Antiviral Therapy Improves Hepatocellular Cancer Survival
Background: Chronic hepatitis C virus (HCV) infection is a common risk factor for hepatocellular cancer (HCC). Patients with HCV infection are at a higher risk of developing HCC because the virus induces fibrosis in the liver, which may lead to cirrhosis. Early treatment of HCV and achieving a sustained virologic response (SVR) may lead to decreased incidence and mortality associated with HCC.
Methods: We performed a retrospective review of patients at the Memphis Veterans Affairs Medical Center (VAMC) in Tennessee from November 2008 to March 2019 to determine whether treatment of HCV infection makes a difference in overall survival (OS) among patients who develop HCC. Patients were treated with an interferon-based regimen or direct-acting antiviral agents (DAAs). Among the patients with HCV infection who were treated, we identified those who did achieve or did not achieve SVR.
Results: We identified 111 patients with HCV and HCC; 68 were treated for HCV infection. Forty-eight patients received DAA and 20 patients received an interferon-based regimen and 51 achieved SVR. In a multivariate analysis accounting for severity of liver disease, treated patients had an improved 5-year OS rate, median 1338 days (95% CI, 966-3202) when compared with untreated patients whose median OS was 452 days (95% CI, 242-853) ( P = .0005). The treatment group had a longer median progression-free survival (PFS) than did the nontreatment group (460 days [95% CI, 294-726] vs 286 days [95% CI, 205-405], P = .04). Patients with SVR had an increased 5-year OS compared with patients without SVR (median 1973 days [95% CI, 1222-NA] vs 470 days [95% CI, 242-853], P < .001). HCV treatment type (interferon vs DAA) was not found to be associated with either OS or PFS, regardless of time period. Advanced liver disease stage as characterized by a high model for end-stage liver disease (MELD) score (> 10) or high Child-Pugh score (B or C) was associated with worse survival outcome.
Conclusions: A retrospective analysis of patients with HCV infection and HCC confirms that treatment of HCV infection leads to OS benefit among patients with HCC. We further demonstrate that patients with HCV infection who achieve SVR have an OS benefit over patients unable to achieve SVR. The type of treatment, DAA vs an interferon-based regimen, did not show a significant survival benefit.
A higher MELD score (> 10) and a higher Child-Pugh class (B or C) score are associated with worse survival outcome regardless of SVR status. While patients with a low MELD score (≤ 10) have a better survival rate (HR 0.49), a higher MELD score has a significantly higher HR and therefore worse survival outcomes (HR, 2.20). Similarly, patients with Child-Pugh A (HR, 0.39) have a better survival outcome compared with those patients with Child-Pugh class B or C (HR, 2.57). This finding is consistent with results of multiple studies indicating that advanced liver disease, as measured by a high MELD score and Child-Pugh class score, can be used to predict the survival outcome in patients with HCV-related HCC.20-22
Unlike other studies that look at a single prognostic variable, our study evaluated prognostic impacts of multiple variables (age, SVR status, the order of SVR in relation to HCC development, HCV treatment type, MELD score and Child-Pugh class) in patients with HCC. The study included patients treated for HCV after development of HCC along with other multiple variables leading to OS benefit. It is one of the only studies in the United States that compared 5-year OS and PFS among patients with HCC treated for HCV and achieved SVR. The studies by Nagaoki and colleagues and Sou and colleagues were conducted in Japan, and some of their subset analyses were univariate. Among our study population of veterans, 50% were African American patients, suggesting that they may have similar OS benefit when compared to White patients with HCC and HCV treatment.
Limitations
Our findings were limited in that our study population is too small to conduct further subset analysis that would allow statistical significance of those subsets, such as the suggested benefit of SVR in patients who presented with HCC after antiviral therapy. Another limitation is the all-male population, likely a result of the older veteran population at the Memphis VAMC. The mean age at diagnosis was 65 years, which is slightly higher than the general population. Compared to the SEER database, HCC is most frequently diagnosed among people aged 55 to 64 years.23 The age difference was likely due to our aging veteran population.
Further studies are needed to determine the significance of SVR on HCC recurrence and treatment. Immunotherapy is now first-line treatment for patients with local advanced HCC. All the immunotherapy studies excluded patients with active HCV infection. Hence, we need more data on HCV treatment timing among patients scheduled to start treatment with immunotherapy.
Conclusions
In a population of older veterans, treatment of HCV infection leads to OS benefit among patients with HCC. In addition, patients with HCV infection who achieve SVR have an OS benefit over patients unable to achieve SVR. The type of treatment, DAA vs IFN-based regimen, did not show significant survival benefit.
