肝硬化自发性脾肾分流治疗后再出血及5年生存率的影响因素分析
DOI: 10.12449/JCH240715
Influencing factors for rebleeding and 5-year survival rate after treatment in patients with liver cirrhosis and spontaneous splenorenal shunt
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摘要:
目的 探讨肝硬化自发性脾肾分流(SSRS)患者治疗后再出血及5年生存率的影响因素,以期为临床评估肝硬化患者预后提供依据。 方法 选取2014年6月—2018年6月复旦大学附属中山医院及厦门分院收治的肝硬化合并SSRS患者95例,所有患者均获得5年及以上随访结果。根据随访过程中是否再次发生消化道出血分为再出血组(n=27)和未再出血组(n=68)。计量资料两组间比较采用成组t检验或Mann-Whitney U检验。计数资料组间比较采用χ2检验或Fisher精确概率法。采用单因素和多因素Cox回归分析筛选SSRS患者的预后影响因素,Kaplan-Meier法描述生存结局。相关性采用Pearson或Spearman相关性分析。 结果 再出血组脾肾分流直径[4.60(3.20~5.90)mm vs 3.45(2.10~5.45)mm,Z=1.973,P=0.048]和门静脉压力梯度[(18.57±6.60)mmHg vs (15.06±5.82)mmHg,t=2.280,P=0.026]均显著高于未再出血组,门静脉直径[(14.04±2.90)mm vs (15.45±2.90)mm,t=2.138,P=0.035]显著低于未再出血组。相关性分析结果显示,脾肾分流直径与门静脉直径呈负相关(rs =-0.211,P=0.040)。治疗后5年内的不良事件包括消化道再出血(27.4%)、门静脉血栓(11.6%)、感染(4.2%)、脑出血(1.1%)和脑梗死(1.1%)。脾肾分流直径(RR=1.173,95%CI:1.001~1.374,P=0.048)和肠系膜上静脉直径(RR=0.844,95%CI:0.746~0.956,P=0.007)是治疗后5年消化道再出血的独立影响因素。胆红素(RR=1.028,95%CI:1.010~1.046,P=0.002)和尿素氮(RR=1.347,95%CI:1.116~1.625,P=0.002)是治疗后5年生存率的独立危险因素。 结论 脾肾分流直径与肝硬化患者预后密切相关,对于肝硬化合并SSRS患者,应加强对脾肾分流直径的影像学随访。 Abstract:Objective To investigate the influencing factors for rebleeding and 5-year survival rate after treatment in patients with liver cirrhosis and spontaneous splenorenal shunt (SSRS), and to provide a basis for clinical prognostic assessment. Methods A total of 95 patients with liver cirrhosis and SSRS who were admitted to Zhongshan Hospital and Xiamen Branch of Fudan University from June 2014 to June 2018 were enrolled, and all patients were followed up for at least 5 years. According to the presence or absence of gastrointestinal bleeding during follow-up, the patients were divided into rebleeding group with 27 patients and non-rebleeding group with 68 patients. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. Univariate and multivariate Cox regression analyses were used to investigate the influencing factors for the prognosis of patients with SSRS, and the Kaplan-Meier method was used to describe survival outcomes. A Pearson or Spearman correlation analysis was performed. Results Compared with the non-rebleeding group, the rebleeding group had significantly higher splenorenal shunt diameter [4.60(3.20 — 5.90) mm vs 3.45(2.10 — 5.45) mm, Z=1.973, P=0.048] and hepatic venous pressure gradient(18.57±6.60 mmHg vs 15.06±5.82 mmHg, t=2.280, P=0.026) and a significantly lower portal vein diameter(14.04±2.90 mm vs 15.45±2.90 mm, t=2.138, P=0.035). The correlation analysis showed that splenorenal shunt diameter was negatively correlated with portal vein diameter(rs =-0.211, P=0.040). Adverse events within 5 years after treatment included rebleeding(27.4%), portal vein thrombosis(11.6%), infection(4.2%), cerebral hemorrhage(1.1%), and cerebral infarction(1.1%). Splenorenal shunt diameter(risk ratio [RR]=1.173, 95% confidence interval [CI]: 1.001 — 1.374, P=0.048) and superior mesenteric vein diameter(RR=0.844, 95%CI: 0.746 — 0.956, P=0.007) were