Management of hepatitis C virus infection in hemodialysis patients

The prevalence of hepatitis C virus(HCV) infection in patients on maintenance hemodialysis(MHD) is relatively higher than those without MHD. Chronic HCV infection detrimentally affects the life quality and expectancy, leads to renal transplant rejection, and increases the mortality of MHD patients. With the application of erythropoietin to improve uremic anemia and avoid blood transfusion, the new HCV infections during MHD in recent years are mainly caused by the lack of stringent universal precautions. Strict implementation of universal precautions for HCV transmission has led to markedly decreased HCV infections in many hemodialysis units, but physicians still should be alert for the antiHCV negative HCV infection and occult HCV infection in MHD patients. Standard interferon alpha and pegylated interferon alpha monotherapies at a reduced dose arecurrently the main treatment strategies for MHD patients with active HCV replication, but how to increase the sustained virological response and decrease the side effects is the key problem. IFNα-free treatments with two or three direct-acting antivirals without ribavirin in MHD patients are waiting for future investigations.

Validation of the Nanjing Criteria for Diagnosing Pyrrolizidine Alkaloids-induced Hepatic Sinusoidal Obstruction Syndrome

Background and Aims:Hepatic sinusoidal obstruction syndrome(HSOS)is caused by toxic injury to sinusoidal endothelial cells in the liver.The intake of pyrrolizidine alkaloids(PAs)in some Chinese herbal remedies/plants remains the major etiology for HSOS in China.Recently,new diagnostic criteria for PA-induced HSOS(i.e.PA-HSOS)have been developed;however,the efficacy has not been clinically validated.This study aimed to assess the performance of the Nanjing criteria for PA-HSOS.Methods:Data obtained from consecutive patients in multiple hospitals,which included 86 PA-HSOS patients and 327 patients with other liver diseases,were retrospectively analyzed.Then,the diagnostic performance of the Nanjing criteria and simplified Nanjing criteria were evaluated and validated.The study is registered in www.chictr.org.cn(ID:ChiCTR1900020784).Results:The Nanjing criteria have a sensitivity and specificity of 95.35%and 100%,respectively,while the simplified Nanjing criteria have a sensitivity and specificity of 96.51%and 96.33%,respectively,for the diagnosis of PA-HSOS.Notably,a proportion of patients with Budd-Chiari syndrome(11/49)was misdiagnosed as PA-HSOS on the basis of the simplified Nanjing criteria,and this was mainly due to the overlapping features in the enhanced computed tomography/magnetic resonance imaging examinations.Furthermore,most of these patients(10/11)had occlusion or thrombosis of the hepatic vein,and communicating vessels in the liver were found in 8/11 patients,which were absent in PA-HSOS patients.Conclusions:The Nanjing criteria and simplified Nanjing criteria exhibit excellent performance in diagnosing PA-HSOS.Thus,both could be valuable diagnostic tools in clinical practice.

Efficacy and Safety of 12-week Interferon-based Danoprevir Regimen in Patients with Genotype 1 Chronic Hepatitis C

Background and Aims:Genotype(GT)1 remains the predominant hepatitis c virus(HCV)GT in Chinese patients.Over 80%of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860,which is favorable for interferon-based treatment regimens.This phaseⅢclinical trial aimed to evaluate the efficacy and safety of the ritonavirboosted danoprevir plus pegylated-interferonα-2a and ribavirin regimen for 12 weeks in treatment-na(i)ve mainland Chinese patients infected with HCV GT1 without cirrhosis.Methods:One hundred and forty-one treatment-na(i)ve,non-cirrhotic HCV GT1 Chinese patients(age≥18 years)were enrolled for this single-arm,multicenter,phaseⅢMANASA study(NCT03020082).Patients received a combination of ritonavir-boosted danoprevir(100 mg/100 mg)twice a day plus subcutaneous injection of weekly pegylated-interferonα-2a(180μg)and oral ribavirin(1000/1200 mg/day body weight<75/≥75 kg)for 12 weeks.The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment.The secondary end-points were safety outcomes,tolerability,virologic response over time and relapse rate.Results:All enrolled patients were HCV GT1-infected,and most among them(97.9%,123/141)had the HCV GT1b subtype.Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype(87.2%,123/141).Overall,140 patients completed the 12-week treatment,and 97.1%(136/140)patients achieved sustained virologic response at 12 weeks(per protocol population group,95%confidence interval:92.9-99.2%).Only drug-related serious adverse event occurred.Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction.One patient discontinued treatment because of severe head injury in a car accident.Conclusions:The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferonα-2a and ribavirin produced a sustained virologic response rate of 97.1%after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients,and was safe and well tolerated.