Albumin is synthesized in the liver， and in case of severe liver injury， albumin synthesis is reduced with structural alterations （such as an increase in methylation and glycosylation）， leading to a significant reduction in effective albumin in circulation. Albumin not only maintains plasma oncotic pressure， but also has the functions of antioxidation， anti-inflammation， immunomodulation， and transport. Current guidelines recommend the short-term application of human serum albumin in the treatment of large-volume paracentesis， hepatorenal syndrome， and spontaneous bacterial peritonitis in patients with liver cirrhosis， as it is shown that human serum albumin can help to reduce mortality. In addition， human serum albumin may improve the prognosis of cirrhotic patients with hyponatremia， non-SBP infections， and hepatic encephalopathy. However， there are still controversies over the application of human serum albumin in liver cirrhosis and related complications in terms of optimal dose and long-term efficacy.

Objective To investigate the virological features of patients with chronic hepatitis B(CHB)and metabolic associated fatty liver disease(MAFLD)through a stratified analysis.Methods A retrospective analysis was performed for 131 patients with CHB and MAFLD and 168 patients with CHB alone who underwent percutaneous liver biopsy and did not receive antiviral therapy or withdrew from drugs for more than 6 months in Beijing YouAn Hospital,Capital Medical University,from January 1,2013 to December 31,2019.The two groups were compared in terms of general data,biochemical parameters,and virological parameters.The patients in the two groups were stratified according to liver inflammation grade(G)and liver fibrosis stage(S),and the patients with CHB and MAFLD were further analyzed based on the degree of hepatic steatosis and NAFLD activity score(NAS).Virological features(the serum levels of HBV DNA and HBV HBsAg)were compared between groups.The Wilcoxon test was used for comparison of continuous data between two groups,and the Kruskal-Wallis H test was used for comparison between multiple groups and further comparison between two groups;the chi-square test was used for comparison of categorical data between two groups.Results Compared with the CHB group,the CHB+MAFLD group had a significantly higher proportion of male patients,a significantly higher proportion of patients with hypertension or type 2 diabetes mellitus,and significantly higher levels of the blood biochemical parameters of triglyceride,low-density lipoprotein cholesterol,apolipoprotein B,alanine aminotransferase,gamma-glutamyl transpeptidase,uric acid,and fasting blood glucose(all P<0.05),as well as significantly lower levels of high-density lipoprotein cholesterol,apolipoprotein A1,and HBV DNA(all P<0.05).The stratified analysis based on liver fibrosis stage showed that for both the patients with CHB alone and those with CHB and MAFLD,the significant fibrosis(S2—4)group had a significantly lower level of HBV DNA than the non-significant fibrosis(S0—1)group(P<0.05),and for the patients with CHB alone,the significant fibrosis(S2—4)group had a significantly lower level of HBsAg than the non-significant fibrosis(S0—1)group(P<0.05).The stratified analysis based on inflammation grade showed that for the patients with CHB and MAFLD,the high inflammation grade(G3)group had a significantly higher level of HBV DNA than the low inflammation grade(G1—2)group(P<0.05),and in the low inflammation grade(G1—2)group,the patients with CHB and MAFLD had a significantly lower level of HBsAg than the patients with CHB alone(P<0.05).The stratified analysis based on the degree of hepatic steatosis showed that the level of HBV DNA gradually decreased with the increase in the degree of steatosis,and the severe steatosis group had a significantly lower level of HBV DNA than the mild group(P<0.05),while there was no significant difference in HBsAg level between the groups with different degrees of hepatic steatosis(P>0.05).The stratified analysis based on NAS score showed that the NAS≥4 group had significantly higher levels of HBV DNA and HBsAg than the NAS<4 group(both P<0.05).Conclusion Patients with CHB and MAFLD have significant abnormalities in metabolic markers and aminotransferases,while virological indicators show different features in stratified analyses based on various indicators.

