sTREM-1 as promising prognostic biomarker for acute-on-chronic liver failure and mortality in patients with acute decompensation of cirrhosis.

BACKGROUND: Acute decompensation (AD) of cirrhosis is associated with high short-term mortality, mainly due to the development of acute-on-chronic liver failure (ACLF). Thus, there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and mortality. Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is released from activated innate immune cells and correlated with various inflammatory processes. AIM: To explore the prognostic value of sTREM-1 in patients with AD of cirrhosis. METHODS: A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort (n = 309) and validation cohort (n = 133). Demographic and clinical data were collected, and serum sTREM-1 was measured at admission. All enrolled patients were followed-up for at least 1 year. RESULTS: In patients with AD and cirrhosis, serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver, coagulation, cerebral and kidney failure. A new prognostic model of AD (P-AD) incorporating sTREM-1, blood urea nitrogen (BUN), total bilirubin (TBil), international normalized ratio (INR) and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease (MELD), MELD-sodium (MELD-Na), chronic liver failure-consortium (CLIF-C) ACLF and CLIF-C AD scores. Additionally, sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d follow-up. The ACLF risk score incorporating serum sTREM-1, BUN, INR, TBil and aspartate aminotransferase levels was established and significantly superior to MELD, MELD-Na, CLIF-C ACLF, CLIF-C AD and P-AD in predicting risk of ACLF development. CONCLUSION: Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.

Histological characteristics in patients admitted to the hospital with alcoholic hepatitis complicated by acute-on-chronic liver failure.

OBJECTIVES: Alcoholic hepatitis (AH) is a frequent precipitating event for the development of acute-on-chronic liver failure (ACLF), a syndrome characterised by organ failures due to immune dysfunction. The histological features of this complication are not well characterized. We investigated whether ACLF has specific histological characteristics. METHODS: Prospective cohort study in consecutive adult patients admitted between 03-2008 and 04-2021 to a tertiary referral centre with suspected AH. Diagnosis of AH was based on clinical presentation and confirmed by transjugular liver biopsy. All biopsies were assessed by a dedicated liver pathologist, blinded for clinical data and outcome. Diagnosis of ACLF was based on EASL-CLIF criteria. Histological and clinical characteristics of patients with and without ACLF at baseline were compared. RESULTS: 184 patients with biopsy-proven AH were enrolled. Median time from hospital admission to transjugular biopsy was 4.5 days (IQR 2-8). At baseline, ACLF was present in 73 patients (39.7%). Out of the 110 patients without ACLF at baseline, 30 (27.3%) developed ACLF within 28 days (median 7.5 days (IQR 2-20)). At baseline, ductular bilirubinostasis (DB) was the only histological feature significantly more frequently present in patients with ACLF compared to patients without ACLF (50.7% vs. 30.6%, p = 0.003). No clear association between histological features and the development of ACLF later on could be demonstrated. CONCLUSIONS: In this well-defined cohort of patients with biopsy-proven AH, DB was associated with the presence of ACLF. This finding fits with the pathophysiology of this syndrome, which is characterized by systemic inflammation and an increased risk of infections.

Acute decompensation of cirrhosis versus acute-on-chronic liver failure: What are the clinical implications?

It is essential to identify the subgroup of patients who experience poorer outcomes in order to adapt clinical management effectively. In the context of liver disease, the earlier the identification occurs, the greater the range of therapeutic options that can be offered to patients. In the past, patients with acute decompensation (AD) of chronic liver disease were treated as a homogeneous group, with emphasis on identifying those at the highest risk of death. In the last 15 years, a differentiation has emerged between acute-on-chronic liver failure syndrome (ACLF) and AD, primarily due to indications that the latter is linked to a less favorable short-term prognosis. Nevertheless, the definition of ACLF varies among the different knowledge societies, making it challenging to assess its true impact compared with AD. Therefore, the purpose of this review is to provide a detailed analysis emphasizing the critical importance of identifying ACLF in the field of advanced liver disease. We will discuss the differences between Eastern and Western approaches, particularly in relation to the occurrence of liver failure and disease onset. Common characteristics, such as the dynamic nature of the disease course, will be highlighted. Finally, we will focus on two key clinical implications arising from these considerations: the prevention of ACLF before its onset and the clinical management strategies once it develops, including liver transplantation and withdrawal of care.

