QuantiFERON-Monitor as prognostic marker of mortality in patients with decompensated cirrhosis: A prospective cohort study.

Prognostic and therapeutic significance of microbial cell-free DNA in plasma of people with acute decompensation of cirrhosis

B-cell compartment abnormalities are associated with ACLF and mortality in patients with liver cirrhosis

Objectives: Acute decompensation (AD) of cirrhosis is characterized by high mortality. We aimed to validate the performance in predicting mortality of both the chronic-liver-failure-consortium (CLIF-C) acute-on-chronic liver failure (ACLF) and CLIF-C AD scores in a cohort of patients admitted for AD.Methods: In this prospective cohort study, patients were followed-up during their hospital stay and for 365 days thereafter.Results: About 182 patients with AD were enrolled including 78 (42.8%) who met the criteria for ACLF (ACLF-group) while the remaining had AD without ACLF (AD-group). 56.4% and 56.7% of the ACLF- and AD-groups, respectively, had alcoholic cirrhosis and 85.9% of the ACLF-group hepatic encephalopathy. Only few patients were hospitalized in the intensive care unit (ICU) or transplanted. The probabilities of death estimated for both scores were similar to the overall mortality rates observed at all time points. The model had a good fit in the AD-group at 90 days (p = .974) but a worse, yet adequate, in the ACLF-group at 28 days (p = .08). The CLIF-C ACLF or AD scores had an adequate, predictive discrimination ability for mortality at all time points, with Harrel’s concordance index-C ranging between 0.64 and 0.65 or 0.64 and 0.68, respectively. Both scores showed a similar predictive accuracy for mortality compared to those of MELD, MELD-Na and Child-Pugh.Conclusions: In this population without access to appropriate ICU treatment, the CLIF-C ACLF and AD performed worse than in studies with patients having ICU access. In addition, the CLIF scores were not superior to classical ones in this setting.

Background and aim: Acute-on-chronic liver failure (ACLF) is characterized by the presence of acute decompensation (AD) of cirrhosis, organ failures, and high short-term mortality rates. In present study, we explored whether Pro-adrenomedullin (Pro-ADM), a biomarker of sepsis, is a potential marker of outcome in patients admitted for AD or ACLF and whether it might be of additional value to conventional prognostic scoring systems in these patients.Methods: 332 consecutive patients with AD of cirrhosis were prospectively enrolled. Pro-ADM was measured for all patients at baseline. Cox regression analysis was used to evaluate the impact of pro-ADM on short-term survival and developing ACLF during hospital stay.Results: Serum pro-ADM levels were significantly high in non-survivors (p < .001) and showed significant correlation with ALT (r = 0.181, p = .001), INR (r = 0.144, p = .009), TB (r = 0.368, p < .001), Creatinine (r = 0.145, p = .004), MELD score (r = 0.334, p = <.001) and CLI-C OF score (r = 0.375, p= <.001). Serum pro-ADM at admission was shown to be a predictor of 28-day mortality independently of MELD and CLIF-C OF scores. Prognostic models incorporating pro-ADM achieved high C index for predicting 28-day mortality in AD patients of cirrhosis. Moreover, baseline pro-ADM was found to be predictive of ACLF development during hospital stay.Conclusions: Serum pro-ADM levels correlate with multiorgan failure and are independently associated with short-term survival and ACLF development in patients admitted for AD or ACLF.

Annotation. In recent years, new data have been obtained regarding the course of liver cirrhosis (LC) and ways of its decompensation. Acute-on-chronic liver failure (ACLF) is a newly identified separate clinical syndrome that develops in 30% of patients with acute LC decompensation, characterized by hepatic and extrahepatic organ failure and high short-term mortality. The aim of this review was to describe the clinical and prognostic value of acute LC decompensation and ACLF, the pathophysiological mechanisms of their development, and existing diagnostic and treatment approaches. A search in the PubMed database using the keywords "liver cirrhosis, acute decompensation of cirrhosis, acute-on-chronic liver failure" allowed us to select 46 sources published in 2005-2022. This review discusses new concepts about the stages of the course of compensated and decompensated LC, which differ in the severity of portal hypertension, the number and type of decompensation events, and patient survival. The clinical and prognostic value of acute LC decompensation, which manifests as recent ascites, bleeding, hepatic encephalopathy, bacterial infection, and requires hospitalization of the patient, was considered. The trajectories of the further development of acute decompensation, which are represented by stable or unstable decompensated LC, pre-ACLF, and ACLF, were discussed. Current European diagnostic criteria for ACLF, severity criteria for ACLF, and tools for predicting patient survival were reviewed. The latest data on the pathophysiological role of portal hypertension, systemic inflammation, metabolic disorders, and immunopathological cell damage in the development of organ failure in ACLF was given. The existing therapeutic measures and promising methods of treatment of patients with acute LC decompensation and ACLF were considered.

Defining Acute-on-Chronic Liver Failure: Will East and West Ever Meet?

