{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T18:10:17Z","timestamp":1785175817020,"version":"3.55.0"},"reference-count":159,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,10]],"date-time":"2020-10-10T00:00:00Z","timestamp":1602288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01DA043396-05"],"award-info":[{"award-number":["5R01DA043396-05"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic HCV (CHC) infection is the only chronic viral infection for which curative treatments have been discovered. These direct acting antiviral (DAA) agents target specific steps in the viral replication cycle with remarkable efficacy and result in sustained virologic response (SVR) or cure in high (&gt;95%) proportions of patients. These treatments became available 6\u20137 years ago and it is estimated that their real impact on HCV related morbidity, including outcomes such as cirrhosis and hepatocellular carcinoma (HCC), will not be known for the next decade or so. The immune system of a chronically infected patient is severely dysregulated and questions remain regarding the immune system\u2019s capacity in limiting liver pathology in a cured individual. Another important consequence of impaired immunity in patients cleared of HCV with DAA will be the inability to generate protective immunity against possible re-infection, necessitating retreatments or developing a prophylactic vaccine. Thus, the impact of viral clearance on restoring immune homeostasis is being investigated by many groups. Among the important questions that need to be answered are how much the immune system normalizes with cure, how long after viral clearance this recalibration occurs, what are the consequences of persisting immune defects for protection from re-infection in vulnerable populations, and does viral clearance reduce liver pathology and the risk of developing hepatocellular carcinoma in individuals cured with these agents. Here, we review the recent literature that describes the defects present in various lymphocyte populations in a CHC patient and their status after viral clearance using DAA treatments.<\/jats:p>","DOI":"10.3390\/ijms21207473","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T22:02:02Z","timestamp":1602626522000},"page":"7473","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Lymphocyte Landscape after Chronic Hepatitis C Virus (HCV) Cure: The New Normal"],"prefix":"10.3390","volume":"21","author":[{"given":"Alip","family":"Ghosh","sequence":"first","affiliation":[{"name":"Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Romani","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam","family":"Kottilil","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhawna","family":"Poonia","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1016\/S0140-6736(18)32326-2","article-title":"Direct-acting antiviral treatment for hepatitis C","volume":"393","author":"Holmes","year":"2019","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1001\/jama.2013.109309","article-title":"Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: A randomized clinical trial","volume":"310","author":"Osinusi","year":"2013","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"634","DOI":"10.7326\/M14-1211","article-title":"Re-treatment of chronic hepatitis C virus genotype 1 infection after relapse: An open-label pilot study","volume":"161","author":"Osinusi","year":"2014","journal-title":"Ann. 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