[Epidemiological characteristics of inpatients with liver failure at the Beijing You'an Hospital from 2012 to 2021].

Objective: To elucidate the epidemiological characteristics and changing trends of liver failure in order to provide evidence-based strategies for prevention and treatment. Methods: The epidemiological information of inpatients with liver failure admitted and treated at Beijing You'an Hospital from 2012 to 2021 was retrospectively collected. The trend test was used to analyze age, gender, as well as the year-by-year changes in the underlying acute and chronic etiology of acute liver failure (ALF), sub-acute liver failure (SALF), acute-on-chronic liver failure (ACLF), and chronic liver failure (CLF). Results: During the study period, information on a total of 8512 inpatients, aged 51.3±13.5 years and mainly male (71.9%) with liver failure, was collected. The highest to lowest proportions of liver failure types were ACLF 4 023 (47.3%), CLF 3 571(42.0%), SALF 670 (7.9%), and ALF 248 (2.9%). The top five causes of liver failure in the overall population, accounting for 87.6% of the total, were hepatitis B 3 199 (37.58%), alcoholic liver disease 2 237 (26.28%), cryptogenic liver disease 906(10.61%), hepatitis B + alcoholic liver disease 603 (7.08%), drugs 488 (5.73%), The top three etiologies of patients with different types of liver failure were acute etiologies for acute liver failure (ALF), followed by drugs 107 (43.1%), hepatitis B 47(19.0%), and unknown etiology 36 (14.5%); sub-acute liver failure (SALF), followed by drugs 381(56.9%), unknown etiology 106 (15.8%), and sepsis 56 (8.4%); and acute-on-chronic liver failure (ACLF), followed by drugs 2 092(52.0%), alcoholic liver disease 813(20.2%), and cryptogenic liver disease 398(9.9%); and chronic etiologies for chronic liver failure (CLF), followed by alcoholic liver disease 1 410(39.5%), hepatitis B 1 028(28.8%), and cryptogenic liver disease 364(10.2%). Longitudinal analysis showed that the average age of patients with liver failure increased year by year, but the sex ratio trend did not change significantly, with male patients predominating throughout. The proportion of drug-induced liver failure in patients with ALF and SALF increased year by year, and the difference in the trend test was statistically significant (P < 0.05). The proportion of patients with chronic etiologies of ACLF and CLF decreased year by year among hepatitis B, while the proportion of alcoholic liver disease, autoimmune liver disease, and cryptogenic liver disease increased year by year (the difference was statistically significant, P < 0.05). Conclusion: The etiological spectrum of liver failure is changing in our country. Although hepatitis B is still the main cause of liver failure, its proportion shows a decreasing trend year by year, with the exception of ACLF, which is no longer the primary etiology of other types of liver failure, while drug-induced liver disease, alcoholic liver disease, autoimmune liver disease, and cryptogenic liver disease are increasing year by year and will become the focus of liver disease prevention and treatment in the future.

The Role of Hypoxia-Inducible Factor 1 Alpha in Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is associated with increased mortality. Specific therapy options are limited. Hypoxia-inducible factor 1 alpha (HIF-1α) has been linked to the pathogenesis of chronic liver disease (CLD), but the role of HIF-1α in ACLF is poorly understood. In the current study, different etiologies of CLD and precipitating events triggering ACLF were used in four rodent models. HIF-1α expression and the intracellular pathway of HIF-1α induction were investigated using real-time quantitative PCR. The results were verified by Western blotting and immunohistochemistry for extrahepatic HIF-1α expression using transcriptome analysis. Exploratory immunohistochemical staining was performed to assess HIF-1α in human liver tissue. Intrahepatic HIF-1α expression was significantly increased in all animals with ACLF, regardless of the underlying etiology of CLD or the precipitating event. The induction of HIF-1α was accompanied by the increased mRNA expression of NFkB1 and STAT3 and resulted in a marked elevation of mRNA levels of its downstream genes. Extrahepatic HIF-1α expression was not elevated. In human liver tissue samples, HIF-1α expression was elevated in CLD and ACLF. Increased intrahepatic HIF-1α expression seems to play an important role in the pathogenesis of ACLF, and future studies are pending to investigate the role of therapeutic HIF inhibitors in ACLF.

