Sustained Virologic Response for Chronic Hepatitis C Infection after 27 Days of Treatment with Sofosbuvir and Ribavirin.
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ABSTRACT:
SUBMITTER: Meissner EG
PROVIDER: S-EPMC4233673 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
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Sustained Virologic Response for Chronic Hepatitis C Infection after 27 Days of Treatment with Sofosbuvir and Ribavirin.
Meissner Eric G EG Nelson Amy A Marti Miriam M Masur Henry H Osinusi Anu A Kottilil Shyam S
Open forum infectious diseases 20140101 1
Successful treatment of chronic hepatitis C virus infection can now be achieved using directly acting antiviral agents without interferon. We report a patient who achieved a sustained virologic response after 27 days of treatment with sofosbuvir and ribavirin. Identifying factors that allow for shorter treatment in some individuals is imperative. ...[more]
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Project description:In Myanmar, hepatitis C virus (HCV) infection prevalence is 2%. A combination therapy of pegylated interferon alfa-2a and ribavirin (PEG-IFNa/RBV) is a standard treatment, but the effect of this antiviral therapy needs evaluation as to determine the efficacy and safety of dual PEG-IFNa/RBV therapy in treating patients infected with HCV in Myanmar.This was a retrospective analysis of data from a single clinic exclusively for gastrointestinal diseases in Yangon, Myanmar. We assessed treatment responses at the defined time points and stratified by genotypes of HCV. We also determined incidences of adverse events (AEs). We investigated independent predictors of sustained virologic response (SVR) in the participants.A total of 362 HCV-infected cases were included in this study. The majority were females (51.7%) with mean age of 47.12 years (±11.6) and noncirrhosis patients (82%). Rapid virologic response (RVR), early virologic response (EVR), end of treatment response (ETR), and SVR 24 weeks after completion of the dual treatment were 50.3% (178/362), 88% (314/357), 80.1% (286/357), and 85.6% (167/195), respectively. The most frequently reported AEs were nausea/anorexia (72.8%) and flu-like symptoms (62.4%). In multivariate analysis, 4 factors were independently associated with SVR; SVR to genotype 3 (odds ratio [OR] 2.4, 95% CI: 1.24-4.62), EVR (OR 0.54, 95% CI: 0.3-0.95), and duration of treatment (OR 1.52, 95% CI: 1.18-1.98). Study limitations were acknowledged.The efficacy and safety of the dual therapy in treating HCV-infected patient in Myanmar was acceptable. We recommend a prospective randomized control trial looking at duration of therapy and rates of achieving SVR, which could significantly impact the care of HCV-infected patients in Myanmar and perhaps other countries as well.
| S-EPMC4554122 | biostudies-literature
Project description:Background/aimsReal-world, clinical practice data are lacking about sofosbuvir/ ribavirin (SOF/RBV) treatment of Korean patients with hepatitis C virus genotype 2 (HCV GT2) infection. This study investigated the efficacy and safety of SOF/RBV in Korean patients with HCV GT2 infection and clinical factors predicting sustained virological response 12 weeks (SVR12) after the end of SOF/RBV treatment.MethodsA total of 181 patients with HCV GT2 with/without cirrhosis were treated with SOF/RBV for 16/12 weeks. Rapid virological response (RVR) was defined as non-detectable HCV RNA at 4 weeks.ResultsThe RVR rate was 80.7% (146/181), the end of treatment response rate was 97.8% (177/181) and the SVR12 rate was 92.8% (168/181). Of eight patients with relapse, four did not achieve RVR. Three patients had a history of hepatocellular carcinoma (HCC). Multivariable analysis showed that RVR (p = 0.015) and no previous history of HCC (p = 0.007) were associated with SVR12. Factors significantly contributing to RVR included cirrhosis, creatinine concentration, and pre-treatment HCV RNA level. SVR12 rate was significantly higher in RVR (+) than RVR (-) patients (95.2% vs. 82.9%, p = 0.011) and also significantly higher in patients without than with a history of HCC (94.1% vs. 72.7%, p = 0.008). During treatment, 80/181 patients (44.2%) experienced mild to moderate adverse events, with 32 (17.7%) requiring RBV dose reductions due to anemia.ConclusionSOF/RBV treatment was effective and tolerable in HCV GT2 patients. RVR and no previous history of HCC were positive predictors of SVR12.
