Continuous venovenous hemodiafiltration for hyperlactatemia caused by telbivudine in a patient with chronic hepatitis B: A case report and update review

Although there have been reports on telbivudine‐induced myopathy and creatine kinase (CK) elevation, few reports focus on its effect on hyperlactatemia in patients with chronic hepatitis B (CHB). Here we reported a case of hyperlactatemia during telbivudine treatment. A 26‐year‐old Chinese man had been receiving telbivudine for CHB since July 2011, with a CK level of 68 U/L before the antiviral therapy. After 3 months he felt muscular weakness in both upper and lower extremities. A check in the local clinic found his CK level was increased to 222 U/L (upper limit of normal 170 U/L). However, he did not visit his doctor or stop the telbivudine treatment until he felt myalgia throughout his body. By this time his CK level had increased to 4151 U/L. Even after the withdrawal of telbivudine, his myalgia was exacerbated and his CK level was decreased extremely slowly. His constant myolysis developed into hyperlactatemia and he finally recovered after successful venovenous hemodiafiltration. The findings in this patient suggest that telbivudine may lead to high CK levels and hyperlactatemia may occur if telbivudine is not discontinued immediately when CK levels are clearly increased. Moreover, we emphasized that serum CK and lactate levels should be monitored closely during treatment with telbivudine in patients with CHB.     

替比夫定(素比伏)体外抑制乙型肝炎病毒复制的研究

目的观察替比夫定体外对乙型肝炎病毒（HBV）复制的抑制作用。方法HBV复制子pHBV1．3质粒转染Huh7细胞,在转染细胞培养液中加入不同浓度的替比夫定,然后在不同时间段观察替比夫定的抗病毒作用。用ELISA检测培养上清中HBsAg、HBeAg水平,用荧光定量PCR（FQ—PCR）检测培养上清中HBVDNA拷贝数,用Southern blot分析转染细胞中HBV复制中间体。结果替比夫定减少了培养上清中HBsAg、HBeAg的表达及HBVDNA拷贝数,抑制了转染细胞中HBV复制中间体的形成。替比夫定对HBV复制子体外复制的抑制作用依赖于药物浓度及作用时间。结论替比夫定在体外对HBV有较强的抑制作用。     

Antiviral therapy decreases viral reactivation in patients with hepatitis B virus–related hepatocellular carcinoma undergoing hepatectomy: a randomized controlled trial

This prospective randomized controlled trial investigated whether antiviral therapy decreases the risk of perioperative viral reactivation in patients with hepatitis B virus–induced hepatocellular carcinoma. Patients with hepatitis B virus–related hepatocellular carcinoma undergoing liver resection were screened. Eighty‐four patients with low viral load were randomly assigned to receive either antiviral treatment with telbivudine or no therapy. The primary outcome was reactivation of viral replication. Secondary outcomes included liver function recovery and postoperative liver insufficiency. A total of 15 patients developed HBV reactivation during the perioperative period, of which 8 (57.1%) were within the first week after hepatectomy. The incidence of viral reactivation during the perioperative period was 2.5% (1/40) in the antiviral‐treated group, compared with 31.8% (14/44) in the control group [HR 0.07 (95%CI 0.01–0.65); P = 0.001]. Liver function recovery was achieved in 82.5% (33/40) patients in the antiviral group on day 30 after hepatectomy, compared with 91.0% (40/44) in the nonantiviral group [HR 1.23 (95%CI 0.98–2.55); P = 0.109]. A total of 7 patients (8.9%) had postoperative liver insufficiency in both groups, but there was no relevant difference between the two groups. Antiviral therapy with telbivudine can significantly decrease the perioperative reactivation of viral replication in patients with hepatitis B virus–related hepatocellular carcinoma undergoing liver resection. Antiviral therapy is an appropriate option for all patients with viral replication undergoing liver resection. (Chinese Clinical Trial Registry, number ChiCTR‐TRC‐0900615).     

