Analysis of prognostic factors for 24-month survival of hepatitis B virus-associated acute-on-chronic liver failure patients treated with telbivudine

Hai-bing Gao, Xiangmei Wang, H. Ma, Shenglong Lin, Dongqin Zhang, Wenjun Wu, Jiankai Fang, Minghua Lin
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Abstract

Objective To investigate the baseline independent prognostic factors for 24 months survival of hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF) patients treated with telbivudine. Methods The prospective cohort study was conducted in HBV-associated ACLF patients who were hospitalized in Mengchao Hepatobiliary Hospital of Fujian Medical University and volunteered to be treated with telbivudine for more than 24 months. The patients were observed for survival at month 1, 3, 6, 12, and 24 after treatment. The baseline biochemical index, coagulant function, model for end-stage liver disease (MELD) score, HBV DNA level as well as comorbidities were analyzed in this study. The count data were compared with kappa test or Fisher′s exact test. For the normal distributed measurement data, the homogeneity test of variances (Levene test) was firstly used for comparison between groups. Further, the group t test was applied for variance homogeneity, while the approximate t test was applied for variance non-homogeneity and the Mann-Whitney U test was applied for the non-distributed measurement data. Results A total of 41 patients were enrolled, including 3 drop-outs and 38 accomplishments. Among these 38 patients, there were 3 females (7.9%) and 35 males (92.1%), with ages (38.5±11.1) years. There were 32 patients alive and 6 dead during 1 month′s follow-up, while baseline MELD score was the independent prognostic factor (RR=1.864, 95%CI: 1.151-3.019) for survival. There were 31 patients alive and 7 dead during 3 months′ follow-up, while baseline MELD score and upper gastrointestinal hemorrhage (UGH) were the independent prognostic factors (RR=2.053, 95%CI: 1.163-3.625; RR=394.939, 95%CI: 1.880-82 948.817). There were both 26 patients alive and 12 dead during 6 and 12 months′ follow-up, while baseline MELD score was the independent prognostic factor (RR=1.761, 95% CI: 1.230-2.523). At the end of 24 months′ follow-up, there were 15 patients alive and 23 dead. Viral rebounds were observed in 6 patients and 3 of them were dead. Baseline HBV DNA level, MELD score and electrolyte imbalance were the independent prognostic factors (RR=9.722, 95% CI: 1.607-58.821; RR=1.518, 95% CI: 1.066-2.162; RR=87.505, 95% CI: 2.263-3 384.232) for 24 months′survival. Conclusions Although telbivudine is not recommended as the first-line treatment, ACLF patients with low MELD score and low HBV DNA level at baseline, individualized treatment may improve patient's survival rate. UGH and electrolyte imbalance may affect the efficacy of telbivudine and reduce the survival rate of ACLF patient. Key words: Hepatitis B virus; Liver failure; Telbivudine; Survival analysis
替比夫定治疗乙型肝炎病毒相关急性慢性肝衰竭患者24个月生存率的预后因素分析
目的探讨替比夫定治疗的乙型肝炎病毒(HBV)相关性急慢性肝功能衰竭(ACLF)患者24个月生存率的基线独立预后因素。方法对福建医科大学孟超肝胆医院住院并自愿接受替比夫定治疗超过24个月的HBV相关ACLF患者进行前瞻性队列研究。观察患者在治疗后第1、3、6、12和24个月的生存情况。本研究分析了基线生化指标、凝血功能、终末期肝病模型(MELD)评分、HBV DNA水平以及合并症。计数数据与kappa检验或Fisher精确检验进行比较。对于正态分布的测量数据,首先使用方差的同质性检验(Levene检验)进行组间比较。此外,t组检验用于方差同质性,近似t检验用于方差非同质性,Mann-Whitney U检验用于非分布测量数据。结果共有41名患者入选,其中3名退出,38名取得成就。38例患者中,女性3例(7.9%),男性35例(92.1%),年龄(38.5±11.1)岁。在1个月的随访中,有32名患者存活,6名患者死亡,而基线MELD评分是生存的独立预后因素(RR=1.864,95%CI:1.151-3.019)。在3个月的随访中,有31名患者存活,7名患者死亡,而基线MELD评分和上消化道出血是独立的预后因素(RR=2.053,95%CI:1.133-3.625;RR=394.939,95%CI:1.880-82 948.817),而基线MELD评分是独立的预后因素(RR=1.761,95%CI:1230-2.523)。在24个月的随访结束时,有15名患者存活,23名患者死亡。6例患者出现病毒反弹,其中3例死亡。基线HBV DNA水平、MELD评分和电解质失衡是24个月生存的独立预后因素(RR=9.722,95%CI:1.607-58.821;RR=1.518,95%CI:1.066-2.162;RR=87.505,95%CI:2.263-3 384.232)。结论尽管不建议将替比夫定作为一线治疗,但ACLF患者在基线时MELD评分低,HBV DNA水平低,个体化治疗可以提高患者的生存率。UGH和电解质失衡可能影响替比夫定的疗效,降低ACLF患者的生存率。关键词:乙型肝炎病毒;肝功能衰竭;替比夫定;生存分析
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