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Early confirmation of sustained virologic response (SVR) or viral relapse after direct‐acting antivirals (DAAs) for hepatitis C virus (HCV) infection is essential based on public health perspectives, particularly for patients with high risk of nonadherence to posttreatment follow‐ups. A total of 1011 patients who achieved end‐of‐treatment virologic response, including 526 receiving fixed‐dose pangenotypic DAAs, and 485 receiving other types of DAAs, who had available off‐treatment weeks 4 and 12 serum HCV RNA data to confirm SVR at off‐treatment week 12 (SVR12) or viral relapse were included. The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 to predict patients with SVR12 or viral relapse were reported. Furthermore, we analyzed the proportion of concordance between SVR12 and SVR24 in 943 patients with available SVR24 data. The PPV and NPV of SVR4 to predict SVR12 were 98.5% (95% confidence interval [CI]: 98.0–98.9) and 100% (95% CI: 66.4–100) in the entire population. The PPV of SVR4 to predict SVR12 in patients receiving fixed‐dose pangenotypic DAAs was higher than those receiving other types of DAAs (99.8% [95% CI: 98.9–100] vs. 97.1% [95% CI: 96.2–97.8], p < 0.001). The NPVs of SVR4 to predict viral relapse were 100%, regardless of the type of DAAs. Moreover, the concordance between SVR12 and SVR24 was 100%. In conclusion, an off‐treatment week 4 serum HCV RNA testing is sufficient to provide an excellent prediction power of SVR or viral relapse at off‐treatment week 12 among patients with HCV who are treated with fixed‐dose pangenotypic DAAs. [ABSTRACT FROM AUTHOR]

Aim of the study: Despite the excellent effectiveness of direct-acting antivirals (DAA) in the treatment of hepatitis C virus (HCV) infection, still a few percent of patients fail therapy. The study aimed to determine the effectiveness of triple vs double rescue treatment in such a population. Material and methods: The study included all consecutive DAA-experienced patients retreated with pangenotypic options from the EpiTer-2 database, a retrospective national multicenter real-world project evaluating antiviral treatment in HCV-infected patients in 2015-2023. Results: The studied population consisted of 269 patients, of whom 208 were treated with the double (P2) and 61 with the triple (P3) pangenotypic option. No statistically significant differences were found between these subpopulations, except a significantly more frequent history of liver transplantation in the P3 group (6.6% vs. 0.5%, p = 0.01). In the P2 group, two-thirds of patients were treated with velpatasvir/sofosbuvir, while in the P3 group the majority of patients received a combination of velpatasvir/sofosbuvir/voxilaprevir. Virological response at the end of therapy was comparable in both analyzed subpopulations, but the sustained virologic response (SVR) rate was significantly higher in triple retherapy, 98.3% vs. 88.7%, p = 0.02, calculated after exclusion of patients lost to follow-up. Lower SVR was achieved in genotype 3-infected men with cirrhosis, 88.9% and 80% in P3 and P2, respectively. Conclusions: A comparison of double and triple pangenotypic retherapy in patients after failure of DAA therapy showed a higher sustained virological response in the triple option with a comparable response at the end of therapy. The factors reducing the chances of cure were cirrhosis, genotype 3 infection and male gender. [ABSTRACT FROM AUTHOR]

