Development and validation of a prognostic model for 90-day survival in patients with alcohol-associated cirrhosis and acute decompensation.

BACKGROUND/PURPOSE: Patients with alcohol-associated cirrhosis and acute decompensation are considered critically ill and have a higher risk of short-term mortality. This study aimed to establish a nomogram to evaluate their 90-day survival and identify factors that affect disease progression. METHODS: We included patients from September 2008 to December 2016 (n = 387 in the derivation group) and from January 2017 to August 2020 (n = 157 in the validation group). LASSO regression and Cox multivariate risk regression were used to analyze the influencing factors of the 90-day mortality risk, and a nomogram was constructed. The performance of a model was analyzed based on the C-index, area under the receiver operating curve, calibration curve, and decision curve analysis. RESULTS: Total bilirubin >10 upper limit of normal, high-density lipoprotein cholesterol, lymphocyte and monocyte ratios ≤2.33, white blood cells, and hemoglobin were identified as independent risk factors affecting the 90-day mortality risk of patients and the nomogram was developed. A nomogram demonstrated excellent model predictive accuracy in both the derivation and validation cohorts (C-index: 0.976 and 0.945), which was better than other commonly used liver scoring models (p < 0.05). The nomogram also performed good calibration ability and more clinical net benefit. According to the nomogram score, patients were divided into high- and low-risk groups. Mortality was significantly higher in the high-risk group than in the low-risk group (p < 0.0001). CONCLUSION: The nomogram could accurately predict the 90-day mortality risk in patients with alcohol-associated cirrhosis and acute decompensation, helping to identify high-risk patients and personalize treatment at their first admission.

The neutrophil-to-lymphocyte ratio represents a systemic inflammation marker and reflects the relationship with 90-day mortality in non-cirrhotic chronic severe hepatitis.

OBJECTIVES: To investigate the relationship between systemic inflammatory response and short-term mortality in patients with non-cirrhotic chronic severe hepatitis (CSH) by using several indicators of inflammation including neutrophil-to-lymphocyte ratio (NLR), neutrophil (NEU), white blood cell (WBC), platelet-to lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR). METHODS: Data were collected from two prospectively enrolled CATCH-LIFE noncirrhotic cohorts. Cox regression analysis was used to investigate the association between systemic inflammatory biomarkers and 90-day liver transplant (LT)-free mortality. A generalized additive model (GAM) was used to illustrate the quantitative curve relationship between NLR and 90-day LT-free mortality. Kaplan-Meier method was used to estimate the 90-year LT-free survival. RESULTS: The prevalence of CSH was 20.5% (226/1103). The 28-day and 90-day LT-free mortality rates were 17.7% and 26.1%, respectively, for patients with non-cirrhotic CSH. Patients with no infection accounted for 75.0% of all CSH patients, and NLR was independently associated with 90-day LT-free mortality. NLR of 2.9 might be related to disease deterioration in CSH patients without infection. CONCLUSIONS: NLR may be an independent risk factor for 90-day LT-free mortality in patients with non-cirrhotic chronic liver disease. A NLR of 2.9 as the cut-off value can be used to predict disease aggravation in CSH patients without infection.

Prevalence and clinical characteristics of autoimmune liver disease in hospitalized patients with cirrhosis and acute decompensation in China.

