[英语，临床 ]Kidney Toxicity Uncommon among People Taking Tenofovir for Hep

StephenW

Kidney  Toxicity Uncommon among People Taking Tenofovir for Hepatitis  B
               

SUMMARY:   People taking tenofovir to treat chronic hepatitis B seldom           experience kidney impairment, and this population does not    appear predisposed to bone problems, researchers reported  at EASL 2011.

By Liz Highleyman
              
              

Tenofovir (Viread, also in the Truvada andAtripla  coformulations) is highly effective in treating hepatitis B virus (HBV), but it can potentially cause kidney problems in susceptible individuals and may lead to bone loss over time. At  the European Association for the Study of the Liver's International Liver Congress (EASL 2011) this month in Berlin, investigators presented findings from 2 studies of tenofovir side effects in people treated for hepatitis B.
                  
                   Kidney  Function[
                  
                  Patrick Marcellin and colleagues analyzed the effect of tenofovir on kidney function among 675 chronic hepatitis B patients in 3   large randomized clinical trials, Gilead's Study 102, 103, and 106. The first 2 studies compared tenofovir vs adefovir (Hepsera)  for 48 weeks, then patients could continue open-label tenofovir through 8 years. Study 106 compared tenofovir alone vs tenofovir  plus emtricitabine (Emtriva). These studies included only HIV  negative people; another analysis presented at EASL looked at  HIV/HBV coinfected patients.
                  
Overall, about 75% of study participants were men, nearly 60%  were white, about 30% were Asian, and less than 5% were black.The median age was 41 years and more than three-quarters were younger than 50. Just over 40% were hepatitis B "e" antigen (HBeAg) positive. Some patients had and some had not  previously used adefovir, a related nucleotide analog that can also cause kidney toxicity.
                  
With regard to other kidney risk factors, about 15% had a history  of hypertension (high blood pressure) and about 5% had diabetes.At baseline, less than 1% had poor creatinine clearance (< 50 mL/min) and about 8% had somewhat impaired clearance (50-80      mL/min).
                  
Researchers analyzed data collected through 144 weeks, evaluating kidney function based on serum creatinine and estimated glomerular  filtration rate (eGFR) using the Cockcroft-Gault equation. Kidney events were defined as either a confirmed increase in serum creatinine by at least 0.5 mg/dL from baseline or confirmed eGFR < 50 mL/min.
                  
Among 426 treatment-naive patients receiving tenofovir, there was a low incidence of kidney events through 144 weeks of treatment. No treatment-naive study participants had confirmed eGFR <   50 mL/min; 2 patients (0.5%) had at least a 0.5 mg/dL increase            in creatinine. Results did not differ significantly between subgroups with and without hypertension or diabetes.
                  
Among 249 adefovir-experienced study participants, 1 person   (0.4%) had confirmed eGFR < 50 mL/min and 3 (1.2%) experienced at least a 0.5 mg/dL increase in creatinine. Again, results  were similar for patients with and without hypertension or diabetes,           though numbers were small.
                  
Based on these findings, the researchers concluded, "Tenofovir monotherapy over 144 weeks was safe and well tolerated without clinically relevant changes in renal function across a broad range of patient populations including those with co-morbidities                   typically associated with renal impairment."
Overall,  they continued, "few patients experienced a decline in  renal function." Taken together, 5 of 675 patients (0.7%) had at least a 0.5 mg/mL increase in creatinine (including 3 with pre-existing hypertension and 1 with pre-existing diabetes).                   Just 1 patient (0.1%), who had pre-existing hypertension, had an eGFR decline to < 50mL/min.
                  
The investigators noted, however, that the lack of a placebo  group in these long-term studies -- as opposed to a control group that took a different potentially kidney-toxic drug --"makes conclusions concerning the potential role of tenofovir  in decreasing renal function more difficult to assess."
                  
                   Bone  Loss
                  
                  As  described in a related poster, an international team of investigators  looked at prevalence of bone problems among chronic hepatitis  B patients.
                  
Metabolic bone disease is a known potential complication among people with chronic liver disease. Since tenofovir has been linked to bone loss, it would be useful to know how many people in the hepatitis B patient population might be especially prone   to this side effect.
                  
Gilead's Study GS-US-174-0121 randomly assigned 250 lamivudine  (Epivir-HBV)-resistant chronic hepatitis B patients to receive  either tenofovir alone or tenofovir plus emtricitabine. About  75% were men, the median age was 48 years, 60% were white, 35%  were Asian, 48% were HBeAg positive, and the average body mass index was 25.1; less than 2% had thyroid disease or a history of past fractures.
                  
