Impact of Underlying Portal Hypertension on Severity and Course of Acute‐On‐Chronic Liver Failure

Background and Aims The impact of portal hypertension (PH) during acute‐on‐chronic liver failure (ACLF) remains unclear. This study investigated the link between underlying PH severity, systemic inflammation (SI), and the course of ACLF. Methods Consecutive patients with ACLF ( n = 192) who met the EASL‐CLIF criteria were retrospectively included. PH severity (hepatic venous pressure gradient, HVPG; platelet count, PLT; and other clinical/radiologic PH surrogates) and SI (white blood cell count; C‐reactive protein [CRP], interleukin‐6) were assessed at the last pre‐ACLF visit, ACLF diagnosis (D0), and after 7 (D7), 28 (D28), and 90 (D90) days. Results All patients had clinical/radiological signs of PH, and 91 (47%) patients developed ACLF grade 1, 62 (32%) ACLF‐2, and 39 (21%) ACLF‐3. Patients with different D0‐ACLF grades showed similar SI biomarker levels pre‐ACLF, whereas these increased significantly during ACLF. Median PLT decreased in parallel with the ACLF grade and from D0 (ACLF‐3:72; vs. ACLF‐2:81; vs. ACLF‐1:91 G/L; p = 0.094) to D7 (ACLF‐3:39 vs. ACLF‐2:64; vs. ACLF‐1:89 G/L; p < 0.001). In multivariable Cox regression models, D0‐PLT (aHR: 0.96 per 10 G/L [95% CI: 0.93–0.99], p = 0.015) independently predicted D28 mortality. A logistic regression model including sex, D0‐PLT, D0‐CRP, and CLIF‐C ACLF score predicted D28 mortality (AUROC: 0.79 [0.73–0.86]; p < 0.001) and outperformed ( p = 0.036) the MELD‐Na score (AUROC: 0.71 [0.63–0.78]; p < 0.001). Conclusions Although PH is a necessary condition for ACLF development, underlying PH severity does not confer a risk for higher ACLF severity but impacts survival after ACLF resolution. PLT emerged as a predictor of D28 mortality, independent of the CLIF‐C ACLF score.