Objective As important components in the microenvironment of hepatocellular carcinoma(HCC),hepatic stellate cells(HSCs)and hydrogen sulfide(H2S)participate in various biological processes that regulate the development and progression of HCC.Through the co-culture of HSCs and HCC cells,this article aims to investigate the role and mechanism of HSCs in regulating the apoptosis of HCC cells by secreting H2S.Methods The HSC cell line(LX-2)and HCC cell lines(HepG2 and PLC/PRF/5)were used for experiment.RT-qPCR and Western Blot(WB)were used to measure the mRNA and protein expression levels of cystathionine γ-lyase(CSE),a key synthase for H2S;ELISA was used to measure the concentration of H2S in supernatant;next-generation sequencing,cell immunofluorescence assay,chromatin immunoprecipitation(ChIP),and WB were used to measure the JNK/JunB-TNFSF14 signaling pathway genes,binding sites,and related proteins after HepG2 cells were treated by H2S.LX-2 cells were co-cultured with HepG2 or PLC/PRF/5 cells in a Transwell chamber;CCK-8 assay and flow cytometry were used to measure the viability and apoptosis of HCC cells,and WB was used to measure the H2S-TNFSF14 signaling pathway-related proteins.All cell experiments were repeated three times.The independent-samples t test was used for comparison of continuous data between two groups;a one-way analysis of variance or the analysis of variance with repeated measures was used for comparison between multiple groups,and the Dunnett-t test was used for further comparison between two groups.Results LX-2 cells synthesized H2S mainly through CSE,and the concentration of H2S in supernatant of LX-2 cells gradually increased over time(22.89±0.08 pg/mL vs 28.29±0.15 pg/mL vs 36.19±1.90 pg/mL,F=79.63,P<0.05).In LX-2 cells,the mRNA expression level of CSE was significantly higher than that of CBS and MPST(1.008±0.13 vs 0.320±0.014 vs 0.05±0.02,F=80.84,P<0.05).When CSE was inhibited by PPG,the concentration of H2S decreased with the increase in the concentration of PPG(P<0.05).LX-2 cells were co-cultured with HepG2 or PLC/PRF/5 cells,and over the time of culture,there were significant reductions in the viability of HepG2 cells(87.48%±0.82%vs 70.48%±0.641%vs 52.89%±0.57%vs 45.20%±0.69%,F=1 517.13,P<0.001)and PLC/PRF/5 cells(92.41%±0.48%vs 74.10%±0.73%vs 53.70%±0.60%vs 44.00%±0.27%,F=2626.21,P<0.001)and significant increases in the apoptosis of HepG2 cells(12.88%±0.64%vs 15.5%±0.16%vs 18.43%±0.37%vs 13.01%±0.58%,F=142.15,P<0.001)and PLC/PRF/5 cells(8.51±0.05 vs 12.80±0.33 vs 15.59±0.21 vs 10.72±0.30,F=676.40,P<0.001),with the most significant changes on day 3.Next-generation sequencing showed that endogenous H2S and NaHS(endogenous H2S donor)were involved in regulating the expression of various genes in HepG2 cells.By releasing H2S,NaHS and LX2 activated the JNK/JunB signaling pathway and upregulated the expression of the apoptosis gene TNFSF14 in HCC cells,with increased binding between p-JunB and the transcriptional regulatory regions of the TNFSF14 gene.Conclusion In the microenvironment of HCC,HSCs activate the JNK/JunB signaling pathway in HCC cells through the signal molecules CSE/H2S,and there is an increase in the expression of TNFSF14,thereby promoting the apoptosis of HCC cells.

Extrahepatic non-cirrhotic portal hypertension(NH-PH),a disease of portal hypertension repre-sented by extrahepatic non-cirrhotic portal vein thrombosis and budd-chiari syndrome,both of which are caused by splanchnic vein thrombosis and share a variety of common genetic susceptibility factors.The review summarized the research progress on genetic susceptibility to thrombotic NH-PH in recent decades,collating the reported genetic susceptibility genes and their mutation loci,as well as suggesting other potential gene tar-gets.The results of the study provided screening targets for subsequent large-sample validation in clinic,and delivered new ideas for the development of early diagnostic methods and pathogenesis of NH-PH.

