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

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.

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.

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).

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.