Hospitalized patients with acute decompensation (AD) of cirrhosis are at risk of progressing to acute-on-chronic liver failure (ACLF), significantly increasing their mortality. The aim of this study was to identify key predictors and patient trajectories predisposing to ACLF. In this multicenter, prospective study spanning 2 years, clinical, biochemical, and 90-day survival data were collected from 625 patients with AD (European Association for the Study of the Liver criteria) across North, South, and East India. We divided the cohort into a Derivation cohort (DC: 318 patients) and a Validation cohort (VC: 307 patients). Predictive models for pre-ACLF were derived, validated, and compared with established scores such as model for end-stage liver disease (MELD) 3.0 and chronic liver failure Consortium acute decompensation. Of 625 patients (mean age 49 years, 83% male, 77.5% with alcohol-related liver disease), 32.2% progressed to ACLF. Patients progressing to ACLF showed significantly higher bilirubin (10.9 vs 8.1 mg/dL), leukocyte counts (9,400 vs 8,000 per mm 3 ), international normalized ratio (1.9 vs 1.8), and MELD 3.0 (28 vs 25) but lower sodium (131 vs 134 mEq/L) and survival (62% vs 86%) compared with those without progression ( P < 0.05) in the DC. Consistent results were noted with alcohol-associated hepatitis, infection and hepatic encephalopathy as additional risk factors in VC. Liver failure at presentation (odds ratio: 2.4 [in DC], 6.9 [in VC]) and the 7-day trajectories of bilirubin, international normalized ratio, and MELD 3.0 significantly predicted ACLF progression ( P < 0.001). A new pre-ACLF model showed superior predictive capability (area under the curve of 0.71 in DC and 0.82 in VC) compared with MELD 3.0 and chronic liver failure Consortium acute decompensation scores ( P < 0.05). Approximately one-third of AD patients in this Indian cohort rapidly progressed to ACLF, resulting in high mortality. Early identification of patients at risk can guide targeted interventions to prevent ACLF.

Toward an Improved Definition of Acute-on-Chronic Liver Failure

Targeted lipidomics reveals extensive changes in circulating lipid mediators in patients with acutely decompensated cirrhosis

From the Editor’s Desk...

Background and AimSystemic inflammation and organ dysfunction/failure can complicate acute decompensation (AD) of cirrhosis with progression to acute‐on‐chronic liver failure (ACLF), leading to increased mortality. There are few studies on serum biomarkers predicting renal dysfunction (RD) or ACLF in AD. Serum cystatin C (CysC) and interleukin‐6 (IL‐6) were evaluated for predicting RD, ACLF, and mortality in AD patients.MethodsConsecutive AD patients seen from January 2018 to June 2019 were included. IL‐6 and CysC were measured in serum at the time of index presentation. Patients were followed for 90 days or until primary (development of RD) or secondary outcomes (development of ACLF or mortality). Multivariate analysis was performed to find whether CysC and IL‐6 can independently predict primary and secondary outcomes.ResultsA total of 124 patients were screened; 88 patients were included. On follow up, 22 (27.3%) developed RD, 11 (11/57, 19.3%) developed ACLF, and 21 (24%) died. The CysC predicted RD (odds ratio [OR] 7.97, 95% confidence interval [CI] 2.70–23.53, P = 0.001) and ACLF (OR 5.486, 95% CI 1.456–20.6, P = 0.012) development. IL‐6 was not an independent predictor of RD (P = 0.315), ACLF (P = 0.168), and mortality (P = 0.225).ConclusionSerum CysC can predict the development of RD and ACLF in patients of cirrhosis with AD.

Patients with chronic hepatitis B (CHB) have a dynamic disease process and risk of end-stage liver disease. It is critical to unambiguously differentiate the stages of the disease and focus on therapy prior to onset of an irreversible clinical endpoint. We retrospectively analyzed a wide range of CHB patients at different stages. The predictive power of serum complement component 3 (C3) levels for the development of acute-on-chronic liver failure (ACLF) in patients with decompensated cirrhosis was established and validated. The decrease in serum C3 levels paralleled the severity of diseases related to hepatitis B virus. Patients with decompensated cirrhosis who developed ACLF had significantly lower serum C3 levels than others on admission (0.50 vs. 0.80g/L, P<0.001). Data analysis also revealed that low serum C3 was a significant risk factor for developing ACLF (hazard ratio=0.32, P<0.01). The area under the receiver operating characteristic curve (auROC) for serum C3 levels that predicted the development of ACLF in patients with decompensated cirrhosis was 0.90, which had sensitivity and specificity of 88.2% and 88.7%, respectively. A similar result was observed in the validation set (auROC=0.86 for predicting development of ACLF in patients with decompensated cirrhosis). Serum C3 levels are valuable in assessing the severity of CHB-related stages. Low C3 levels signifies the development of ACLF in patients with decompensated cirrhosis.

P-74 ELEVATED CALPROTECTIN LEVELS ARE ASSOCIATED WITH MORTALITY IN PATIENTS WITH ACUTE DECOMPENSATION OF CIRRHOSIS

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. To explore the prognostic value of sTREM-1 in patients with AD of cirrhosis. 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. 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. Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.

Innate immune cells in cirrhosis