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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).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.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.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.

Definitions and descriptions of acute-on-chronic liver failure (ACLF) vary between Western and Eastern types, and alcoholism and hepatitis B virus (HBV) are, respectively, the main etiologies. To determine whether there are unified diagnostic criteria and common treatment programs for different etiologies of ACLF, a multicenter prospective cohort with the same inclusion criteria and disease indicators as those used in the European Consortium Acute-on-Chronic Liver Failure in Cirrhosis Study is urgently needed in Asia, where the prevalence of HBV is high. A multicenter prospective cohort of 2,600 patients was designed, drawing from 14 nationwide liver centers from tertiary university hospitals in China, and 2,600 hospitalized patients with chronic liver disease (both cirrhotic and noncirrhotic) of various etiologies with acute decompensation or acute hepatic injury were continuously recruited from January 2015 to December 2016. Data were collected during hospitalization, and follow-ups were performed once a month, with plans to follow all patients until 36 months after hospital discharge. Of these patients, 1,859 (71.5%) had HBV-related disease, 1,833 had cirrhotic disease, and 767 had noncirrhotic disease. The numbers and proportions of enrolled patients from each participating center and the baseline characteristics of the patients with or without cirrhosis are presented.

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.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.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.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.

This study was designed to determine whether a transjugular intrahepatic portosystemic shunt (TIPS) combined with embolotherapy was superior to TIPS alone.Seventy-nine patients were included in the study (43 in the TIPS and embolotherapy group and 36 in the TIPS alone group). Embolotherapy was performed after TIPS using coils and a tissue adhesive agent. The portosystemic pressure gradient (PPG) after TIPS was lower than 12 mm Hg in all patients. Multivariate analyses were performed using a Cox regression model, and the probabilities of survival and rebleeding were estimated with the Kaplan-Meier method.Baseline patient survey data showed similar distributions in both groups. The mean follow-up time was 45.6 months (range: 1 to 85.6 mo). There were no significant differences in the incidences of rebleeding (P=0.889), stent revision (P=0.728), encephalopathy (P=0.728), the cumulative survival rate (P=0.552), or the probability of being free of rebleeding (P=0.806) between the 2 groups. Of 9 patients with rebleeding after TIPS plus embolotherapy, 7 had a history of esophageal variceal bleeding and 2 had gastric variceal bleeding. Of 8 patients with rebleeding after TIPS alone, 4 had a history of esophageal variceal bleeding and 4 had gastric variceal bleeding (P=0.247). Multivariate analysis showed that PPG after TIPS was an independent predictor of rebleeding (P=0.036). Age and Model of End-stage Liver Disease score were independent predictors of survival (P=0.048 and 0.037).The results suggest that TIPS with embolotherapy cannot reduce the risk of rebleeding if PPG is less than 12 mm Hg after TIPS. PPG after TIPS is an independent predictor of rebleeding.

To analyse the difference of genome-wide DNA methylation status of CpG island between the monozygotic twins with disconcordant phenotype of HBV infection and to discover possible differentially methylated genes.Modified AIMS (amplification of inter-methylated sites) method was adopted. According to the frequent sites of CpG islands (-CGCG- and -CCGG-), three groups of isochizomers with distinct methylation sensitivity (Sma I-Xma I, Hpa II-Msp I and BssH II-Pau I/BseP I) were used to modify the AIMS method. The modified AIMS method combined with Personal Molecular Imager FX system analysis and radioautographic analysis was used to make the global detection of the methylome of CpG islands. Multiple anonymous bands were compared between the twins with the Quantity One bio-soft. The different bands were cloned into T vectors and positive clones were sequenced. BLAST analysis of positive clone sequences was conducted to give the clues for the differential methylated genes between monozygotic twins with discordant phenotype of HBV infection.Nearly the same bands were found between one pair of twins with concordant phenotype of HBV infection. Different methylated bands were found not only between monozygotic twins with concordant phenotype but also between those with disconcordant phenotype. More differential methylated bands were found in the latter groups. By BLAST analysis with sequences of differential methylated bands, four possible genes were got. These genes might relate to the monozygotic twins with disconcordant phenotype of chronic HBV infection.Differential methylation of genes occurs in monozygotic twins with discordant phenotype of HBV infection. Whether these changes are involved in the pathogenesis of different phenotypes needs further elucidation.

The primary comparative analysis between the host genetic factors and their relationships with clinical phenotype of 20 pairs of HBV infected and high risk twins.Zygosity of twins was diagnosed by STR microsatellite polymorphism analysis. To identify the serological model and exclude the evidence of coinfection with other virus, we detected HAV, HBV, HCV, HDV, HEV serological markers by electrochemiluminescence method. HBV DNA level was detected by Lightcycler Fluorescent Quantitative system and Liver function (ALT, AST, TBil) was detected by HITACHI7250 Biochemistry Detection System. The data was analysis by Fisher's exact test to comparatively analyze among the monozygotic twins (MZ), dizygotic twins (DZ) and control groups.The significant difference was found in the concordance rate of disease, concordance of clinical phenotype and serological patterns of HBV infection between the MZ and DZ twins (P0.05), it was also found between MZ and control groups (P0.05), but not between DZ and control groups (P0.05). No significant difference in the concordance of other HBV infection markers was observed (P0.05). Concordance of clinical phenotype may be related to patients' age and antivirus therapy. Injection with the HBIg and initiative vaccination right after birth can prevent twins with high risk to infection to be victims.The significant difference was found in the concordance rate, concordance of clinical phenotype and serological patterns between MZ and control groups, it was also found between MZ and DZ groups, which is correspond to the opinion of the high concordance of MZ and indicated the host genetic factors may play role in influencing the clinical phenotype, while other factors such as the vaccination may have an effect on the clinical phenotype in some extent.