Patients
Sixty-four patients with HBV-ACLF/HIV(+) and 81 patients with HBV-ACLF/HIV(−), all of whom were admitted to the Chengdu Public Health Clinical Medical Center between January 2019 and January 2025, were retrospectively included in this study. All patients were between 18 and 80 years of age. A minimum hospital stay of 2 days was required to ensure patients received effective and adequate treatment.
The diagnostic criteria for ACLF were based on the 2025 guidelines for the diagnosis and treatment of ACLF issued by the Chinese Medical Association [7]. These diagnostic criteria are as follows: acute severe liver injury on the basis of chronic liver disease (primarily chronic hepatitis or compensated cirrhosis), characterized by elevated total bilirubin (TBil) (≥ 12 mg/dL [205.2 µmol/L] or an increase of ≥ 1 mg/dL [17.1 µmol/L] per day) and coagulation dysfunction (international normalized ratio [INR] of ≥ 1.5 or prothrombin activity of ≤ 40%). During disease progression, complications such as infection, hepatic encephalopathy, ascites, gastrointestinal hemorrhage, acute kidney injury, or extrahepatic organ failure may occur.
The exclusion criteria were severe active bleeding (common sites include bleeding from the skin and mucous membranes, gastrointestinal, genitourinary, and respiratory tracts, as well as occult sites such as hepatic or splenic rupture and intracranial bleeding), disseminated intravascular coagulation, severe allergies to blood products or medications used in the course of treatment (such as plasma, heparin, and Fischer’s protein), unstable hemodynamics, and unstable stages of cardiac or cerebral infarction.
Treatment methods
All patients with ACLF in the study received comprehensive medical management combined with an artificial liver support treatment program.
Internal medicine treatment
According to the Guidelines for the Diagnosis and Treatment of Acute-on-Chronic Liver Failure (2025 Edition) developed by the Liver Failure and Artificial Liver Group of the Infectious Diseases Branch of the Chinese Medical Association and the Nutrition and Regeneration of End-Stage Liver Disease Group of the Hepatology Branch of the Chinese Medical Association [7], all patients received general supportive care, symptomatic treatment, etiologic treatment, and internal medicine treatment for complications during hospitalization. Among these, etiologic treatment varied: for HBV-DNA-positive patients with ACLF, antiviral therapy with nucleoside (acid) analogs should be initiated immediately, regardless of the detected HBV-DNA load.
According to the China AIDS Treatment Guidelines (2024 Edition) [8], developed by the AIDS Hepatitis C Group of the Infectious Diseases Branch of the Chinese Medical Association and the Chinese Center for Disease Control and Prevention, patients co-infected with HIV and HBV should be treated with tenofovir disoproxil fumarate (or tenofovir alafenamide) plus lamivudine (or emtricitabine), regardless of the cluster of differentiation (CD)4 + T-lymphocyte count. ART is recommended to be initiated as early as possible, provided there are no contraindications for anti-HIV treatment. HIV/HBV co-infected patients should receive therapy targeting both viruses, including two agents with anti-HBV activity. The recommended ART regimen based on nucleoside analogs consists of tenofovir disoproxil fumarate (or tenofovir alafenamide) plus lamivudine (or emtricitabine).
HBV-related indicators, such as HBV-DNA quantification, liver biochemistry, liver imaging, and testing for HBV drug resistance, should be monitored during treatment to detect the development of cirrhosis and hepatocellular carcinoma.
PP + PE treatment
Patients were evaluated for PP + PE treatment according to the Guidelines for the Diagnosis and Treatment of Acute-on-Chronic Liver Failure (2025 Edition) [7], the Guidelines for the Treatment of Artificial Liver Blood Purification Systems (2023 Edition) [9], and the Expert Consensus on the Clinical Application of Artificial Liver Blood Purification Techniques (2022 Edition) [4]. Blood purification equipment used included the Plasauto IQ21 (Asahi Kasei Kuraray Medical Co., Ltd.) and the Diapact® CRRT system (B. Braun Avitum Italy S.P.A). All patients were evaluated for indications for PP + PE therapy both on admission and during hospitalization.
PP involves directing the patient’s blood into an extracorporeal circulation system, separating the plasma via a membrane plasma filter, and removing liver failure-related toxins using adsorbents (such as activated charcoal or resin) in the perfusion apparatus. The membrane PP parameters were as follows: the plasma volume processed per session was 2800–3000 mL, blood flow rate was 150 mL/min;,and plasma separation rate was 20–25%.
