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. 2019 Oct 28;25(40):6094-6106.
doi: 10.3748/wjg.v25.i40.6094.

Sustained virologic response to direct-acting antiviral agents predicts better outcomes in hepatitis C virus-infected patients: A retrospective study

GianLuca Colussi  1 , Debora Donnini  1 , Rosario Francesco Brizzi  1 , Silvia Maier  1 , Luca Valenti  1 , Cristiana Catena  1 , Alessandro Cavarape  1 , Leonardo Alberto Sechi  1 , Giorgio Soardo  2
Affiliations

Sustained virologic response to direct-acting antiviral agents predicts better outcomes in hepatitis C virus-infected patients: A retrospective study

GianLuca Colussi et al. World J Gastroenterol. .

Abstract

Background: Direct-acting antiviral agents (DAAs) are extremely effective in eradicating hepatitis C virus (HCV) in chronically infected patients. However, the protective role of the sustained virologic response (SVR) achieved by second- and third-generation DAAs against the onset of hepatocellular carcinoma (HCC) and mortality is less well established.

Aim: To examine the occurrence of HCC or death from any cause in a retrospective-prospective study of patients treated with DAAs.

Methods: Patients were enrolled from a tertiary academic hospital center for liver disease management that collects subject data mainly from northeastern Italy. The study was conducted in 380 patients (age: 60 ± 13 years, 224 males, 32% with cirrhosis) treated with DAAs with or without SVR (95/5%), with a median follow up of 58 wk (interquartile range: 38-117). The baseline anthropometric features, HCV viral load, severity of liver disease, presence of extra-hepatic complications, coinfection with HIV and/or HBV, alcohol consumption, previous interferon use, alpha-fetoprotein levels, and renal function were considered to be confounders.

Results: The incidence rate of HCC in patients with and without SVR was 1.3 and 59 per 100 person-years, respectively (incidence rate ratio: 44, 95%CI: 15-136, P < 0.001). Considering the combined endpoint of HCC or death from any cause, the hazard ratio (HR) for the SVR patients was 0.070 (95%CI: 0.025-0.194, P < 0.001). Other independent predictors of HCC or death were low HCV viremia (HR: 0.808, P = 0.030), low platelet count (HR: 0.910, P = 0.041), and presence of mixed cryoglobulinemia (HR: 3.460, P = 0.044). Considering SVR in a multi-state model, the independent predictors of SVR achievement were absence of cirrhosis (HR: 0.521, P < 0.001) and high platelet count (HR: 1.019, P = 0.026). Mixed cryoglobulinemia predicted the combined endpoint in patients with and without SVR (HR: 5.982, P = 0.028 and HR: 5.633, P = 0.047, respectively).

Conclusion: DAA treatment is effective in inducing SVR and protecting against HCC or death. A residual risk of HCC persists in patients with advanced liver disease or with complications, such as mixed cryoglobulinemia or renal failure.

Keywords: Cirrhosis; Direct-acting antiviral agents; Hepatitis C virus; Mixed cryoglobulinemia; Survival analysis; Sustained virologic response.

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Conflict of interest statement

Conflict-of-interest statement: Authors do not have any conflict-of-interest to disclose.

Figures

Figure 1
Figure 1
Multi-state transition model. DAAs: Direct-acting antiviral agents; SVR: Sustained virologic response; HCC: Hepatocellular carcinoma.
Figure 2
Figure 2
Kaplan-Meier curves and risk table representing survival free of hepatocellular carcinoma or death from any cause according to sustained virologic response to hepatitis C virus direct-acting antiviral agents. Plain areas represent the 95% confidence interval. P value by the nonparametric log-rank test. SVR: Sustained virologic response; HCC: Hepatocellular carcinoma.
Figure 3
Figure 3
Kaplan-Meier curves and risk table representing survival free of hepatocellular carcinoma or death from any cause according to the presence of mixed cryoglobulinemia and sustained virologic response to hepatitis C virus direct-acting antiviral agents. P value by nonparametric log-rank test. +: with; -: without; MC: Mixed cryoglobulinemia; SVR: Sustained virologic response; HCC: Hepatocellular carcinoma.
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References

    1. Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol. 2014;61:S45–S57. - PubMed
    1. Cacoub P, Poynard T, Ghillani P, Charlotte F, Olivi M, Piette JC, Opolon P. Extrahepatic manifestations of chronic hepatitis C. MULTIVIRC Group. Multidepartment Virus C. Arthritis Rheum. 1999;42:2204–2212. - PubMed
    1. Reddy KR, Wright TL, Pockros PJ, Shiffman M, Everson G, Reindollar R, Fried MW, Purdum PP, 3rd, Jensen D, Smith C, Lee WM, Boyer TD, Lin A, Pedder S, DePamphilis J. Efficacy and safety of pegylated (40-kd) interferon alpha-2a compared with interferon alpha-2a in noncirrhotic patients with chronic hepatitis C. Hepatology. 2001;33:433–438. - PubMed
    1. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958–965. - PubMed
    1. Andreone P, Colombo MG, Enejosa JV, Koksal I, Ferenci P, Maieron A, Müllhaupt B, Horsmans Y, Weiland O, Reesink HW, Rodrigues L, Jr, Hu YB, Podsadecki T, Bernstein B. ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection. Gastroenterology. 2014;147:359–365.e1. - PubMed

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