Background: Real-world data are scarce about the effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for retreating East Asian patients with hepatitis C virus (HCV) infection who previously received NS5A direct-acting antivirals (DAAs). We conducted a multicenter study to assess the performance of SOF/VEL/VOX in patients who were not responsive to prior NS5A inhibitors in Taiwan. Methods: Between September 2021 and May 2022, 107 patients who failed NS5A inhibitor-containing DAAs with SOF/VEL/VOX salvage therapy for 12 weeks were included at 16 academic centers. The sustained virologic response at off-treatment week 12 (SVR12) was assessed in the evaluable (EP) and per-protocol (PP) populations. The safety profiles were also reported. Results: All patients completed 12 weeks of treatment and achieved an end-of-treatment virologic response. The SVR12 rates were 97.2% (95% confidence interval (CI) 92.1–99.0%) and 100% (95% CI 96.4–100%) in EP and PP populations. Three (2.8%) patients were lost to off-treatment follow-up and did not meet SVR12 in the EP population. No baseline factors predicted SVR12. Two (1.9%) not-fatal serious adverse events (AE) occurred but were unrelated to SOF/VEL/VOX. Sixteen (15.0%) had grade 2 total bilirubin elevation, and three (2.8%) had grade 2 alanine transaminase (ALT) elevation. Thirteen (81.3%) of the 16 patients with grade 2 total bilirubin elevation had unconjugated hyperbilirubinemia. The estimated glomerular filtration rates (eGFR) were comparable between baseline and SVR12, regardless of baseline renal reserve. Conclusions: SOF/VEL/VOX is highly efficacious and well-tolerated for East Asian HCV patients previously treated with NS5A inhibitor-containing DAAs. Clinical trials registration: The study was not a drug trial. There was no need for clinical trial registration. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection remains a major health problem and one of the leading causes of chronic liver disease worldwide. The purpose of this paper was to summarize knowledge about the epidemiology of HCV genotype (GT) 4 infection, similarities and differences with other genotypes, specific problems associated with this genotype, and treatment regimens used to treat GT4-infected patients. We performed an accurate search for literature using the PubMed database to select high-quality reviews and original articles concerning this topic. GT4 with a global prevalence of 8% takes third place, closing the global HCV podium in terms of frequency. However, there are regions where GT4 infections are dominant, such as sub-Saharan and North Africa, and the Middle East. The disease course and complications are generally similar to those of chronic hepatitis C caused by other genotypes, although the faster progression of fibrosis was demonstrated in patients with coexisting schistosomiasis. In the era of interferon-based therapy, GT4-infected patients were described as difficult to treat due to suboptimal response. A breakthrough in the treatment of HCV-infected patients, including those with GT4 infection, was the introduction of direct-acting antiviral drugs. The availability of safe and effective therapy has created a real opportunity for HCV eradication in line with the goal set by the World Health Organization. An example of a country where this is happening is Egypt, where GT4 accounts for more than 90% of HCV infections. There, broad access to therapy has been effectively supported by population-based screening. [ABSTRACT FROM AUTHOR]

Direct-acting antivirals (DAA) regimens have provided hope for eliminating hepatitis C virus (HCV) infection. Patients following ineffective therapy with DAA, especially those previously treated with inhibitors of non-structural protein 5A (NS5A), remain a challenge. The study aimed to assess the effectiveness of DAA pangenotypic options in patients after failure of NS5A containing genotype-specific regimens. The analysis included 120 patients selected from the EpiTer-2 database with data on 15675 HCV-infected individuals treated with IFN-free therapies from 1 July 2015 to 30 June 2022 at 22 Polish hepatology centres. The majority of them were infected with genotype (GT) 1b (85.8%) and one-third was diagnosed with fibrosis F4. Among the rescue pangenotypic regimens, the most commonly used was the sofosbuvir/velpatasvir (SOF/VEL) ± ribavirin (RBV) combination. The sustained virologic response, which was a measure of treatment effectiveness, was achieved by 102 patients, resulting in cure rate of 90.3% in the per protocol analysis. All 11 non-responders were infected with GT1b, 7 were diagnosed with cirrhosis, and 9 were treated with SOF/VEL±RBV. We demonstrated the high effectiveness of the pangenotypic rescue options in patients after genotype specific NS5A-containing regimens failures, identifying cirrhosis as a negative prognostic factor of treatment effectiveness. [ABSTRACT FROM AUTHOR]