PE uses membrane plasma filters to separate the patient’s plasma, which is then replaced with an equal volume of donor plasma to remove toxins and replenish essential components such as coagulation factors and albumin (ALB). The membrane PE parameters were set as follows: replacement volume of 1200–1500 mL per session, plasma exchange rate of 130 mL/min, and plasma separation rate of 20–25% of the blood flow rate.
In this study, artificial liver treatment was conducted in strict accordance with China’s Hospital Disinfection Hygiene Standard (GB15982 − 2023), using an artificial liver treatment machine, extracorporeal circulation tubing, plasma insufflator, and plasma separator for both PP and PE. Patients with HBV alone and those with HIV/HBV co-infection were treated in separate rooms to prevent cross-infection.
Treatment began with PP, preceded by preflushing of the circulatory lines with saline and heparin. Patients without a history of allergies did not require pre-treatment with antiallergic drugs. Following PP, PE was performed. To prevent allergic reactions and hypocalcemia, patients received 250 mL of 10% dextrose with 3 g of calcium 10 min prior to PE. Additionally, dexamethasone (5 mg, intravenous push) was administered 1–2 min before treatment. Heparin anticoagulation was used, starting with an initial dose of 2500 U, followed by a maintenance dose of 1250 U/hour. Anticoagulation was discontinued after PP treatment.
Vital signs—including temperature, respiratory rate, heart rate, and blood pressure—were monitored throughout the procedure. Clinical parameters were assessed 2–3 days after each PP + PE session, and treatment was repeated as indicated.
Observational indicators
Data were collected from the patients during their hospitalization, and all data were recorded in a predefined case report form. Based on our hospital’s electronic medical record system and paper charts, the following clinical data were collected: medical history, demographic data, vital signs (temperature, respiratory rate, heart rate, blood pressure, and pulse oximetry), physical examination findings, predisposing factors, ART plan, and pre- and post-treatment laboratory measurements, including the following: alanine aminotransferase (ALT), aspartate transferase (AST), ALB, TBil, indirect bilirubin (IBil), creatinine (Cr), serum potassium, serum sodium, INR, prothrombin time activity (PT%), fibrinogen (FBG), plasma ammonia (NH3), hemoglobin (Hb), platelet count (Plt), blood NH3,Model for End-stage Liver Disease score(MELDs), biological markers associated with HBV infection, and HBV-DNA. Receipt of ART, HIV viral markers (HIV-DNA), and immune markers (CD4+, CD8+) were also recorded.
We regularly followed up with discharged patients and scheduled appointments for follow-up. Treatment plans at discharge (including liver transplantation and artificial liver therapy) and confirmed survival status were documented.
Statistical methods
Because the distribution of patients’ baseline characteristics was not comparable between the HBV-ACLF/HIV(−) and HBV-ACLF/HIV(+) groups, 1:1 propensity score matching (PSM) was performed to adjust for baseline bias, using a caliper value with a standard deviation of 0.2 [10]. Propensity scores were estimated using logistic regression based on baseline age, sex, number of artificial liver treatments, HBV-DNA, ALT, AST, ALB, TBil, IBil, serum potassium, Cr, serum sodium, INR, PT%, FBG, leukocyte counts, Hb, Plt, and blood NH3,MELDs.
All data were analyzed using SPSS 25 and R 4.5.0 software. Normality tests were conducted using the Kolmogorov–Smirnov test. For variables with a normal distribution, data are presented as mean ± standard deviation; for categorical variables, percentages are used. Between-group comparisons were conducted using the independent-samples t-test, while within-group pre- and post-treatment comparisons were performed using the paired t-test. For non-normally distributed variables, data are presented as median (interquartile range); between-group comparisons used the Mann–Whitney U test, and within-group comparisons used the Wilcoxon signed-rank test. Categorical variables were compared using the chi-square test. Survival curves were generated using the Kaplan–Meier method, and differences in survival were assessed with the log rank test. Variables with statistical significance in the univariate analysis were included in the multivariate analysis. The multivariate analysis was performed using a Cox proportional hazards regression model. All statistical tests were two-tailed, and a P value of < 0.05 was considered statistically significant.
Ethical review
This research project was approved by the relevant ethics committee or institution ([YJ-K2024-72-01]) and was conducted in strict accordance with applicable ethical guidelines. The rights and privacy of all participants were respected and protected, and the confidentiality of personal information was fully maintained.