Influence of metabolic dysfunction-associated fatty liver disease on the prognosis of patients with HBV-related acute-on-chronic liver failure.

OBJECTIVES: Metabolic-associated fatty liver disease (MAFLD) has clinical relevance in patients with acute-on-chronic liver failure (ACLF). We investigated the association between MAFLD and prognosis in patients with ACLF. METHODS: We included patients with ACLF with available clinical data who visited our hospital for nearly 9 years. We compared the prognosis of patients in the different subgroups of ACLF and predicted the incidence of adverse outcomes. Moreover, a new model based on MAFLD was established. RESULTS: Among 339 participants, 75 had MAFLD. The prognosis of patients with ACLF was significantly correlated with MAFLD. Patients with ACLF with concomitant MAFLD tended to have a lower cumulative survival rate (p = 0.026) and a higher incidence of hepatorenal syndrome (9.33% versus 3.40%, p = 0.033) than those without MAFLD. We developed an TIM2 model and the area under the ROC curve of the new model for 30-day and 60-day mortality (0.759 and 0.748) was higher than other predictive methods. CONCLUSION: The presence of MAFLD in patients with HBV-related ACLF was associated with an increased risk of in-hospital mortality. Moreover, The TIM2 model is a high-performance prognostic score for HBV-related ACLF.

The First Successful Living Donor Liver Transplantation for Acute-on-Chronic Liver Failure Caused by Severe Acute Necrotizing Pancreatitis: A Case Report.

Liver transplantation (LT) is the only life-saving option when acute-on-chronic liver failure (ACLF) does not improve with conservative therapy. Acute pancreatitis (AP) can cause chronic liver disease progression to ACLF. However, deceased donor LT for patients with AP has had mixed results, and no consensus has been established regarding the indication for LT. We report the first successful living donor LT (LDLT) for ACLF caused by severe AP. The 38-year-old patient with alcoholic liver disease was transferred to our institute with worsening refractory ascites. During the pretransplant workup, she developed severe acute necrotizing pancreatitis, resulting in grade 3 ACLF. The patient's clinical course was further complicated by high levels of donor-specific antibodies and immune thrombocytopenia. The AP gradually improved after intensive care combined with artificial liver support. The patient successfully underwent urgent LDLT with upfront splenectomy and desensitization therapy, including plasm exchange, high-dose intravenous immunoglobulin, and anti-thymocyte globulin. No infection or recurrence of AP was observed postoperatively. We conclude that LDLT is a feasible option for ACLF patients caused by severe AP if a deceased donor is not readily available.

Plasma exchange for acute and acute-on-chronic liver failure: A systematic review and meta-analysis.

Plasma exchange (PE) is a promising therapeutic option in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). However, the impact of PE on patient survival in these syndromes is unclear. We aimed to systematically investigate the use of PE in patients with ALF and ACLF compared with standard medical therapy (SMT). We searched PubMed/Embase/Cochrane databases to include all studies comparing PE versus SMT for patients ≥ 18 years of age with ALF and ACLF. Pooled risk ratios (RR) with corresponding 95% CIs were calculated by the Mantel-Haenszel method within a random-effect model. The primary outcome was 30-day survival for ACLF and ALF. Secondary outcomes were overall and 90-day survival for ALF and ACLF, respectively. Five studies, including 343 ALF patients (n = 174 PE vs. n = 169 SMT), and 20 studies, including 5,705 ACLF patients (n = 2,856 PE vs. n = 2,849 SMT), were analyzed. Compared with SMT, PE was significantly associated with higher 30-day (RR 1.41, 95% CI 1.06-1.87, p = 0.02) and overall (RR 1.35, 95% CI 1.12-1.63, p = 0.002) survival in ALF patients. In ACLF, PE was also significantly associated with higher 30-day (RR 1.36, 95% CI 1.22-1.52, p < 0.001) and 90-day (RR 1.21, 95% CI 1.10-1.34, p < 0.001) survival. On subgroup analysis of randomized controlled trials, results remained unchanged in ALF, but no differences in survival were found between PE and SMT in ACLF. In conclusion, PE is associated with improved survival in ALF and could improve survival in ACLF. PE may be considered in managing ALF and ACLF patients who are not liver transplant (LT) candidates or as a bridge to LT in otherwise eligible patients. Further randomized controlled trials are needed to confirm the survival benefit of PE in ACLF.