Background: Data regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) for East Asian patients with chronic hepatitis C virus (HCV) infection and compensated liver disease are limited. We evaluated the performance of SOF/VEL for 12 weeks for HCV-infected patients with compensated liver disease in a large real-world cohort in Taiwan. Methods: Between July 2019 and March 2020, 1880 HCV-infected patients with compensated liver disease who received SOF/VEL 400/100 mg once daily for 12 weeks were included at 15 academic centers in Taiwan. The sustained virologic response at off-treatment week 12 (SVR12) was assessed for evaluable (EP) and per-protocol populations (PP). The tolerance was also reported. Results: The SVR12 rates by EP and PP analyses were 95.6% [1798 of 1880 patients; 95% confidence interval (CI) 94.6–96.5%] and 99.3% (1798 of 1811 patients; 95% CI 98.8–99.6%), respectively. Among 82 patients who failed to achieve SVR12, 13 (15.9%) were attributed to virologic failures. The SVR12 rates were comparable regardless of baseline characteristics. A total of 1859 (98.9%) patients completed 12-week SOF/VEL treatment. Four (0.2%) patients discontinued treatment due to adverse events (AEs). All patients with serious AEs or deaths were judged not related to SOF/VEL. The AEs occurring in ≥ 10% included headache (16.8%), fatigue (16.2%), nausea (11.8%), and insomnia (11.1%). Nine (0.5%) and 2 (0.1%) patients had grade 3 total bilirubin and alanine aminotransferase elevations. Conclusions: SOF/VEL for 12 weeks is efficacious and well-tolerated by chronic HCV-infected patients with compensated liver disease in Taiwan. [ABSTRACT FROM AUTHOR]

Long-term efforts of the international community led to the development of highly efficient direct-acting antivirals (DAAs) that allow treatment of the vast majority of patients with chronic hepatitis C. The proteins encoded in the genome of the hepatitis C virus (HCV) that play a key role in its life cycle (NS3, NS5A, and NS5B) are the targets of this type of drug. There are three classes of DAAs each of which is directed to the inhibition of a specific target protein. Since the HCV has a sufficiently high rate of accumulation of mutations, the development of resistance to these drugs is a big problem. The current recommended treatment regimens with DAAs without the use of interferon and ribavirin are a combination of drugs of different classes providing an increase in the barrier of resistance. Due to the emergence of DAAs, a number of countries (WHO members, with the involvement of Russia) put forward a global strategy to eradicate the HCV. Taking into account the high cost of DAAs and a large number of HCV-infected individuals in Russia, achieving the goals declared by the WHO presents great financial difficulties for our country. However, federal funds allocated for hepatitis C therapy increased significantly over the past 3 years. In addition to increased funding, there is a great potential for reducing the cost of treatment, but its implementation is impossible without the organization of national production of quality generics, issuance of compulsory licenses (given that it is impossible to negotiate with patent holders on licensing), and/or negotiations on price reduction in exchange for volume (for example, the experience of Australia and Portugal). Anyways, Russia faces a very important task to provide therapy for several million patients with hepatitis C in the coming years to get closer to the goal of eradication of the HCV set by the international community. [ABSTRACT FROM AUTHOR]

Glecaprevir/pibrentasvir is approved for treating adults infected with HCV genotypes 1–6. In clinical trials, glecaprevir/pibrentasvir was associated with high rates of sustained virologic response at post-treatment week 12 (SVR12) and was well tolerated. A systematic review and meta-analysis of the real-world effectiveness and safety of glecaprevir/pibrentasvir were undertaken. Real-world studies reporting SVR12 in adults with HCV infection (n ≥20) treated with glecaprevir/pibrentasvir were identified in journal publications from January 1, 2017, to February 25, 2019, and congress presentations through April 14, 2019. Random-effects meta-analysis was used to determine SVR12 rates using data from ≥2 cohorts; intention-to-treat (ITT) analyses included patients treated with glecaprevir/pibrentasvir who had SVR12 data available, discontinued early, or were lost to follow-up; modified ITT (mITT) analyses excluded those with non-virologic failure. Naïve pooling was used to calculate adverse event (AE) rates. Overall, 12,531 adults were treated with glecaprevir/pibrentasvir (18 cohorts). Of patients with post-treatment week 12 data, SVR12 rates were 96.7% (95% CI 95.4–98.1) in the ITT population (n = 8,583, 15 cohorts) and 98.1% (95% CI 97.1–99.2) in the mITT population (n = 7,001, 14 cohorts). SVR12 rates were ≥95% across subgroups (HCV genotype, cirrhosis status, treatment history, treatment duration, on-label treatment, and subgroups of interest). AEs were reported in 17.7% (1,271/7,199) of patients (8 cohorts). Serious AEs were reported in 1.0% (55/5,522) of patients (6 cohorts). The most frequent AEs were pruritus, fatigue, and headache. AE-related treatment discontinuations were reported in 0.6% (33/5,595) of patients (6 cohorts). Consistent with clinical trials, real-world evidence indicates that glecaprevir/pibrentasvir is a well-tolerated and highly effective pangenotypic treatment for a broad range of HCV-infected patients. It is important to assess treatments for hepatitis C virus (HCV) in the real world, as patient populations tend to be more diverse and potentially less adherent to treatment compared to those in clinical trials. Results from 18 studies performed in real-world clinics were pooled and analyzed to investigate the effectiveness and safety of a direct-acting antiviral combination (glecaprevir/pibrentasvir) in routine clinical practice. This analysis showed that glecaprevir/pibrentasvir is highly effective and well tolerated across all HCV genotypes and patient groups studied. It also showed that results seen in the real world are similar to the results seen in clinical trials, even in patients historically considered more challenging to treat. • Meta-analysis of real-world data from 12,583 patients taking glecaprevir/pibrentasvir. • Glecaprevir/pibrentasvir achieved 96.7% virologic cure overall. • Virologic cure was ≥95% across subgroups of interest. • Serious adverse events were reported in 1.0% of patients. • Effectiveness and safety results were consistent with those from clinical trials. [ABSTRACT FROM AUTHOR]