Telbivudine: a new option for the treatment of chronic hepatitis B

Chronic hepatitis B virus (HBV) infection affects > 350 million individuals worldwide. Chronic hepatitis B is associated with complications of end-stage liver disease, including cirrhosis and hepatocellular carcinoma. HBV replication is the best predictor of liver disease progression to cancer, and antiviral therapy may diminish or halt this unfavorable outcome. Six drugs have been approved for the treatment of chronic hepatitis B: interferon-α_2b, pegylated interferon-α_2a, lamivudine, adefovir, entecavir and telbivudine. Most agents designed to target hepatitis B are hindered by the development of resistance, poor tolerability or limited efficacy; therefore, new agents and treatment strategies are needed. Telbivudine is the latest approved anti-HBV agent; it is an orally administered nucleoside analog that selectively inhibits HBV replication. It has demonstrated potent activity against HBV in Phase III clinical studies, with good tolerance, lack of mitochondrial toxicity and no dose-limiting side effects.     

Prevention of mother-to-child transmission of hepatitis B virus and hepatitis C virus

About 240 million people worldwide are chronically infected with hepatitis B virus (HBV). Vertical transmission is the most important mechanism of infection persistence in endemic areas. About 150 million people worldwide are chronically infected with hepatitis C virus (HCV). Mother-to-child transmission of HCV, which occurs in 3–10% of cases, is the leading route of infection in childhood. This review focuses on strategies to reduce the vertical transmission of HBV and HCV. The at-birth prophylaxis of newborns of HBV-infected mothers with specific immunoglobulin and vaccine plus administration of antivirals (tenofovir or telbivudine) in the third trimester of pregnancy (in case of high maternal viral load) greatly reduces the risk of transmission. In contrast, currently there is no drug able to reduce the vertical transmission of HCV infection. We discuss the possibility of reducing mother-to-child HCV transmission using newly available antivirals or antivirals in the pipeline for the treatment of hepatitis C.     

Monotherapy for hepatitis B infection: a review of treatment options

Chronic hepatitis B (CHB) is a global health problem, causing liver failure, cirrhosis and hepatocellular carcinoma. CHB treatment aims to prevent liver-related complication. The treatment of CHB infection includes monotherapy with either interferons (IFNs) or nucleos(t)ide (NUC) analogs. IFNs have moderate antiviral effects, and their use is limited by side effects. With the availability of NUCs, IFN-intolerant and decompensated cirrhotic patients began to be treated. Lamivudine and telbivudine, nucleoside analogs, have low genetic barrier to resistance. Adefovir, a nucleotide analog, has moderate potency and potential nephrotoxicity. Entecavir and tenofovir, with their high potency, high genetic barrier to resistance and favorable safety profile are the standard of care in CHB treatment. Long-term use of NUCs with maintained viral suppression results in a decrease in liver-related complications.     

替比夫定治疗慢性乙型肝炎临床疗效及影响因素的研究

目的：观察替比夫定抗乙型肝炎病毒的疗效并评估影响疗效的因素。方法：采用替比夫定治疗200例慢性乙型肝炎患者,分别于治疗前及治疗后12、24、48周进行病毒学、血清学及生化学指标的检测,观察抗病毒疗效并评估影响疗效的因素。结果：替比夫定治疗48周,HBV DNA转阴率为85.5%,HBeAg血清转换率为26.76%,ALT复常率为76%,耐药率为3.5%;HBeAg阴性患者的HBV DNA转阴率高于HBeAg阳性患者（P〈0.05）;基线ALT〉5×ULN患者的HBV DNA转阴率、HBeAg血清学转换率均高于ALT2～5×ULN的患者（P〈0.05）;治疗24周后HBV DNA转阴的患者与未转阴患者相比,其48周HBV DNA转阴、ALT复常和HBeAg血清转换的比例明显增高（P〈0.05）。治疗48周过程中,43.5%患者曾出现肌酸激酶（CK）升高,无1例发生严重不良事件而停药。结论：替比夫定能显著抑制HBVDNA复制,使ALT复常,促进HBeAg血清转换,且耐药率较低,是一种安全有效的抗病毒药物。     

Telbivudine: an effective anti-HBV drug for chronic hepatitis B patients with early on-treatment responses

Importance of the field: Hepatitis B virus (HBV) is a significant hepatocarcinogen. HBV replication is a major cause for the development of hepatocellular carcinoma (HCC). Past studies have documented that lamivudine (LAM) therapy deterred progression to cirrhosis and HCC. This risk reduction is attributed to effective viral suppression. There is a need for as many effective anti-HBV drugs as possible.

