Abstract 1 

NON-SELECTIVE BETA-BLOCKERS MIGHT DECREASE SURVIVAL IN SEVERE ALCOHOLIC CIRRHOSIS

非选择性β受体阻滞剂可能降低重型酒精性肝硬化患者的生存率

Background and Aim: The effect of beta-blockers (BB) on survival in cirrhotic patients with poor liver function, especially with refractory ascites, is debated. Recently, the window hypothesis has suggested 3 phases: no effect, improved survival, decreased survival by BB. Therefore, we evaluated the BB effect on survival according to liver severity.

Methods: Consecutive patients with alcoholic cirrhosis and no history of hepatocellular carcinoma were prospectively included in a single tertiary center. The date and cause of death were recorded and checked using the national death registry.

Results: Baseline characteristics of 361 included patients were: age: 60.0±9.8 yrs, male: 71.7%, Child Pugh score: 6.1±1.8 (A: 69.7%, B: 23.3%, C: 7.0%), Meld score: 11.3±4.5, follow-up: 3.1±1.4 yrs,death rate: 28.8% (liver related death in 62.5%). The 144 patients with non-selective BB were compared to the 190 controls without BB; 27 patients with selective BB were excluded. At baseline, there were higher frequencies of esophageal (p < 0.001) or gastric varices (p = 0.019) and alcohol withdrawal (p = 0.001) in the BB group. Child–Pugh (p = 0.56) and Meld (p = 0.25) scores did not differ. The independent predictors of overall survival were Meld(p < 0.001) and age (p = 0.028) by Cox model. The independent predictors of liver related survival included Meld (p < 0.001) and gastric varices (p = 0.026), and a significant interaction between Meld and BB (p = 0.035). Therefore, we assessed the BB effect according to baseline Meld score: in the lowest tertile, BB group had an improved overall survival as compared to controls (logrank:p = 0.071); a beneficial BB effect was also observed in the second tertile until 4 years of follow-up; in contrast, in the highest tertile, patients treated with BB had decreased survival beyond 2 years (p = 0.095). Liver survival showed the same trends in the first (p = 0.140) and second (p = 0.306) tertiles; in the highest tertile, the poorer survival in BB group was more pronounced than for overall survival (p = 0.019).

Conclusion: The BB effect on survival differed according to liver disease severity in alcoholic cirrhosis: in good condition patients, BB tended to improve survival during the first years whereas there was a significantly decreased liver survival in the most severe patients.

背景及目的：β受体阻滞剂用于肝功能较差，尤其是存在顽固性腹水的患者，其疗效存在争议。最近，窗口假说提出了三种状态：没有效果、改善生存和生存率下降。因此，我们对不同程度肝功能损害的患者使用非选择性β受体阻滞剂的疗效进行评估。

方法：研究对象为某三级医疗中心非肝癌的酒精性肝硬化患者，患者的死亡日期和原因都记录于国家死亡人口登记处。

结果：361例患者纳入研究，平均年龄60.0±9.8岁，71.7%为男性，平均Child评分为6.1±1.8（其中A：69.7%，B：23.3%，C：7.0%），平均MELD评分为11.3±4.5，平均随访3.1±1.4年，死亡率为28.8%（其中肝脏疾病相关性死亡占据62.5%）。所有患者中有144例服用了非选择性β受体阻滞剂，190例未服用β受体阻滞剂，排除27例服用选择性β受体阻滞剂的患者。在服药组中，患者发生食管静脉曲张（P<0.001）、胃底静脉曲张（P=0.019）、以及酒精戒断（P=0.001）的比例显著高于未服药组，Child评分和MELD评分两组差异没有统计学意义。回归分析显示，MELD评分（P<0.001）和年龄（P=0.028）是总体生存率的独立预测因子，而MELD评分（P<0.001）和胃底静脉曲张（P=0.026）是肝脏相关性生存率的独立预测因子，并且MELD评分和服用β受体阻滞剂有明显的相互作用（P=0.035）。因此，我们通过MELD评分的不同来评估服用非选择性β受体阻滞剂对患者生存临床的影响。根据MELD从高到低的顺序排列，同时将患者均匀的分为三组。低MELD评分组，服用非选择性β受体阻滞剂组能提高总体生存率（P=0.071）；中MELD评分组的患者随访4年后，我们也发现服用非选择性β受体阻滞剂有利于患者的生存率。相反，高MELD评分组，服用非选择性β受体阻滞剂的患者生存率显著低于对照组（P=0.095），肝脏相关性的生存率显示出类似的趋势，中、低MELD评分组差异没有统计学意义。在高MELD评分组中，服用非选择性β受体阻滞剂患者的生存率甚至明显低于总体生存率（P=0.019）。

结论：非选择性β受体阻滞剂对重型酒精性肝硬化患者生存率的影响可以归结为：在一般情况较好的患者中，非选择性β受体阻滞剂可以提高患者第一年的生存率，而在一般情况较差的患者中，服用非选择性β受体阻滞剂的患者生存率显著降低。

非选择性β受体阻滞剂对重型酒精性肝硬化患者生存率的影响可以归结为：在一般情况较好的患者中，非选择性β受体阻滞剂可以提高患者第一年的生存率，而在一般情况较差的患者中，服用非选择性β受体阻滞剂的患者生存率显著降低。————提示我们对于该药物的使用应因人而异。