Living donor liver transplant in acute on chronic liver failure grade 3: Who not to transplant.

BACKGROUND AND AIM: Liver transplantation(LT)offers definitive treatment for acute on chronic liver failure(ACLF) patients. This study was done to analyze and compare the outcomes of living donor LT(LDLT) in patients with ACLF versus Chronic liver disease(CLD) and within the grades of ACLF. Factors affecting mortality in patients with ACLF and ACLF grade3 (ACLF3) following LDLT were also derived. METHODS: Records of adult LDLT between 1/2/2017 and 30/9/2021 were analyzed. ACLF was classified based on EASL-CLIF definition. Post-transplant outcomes of ACLF were compared with CLD and within ACLF grades. Post LDLT mortality predictors were identified in ACLF and ACLF3 patients. RESULTS: Out of 853 patients who had LT in that period; 704 patients with CLD and 103 with ACLF [of which 54 (52.42%) had ACLF3] underwent LDLT. The one month and one-year post LDLT mortality was 8.81% and 9.80% in CLD; 19.42% and 31.06% in ACLF; and 25.92% and 38.89% in ACLF3 respectively. On log regression analysis, use of grafts from older donors and pre-operative respiratory failure in recipients was associated with poor survival in ACLF, while respiratory failure was a predictor of poor survival in ACLF3 following LDLT. CONCLUSION: Outcomes following LDLT are poorer in ACLF as compared to after CLD. Higher donor age and preoperative respiratory failure with PF Ratio<200 were associated with poor survival post LDLT in ACLF and ACLF3.

A nomogram based on psoas muscle index predicting long-term cirrhosis incidence in non-cirrhotic patients with HBV-related acute­on­chronic liver failure.

There is a lack of scoring system to predict the occurrence of cirrhosis in individuals with acute-on-chronic liver failure (ACLF) in the absence of cirrhosis. The goal of this study was to develop a psoas muscle index (PMI)-based nomogram for cirrhosis risk in non-cirrhotic patients with HBV-related ACLF. We included 274 non-cirrhotic HBV-ACLF patients who were randomly assigned to training and validation groups. Logistic analyses were performed to identify risk factors for cirrhosis. A nomogram was then constructed. The predictive performance of the nomogram was assessed using the area under the receiver operating characteristic curve (AUROC), calibration curve, and decision curve analysis (DCA). During the 360-day follow-up, 44.5% (122/274) of non-cirrhotic HBV-ACLF patients developed cirrhosis. A higher PMI at the L3 level was correlated with a decreased risk of long-term cirrhosis occurrence (OR 0.677, 95% CI 0.518-0.885, P = 0.004). The nomogram incorporating PMI, age, neutrophil-to-lymphocyte ratio (NLR), and international normalized ratio (INR), indicated satisfactory predictive performance for cirrhosis risk stratification in ACLF population. The nomograms had an AUROC of 0.812 (95% CI 0.747-0.866) and 0.824 (95% CI 0.730-0.896) in the training and validation cohorts, respectively. The calibration curves displayed excellent predictive accuracy of the nomogram in both sets. In both cohorts, the DCA verified the nomogram's clinical efficacy. In non-cirrhotic HBV-ACLF patients, a greater PMI appears to protect against long-term cirrhosis occurrence. Strong predictive performance has been demonstrated by PMI-based nomograms in assessing the likelihood of 1-year cirrhosis in those with HBV-ACLF.