Background and Aims: Chronic hepatitis C virus (HCV) infection increases the risk of incident chronic kidney disease (CKD) and progression to end‐stage renal disease (ESRD). Previously available direct‐acting antiviral regimens are not approved for patients with advanced CKD across all HCV genotypes. Methods: EXPEDITION‐5 is a phase 3 study to evaluate efficacy and safety of the fixed‐dose combination of glecaprevir and pibrentasvir (G/P) for chronic HCV infection (genotype 1 through 6) in adults without cirrhosis or with compensated cirrhosis and with stage 3b, 4 or 5 CKD. Patients received approved duration of G/P according to HCV genotype, cirrhosis status and prior HCV treatment experience. The primary efficacy endpoint was percentage of patients with sustained virologic response at 12 weeks post‐treatment (SVR12). Results: Among the 101 patients enrolled in the study, 24% had predialysis CKD and 76% were on dialysis. Eighty‐four patients were treated with G/P for 8 weeks, 13 patients for 12 weeks and four patients for 16 weeks. Fifty‐five per cent of patients had genotype 1, 27% had genotype 2, 15% had genotype 3 and 4% had genotype 4, and none had genotype 5 or 6 infection. The SVR12 rate was 97% (98/101, 95% confidence interval, 91.6‐99.0). No patients experienced virologic failure. Adverse events (AEs) reported in at least 5% of the patients were pruritus, bronchitis, hypertension and generalized pruritus. Serious AEs were reported in 12% of patients; none related to study drug. Conclusions: G/P treatment yielded high SVR12 rates irrespective of the presence of stage 3b, 4 or 5 CKD. No safety signals were detected. Clinicaltrials.gov identifier: This Phase 3 clinical trial was funded by AbbVie and registered with clinicaltrials.gov as NCT03069365 (EXPEDITION‐5). [ABSTRACT FROM AUTHOR]

