History of Hepatocellular Carcinoma Increases Risk of Liver-Related Mortality After SVR

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Patients with a history of hepatocellular carcinoma face a greater risk of liver-related mortality after achieving sustained virologic response (SVR) following direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV), according to findings from a prospective study.

Results were presented at The Liver Meeting 2023 from the American Association for the Study of Liver Diseases (AASLD) by Yuki Tahata, of the department of gastroenterology and hepatology at Osaka University Graduate School of Medicine in Japan, and showed older age, history of hepatocellular carcinoma, and decreased albumin level at SVR were significantly associated with liver-related mortality after SVR.¹

“Direct-acting antiviral treatment enables almost all patients with hepatitis C virus, including those with decompensated cirrhosis to achieve sustained virologic response, and improves prognosis in SVR patients. However, factors associated with long-term prognosis after SVR are unclear,” wrote investigators.¹

The World Health Organization estimates 58 million people have chronic HCV, with about 1.5 million new infections occurring every year. Although there is currently no effective vaccine against HCV, DAAs can cure more than 95% of persons with hepatitis C infection and help them achieve SVR. However, little is known about the factors associated with long-term prognosis after SVR.²

To identify risk factors associated with long-term prognosis according to liver and non-liver related death in patients who achieved SVR after DAA treatment, investigators enrolled 3,238 patients with HCV who started DAA treatment between September 2014 and June 2021 and achieved SVR in Japanese hospitals. Patients who developed hepatocellular carcinoma before SVR were excluded from the study. SVR was defined as serum HCV-RNA undetectable at 24 weeks after the end of treatment, and the study observation period began at the time of SVR confirmation.¹

Investigators used Cox proportional hazard analysis to examine factors associated with liver-related and non-liver related death after SVR. Liver-related death was defined as death from hepatocellular carcinoma, liver failure, or varix rupture.¹

Among the cohort, the mean age was 69 years and 43% of participants were male. Investigators noted 9% of patients had a history of HCC and 18% of patients had liver cirrhosis. The median follow-up was 50.4 months from achieving SVR, during which 24 participants died of liver-related causes including hepatocellular carcinoma (n = 20), liver failure (n = 3), and varix rapture (n = 1). An additional 103 participants died of non-liver related causes, with the most common causes of death being malignant tumors other than hepatocellular carcinoma (n = 20), cerebrovascular and cardiovascular events (n = 14), and infections (n = 12).¹

Investigators pointed out the proportion of patients who died of liver-related causes was significantly greater in patients with a history of hepatocellular carcinoma (46%) compared to those without (11%; P < .001). Among participants with a history of hepatocellular carcinoma, annual liver-related mortality at 3, 4, and 5 years after SVR was 1.5%, 1.3%, and 3.6%, respectively.¹

In the multivariate analysis, older age (P = .008), history of hepatocellular carcinoma (P = .002), and decreased albumin level at SVR (P = .014) were significantly associated with liver-related mortality after SVR, while older age (P < .001), male sex (P = .006), and lower albumin level at SVR (P < 0.001) were significantly associated with non-liver-related mortality after SVR.¹

“In patients with a history of HCC, the risk of liver-related death persists over the long term after SVR,” investigators concluded.¹

References:

1. Hikita H, Nozaki Y, Ishida H, et al. 54: LONG-TERM RISK OF LIVER-RELATED AND NON-LIVER-RELATED DEATH AFTER DIRECT-ACTING ANTIVIRAL-MEDIATED SUSTAINED VIROLOGIC RESPONSE IN HEPATITIS C VIRUS PATIENTS. Paper presented at: The Liver Meeting. Boston, MA. November 10 - 14, 2023.
2. World Health Organization. Hepatitis C. Newsroom. July 18, 2023. Accessed November 13, 2023. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c