Portal vein thrombosis (PVT) is divided into cirrhotic and non-cirrhotic PVTs. The incidence rate of PVT varies greatly among different clinical stages of cirrhosis, with an overall incidence rate of about 13.92%, and the prevalence of cirrhotic PVT following splenectomy is as high as 60%. The pathogenesis of cirrhotic PVT is still unclear. However, the activation of Janus kinase/signal transduction and activator transcription signaling pathways, the rise in the expression of von Willebrand factor, and the gut microbiota along with its metabolite trimethylamine-N-oxide play an important role in the injury of vascular endothelial cells and the formation of PVT in cirrhosis. Therefore, these could be a new target for cirrhotic PVT prevention and treatment.

Background/Aims: Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT). Methods: Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict threeyear HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test. Results: The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65–0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61–0.68; untreated models: 0.51–0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis. Conclusions The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted.

Liver stiffness measurement (LSM) has been widely used in predicting portal hypertension in clinical practice, and in recent years, spleen stiffness measurement (SSM) has also become a diagnostic tool. Studies have shown that SSM can predict portal hypertension and its complications such as esophagogastric variceal bleeding in patients with chronic liver diseases and assist in the risk stratification management of portal hypertension and esophagogastric variceal bleeding. It can accurately predict clinically significant portal hypertension, high-risk esophageal and gastric varices, decompensation rate, and mortality rate in patients with chronic liver diseases. At present, SSM data in most studies are obtained by detection using the liver equipment FibroScan Ⓡ (SSM@50 Hz). FibroScan Ⓡ 630 is a new scanner dedicated for SSM with a special mode for SSM (SSM@100 Hz). This article elaborates on the significance of SSM in predicting portal hypertension and briefly introduces the advantages and disadvantages of the new equipment for SSM.

Objective:intrahepatic portocaval shunt (TIPS) in the treatment of hepatic sinusoidal obstruction syndrome (HSOS).Methods:A retrospective analysis was performed on 27 patients with HSOS who were treated with TIPS in our center from July 2018 to July 2020. The changes of portal vein pressure (PVP), portal vein pressure gradient (PPG) and liver function were observed, so as to evaluate the efficacy. Paired t test was adopted to evaluate the quantitative parameters, while χ2 test was used to analyze qualitative parameters, with P < 0.05 as statistical difference. Results:PVP decreased from (4.41 ± 0.18) kPa before shunt to (2.69 ± 0.11) kPa after shunt ( t = 82.41, P < 0.001), PPG decreased from (3.23 ± 0.18) kPa before shunt to (1.46 ± 0.23) kPa after shunt ( t = 32.41, P < 0.001). The liver function improved significantly after operation. After 24 months of follow-up, 3 patients developed stent restenosis and recanalized after balloon dilation. Three patients developed hepatic encephalopathy, which was improved after drug treatment. One patient underwent liver transplantation due to liver failure. Conclusion:TIPS is effective in the treatment of HSOS in the short and medium term, and can provide time for liver transplantation patients to wait for liver source.

