Consenso Mexicano para el Tratamiento de la Hepatitis C

The aim of the Mexican Consensus on the Treatment of Hepatitis C was to develop clinical practice guidelines applicable to Mexico. The expert opinion of specialists in the following areas was taken into account: gastroenterology, infectious diseases, and hepatology. A search of the medical literature was carried out on the MEDLINE, EMBASE, and CENTRAL databases through keywords related to hepatitis C treatment. The quality of evidence was subsequently evaluated using the GRADE system and the consensus statements were formulated. The statements were then voted upon, using the modified Delphi system, and reviewed and corrected by a panel of 34 voting participants. Finally, the level of agreement was classified for each statement. The present guidelines provide recommendations with an emphasis on the new direct-acting antivirals, to facilitate their use in clinical practice. Each case must be individualized according to the comorbidities involved and patient management must always be multidisciplinary.     

The accuracy of baseline viral load for predicting the efficacy of elbasvir/grazoprevir in participants with hepatitis C virus genotype 1a infection: An integrated analysis

European treatment guidelines for hepatitis C virus (HCV) infection recommend that people with genotype (GT) 1a infection and baseline viral load ≤800 000 IU/mL receive elbasvir/grazoprevir (EBR/GZR) for 12 weeks, and those with baseline viral load >800 000 IU/mL receive EBR/GZR plus ribavirin for 16 weeks. This analysis was conducted to clarify whether baseline viral load can serve as an accurate, sensitive or specific stratification factor for defining EBR/GZR regimens. In this post hoc, integrated analysis, participants with GT1a infection who received EBR 50 mg/GZR 100 mg for 12 weeks were stratified according to baseline viral load. Sustained virologic response at 12 weeks post‐treatment was achieved by 95.2% (911/957) of participants and was higher among participants with baseline viral load ≤800 000 IU/mL vs >800 000 IU/mL (98.5% vs 93.9%). The 800 000 IU/mL threshold had a positive predictive value of 98.5%, a negative predictive value of 6.1%, a specificity of 91.3%, a sensitivity of 28.4% and an overall accuracy of 31.5%. A baseline viral load cutpoint of 800 000 IU/mL had high positive predictive value and specificity but poor negative predictive value, sensitivity and accuracy in predicting treatment outcomes in this population. Baseline NS5A resistance‐associated substitutions (RASs) were detected in 25% (1/4) of virologic failures with baseline viral load ≤800 000 IU/mL and 59.5% (25/42) of those with baseline viral load >800 000 IU/mL. Overall, these data suggest that, compared with the use of a baseline viral load cutpoint, baseline testing for NS5A RASs enables more individuals to receive the 12‐week EBR/GZR regimen without compromising the opportunity for SVR.     

Effectiveness and safety of elbasvir/grazoprevir therapy in patients with chronic HCV infection: Results from the Spanish HEPA‐C real‐world cohort

In randomized controlled trials of patients with chronic HCV infection, elbasvir/grazoprevir (EBR/GZR) demonstrated high cure rates and a good safety profile. This study assessed the effectiveness and safety of EBR/GZR, with and without ribavirin, in a real‐world HCV patient cohort. HEPA‐C is a collaborative, monitored national registry of HCV patients directed by the Spanish Association for the Study of the Liver and the Networked Biomedical Research Centre for Hepatic and Digestive Diseases. Patients entered into HEPA‐C between December 2016 and May 2017, and treated with EBR/GZR with at least end‐of‐treatment response data, were included. Demographic, clinical and virologic data were analysed, and adverse events (AEs) recorded. A total of 804 patients were included in the study. The majority were male (57.9%), with a mean age of 60 (range, 19‐92) years. Genotype (GT) distribution was GT 1, 86.8% (1a, 14.3%; 1b, 72.5%); GT 4, 13.2% and 176 patients (21.9%) were cirrhotic. Overall, among 588 patients with available data, 570 (96.9%) achieved sustained virologic response at 12 weeks post‐treatment (SVR12). SVR12 rates by genotype were GT 1a, 97.7%; GT 1b, 98.6%; and GT 4, 98.1%. No significant differences in SVR12 according to fibrosis stage were observed. Eighty patients experienced an AE, resulting in treatment discontinuation in three. In this large cohort of patients with chronic HCV managed in a real‐world setting in Spain, EBR/GZR achieved high rates of SVR12, comparable to those observed in randomized controlled trials, with a similarly good safety profile.     

