Old Antivirals Rival New for Cancer Prevention in Hepatitis B

StephenW

http://www.oncologyreport.com/news/clinical/single-article/old-antivirals-rival-new-for-cancer-prevention-in-hepatitis-b/96446ff3b5.html
Clinical
Old Antivirals Rival New for Cancer Prevention in Hepatitis B

By: SUSAN LONDON,  Oncology Report Digital Network

SAN FRANCISCO – Older and newer oral antiviral agents are similarly effective at preventing hepatocellular carcinoma in patients with chronic hepatitis B, according to a systematic review of 45 studies involving 9,330 patients.

The rate of hepatocellular carcinoma (HCC) was almost identical in patients given older drugs (lamivudine or adefovir) and patients given newer ones (entecavir, telbivudine, or tenofovir), ranging from just 0.012 to 0.017 per person-year of follow-up, Dr. Ashwani K. Singal reported at the annual meeting of the American Association for the Study of Liver Diseases.

"This is a surprising finding, that it doesn’t make a difference," he commented in an interview. "Whatever medication you use, the occurrence is similar – it’s low but it’s similar."

The surprise stems from the fact that the newer agents have a low rate of drug resistance and achieve continued suppression of hepatitis B virus DNA during prolonged therapy, Dr. Singal explained. And indeed, undetectable DNA at last follow-up was associated with a lower risk of HCC in the study.

He speculated that the apparent nonsuperiority of the newer agents in terms of this outcome may be related to the relatively small number of patients treated with them thus far. "Now that we have newer antiviral agents, maybe we need more larger studies done in a prospective fashion to see whether one is better than the other," he commented.

In addition to patients having detectable viral DNA at last follow-up, patients aged 50 years or older and patients having cirrhosis at the start of antiviral therapy had higher rates of HCC than did their respective counterparts. The take-home message is that "these populations should be more carefully followed up, even on treatment," maintained Dr. Singal, a gastroenterologist with the Mayo Clinic in Rochester, Minn.

The investigators conducted the systematic review because at least 10 additional studies, several involving the newer antivirals, have been published since the last large meta-analysis looking at this issue in 2010.

They identified studies of oral antiviral therapy among patients with chronic hepatitis B that were published in full in English, regardless of whether patients had cirrhosis or not, and were treatment naive or treatment experienced. But the studies had to have had a treatment duration of at least 12 months and a follow-up duration of at least 2 years. Patients coinfected with HIV or hepatitis C were excluded.

In contrast to the previous meta-analysis, the review used a statistical method that took into account the greater likelihood of detecting HCC with longer follow-up, Dr. Singal noted.

Overall, 42% of the patients had received lamivudine (Epivir), 32% had received adefovir (Hepsera), 10% had received tenofovir (Viread), 9% had received telbivudine (Tyzeka), and 7% had received entecavir (Baraclude).

Results of the review showed that the rate of HCC did not differ significantly with older vs. newer antiviral agents: It was at 0.013 per person-year of follow-up with lamivudine in controlled studies, 0.017 with lamivudine in uncontrolled studies, 0.015 with adefovir
with or without lamivudine, and 0.012 with entecavir, telbivudine, or tenofovir.
But the rate was significantly higher in patients having detectable vs. undetectable viral DNA at last follow-up (0.019 vs. 0.01 per person-year of follow-up), patients aged 50 years or older vs. younger at the start of therapy (0.02 vs. 0.009), and patients with vs. without cirrhosis at the start of therapy (0.03 vs. 0.003).

Among those with cirrhosis, there was no difference according to whether the cirrhosis was compensated or decompensated. "The way I can explain that is before they get HCC, there are other things that kill these people: liver failure, bleeding, infections, those kind of things," commented Dr. Singal.

In the six studies having untreated control groups, all of which evaluated lamivudine, there was a significant 56% reduction in the risk of HCC for treated patients as compared with their untreated counterparts, confirming the marked benefit of antiviral therapy in general for reducing this outcome, he said.

"People say there are so many good drugs available now, the research on hepatitis B has almost come to a dead end," Dr. Singal concluded. "But I think there is still scope for doing research. For example ... most of the prospective studies on newer drugs are looking at 1-year outcomes of e antigen loss or surface antigen loss, but I think there should be ... longer follow-up and specifically aiming to look at whether newer drugs are different from older drugs when comparing hepatocellular carcinoma. That will have to be ... at least 5 or 7 years."