Interleukin-8 predicts short-term mortality in acute-on-chronic liver failure patients with hepatitis B-related-related cirrhosis background.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a distinctive and severe syndrome, marked by an excessive systemic inflammatory response. In vivo, interleukin 8 (IL-8) is an essential pro-inflammatory cytokine. We aimed to investigate the value of serum IL-8 levels in predicting mortality in ACLF patients in the background of hepatitis B virus-related cirrhosis. METHODS: In this study, we conducted a retrospective analysis of the clinical baseline characteristics of 276 patients with ACLF in the context of HBV-related cirrhosis. Logistic regression analysis was employed to identify independent risk factors for short-, intermediate-, and long-term mortality. Using these independent risk factors, we developed a nomogram model, which was subsequently validated. To assess the clinical usefulness of the nomogram model, we performed decision curve analysis (DCA). RESULTS: Out of the 276 patients with ACLF, 98 (35.5%), 113 (40.9%), and 128 (46.4%) died within 28, 90, and 180 days, respectively. Serum IL-8 levels were only an independent predictor of 28-day mortality and could simply classify ACLF patients. Conversely, mean arterial pressure (MAP), HBV-DNA, and COSHACLF IIs were independent predictors of mortality across all three observation periods. We constructed a nomogram based on IL-8 that was able to visualise and predict 28-day mortality with a C-index of 0.901 (95% CI: 0.862-0.940). Our calibration curves, Predicted Probability of Death & Actual Survival Status plot, and Confusion Matrix demonstrated the nomogram model's strong predictive power. DCA indicated the nomogram's promising clinical utility in predicting 28-day mortality in ACLF patients. CONCLUSION: Serum IL-8 levels predict short-term mortality in ACLF patients in the background of HBV-associated cirrhosis, and the developed Nomogram model has strong predictive power and good clinical utility.

Systemic inflammatory response is a pathophysiological feature of patients with acute-on-chronic liver failure, and the serum level of interleukin-8 can predict the short-term prognosis of patients.

Application of extended criteria donor grafts in liver transplantation for acute-on-chronic liver failure: A retrospective cohort study.

BACKGROUND: There is no consensus on the usage of extended criteria donor (ECD) grafts in liver transplantation (LT) for acute-on-chronic liver failure (ACLF) patients. AIM: To summarize the experience of using ECD livers in ACLF-LT. METHODS: A retrospective cohort study was conducted, enrolling patients who underwent LT at the First Affiliated Hospital of Sun Yat-Sen University from January 2015 to November 2021. The patients were divided into ECD and non-ECD groups for analysis. RESULTS: A total of 145 recipients were enrolled in this study, of which ECD and non-ECD recipients accounted for 53.8% and 46.2%, respectively. Donation after cardiac death (DCD) recipients accounted for the minority compared with donation after brain death (DBD) recipients (16.6% vs 83.4%). Neither overall survival nor graft survival significantly differed between ECD and non-ECD and DCD and DBD recipients. ECD grafts were associated with a significantly higher incidence of early allograft dysfunction (EAD) than non-ECD grafts (67.9% vs 41.8%, P = 0.002). Postoperative outcomes between DCD and DBD recipients were comparable (P > 0.05). ECD graft (P = 0.009), anhepatic phase (P = 0.034) and recipient gamma glutamyltransferase (P = 0.016) were independent risk factors for EAD. Recipient preoperative number of extrahepatic organ failures > 2 (P = 0.015) and intraoperative blood loss (P = 0.000) were independent predictors of poor post-LT survival. CONCLUSION: Although related to a higher risk of EAD, ECD grafts can be safely used in ACLF-LT. The main factors affecting post-LT survival in ACLF patients are their own severe preoperative disease and intraoperative blood loss.

A novel imaging index for predicting adverse progression in acute-on-chronic liver failure related to hepatitis B virus: the low erector spine index.