• 343 treatment-naïve patients with chronic HCV genotypes 1–6 and compensated cirrhosis. • Glecaprevir/pibrentasvir for 8 weeks achieved 99.7% virologic cure. • One patient experienced relapse at post-treatment week 4. • Efficacy did not depend on any pre-treatment patient or viral characteristics. • No drug-related serious adverse events or discontinuations due to adverse events occurred. Eight-week glecaprevir/pibrentasvir leads to high rates of sustained virological response at post-treatment week 12 (SVR12) across HCV genotypes (GT) 1–6 in treatment-naïve patients without cirrhosis. We evaluated glecaprevir/pibrentasvir once daily for 8 weeks in treatment-naïve patients with compensated cirrhosis. EXPEDITION-8 was a single-arm, multicenter, phase IIIb trial. The primary and key secondary efficacy analyses were to compare the lower bound of the 95% CI of the SVR12 rate in i) patients with GT1,2,4–6 in the per protocol (PP) population, ii) patients with GT1,2,4–6 in the intention-to-treat (ITT) population, iii) patients with GT1–6 in the PP population, and iv) patients with GT1–6 in the ITT population, to pre-defined efficacy thresholds based on historical SVR12 rates for 12 weeks of glecaprevir/pibrentasvir in the same populations. Safety was also assessed. A total of 343 patients were enrolled. Most patients were male (63%), white (83%), and had GT1 (67%). The SVR12 rate in patients with GT1–6 was 99.7% (n/N = 334/335; 95% CI 98.3–99.9) in the PP population and 97.7% (n/N = 335/343; 95% CI 96.1–99.3) in the ITT population. All primary and key secondary efficacy analyses were achieved. One patient (GT3a) experienced relapse (0.3%) at post-treatment week 4. Common adverse events (≥5%) were fatigue (9%), pruritus (8%), headache (8%), and nausea (6%). Serious adverse events (none related) occurred in 2% of patients. No adverse event led to study drug discontinuation. Clinically significant laboratory abnormalities were infrequent. Eight-week glecaprevir/pibrentasvir was well tolerated and led to a similarly high SVR12 rate as the 12-week regimen in treatment-naïve patients with chronic HCV GT1–6 infection and compensated cirrhosis. Trial registration: ClinicalTrials.gov, NCT03089944. This study was the first to evaluate an 8-week direct-acting antiviral (DAA) regimen active against all major types of hepatitis C virus (HCV) in untreated patients with compensated cirrhosis. High virological cure rates were achieved with glecaprevir/pibrentasvir across HCV genotypes 1–6, and these high cure rates did not depend on any patient or viral characteristics present before treatment. This may simplify care and allow non-specialist healthcare professionals to treat these patients, contributing to global efforts to eliminate HCV. [ABSTRACT FROM AUTHOR]

A simple, pangenotypic and effective treatment regimen for patients with a broad range of chronic hepatitis C virus (HCV) infections remains an unmet medical need. We conducted a phase 2, randomized, open study involving untreated patients with chronic HCV genotypes 1, 2, 3, or 6 infections. Patients without cirrhosis were randomly assigned in a 1:2 ratio to receive capsules of the NS5A inhibitor coblopasvir at a dose of 30 or 60 mg plus tablets of the nucleotide polymerase inhibitor sofosbuvir (400 mg) once daily for 12 weeks. Patients with cirrhosis received 60 mg coblopasvir plus sofosbuvir for 12 weeks. The primary endpoint was the sustained virologic response at 12 weeks after the end of therapy (SVR12). Of the 110 patients who were enrolled in the study, 59 were male, 62.7% had HCV genotype 1, 24.5% had genotype 2, 6.4% had genotype 3, and 6.4% had genotype 6. The average age was 45.5 years. A total of 10.9% of patients had compensated cirrhosis. The rate of SVR12 was 98.2% in the intention‐to‐treat (ITT). One genotype 6 patient with cirrhosis experienced virologic relapse. One genotype 2 patient without cirrhosis failed to complete the follow‐up and quit the study. Serious adverse events (SAEs) were reported in 2 patients and were not related to coblopasvir and sofosbuvir. Most adverse events (AEs) did not require treatment. Coblopasvir plus sofosbuvir taken once daily for 12 weeks provided high rates of sustained virologic response (SVR) and had a good safety profile among patients with HCV genotypes 1, 2, 3, or 6 infections, including those with compensated cirrhosis. [ABSTRACT FROM AUTHOR]

Background: In both Russia and Sweden, the dominant hepatitis C virus (HCV) is genotype 1, but around one-third of patients have genotype 3 infection. For such countries, HCV genotype testing is recommended prior to therapy. An effective pangenotypic therapy may potentially eliminate the need for genotyping. In this study, we evaluated the efficacy and safety of sofosbuvir/velpatasvir for 12 weeks in patients from Russia and Sweden. Methods: In an open-label, single-arm phase-3 study, patients could have HCV genotype 1–6 infection and were treatment-naïve or interferon treatment-experienced. All patients received sofosbuvir/velpatasvir, once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). Results: Of 122 patients screened, 119 were enrolled and treated. Overall, half (50%) were male, 18% had cirrhosis, and 24% had failed prior interferon-based therapy. In total, 66% of patients were infected with HCV genotype 1 (59% 1b and 7% 1a), 6% with genotype 2, and 29% with genotype 3. The overall SVR12 rate was 99% (118/119, 95% confidence interval 95–100%). One treatment-experienced patient infected with HCV genotype 3 experienced virologic relapse after completing treatment. The most common adverse events were headache (16%) and fatigue (7%). Serious adverse events were observed in four patients, but none were related to treatment. No patients discontinued treatment due to adverse events. Conclusion: Sofosbuvir/velpatasvir as a pangenotypic treatment for 12 weeks was highly effective in patients from Russia and Sweden infected with HCV genotypes 1, 2, or 3. Sofosbuvir/velpatasvir was safe and well-tolerated. Clinical trial number: ClinicalTrials.gov NCT02722837. [ABSTRACT FROM AUTHOR]

