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The present narrative review on albumin dialysis provides evidence-based and expert opinion guidelines for clinicians caring for adult patients with different types of liver failure. The review was prepared by an expert panel of 13 members with liver and ntensive care expertise in extracorporeal liver support therapies for the management of patients with liver failure. The coordinating committee developed the questions according to their importance in the management of patients with liver failure. For each indication, experts conducted a comprehensive review of the literature aiming to identify the best available evidence and assessed the quality of evidence based on the literature and their experience. Summary statements and expert’s recommendations covered all indications of albumin dialysis therapy in patients with liver failure, timing and intensity of treatment, efficacy, technical issues related to the device and safety. The panel supports the data from the literature that albumin dialysis showed a beneficial effect on hepatic encephalopathy, refractory pruritus, renal function, reduction of cholestasis and jaundice. However, the trials lacked to show a clear beneficial effect on overall survival. A short-term survival benefit at 15 and 21 days respectively in acute and acute-on-chronic liver failure has been reported in recent studies. The technique should be limited to patients with a transplant project, to centers experienced in the management of advanced liver disease. The use of extracorporeal albumin dialysis could be beneficial in selected patients with advanced liver diseases listed for transplant or with a transplant project. Waiting future large randomized controlled trials, this panel experts’ statements may help careful patient selection and better treatment modalities.

Patients with liver failure may suffer citrate accumulation when using regional citrate anticoagulation for artificial liver support system therapy (RCA-ALSS therapy). This study aimed to develop a predictive scoring system to stratify the risk of citrate accumulation. A total of 338 patients treated with RCA-ALSS therapy were retrospectively enrolled and randomly divided into derivation and validation cohorts. Longer duration of citrate accumulation (LDCA) was defined as the presence of citrate accumulation 2 h after RCA-ALSS therapy. Four baseline variables were found to be independently associated with LDCA: gender, international normalized ratio of prothrombin time, serum creatinine, and serum chloride. A predictive R-CA model and its simplified R-CA score were developed. The R-CA model (AUROC = 0.848) was found to be superior to the MELD score (AUROC = 0.725; p  = 0.022) and other univariate predictors (AUROCs < 0.700; all p  ≤ 0.001) in predicting LDCA. The R-CA score (AUROC = 0.803) was as capable as the R-CA model ( p  = 0.369) and the MELD score ( p  = 0.174), and was superior to other univariate predictors (all p  < 0.05) in predicting LDCA. An R-CA score of 0–2 had a negative predictive value of 90.2% for LDCA. Our R-CA score reliably predicts LDCA in patients with RCA-ALSS therapy, and it is easy to use. Patients with R-CA score of 0–2 can safely receive RCA-ALSS therapy, while others should be carefully evaluated before treatment. Trial registration : Chinese Clinical Trial Registry, ChiCTR2000029179. Registered 17 January 2020, https://www.chictr.org.cn/showproj.aspx?proj=48084 .

Artificial liver support system (ALSS) therapy is widely used in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). We aimed to develop a predictive score to identify the subgroups who may benefit from plasma exchange (PE)-centered ALSS therapy. A total of 601 patients were retrospectively enrolled and randomly divided into a derivation cohort of 303 patients and a validation cohort of 298 patients for logistic regression analysis, respectively. Five baseline variables, including liver cirrhosis, total bilirubin, international normalized ratio of prothrombin time, infection and hepatic encephalopathy, were found independently associated with 3-month mortality. A predictive PALS model and the simplified PALS score were developed. The predicative value of PALS score (AUROC = 0.818) to 3-month prognosis was as capable as PALS model (AUROC = 0.839), R score (AUROC = 0.824) and Yue-Meng’ score (AUROC = 0.810) (all p  > 0.05), and superior to CART model (AUROC = 0.760) and MELD score (AUROC = 0.765) (all p  < 0.05). The PALS score had significant linear correlation with 3-month mortality (R 2  = 0.970, p  = 0.000). PALS score of 0–2 had both sensitivity and negative predictive value of > 90% for 3-month mortality, while PALS score of 6–9 had both specificity and positive predictive value of > 90%. Patients with PALS score of 3–5 who received 3–5 sessions of ALSS therapy had much lower 3-month mortality than those who received 1–2 sessions (32.8% vs. 59.2%, p  < 0.05). The more severe patients with PALS score of 6–9 could still benefit from ≥ 6 sessions of ALSS therapy compared to ≤ 2 sessions (63.6% vs. 97.0%, p  < 0.05). The PALS score could predict prognosis reliably and conveniently. It could identify the subgroups who could benefit from PE-centered ALSS therapy, and suggest the reasonable sessions. Trial registration: Chinese Clinical Trial Registry, ChiCTR2000032055. Registered 19th April 2020, http://www.chictr.org.cn/showproj.aspx?proj=52471 .