BACKGROUND: It is widely known that muscle mass influences the outcomes of many chronic diseases. Erector spine mass is a convenient parameter obtained from routine abdominal computed tomography (CT). The clinical application value of erector spine mass, and whether erector spine mass could predict the outcome of disease has not been studied. AIM: To evaluate the role of the erector spine index (ESI) calculated based on abdominal CT imaging in the progression of acute-on-chronic liver failure related to the hepatitis B virus (HBV-ACLF). METHODS: We performed a retrospective study of 118 HBV-ACLF patients and calculated the ESI (the total erector spine area normalized for height2 in meters) for each patient through abdominal CT. The findings were analyzed regarding the progression of HBV-ACLF and the ESI at baseline, including mortality and the development of complications. RESULTS: The ESI level was associated with mortality and the development of complications. During the 90-day follow-up period, patients with a low ESI (<12.05 cm2/m2) had higher mortality than those with a high ESI (≥ 12.05 cm2/m2) (51.7% vs. 26.7%), and the cumulative survival rates were 71.0%±4.6 and 85.8%±3.9, respectively (log-rank P = 0.003). The hazard ratios (HRs) calculated using univariable and multivariable analyses were 2.23(95% confidence interval (CI): 1.25-4.21, P = 0.005) and 2.52 (95% CI: 1.34-9.24, P = 0.011), respectively. Patients with a low ESI (<12.05 cm2/m2) had higher incidences of kidney dysfunction (43.5% vs. 23.2%, P = 0.029; log-rank P = 0.017) and hepatic encephalopathy (39.6% vs. 14.0%, P = 0.003; log-rank P = 0.010) than those with a high ESI. A low ESI was an independent risk factor for kidney dysfunction (adjusted HR = 1.36, 95% CI: 1.05-2.93, P = 0.043) and the development of hepatic encephalopathy (adjusted HR = 2.26; 95% CI: 2.05-3.13, P = 0.036). In addition, the presence of hepatic encephalopathy (the odds ratio (OR) = 2.26, 95% CI: 2.05-3.18, P = 0.006), spontaneous bacterial peritonitis (OR = 3.95, 95% CI: 1.01-5.46, P = 0.037), and kidney dysfunction (OR = 4.47, 95% CI: 1.02-9.64, P = 0.032) was independently associated with a low ESI in patients. CONCLUSION: A low ESI is an independent risk factor for mortality in patients with HBV-ACLF, as well as the development of kidney dysfunction and hepatic encephalopathy.

Effect of CD163 Modification on Glucocorticoid-Related Mortality in Patients with Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.

Objective: This study aimed to assess the relationship between glucocorticoid treatment and mortality among patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Methods: We conducted a retrospective, hospital-based cohort study from 2019 to 2022, including 394 consecutively enrolled HBV-ACLF patients at the Third Affiliated Hospital of Chongqing Medical University. We recorded patient demographics, liver function, CD163 concentration, Model for End-Stage Liver Disease (MELD) score, and complications. The primary endpoint was 30-day mortality. Results: No significant differences were observed between the glucocorticoid-treated and non-glucocorticoid groups regarding sex, age, liver function, complications, or plasma CD163 concentration. After treatment, the median levels of total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), international normalized ratio (INR), and HBV DNA were 322.9 (IQR 258.6-383.3) µmol/L, 354.4 (IQR 253.1-444.6) U/L, 258.4 (IQR 186.4-322.4) U/L, 2.3 (IQR 2.1-2.5), and 5.0 (IQR 4.0-6.0) log IU/mL, respectively. Changes in ALT, AST, sCD163, TBil, INR, and MELD score before and after treatment showed no statistical differences between the glucocorticoid and non-glucocorticoid groups (P > .05). However, the mortality rate was significantly lower in the glucocorticoid group compared to the non-glucocorticoid group (11.2% vs. 29.9%, respectively; P < .001). Multivariable analysis revealed that, after adjusting for confounders, non-glucocorticoid treatment was associated with a higher adjusted hazard ratio (HR) for mortality (HR = 3.7, 95% CI 2.2-6.2) compared to glucocorticoid treatment. Additionally, an interaction test indicated that the association between non-glucocorticoid treatment and mortality was more robust in the sCD163 ≥ 18.2 mg/L group (HR = 7.6, 95% CI 2.9-19.9) but weaker in the sCD163 < 18.2 mg/L group (HR = 2.2, 95% CI 1.2-4.3) (P for interaction < .05). Conclusions: These findings suggest that glucocorticoids are an effective treatment for reducing mortality in HBV-ACLF patients, with particular effectiveness observed in patients with high sCD163 concentrations.

Risk factors for the mortality of hepatitis B virus-associated acute-on-chronic liver failure: a systematic review and meta-analysis.