independent influencing factors for gastrointestinal rebleeding within 5 years after treatment. Bilirubin(RR=1.028, 95%CI: 1.010 — 1.046, P=0.002) and blood urea nitrogen(RR=1.347, 95%CI: 1.116 — 1.625, P=0.002) were independent risk factors for 5-year survival rate after treatment. Conclusion Splenorenal shunt diameter is closely associated with the prognosis of cirrhotic patients, and it is recommended to enhance imaging follow-up of splenorenal shunt diameter for cirrhotic patients with SSRS. -
Key words:
- Liver Cirrhosis /
- Splenorenal Shunt /
- Prognosis
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表 1 肝硬化合并SSRS患者未再出血组与再出血组基线资料比较
Table 1. Comparison of baseline data between the non-rebleeding group and the rebleeding group in patients with liver cirrhosis associated with spontaneous splenorenal shunts
项目 未再出血组(n=68) 再出血组(n=27) 统计值 P值 年龄(岁) 52.70±12.08 56.59±12.39 t=1.388 0.169 男[例(%)] 45(66.2) 18(66.7) χ2=0.002 0.964 白细胞(×109/L) 2.62(2.15~4.51) 2.22(1.51~3.21) Z=2.269 0.023 血红蛋白(g/L) 103.06±27.12 90.37±32.90 t=1.933 0.056 血小板(×109/L) 67(40~83) 61(39~85) Z=0.238 0.812 凝血酶原时间(s) 14.64±3.86 14.82±2.21 t=0.227 0.821 国际标准化比值 1.26±0.16 1.31±0.23 t=1.284 0.202 胆红素(μmol/L) 21.50(14.80~29.50) 18.30(11.60~36.05) Z=0.359 0.720 丙氨酸转氨酶(U/L) 27(18~35) 21(14~29) Z=1.532 0.126 天冬氨酸转氨酶(U/L) 34(26~47) 28(21~41) Z=1.375 0.169 白蛋白(g/L) 35.29±5.41 34.78±6.68 t=0.392 0.696 尿素氮(mmol/L) 4.4(3.3~7.1) 4.3(3.0~5.7) Z=0.146 0.884 肌酐(μmol/L) 66(60~71) 77(54~86) Z=1.401 0.161 C反应蛋白(mg/L) 1.5(0.6~5.0) 2.9(0.7~13.9) Z=0.991 0.332 脑钠肽(ng/L) 80.5(44.8~124.6) 216.0(53.8~541.5) Z=1.309 0.191 HVPG(mmHg) 15.06±5.82 18.57±6.60 t=2.280 0.026 血氨(μmol/L) 39(25~44) 17(11~43) Z=1.465 0.143 中重度腹腔积液[例(%)] 20(29.4) 11(40.7) χ2=1.128 0.288 Child-Pugh评分(分) 6(5~8) 7(6~8) Z=1.424 0.155 MELD评分(分) 6.98(4.14~9.53) 6.24(3.97~11.21) Z=0.528 0.601 门静脉直径(mm) 15.45±2.90 14.04±2.90 t=2.138 0.035 脾静脉直径(mm) 11.59±3.08 10.06±4.22 t=1.713 0.095 脾肾分流直径(mm) 3.45(2.10~5.45) 4.60(3.20~5.90) Z=1.973 0.048 肠系膜上静脉直径(mm) 11.70(10.40~13.63) 10.70(8.90~12.40) Z=1.939 0.052 门静脉血栓[例(%)] 8(11.8) 3(11.1) χ2=0.008 0.928 治疗方式1)[例(%)] χ2=3.541 0.170 内镜 53(80.3) 16(61.5) TIPS 10(15.2) 8(30.8) 外科手术 3(4.5) 2(7.7) 注:1)未再出血组2例患者治疗方式缺失,再出血组1例患者治疗方式缺失。 表 2 肝硬化合并SSRS患者消化道再出血的Cox单因素分析
Table 2. Cox univariate analysis of gastrointestinal rebleeding factors in cirrhotic patients complicated by spontaneous splenorenal shunts
项目 B值 SE Wald P值 RR(95%CI) 年龄(岁) -0.021 0.016 1.761 0.184 0.979(0.949~1.010) 性别(男/女) -0.082 0.417 0.039 0.844 0.921(0.407~2.085) 白细胞(×109/L) -0.244 0.150 2.626 0.105 0.784(0.584~1.052) 血红蛋白(g/L) -0.012 0.007 2.589 0.108 0.988(0.974~1.003) 血小板(×109/L) 0.000 0.005 0.005 0.942 1.000(0.990~1.011) 凝血酶原时间(s) -0.001 0.057 0.000 0.986 0.999(0.893~1.117) 国际标准化比值 1.176 1.231 0.912 0.339 3.243(0.290~36.236) 胆红素(μmol/L) -0.002 0.012 0.021 0.886 0.998(0.974~1.023) 丙氨酸转氨酶(U/L) -0.022 0.019 1.285 0.257 0.979(0.943~1.016) 天冬氨酸转氨酶(U/L) -0.028 0.018 2.488 0.115 0.972(0.939~1.007) 白蛋白(g/L) -0.009 0.035 0.067 0.796 0.991(0.924~1.062) C反应蛋白(mg/L) 