The impact of neutrophil percentage-to-albumin ratio (NPAR) on the outcome of acute-on-chronic liver failure (ACLF) is scant. A retrospective cohort study was conducted in patients with ACLF treated with artificial liver support system (ALSS). The ACLF was diagnosed according to the Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH ACLF) criteria. Disease severity was rated according to the COSSH ACLF score. Restricted cubic splines, linear or Cox regression models were used to investigate the relationships of baseline NPAR with disease severity and 90-day prognosis. The 90-day transplant-free and overall survival rates of 258 eligible patients were 58.5% and 66.3%, respectively. The NPAR in transplant-free survivors was lower than that in transplant or death patients (22.8 ± 4.4 vs. 25.3 ± 3.7, P  < 0.001). NPAR was positively associated with COSSH ACLF score (adjusted β (95% CI) > 0, P  < 0.001), transplant-free survival (adjusted HR (95% CI) for transplant or death: 1.07 (1.02–1.13), P  = 0.007), and overall survival (adjusted HR (95% CI) for death: 1.09 (1.03–1.15), P  = 0.003). Patients with NPAR ≥ 22.4 had poor 90-day prognosis compared to the rest (all adjusted HR (95% CI) > 1, P  < 0.05). NPAR was positively associated with disease severity and poor short-term prognosis in patients with COSSH ACLF who underwent ALSS treatment. Thus, it could be used as a prognostic biomarker for COSSH ACLF.

The liver is a very complex organ that ensures numerous functions; it is thus susceptible to multiple types of damage and dysfunction. Since 1983, orthotopic liver transplantation (OLT) has been considered the only medical solution available to patients when most of their liver function is lost. Unfortunately, the number of patients waiting for OLT is worryingly increasing, and extracorporeal liver support devices are not yet able to counteract the problem. In this review, the current and expected methodologies in liver regeneration are briefly analyzed. In particular, human pluripotent stem cells (hPSCs) as a source of hepatic cells for liver therapy and regeneration are discussed. Principles of hPSC differentiation into hepatocytes are explored, along with the current limitations that have led to the development of 3D culture systems and organoid production. Expected applications of these organoids are discussed with particular attention paid to bio artificial liver (BAL) devices and liver bio-fabrication.

