Long-term efficacy and safety of switching from lamivudine + adefovir to tenofovir disoproxil fumarate in virologically suppressed patients

Background and AimTenofovir disoproxil fumarate (TDF) is recommended as first-line monotherapy for nucleos(t)ide (NA)-naïve chronic hepatitis B (CHB) patients and as a second-line rescue therapy for NA-experienced patients with a previous treatment failure. However, data regarding the efficacy of TDF monotherapy in patients with lamivudine resistance (LAM-R) successfully treated with LAM + adefovir (ADV) are limited. Herein, the efficacy and safety of switching from LAM + ADV to TDF monotherapy in clinical practice have been evaluated.MethodsSixty LAM-R HBeAg-negative CHB patients treated with ADV add-on therapy and stable viral suppression, were switched to TDF monotherapy and prospectively evaluated for virological response, liver and renal function, and bone mineral density.ResultsDuring a median period of 57 months of TDF monotherapy, all patients maintained a virological response, four of whom cleared HBsAg (6.6%) and discontinued treatment. Monitoring of renal function showed no case of the Fanconi syndrome, no significant alterations of median serum creatinine, eGFR and phosphate levels, although a reduction of TDF dosage was required in five patients (8.3%). Despite the stable virological suppression, five cirrhotic patients and one CHB patient developed hepatocellular carcinoma.ConclusionsOur results demonstrate the efficacy of switching to TDF monotherapy in virologically suppressed CHB patients receiving long-term LAM + ADV therapy, with a low rate of adverse events.     

替诺福韦酯单独与联合恩替卡韦挽救治疗恩替卡韦治疗拉米夫定经治慢性乙型肝炎失败患者疗效比较

目的比较替诺福韦酯单药与联合恩替卡韦对恩替卡韦治疗慢性乙型肝炎拉米夫定经治患者仍应答不佳或发生病毒学突破的挽救方案的临床疗效及安全性。方法将80例恩替卡韦序贯治疗仍效果欠佳的拉米夫定经治慢性乙型肝炎患者随机分为单药组40例和联合组40例。单药组给予替诺福韦酯(300 mg/d)替换治疗;联合组使用替诺福韦酯(300 mg/d)和恩替卡韦(0.5 mg/d)治疗。所有患者均治疗48周,检测基线,治疗12、24和48周时病毒学、生化学、血清学指标。比较两组患者上述治疗时间点的完全病毒学应答率、ALT复常率、病毒学突破率和HBeAg血清学转换率及观察药物不良反应。结果单药组患者治疗48周后完全病毒学应答率、ALT复常率、病毒学突破率、HBeAg血清学转换率分别为85.0%(34/40)、76.2%(16/21)、0、13.1%(3/23),联合组分别为87.5%(35/40)、77.3%(17/22)、0、16.0%(41/25),两组比较差异无统计学意义(均P0.05)。两组患者耐受性均良好,无一例出现严重不良反应而导致停药。结论对于恩替卡序贯治疗后仍应答不佳或发生病毒学突破的拉米夫定经治慢性乙型肝炎患者,替诺福韦酯单药替换恩替卡韦的挽救治疗仍能有效抑制HBV DNA复制,是一种行之有效的优化治疗方案。     

Prevention of vertical transmission of hepatitis B virus infection

Hepatitis B virus (HBV) is the leading cause of chronic viral hepatitis. Annually, almost two million children younger than 5 years acquire the infection, mostly through vertical or horizontal transmission in early life. Vertical transmission of HBV is a high efficacy phenomenon ranging, in the absence of any preventive interventions, from 70% to 90% for hepatitis e antigen positive mothers and from 10% to 40% for hepatitis e antigen-negative mothers. Maternal viraemia is a preeminent risk factor for vertical transmission of HBV. Maternal screening is the first step to prevent vertical transmission of HBV. Hepatitis B passive and active immunoprophylaxis at birth together with antiviral treatment of highly viraemic mothers are the key strategies for global elimination of HBV infection. Strategies are needed to promote implementation of birth-dose vaccination and hepatitis B immunoglobulins in low- and middle-income countries where the prevalence of the infection is at the highest.     

Management of hepatitis B and C in special population

Chronic viral hepatitis is one of the leading causes of cirrhosis worldwide. Chronic hepatitis B is more common in the Asia-Pacific region due to the larger population and lower screening availability. Hepatitis C predominates in the west due to injection drug abuse. The discovery of (oral) direct-acting antiviral agents (DAAs) has changed the landscape of chronic hepatitis C (CHC) management. Nucleos(t)ide analogs (NUCs) have also changed the approach to the treatment of chronic hepatitis B (CHB). Oral NUCs and DAAs have excellent efficacy and patient acceptance as well as a lower risk of resistance. However, certain populations have no robust data and safety and efficacy of such oral drugs is still evolving. In this review, we provide an overview of the management of CHB and CHC in special populations, such as those with chronic kidney disease, pregnant women, healthcare workers, and those undergoing chemo- or immunosuppressive therapy.     

