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Acute-on-chronic liver failure (ACLF) exhibits etiological heterogeneity across regions, with hepatitis B virus (HBV)-related ACLF predominant in China and alcohol-related ACLF dominating Western populations. This multicenter retrospective study systematically compared clinical profiles of HBV-related (n = 659) and alcohol-related ACLF (n = 296) stratified by the World Gastroenterology Organization (WGO) A/B/C classification, reflecting underlying chronic liver disease severity. Compared to HBV-related ACLF, alcohol-related ACLF showed higher systemic inflammation (leukocytosis, neutrophilia), bacterial infection ( P  < 0.001), extrahepatic organ failures (single-organ: renal, brain and respiratory, all P  < 0.05; multi-organ: P  < 0.001) and higher CLIF-C ACLF/COSSH-ACLF II scores. Conversely, HBV-related ACLF exhibited acute hepatocellular injury (elevated ALT/AST), and higher MELD/MELD-Na scores. These etiological disparities were most pronounced in type C ACLF. Despite these distinct profiles, mortality did not differ between etiologies. Type C ACLF demonstrated poorest profiles and uniformly high 90-day mortality (> 45%) regardless of etiology driven by cumulative organ failure burden. Importantly, CLIF-C ACLF and COSSH-ACLF II scores outperformed MELD and MELD-Na scores in predicting outcomes for type C patients. These findings underscore the critical influence of diverse etiologies and severity stages of underlying chronic liver diseases on ACLF profiles and outcomes, thereby necessitating stratified management approaches tailored to underlying chronic liver disease to ultimately improve patient outcomes.

Very recently, we creatively put forward a new classification for ACLF patients, which lays the foundation for the establishment of prognostic model that can accurately predict the prognosis of ACLF patients. Herein, we found: galectin-3 levels were higher in type A ACLF patients compared to those of type B patients; galectin-3 expression was closely correlated with TBil, PTA/INR and MELD; galectin-3 is an independent predictive factor for rapid progression in ACLF, and exhibited superior predictive value for the prognosis of type A ACLF patients than MELD score; and the survival rate was remarkably higher in ACLF patients with lower galectin-3 expression. Collectively, galectin-3 can be considered as a non-invasive biomarker to predict the prognosis of ACLF patients with new typing. Our findings help advance the time window of prognosis prediction for type A and type B ACLF patients from 4 weeks to the baseline, thereby identifying ACLF patients who really need liver transplantation earlier and improving the survival of ACLF patients.

Acute-on-chronic liver failure (ACLF) is defined by the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) consortium and the North American Consortium for the Study of End-Stage Liver Disease (NACSELD) as an acute deterioration of cirrhosis with multiple organ failures and high short-term mortality. However, their diagnostic criteria differ. We aimed to compare these 2 criteria in the prediction of prognosis in hospitalized cirrhosis. This was a prospective study of nonelectively hospitalized patients with cirrhosis (N = 468) from a single tertiary hospital between 2016 and 2018. Baseline characteristics, incidence, and types of organ failure and survival data at 7, 28, and 90 days were collected. Prognostic utilities of the 2 criteria were compared. One hundred thirty-seven of 468 patients (29.3%) had EASL-CLIF ACLF, and 35 of 468 (7.4%) had NACSELD ACLF. The 28-day transplant-free survival of ACLF was 58.4% using EASL-CLIF and 37.1% using the NACSELD criteria. In predicting 28-day mortality, the NACSELD criteria demonstrated significantly higher overall accuracy (92.0% vs 85.3%, P < 0.01), specificity (99.7% vs 84.0%, P < 0.001), and positive predictive value (97.1% vs 50.4%, P < 0.001) but lower sensitivity (49.3% vs 92.5%, P < 0.001) and negative predictive value (91.6% vs 98.5%, P < 0.001) than those of EASL-CLIF. The results were similar in predicting 7-day outcome. However, the overall accuracy became similar between NACSELD and EASL-CLIF ACLF criteria in predicting 90-day mortality (86.3% vs 88.7%, P = 0.27) because of the decrease of sensitivity and negative predictive value of NACSELD ACLF criteria. The prognostic performance of these 2 ACLF criteria was similar when applied to patients with or without hepatitis B virus infection as an etiology of cirrhosis. There are both caveats and utilities of NACSELD and EASL-CLIF ACLF criteria in prognosis prediction in patients with cirrhosis. NACSED criteria is highly accurate in predicting morality, whereas the EASL-CLIF criteria is more sensitive to identify patients who would benefit from liver transplantation.

