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Introduction: A pan-genotypic and effective treatment regimen for patients with chronic hepatitis C virus (HCV) infection remains an unmet medical need in China. Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. We conducted a phase 3 study to evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV infection. Methods: All patients received 600 mg alfosbuvir tablets plus 60 mg daclatasvir tablets once daily for 12 weeks. The primary endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). A follow-up visit was done at week 4 and 12, and those who achieved SVR12 were followed up at post-treatment week 24. Results: Of the 326 patients who received at least one dose of the study drug, 320 (98.2% [95% confidence interval (CI): 96.5%–99.5%]) achieved sustained virological response at post-treatment week 12 (SVR12), which was superior to the historical SVR12 rate of 88% (p < 0.0001). The SVR12 rates were similar regardless of most baseline characteristics. The most common adverse event (AE) (≥ 10%) was hypercholesterolemia. Serious adverse events (SAEs) were reported in 25 (7.7%) patients, none of which was judged to be related to the study drug. The majority of AEs were mild to moderate in severity. Conclusions: Alfosbuvir plus daclatasvir for 12 weeks was highly effective and safe in Chinese patients infected with HCV genotype 1, 2, 3, or 6, suggesting that this regimen could be a promising option for HCV treatment in China irrespective of genotype. Trial Registration: ClinicalTrial.gov identifier, NCT04070235. [ABSTRACT FROM AUTHOR]

Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. Our previous studies indicated that alfosbuvir monotherapy was well‐tolerated and druggable in healthy subjects and HCV‐infected patients. Here, we evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV genotype 1, 2, 3 or 6. In this open‐label study, patients with chronic HCV infection were randomly assigned with a 1:1:1 ratio to receive 12 weeks of daclatasvir 60 mg plus alfosbuvir at a dose of 400, 600 or 800 mg (Cohort A, B or C) daily. Randomization was stratified by HCV genotype and the presence or absence of cirrhosis at screening. The primary endpoint was a sustained virologic response 12 weeks after the end of treatment (SVR12). A total of 124 patients were enrolled in the study, all of whom were available for post‐treatment week 12 assessments. SVR12 was achieved in 92.7% (38/41), 95.2% (40/42) and 100% (41/41) of patients in Cohort A, B and C respectively. The most common adverse events were hepatic steatosis, upper respiratory tract infection, hypercholesterolaemia, hypertriglyceridaemia, blood bilirubin increased, and total bile acids increased. There were no discontinuations due to adverse events, and no treatment‐related serious adverse events were reported. Once‐daily oral administration of alfosbuvir plus daclatasvir were highly effective and safe in Chinese patients infected with HCV genotype 1, 2, 3 or 6, suggesting this regimen could be a promising drug candidate for HCV treatment irrespective of genotype. (ClinicalTrials.gov number, NCT04070235). [ABSTRACT FROM AUTHOR]

Background and Aim: This single‐arm, open‐label, multicenter, phase 3 trial evaluated the efficacy and safety of seraprevir, an hepatitis C virus (HCV) nonstructural protein 3/4A (NS3/4A) inhibitor, combined with sofosbuvir for treating Chinese patients with chronic HCV infection without cirrhosis. Methods: Treatment‐naive or interferon‐experienced adult patients without cirrhosis were treated with a universal, combinational regimen of seraprevir 100 mg, twice daily and sofosbuvir 400 mg, once daily, for 12 or 24 weeks. The primary efficacy endpoint was sustained virologic response at week 12 after treatment (SVR12). Results: Overall, 205 patients with genotype 1 HCV infection without cirrhosis were enrolled from 23 sites, 202 of whom completed the full treatment and post‐treatment course and 3 discontinued follow‐up. In total, 27 patients (13.2%) were interferon experienced. SVR12 was achieved by 201 out of 205 (98.0% [95% CI, 95.1%, 99.5%]) patients, 100.0% of patients with genotype 1a, and 98.0% of genotype 1b. In the other exploratory study, SVR 12 was achieved by 100% patients with genotype 2 (n = 21), genotype 3 (n = 7), and genotype 6 (n = 8). The majority of adverse events were mild to moderate and transient and did not require a specific medical intervention. Conclusions: The all‐oral, ribavirin‐free regimen of seraprevir and sofosbuvir is an effective and well‐tolerated treatment option for Chinese patients mono‐infected with HCV, including those with a history of interferon treatment. [ABSTRACT FROM AUTHOR]

