Abstract：
BACKGROUND: Severe alcohol-associated hepatitis (SAH) presenting as acute-on-chronic liver failure (ACLF) has high mortality. Severe hepatic inflammation and ongoing hepatocellular cell death lead to rapid rise in portal pressure, a hyperdynamic circulation that might precipitate infections and organ failures.
METHODS: Consecutive SAH patients were classified based on baseline HVPG measurement as 6to < 12 mmHg, 12to < 20 mmHg, and ≥ 20 mmHg. We analyzed portal hypertension severity in relation to fibrosis stage, ACLF at presentation, response to prednisolone, severity scores(MELD and Maddrey\'s Discriminant Function, mDF), and 90-day mortality.
RESULTS: Of 819 SAH patients (94.6% ACLF, 85.4% histological cirrhosis, median MELD and mDF scores 25 and 66, respectively), 250(30.5%) had HVPG ≥ 20 mmHg. Patients with HVPG ≥ 20 mmHg more often had large esophageal varices (25.2%vs.13.2%; p-0.001), higher baseline MELD (27.1 ± 5.6vs.25.3 ± 5.2; p-0.001), and mDF(76.1 ± 16vs.68.4 ± 15.1; p-0.01) scores. No patient without ACLF had HVPG ≥ 20 mmHg. Moreover, during hospital course these patients had higher incidence of variceal bleed (17.2%vs.8.8%; p-0.001), acute kidney injury (36.4%vs.25.3%; p-0.001), and spontaneous bacterial peritonitis (6.4%vs.3.5%; p-0.05). Of 412(50.3%) eligible patients treated with prednisolone, 69.2% showed response at day 7(Lille\'s score < 0.45). 90-day mortality was 27.6%; and baseline MELD > 25.5[HR 1.78], HVPG ≥ 20 mmHg [HR 1.86], the presence of HE[HR 1.63], and prednisolone ineligibility due to sepsis[HR 1.27] were independent predictors. Mortality was unrelated to varices grade, variceal bleed, and histological cirrhosis. Repeat HVPG performed in 114(19.2%) patients after a median of 5.2 months showed significant decrease (3.6 mmHg; p-0.001) which correlated with improvement in MELD score(13points; p-0.05).
CONCLUSIONS: Development of ACLF and complications in SAH are likely a result of acute rise in HVPG. \"High-risk\" SAH are SAH patients with HVPG ≥ 20 mmHg in the presence of ascites. Understanding the drivers for acute rise in portal pressure in SAH ACLF might help introduction of newer therapies.
METHODS: Consecutive SAH patients were classified based on baseline HVPG measurement as 6to < 12 mmHg, 12to < 20 mmHg, and ≥ 20 mmHg. We analyzed portal hypertension severity in relation to fibrosis stage, ACLF at presentation, response to prednisolone, severity scores(MELD and Maddrey\'s Discriminant Function, mDF), and 90-day mortality.
RESULTS: Of 819 SAH patients (94.6% ACLF, 85.4% histological cirrhosis, median MELD and mDF scores 25 and 66, respectively), 250(30.5%) had HVPG ≥ 20 mmHg. Patients with HVPG ≥ 20 mmHg more often had large esophageal varices (25.2%vs.13.2%; p-0.001), higher baseline MELD (27.1 ± 5.6vs.25.3 ± 5.2; p-0.001), and mDF(76.1 ± 16vs.68.4 ± 15.1; p-0.01) scores. No patient without ACLF had HVPG ≥ 20 mmHg. Moreover, during hospital course these patients had higher incidence of variceal bleed (17.2%vs.8.8%; p-0.001), acute kidney injury (36.4%vs.25.3%; p-0.001), and spontaneous bacterial peritonitis (6.4%vs.3.5%; p-0.05). Of 412(50.3%) eligible patients treated with prednisolone, 69.2% showed response at day 7(Lille\'s score < 0.45). 90-day mortality was 27.6%; and baseline MELD > 25.5[HR 1.78], HVPG ≥ 20 mmHg [HR 1.86], the presence of HE[HR 1.63], and prednisolone ineligibility due to sepsis[HR 1.27] were independent predictors. Mortality was unrelated to varices grade, variceal bleed, and histological cirrhosis. Repeat HVPG performed in 114(19.2%) patients after a median of 5.2 months showed significant decrease (3.6 mmHg; p-0.001) which correlated with improvement in MELD score(13points; p-0.05).