Acute-on-chronic liver failure (ACLF) is an extremely severe clinical syndrome, often associated with systemic inflammation, coagulation dysfunction, and fibrinolysis abnormalities. Fibrin degradation product (FDP), as a byproduct of fibrinolysis, is a crucial indicator reflecting the state of fibrinolysis. The objective of this study is to investigate the relationship between FDP levels and the 28-day mortality rate in patients with ACLF. We retrospectively enrolled 520 patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) who underwent artificial liver support system therapy and collected relevant clinical data at admission. Cox regression analysis was employed to investigate the relationship between FDP levels and the 28-day mortality rate, and the predictive value of FDP was evaluated using receiver operating characteristic (ROC) curves. Among the 520 eligible patients, the 28-day mortality rate was 20.2%. The FDP levels of surviving patients were significantly lower than those of deceased patients [6.15 (3.23-10.97) vs. 16.98 (9.58-28.93), P < 0.001]. Through multivariate Cox proportional hazards analysis, after adjusting for confounding factors, It was observed that for every 10 µg/mL increase in FDP levels, the risk increased by 12.8% [HR = 1.128 (95% CI: 1.044-1.219), P < 0.001]. Compared to patients with low FDP levels (< 11.1 µg/mL), patients with high FDP levels (≥ 11.1 µg/mL) demonstrated a markedly higher mortality risk [HR = 3.222 (95% CI: 1.999-5.192), P < 0.001]. Among various prognostic scores, the COSSH-ACLF score exhibited the largest area under the receiver operating characteristic curve (AUROC), comparable to that of FDP (P = 0.891), and its predictive performance was superior to that of FIB and D-dimer. Additionally, for patients who received three or more sessions of artificial liver support system therapy, those with high FDP levels had a significantly reduced 28-day mortality risk. Elevated FDP levels are associated with the 28-day prognosis in patients with HBV-ACLF. Moreover, undergoing multiple sessions of artificial liver treatment is associated with favorable survival outcomes for patients with high FDP levels (≥ 11.1 µg/mL).

Objective Our objective was to compare the effectiveness of nonbiological artificial liver (NBAL) support, particularly short-term (28-day) survival rates, in patients who underwent treatment using double plasma molecular adsorption system (DPMAS), plasma exchange (PE), or combined PE+DPMAS, in addition to comprehensive physical treatment for different stages of acute-on-chronic liver failure (ACLF). Methods We retrospectively reviewed clinical data of 135 patients with ACLF who received NBAL treatment between November 2015 and February 2019. The patients were categorized into PE, DPMAS, and PE+DPMAS groups. Short-term effectiveness of treatment was assessed and compared based on selected clinical findings, laboratory parameters, and liver function markers. Results Coagulation function improved significantly in all groups after treatment. In the PE and PE+DPMAS groups, prothrombin time decreased to different degrees, whereas plasma thromboplastin antecedent increased significantly after treatment. White blood cell counts increased and platelet counts decreased in all groups after treatment. The model for end-stage liver disease score, Child–Pugh grade, systematic inflammatory syndrome score, and sepsis-related organ failure score decreased in all three groups after treatment. Conclusions PE, DPMAS, and PE+DPMAS improved disease indicators in all patients with ACLF. The combined treatment improved the short-term effectiveness of treatment, especially in patients with mild ACLF.

Objective To compare the effectiveness of plasma perfusion combined with plasma exchange (PP + PE) artificial liver support system in patients with hepatitis B virus-associated acute-on-chronic liver failure with and without HIV infection (HBV-ACLF/HIV(+) and HBV-ACLF/HIV(−), respectively) and to assess the clinical value and safety of the artificial liver support system. Methods This study involved 162 patients diagnosed with HBV-ACLF and hospitalized at Chengdu Public Health Clinical Medical Center from January 2020 to January 2025, in accordance with the diagnostic criteria of the Chinese Guidelines for the Diagnosis and Treatment of Acute-on-Chronic Liver Failure (2025 edition) . Seventeen patients with tumors, severe underlying diseases, or other hepatitis virus infections were excluded. Patients were divided into the HBV-ACLF/HIV(+) and HBV-ACLF/HIV(−) groups. Propensity score matching (PSM) was used to correct baseline bias. Laboratory indices, Model for End-stage Liver Disease score (MELDs), and 28- and 90-day cumulative survival or mortality rates before and after artificial liver therapy were used as effectiveness indicators. Kaplan–Meier analysis was used to plot survival curves, and the log rank test was used to assess survival differences. Cox proportional hazards regression modeling was used for multifactorial analysis to further evaluate the effectiveness of PP + PE therapy and prognostic factors. Results In total, 145 patients with HBV-ACLF were included, with 64 in the HBV-ACLF/HIV(+) group and 81 in the HBV-ACLF/HIV(−) group. After 1:1 PSM, 29 patients remained in each group. Alanine aminotransferase, glutamate transferase, total bilirubin, indirect bilirubin, international normalized ratio, prothrombin time activity, and MELDs significantly improved in both groups after PP + PE treatment ( P  < 0.05). Before and after PSM, there was no statistically significant difference in 28- or 90-day cumulative survival between the HBV-ACLF/HIV(+) and HBV-ACLF/HIV(−) groups (after PSM: log rank, P  = 0.572). Multifactorial Cox regression analysis showed that improvements in total bilirubin, creatinine, leukocytes, blood ammonia, MELDs, international normalized ratio, and prothrombin time activity were associated with better short-term prognosis in patients with HBV-ACLF/HIV(+) ( P  < 0.005). Conclusion The PP + PE artificial liver treatment model effectively promotes liver function recovery and improves clinical status in HBV-ACLF patients, including those with HIV co-infection. This provides a valuable basis for clinical management of co-infected cases. Multicenter prospective studies are needed to confirm its long-term efficacy.