The study aimed to assess the phenomenon of achieving sustained virologic response (SVR) in patients with detectable ribonucleic acid (RNA) of hepatitis C virus (HCV) at the end of treatment (ET) with direct-acting antivirals (DAA), find how this is affected by the type of regimen, and how patients experiencing this differed from non-responders with detectable HCV RNA at the ET. The study included all consecutive patients with detectable HCV RNA at the ET selected from the EpiTer-2 database, a retrospective national multicentre project evaluating antiviral treatment in HCV-infected patients in 2015–2023. Of the 16106 patients treated with IFN-free regimens with available HCV RNA assessment at the ET and at follow-up 12 weeks after treatment completion (FU), 1253 (7.8%) had detectable HCV RNA at the ET, and 1120 of them (89%) finally achieved SVR. This phenomenon was significantly more frequent in pangenotypic regimens, 10.3% vs. 4.7% in genotype-specific options (p < 0.001), and the highest proportion was documented for glecaprevir/pibrentasvir (13.7%), and velpatasvir/sofosbuvir ± ribavirin (6.9%). Patients ET + FU- treated with these two pangenotypic regimens (n = 668) had less advanced liver disease, were less frequently infected with genotype (GT) 3, and were significantly more likely to be treatment-naïve than 61 non-responders. We documented 7.8% rate of patients with detectable HCV RNA at the ET, of whom 89% subsequently achieved SVR, significantly more frequently in the population treated with pangenotypic regimens. Less severe liver disease, more often GT3 infection, and a higher percentage of treatment-naive patients distinguished this group from non-responders. • Frequency of detectable HCV RNA at the end of DAA therapy and factors associated with this phenomenon were explored. • Detectable HCV RNA was documented in 8% of patients treated with DAA, more frequently in pangenotypic regimens. • SVR was achieved in 89% of patients with detectable HCV RNA at ET. • The highest SVR rate in patients with detectable HCV RNA (94%) was observed for GLE/PIB. • Non-responders were more likely to have severe liver disease, GT3 infection and were treatment-experienced. [ABSTRACT FROM AUTHOR]

Background & Aims Glecaprevir plus pibrentasvir (G/P) is a pangenotypic, once-daily, ribavirin-free direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection. In nine phase II or III clinical trials, G/P therapy achieved rates of sustained virologic response 12 weeks after treatment (SVR12) of 93–100% across all six major HCV genotypes (GTs). An integrated efficacy analysis of 8- and 12-week G/P therapy in patients without cirrhosis with HCV GT 1–6 infection was performed. Methods Data were pooled from nine phase II and III trials including patients with chronic HCV GT 1–6 infection without cirrhosis who received G/P (300 mg/120 mg) for either 8 or 12 weeks. Patients were treatment naïve or treatment experienced with peginterferon, ribavirin, and/or sofosbuvir; all patients infected with HCV GT 3 were treatment naïve. Efficacy was evaluated as the SVR12 rate. Results The analysis included 2,041 patients without cirrhosis. In the intent-to-treat population, 943/965 patients (98%) achieved SVR12 when treated for eight weeks, and 1,060/1,076 patients (99%) achieved SVR12 when treated for 12 weeks; the difference in rates was not significant ( p  = 0.2). A subgroup analysis demonstrated SVR12 rates > 95% across baseline factors traditionally associated with lower efficacy. G/P was well tolerated, with one DAA-related serious adverse event (<0.1%); grade 3 laboratory abnormalities were rare. Conclusions G/P therapy for eight weeks in patients with chronic HCV GT 1–6 infection without cirrhosis achieved an overall SVR12 rate of 98% irrespective of baseline patient or viral characteristics; four additional weeks of treatment did not significantly increase the SVR12 rate, demonstrating that the optimal treatment duration in this population is eight weeks. Lay summary In this integrated analysis of nine clinical trials, patients with chronic HCV genotype 1–6 infection without cirrhosis were treated for either 8 or 12 weeks with the direct-acting antiviral regimen glecaprevir/pibrentasvir (G/P). The cure rate was 98% and 99% following 8 and 12 weeks of treatment, respectively; the difference in rates was not significant ( p  = 0.2), nor was there a significant difference in the cure rates across the two treatment durations on the basis of baseline patient or viral characteristics. These results, along with a favourable safety profile, indicate that G/P is a highly efficacious and well-tolerated pangenotypic eight-week therapy for most patients with chronic HCV infection. [ABSTRACT FROM AUTHOR]