Objective To analyze the clinical characteristics and prognostic factors of chronic hepatitis B (CHB) patients complicated with metabolic associated fatty liver disease (MAFLD). Methods A total of 114 CHB patients and 101 CHB patients complicated with MAFLD who underwent liver biopsy between 2005 and 2018 were included. A long-term cohort was established with the time of liver puncture as the baseline, and decompensated cirrhosis, liver cancer, liver transplantation and death related to liver disease as the clinical endpoints. The patient's NAS score, hepatitis inflammation activity (G) and fibrosis stage (S) were scored for the liver biopsy. According to fibrosis stage, patients were divided into no significant fibrosis (S0-1) and significant fibrosis (S2-4) groups. The clinical characteristics and prognosis of the CHB patients with or without MAFLD at the same fibrosis stage were compared. CHB patients with MAFLD were divided into NAS < 4 and NAS≥4 groups according to NAS score, and the influence of NAS score on clinical outcomes of patients was analyzed. The independent samples t -test / Wilcoxin test was performed for comparison of continuous data and the chi-square test was used for comparison of categorical data between groups. Survival analysis was performed using Kaplan-Meier survival cure and compared using log-rank test. Cox multivariate regression analysis was used to identify prognostic factors. Results The BMI, blood glucose and TC in CHB patients with MAFLD group were significantly higher than those in CHB alone in each fibrosis stage ( P < 0.05). In patients without significant fibrosis, the levels of ALT ( Z =-2.249, P =0.025), AST ( Z =-2.512, P =0.012) and GGT ( Z =-5.261, P < 0.001) in the complicated group were higher than those in the CHB group. With a median follow-up time of 8.0 years, the Kaplan-Meier survival analysis revealed that the complicated MAFLD significantly reduced the liver event-free survival rate of CHB patients ( χ 2 =7.607, P =0.006). Cox multivariable analysis revealed MAFLD ( HR =5.76, 95% CI : 1.54 - 21.48, P =0.009) was an independent risk factor for liver-related outcomes. In CHB patients with MAFLD, the ALT ( Z =-3.139, P =0.002), AST ( Z =-2.898, P =0.004), and GGT ( Z =-2.260, P =0.024) of patients with NAS≥4 were higher than those of patients with NAS < 4. We found that significant fibrosis ( HR =4.83, 95% CI : 1.23 - 18.91, P =0.024) was associated with the poor prognosis of CHB patients with MAFLD. Conclusions CHB patients with MAFLD are more likely to have impaired liver function in the early stage and the disease progresses more rapidly. Complicated MAFLD will increase the risk of liver-related events in patients with CHB, and significant fibrosis is an independent risk factor for adverse outcomes in CHB patients with MAFLD.

Objective:To study the impact and the mechanism of splenectomy combined with pericardial devascularization on cirrhotic livers.Methods:Serum samples and clinical data were collected preoperatively and postoperatively from 54 patients with cirrhosis who underwent splenectomy combined with pericardial devascularization from May 2013 to Oct 2014 at Beijing You’an Hospital, Capital Medical University. Changes in hepatic arterial and portal venous blood flow, liver function and fibroscan results were analyzed. The levels of nitric oxide (NO), endothelin-1 (ET-1), interleukin-6 (IL-6), hepatocyte growth factor (HGF), transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase 1 (MMP1) were measured.Results:There were 31 males and 23 females, aged(45.48±10.21)years. Free portal vein pressure decreased significantly from (37.0±7.1) cmH 2O (1 cmH 2O=0.098 kPa) to (26.1±5.7) cmH 2O after surgery ( P<0.05). Significant increases in postoperative lumen diameter (4.0±1.0) mm vs (3.1±0.7) mm were observed, accompanied by increase in peak flow velocity and blood flow of the hepatic artery. Significant deductions in lumen diameter (11.9±2.0) mm vs (13.1±1.9) mm, accompanied by reduction of peak flow velocity and blood flow of the portal vein were observed following surgery (all P<0.05). The NO level was significantly elevated immediately after splenectomy and was subsequently remained at high levels. The ET-1 level decreased 2 days after surgery and became fluctuated at low levels. The IL-6 and HGF levels increased significantly 2 days after surgery and decreased gradually after 7 days and 1 month, respectively. The TGF-β1 and the MMP1 levels increased after surgery. The endotoxin level decreased significantly after surgery (all P<0.05). Conclusion:Splenectomy combined with pericardial devascularization induced hepatic blood flow restoration, hepatocyte regeneration and reversal of fibrosis in cirrhotic livers. Splenectomy has a protective effect on cirrhotic liver when combined with pericardial devascularization.