Background Hyperthyroidism complicated by liver failure is associated with high mortality, and the optimal treatment strategy remains unclear. We aimed to compare the clinical characteristics of patients who received different treatments for hyperthyroidism and liver failure. Methods This retrospective cohort study included 137 patients diagnosed with hyperthyroidism and Liver failure between January 2013 and December 2022. The patients were treated with methimazole (MMI) plus artificial liver support system (ALSS), radioactive iodine ( 131 I) plus ALSS, or MMI alone for 24 weeks. Liver and thyroid function were monitored to determine treatment efficacy and potential complications. Results After propensity score matching, no significant differences in treatment efficacy were observed between MMI plus ALSS and MMI alone at discharge ( P  = 0.425), 12 weeks ( P  = 0.104), or 24 weeks ( P  = 0.104). There were also no significant differences in treatment efficacy between 131 I plus ALSS and MMI alone. However, hospital stays were shorter in the MMI and 131 I plus ALSS groups than in the MMI alone group ( P  = 0.014 and P  = 0.010, respectively). The incidence of adverse events did not differ significantly between the groups. Conclusions Our results suggest that 131 I plus ALSS, MMI plus ALSS or MMI are effective in treating hyperthyroidism and liver failure, and that the addition of ALSS reduces recovery times. Therefore, clinicians can select any of these treatment options based on specific patient characteristics.

Background and aims Different modes of artificial liver support (ALS) therapy can improve the survival of patients with acute-on-chronic liver failure (ACLF). This study aimed to compare the effects of mixed using different modes of ALS (MALS) and single using one mode of ALS (SALS) on 28- and 90-day survival rates of ACLF. Methods Clinical data and survival times of patients with ACLF treated for ALS between January 1, 2018 and December 30, 2021 were retrospectively collected. Cox regression analysis was performed to identify risk factors of 28- and 90-day mortalities. Results Of the 462 eligible ACLF patients, 388 belonged to the SALS group (76.3% male, 74.2% cirrhosis) and 74 to the MALS group (86.5% male, 71.6% cirrhosis). Comparison of 28-day and 90-day crude mortality between the SALS and MALS groups showed no significant differences (28-day: 20.4% vs. 14.9%, p  = 0.27; 90-day: 44.6% vs. 52.7%, p  = 0.20). After adjusting for confounders, the 28-day mortality (adjusted hazard ratio [aHR]: 0.32, 95% confidence interval [CI] 0.16–0.65) and 90-day mortality (aHR: 0.65, 95% CI 0.44–0.95) in the MALS group were significantly lower than those in the SALS group. These associations were consistently observed across pre-specified subgroups according to age, sex, etiology, and Child–Pugh grade. However, positive interactions between MALS and 90-day mortality were found between MALS and 90-day mortality in those with MELD score ≥ 22 and international normalized ratio ≥ 1.9 ( p for interaction < 0.05). Conclusion MALS therapy significantly decreased 28- and 90-day mortalities of ACLF than SALS did, especially in advanced stages. Graphical abstract