[EASL2013]肝纤维化与抗逆转录病毒治疗相关

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尽管通过现有的药物可以使乙型肝炎病毒得到抑制，但许多同时感染HBV和艾滋病（HIV）的患者出现进展性肝纤维化，根据2013年欧洲肝病学会（European Association for the Study of the Liver,EASL）主办的国际肝病大会上一项新的研究报告显示。

       抗逆转录病毒疗法（ART）广泛应用于抗HIV和HBV，但在HIV感染者中，肝脏相关死亡率仍然很高。肝活检很少在HBV DNA已得到抑制后进行，然而，合并感染者在治疗开始之前的很多年里已处于肝损伤发展的风险中。


       研究人员对5个中心的HBV/HIV患者的肝组织进行回顾性分析。有失代偿的，伴HCV或其他的肝脏疾病被排除在外。肝活检结果、人口学和临床数据在活检记录时获得。对肝纤维化的预测因素（将桥接纤维化/肝硬化与0–2期纤维化进行对比）进行了评估。


        最终纳入53例患者，平均年龄为42岁，96%为男性，30%为非裔美国人，66%应用了ART，绝大多数（95%）都检测不到HIV RNA。62%的患者e抗原阳性，35%的患者HBV DNA＜1000 U/L，30%检测不到HBV DNA。6%的测试者抗-HDV（N=30）呈阳性。ALT:52 U/L，AST:57 U/L，CD4:420。肝组织学显示31例患者有晚期肝纤维化（58%）。相比那些轻微疾病的患者，有进展性肝纤维化的患者更有可能使用了ART，有一个较低的CD4最低点（P=0.04）和较高的AST（P=0.08）。就HBeAg状态或HDV存在而言，群组之间没有差异。在现有数据的子集中（N=46），HBVD NA＜1000 IU/mL与疾病的严重程度不相关。对于鉴别晚期肝纤维化与轻微疾病，FIB-4表现略优于APRI[AUROCs 0.78（95% CI 0.71-0.85）和0.68（95%CI 0.48-089）]。


        HBV–HIV合并感染病人晚期肝纤维化的比例高，尽管HBV病毒得到抑制。使用了ART疗法的患者更易出现肝脏疾病，这可能掩盖了与HBV治疗相关的任何益处。需要更大的，设计良好的肝组织学及其相关因素的研究，来更好地确定这些缺乏研究的人群的肝脏疾病谱。

论文摘要：


Liver disease in hbv–hiv co-infection: significant fibrosis is present despite hbv suppression with anti-retroviral therapy


Background: Despite the widespread use of anti-retroviral therapy (ART) active against both HIV and HBV, liver-related mortality remains high among HIV infected persons. Liver biopsy is rarely performed in the setting of suppressed HBVDNA, yet co- infected individuals were at risk of developing liver injury for many years prior to treatment initiation. We sought to better define the spectrum of histologic liver disease, and correlates of liver disease, in HBV–HIV co-infection.


Methods: A retrospective analysis of liver histology in HBV–HIV patients from 5 centers was performed. Those with decompensation, HCV or other liver disease were excluded. Liver biopsy results and demographic and clinical data obtained at the time of the biopsy were recorded. Predictors of fibrosis (comparing those with bridging fibrosis/cirrhosis to those with stage 0–2 fibrosis) were assessed.


Results: Fifty-three patients were included. The mean age was 42, 96% were male, 30% were African American, 66% were on ART and the vast majority (95%) had undetectable HIV RNA. 62% were eAg+, 35% had HBVDNA <1000 U/L and 30% had an undetectable HBVDNA. 6% of those tested for anti-HDV (n = 30) were positive. Mean laboratories were AST 52 U/L, ALT 57 U/L, and CD4 420. Liver histology showed advanced fibrosis in 31 (58%). Compared to those with mild disease, those with advanced histology were more likely to be on ART (p = 0.02), to have a lower CD4 nadir (p = 0.04) and higher AST (p = 08). There was no difference between groups with respect to HBeAg status or presence of HDV. In a subset with available data (n = 46), HBVDNA <1000 IU/mL was not associated with disease severity. FIB-4 performed slightly better than APRI in differentiating advanced fibrosis from mild disease [AUROCs 0.78 (95% CI 0.71–0.85) and 0.68 (95% CI 0.48–089), respectively].


Conclusions: A high proportion of HBV–HIV co-infected patients have advanced fibrosis despite HBV suppression. Those on ART appear to have more advanced liver disease, and this may have masked any benefit associated with HBV treatment. Larger, welldesigned studies of liver histology and its correlates are needed to better define the spectrum of liver disease in this understudied population.