Study participants underwent dual energy x-ray absorptiometry (DEXA) scans of the spine and hip prior to starting study drugs. The researchers found that more people had reduced bone mineral density according to baseline DEXA scans than had bone loss  reported in their medical records; 6 had osteopenia, or low  bone density, while 4 had more severe osteoporosis.
There was some indication that duration of chronic HBV infection and HBeAg status may contribute to greater risk of reduced bone density, but duration of treatment with lamivudine or adefovir  did not appear to have an effect.
                  
"In our study, baseline median Z- and T- scores [standard measures of bone density] suggest that males and Asians have  greater reductions in bone mineral density compared to females  and non-Asians," the researchers reported.
                  
"Our data demonstrate a higher prevalence of baseline bone disease among patients with chronic HBV," they concluded."Duration of chronic HBV but not duration of treatment           appears to impact bone mineral density."
                  
  Investigator affiliations:
                  
Marcellin et al: Hopital Beaujon, Clichy, France; Toronto Western  Hospital, University of Toronto, Toronto, Canada; Universitätsklinik   Leipzig, Leipzig, Germany; Gilead Sciences, Inc., Durham, NC;  Gilead Sciences, Inc., Foster City, CA.
                  
Fung et al: University Health Network, Toronto General Hospital, Toronto, Canada; Clinical Centre Vojvodina, Clinic of Infectious Diseases, Clinical Centre of Serbia, Novi Sad, Serbia; Toronto  Western Hospital, University Health Network, Toronto, Canada;                 Uludag University Medical Faculty Hospital, Bursa, Turkey; Hepatitis Program, Vancouver Hospital, Vancouver, BC, Canada; Prof. Dr.   Matei Bals Institute for Infectious Diseases, Bucharest, Romania; Faculty Hospital Brno and Faculty of Medicine, Masaryk University    Brno, Brno, Czech Republic; Clinical Department of Infectious Diseases, Silesian Medical School, Chorzów, Poland; Clinic for Infectious and Tropical Diseases, Belgrade, Serbia; Auckland City Hospital, Auckland, New Zealand; Gilead Sciences Inc.,                   Durham, NC.
4/19/11
References
P  Marcellin, EJ Heathcote, T Berg, et al. Effects of tenofovir   disoproxil fumarate on renal function in chronic HBV patients in three global randomized studies. 46th Annual Meeting of the  European Association for the Study of the Liver (EASL 2011). Berlin. March 30-April 3. Abstract 616.
S  Fung, M Fabri, F Wong, et al. Reduced bone mineral density derived from dual x-ray absorptiometry assessments in patients with  chronic hepatitis B (CHB). 46th Annual Meeting of the European Association for the Study of the Liver (EASL 2011). Berlin.           March 30-April 3. Abstract 175.

         

StephenW

少见在服用肾毒性乙型肝炎泰诺福韦人
摘要：人们服用泰诺福韦治疗慢性乙型肝炎的经验很少肾损害，这部分人口没有出现易患骨骼问题，研究人员在欧洲肝病学会2011年。

由Liz Highleyman
泰诺福韦（VIREAD的，也是在Truvada和Atripla coformulations）治疗高度乙型肝炎病毒（HBV）的有效，但它有可能导致易感个体肾脏问题，随着时间的推移可能导致骨质流失。

同时对于肝脏的国际肝病会议研究（欧洲肝病学会2011年）本月份在柏林欧洲协会，调查人员介绍，在人们从2泰诺福韦侧B型肝炎治疗效果的研究结果

肾功能

帕特里克Marcellin和同事分析了其中675例慢性乙型肝炎患者在3个大型随机临床试验中泰诺福韦对肾脏功能的影响，Gilead公司的研究102，103，106。前2个研究比较了48周泰诺福韦与阿德福韦（Hepsera），那么病人可以继续通过8年的开放标签泰诺福韦。研究单独与106相比泰诺福韦泰诺福韦和emtricitabine（Emtriva）。这些研究只包括艾滋病毒阴性的人;在欧洲肝病学会提出的另一个分析在艾滋病毒/乙型肝炎合并感染患者的照顾。

总体而言，约75％的研究对象是男性，近60％是白人，大约30％是亚洲人，只有不到5％是黑人。平均年龄为41岁和超过四分之三比50。刚刚超过40％是B型肝炎的“e”抗原（HBeAg）阳性。有些病人和一些以前没有使用阿德福韦，相关的核苷酸类似物，也可能导致肾毒性。

至于其他肾脏的危险因素，约15％有高血压（高血压），约5％有糖尿病史。在基线，少​​于1％的肌酐清除率差“（<50毫升/分），约8％有一定程度受损间隙（50-80毫升/分钟）。

研究人员分析了144周，通过收集数据，评估肾功能的血清肌酐和估计肾小球滤过率（eGFR）使用Cockcroft - Gault公式。肾脏事件被定义为血中肌酐证实至少增加0.5毫克/升或证实eGFR值从基线“50毫升/分钟。

