Efficacy and safety of double plasma molecular adsorption system combined with plasma exchange for acute-on-chronic liver failure: updated systematic review and meta-analysis of randomized controlled trials

Acute-on-chronic liver failure (ACLF) carries a high short-term mortality. Double plasma molecular adsorption system (DPMAS) combined with plasma exchange (PE) has been proposed to enhance toxin removal while lowering donor-plasma requirements. Previous meta-analyses included fewer trials and limited outcomes. This study aims to evaluate the efficacy and safety of DPMAS + PE vs. PE alone in patients with ACLF. PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang and VIP were searched from inception to 31 December 2024. Randomized controlled trials (RCTs) comparing DPMAS + PE vs. PE alone were included. Two reviewers independently screened articles, extracted data and appraised risk of bias using the Cochrane RoB1 tool. A modified 7-point Jadad scale assessed methodological quality. Random- or fixed-effects meta-analyses were performed in RevMan 5.4, heterogeneity was explored by subgroup and sensitivity analyses. Continuous outcomes were summarized as mean differences (MD) and dichotomous outcomes as odds ratios (OR) with 95% confidence intervals (CI). Publication bias was assessed by a funnel plot, where ≥ 10 studies were available. Twenty RCTs with 1663 patients met inclusion criteria. Compared with PE alone, DPMAS + PE significantly reduced total bilirubin [MD = − 49.66, 95% CI (− 65.88, − 33.44), P < 0.00001], alanine aminotransferase [MD = − 36.58, 95% CI (60.24, − 12.93), P = 0.002] and aspartate aminotransferase [MD = − 81.22, 95% CI (− 134.95, − 27.48), P = 0.003]; heterogeneity was high (I2 ≥ 90%). No significant group differences were observed for direct bilirubin, albumin, prothrombin time activity, international normalized ratio, hemoglobin or serum creatinine. Immunomodulatory profiles favored DPMAS + PE: pro-inflammatory cytokines IL-6, TNF-α and CRP declined, whereas anti-inflammatory IL-10 and TGF-β rose (all P < 0.01). Clinical efficacy rate was higher with combination therapy [OR = 2.36, 95% CI (1.86, 2.99)], with no increase in adverse event rates (P > 0.05). Visual inspection of the funnel plot did not reveal marked asymmetry, whereas Egger’s test suggested potential publication bias. Leave-one-out analyses confirmed result robustness. DPMAS + PE offers superior liver function improvement and greater clinical efficacy, enhancing inflammatory regulation compared to PE alone, without increasing adverse events. The findings support the clinical application of DPMAS + PE, but its long-term efficacy and optimal role in treatment paradigms require further validation through high-quality, multicenter trials.