Artificial Liver Support Systems for Hepatitis B Virus-associated Acute-on-Chronic Liver Failure

A Meta-analysis of the Clinical Literature

Guotao Li; Pan Zhang; Yumeng Zhu


J Viral Hepat. 2023;30(2):90-100. 

In This Article

Abstract and Introduction


To evaluate the short-term and long-term survival efficacy of an artificial liver support system (ALSS) in patients with acute-on-chronic liver failure (ACLF). A systematic search was performed for relevant published data in PubMed, Web of Science and Cochrane Library databases. Studies that evaluated the efficacy of ALSS in patients with ACLF and provided the short-term or long-term survival rate were included. A total of 10 studies involving 3685 patients were included in this analysis. The pooled 28-day survival rate and 90-day survival rate were 68.7% (95% CI: 64.5%–72.9%) and 53.4% (95% CI: 45.5%–61.4%), respectively. The pooled estimates of the OR for the 28-day and 90-day survival rates between the ALSS group and the control group were 1.91 (95% CI: 1.21–3.04) and 1.41 (95% CI: 1.17–1.70), respectively. Subgroup analysis showed that patients treated with lower levels of TBIL and MELD scores had a higher 28-day survival rate (χ 2 = 15.75, p < 0.01; χ 2 = 13.80, p < 0.01). The present meta-analysis suggests that ALSS treatment could remarkably improve short-term survival rates in HBV-ACLF patients, which implies that treatment with ALSS may help to reduce high mortality. Further prospective randomized trials are needed to validate these findings.


Acute-on-chronic liver failure (ACLF) is a complicated clinical syndrome manifesting as acute and severe hepatic dysfunction resulting from virus, alcohol or drugs and chronic decompensation in any type of end-stage liver disease.[1] Hepatitis B virus (HBV) infection accounts for the majority of ACLF in Asians.[2] China has been recognized as an HBV high-prevalence area with approximately 130 million carriers and 30 million chronically infected individuals.[3] ACLF is characterized by jaundice, coagulopathy, hepatic encephalopathy (HE) and a high incidence of short-term (28-day) mortality of 30%–40%.[4] Although the most useful therapy for ACLF is liver transplantation (LT), healthy livers are extremely lacking, and the operation is very costly.[5] Unfortunately, many ACLF patients will die prior to suitable organ availability and/or evolve to multisystem organ failure, at which point LT is contraindicated. Furthermore, due to medical or psychosocial reasons, many ACLF patients are ineligible for LT.

The artificial liver support system (ALSS) was first applied in the treatment of liver failure in the 1970 s.[6] In the past several decades, many types of ALSS have been developed to bridge patients to LT or to support the failing liver temporarily until it is able to regenerate.[7] Specifically, ALSS should be able to selectively remove accumulating toxins propagating liver failure and provide temporary support of liver and kidney function. Plasma exchange (PE) represents complete detoxification but may result in a risk of allergy and infection owing to exposure to exogenous plasma.[8] Albumin dialysis allows the removal of albumin-bound toxins and soluble toxins with external albumin in MARS (molecular adsorbent recirculating system)[9] or the patient's own albumin in FPSA (fractionated plasma separation and adsorption).[10] Although some meta-analyses of clinical trials have demonstrated the beneficial effects of ALSS on ACLF,[11,12] systematic studies on survival outcomes of HBV-ACLF are deficient. Several cohort studies have reported a positive association of ALSS with short-term or long-term survival of HBV-ACLF.[13,14] Meanwhile, inclusive evidence, namely negative association, no relation or positive without significance, was suggested in other cohort studies. Moreover, few meta-analyses focusing on the association of ALSS and HBV-ACLF have been reported. Thus, it is imperative to perform a more comprehensive and systematic meta-analysis to re-evaluate the effects of ALSS on the survival outcomes of patients with HBV-ACLF.

In this study, a meta-analysis was conducted to evaluate the short-term and long-term survival efficacy of ALSS in patients with ACLF and compare the effects of ALSS plus standard medical treatment (SMT) versus SMT alone on survival and to evaluate the safety profile of therapy.