Odds Of Sustained Virological Response Research Articles

Evaluation of a pilot emergency department linkage to care program for patients previously diagnosed with Hepatitis C.

There is a significant number of Emergency Department (ED) patients with known chronic hepatitis C virus (HCV) infection who have not been treated with directly acting antivirals. We implemented a pilot ED-based linkage-to-care program to address this need and evaluated the impact of the program using the HCV Care Continuum metrics. Between March 2015 and May 2016, dedicated patient care navigators identified HCV RNA-positive patients in an urban ED and offered expedited appointments with the on-site viral hepatitis clinic. Patient demographics and care continuum outcomes were abstracted from the EMR and analysed to determine significant factors influencing linkage-to-care (LTC) and treatment initiation rates. The ED linkage-to-care program achieved a 43% linkage-to-care rate (165/384), 22% treatment rate (84/384) and 16% sustained virologic response rate (63/384). Significant associations were found between linkage-to-care and increasing age (OR=1.03), Medicare insurance (OR=2.21) and having a primary care physician (PCP) (OR=4.03). For patients who were linked, the odds of initiating treatment were also positively significantly associated with increasing age (OR=1.04) and having a PCP (OR=2.77). For patients who initiated treatment, the odds of sustained virologic response were marginally associated with having a PCP (OR=4.92).Our ED linkage-to-care program utilized care coordination to successfully link nearly half of approached HCV RNA-positive patients to care. This design can be feasibly replicated by other EDs given limited non-clinical training required for linkage-to-care staff. Adoption of similar programs in other EDs may improve the rates of LTC and treatment initiation for previously diagnosed HCV patients.

English hepatitis C registry data show high response rates to directly acting anti-virals, even if treatment is not completed.

In England, choice of hepatitis C therapy is determined by national contracts that change with time, facilitating comparisons between different regimens. England has a diverse population with hepatitis C including large proportions of uncommon viral genotypes. To evaluate efficacy of directly acting anti-viral treatments for hepatitis C in England using real-world data from the national treatment registry. Sustained virological response (SVR) rates 12weeks after treatment completion for patients treated between 2014 and August 2018 who attended for SVR tests were analysed in univariate subgroups using Chi-squared tests. Multivariate models were constructed with clinically relevant variables to determine predictors of SVR and evaluate the impact of treatment regimens. SVR data were available on 14,603 treated patients. The overall SVR rate was 95.59% [95% CI 95.25%-95.91%]. Multivariable regression modelling in patients with genotype 1 infection showed that the odds of SVR with elbasvir/grazoprevir were higher than for those treated with sofosbuvir/ledipasvir (OR 1.891, 95% CI 1.072-3.336, P=0.028). For genotype 3, we found no significant difference between any of the treatment regimens. Patients who completed at least one third of the planned treatment duration achieved SVR rates in excess of 80%. All of the currently licensed hepatitis C direct-acting anti-viral regimens had similar efficacy (>95%) in an unselected population. Noncompletion of planned treatment duration still resulted in over 80% SVR rates provided that more than one third of treatment was completed.

Amino Acid Substitutions in Genotype 3a Hepatitis C Virus Polymerase Protein Affect Responses to Sofosbuvir

Background & AimsSofosbuvir is a frequently used pan-genotype inhibitor of hepatitis C virus (HCV) polymerase. This drug eliminates most chronic HCV infections, and resistance-associated substitutions in the polymerase are rare. However, HCV genotype 3 responds slightly less well to sofosbuvir-based therapies than other genotypes. We collected data from England’s National Health Service Early Access Program to search for virus factors associated with sofosbuvir treatment failure.MethodsWe collected patient serum samples and used the capture-fusion assay to assess viral sensitivity to sofosbuvir in 14 HCV genotype 3 samples. We identified polymorphisms associated with reduced response and created modified forms of HCV and replicons containing the substitutions of interest and tested their sensitivity to sofosbuvir and ribavirin. We examined the effects of these polymorphisms by performing logistic regression multivariate analysis on their association with sustained virologic response in a separate cohort of 411 patients with chronic HCV genotype 3 infection who had been treated with sofosbuvir and ribavirin, with or without pegylated interferon.ResultsWe identified a substitution in the HCV genotype 3a NS5b polymerase at amino acid 150 (alanine [A] to valine [V]), V at position 150 was observed in 42% of patients) with a reduced response to sofosbuvir in virus replication assays. In patients treated with sofosbuvir-containing regimens, the A150V variant was associated with a reduced response to treatment with sofosbuvir and ribavirin, with or without pegylated interferon. In 326 patients with V at position 150, 71% achieved an sustained virologic response compared to 88% with A at position 150. In cells, V at position 150 reduced the response to sofosbuvir 7-fold. We found that another rare substitution, glutamic acid (E) at position 206, significantly reduced the response to sofosbuvir (8.34-fold reduction); the combinations of V at position 150 and E at position 206 reduced the virus response to sofosbuvir 35.77-fold. Additionally, in a single patient, we identified 5 rare polymorphisms that reduced sensitivity to sofosbuvir our cell system.ConclusionsA common polymorphism, V at position 150 in the HCV genotype 3a NS5b polymerase, combined with other variants, reduces the virus response to sofosbuvir. Clinically, infection with HCV genotype 3 containing this variant reduces odds of sustained virologic response. In addition, we identified rare combinations of variants in HCV genotype 3 that reduce response to sofosbuvir.