| S-EPMC8137398 | biostudies-literature
Project description:BACKGROUND & AIMS:The combination of ledipasvir and sofosbuvir has been approved for treatment of genotype 1 hepatitis C virus (HCV) infection, including an 8-week regimen for treatment-naïve patients without cirrhosis and a baseline level of HCV RNA <6 million IU/mL. We analyzed data from a multicenter, prospective, observational study to determine real-world sustained virologic responses 12 weeks after treatment (SVR12) with regimens containing ledipasvir and sofosbuvir and identify factors associated with treatment failure. METHODS:We collected data from 2099 participants in the HCV-TARGET study with complete virologic data (per-protocol population). We analyzed data from 1788 patients receiving ledipasvir-sofosbuvir (282 for 8 weeks, 910 for 12 weeks, 510 for 24 weeks, and 86 for a different duration) and 311 receiving ledipasvir-sofosbuvir plus ribavirin (212 for 12 weeks and 81 for 24 weeks, 18 for other duration) to estimate SVR12 (with 95% confidence interval [CI]), and logistic regression methods to identify factors that predicted an SVR12. RESULTS:The overall study population was 25% black, 66% with HCV genotype 1A infection, 41% with cirrhosis, 50% treatment-experienced, and 30% receiving proton pump inhibitors at start of treatment. In the per-protocol population, SVR12s were achieved by 96% of patients receiving ledipasvir-sofosbuvir for 8 weeks (95% CI, 93%-98%), 97% receiving the drugs for 12 weeks (95% CI, 96%-98%), and 95% receiving the drugs for 24 weeks (95% CI, 93%-97%). Among patients also receiving ribavirin, SVR12 was achieved by 97% of the patients receiving the drugs for 12 weeks (95% CI, 94%-99%) and 95% receiving the drugs for 24 weeks (95% CI, 88%-99%). Of the 586 patients who qualified for 8 weeks of treatment, only 255 (44%) received the drugs for 8 weeks. The rate of SVR12 among those who qualified for and received 8 weeks of therapy was similar in those who qualified for 8 weeks but received 12 weeks therapy (96%; 95% CI, 92%-99% vs 98%; 95% CI, 95%-99%). Factors that predicted SVR12 were higher albumin (?3.5 g/dL), lower total bilirubin (?1.2 g/dL), absence of cirrhosis, and absence of proton pump inhibitor use. CONCLUSIONS:Regimens containing ledipasvir and sofosbuvir are highly effective for a broad spectrum of patients with HCV genotype 1 infection treated in different clinical practice settings. Expanded use of 8-week treatment regimens for eligible patients is supported by these real-world results. Modification of proton pump inhibitor use may increase rates of SVR. ClinicalTrials.gov no. NCT01474811.
| S-EPMC5300778 | biostudies-literature
Project description:BACKGROUND: The standard treatment for chronic hepatitis C virus (HCV) infection in HIV-infected subjects is the combination of alfapeginterferon (PEG-IFN) plus ribavirin. We designed this study to evaluate the rate of SVR and predictors of SVR in a public health setting in Rio de Janeiro, Brazil. METHODS: Retrospective cohort study of HCV/HIV co-infected patients treated with PEG-IFN plus ribavirin from 2004 to 2011 in 3 outpatient units in Rio de Janeiro. Exposure variables included age, sex, CD4+ cell count, HCV genotype, HCV and HIV viral loads, liver histology (METAVIR fibrosis scoring system) and previous treatment. The main outcome measurement was SVR. RESULTS: 100 patients were included in this analysis. Median age was 47 years and 68% were male. 80%, 4%, 14% and 2% were infected with HCV genotypes 1, 2, 3 and 4, respectively. At baseline, 77% had HCV viral load greater than 800,000 IU/ml, 99% had CD4+ greater than 200 cells/mm(3) and 10% had a diagnosis of cirrhosis. The treatment was withdrawn in 9% of the subjects (5% with adverse effects and 4% dropped out). SVR was observed in 27 (27%) of the 100 patients included. 13 (13%) subjects were classified as null-responders, 33(33%) as non-responders, 9 (9%) as breakthrough and 9(9%) as relapsers. In the multivariate model only being infected with genotype 2 or 3 (p<0.01) and having low levels of gamma glutamyl transferase (GGT) at baseline (p = 0.04), were predictive of SVR. CONCLUSION: SVR in HCV/HIV co-infected subjects in a public health setting is similar to that observed in clinical trials, albeit very low. A delay in therapy initiation should be considered until new therapies as direct acting antiviral drugs (DAA) become widely available and tested in coinfected subjects.