Background & Aim: An affordable, pangenotypic regimen remains as an unmet medical need for chronic hepatitis C patients in China. This single‐arm, open‐label, multicenter, phase 3 trial evaluated the efficacy and safety of coblopasvir, a pangenotypic non‐structural protein 5A (NS5A) inhibitor, combined with sofosbuvir for treating Chinese patients with chronic hepatitis C virus (HCV) infection. Methods: Treatment‐naïve and interferon‐experienced adult patients, including those with advanced fibrosis (F3) or compensated cirrhosis (F4), were treated with a universal, combinational regimen of coblopasvir 60 mg and sofosbuvir 400 mg, once daily, for 12 weeks. The primary efficacy endpoint was sustained virological response at post‐treatment week 12 (SVR12). Results: Overall, 371 patients (men, 51%; age, 47 ± 11 years; genotype 1a < 1%, 1b 48%, 2a 26%, 3a 6%, 3b 7% and 6 12%) were enrolled from 19 sites. Fifty‐one patients (14%) had F3, 39 patients (11%) had F4 and 39 patients (11%) were interferon experienced. The overall SVR12 was 97% (95% CI, [94%, 98%]) for the full analysis set and was equal to or above 90% for all predefined subsets. Ten patients (3%) experienced virological relapse and two patients did not complete follow‐up. No adverse events (AEs) occurred at a frequency ≥5%, and the most often reported AEs (≥1%) were neutropenia and fatigue. The majority of AEs were mild to moderate and transient without specific medical intervention. Conclusions: The universal, pangenotypic combo of coblopasvir plus sofosbuvir is an efficacious and safe treatment for Chinese patients monoinfected with HCV of genotype 1, 2, 3 and 6, including those with compensated cirrhosis. Lay summary: The regimen of coblopasvir and sofosbuvir is a safe and effective treatment for Chinese patients with genotype 1, 2, 3 and 6 HCV infection, including those with compensated cirrhosis. Therefore, this regimen would be a novel choice of treatment for this patient population. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) infection is a public health issue for which an effective universal screening method is urgently needed. An oral anti-HCV test could provide a noninvasive and rapid screening strategy for HCV infection. This study evaluated the performance of a new point-of-care oral assay developed by Well for the detection of HCV antibody. Methods: Individuals from three centers with and without HCV infection were enrolled. All participants were tested for oral HCV antibody using the Well assay and for serum HCV antibody using established tests (ARCHITECT i2000 anti-HCV assay and InTec serum anti-HCV assay). For participants who obtained positive results, HCV RNA was tested for verification. Some patients underwent the OraQuick HCV test at the same time, and some self-tested with the Well assay during the same period. Results: A total of 1179 participants, including 486 patients with chronic HCV infection, 108 patients with other liver diseases, and 585 individuals who underwent physical examination, were enrolled. The Well anti-HCV test had a sensitivity of 91.88% (95% confidence interval [CI]: 88.97–94.09%) and a specificity of 98.00% (96.58–98.86%) for oral HCV antibody detection. The consistency between the Well and InTec assays was 97.02% (1138/1179). The consistency between the Well and OraQuick assays was 98.50% (197/200). Furthermore, the results of self-testing were highly consistent with those of researcher-administered tests (Kappa = 0.979). In addition, the HCV RNA results also showed that HCV RNA could only be detected on 1 of the 39 false-negative samples, and for 172 positive HCV RNA results, 171 could be detected by the Well oral anti-HCV assay. Conclusions: The Well oral anti-HCV test offers high sensitivity and specificity and performed comparably to both the OraQuick assay and InTec assay for HCV diagnosis. Thus, the Well test represents a new tool for universal HCV screening to identify infected patients, particularly in regions with limited medical resources. [ABSTRACT FROM AUTHOR]