Absence of Relationship between Serum Vitamin D Levels, Degree of Hepatic Fibrosis, and Virologic Response to Pegylated Interferon and Ribavirin Therapy in Patients with Chronic Hepatitis C

Introduction: In patients with chronic hepatitis C virus (HCV) infection, 25-hydroxyvitamin D3 [25(OH)D] deficiency has been associated with disease progression and decreased odds of sustained virologic response (SVR) to pegylated interferon and ribavirin combination therapy (PegIFN+RBV). Methods: In this retrospective study, the pretreatment 25(OH)D levels of patients with genotype 1 HCV infection treated with PegIFN + RBV for 48 weeks were measured and correlated with disease stage and periportal necroinflammatory activity (PPA) on liver biopsy, as well as to virologic response at the end of the treatment period. Serum 25(OH)D levels were quantitated by chemiluminescence. Results: Of the 201 patients included, 53% were male and 70% were white, with a mean (SD) age of 46 (±11) years. Subtype 1b was identified in 48% of cases, and 57% of patients had a viral load over 800,000 IU/mL. Overall, 29% of patients had stage 3/4 fibrosis and 40% had grade 3/4 PPA. SVR was achieved in 47% of patients. The mean 25(OH)D concentration was 26.3 (±11.5) ng/mL. Low 25(OH)D levels (<30 ng/dL) were detected in 69% of patients, and were not associated with staging (rS=-0.003; p=0.895) or grading (rS=0.045; p=0.105). There were no significant differences in SVR rate between patients with vs. those without 25(OH)D deficiency (49% vs. 40%, p=0.359). The only variables associated with 25(OH)D insufficiency or deficiency were serum albumin (rS=0.199; p=0.006), female sex (rS=0.249; p=0.002), and age (rS=-0.227; p=0.001). Conclusion: In this sample of patients with chronic HCV infection, vitamin D deficiency was not associated with increased histologic severity, nor with increased likelihood of SVR.

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Response rates to pegylated interferon and ribavirin in HCV/HIV coinfection: a research synthesis

Several recent trials have determined varying rates of response to pegylated interferon plus ribavirin (peg-IFN + RIB) in hepatitis C virus (HCV)/human immunodeficiency virus-coinfected patients. We sought to identify a pooled response rate and sources of interstudy variability. A literature search was conducted to identify randomized or prospective studies evaluating response rates to peg-IFN + RIB in coinfected patients. A Bayesian hierarchical model was used to estimate overall response rate. Between-study variance was calculated and sensitivity analyses were conducted. Meta-regression was employed to identify sources of between-study variability. The literature search yielded seven studies of 146, which matched keywords and inclusion criteria. The combined patient total was 784. Individual intention-to-treat response rates ranged from 27.3% to 44.2%. The pooled Bayesian estimate of percent response was 33.3%. Significant interstudy heterogeneity was detected. Meta-regression yielded no significant effects of covariates on response rate. Subanalyses by CD4+, HCV viral load and genotype yielded sustained virological response (SVR) odds ratios of 0.73 for low CD4+, 0.41 for high viral load and 0.30 for genotype 1/4. The pooled response rate is not attributable to any one study. Response is poor compared with HCV-monoinfected patients. Interstudy variability is not satisfactorily explained by factors influencing individual response, but may be due to differences between studies unavailable for inclusion in this analysis. However, both genotype 1/4 and high HCV viral load at baseline were significantly associated with a reduction in odds of SVR in pooled subanalysis. Improved treatments are needed in coinfected patients, especially with genotype 1/4 and high viral load.