Barriers to initiation of hepatitis C virus therapy in Germany: A retrospective, case-controlled study.

Despite the availability of highly effective and well-tolerated direct-acting antivirals, not all patients with chronic hepatitis C virus infection receive treatment. This retrospective, multi-centre, noninterventional, case-control study identified patients with chronic hepatitis C virus infection initiating (control) or not initiating (case) treatment at 43 sites in Germany from September 2017 to June 2018. It aimed to compare characteristics of the two patient populations and to identify factors involved in patient/physician decision to initiate/not initiate chronic hepatitis C virus treatment, with a particular focus on historical barriers. Overall, 793 patients were identified: 573 (72%) who received treatment and 220 (28%) who did not. In 42% of patients, the reason for not initiating treatment was patient wish, particularly due to fear of treatment (17%) or adverse events (13%). Other frequently observed reasons for not initiating treatment were in accordance with known historical barriers for physicians to initiate therapy, including perceived or expected lack of compliance (14.5%), high patient age (10.9%), comorbidities (15.0%), alcohol abuse (9.1%), hard drug use (7.7%), and opioid substitution therapy (4.5%). Patient wish against therapy was also a frequently reported reason for not initiating treatment in the postponed (35.2%) and not planned (47.0%) subgroups; of note, known historical factors were also common reasons for postponing treatment. Real-world and clinical trial evidence is accumulating, which suggests that such historical barriers do not negatively impact treatment effectiveness. Improved education is key to facilitate progress towards the World Health Organization target of eliminating viral hepatitis as a major public health threat by 2030.

HCV Viral Load Greater Than 1000 IU/ml at Time of Virologic Failure in Direct-Acting Antiviral-Treated Patients.

INTRODUCTION: One of the remaining barriers to reaching WHO elimination targets of achieving global hepatitis C (HCV) cure is a lack of an established lower limit of detection (LLOD) to confirm cure post-treatment in near-patient technologies. Determining a LLOD at virologic failure aids in increasing testing feasibility through point-of-care assays in resource-limited settings. METHODS: We described the level of viremia in 69 patients experiencing virologic failure across 20 clinical trials (ENDURANCE-1, ENDURANCE-2, ENDURANCE-3, ENDURANCE-4, ENDURANCE 5-6, MAGELLAN-1, MAGELLAN-2, EXPEDITION-1, EXPEDITION-2, EXPEDITION-3, EXPEDITION-4, EXPEDITION-5, EXPEDITION-8, SURVEYOR-1, SURVEYOR-2, VOYAGE-1, VOYAGE-2, CERTAIN-1, CERTAIN-2 and APRI). These findings were categorized as on-treatment, post-treatment week (PTW) 4 or PTW12 failures. RESULTS: The mean HCV RNA level at baseline in the overall population of 5033 patients was 4,193,712 IU/ml ± 5,955,028 (6.2 log10 IU/ml ± 0.8) compared to 9,585,957 IU/ml ± 8,247,669 (6.8 log10 IU/ml ± 0.5) in 69 patients experiencing virologic failure by PTW12. The mean HCV RNA level at the time of virologic failure for all patients was 6,004,980 IU/ml ± 7,077,728 (6.4 log10 IU/ml ± 0.7). Twenty patients had on-treatment virologic failure with a mean HCV RNA level at the time of failure of 9,136,360 IU/ml ± 8,572,113 (6.7 log10 IU/ml ± 0.7), 36 patients had relapsed by PTW4 with a mean HCV RNA level at the time of relapse of 4,131,344 IU/ml ± 5,246,954 (6.3 log10 IU/ml ± 0.6), and 13 patients, who experienced relapse between PTW4 and PTW12, had a mean HCV RNA at relapse of 6,376,003 IU/ml ± 7,758,968 (6.3 log10 IU/ml ± 1.0). CONCLUSIONS: At PTW12, 100% of virologic failures had an HCV RNA > 3.0 log10 IU/ml. The data are encouraging that with a LLOD of 3.0 log10 IU/ml, a point-of-care test could identify all treatment failures accurately; larger studies, including real-world data, are needed to confirm these findings.

Eight Weeks of Treatment With Glecaprevir/Pibrentasvir Is Safe and Efficacious in an Integrated Analysis of Treatment-Naïve Patients With Hepatitis C Virus Infection.

BACKGROUND & AIMS: The direct-acting antiviral combination glecaprevir/pibrentasvir has been approved by the Food and Drug Administration for 8 weeks of treatment in treatment-naïve patients with hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis. We performed an integrated analysis of data from trials to evaluate the overall efficacy and safety of 8 weeks of glecaprevir/pibrentasvir in treatment-naïve patients without cirrhosis or with compensated cirrhosis. METHODS: We pooled data from 8 phase 2 or phase 3 trials of treatment-naïve patients with HCV genotype 1 to 6 infections, without cirrhosis or with compensated cirrhosis, who received 8 weeks of glecaprevir/pibrentasvir. RESULTS: Of 1248 patients, 343 (27%) had cirrhosis. Most patients were white (80%) and had HCV genotype 1 infection (47%) or genotype 3 infection (22%); the median age was 54 years. Overall rates of sustained virologic response at post-treatment week 12 were 97.6% (1218 of 1248) in the intention to treat (ITT) and 99.3% (1218 of 1226) in the modified ITT populations. When we excluded patients with genotype 3 infections with compensated cirrhosis (consistent with the European label), rates of sustained virologic response at post-treatment week 12 were 97.6% in the ITT and 99.4% in the modified ITT populations. Eight virologic failures (7 in patients without cirrhosis and 1 in a patient with cirrhosis) occurred in the ITT population. Virologic failure was not associated with markers of advanced liver disease or populations of interest (current alcohol use, opioid substitution therapy, history of injection-drug use, and severe renal impairment). Treatment-emergent adverse events (AEs) occurred in 58% of patients. The most frequent AEs (>10%) were headache (12%) and fatigue (12%). Serious AEs and AEs that led to glecaprevir/pibrentasvir discontinuation were reported in 2% and less than 1% of patients, respectively. CONCLUSIONS: In a pooled analysis of data from 8 trials, we found that 8 weeks of treatment with glecaprevir/pibrentasvir is efficacious and well tolerated in treatment-naïve patients with HCV genotype 1 to 6 infections, with or without cirrhosis.