Dataset Information

Steatosis is an independent predictor of relapse following rapid virologic response in patients with HCV genotype 3.

ABSTRACT:

Background & aims

It is recommended that patients with chronic hepatitis C virus (HCV) genotype 3 infections receive 24 weeks of treatment. A rapid virologic response (RVR; at week 4) predicts a sustained virologic response (SVR), although not all patients with an RVR achieve an SVR. We explored the relationships among hepatic steatosis, level of HCV RNA, relapse, and RVR in a phase 3 randomized controlled trial of 932 patients infected with HCV genotype 2 (n = 427) or 3 (n = 505) who received 24 weeks of therapy with interferon-?.

Methods

In patients with an RVR (HCV RNA <43 IU/mL), the presence of an SVR was modeled using multivariate logistic regression as a function of age, sex, weight, body mass index, insulin resistance, steatosis, and levels of ?-glutamyl transpeptidase, alanine aminotransferase, liver fibrosis, and baseline HCV RNA.

Results

RVR, SVR, and relapse rates among patients with HCV genotype 3 were 79.6%, 79.2%, and 15.6%, respectively; corresponding rates among patients with HCV genotype 2 were 86.7%, 84.3%, and 10.1%. An RVR had high predictive value for an SVR in patients with HCV genotypes 2 (88.9%) and 3 (88.1%). The strongest independent predictors of relapse in patients with genotype 3 and an RVR were steatosis (odds ratio 3.0; P = .003) and HCV RNA ?400,000 IU/mL (odds ratio 2.5; P = .04). Relapse rates in patients with steatosis were 17.4% and 20.9% for low and high baseline levels of HCV RNA, respectively; corresponding rates in those without steatosis were 2.5% and 8.8%.

Conclusions

Steatosis was associated with significantly higher rates of relapse, irrespective of viral load, in patients infected with HCV genotype 3 who had an RVR. Further studies are needed to determine if longer treatment durations are effective in patients with an RVR and these risk factors.

SUBMITTER: Shah SR

PROVIDER: S-EPMC3155986 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Publications

Steatosis is an independent predictor of relapse following rapid virologic response in patients with HCV genotype 3.

Shah Samir R SR Patel Keyur K Marcellin Patrick P Foster Graham R GR Manns Michael M Kottilil Shyam S Healey Letha L Pulkstenis Erik E Subramanian G Mani GM McHutchison John G JG Sulkowski Mark S MS Zeuzem Stefan S Nelson David R DR

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 20110513 8

<h4>Background & aims</h4>It is recommended that patients with chronic hepatitis C virus (HCV) genotype 3 infections receive 24 weeks of treatment. A rapid virologic response (RVR; at week 4) predicts a sustained virologic response (SVR), although not all patients with an RVR achieve an SVR. We explored the relationships among hepatic steatosis, level of HCV RNA, relapse, and RVR in a phase 3 randomized controlled trial of 932 patients infected with HCV genotype 2 (n = 427) or 3 (n = 505) who re ...[more]

PMID: 21640198

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Project description:ImportanceThere is an unmet need for interferon- and ribavirin-free treatment for chronic hepatitis C virus (HCV) infection in patients co-infected with human immunodeficiency virus (HIV).ObjectiveTo evaluate the rates of sustained virologic response (SVR) and adverse events in previously untreated patients with HCV genotype 1 and HIV co-infection following a 12-week treatment of the fixed-dose combination of ledipasvir and sofosbuvir.Design, setting, and participantsOpen-label, single-center, phase 2b pilot study of previously untreated, noncirrhotic patients with HCV genotype 1 and HIV co-infection conducted at the Clinical Research Center of the National Institutes of Health, Bethesda, Maryland, from June 2013 to September 2014. Patients included those receiving antiretroviral therapy with HIV RNA values of 50 copies/mL or fewer and a CD4 T-lymphocyte count of 100 cells/mL or greater or patients with untreated HIV infection with a CD4 T-lymphocyte count of 500 cells/mL or greater. Serial measurements of safety parameters, virologic and host immune correlates, and adherence were performed.InterventionsFifty patients with HCV genotype 1 never before treated for HCV were prescribed a fixed-dose combination of ledipasvir (90 mg) and sofosbuvir (400 mg) once daily for 12 weeks.Main outcomes and measuresThe primary study outcome was the proportion of patients with sustained viral response (plasma HCV RNA level <12 IU/mL) 12 weeks after end of treatment.ResultsForty-nine of 50 participants (98% [95% CI, 89% to 100%]) achieved SVR 12 weeks after end of treatment, whereas 1 patient experienced relapse at week 4 following treatment. In the patient with relapse, deep sequencing revealed a resistance associated mutation in the NS5A region conferring resistance to NS5A inhibitors, such as ledipasvir. The most common adverse events were nasal congestion (16% of patients) and myalgia (14%). There were no discontinuations or serious adverse events attributable to study drug.Conclusions and relevanceIn this open-label, uncontrolled, pilot study enrolling patients co-infected with HCV genotype 1 and HIV, administration of an oral combination of ledipasvir and sofosbuvir for 12 weeks was associated with high rates of SVR after treatment completion. Larger studies that also include patients with cirrhosis and lower CD4 T-cell counts are required to understand if the results of this study generalize to all patients co-infected with HCV and HIV.Trial registrationclinicaltrials.gov Identifier:NCT01878799.

Dataset Information

Steatosis is an independent predictor of relapse following rapid virologic response in patients with HCV genotype 3.

Background & aims

Methods

Results

Conclusions

Publications

Steatosis is an independent predictor of relapse following rapid virologic response in patients with HCV genotype 3.

Similar Datasets

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