Areas covered in this review: Telbivudine, the fourth FDA-approved oral antiviral drug, is highly potent for viral suppression for HBV. It is more potent than LAM and adefovir; its therapeutic response is superior to that of LAM in both HBeAg-positive and -negative patients, and it produces higher HBeAg seroconversion in patients with baseline ALT ≥ 2 times normal. Telbivudine has a resistance rate lower than that of LAM and higher than that of entecavir or tenofovir.

What the reader will gain: There is a specific group of patients who are likely to achieve good therapeutic response with telbivudine.

Take home message: Patients with low baseline HBV DNA combined with negative HBV DNA at week 24 obtain good therapeutic results with telbivudine. Therefore, selecting patients who meet the above conditions is important.     

恩替卡韦与替比夫定治疗e抗原阳性慢性乙型肝炎患者24周疗效比较

目的观察比较恩替卡韦与替比夫定治疗e抗原阳性慢性乙型肝炎患者的近期疗效。方法将60例HBeAg阳性慢性乙型肝炎患者随机分为恩替卡韦组和替比夫定组,每组各30例,分别检测治疗前、治疗12周和24周时患者血清HBV DNA定量、HBV血清标志物及肝功能。结果治疗12周时,恩替卡韦和替比夫定组患者HBVDNA低于检测值的比例分别为76.7%和36.7%（P〈0.01）;HBVDNA较基线下降≥3log10copy/ml比例分别为90.0%和66.7%（P〈0.05）,HBV DNA降幅分别为（5.60±1.96）log10copy/ml和（4.47±1.41）log10copy/ml（P〈0.05）;HBeAg转阴率分别为46.7%与20.0%（P〈0.05）;HBeAg血清学转换率分别为36.7%和13.3%（P〈0.05）;ALT复常率分别为73.3%和53.3%（P〉0.05）。治疗24周时,两组HBV DNA低于检测值的比例分别为70.0%和60.0%（P〉0.05）;HBV DNA较基线下降≥3log10copy/ml比例分别为100.0%和80.0%（P〈0.05）;HBV DNA降幅分别为（5.60±1.68）log10copy/ml和（5.60±2.10）log10copy/ml（P〉0.05）;HBeAg转阴率分别为33.3%与26.7%（P〉0.05）;HBeAg血清学转换率分别为20.0%和26.7%（P〉0.05）;ALT复常率分别为90.0%和73.3%（P〉0.05）。24周综合疗效评价两组差异无统计学意义（P〉0.05）。除替比夫定组有1例出现临床耐药外,两组均未发生严重不良反应。结论恩替卡韦与替比夫定治疗HBeAg阳性慢性乙型肝炎的近期ALT复常率和综合疗效评价差异无统计学意义;12周时恩替卡韦抑制HBV DNA能力、HBeAg转阴率和HBeAg血清学转换率高于替比夫定,但24周时两组间差异基本无统计学意义。     

替比夫定治疗HBeAg阳性慢乙肝患者的HBeAg血清转换预测因素探讨

目的:观察替比夫定治疗HBeAg阳性慢性乙型肝炎52周的临床疗效并探讨HBeAg血清转换预测因素。方法:100例入组患者,口服替比夫定600 mg,每天1次,治疗52周进行疗效评估。以52周出现HBeAg血清转换有无为应变量,以年龄、性别、基线ALT、基线HBeAg、基线HBV DNA、治疗期间HBV DNA变化模式(12、24、36周HBV DNA低于检测下限)、治疗期间HBeAg变化模式(12、24、36周HBeAg下降>1 log及12、24、36周HBeAg下降>2 log)14个因素作为自变量进行多因素Lo-gistic回归分析。结果:替比夫定治疗52周完全病毒学应答率81%,HBeAg血清转换率31%,病毒学突破率4%。治疗52周时HBeAg血清转换与基线HBeAg值相关(P<0.01),而与基线ALT值和基线HBV DNA无相关性。其中基线HBeAg≤500 PEIU/ml与HBeAg>500 PEIU/ml的患者52周时HBeAg血清转换率有统计学差异(P<0.01)。多因素Logistic回归分析显示3个因素进入Logistic回归方程,按其作用强弱依次为:24周时HBeAg下降>2 log...