Recently, the dinucleotide variant ss469415590 (TT/ΔG) in a novel gene, interferon lambda 4 ( IFNL4 ), was identified as a stronger predictor of hepatitis C virus (HCV) clearance in individuals of African ancestry compared with rs12979860. We aimed to determine whether this variant contributes to treatment decisions in a Chinese population. A total of 447 chronic hepatitis C (CHC) patients (including 328 treated with interferon alpha-2b and ribavirin), 129 individuals who had spontaneously cleared HCV (SHC), and 169 healthy controls were retrospectively investigated. ss469415590 genotyping was performed using a mass spectrometry method (SEQUENOM). A higher proportion of SHC individuals carried the TT/TT genotype compared with CHC patients (95.3% vs. 88.8%, P = 0.027). In patients with HCV genotype 1b, the ss469415590 variant was independently associated with sustained virologic response (SVR) (odds ratio [OR] = 3.247, 95% confidence interval [CI] = 1.038–10.159, P = 0.043) and on-treatment virological responses, including rapid (RVR), complete early (cEVR), early (EVR), and end-of-treatment (ETVR), with a minimal OR of 3.73. Especially for patients with high viral load (≥ 4 × 10 5 IU/ml), ΔG allele carriers had a lower chance of achieving SVR compared with those carrying the TT/TT genotype (7.1% vs. 36.0%, P = 0.034, OR [95% CI] = 7.24 [1.02–318.45], negative predictive value = 92.9%). In patients with HCV genotype 2a, no significant association between the ss154949590 variant and the virological response was identified ( P > 0.05). Additionally, we found that ss154949590 was in complete linkage disequilibrium with rs12979860. In conclusion, the IFNL4 ss154949590 TT/TT genotype favors spontaneous clearance of HCV. This same variant is associated with treatment-induced clearance in patients with genotype 1b, but not 2a. ss469415590 (or rs12979860) genotyping should be considered for patients with HCV genotype 1b and high viral load when making a choice between standard dual therapy and an IFN-free direct-acting antiviral regimen. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infections contributes to a substantial proportion of liver disease worldwide. The aim of this study was to assess the clinical and virological features of HBV-HCV co-infection. Methods: Demographic data were collected for 3238 high-risk people from an HCV-endemic region in China. Laboratory tests included HCV antibody and HBV serological markers, liver function tests, and routine blood analysis. Anti-HCV positive samples were analyzed for HCV RNA levels and subgenotypes. HBsAg-positive samples were tested for HBV DNA. Results: A total of 1468 patients had chronic HCV and/or HBV infections. Among them, 1200 individuals were classified as HCV mono-infected, 161 were classified as HBV mono-infected, and 107 were classified as co-infected. The HBV-HCV co-infected patients not only had a lower HBV DNA positive rate compared to HBV mono-infected patients (84.1% versus 94.4%, respectively; P<0.001). The median HCV RNA levels in HBV-HCV co-infected patients were significantly lower than those in the HCV mono-infected patients (1.18[Interquartile range (IQR) 0–5.57] versus 5.87[IQR, 3.54–6.71] Log10 IU/mL, respectively; P<0.001). Furthermore, co-infected patients were less likely to have detectable HCV RNA levels than HCV mono-infected patients (23.4% versus 56.5%, respectively; P<0.001). Those HBV-HCV co-infected patients had significantly lower median HBV DNA levels than those mono-infected with HBV (1.97[IQR, 1.3–3.43] versus 3.06[IQR, 2–4.28] Log10 IU/mL, respectively; P<0.001). The HBV-HCV co-infection group had higher ALT, AST, ALP, GGT, APRI and FIB-4 levels, but lower ALB and total platelet compared to the HBV mono-infection group, and similar to that of the HCV mono-infected group. Conclusion: These results suggest that co-infection with HCV and HBV inhibits the replication of both viruses. The serologic results of HBV-HCV co-infection in patients suggests more liver injury compared to HBV mono-infected patients, but is similar to HCV mono-infection. [ABSTRACT FROM AUTHOR]