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慢性乙型肝炎管理中的未满足需求。

Unmet need in chronic hepatitis B management.

机构信息

Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong SAR, China.

出版信息

Clin Mol Hepatol. 2019 Jun;25(2):172-180. doi: 10.3350/cmh.2018.0106. Epub 2019 Feb 12.

Abstract

Despite all these exciting developments, there remain some unmet needs in the management for patients with chronic hepatitis B (CHB). As majority of CHB patients are going to use oral nucleos(t)ide analogues (NAs) for decades, Safety profile of NAs is of no doubt an important issue. The newest nucleotide analogue tenofovir alafenamide is potent in terms of viral suppression, together with favourable renal and bone safety profile. Biochemical response as reflected by alanine aminotransferase (ALT) normalization is recently found to be prognostically important. Patients who achieved ALT normalization have reduced the risk of hepatic events by 49%. Functional cure as reflected by hepatitis B surface antigen seroclearance not only implies patients may stop NA treatment, it also confers to a reduced risk of hepatocellular carcinoma and other hepatic events. Hence functional cure should be the ultimate treatment goal in CHB patients. Preemptive antiviral treatment may reduce mother-to-child transmission of hepatitis B virus, especially if birth dose of vaccination cannot be given in the first two hours after delivery. Lastly, despite the currently first-line NAs have high-genetic barrier to drug resistance mutations, there are still are many patients who were previously treated with low barrier of resistance including lamivudine, telbivudine or adefovir dipivoxil which could lead to antiviral resistance and affecting the choice of NAs.

摘要

尽管取得了这些令人兴奋的进展,但慢性乙型肝炎(CHB)患者的管理仍存在一些未满足的需求。由于大多数 CHB 患者将在未来几十年内使用口服核苷(酸)类似物(NAs),因此 NAs 的安全性无疑是一个重要问题。新型核苷酸类似物替诺福韦艾拉酚胺在抑制病毒方面具有很强的效果,同时具有良好的肾脏和骨骼安全性。最近发现,丙氨酸氨基转移酶(ALT)正常化所反映的生化应答具有预后意义。达到 ALT 正常化的患者,其肝脏事件风险降低了 49%。反映乙肝表面抗原清除的功能性治愈不仅意味着患者可能停止 NA 治疗,还可降低肝细胞癌和其他肝脏事件的风险。因此,功能性治愈应该是 CHB 患者的最终治疗目标。预防性抗病毒治疗可以降低乙型肝炎病毒母婴传播的风险,尤其是如果不能在分娩后两小时内给予出生剂量的疫苗接种。最后,尽管目前的一线 NAs 对耐药基因突变具有高遗传屏障,但仍有许多患者以前接受过低耐药屏障的治疗,包括拉米夫定、替比夫定或阿德福韦酯,这可能导致抗病毒耐药并影响 NAs 的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ed7/6589853/4debe26a6bf2/cmh-2018-0106f1.jpg

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