ObjectivePrognostic stratification of patients with cirrhosis is common clinical practice. This study compares the prognostic accuracy (28-day and 90-day transplant-free mortality) of the acute-on-chronic liver failure (ACLF) classification (no ACLF, ACLF grades 1, 2 and 3) with that of acute kidney injury (AKI) classification (no AKI, AKI stages 1, 2 and 3).DesignThe study was performed in 510 patients with an acute decompensation of cirrhosis previously included in the European Association for the Study of the Liver–Chronic Liver Failure consortium CANONIC study. ACLF was evaluated at enrolment and 48 h after enrolment, and AKI was evaluated at 48 h according to Acute Kidney Injury Network criteria.Results240 patients (47.1%) met the criteria of ACLF at enrolment, while 98 patients (19.2%) developed AKI. The presence of ACLF and AKI was strongly associated with mortality. 28-day transplant-free mortality and 90-day transplant-free mortality of patients with ACLF (32% and 49.8%, respectively) were significantly higher with respect to those of patients without ACLF (6.2% and 16.4%, respectively; both p<0.001). Corresponding values in patients with and without AKI were 46% and 59%, and 12% and 25.6%, respectively (p<0.0001 for both). ACLF classification was more accurate than AKI classification in predicting 90-day mortality (area under the receiving operating characteristic curve=0.72 vs 0.62; p<0.0001) in the whole series of patients. Moreover, assessment of ACLF classification at 48 h had significantly better prognostic accuracy compared with that of both AKI classification and ACLF classification at enrolment.ConclusionsACLF stratification is more accurate than AKI stratification in the prediction of short-term mortality in patients with acute decompensation of cirrhosis.

[...]the authors demonstrated that hypovolemic shock (ref. 1 , table 6) was the cause of death in 16% of the patients with ACLF. [...]bleeding and impaired coagulation seem to contribute significantly to the prognosis of patients with acutely decompensated liver cirrhosis. [...]much less PCC (6500 IU vs 35 750 IU; figure 1 A) and FFP (0 vs 2 units; figure 1 C) were transfused than under a conventional regime. Since it is already difficult to manage patients with advanced cirrhosis, especially in situations of ACLF, every option to reduce potential causes for complication (ie, prophylaxis of variceal bleeding) should be evaluated.

Background Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is characterized by immune dysregulation and systemic inflammation, which lead to high mortality. Although immunosuppressive CD45 + erythroid progenitor cells (EPCs) percentages are elevated in chronic hepatitis B (CHB) and are associated with disease progression, their role in HBV-ACLF remains unclear. This study aims to evaluate the impact of CD45 + EPCs on disease progression in patients with HBV-ACLF. Methods In this retrospective study, we analyzed the data of 102 patients with CHB and 65 patients with HBV-ACLF receiving standard drugs treatment from the Third Affiliated Hospital of Sun Yat-sen University between January 2021 and December 2023. HBV-ACLF diagnosis followed the Chinese Group on the Study of Severe Hepatitis B–Acute-on-Chronic Liver Failure criteria, with strict exclusion of comorbidities. Peripheral blood mononuclear cells (PBMCs) were isolated via density gradient centrifugation, and CD45 + EPCs (CD45 + CD71 + CD235a + ) were quantified using flow cytometry. Liver tissue EPCs were assessed by immunofluorescence in biopsy/transplant specimens. Receiver operating characteristic (ROC) and multivariable logistic regression analyses identified prognostic factors associated with disease progression. Results Our findings revealed that patients with HBV-ACLF had significantly elevated percentages of CD45 + EPCs compared with those with CHB. We also observed strong correlations between CD45 + EPC percentages and creatinine concentration, leukocyte count, and neutrophil-to-lymphocyte ratio (NLR). The area under the ROC curve for CD45 + EPCs was 0.718, indicating a significant predictive value [95% confidence interval (CI): 0.586–0.851, p =  0.004]. High CD45 + EPC percentage was associated with a greater incidence of hepatic encephalopathy (30.8% vs. 10.3%, p  = 0.037) and higher rates of disease progression (73.1% vs. 35.9%, p  = 0.003). Multivariate logistic regression analysis identified international normalized ratio (INR) and NLR as independent predictors of poor 28-day outcomes (INR odds ratio [OR] = 6.098, p  < 0.001; NLR OR = 1.354, p =  0.005). Conclusions The percentage of CD45 + EPCs in PBMCs may be a potential biomarker for predicting 28-day disease progression in patients with HBV-ACLF. These findings highlight their possible clinical utility for risk stratification.