0.028 0.018 2.493 0.114 1.028(0.993~1.065) HVPG(mmHg) 0.084 0.033 6.578 0.010 1.088(1.020~1.160) 血氨(μmol/L) -0.004 0.010 0.194 0.659 0.996(0.976~1.015) Child-Pugh评分 0.079 0.100 0.622 0.430 1.082(0.889~1.318) Child-Pugh分级 A级 1.846 0.397 B级 -0.266 0.775 0.118 0.731 0.766(0.168~3.498) C级 0.304 0.760 0.161 0.689 1.356(0.306~6.010) MELD评分 0.074 0.051 2.115 0.146 1.077(0.974~1.191) 门静脉直径(mm) -0.135 0.075 3.288 0.070 0.873(0.754~1.011) 脾静脉直径(mm) -0.109 0.055 3.882 0.049 0.896(0.804~0.999) 脾肾分流直径(mm) 0.162 0.081 4.025 0.045 1.176(1.004~1.377) 肠系膜上静脉直径(mm) -0.194 0.068 8.079 0.004 0.823(0.720~0.941) 治疗方式 内镜 2.311 0.315 TIPS -0.156 1.031 0.023 0.880 0.856(0.113~6.456) 手术治疗 0.533 1.069 0.249 0.618 1.705(0.210~13.858) 门静脉血栓(有 vs 无) 0.022 0.616 0.001 0.971 1.023(0.306~3.418) 腹腔积液(有 vs 无) 0.577 0.429 1.812 0.178 1.781(0.768~4.129) 表 3 肝硬化合并SSRS患者5年生存情况的Cox单因素分析
Table 3. Cox univariate analysis of the 5-year survival status in cirrhotic patients complicated by spontaneous splenorenal shunts
项目 B值 SE Wald P值 RR(95%CI) 年龄(岁) 0.002 0.031 0.005 0.944 1.002(0.944~1.064) 性别(男/女) 0.244 0.837 0.085 0.771 1.276(0.248~6.577) 白细胞(×109/L) 0.183 0.137 1.781 0.182 1.201(0.918~1.573) 血红蛋白(g/L) -0.025 0.015 2.937 0.087 0.975(0.948~1.004) 血小板(×109/L) -0.017 0.014 1.392 0.238 0.983(0.956~1.011) 凝血酶原时间(s) 0.067 0.051 1.708 0.191 1.069(0.967~1.182) 国际标准化比值 5.498 1.688 10.609 0.001 244.313(8.934~6 681.139) 胆红素(μmol/L) 0.023 0.008 8.338 0.004 1.023(1.007~1.039) 丙氨酸转氨酶(U/L) 0.014 0.016 0.730 0.393 1.014(0.982~1.047) 天冬氨酸转氨酶(U/L) 0.020 0.013 2.378 0.123 1.020(0.995~1.046) 白蛋白(g/L) -0.107 0.055 3.794 0.051 0.898(0.807~1.001) 尿素氮(mmol/L) 0.255 0.067 14.461 <0.001 1.291(1.132~1.472) 肌酐(μmol/L) 0.021 0.006 13.592 <0.001 1.022(1.010~1.033) 脑钠肽(ng/L) 0.003 0.002 3.831 0.050 1.003(1.000~1.007) HVPG(mmHg) 0.048 0.078 0.388 0.534 1.050(0.901~1.222) 血氨(μmol/L) -0.013 0.021 0.358 0.550 0.988(0.948~1.029) Child-Pugh评分 0.316 0.162 3.788 0.052 1.371(0.998~1.884) Child-Pugh分级 A级 3.517 0.172 B级 -1.837 1.001 3.373 0.066 0.159(0.022~1.132) C级 -1.211 0.914 1.756 0.185 0.298(0.050~1.786) MELD评分 0.330 0.081 16.660 <0.001 1.390(1.187~1.629) 门静脉直径(mm) -0.421 0.174 5.836 0.016 0.656(0.467~0.924) 脾静脉直径(mm) -0.190 0.097 3.809 0.051 0.827(0.684~1.001) 脾肾分流直径(mm) 0.260 0.147 3.123 0.077 1.297(0.972~1.732) 肠系膜上静脉直径(mm) -0.447 0.113 15.641 <0.001 0.639(0.512~0.798) 治疗方式 内镜 6.917 0.031 TIPS -2.401 0.913 6.912 0.009 0.091(0.015~0.543) 手术治疗 -1.379 1.000 1.901 0.168 0.252(0.035~1.788) 门静脉血栓(有 vs 无) -0.012 0.614 0.000 0.984 0.988(0.297~3.291) 腹腔积液(有 vs 无) 0.478 0.412 1.344 0.246 1.613(0.719~3.619) 表 4 肝硬化合并SSRS患者短期和长期随访的不良事件
Table 4. Adverse event analysis of short-term and long-term follow-up in cirrhotic patients complicated by spontaneous splenorenal shunts
不良事件 短期累积事件 长期累积事件 5年无事件率(95%CI) 全因死亡 2 7 92.6%(91.3%~94.0%) 再出血 9 26 72.6%(68.6%~76.6%) 肝性脑病 1 3 96.8%(96.2%~97.5%) 感染 4 4 95.8%(95.0%~96.6%) 门静脉血栓 2 11 88.4%(86.4%~90.5%) 脑出血 1 1 98.9%(98.7%~99.2%) 脑梗死 0 1 98.9%(98.7%~99.2%) -
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