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 explore the characteristics of portal vein thrombosis (PVT) formation in patients with hepatitis B cirrhosis and its effect on long-term prognosis.Methods:The clinical data of a cohort of patients with hepatitis B cirrhosis who visited Beijing Youan Hospital from May 2009 to August 2020 were retrospectively analyzed. Enhanced CT examination was used as the standard for diagnosing PVT and its classification. Patients with hepatitis B cirrhosis without PVT at baseline were selected as the research subjects. According to whether PVT was formed during the follow-up period, they were divided into the PVT and control groups including 99 and 168 patients in the PVT and control groups with a follow-up time of 52.0 (46.7, 57.3) months. The changes in baseline and endpoint clinical indicators of the two groups were compared. Kaplan-Meier survival curve, log-rank test, and Cox regression were used to analyze the effect of PVT on prognosis.Results:In the PVT group, 28.28% (28/99) of patients underwent splenectomy, and 74.75% (74/99) did not receive anticoagulation therapy. The main portal vein thrombosis, portal vein branch thrombosis, and thrombosis in both groups accounted for 34.34% (34/99), 23.23% (23/99), and 15.15% (15/99), respectively. The splenic vein or superior mesenteric vein accounted for 27.27% (27/99). PVT was stable in 63.27% (63/99), progressed in 31.31% (31/99), and relieved in 5.05% (5/99) during the follow-up period. The white blood cell, hemoglobin, and platelet counts were all decreased in the PVT group compared with the baseline ( P<0.05). The international normalized ratio (INR) [1.28 (1.14, 1.39) vs. 1.33 (1.19, 1.46), P=0.041] and spleen length [(163.84±30.68) mm vs. (177.26±32.61) mm, P<0.001] was increased compared with the baseline. The proportion of gastroesophageal variceal bleeding was higher in the PVT group than in the control group (57.0% vs. 28.7%, P<0.001), and the constituent ratio of hepatic encephalopathy was not statistically significantly different ( P>0.05). The proportion of patients with ascites in the control group decreased (63.1% vs. 41.7%, P<0.001), while the proportion of patients with ascites in the PVT group was not statistically significantly different ( P>0.05). The incidence of composite clinical endpoint events in the PVT and the control group was 21.21% (21/99) and 4.17% (7/168), respectively ( P＜0.05). The incidence of composite clinical endpoint events in PVT patients without anticoagulation and anticoagulation treatment was 25.68% (19/74) and 8.00% (2/25), respectively ( P=0.062). Cox regression analysis found that PVT formation was an independent risk factor for liver-related adverse events in patients with hepatitis B cirrhosis ( HR=9.36, 95% CI: 3.65～24.02, P=0.001). Conclusions:The presence of PVT in patients with hepatitis B cirrhosis is assoliated with worse prognosis. The formation of PVT is closely related to the increased risk of liver-related adverse prognosis in patients with hepatitis B cirrhosis.

Objective:To analyze the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with main splenic artery embolization in the treatment of patients with portal hypertension upper gastrointestinal bleeding complicated with extensive portal vein thrombosis (PVT).Methods:This study was a prospective, single-center, open-label, single-arm clinical trial. In the first phase, 81 patients with portal hypertension upper gastrointestinal bleeding who were admitted to Beijing Shijitan Hospital, Capital Medical University from January 2018 to December 2018 were consecutively enrolled, including 57 males and 24 females, with the age of (51.3±10.4) years. During TIPS surgery, the pressure of the portal vein before and after the balloon blocking the splenic artery was measured to clarify the contribution of the splenic artery to portal hypertension. In the second stage, from January 2019 to December 2022, 104 patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT were re-enrolled, including 71 males and 33 females, with the age of (50.9±12.5) years. TIPS combined with main splenic artery embolization was performed, and portal vein pressure was measured before and after embolization. Follow up on the postoperative esophageal and gastric varices of the patients in the second stage.Results:The portal vein pressures before and after the first stage of balloon occlusion of the splenic artery were (35.2±8.4) mmHg (1 mmHg=0.133 kPa) and (24.2±6.3) mmHg, respectively. The pressure after occlusion was lower than that before occlusion, and the difference was statistically significant ( t=10.54, P<0.001). The portal vein pressures before and after the second stage embolization were (36.1±9.5) mmHg and (21.1±4.7) mmHg respectively. The pressure after embolization was lower than that before embolization, and the difference was statistically significant ( t=13.47, P<0.001). In the second stage, among the 104 patients, the proportion of those whose varicose veins disappeared or improved 6 months after the operation was 43.3%(45/104) and 51.0%(53/104), respectively. There were no patients with aggravation or rebleeding due to rupture. One year later, 8 patients (7.7%) had aggravated or ruptured esophageal and gastric varices with bleeding. Two years later, 12 patients (11.5%) had aggravated or bleeding. Conclusion:TIPS combined with main splenic artery embolization can effectively reduce the portal vein pressure in patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT, improve the degree of esophageal and gastric varices, and reduce the risk of gastrointestinal bleeding.

Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.