BACKGROUND: Hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) has been confirmed as a prevalent form of end-stage liver disease in people subjected to chronic HBV infection. However, there has been rare in-depth research on the risk factors for the mortality of HBV-ACLF. This study aimed at determining the risk factors for the mortality of HBV-ACLF. METHODS: The relevant research was selected from four electronic databases that have been published as of August 2023. The existing research was reviewed in accordance with the inclusion and exclusion criteria. The level of quality of previous research was evaluated using the Newcastle-Ottawa scale. Moreover, a pooled estimate of the odds ratios (ORs) with their associated 95% confidence intervals (CIs) was provided through a meta-analysis. The data were combined, and the risk variables that at least two studies had considered were analyzed. The publication bias was examined through Egger's test and Begg's test. RESULTS: Twenty two studies that conformed to the inclusion criteria were selected from 560 trials. Eight risk variables in terms of HBV-ACLF mortality were determined, which covered INR (OR = 1.923, 95% CI = 1.664-2.221, P < 0.001), Monocytes (OR = 1.201, 95% CI = 1.113-1.296, P < 0.001), Cirrhosis (OR = 1.432, 95% CI = 1.210-1.696, P < 0.001), HE (OR = 2.553, 95% CI = 1.968-3.312, P < 0.001), HE grade (OR = 2.059, 95% CI = 1.561-2.717, P < 0.001), SBP (OR = 1.383, 95% CI = 1.080-1.769, P = 0.010), Hyponatremia (OR = 1.941, 95% CI = 1.614-2.334, P < 0.001), as well as HRS (OR = 2.610, 95% CI = 1.669-4.080, P < 0.001). CONCLUSION: The most significant risk factors for HBV-ACLF mortality comprise HRS, HE, and HE grade, followed by INR and hyponatremia. The Monocytes, cirrhosis, and SBP have been confirmed as the additional key risk factors for HBV-ACLF mortality.

Toward a more precise prognostic stratification in acute decompensation of cirrhosis: The Padua model 2.0.

BACKGROUND: The clinical course of acutely decompensated cirrhosis (AD) is heterogeneous. Presepsin (PSP) is a plasmatic biomarker that reflects Toll-like receptor activity and systemic inflammation. We conducted a prospective study to: (1) measure PSP in AD and (2) assess whether PSP in AD can predict the development of acute-on-chronic liver failure (ACLF). METHODS: Patients with AD were prospectively recruited at admission and underwent determination of PSP. In study part 1, we compared PSP in AD versus controls (stable decompensated and compensated cirrhosis). In study part 2, we prospectively followed patients with AD for 1 year and evaluated predictors of ACLF. RESULTS: One hundred and seventy three patients with AD were included (median MELD: 18; CLIF-C AD score: 54). Compared with controls, patients with AD had higher levels of PSP (674 ng/L vs. 310 ng/L vs. 157 ng/L; p < 0.001). In patients with AD, Child-Pugh C and acute kidney injury were associated with higher levels of PSP. During the follow-up, 52 patients developed ACLF (median time from recruitment: 66 days). PSP, CLIF-C AD score, and Child-Pugh stage were independently associated with ACLF. A predictive model combining these variables (Padua model 2.0) accurately identified patients at higher risk of ACLF (AUROC 0.864; 95% CI 0.780-0.947; sensitivity 82.9%, specificity 76.7%). In patients at lower risk of ACLF based on a CLIF-C AD <50, a PSP >674 ng/L could discriminate between two groups at significantly different risk of ACLF. Finally, in patients who did not develop ACLF, baseline PSP was significantly higher in those who progressed toward unstable versus stable decompensated cirrhosis. CONCLUSION: The Padua model 2.0 can be used to identify patients with AD at high risk of ACLF. If these results are validated by external cohorts, PSP could become a new biomarker to improve risk stratification in AD.

Fecal calprotectin in patients with liver cirrhosis.

