肝硬化拨回：乙肝抗病毒治疗的一个可以实现的目标

StephenW

Reversal of cirrhosis: An achievable goal of hepatitis B antiviral therapy
Universally Available

    Yun-Fan Liaw Corresponding author contact information, E-mail the corresponding author

    Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan

    http://dx.doi.org/10.1016/j.jhep.2013.05.007, How to Cite or Link Using DOI

   
Abstract
Background

Whether long-term suppression of replication of hepatitis B virus (HBV) has any beneficial effect on regression of advanced liver fibrosis associated with chronic HBV infection remains unclear. We aimed to assess the effects on fibrosis and cirrhosis of at least 5 years’ treatment with tenofovir disoproxil fumarate (DF) in chronic HBV infection.
Methods

After 48 weeks of randomised double-blind comparison (trials NCT00117676 and NCT00116805) of tenofovir DF with adefovir dipivoxil, participants (positive or negative for HBeAg) were eligible to enter a 7-year study of open-label tenofovir DF treatment, with a pre-specified repeat liver biopsy at week 240. We assessed histological improvement (⩾2 point reduction in Knodell necroinflammatory score with no worsening of fibrosis) and regression of fibrosis (⩾1 unit decrease by Ishak scoring system).
Findings

Of 641 patients who received randomised treatment, 585 (91%) entered the open-label phase, and 489 (76%) completed 240 weeks. 348 patients (54%) had biopsy results at both baseline and week 240. 304 (87%) of the 348 had histological improvement, and 176 (51%) had regression of fibrosis at week 240 (p<0·0001). Of the 96 (28%) patients with cirrhosis (Ishak score 5 or 6) at baseline, 71 (74%) no longer had cirrhosis (⩾1 unit decrease in score), whereas three of 252 patients without cirrhosis at baseline progressed to cirrhosis at year 5 (p<0·0001). Virological breakthrough occurred infrequently and was not due to resistance to tenofovir DF. The safety profile was favourable: 91 (16%) patients had adverse events but only nine patients had serious events related to the study drug.
Interpretation

In patients with chronic HBV infection, up to 5 years of treatment with tenofovir DF was safe and effective. Long-term suppression of HBV can lead to regression of fibrosis and cirrhosis.
Keywords

    None

Corresponding author contact information
    Corresponding author. Liver Research Unit, Chang Gung Memorial Hospital, 199, Tung Hwa North Road, Taipei, 105, Taiwan, Tel.: +886 3 3281200x8120; fax: +886 3 3282824.

StephenW

背景

无论是长期抑制B型肝炎病毒（HBV）复制回归先进的肝纤维化伴有慢性HBV感染任何有益的影响仍不清楚。我们的目的是至少5年的富马酸替诺福韦酯（DF）治疗慢性乙肝病毒感染的肝纤维化和肝硬化的影响进行评估。
方法

经过48周的随机双盲比较（试验NCT00117676和NCT00116805）替诺福韦与阿德福韦酯，参与者（积极或消极的大三阳）资格进入了7年的开放标签研究，替诺福韦治疗，与预指定重复肝活检周240。我们评估组织学改善纤维化（⩾2点Knodell坏死性炎症评分减少与无纤维化恶化）和回归（⩾1单位减少伊沙克评分系统）。
发现

谁接受随机治疗的641例患者中，有585（91％）进入开放标签阶段，完成了240周和489（76％）。 348例（54％），活检结果在基线和240周。 348 304（87％），组织学改善，和176（51％），在240周（P <0.0001）回归纤维化。 96（28％）在基线（伊沙克得分5或6）肝硬化患者，71例（74％）不再有肝硬化（⩾减少1个单位得分），而3 252基线肝硬化患者无进展到肝硬化在5年（P <0.0001）。病毒学突破不常发生，不是由于耐替诺福韦DF。安全性是有利的：91例患者（16％）的不良事件，但只有9名患者与研究药物相关的严重不良事件。
解释

在慢性乙肝病毒感染的患者，长达5年的替诺福韦治疗是安全和有效的。长期抑制HBV，可导致纤维化和肝硬化的回归。

咬牙硬挺

肝硬化不再是无解的了，精力可以放在避免癌变上了