Sofosbuvir plus ribavirin with or without peginterferon for the treatment of hepatitis C virus: Results from a phase 3b study in China.

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.

Nationwide survey of specialist knowledge on current standard of care (Peg-IFN/RBV) and barriers of care in chronic hepatitis C patients in China.

BACKGROUND AND AIM: Chronic hepatitis C virus (HCV) infection is the leading cause of liver diseases including cirrhosis and hepatocellular carcinoma. In China, it is a major national health problem that demands nationwide coordinated emphasis on prevention and treatment. To inform these initiatives, a nationwide survey was conducted from January to April 2015 to evaluate the knowledge, awareness, and perceived obstacles to HCV care. METHODS: A sample of 1000 HCV specialists across mainland China were recruited. Respondents were asked a series of 30 open-ended single or multiple response and Likert-scale questions about their HCV treatment knowledge, experience, assessment of HCV care status in China, and perceptions about treatment barriers. RESULTS: Sixty percent of the respondents answered incorrectly to more than half of the questions on basic HCV treatment principles. Over half of them incorrectly believed that maintenance therapy should be prescribed for non-responders (72%) and longer treatment duration improved sustained viral response rates (62%), regardless of HCV RNA level changes. Sixty-six percent of them believed that HCV treatment would still be interferon-based therapy in the next 5 years in China. Patient-related barriers, in particular lack of disease awareness, were considered to be the most significant barriers to HCV care. Payer and medical-provider barriers included affordability issues, lack of reimbursement coverage for testing and treatments, and lack of referral to HCV specialists. CONCLUSIONS: Focused and intense patient and provider education should be carried out to increase awareness. More effective direct-acting antivirals should be made available and affordable in China.

Exploring the Diagnostic Potential of Serum Golgi Protein 73 for Hepatic Necroinflammation and Fibrosis in Chronic HCV Infection with Different Stages of Liver Injuries.

BACKGROUND AND AIM: Serum Golgi protein 73 (GP73) is a promising alternative biomarker of chronic liver diseases, but most data are from patients with HBV infection rather than HCV. MATERIALS AND METHODS: Two independent cohorts of chronic hepatitis C (CHC) patients from the 5th Medical Centre of the Chinese PLA General Hospital (n = 174) and Beijing Youan Hospital (n = 120) with different histories of HCV infection were enrolled. The correlations between serum GP73 and other biochemical indices, as well as its correlations with different stages of liver disease progression, were investigated. The receiver operating characteristic (ROC) curve was employed to evaluate the diagnostic potential of serum GP73 for liver necroinflammation and fibrosis, and comparisons of the diagnostic efficiency with traditional indices of hepatic liver injuries were further investigated. RESULTS: Levels of serum GP73 were found significantly elevated in patients with moderate to severe inflammatory grade (G ≥ 2) and/or with advanced fibrotic stages (F ≥ 3) in both cohorts (P < 0.05, respectively), as compared to those with a normal or mild liver lesion. Further ROC analysis demonstrated that serum GP73 was comparable to serum ALT and AST in diagnosing the liver necroinflammation grade at G ≥ 2, but its diagnostic values for advanced fibrosis (F ≥ 3) and cirrhosis (F = 4) were limited when compared to APRI and FIB-4, and FIB-4 exhibited the best performance. Notably, an obvious elevation of serum GP73 was observed after patients received PEG-IFN and ribavirin treatment. CONCLUSIONS: Serum GP73 is an important biomarker in evaluating and monitoring the disease progression including liver necroinflammation and fibrosis in patients with chronic HCV infection, but the value is limited for diagnosing advanced fibrosis and cirrhosis in comparison with APRI and FIB-4.

Current treatment status and barriers for patients with chronic HCV infection in mainland China: A national multicenter cross-sectional survey in 56 hospitals.

Chronic hepatitis C virus (HCV) infection is a serious public health problem worldwide. China, as the country with the largest number of HCV infections in the world, plays a significant role in eliminating hepatitis C. Due to different financial situations and education background, hepatitis C patients take different actions for their disease treatment and management. Therefore, antiviral treatment status should be attached great importance to learn the medical demand of patients. A nationwide, multicenter survey was conducted from July 2015 to June 2016. Of 1798 inpatients and outpatients with chronic HCV from 56 hospitals participated in the survey. Each patient completed the questionnaire with questions about his/her antiviral therapy status, perception of treatment barriers, and expectations for future treatment. In total 1622 patients, including 1241 with chronic hepatitis C, 344 with cirrhosis, and 37 patients with hepatocellular carcinoma, fulfilled data collection requirements and finally were included in analysis. Overall, up to 30.7% of the patients had not or currently does not intend to receive antiviral therapy. The main reason was expecting more potent and well-tolerance medication (31.5%), followed by the fear of interferon related side effects (27.5%). Multiple regression analysis showed that the patient's annual income, the severity of HCV, and comorbidity were independent predictors of not receiving antiviral therapy. The whole patients were expecting more potent and well tolerance medication available soon. In summary, Peg-IFN/RBV treatment regimen cannot meet the need of patients well, and safe and efficient direct-acting antivirals are urgently needed in mainland China.

Cationic Polystyrene Resolves Nonalcoholic Steatohepatitis, Obesity, and Metabolic Disorders by Promoting Eubiosis of Gut Microbiota and Decreasing Endotoxemia.

A pandemic of metabolic diseases, consisting of type 2 diabetes, nonalcoholic fatty liver disease, and obesity, has imposed critical challenges for societies worldwide, prompting investigation of underlying mechanisms and exploration of low-cost and effective treatment. In this report, we demonstrate that metabolic disorders in mice generated by feeding with a high-fat diet without dietary vitamin D can be prevented by oral administration of polycationic amine resin. Oral administration of cholestyramine, but not the control uncharged polystyrene, was able to sequester negatively charged bacterial endotoxin in the gut, leading to 1) reduced plasma endotoxin levels, 2) resolved systemic inflammation and hepatic steatohepatitis, and 3) improved insulin sensitivity. Gut dysbiosis, characterized as an increase of the phylum Firmicutes and a decrease of Bacteroidetes and Akkermansia muciniphila, was fully corrected by cholestyramine, indicating that the negatively charged components in the gut are critical for the dysbiosis. Furthermore, fecal bacteria transplant, derived from cholestyramine-treated animals, was sufficient to antagonize the metabolic disorders of the recipient mice. These results indicate that the negatively charged components produced by dysbiosis are critical for biogenesis of metabolic disorders and also show a potential application of cationic polystyrene to treat metabolic disorders through promoting gut eubiosis.