在426治疗初治患者接受替诺福韦，有一个肾事件144周的治疗，通过低发病率。无治疗天真的研究对象已证实的eGFR“50毫升/分; 2例（0.5％）至少有一0.5毫克/升肌酐增加。结果没有差异显着亚组和无高血压或糖尿病。

在249阿德福韦经验丰富的研究对象，1人（0.4％）已证实的eGFR“50毫升/分钟和第3（1.2％）经历了至少0.5毫克/升肌酐增加。再次，结果为与无高血压或糖尿病患者类似，但数量不大。

基于这些发现，研究者总结说：“泰诺福韦超过144周单药治疗是安全且无临床相关的肾功能变化之间的患者人群广泛，包括与合作的发病率通常与肾功能受损有关不能容忍的。​​”

总体而言，他们继续说，“经历了几个病人肾功能衰退。”两者合计，5 675例（0.7％）至少有一0.5毫克/毫升增加肌酐（包括与预先存在的高血压与预先存在的糖尿病，1 3）。仅1例（0.1％），谁预先存在的高血压，有一个以<50mL/min的eGFR下降。

研究者指出，然而，这些中的一个长期研究安慰剂组的缺乏 - 而不是一个控制组，采取了不同的潜在的肾毒性药物 - “关于减少的结论，使肾的泰诺福韦的潜在作用功能更加难以评估。“

骨质流失

正如相关海报介绍，一国际研究小组的研究人员在慢性乙型肝炎患者中骨问题的发生。

代谢性骨病是一个已知的慢性肝病患者中的潜力并发症。由于泰诺福韦一直与骨质流失，这将是有益的知道如何在乙肝患者人群很多人可能要特别容易出现这种副作用。

Gilead公司的研究广深高速美- 174 - 0121随机分配250拉米夫定（拉米- HBV）的抗慢性乙型肝炎患者，接受替诺福韦单独或tenofovir和emtricitabine。约75％为男性，平均年龄为48岁，60％是白人，35％是亚洲人，48％为HBeAg阳性，平均身体质量指数为25.1，低于2％有甲状腺疾病或对过去的历史骨折。

研究对象接受双能X线骨密度仪（DEXA）的脊柱和髋关节扫描之前，要启动研究药物。研究人员发现，越来越多的人已经减少骨质密度扫描，根据基线DEXA的骨质流失比过去在他们的医疗记录报告; 6例骨质疏松或低骨密度，而4有较严重的骨质疏松症。

有一些迹象表明，慢性乙肝病毒感染和HBeAg状态的持续时间可能有助于降低骨骼密度更大的风险，但与拉米夫定或阿德福韦治疗期间并未产生效果。

“在我们的研究中，开始位数的Z -和T -分数[骨质密度标准措施]表明，男性和亚洲人的骨质密度较大相比，女性和非亚洲人，减”的研究人员报告。

“我们的数据表明，在慢性乙肝患者的基准​​骨骼疾病的发病率较高，”他们的结论。 “慢性乙肝病毒，但持续时间不治疗期间出现的影响骨质密度。”

调查背景：

Marcellin等：总医院Beaujon，克利希，法国;多伦多西区医院，多伦多大学，多伦多，加拿大; Universitätsklinik莱比锡，莱比锡，德国; Gilead Sciences公司，公司，达勒姆，数控; Gilead Sciences公司，公司，福斯特城，加利福尼亚。

凤等人：，多伦多总医院，加拿大多伦多大学健康网络;伏伊伏丁临床中心，传染病门诊，临床中心的塞尔维亚，诺维萨德，塞尔维亚;多伦多西区医院，大学健康网络，多伦多，加拿大; Uludag大学医学学院医院，布尔萨，土耳其;肝炎计划，温哥华医院，温哥华，不列颠哥伦比亚省，加拿大教授马太Bals传染病研究所，布加勒斯特，罗马尼亚;学院医院和医学院布尔诺，马萨里克大学布尔诺，布尔诺，捷克共和国;临床科室传染病，西里西亚医学院，霍茹夫，波兰;奥克兰市医院，奥克兰，新西兰;;公司Gilead Sciences公司，达勒姆，数控传染病和热带病，贝尔格莱德，塞尔维亚诊所。

4/19/11

参考文献

P Marcellin，EJ希思科特，T伯格等人。泰诺福韦影响肾功能的慢性乙肝患者disoproxil富马酸三个全球随机研究。第46届年会的欧洲协会的肝脏（欧洲肝病学会2011年）的研究。柏林。 3月30日至四月三号。摘要616。

S凤，男飞达，女黄，等。减少骨质密度双能X射线与慢性乙型肝炎（CHB）患者骨密度评估而​​得。第46届年会的欧洲协会的肝脏（欧洲肝病学会2011年）的研究。柏林。 3月30日至四月三号。摘要175。