Documento de consenso de la Asociación Española para el Estudio del Hígado sobre el tratamiento de la infección por el virus de la hepatitis B (2020)

Hepatitis B virus (HBV) infection remains a global public health problem. HBV vaccination is the most effective tool to reduce the incidence of HBV disease. Despite there has not been new clinical developments for the treatment of chronic hepatitis B in the last few years, changing epidemiology and current insights on natural history, diagnostic tools and therapy indications make necessary an update of the former version of the consensus document of the Spanish Association for Study of the Liver on the treatment of hepatitis B infection published in 2012. The current document updates the management of chronic hepatitis B. The treatment of choice is the long-term administration of a nucleos(t)ide analogue with high barrier to resistance (entecavir, tenofovir or tenofovir alafenamide). Pegylated interferon may be an option in patients with non-advanced liver disease, but its applicability is limited due to the low efficacy and poor tolerability. All patients must be monitored for the risk of progression to advanced liver disease and development of hepatocellular carcinoma.     

替诺福韦联合苄星青霉素在阻断乙肝合并梅毒感染患者母婴传播中的效果

目的探讨替诺福韦联合苄星青霉素在阻断乙肝合并梅毒感染患者母婴传播中的效果。方法选取2016年1月至2018年1月百色市人民医院诊治的70例乙肝合并梅毒患者为研究对象,按照入院先后排序,单数序号患者设为研究组,双数序号患者设为对照组,每组35例患者。研究组患者给予替诺福韦联合苄星青霉素治疗,对照组患者给予常规保肝联合苄星青霉素治疗。在孕晚期对两组患者进行治疗后的效果评定。在分娩后对两组新生儿进行是否为先天性梅毒儿的检测和判定;在6个月时对两组婴儿检测HBsAg阳性表达率。结果对两组患者治疗后的效果显示,研究组患者梅毒治疗有效率(91.4%)高于对照组(88.6%),其差异无统计学意义(P>0.05);研究组患者乙肝治疗有效率(94.3%)高于对照组(80.0%),其差异具有统计学意义(P<0.05)。研究组正常新生儿比例(82.9%)高于对照组(51.4%),其差异具有统计学意义(P<0.05);研究组先天梅毒儿比例(8.6%)低于对照组(14.3%),其差异无统计学意义(P>0.05);研究组6个月婴儿HBsAg阳性率(5.7%)低于对照组(22.9%),其差异具有统计学意义(P<0.05)。结论替诺福韦联合苄星青霉素在阻断乙肝合并梅毒感染患者母婴传播中具有较好的治疗效果,值得临床推广。     

Predictive factors of renal impairment in HIV-infected patients on antiretroviral therapy: Results from the VACH longitudinal cohort study

BackgroundThe use of combination antiretroviral therapy has led to dramatic improvements in the life expectancy of HIV-infected persons. As result, the HIV population is aging and increasingly facing illnesses typically seen in the elderly, such as chronic kidney disease (CKD).MethodsA retrospective longitudinal study was conducted using data from years 2010 and 2014 in all HIV-infected persons enrolled at the Spanish VACH cohort. We analyzed the prevalence and the predictive factors for developing CKD (estimated glomerular filtration rate, eGFR < 60 mL/min/1.73 m²).ResultsThe CKD prevalence at baseline was 456/8968, 5.1% [4.6–5.6%]. Of 8512 HIV-positive individuals examined without CKD at baseline (73.7% male, median age 44 years-old), 2.15% developed CKD (eGFR < 60 mL/min/1.73 m²). The odds ratios [95%CI] for the independent predictive factors identified were gender (male) 0.54 [0.39–0.75], age (per year) 1.08 [1.07–1.10], AIDS diagnosis 1.40 [1.03–1.91], protease inhibitor-based regimens 1.49 [1.10–2.02], hypertension 1.37 [0.94–1.99], diabetes 1.84 [1.33–2.55] and history of cardiovascular events 1.66 [0.96–2.86].ConclusionThe prevalence and risk factors for CKD and its progression are high in the VACH cohort. Thus, preventive measures such as control of hypertension, diabetes and obesity, as well as efforts for avoiding exposure to nephrotoxic drugs, including some antiretrovirals, are warranted in this aging HIV population.     

A simple stability indicating RP-HPLC-DAD method for concurrent analysis of Tenofovir Disoproxil Fumarate,Doravirine and Lamivudine in pure blend and their combined film coated tablets

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暴露前预防:探索适合中国的HIV预防策略

暴露前预防(PrEP)是国际指南推荐预防HIV感染的主要方式之一,在我国受到越来越多的关注。2019年,恩曲他滨联合丙酚替诺福韦(F/TAF)在美国获批成为继恩曲他滨联合富马酸替诺福韦二吡呋酯(F/TDF)后,第二个可用于PrEP的药物。本文结合最新国际指南、PrEP临床研究数据和我国实际情况,讨论PrEP在我国临床运用中的考量和挑战,并对提高PrEP认知、可及性、可负担性及用药依从性提出具体建议。