BACKGROUND: Autoimmune liver disease (AILD) has been considered a relatively uncommon disease in China, epidemiological data for AILD in patients with cirrhosis and acute decompensation (AD) is sparse. AIM: To investigate the prevalence, outcome and risk factors for AILD in cirrhotic patients complicated with AD in China. METHODS: We collected data from patients with cirrhosis and AD from two prospective, multicenter cohorts in hepatitis B virus endemic areas. Patients were regularly followed up at the end of 28-d, 90-d and 365-d, or until death or liver transplantation (LT). The primary outcome in this study was 90-d LT-free mortality. Acute-on-chronic liver failure (ACLF) was assessed on admission and during 28-d hospitalization, according to the diagnostic criteria of the European Association for the Study of the Liver (EASL). Risk factors for death were analyzed with logistic regression model. RESULTS: In patients with cirrhosis and AD, the overall prevalence of AILD was 9.3% (242/2597). Prevalence of ACLF was significantly lower in AILD cases (14%) than those with all etiology groups with cirrhosis and AD (22.8%) (P < 0.001). Among 242 enrolled AILD patients, the prevalence rates of primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH) and PBC-AIH overlap syndrome (PBC/AIH) were 50.8%, 28.5% and 12.0%, respectively. In ACLF patients, the proportions of PBC, AIH and PBC/AIH were 41.2%, 29.4% and 20.6%. 28-d and 90-d mortality were 43.8% and 80.0% in AILD-related ACLF. The etiology of AILD had no significant impact on 28-d, 90-d or 365-d LT-free mortality in patients with cirrhosis and AD in both univariate and multivariate analysis. Total bilirubin (TB), hepatic encephalopathy (HE) and blood urea nitrogen (BUN) were independent risk factors for 90-d LT-free mortality in multivariate analysis. The development of ACLF during hospitalization only independently correlated to TB and international normalized ratio. CONCLUSION: AILD was not rare in hospitalized patients with cirrhosis and AD in China, among which PBC was the most common etiology. 90-d LT-free mortality were independently associated with TB, HE and BUN.

Development and Validation of a Prognostic Model for One-year Survival of Cirrhosis Patients with First-ever Spontaneous Bacterial Peritonitis.

BACKGROUND AND AIMS: Spontaneous bacterial peritonitis (SBP) is one of the leading causes of death in patients with liver cirrhosis. We aimed to establish a prognostic model to evaluate the 1-year survival of cirrhosis patients after the first episode of SBP. METHODS: A prognostic model was developed based on a retrospective derivation cohort of 309 cirrhosis patients with first-ever SBP and was validated in a separate validation cohort of 141 patients. We used Uno's concordance, calibration curve, and decision curve (DCA) analysis to evaluate the discrimination, calibration, and clinical net benefit of the model. RESULTS: A total of 59 (19.1%) patients in the derivation cohort and 42 (29.8%) patients in the validation cohort died over the course of 1 year. A prognostic model in nomogram form was developed with predictors including age [hazard ratio (HR): 1.25; 95% confidence interval (CI): 0.92-1.71], total serum bilirubin (HR: 1.66; 95% CI: 1.28-2.14), serum sodium (HR: 0.94; 95% CI: 0.90-0.98), history of hypertension (HR: 2.52; 95% CI: 1.44-4.41) and hepatic encephalopathy (HR: 2.06; 95% CI: 1.13-3.73). The nomogram had a higher concordance (0.79) compared with the model end-stage liver disease (0.67) or Child-Turcotte-Pugh (0.71) score. The nomogram also showed acceptable calibration (calibration slope, 1.12; Bier score, 0.15±0.21) and optimal clinical net benefit in the validation cohort. CONCLUSIONS: This prediction model developed based on characteristics of first-ever SBP patients may benefit the prediction of patients' 1-year survival.

Effects of Adjuvant Chinese Patent Medicine Therapy on Prevention of Variceal Rebleeding: A Retrospective Cohort Study.