Background and Aim: Sofosbuvir is a nucleotide analog inhibitor of the hepatitis C virus (HCV) NS5B RNA polymerase with pangenotypic potency. This phase 3b study evaluated the safety and efficacy of sofosbuvir + ribavirin ± peginterferon in Chinese patients infected with HCV genotype 1, 2, 3, or 6. Methods: Patients with genotype 1 or 6 received sofosbuvir + peginterferon/ribavirin for 12 weeks or sofosbuvir + ribavirin for 24 weeks, depending on prior treatment and interferon eligibility. Patients with genotype 2 or 3 received sofosbuvir + ribavirin for 12 or 24 weeks, respectively. The primary endpoint was sustained virologic response at 12 weeks after the end of treatment (SVR12). Results: Of 389 patients, 42% had genotype 1, 16% genotype 2, 32% genotype 3, and 9% genotype 6. Half were male, 58% were treatment-naïve, and 15% had cirrhosis. SVR12 rates for patients receiving 12 weeks of sofosbuvir + peginterferon/ribavirin were 94% (95% confidence interval [CI], 87-98%) for HCV genotype 1 and 97% (95% CI, 84-100%) for genotype 6. SVR12 rates for those receiving sofosbuvir + ribavirin for 24 weeks were 95% (95% CI, 87-99%) for genotype 1, 100% (95% CI, 40-100%) for genotype 6, and 95% (95% CI, 90-98%) for genotype 3. For genotype 2 patients receiving sofosbuvir + ribavirin for 12 weeks, the SVR12 rate was 92% (95% CI, 83-97%). Twenty patients (5%) relapsed. Ten (3%) experienced serious adverse events. Three (< 1%) discontinued treatment because of adverse events, of whom one died because of treatment-unrelated adverse events. Conclusions: Sofosbuvir-based regimens were highly effective and safe in Chinese patients with HCV genotype 1, 2, 3, or 6, suggesting sofosbuvir could serve as the backbone for HCV treatment in China irrespective of genotype. [ABSTRACT FROM AUTHOR]

Background & Aims Hepatitis C virus (HCV) therapy that is highly efficacious, pangenotypic, with a high barrier to resistance and short treatment duration is desirable. The efficacy and safety of 8- and 12-week treatments with glecaprevir (ABT-493; NS3/4 A protease inhibitor) and pibrentasvir (ABT-530; NS5A inhibitor) were evaluated in non-cirrhotic patients with chronic HCV genotype 1–6 infection. Methods SURVEYOR-I and SURVEYOR-II were phase II, open-label, multicenter, dose-ranging trials including patients with chronic HCV genotype 1–6 infection who were either previously untreated or treated with pegylated interferon plus ribavirin. Patients received once-daily glecaprevir plus pibrentasvir at varying doses with or without ribavirin for 8 or 12 weeks. The primary efficacy endpoint was the percentage of patients with a sustained virologic response at post-treatment week 12 (SVR12). Results Of the 449 patients who received varying doses of glecaprevir plus pibrentasvir, 25%, 29%, 39%, and 8% had HCV genotype 1, 2, 3, and 4–6 infection, respectively. Twelve-week treatment achieved SVR12 in 97–100%, 96–100%, 83–94%, and 100% in genotypes 1, 2, 3, and 4–6, respectively. Eight-week treatment with 300 mg glecaprevir plus 120 mg pibrentasvir in genotype 1-, 2-, or 3-infected patients yielded 97–98% SVR12 with no virologic failures. Three (0.7%) patients discontinued treatment due to adverse events; most events were mild (grade 1) in severity. No post-nadir alanine aminotransferase elevations were observed. Conclusions Glecaprevir plus pibrentasvir was well tolerated and achieved high sustained virologic response rates in HCV genotypes 1–6-infected patients without cirrhosis following 8- or 12-week treatment durations. Lay summary The combination of direct-acting antivirals glecaprevir and pibrentasvir comprise a once-daily, all-oral, pangenotypic treatment for HCV genotype 1–6 infection. This article describes results from two phase II trials investigating a range of doses at treatment durations of 8 or 12 weeks in 449 patients without cirrhosis. Efficacy of the optimal dose, as determined by rates of sustained virologic response at post-treatment week 12, ranged from 92%-100%; treatment was well tolerated and significant laboratory abnormalities were rare. Clinical trial registration: clinicaltrials.gov Identifiers: NCT02243280 and NCT02243293. http:// www.clinicaltrials.gov/show/NCT02243280 , http://www.clinicaltrials.gov/show/NCT01939197 . [ABSTRACT FROM AUTHOR]