| S-EPMC3706550 | biostudies-other
Project description:Ribavirin is effective for treating immunocompromised patients with chronic hepatitis E virus infection. However, ribavirin treatment is not always successful. We describe 3 solid organ transplant recipients treated with sofosbuvir and ribavirin after failing ribavirin monotherapy. Complete elimination of hepatitis E virus could not be achieved.
| S-EPMC6690733 | biostudies-literature
Project description:BACKGROUND AND AIM:Hepatitis C virus (HCV) infection is a major health problem worldwide. Genotype-4 is the most common genotype in Saudi Arabia. The response to treatment with pegylated interferon-? combined with ribavirin in chronic HCV infection varies. This study aimed at investigating the pre- and on-treatment predictors of sustained virologic response (SVR) in patients with chronic hepatitis C (CHC) infection. PATIENTS AND METHODS:Clinical data of 48 patients with CHC treated with standard HCV antiviral combination therapy, between January 2005 and December 2010, at a Saudi University hospital, were retrospectively reviewed for age, sex, body mass index, liver enzymes, HCV-RNA viral load, liver biopsy, and response to treatment. The primary end point was SVR defined as undetectable HCV-RNA by polymerase chain reaction (PCR) 24 weeks after the end of treatment. Univariable logistic regression was used to explore the association between the different variables and SVR. These independent predictors of SVR were then analyzed with multivariable logistic regression analysis. RESULTS:Of the 48 treated patients, 25 (52%) were females and 27 (56%) were Saudi. The mean age was 43 years (43 ± 10 years). Twenty-four (50%) had genotype-4, and 26 (54%) had liver biopsy. The overall SVR rate was 75% (36/48) and was 83.3% (20/24) among genotype-4 patients. Baseline factors associated with SVR identified by univariate logistic regression were genotype-4 and early viral response (EVR), defined as a drop of ?2 log in serum HCV viral load after 12 weeks of initiation of combination therapy (P = 0.001). However, in stepwise regression analysis, the independent factor associated with the effect of antiviral therapy was genotype-4. When on-treatment variables were included, EVR (P = 0.003) and low baseline viral load (P = 0.048) were highly predictive of SVR. CONCLUSIONS:Of our HCV-treated patients, 75% had SVR. HCV genotype-4, EVR, and low baseline viral load were predictive of SVR.
| S-EPMC3663162 | biostudies-literature
Project description:BackgroundPatients with hepatitis C virus (HCV) with or without human immunodeficiency virus (HIV) achieve high sustained virological response (SVR) rates on sofosbuvir (SOF)-containing regimens in clinical trials. Real world data on patients coinfected with HCV and HIV treated with SOF-based regimens are lacking.MethodsThis observational cohort study included HIV/HCV-coinfected adults with genotype 1 HCV who initiated treatment with a SOF-containing regimen between December 2013 and December 2014 (n = 89) at the Mount Sinai Hospital or the Brooklyn Hospital Center. The primary outcome was SVR at 12 weeks after the end of treatment. The secondary outcomes were risk factors for treatment failure, serious adverse events, and side effects. A post hoc per protocol analysis of SVR was performed on patients who completed treatment and follow-up.ResultsIn an intention-to-treat analysis, SVR rates were 76% (31/41) for simeprevir (SMV)/SOF, 94% (16/17) for SMV/SOF/ribavirin (RBV), and 52% (16/31) for SOF/RBV. The SVR rates of SMV/SOF/RBV and SMV/SOF did not differ significantly in this small study (P = .15). However the SVR rate of SMV/SOF/RBV was higher than that of SOF/RBV (P < .01). In a per protocol analysis, SMV/SOF/RBV had a higher SVR rate than SOF/RBV: 100% (16/16) vs 57% (16/28) (P < .01). The most commonly reported adverse effects were rash, pruritus, fatigue, and insomnia. One patient who had decompensated cirrhosis prior to treatment initiation died after receiving SMV/SOF.ConclusionsSMV/SOF ± RBV is an effective option with minimal adverse effects for most HIV-positive patients with genotype 1 HCV. SMV should be used with caution in patients with decompensated cirrhosis.
