Black race and Hispanic ethnicity were associated with lower rates of sustained virologic response (SVR) to interferon-based treatments for chronic hepatitis C virus infection, whereas Asian race was associated with higher SVR rates compared to white patients. We aimed to describe the association between race/ethnicity and effectiveness of new direct-acting antiviral regimens in the Veterans Affairs health care system nationally. We identified 21,095 hepatitis C virus-infected patients (11,029 [52%] white, 6,171 [29%] black, 1,187 [6%] Hispanic, 348 [2%] Asian/Pacific Islander/American Indian/Alaska Native, and 2,360 [11%] declined/missing race or ethnicity) who initiated antiviral treatment with regimens containing sofosbuvir, simeprevir + sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ombitasvir/ritonavir/dasabuvir during the 18-month period from January 1, 2014, to June 30, 2015. Overall SVR rates were 89.8% (95% confidence interval [CI] 89.2-90.4) in white, 89.8% (95% CI 89.0-90.6) in black, 86.0% (95% CI 83.7-88.0) in Hispanic, and 90.7% (95% CI 87.0-93.5) in Asian/Pacific Islander/American Indian/Alaska Native patients. However, after adjustment for baseline characteristics, black (adjusted odds ratio = 0.77, P
Little is known about factors associated with a sustained virologic response (SVR) among patients with hepatitis C virus (HCV) infection to treatment with protease inhibitors.
Previously untreated patients (from the Serine Protease Inhibitor Therapy 2 [SPRINT-2] trial) and those who did not respond to prior therapy (from the Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 [RESPOND-2] trial) received either a combination of peginterferon and ribavirin for 48 weeks or boceprevir, peginterferon, and ribavirin (triple therapy) after 4 weeks of peginterferon and ribavirin (total treatment duration, 28-48 wk). A good response to interferon was defined as a = 1 log(10) decrease in HCV RNA at week 4; a poor response was defined as a
Outcomes of chronic hepatitis C therapy in patients treated in community versus academic centres in Canada: final results of APPROACH (a prospective study of peginterferon alfa-2a and ribavirin at academic and community centres in Canada).
In patients chronically infected with the hepatitis C virus (HCV), it is not established whether viral outcomes or health-related quality of life (HRQoL) differ between individuals treated at academic or community centres.
In the present observational study, adults with chronic HCV were treated with peginterferon alfa-2a 180 Ã¬g/week plus ribavirin at 45 Canadian centres (16 academic, 29 community). The primary efficacy end point was sustained virological response (SVR). Other outcome measures included HRQoL (assessed using the 36-item Short-Form Health Survey), heath resource use, and workplace productivity and absences within a 60-day interval.
In treatment-naive patients infected with HCV genotype 1, significantly higher SVR rates were achieved in those treated at academic (n=54) compared with community (n=125) centres (52% versus 32% [P=0.01]), although rates of dosage reduction and treatment discontinuation were similar across settings. SVR rates among patients infected with genotype 2/3 were similar between academic (n=59) and community (n=100) centres (64% versus 67% [P=0.73]). Following antiviral therapy, patients with genotype 1 who achieved an SVR (n=67) had significantly higher mean scores on the physical (P=0.005) and mental components of the 36-item Short-Form Health Survey (P=0.043) compared with those without an SVR (n=111). In contrast, HRQoL scores were similar in HCV genotype 2/3 patients with and without an SVR. There were no differences in workplace productivity or absences between patients with and without an SVR. The most frequently used health care resources by all patients were visits and phone calls to hepatitis nurses, and general practice or walk-in clinics.
Patients infected with HCV genotype 1 achieved higher SVR rates when treated at academic rather than community centres in Canada. The reasons for this difference require additional investigation.
Cites: N Engl J Med. 2002 Sep 26;347(13):975-8212324553
Traditional therapy with pegylated interferon and ribavirin combined with the new protease inhibitors boceprevir or telaprevir has demonstrated improved outcomes in hepatitis C virus (HCV)-infected patients. Prevalence data regarding pre-existing drug-resistant variants to these two new virus inhibitors in the Canadian population are not available.
To detect pre-existing mutations conferring resistance to boceprevir and/or telaprevir in Canadian patients infected with HCV genotype 1a.
Resistance-associated mutations (RAMs) were evaluated in 85 patients infected with HCV genotype 1a who had not yet received antiviral therapy. The NS3 protease gene was sequenced and common RAMs were identified based on a recently published list.
The overall prevalence of pre-existing RAMs to boceprevir and telaprevir was higher compared with other similar studies. All of the observed RAMs were associated with a low level of resistance. A surprisingly high proportion of patients had the V55A RAM (10.6%). None of the mutations associated with a high level of resistance were observed. The simultaneous presence of two low-level resistance mutations (V36L and V55A) was observed in only one patient. Three other patients had both T54S RAM and V55I mutations, which may require a higher concentration of the protease drugs. The prevalence of various mutations in Aboriginal Canadian patients was higher (37.5%) compared with Caucasians (16.39%) (P=0.038).
The present study was the first to investigate pre-existing drug resistance to boceprevir/telaprevir in Canadian HCV-infected patients. A relatively high proportion of untreated HCV genotype 1a patients in Manitoba harbour low-level RAMs, especially patients of Aboriginal descent, which may contribute to an increased risk of treatment failure.
