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拉米夫定-阿德福韦酯治疗慢性乙型肝炎肝硬化的临床结局。

Clinical outcomes of lamivudine-adefovir therapy in chronic hepatitis B cirrhosis.

机构信息

Department of Gastroenterology and Hepatology, Yong Yoo Lin School of Medicine, National University of Singapore, Singapore.

出版信息

J Clin Gastroenterol. 2011 Oct;45(9):818-23. doi: 10.1097/MCG.0b013e318214ab5d.

Abstract

GOALS

To determine the clinical outcome of chronic hepatitis B cirrhotics on antiviral therapy.

BACKGROUND

The long-term outcome of hepatitis B cirrhotics on therapy remains to be characterized.

METHODS

A large clinic cohort of chronic hepatitis B cirrhotic patients were enrolled in a treatment program of lamivudine ± adefovir therapy. Patients were analyzed for clinical outcomes, and predictors of these outcomes were evaluated by multivariate analysis. Clinical outcomes of ascites, encephalopathy, hepatocellular carcinoma (HCC), and progression in Child-Pugh score, Model for End-stage Liver Disease score, and mortality were assessed. Data were analyzed by Kaplan-Meier graphs, log-rank test, and Cox regression.

RESULTS

Of 143 chronic hepatitis B cirrhotics, 19.6% had decompensated cirrhosis. At 5 years, the mean survival was 83.6%, development of ascites, HCC, encephalopathy, and deterioration in Child-Pugh score were 7.0%, 15.9%, 10.8%, and 16.9%, respectively. The overall progression of liver-related complications was 32.8% at 5 years. Multivariate analysis showed that ascites, albumin ≤28 g/L, Child-Pugh score ≥7.9, Model for End-stage Liver Disease score ≥10.9 were significantly associated with liver-related complications. Low albumin and low hepatitis B virus DNA were independent factors for liver-associated mortality. Lamivudine resistance did not affect mortality or liver disease progression. When stratified by Child-Pugh status, the mean survival of those with Child C cirrhosis was worse than Child A and B cirrhosis (P<0.001, log-rank test). Early deaths (≤12 mo) were due to liver failure or sepsis, whereas deaths ≥12 mo were mainly due to HCC.

CONCLUSION

Decompensated chronic hepatitis B cirrhotics may suffer early mortality despite antiviral treatment, and therefore should be considered for early liver transplantation.

摘要

目的

确定慢性乙型肝炎肝硬化患者抗病毒治疗的临床转归。

背景

乙型肝炎肝硬化患者长期治疗的结局仍需进一步明确。

方法

本研究纳入了一项大规模的慢性乙型肝炎肝硬化患者临床队列,他们接受了拉米夫定联合阿德福韦酯或单用拉米夫定的治疗方案。分析患者的临床转归,并采用多因素分析评估这些转归的预测因素。评估的临床转归包括腹水、肝性脑病、肝细胞癌(HCC)以及 Child-Pugh 评分、终末期肝病模型评分和死亡率的进展。采用 Kaplan-Meier 图、对数秩检验和 Cox 回归进行数据分析。

结果

在 143 例慢性乙型肝炎肝硬化患者中,19.6%的患者为失代偿性肝硬化。在 5 年时,平均生存率为 83.6%,腹水、HCC、肝性脑病和 Child-Pugh 评分恶化的发生率分别为 7.0%、15.9%、10.8%和 16.9%。5 年内肝相关并发症的总体进展率为 32.8%。多因素分析显示,腹水、白蛋白≤28 g/L、Child-Pugh 评分≥7.9、终末期肝病模型评分≥10.9 与肝相关并发症显著相关。低白蛋白和低乙型肝炎病毒 DNA 是肝相关死亡的独立因素。拉米夫定耐药并不影响死亡率或肝病进展。按 Child-Pugh 状态分层,Child C 级肝硬化患者的平均生存时间差于 Child A 和 Child B 级肝硬化(P<0.001,对数秩检验)。早期死亡(≤12 个月)主要归因于肝功能衰竭或感染,而≥12 个月的死亡主要归因于 HCC。

结论

尽管接受了抗病毒治疗,失代偿性慢性乙型肝炎肝硬化患者仍可能发生早期死亡,因此应考虑早期进行肝移植。

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