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Maintenance of Th1 hepatitis C virus (HCV)-specific responses in individuals with acute HCV who achieve sustained virological clearance after treatment.

ABSTRACT: T-cell responses against hepatitis C are believed to be critical in achieving both natural and treatment-induced clearance. However, rapid clearance of antigen with early treatment of primary infection may result in reduced or poorly sustained cellular immunity. This study longitudinally examined Th1 and Th2 hepatitis C virus (HCV)-specific cytokine production and T-cell effector function from subjects enrolled in the Australian Trial in Acute Hepatitis C comparing three groups: treatment-induced clearance (sustained virological response [SVR]), treatment non-response, and untreated spontaneous clearance.HCV-specific T-cell responses were characterized by HCV peptide ELISpot, in vitro cytokine production, and T-cell flow cytometry assays.Treated subjects with a sustained virological response (SVR) displayed a better maintenance of HCV-specific Th1 responses compared to treatment non-responders (higher interferon [IFN]-? and interleukin (IL)-2 magnitude at week 24, broader IFN-? responses at weeks 24 and 48, P?

SUBMITTER: Flynn JK

PROVIDER: S-EPMC3808486 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Maintenance of Th1 hepatitis C virus (HCV)-specific responses in individuals with acute HCV who achieve sustained virological clearance after treatment.

Flynn Jacqueline K JK Dore Gregory J GJ Hellard Margaret M Yeung Barbara B Rawlinson William D WD White Peter A PA Kaldor John M JM Lloyd Andrew R AR Ffrench Rosemary A RA

Journal of gastroenterology and hepatology 20131101 11

<h4>Background and aim</h4>T-cell responses against hepatitis C are believed to be critical in achieving both natural and treatment-induced clearance. However, rapid clearance of antigen with early treatment of primary infection may result in reduced or poorly sustained cellular immunity. This study longitudinally examined Th1 and Th2 hepatitis C virus (HCV)-specific cytokine production and T-cell effector function from subjects enrolled in the Australian Trial in Acute Hepatitis C comparing thr ...[more]

PMID: 23663030

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Project description:OBJECTIVE:The role of ribavirin (RBV) in the treatment of recent hepatitis C virus (HCV) (acute/early chronic) is unclear, particularly in HIV-infected individuals. This study evaluated early virological decline during recent HCV therapy in HIV-uninfected individuals receiving pegylated interferon (PEG-IFN) monotherapy and HIV-infected individuals receiving PEG-IFN/RBV. DESIGN:The Australian Trial in Acute Hepatitis C was a nonrandomized prospective study of patients with recent HCV. METHODS:All participants received PEG-IFN (24 weeks); HCV/HIV participants also received RBV. Early HCV RNA decline was assessed among adherent participants (?80% PEG-IFN, ?80% treatment). Logistic regression identified predictors of rapid virological response (RVR) (<10 IU/ml). RESULTS:Of 109 treated, 82% were adherent (HCV, n=57; HCV/HIV, n=32). Overall, RVR was 51% (HCV: 55% vs. HCV/HIV: 43%; P=0.323). Factors independently associated with RVR included duration of infection less than 26 weeks, HCV RNA below 5.6 log(10) IU/ml at baseline and HCV genotype 2/3 infection. Between baseline and week 12, mean decline in HCV RNA was greater in HCV/HIV participants (PEG-IFN/RBV) compared to HCV participants (PEG-IFN) (4.19 vs. 3.32 log(10) IU/ml; P=0.029). Greater HCV RNA decline was observed in those treated with RBV, particularly amongst those with an estimated duration of infection at least 26 weeks and those with unfavourable IL28B genotypes. Adherent HIV-uninfected and infected participants had similar early virological response (76 vs. 90%; P=0.102) and sustained virological response (63 vs. 75%; P=0.253), respectively. RVR was highly predictive of sustained virological response (adjusted odds ratio 4.09; 1.49, 11.25). CONCLUSION:The results of this study suggest a potential benefit for PEG-IFN and RBV combination therapy in maximizing virological responses in HCV/HIV participants with recent HCV, particularly those with a longer duration of HCV infection and unfavourable IL28B genotypes.

Project description:UNLABELLED:Retrospective studies suggest that subjects with chronic hepatitis C and advanced fibrosis who achieve a sustained virological response (SVR) have a lower risk of hepatic decompensation and hepatocellular carcinoma (HCC). In this prospective analysis, we compared the rate of death from any cause or liver transplantation, and of liver-related morbidity and mortality, after antiviral therapy among patients who achieved SVR, virologic nonresponders (NR), and those with initial viral clearance but subsequent breakthrough or relapse (BT/R) in the HALT-C (Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis) Trial. Laboratory and/or clinical outcome data were available for 140 of the 180 patients who achieved SVR. Patients with nonresponse (NR; n = 309) or who experienced breakthrough or relapse (BT/R; n = 77) were evaluated every 3 months for 3.5 years and then every 6 months thereafter. Outcomes included death, liver-related death, liver transplantation, decompensated liver disease, and HCC. Median follow-up for the SVR, BT/R, and NR groups of patients was 86, 85, and 79 months, respectively. At 7.5 years, the adjusted cumulative rate of death/liver transplantation and of liver-related morbidity/mortality in the SVR group (2.2% and 2.7%, respectively) was significantly lower than that of the NR group (21.3% and 27.2%, P < 0.001 for both) but not the BT/R group (4.4% and 8.7%). The adjusted hazard ratio (HR) for time to death/liver transplantation (HR = 0.17, 95% confidence interval [CI] = 0.06-0.46) or development of liver-related morbidity/mortality (HR = 0.15, 95% CI = 0.06-0.38) or HCC (HR = 0.19, 95% CI = 0.04-0.80) was significant for SVR compared to NR. Laboratory tests related to liver disease severity improved following SVR. CONCLUSION:Patients with advanced chronic hepatitis C who achieved SVR had a marked reduction in death/liver transplantation, and in liver-related morbidity/mortality, although they remain at risk for HCC.

Dataset Information

Maintenance of Th1 hepatitis C virus (HCV)-specific responses in individuals with acute HCV who achieve sustained virological clearance after treatment.

Publications

Maintenance of Th1 hepatitis C virus (HCV)-specific responses in individuals with acute HCV who achieve sustained virological clearance after treatment.

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