The introduction of the direct-acting antivirals (DAA) has substantially improved the effectiveness of the therapy in patients with chronic hepatitis C. We aimed to compare the efficacy of pangenotypic and genotype-specific DAA in the cohort of genotype (GT) four patients with HCV monoinfection and HIV coinfection. A total of 662 GT4-infected patients treated in 2015–2020—of whom 168 (25.3%) were coinfected with HIV, selected from the retrospective EpiTer-2 database—were enrolled in the analysis. Among HIV-coinfected patients, 54% (90) were treated with genotype-specific regimens and 46% (78) with pangenotypic options, while among HCV-monoinfected patients, the rates were 72% and 28%, respectively. Significantly higher rate of males (67.9% vs. 57.7%, p = 0.01), a lower rate of liver cirrhosis (10.2% vs. 18.1%, p = 0.02), and higher of treatment-naïve patients (87.5% vs. 76.7%, p = 0.003) were documented in the HIV coinfected population. The overall sustained virologic response after exclusion of non-virologic failures was achieved in 98% with no significant difference between HIV-positive and HIV-negative patients, 96.2% vs. 98.5%, respectively. While the genotype-specific regimens resulted in a similar cure rate regardless of the HIV status, the pangenotypic options were more efficacious in patients with HCV monoinfection (99.3% vs. 94.4%, p = 0.05). Hereby, we demonstrated the high effectiveness and good safety profile of the DAA therapy in the population of HCV GT4 infected patients with HIV coinfection supporting the current recommendations to treat HCV/HIV coinfected patients with the same options as those with HCV monoinfection. [ABSTRACT FROM AUTHOR]

There is still limited data available from real-world experience studies on the pangenotypic regimens in patients with genotype (GT) 3 hepatitis C virus (HCV) infection and liver cirrhosis. The current study aimed to evaluate the efficacy and safety of pangenotypic regimens in this difficult-to-treat population. A total of 236 patients with mean age 52.3 ± 11.3 years and male predominance (72%) selected from EpiTer-2 database were included in the analysis; 72% of them were treatment-naïve. The majority of patients (55%) received the combination of sofosbuvir/velpatasvir (SOF/VEL), 71 without and 58 with ribavirin (RBV), whereas the remaining 107 individuals were assigned to glecaprevir/pibrentasvir (GLE/PIB). The effectiveness of the treatment following GLE/PIB and SOF/VEL regimens (96% and 93%) was higher compared to SOF/VEL + RBV option (79%). The univariate analysis demonstrated the significantly lower sustained virologic response in males, in patients with baseline HCV RNA ≥ 1,000,000 IU/mL, and among those who failed previous DAA-based therapy. The multivariate logistic regression analysis recognized only the male gender and presence of ascites at baseline as the independent factors of non-response to treatment. It should be emphasized that despite the availability of pangenotypic, strong therapeutic options, GT3 infected patients with cirrhosis still remain difficult-to-treat, especially those with hepatic impairment and DAA-experienced. [ABSTRACT FROM AUTHOR]