Severity of Acute Portal Hypertension Determines the Clinical Outcomes in Severe Alcoholic Hepatitis

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). Conclusion 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.