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J. Clin. Med., Published: 10 January 2021, 10(2), 221 | https://doi.org/10.3390/jcm10020221 Immunological Mechanisms for Hepatocellular Carcinoma Risk after Direct-Acting Antiviral Treatment of Hepatitis C Virus Infection

Pil Soo Sung^1,2,*, and Eui-Cheol Shin^3,4,*

¹Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea
²The Catholic Liver Research Center, The Catholic University of Korea, Seoul 06591, Korea
³Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea
⁴The Center for Epidemic Preparedness, KAIST Institute, Daejeon 34141, Korea

^*Authors to whom correspondence should be addressed.

Abstract

Direct-acting antiviral agents (DAAs) that allow for rapid clearance of hepatitis C virus (HCV) may evoke immunological changes. Some cases of rapid de novo hepatocellular carcinoma (HCC) development or early recurrence of HCC after DAA treatment have been reported. During chronic HCV infection, natural killer (NK) cells exhibited a deviant functional phenotype with decreased production of antiviral cytokines and increased cytotoxicity; however, DAA treatment rapidly decreased their cytotoxic function. Effective DAA therapy also suppressed the intrahepatic activation of macrophages/monocytes. This was followed by a decrease in mucosal-associated invariant T (MAIT) cell cytotoxicity without normalization of cytokine production. Rapid changes in the phenotypes of NK and MAIT cells after DAA treatment may attenuate the cytotoxicity of these cells against cancer cells. Moreover, DAA treatment did not normalize the increased frequencies of regulatory T cells even after clearance of HCV infection. Thus, the persistently increased frequency of regulatory T cells may contribute to a local immunosuppressive milieu and hamper the clearance of cancer cells. This review will focus on recent studies describing the changes in innate and adaptive immune responses after DAA treatment in patients with chronic HCV infection in the context of de novo occurrence or recurrence of HCC.

Keywords: hepatitis C virus; hepatocellular carcinoma; direct-acting antivirals

논문정보

형식Review Paper
게재일2021년 01월 (BRIC 등록일 2021-04-12)
연구진국내 연구진
분야 의약학 > 면역의학
구분구・추천논문

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