Dataset Information

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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Publications

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.

Project description:Abstract Background and Aim The aim of this study was to identify the factors associated with liver‐related and non‐liver‐related mortality of patients with hepatitis C virus (HCV) after sustained virologic response (SVR) to direct‐acting antiviral agents (DAAs). Methods We conducted a retrospective, single‐center cohort study of HCV patients cured by DAAs. Results A total of 330 patients with SVR to DAAs were eligible. The median follow‐up period was 3.38 years (inter‐quartile range: 2.03–4.58). The cumulative liver‐related or non‐liver‐related mortality rates at 1, 3, and 5 years were 0.00 or 1.29%, 2.87 or 3.60%, and 5.10 or 9.46, respectively. Among the liver‐related deaths, 9 of the 10 were from liver cancer. Among the non‐liver‐related deaths, the most common cause was malignancy. Through multivariate analysis using the Cox proportional hazard model, diabetes mellitus (DM, hazard ratio 13.1, 95% confidence interval 2.81–61.3) and a history of hepatocellular carcinoma (HCC, 12.8, 2.76–59.2), independently predicted liver‐related death. No variables were associated with non‐liver‐related death. Conclusion Our findings suggest that DM and a history of HCC are risk factors for liver‐related mortality of HCV patients cured by DAAs. These results indicate that early management of HCV and HCC surveillance of diabetic patients after SVR are important to increase the chance of survival. Further studies are needed to confirm the association of DM and HCC history with survival. Very few studies have assessed the factors associated with liver‐related mortality in patients with sustained virologic response (SVR) following direct‐acting antiviral agents (DAA) treatment. The findings of our cohort study are that diabetes mellitus and a history of hepatocellular carcinoma (HCC) are risk factors for the liver‐related mortality of HCV patients cured by DAA. The results indicate that early management of HCV and HCC surveillance of diabetic patients after SVR are important to increase the chance of survival.

Project description:BackgroundSelf-reported adherence to direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV) among persons who inject drugs (PWID) is often an overreport of objectively measured adherence. The association of such overreporting with sustained virologic response (SVR) is understudied. This study among PWID aimed to determine a threshold of overreporting adherence that optimally predicts lower SVR rates, and to explore correlates of the optimal overreporting threshold.MethodsThis study analyzed per-protocol data of participants with adherence data (N = 493) from the HERO (Hepatitis C Real Options) study. Self-reported and objective adherence to a 12-week DAA regimen were measured using visual analogue scales and electronic blister packs, respectively. The difference (Δ) between self-reported and objectively measured adherence was calculated. We used the Youden index based on receiver operating characteristic (ROC) curve analysis to identify an optimal threshold of overreporting for predicting lower SVR rates. Factors associated with the optimal threshold of overreporting were identified by comparing baseline characteristics between participants at/above versus those below the threshold.ResultsThe self-reported, objective, and Δ adherence averages were 95.1% (SD = 8.9), 75.9% (SD = 16.3), and 19.2% (SD = 15.2), respectively. The ≥ 25% overreporting threshold was determined to be optimal. The SVR rate was lower for ≥ 25% vs. < 25% overreporting (86.7% vs. 95.8%, p <.001). The factors associated with ≥ 25% Δ adherence were unemployment; higher number of days and times/day of injecting drugs; higher proportion of positive urine drug screening for amphetamine, methamphetamine, and oxycodone, and negative urine screening for THC (tetrahydrocannabinol)/cannabis.ConclusionsSelf-reported DAA adherence was significantly greater than objectively measured adherence among PWID by 19.2%. Having ≥ 25% overreported adherence was associated with optimal prediction of lower SVR rates. PWID with risk factors for high overreporting may need to be more intensively managed to promote actual adherence.

Dataset Information

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

Background

Aims

Methods

Results

Conclusions

Publications

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

Similar Datasets

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