OBJECTIVE: To assess whether adjuvant Chinese patent medicines (CPMs) to standard treatment could reduce recurrent bleeding after variceal bleeding in cirrhotic patients. METHODS: This study retrospectively collected 555 consecutive patients who recovered from variceal bleeding. A population-based cohort study was established depending on if adjuvant CPMs were administered to prevent rebleeding. A total of 139 patients who had taken ⩾28 cumulative defined daily doses (cDDDs) of CPMs were included in the CPMs cohort, and 416 patients who used <28 cDDDs of CPMs were enrolled in the non-CPMs cohort. On evaluation of rebleeding incidence, 1:2 propensity score matched was used to estimate for reducing bias. Patients were followed for at least 12 months. The end-point of this study was clinically significant esophagogastric variceal rebleeding. RESULTS: Following multivariate analysis, CPMs therapy was an independent factor for variceal rebleeding [adjusted hazard ratio (AHR)=0.657; 95% confidence interval=0.497-0.868; P=0.003]. After the 1:2 propensity score matching, a significant reduction (23.5%) in the incidence of variceal rebleeding in patients was observed, from 58.3% in the non-CPMs cohort to 44.6% in the CPMs cohort (modified log-rank test, P=0.002) within a year. The AHRs for rebleeding were 0.928, 0.553, and 0.105, for 28-90 cDDDs, 91-180 cDDDs, and >180 cDDDs of CPMs, respectively. The median rebleeding interval in the CPMs cohort was significantly larger compared with the non-CPMs cohort (113.5 vs. 93.0 days; P=0.008). CONCLUSION: Adjuvant CPMs to standard therapy can significantly reduce the incidence of variceal rebleeding and delay the time to rebleeding.

Prevalence and Clinical Significance of Portal Vein Thrombosis in Patients With Cirrhosis and Acute Decompensation.

BACKGROUND & AIMS: Portal vein thrombosis (PVT) is a common and serious complication in patients with cirrhosis. However, little is known about PVT in patients with cirrhosis and acute decompensation (AD). We investigated the prevalence and clinical significance of PVT in nonmalignant patients with cirrhosis and AD. METHODS: We performed a retrospective study of 2 cohorts of patients with acute exacerbation of chronic liver disease who participated in the Chinese AcuTe on CHronic LIver FailurE study, established by the Chinese Chronic Liver Failure Consortium, from January 2015 through December 2016 (n = 2600 patients) and July 2018 through January 2019 (n = 1370 patients). We analyzed data on the prevalence, clinical manifestations, and risk factors of PVT from 2826 patients with cirrhosis, with and without AD. RESULTS: The prevalence of PVT in patients with cirrhosis and AD was 9.36%, which was significantly higher than in patients with cirrhosis without AD (5.24%) (P = .04). Among patients with cirrhosis and AD, 63.37% developed PVT recently (the first detected PVT with no indication of chronic PVT). Compared with patients without PVT, a significantly higher proportion of patients with PVT had variceal bleeding (47.33% vs 19.63%; P < .001) and patients with PVT had a significantly higher median serum level of D-dimer (2.07 vs 1.25; P < .001). Splenectomy and endoscopic sclerotherapy were independent risk factors for PVT in patients with cirrhosis and AD. The 1-year mortality rate did not differ significantly between patients with vs without PVT. CONCLUSIONS: In an analysis of data from 2826 patients with cirrhosis, a significantly higher proportion of those with AD had PVT than those without AD. PVT was associated with increased variceal bleeding, which would increase the risk for AD. Strategies are needed to prevent PVT in patients with cirrhosis, through regular screening, to reduce portal hypertension. ClinicalTrials.gov no: NCT02457637 and NCT03641872.

Effects of matrine on oval cell­mediated liver regeneration and expression of RBP­Jκ and HES1.

In the present study a rat model of oval cell­mediated liver regeneration was constructed to examine the molecular mechanisms of matrine in oval cell­mediated liver regeneration and the effects of matrine on hepatic function and the expression of OV6 protein and recombination signal sequence­binding protein Jκ (RBP­Jκ) and HES1 mRNA. A total of 48 Sprague Dawley rats were equally and randomly assigned to two groups. The model group underwent oval cell­mediated liver regeneration, whereas the matrine group underwent oval cell­mediated liver regeneration and received oral gavage of matrine. Expression of OV6 protein was tested by immunohistochemistry and RBP­Jκ and HES1 mRNA expression was determined by reverse­transcription polymerase chain reaction. Recovery of hepatic function was faster in the matrine group compared with the model (P<0.05). OV6 protein, RBP­Jκ and HES1 mRNA expression levels were lower in the matrine than the model group (P<0.05). Matrine promotes oval cell­mediated liver regeneration through downregulation of the RBP­Jκ­HES1 signaling pathway.