Artificial liver support systems (ALSS) are widely used to treat patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). The aims of the present study were to investigate the subgroups of patients with HBV-ACLF who may benefit from ALSS therapy, and the relevant patient-specific factors. 489 ALSS-treated HBV-ACLF patients were enrolled, and served as derivation and validation cohorts for classification and regression tree (CART) analysis. CART analysis identified three factors prognostic of survival: hepatic encephalopathy (HE), prothrombin time (PT), and total bilirubin (TBil) level; and two distinct risk groups: low (28-day mortality 10.2–39.5%) and high risk (63.8–91.1%). The CART model showed that patients lacking HE and with a PT ≤ 27.8 s and a TBil level ≤455 μmol/L experienced less 28-day mortality after ALSS therapy. For HBV-ACLF patients with HE and a PT > 27.8 s, mortality remained high after such therapy. Patients lacking HE with a PT ≤ 27.8 s and TBil level ≤ 455 μmol/L may benefit markedly from ALSS therapy. For HBV-ACLF patients at high risk, unnecessary ALSS therapy should be avoided. The CART model is a novel user-friendly tool for screening HBV-ACLF patient eligibility for ALSS therapy, and will aid clinicians via ACLF risk stratification and therapeutic guidance.

Background and aim Liver failure, which is predominantly caused by hepatitis B (HBV) can be improved by an artificial liver support system (ALSS). This study investigated the phenotypic heterogeneity of immunocytes in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF) before and after ALSS therapy. Methods A total of 22 patients with HBV-ACLF who received ALSS therapy were included in the study. Patients with Grade I according to the ACLF Research Consortium score were considered to have improved. Demographic and laboratory data were collected and analyzed during hospitalization. Immunological features of peripheral blood in the patients before and after ALSS were detected by mass cytometry analyses. Results In total, 12 patients improved and 10 patients did not. According to the immunological features data after ALSS, the proportion of circulating monocytes was significantly higher in non-improved patients, but there were fewer γδT cells compared with those in improved patients. Characterization of 37 cell clusters revealed that the frequency of effector CD8 + T ( P  = 0.003), CD4 + T CM ( P  = 0.033), CD4 + T EM ( P  = 0.039), and inhibitory natural killer (NK) cells ( P  = 0.029) decreased in HBV-ACLF patients after ALSS therapy. Sub group analyses after treatment showed that the improved patients had higher proportions of CD4 + T CM ( P  = 0.010), CD4 + T EM ( P  = 0.021), and γδT cells ( P  = 0.003) and a lower proportion of monocytes ( P  = 0.012) compared with the non-improved patients. Conclusions Changes in effector CD8 + T cells, effector and memory CD4 + T cells, and inhibitory NK cells are associated with ALSS treatment of HBV-ACLF. Moreover, monocytes and γδT cells exhibited the main differences when patients obtained different prognoses. The phenotypic heterogeneity of lymphocytes and monocytes may contribute to the prognosis of ALSS and future immunotherapy strategies.

Acute-on-chronic liver failure (ACLF) is a newly defined clinical entity with significant morbidity and mortality (~40–90 % at 1 year dependent on need for organ support at presentation). It defines a presentation with acute severe liver injury, often with multiorgan dysfunction, on a background of previously known or unknown cirrhosis. In its severest form, it is almost indistinguishable from acute liver failure, as similarly in around 5 % may rapidly progress to intracranial hypertension and cerebral oedema culminating in coma and/or death. Our understanding of such cerebral sequelae is currently limited to clinical observation, though our knowledge base is rapidly expanding since recent consensus clinical definition and guidance. Moreover, there are now animal models of ACLF and imaging modalities to better characterize events in the brain that occur with ACLF. However, as yet there has been little in the way of interventional study of this condition which are much needed. In this review we dissect existing clinical and experimental data to better characterise the manifestations of ACLF on the brain and allow for the development of targeted therapy as currently the plethora of existing interventions were designed to treat either the effects of cirrhosis or acute liver injury independently.