Elbasvir and grazoprevir for chronic hepatitis C genotypes 1 and 4

Introduction: During the last few years, treatment of hepatitis C virus (HCV) revolutionized with the appearance of direct antiviral agents especially for patients with HCV genotypes 1 and 4 infections. Elbasvir (NS5A inhibitor) and grazoprevir (NS3/4A protease inhibitor) are newly developed drugs that are presented in fixed dose combination tablets.

Areas covered: This review covers the mechanism of action, pharmacokinetic and pharmacodynamics properties, clinical uses, safety and efficacy of elbasvir/grazoprevir in managing a wide variety of easy and difficult to treat populations (such as presence of cirrhosis, treatment experienced, co-infection with HIV and patients with inherited blood disorders).

Expert commentary: Elbasvir/grazoprevir combination showed great efficacy with high rates of sustained virological response rates in genotypes 1 and 4 HCV infection. In addition, it retained a good safety profile and is generally well tolerated.     

艾尔巴韦/格拉瑞韦治疗透析患者1b型丙型肝炎病毒感染的疗效——3例病例报告及文献复习

目的了解艾尔巴韦/格拉瑞韦治疗丙型肝炎病毒(HCV)1b型感染透析患者的临床疗效及不良反应。方法回顾性收集3例使用艾尔巴韦/格拉瑞韦抗病毒治疗的HCV 1b型感染透析患者的临床资料,查阅相关文献进行分析、总结。结果 2例血液透析及1例腹膜透析患者采用艾尔巴韦/格拉瑞韦抗病毒治疗,均获得持续病毒应答(SVR12),达到临床治愈标准。1例患者用药4周后出现明显血红蛋白下降,但在治疗12周时改善。1例患者新增疲乏表现,治疗结束后症状消失。治疗中3例患者均未因并发症而停药。结论使用艾尔巴韦/格拉瑞韦治疗合并HCV 1b型感染的血液透析及腹膜透析患者均有效,且无严重不良反应。     

艾尔巴韦/格拉瑞韦治疗透析患者1b型丙型肝炎病毒感染的疗效——3例病例报告及文献复习

目的 了解艾尔巴韦/格拉瑞韦治疗丙型肝炎病毒（HCV）1b型感染透析患者的临床疗效及不良反应。方法 回顾性收集3例使用艾尔巴韦/格拉瑞韦抗病毒治疗的HCV 1b型感染透析患者的临床资料，查阅相关文献进行分析、总结。结果 2例血液透析及1例腹膜透析患者采用艾尔巴韦/格拉瑞韦抗病毒治疗，均获得持续病毒应答（SVR12），达到临床治愈标准。1例患者用药4周后出现明显血红蛋白下降，但在治疗12周时改善。1例患者新增疲乏表现，治疗结束后症状消失。治疗中3例患者均未因并发症而停药。结论 使用艾尔巴韦/格拉瑞韦治疗合并HCV 1b型感染的血液透析及腹膜透析患者均有效，且无严重不良反应。     

Use of direct‐acting agents for hepatitis C virus‐positive kidney transplant candidates and kidney transplant recipients

In some parts of the world, hepatitis C virus (HCV) infection remains a huge problem for kidney transplant candidates and kidney transplant (KT) recipients. Until 2 years ago, anti‐HCV treatment for the general population relied on pegylated alpha‐interferon plus ribavirin, but led to a sustained viral response (SVR) in <50% of cases. This treatment was contraindicated in KT patients because of acute‐rejection issues and was poorly tolerated in patients with end‐stage renal disease (ESRD). Over the last year, direct‐acting antiviral agents (DAAs) have entered the market and are associated in the general population with a SVR of >90%, whatever the patient's HCV genotype. In KT patients, sofosbuvir‐based therapy is associated with a SVR at nearly 100% in patients with a HCV genotype‐1 infection, with almost no side effects and only mild interference with immunosuppressive drugs. Most HCV(+) patients with ESRD are genotype 1: in that setting, a recent study reported that the association of grazoprevir/elbasvir 100/50 mg/day led to a SVR of nearly 95% with very few side effects. Thus, it is concluded that DAAs can be safely used and lead to results in KT candidates and KT patients that are as good as those observed in the nonrenal population.