Objective:To analyze the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with main splenic artery embolization in the treatment of patients with portal hypertension upper gastrointestinal bleeding complicated with extensive portal vein thrombosis (PVT).Methods:This study was a prospective, single-center, open-label, single-arm clinical trial. In the first phase, 81 patients with portal hypertension upper gastrointestinal bleeding who were admitted to Beijing Shijitan Hospital, Capital Medical University from January 2018 to December 2018 were consecutively enrolled, including 57 males and 24 females, with the age of (51.3±10.4) years. During TIPS surgery, the pressure of the portal vein before and after the balloon blocking the splenic artery was measured to clarify the contribution of the splenic artery to portal hypertension. In the second stage, from January 2019 to December 2022, 104 patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT were re-enrolled, including 71 males and 33 females, with the age of (50.9±12.5) years. TIPS combined with main splenic artery embolization was performed, and portal vein pressure was measured before and after embolization. Follow up on the postoperative esophageal and gastric varices of the patients in the second stage.Results:The portal vein pressures before and after the first stage of balloon occlusion of the splenic artery were (35.2±8.4) mmHg (1 mmHg=0.133 kPa) and (24.2±6.3) mmHg, respectively. The pressure after occlusion was lower than that before occlusion, and the difference was statistically significant ( t=10.54, P<0.001). The portal vein pressures before and after the second stage embolization were (36.1±9.5) mmHg and (21.1±4.7) mmHg respectively. The pressure after embolization was lower than that before embolization, and the difference was statistically significant ( t=13.47, P<0.001). In the second stage, among the 104 patients, the proportion of those whose varicose veins disappeared or improved 6 months after the operation was 43.3%(45/104) and 51.0%(53/104), respectively. There were no patients with aggravation or rebleeding due to rupture. One year later, 8 patients (7.7%) had aggravated or ruptured esophageal and gastric varices with bleeding. Two years later, 12 patients (11.5%) had aggravated or bleeding. Conclusion:TIPS combined with main splenic artery embolization can effectively reduce the portal vein pressure in patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT, improve the degree of esophageal and gastric varices, and reduce the risk of gastrointestinal bleeding.

Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.

Objective:To explore the characteristics of portal vein thrombosis (PVT) formation in patients with hepatitis B cirrhosis and its effect on long-term prognosis.Methods:The clinical data of a cohort of patients with hepatitis B cirrhosis who visited Beijing Youan Hospital from May 2009 to August 2020 were retrospectively analyzed. Enhanced CT examination was used as the standard for diagnosing PVT and its classification. Patients with hepatitis B cirrhosis without PVT at baseline were selected as the research subjects. According to whether PVT was formed during the follow-up period, they were divided into the PVT and control groups including 99 and 168 patients in the PVT and control groups with a follow-up time of 52.0 (46.7, 57.3) months. The changes in baseline and endpoint clinical indicators of the two groups were compared. Kaplan-Meier survival curve, log-rank test, and Cox regression were used to analyze the effect of PVT on prognosis.Results:In the PVT group, 28.28% (28/99) of patients underwent splenectomy, and 74.75% (74/99) did not receive anticoagulation therapy. The main portal vein thrombosis, portal vein branch thrombosis, and thrombosis in both groups accounted for 34.34% (34/99), 23.23% (23/99), and 15.15% (15/99), respectively. The splenic vein or superior mesenteric vein accounted for 27.27% (27/99). PVT was stable in 63.27% (63/99), progressed in 31.31% (31/99), and relieved in 5.05% (5/99) during the follow-up period. The white blood cell, hemoglobin, and platelet counts were all decreased in the PVT group compared with the baseline ( P<0.05). The international normalized ratio (INR) [1.28 (1.14, 1.39) vs. 1.33 (1.19, 1.46), P=0.041] and spleen length [(163.84±30.68) mm vs. (177.26±32.61) mm, P<0.001] was increased compared with the baseline. The proportion of gastroesophageal variceal bleeding was higher in the PVT group than in the control group (57.0% vs. 28.7%, P<0.001), and the constituent ratio of hepatic encephalopathy was not statistically significantly different ( P>0.05). The proportion of patients with ascites in the control group decreased (63.1% vs. 41.7%, P<0.001), while the proportion of patients with ascites in the PVT group was not statistically significantly different ( P>0.05). The incidence of composite clinical endpoint events in the PVT and the control group was 21.21% (21/99) and 4.17% (7/168), respectively ( P＜0.05). The incidence of composite clinical endpoint events in PVT patients without anticoagulation and anticoagulation treatment was 25.68% (19/74) and 8.00% (2/25), respectively ( P=0.062). Cox regression analysis found that PVT formation was an independent risk factor for liver-related adverse events in patients with hepatitis B cirrhosis ( HR=9.36, 95% CI: 3.65～24.02, P=0.001). Conclusions:The presence of PVT in patients with hepatitis B cirrhosis is assoliated with worse prognosis. The formation of PVT is closely related to the increased risk of liver-related adverse prognosis in patients with hepatitis B cirrhosis.

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.

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.

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.