Dr. Singal reported that he had no relevant conflicts of interest.

StephenW

临床
旧抗病毒药物新的竞争对手在B型肝炎预防癌症

：苏珊伦敦，肿瘤报告数字网络

旧金山 - 新老的口服抗病毒药物是同样有效地预防慢性乙型肝炎患者肝癌，根据系统的审查研究涉及9330例患者的45。

率为肝细胞癌（HCC）患者由于旧的药物（拉米夫定或阿德福韦）和较新的（恩替卡韦，替比夫定，或替诺福韦），每人一年不等的后续从0.012到0.017的患者几乎相同，博士Ashwani K.葛肝病研究在美国协会年会上报告。

“他评论道：”这是一个惊人的发现，它不会有所作为，在接受记者采访时。 “无论你使用何种药物，发生类似 - 它的低，但它类似。”

令人惊讶的事实，新制剂的耐药率较低，并实现长期治疗期间继续抑制乙肝病毒DNA的茎，葛博士解释说。事实上，最后检测不到DNA后续低风险的研究与肝癌有关。

他推测，可能涉及到的数量相对较少，迄今为止治疗的患者与他们的这一成果的新制剂的明显nonsuperiority。 “现在，我们有较新的抗病毒药物，也许我们需要更多更大规模的研究，在未来的时尚，看到一个人是否是优于其他的，”他评论道。

除了最后检测病毒DNA的患者随访，患者年龄在50岁或老年人和病人在开始抗病毒治疗肝硬化肝癌的高利率比各自的。葛，博士与明尼苏达州罗切斯特的梅奥诊所肠胃病，带回家的消息是，“这些人群应该更认真地跟进，甚至在治疗，”保持

调查人员进行系统的审查，因为至少10个额外的研究，一些涉及新的抗病毒药物，最后的大荟萃分析看这个问题在2010年以来发表的。

他们发现之间发表的英文全慢性乙型肝炎患者口服抗病毒治疗的研究，无论病人是否有肝硬化或不，以及治疗天真或​​治疗经验。但研究必须有一个至少12个月的治疗时间和至少2年的随访时间。与艾滋病毒或丙型肝炎合并感染的患者被排除在外。

对比以前的荟萃分析，审查所用的统计方法，考虑到的检测与长期随访，葛博士指出肝癌的可能性更大。

总体而言，42％的患者收到拉米夫定（Epivir），32％收到阿德福韦（Hepsera），10％收到替诺福韦（Viread），收到了9％的替比夫定（TYZEKA），并收到了7％恩替卡韦（博路定） 。

审查结果表明，肝癌率没有差异，与旧与较新的抗病毒药物显著：这是在后续不受控制的研究拉米夫定与拉米夫定对照研究，0.017，0.013每人年阿德福韦0.015
有或没有拉米夫定，恩替卡韦，替比夫定，替诺福韦和0.012。
但率为患者最后检测的对比检测不到病毒DNA的后续行动（0.019与后续每人每年0.01）显着高于中，开始治疗年龄在50岁以上的老年人与年轻的患者（ 0.02与0.009），与无肝硬化的患者在治疗开始（0.03与0.003）。

在肝硬化，有没有什么区别，根据是否补偿或代偿期肝硬化。博士评论说，“葛”的方式，我可以解释，才得到肝癌，还有其他的事情，杀死这些人：肝功能衰竭，出血，感染，这些东西。

在6个未经处理的对照组的研究，所有这些评估拉米夫定，有一个显著减少56％，在肝癌治疗的患者的风险较其未经处理的，一般的抗病毒治疗有显着的好处，为减少这一结果证实他说，。

“人们说，有这么多好药现已，对B型肝炎的研究几乎已经到了穷途末路，”葛博士的结论。 “但我认为还有做研究的范围，例如... ...新的药物的前瞻性研究大多数是在e抗原损失或表面抗原的损失1年的成果，但我觉得应该有... ...更长时间的随访，特别要看看是否新药老药不同，比较肝癌时。这将是...至少5年或7年。“

葛博士报告说，他没有相关的利益冲突。