BACKGROUND AND OBJECTIVES: Sepsis is the most challenging complication in patients with liver cirrhosis. It destabilizes patients leading to worsening of liver dysfunction and increased mortality. Intestinal bacterial dysbiosis, release of endotoxins, increased gut permeability and associated immune dysregulation have been described in cirrhotic patients with septic complications. Calprotectin is a major cytosolic protein secreted by the inflammatory cells and has been widely studied in patients with inflammatory bowel disease. We aimed at evaluating the role of fecal calprotectin (FCAL) in patients with liver cirrhosis. METHODS: A prospective, observational study on the utility of FCAL test was conducted in patients with liver cirrhosis. Fifteen milligrams of fecal specimen was collected and analyzed within 48 hours of hospitalization from patients with end-stage liver disease (ESLD), acute-on-chronic liver failure (ACLF) and at the time of outpatient visit for stable cirrhotics. Five healthy volunteers underwent FCAL test as control population. RESULTS: The mean FCAL (µg/g) level in healthy control (n = 5), stable cirrhotics (n = 10), ESLD (n = 10) and ACLF (n = 10) patients was 109.2 (95% CI: - 53.39 to 271.79), 143.3 (95% CI: 50.5-236.45), 176.9 (95% CI: 122.93-230.87) and 543.5 (95% CI: 207.09-879.91) (p = 0.005), respectively. Sepsis was identified in 13 (43.3%) patients. Area under the receiver-operating characteristics curve (AUROC) of FCAL was 0.80 (p = 0.005) and FCAL ≥ 200 µg/g (OR = 10.8, p = 0.006) was associated with sepsis. Nine (25.7%) patients expired. FCAL level was significantly higher in dead patients compared to survivors (mean, 493.67 (95% CI: 142.20-845.14) vs. 199.71 (95% CI: 99.84-299.59) µg/g,p = 0.005. CONCLUSIONS: FCAL levels are increased in patients with chronic liver disease, with highest level in ACLF. An FCAL level of ≥ 200 µg/g was associated with sepsis and mortality in cirrhotic patients. Larger studies are required to identify the role of FCAL in these patients. Early identification and initiation of anti-microbials may mitigate sepsis and reduce mortality.

Granulocyte colony stimulating factor in decompensated cirrhosis, acute alcoholic hepatitis, and acute-on-chronic liver failure: A comprehensive meta-analysis of randomized controlled trials.

BACKGROUND: GCSF may improve the prognosis of severe liver disease by promoting liver regeneration and immune restoration. Our Aim was to investigate its controversial efficacy in decompensated cirrhosis, acute alcoholic hepatitis (AAH), or acute-on-chronic liver failure (ACLF) through meta-analysis. METHODS: Meta-analysis of proportions (random effect model) including 19 RCTs (1287 patients from 16 Asian and 3 European studies including 487 ACLF, 231 AAH and 569 cirrhotic patients) evaluating survival at day-28, day-90, 6 months, one year, and/or occurrence of sepsis as major outcomes. RESULTS: In patients with decompensated cirrhosis, G-CSF administration was associated with a reduction in the weight-adjusted risk of mortality of 9% at day-90 (OR=0.33; 95%CI: 0.18-0.58; p = 0.0002), 16% at 6 months (OR=0.31; 95%CI: 0.15-0.62; p = 0.0009), 26% at one year (OR=0.21; 95%CI:0.12-0.38, p<0.0001) and a weight-adjusted 28% risk reduction for sepsis (OR=0.28; 95%CI: 0.16-0.49; p<0.0001). Only Asian studies were positive. In AAH, G-CSF was associated with an 18% reduction in weight-adjusted mortality risk at day-28 (OR=0.31; 95%CI:0.11-0.83, p = 0.021), 32% at day-90 (OR=0.20; 95%CI:0.09-0.46, p<0.0001) and a weight-adjusted 42% risk reduction for sepsis (OR=0.17; 95%CI: 0.08-0.38; p<0.0001). Only Asian studies, in which corticosteroids were not given systematically in case of severe AAH, were positive. In patients with ACLF, the results on mortality at day-28 were heterogeneous, and GCSF had no beneficial effect on sepsis or survival at day-90. CONCLUSION: G-CSF may be effective in patients with decompensated cirrhosis or AAH by reducing the occurrence of sepsis and mortality. Further meta-analyses of individual data, or new, powerful and methodologically flawless therapeutic trials, are warranted to confirm these results, which harbor wide divergences between Asian and European RCTs.