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Short-term histological evaluations after achieving a sustained virologic response to direct-acting antiviral treatment for chronic hepatitis C.

ABSTRACT: Background:Interferon-free, direct-acting antiviral treatments can result in a sustained virologic response in nearly 100% of patients with chronic hepatitis C virus infection. Aims:The purpose of this study was to evaluate histological improvement after achieving a sustained virologic response to direct-acting antiviral treatments in patients with chronic hepatitis C. Methods:Among 691 patients with chronic hepatitis C who achieved a sustained virologic response to direct-acting antivirals, 51 underwent liver biopsy 41?±?20 weeks after the end of treatment despite normal transaminase levels. In 20 patients, liver biopsy specimens obtained a median of 1.2 years before the start of treatment were available. Results:Among the 51 patients who underwent post-sustained virologic response biopsies, the grade of inflammation was A0 in 18 patients, A1 in 24, A2 in eight, and A3 in one; the stage of fibrosis was F0 in three patients, F1 in 20, F2 in 15, F3 in nine, and F4 in four. Among the nine post-sustained virologic response biopsy specimens with moderate-to-severe inflammation (?A2), four showed S1-to-S3 steatosis (>5% of hepatocytes affected). In the 20 paired biopsy specimens, the inflammation grade significantly regressed (p?=?0.0043), but the fibrosis stage did not (p?=?0.45). Histological improvement, defined as a???2-point decrease in the Knodell inflammatory score and no worsening of the fibrosis, was found in 11 (55%) patients. The iron accumulation had significantly regressed (p?=?0.0093), but the steatosis had not (p?=?0.10). Conclusions:Even if transaminases become normal after obtaining a sustained virologic response, significant histological inflammation of unknown cause was found in some patients. Additionally, improvement in liver fibrosis was not evident in the short term.

SUBMITTER: Enomoto M

PROVIDER: S-EPMC6206535 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Short-term histological evaluations after achieving a sustained virologic response to direct-acting antiviral treatment for chronic hepatitis C.

Enomoto Masaru M Ikura Yoshihiro Y Tamori Akihiro A Kozuka Ritsuzo R Motoyama Hiroyuki H Kawamura Etsushi E Hagihara Atsushi A Fujii Hideki H Uchida-Kobayashi Sawako S Morikawa Hiroyasu H Murakami Yoshiki Y Kawada Norifumi N

United European gastroenterology journal 20180719 9

<h4>Background</h4>Interferon-free, direct-acting antiviral treatments can result in a sustained virologic response in nearly 100% of patients with chronic hepatitis C virus infection.<h4>Aims</h4>The purpose of this study was to evaluate histological improvement after achieving a sustained virologic response to direct-acting antiviral treatments in patients with chronic hepatitis C.<h4>Methods</h4>Among 691 patients with chronic hepatitis C who achieved a sustained virologic response to direct- ...[more]

PMID: 30386612

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Project description:ImportanceSome payers and clinicians require alcohol abstinence to receive direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection.ObjectiveTo evaluate whether alcohol use at DAA treatment initiation is associated with decreased likelihood of sustained virologic response (SVR).Design, setting, and participantsThis retrospective cohort study used electronic health records from the US Department of Veterans Affairs (VA), the largest integrated national health care system that provides unrestricted access to HCV treatment. Participants included all patients born between 1945 and 1965 who were dispensed DAA therapy between January 1, 2014, and June 30, 2018. Data analysis was completed in November 2020 with updated sensitivity analyses performed in 2023.ExposureAlcohol use categories were generated using responses to the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses for alcohol use disorder (AUD): abstinent without history of AUD, abstinent with history of AUD, lower-risk consumption, moderate-risk consumption, and high-risk consumption or AUD.Main outcomes and measuresThe primary outcome was SVR, which was defined as undetectable HCV RNA for 12 weeks or longer after completion of DAA therapy. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% CIs of SVR associated with alcohol category.ResultsAmong 69 229 patients who initiated DAA therapy (mean [SD] age, 62.6 [4.5] years; 67 150 men [97.0%]; 34 655 non-Hispanic White individuals [50.1%]; 28 094 non-Hispanic Black individuals [40.6%]; 58 477 individuals [84.5%] with HCV genotype 1), 65 355 (94.4%) achieved SVR. A total of 32 290 individuals (46.6%) were abstinent without AUD, 9192 (13.3%) were abstinent with AUD, 13 415 (19.4%) had lower-risk consumption, 3117 (4.5%) had moderate-risk consumption, and 11 215 (16.2%) had high-risk consumption or AUD. After adjustment for potential confounding variables, there was no difference in SVR across alcohol use categories, even for patients with high-risk consumption or AUD (OR, 0.95; 95% CI, 0.85-1.07). There was no evidence of interaction by stage of hepatic fibrosis measured by fibrosis-4 score (P for interaction = .30).Conclusions and relevanceIn this cohort study, alcohol use and AUD were not associated with lower odds of SVR. Restricting access to DAA therapy according to alcohol use creates an unnecessary barrier to patients and challenges HCV elimination goals.

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Short-term histological evaluations after achieving a sustained virologic response to direct-acting antiviral treatment for chronic hepatitis C.

Publications

Short-term histological evaluations after achieving a sustained virologic response to direct-acting antiviral treatment for chronic hepatitis C.

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