CONCLUSIONS: Development of ACLF and complications in SAH are likely a result of acute rise in HVPG. \"High-risk\" SAH are SAH patients with HVPG ≥ 20 mmHg in the presence of ascites. Understanding the drivers for acute rise in portal pressure in SAH ACLF might help introduction of newer therapies.
摘要：
背景：表现为慢性急性肝衰竭（ACLF）的严重酒精相关性肝炎（SAH）具有高死亡率。严重的肝脏炎症和持续的肝细胞死亡导致门静脉压力迅速上升，可能导致感染和器官衰竭的高动力循环。
方法：连续SAH患者根据基线HVPG测量值分类为6至<12mmHg，12to<20mmHg，≥20mmHg。我们分析了门静脉高压严重程度与纤维化分期的关系，ACLF在演讲中，对泼尼松龙的反应，严重性评分(MELD和Maddrey的判别函数，mDF)，90天死亡率。
结果：在819例SAH患者中（94.6％ACLF，85.4%的组织学肝硬化，MELD和mDF中位数分别为25和66)，250人（30.5%）的HVPG≥20mmHg。HVPG≥20mmHg的患者更容易出现大的食管静脉曲张（25.2％vs.13％;p-0.001），较高的基线MELD（27.1±5.6vs.25.3±5.2；p-0.001），和mDF(76.1±16vs.68.4±15.1;p-0.01)得分。无ACLF患者HVPG≥20mmHg。此外，在住院期间，这些患者的静脉曲张出血发生率较高(17.2%vs.8%;p-0.001)，急性肾损伤（36.4%vs.25.3%;p-0.001），和自发性细菌性腹膜炎（6.4％vs.5％；p=0.05）。412名（50.3%）合格患者接受泼尼松龙治疗，69.2%在第7天出现反应(里尔评分<0.45)。90天死亡率为27.6%；基线MELD>25.5[HR1.78]，HVPG≥20mmHg[HR1.86]，HE的存在[HR1.63]，和因脓毒症导致的泼尼松龙不合格[HR1.27]是独立预测因素.死亡率与静脉曲张等级无关，静脉曲张出血,和组织学肝硬化。在中位5.2个月后的114例（19.2％）患者中进行的重复HVPG显示出显着降低（3.6mmHg；p-0.001），这与MELD评分的改善（13分；p-0.05）相关。
结论：SAH中ACLF的发展和并发症可能是HVPG急性升高的结果。“高危”SAH是指存在腹水的HVPG≥20mmHg的SAH患者。了解SAHACLF门静脉压力急性升高的驱动因素可能有助于引入新疗法。
方法：连续SAH患者根据基线HVPG测量值分类为6至<12mmHg，12to<20mmHg，≥20mmHg。我们分析了门静脉高压严重程度与纤维化分期的关系，ACLF在演讲中，对泼尼松龙的反应，严重性评分(MELD和Maddrey的判别函数，mDF)，90天死亡率。
结果：在819例SAH患者中（94.6％ACLF，85.4%的组织学肝硬化，MELD和mDF中位数分别为25和66)，250人（30.5%）的HVPG≥20mmHg。HVPG≥20mmHg的患者更容易出现大的食管静脉曲张（25.2％vs.13％;p-0.001），较高的基线MELD（27.1±5.6vs.25.3±5.2；p-0.001），和mDF(76.1±16vs.68.4±15.1;p-0.01)得分。无ACLF患者HVPG≥20mmHg。此外，在住院期间，这些患者的静脉曲张出血发生率较高(17.2%vs.8%;p-0.001)，急性肾损伤（36.4%vs.25.3%;p-0.001），和自发性细菌性腹膜炎（6.4％vs.5％；p=0.05）。412名（50.3%）合格患者接受泼尼松龙治疗，69.2%在第7天出现反应(里尔评分<0.45)。90天死亡率为27.6%；基线MELD>25.5[HR1.78]，HVPG≥20mmHg[HR1.86]，HE的存在[HR1.63]，和因脓毒症导致的泼尼松龙不合格[HR1.27]是独立预测因素.死亡率与静脉曲张等级无关，静脉曲张出血,和组织学肝硬化。在中位5.2个月后的114例（19.2％）患者中进行的重复HVPG显示出显着降低（3.6mmHg；p-0.001），这与MELD评分的改善（13分；p-0.05）相关。
结论：SAH中ACLF的发展和并发症可能是HVPG急性升高的结果。“高危”SAH是指存在腹水的HVPG≥20mmHg的SAH患者。了解SAHACLF门静脉压力急性升高的驱动因素可能有助于引入新疗法。
