizian, Icahn School of Medicine at Mount Sinai, New York, and her team conducted a study to compare the post-LT outcomes among HBV-HCC versus HCV-HCC patients for the periods before and after the widespread availability of DAAs for HCV management. From 2003 to 2019, adult patients (≥18 years) with HCC who underwent primary, single-organ, non-fulminant LT within the United Network for Organ Sharing OPTN/UNOS Registry were recruited. Based on their therapy date, patients were categorized into pre-DAA (January 2003-October 2013) and post-DAA (November 2013-January 2019) groups.

In the pre-DAA era, the 5- and 10-year survival rates of HBV-HCC patients were 80.4% and 70.9%, respectively. Comparatively, the 5- and 10-year survival rates of HCV-HCC patients were significantly lower at 69.5% and 55.1%, respectively (p<0.001). After DAAs were widely adopted, the post-LT survival rate for HCV-HCC was improved by 16%, with now the 5-year survival rate of HBV-HCC patients being similar to those with HCV-HCC at 83% versus 78% (p=0.12). In addition, a higher MELD score (p<0.001), AFP level >20ng/mL (p<0.001), an outside Milan status observed at diagnosis (p=0.03), vascular invasion (p<0.001), and moderate/poor tumor differentiation (p<0.001) were found to be independent predictors of lower post-LT survival rates. Interestingly, HCV status did not predict survival outcome in the post-DAA era after adjusting for tumor characteristics. From this observation, Dr. Tabrizian concluded that, “After the introduction of effective DAA hepatitis C therapy, results of transplantation for HCV-HCC are significantly improved and no longer statistically different from the results in patients with HBV-HCC.”

A similar study conducted among LT-recipients in the European Liver Transplant Registry between 2007-2017 further supported the improved survival among HCV patients in the period after the introduction of DAAs.1 Notably, these patients from the European study also included patients with DC in addition to HCC.1 In this study, the 3-year survival of LT recipients who had HCV-DC have improved significantly from 65.1% in the pre-DAA era to 76.9% in the post-DAA era.1 This gain in survival can be attributed to the combined effort in preventing HCV recurrence and curing HCV infection early after LT.1 Despite a concomitant increase in the LT recipient age, donor age and pre-LT MELD score, adjusted analysis confirmed that the improvement in post-LT survival was independent of these factors.1

Based on these clinical trials, new DAAs are not only highly effective in curing HCV infection, but can also reverse decompensation in 1 of 3 patients with MELD score below 20.1 DAAs are crucial for preventing severe HCV recurrence and limiting other complications such as early graft dysfunction and immunological or infective complications.1 With the introduction of effective DAAs, the post-LT survival rate of HCV-HCC patients can finally match those with HBV-HCC.

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