| S-EPMC4885645 | biostudies-literature
Project description:Genome-wide association studies have recently identified single nucleotide polymorphisms in proximity to the interleukin-28B (IL-28B) gene that can predict sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection who are undergoing therapy with pegylated interferon (IFN) a and ribavirin. IL-28B encodes IFN-λ3, a type III IFN involved in host antiviral immunity. Favorable variants of the 2 most widely studied IL-28B polymorphisms, rs1 2979860 and rs8099917, are strong pretreatment predictors of early viral clearance and SVR in patients with genotype 1 HCV infection. Variations in the distribution of IL-28B alleles may partly explain differences in SVR rates among ethnic groups. Further investigations have implicated IL-28B in the development of chronic HCV infection versus spontaneous resolution of acute infection and suggest that IL-28B may be a key factor involved in host immunity against HCV. Clinical trials of IFN-λ as a therapeutic agent for chronic HCV infection are currently underway. The use of IL-28B polymorphisms as a predictive tool will have a major impact on treatment strategies for chronic HCV infection, particularly in the context of emerging therapies and direct-acting antiviral agents.
| S-EPMC3151409 | biostudies-literature
Project description:BackgroundTreatment of chronic hepatitis C virus infection with direct acting antiviral therapy results in viral elimination in over 90% of cases. The duration of treatment required to achieve cure differs between individuals and relapse can occur. We asked whether cellular and transcriptional profiling of peripheral blood collected during treatment could identify biomarkers predictive of treatment outcome.MethodsWe analyzed peripheral blood collected during treatment of genotype 1 HCV with 24 weeks of sofosbuvir and weight-based or low dose ribavirin in a trial in which 29% of patients relapsed. Changes in host immunity during treatment were assessed by flow cytometry and whole blood gene expression profiling. Differences in expression of immune-relevant transcripts based on treatment outcome were analyzed using the Nanostring Human Immunology V2 panel.ResultsMultiple cellular populations changed during treatment, but pre-treatment neutrophil counts were lower and natural post-treatment killer cell counts were higher in patients who relapsed. Pre-treatment expression of genes associated with interferon-signaling, T-cell dysfunction, and T-cell co-stimulation differed by treatment outcome. We identified a pre- and post-treatment gene expression signature with high predictive capacity for distinguishing treatment outcome, but neither signature was sufficiently robust to suggest viability for clinical use.ConclusionsPatients who relapse after hepatitis C virus therapy differ immunologically from non-relapsers based on expression of transcripts related to interferon signaling and T-cell dysfunction, as well as by peripheral neutrophil and NK-cell concentrations. These data provide insight into the host immunologic basis of relapse after DAA therapy for HCV and suggests mechanisms which may be relevant for understanding outcomes with currently approved regimens.
| S-EPMC7718661 | biostudies-literature
Project description:AimTo determine whether adding vitamin D, a potent immunomodulator, improves the hepatitis C virus (HCV) response to antiviral therapy.MethodsSeventy-two consecutive patients with chronic HCV genotype 1 were randomized into two groups: the treatment group (n = 36, 50% male, mean age 47 ± 11 years) received Peg-α-2b interferon (1.5 μg/kg per week) plus ribavirin (1000-1200 mg/d) together with vitamin D3 (2000 IU/d, target serum level > 32 ng/mL), and the control group (n = 36, 60% male, mean age 49 ± 7 years) received identical therapy without vitamin D. HCV-RNA was assessed by real-time polymerase chain reaction (sensitivity, 10 IU/mL). The sustained virologic response (SVR) was defined as undetectable HCV-RNA at 24 wk post-treatment.ResultsClinical characteristics were similar in both groups. The treatment group had a higher mean body mass index (27 ± 4 kg/m² vs 24 ± 3 kg/m²; P < 0.01), viral load (50% vs 42%, P < 0.01), and fibrosis score (> F2: 42% vs 19%, P < 0.001) than the controls. At week 4, 16 (44%) treated patients and 6 (17%) controls were HCV-RNA negative (P < 0.001). At week 12, 34 (94%) treated patients and 17 (48%) controls were HCV-RNA negative (P < 0.001). At 24 wk post-treatment (SVR), 31 (86%) treated patients and 15 (42%) controls were HCV-RNA negative (P < 0.001). Viral load, advanced fibrosis and vitamin D supplementation were strongly and independently associated with SVR (multivariate analysis). Adverse events were mild and typical of Peg-α-2b/ribavirin.ConclusionAdding vitamin D to conventional Peg-α-2b/ribavirin therapy for treatment-naïve patients with chronic HCV genotype 1 infection significantly improves the viral response.
| S-EPMC3243885 | biostudies-literature