The future treatment of hepatitis C virus (HCV) infection will be combinations of direct-acting antivirals (DAAs) that not only target multiple viral targets, but are also effective against different HCV genotypes. Of the many drug targets in HCV, one promising target is the non-structural 5A protein (NS5A), against which inhibitors, namely daclatasvir, ledipasvir and ombitasvir, have shown potent efficacy. However, since HCV is known to have very high sequence diversity, development of resistance is a problem against but not limited to NS5A inhibitors (i.e. resistance also found against NS3-protease and NS5B non-nucleoside inhibitors), when used in suboptimal combinations. Furthermore, it has been shown that natural resistance against DAAs is present in treatment-naÃ¯ve patients and such baseline resistance will potentially complicate future treatment strategies.
A pan-genotypic population-sequencing method with degenerated primers targeting the NS5A region was developed. We have investigated the prevalence of baseline resistant variants in 127 treatment-naÃ¯ve patients of HCV genotypes 1a, 1b, 2b and 3a.
The method could successfully sequence more than 95% of genotype 1a, 1b and 3a samples. Interpretation of fold resistance data against the NS5A inhibitors was done with the help of earlier published phenotypic data. Baseline resistance variants associated with high resistance (1000-50,000-fold) was found in three patients: Q30H or Y93N in genotype 1a patients and further Y93H in a genotype 3a patient.
Using this method, baseline resistance can be examined and the data could have a potential role in selecting the optimal and cost-efficient treatment for the patient.
Following the approval of two new therapeutic combinations within the European Union in 2017, the former Swedish recommendations for the treatment of hepatitis C virus (HCV) infection from 2016 were deemed in need of updating.
An expert meeting to this end was held in Stockholm, Sweden in October 2017.
An interferon-free combination of direct-acting antiviral agents is now recommended for all patients with chronic HCV infection, regardless of liver fibrosis stage, in order to limit morbidity and spread of the disease. An extended discussion of treatment for people who inject drugs in order to diminish transmission is included.
In a recent expert meeting, Swedish recommendations for the treatment of hepatitis C virus (HCV) infection were updated. An interferon-free combination of direct-acting antiviral agents is considered and indicated for all patients with chronic HCV infection, but the ability to treat all is limited primarily by high cost of medication. The group of patients prioritized for therapeutic intervention has been extended to also include fertile women desiring to become pregnant. A more thorough discussion of treatment for people who inject drugs (PWIDs) in order to diminish transmission is included, and the clinical significance of baseline NS5A resistance associated variants (RAVs), also known as resistance associated substitutions (RASs), for the treatment of HCV genotype 1a or 3 infection is discussed.
Hepatitis C is a major cause of chronic liver disease and cirrhosis in Western countries. Its treatment aims at eradicating the virus and patients are considered cured if the virus is undetectable by PCR in blood 12-24 weeks after end of treatment (sustained virological response, SVR). The aim of this study is to investigate the results of treating hepatitis C in Iceland during the period 2002-2012.
Retrospective study including all patients with hepatitis C receiving treatment with peginterferone and ribavirin at Landspitali University hospital during the period 2002-2012. Patients who had been treated previously were excluded. Information was obtained from medical records and the hospital pharmacy.
A total of 207 patients were included, 136 (66%) males and 71 (34%) females. Mean age was 38 years (range 17-66). Genotyping revealed that 71 (34%) patients had genotype 1, 135 (65%) genotype 3 and one genotype 2. A total of 147 (71%) patients achieved SVR. The rate of SVR was 77.8% for genotype 3 and 57.7% for genotype 1. 9 patients (4%) had cirrhosis and 3 of them had SVR. Of 161 patients who finished treatment per protocol, 87.5% and 77.1% with genotypes 3 and 1 respectively had SVR.
The study demonstrates higher rates of SVR in clinical practice in Iceland compared to controlled clinical trials. The improved effectiveness may be explained by younger patient population, low rate of cirrhosis and close follow-up of patients. Key words: Hepatitis C, peg-interferon, sustained virological response. Correspondence: Sigurdur Olafsson, firstname.lastname@example.org.
Treatment results of hepatitis C have improved markedly during the last years with the combination pegylated interferons and ribavirin. The indications for evaluation for therapy is positive HCV-PCR and lack of contraindications for treatment. Liver biopsy is considered only for those with suspicion of other concomitant liver disease or in patients, where retreatment is considered. The length of therapy is individualised and based on rapid virological response in both genotype 2/3 and in genotype 1. Patients with genotype 2/3 with negative HCV-PCR at week 4 and younger than 40 years are treated for 12 weeks only with 80-90 % response rate. In Finland some 70 % of the patients with genotype 2/3 can successfully be treated with 12 weeks therapy. In genotype 1 patients with rapid virological response, regardless of age are treated for 24 weeks. Treatment is discontinued for those, who are still positive at week 24. Early intervention with tailored combination therapy before cirrhosis has developed improves treatment results, patient's overall prognosis and reduces cost of medication and surveillance. New protease inhibitors, telaprevir and boceprevir combined with PEG-interferons and ribavirin might be a future option for those not achieving early virological response.