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 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 investigate the liver disease phenotypes and clinical features of patients with different genotypes of Wilson's disease(WD).Methods A retrospective analysis was performed for 163 patients with WD who were diagnosed and underwent genetic testing in The Fifth Medical Center of Chinese PLA General Hospital from August 2008 to June 2023,and clinical manifestations,laboratory examination,pathological examination,imaging examination,and ATP7B genetic testing results were collected.According to ATP7B gene mutation,the patients were divided into groups as follows:R778L mutation group and non-R778L mutation group;P992L mutation group and non-P992L mutation group;truncation mutation group and non-truncation mutation group.Liver disease phenotypes and clinical features were analyzed for the patients with c.2333G>T/p.R778L mutation(R778L mutation),c.2975C>T/p.P992L mutation(P992L mutation),and truncation mutation of the ATP7B gene.The Mann-Whitney U test or the Kruskal-Wallis H test was used for comparison of continuous data between groups,and the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Results The 163 patients with WD had varying severities of liver disease phenotypes,among whom 121(74.23%)were diagnosed with chronic liver disease,36(22.09%)were diagnosed with decompensated cirrhosis,and 6(3.68%)were diagnosed with fulminant WD,and in addition,there were 5 patients(2 with chronic liver disease and 3 with decompensated cirrhosis)with neurological abnormalities.For the 163 patients with WD,R778L mutation(with an allele frequency of 28.2%)was the most common mutation in the ATP7B gene,followed by P992L mutation(with an allele frequency of 12.6%),and truncation mutation showed an allele frequency of 11.0%.There was no significant difference in the distribution of the three mutations across different liver disease phenotypes(P>0.05).The R778L mutation group had a significantly lower level of ceruloplasmin(CP)than the non-R778L mutation group[0.04(0.02-0.08)g/L vs 0.08(0.03-0.13)g/L,Z=-2.889,P=0.004].Compared with the non-P992L mutation group,the P992L mutation group had significantly higher levels of alanine aminotransferase[135.0(80.5-237.0)U/L vs 80.5(36.0-173.3)U/L,Z=2.684,P=0.007]and aspartate aminotransferase[121.4(77.0-195.0)U/L vs 84.0(39.0-123.3)U/L,Z=3.388,P<0.001].Compared with the non-truncation mutation group,the truncation mutation group had significantly lower levels of CP[0.03(0.02-0.08)g/L vs 0.06(0.03-0.11)g/L,Z=-3.136,P=0.002]and serum copper[3.20(2.15-5.00)mg/L vs 4.20(2.60-7.50)mg/L,Z=-2.296,P=0.025].Conclusion R778L mutation,P992L mutation and truncation mutation are not associated with liver disease phenotype in WD patients;however,R778L mutation is associated with a lower level of CP,P992L mutation is associated with higher levels of ALT and AST,and truncation mutation is associated with lower levels of CP and serum copper.

Objective:To investigate the clinical manifestations, pathological, and gene mutation characteristics of ABCB4 gene variant-associated cholestatic liver disease in adults. Methods:Eight adult cases of ABCB4 gene variant-associated cholestatic liver disease who were hospitalized in the Department of Hepatology, Fifth Medical Center of the People's Liberation Army General Hospital from May 2010 to December 2022 were enrolled in this study. The clinical manifestations, pathological features, gene variant features, and prognostic conditions were analyzed. Patient gene testing and biological information analysis were performed using whole-exome next-generation sequencing. SPSS 19.0 software was used to conduct descriptive analysis. Results:Among the eight adult cases of the ABCB4 gene variant, there were three males and five females, with a median age of onset of 24 (20, 37) years. There were three cases with a compound heterozygous variant in ABCB4, and the clinical phenotypes included two cases of progressive familial intrahepatic cholestasis type 3 and one case of intrahepatic cholestasis of pregnancy overlapping with low-phospholipid-associated cholelithiasis syndrome. There were five cases with a single heterozygous variant in ABCB4, and the clinical phenotypes included two cases of intrahepatic cholestasis of pregnancy overlapping with drug-induced liver injury and three cases of low-phospholipid-associated cholelithiasis syndrome. Imaging of all eight cases showed liver fibrosis, and six cases already had cirrhosis. All patients underwent liver histopathological examination, which mainly showed cholestasis and portal fibrosis in eight cases, small bile duct hyperplasia in seven cases, copper deposition in three cases, and cirrhosis in five cases. ABCB4 screening revealed 11 different mutations, including eight new mutations. The pathogenicity assessment showed that c.2394+82C>T (intron) was a benign mutation, and the rest were deleterious mutations. Ursodeoxycholic acid was the treatment for all patients, with a follow-up time of 7.5 (0.5, 12.7) years. One case died of end-stage liver disease, two cases developed cholestatic cirrhosis, and five cases were in stable condition. Conclusion:The adult ABCB4 gene variant-associated cholestatic liver disease are mostly single heterozygous mutations, the clinical phenotypes are diverse and overlapping, the disease is more severe in those who carried non-functional mutations.

Objective:To analyze the clinical manifestations, pathology, and gene variant characteristics in children with progressive familial intrahepatic cholestasis type 3 (PFIC3).Methods:This retrospective study assessed the clinical manifestations, pathological features, gene variants, and prognosis data of 11 children with PFIC3 hospitalized in the Department of Hepatology, Fifth Medical Center, PLA General Hospital, from January 2015 to December 2022. Panel or whole exome sequencing was performed on the probands, followed by Sanger sequencing for verification within the family. Detected pathogenic variants were compared with known disease databases. Additionally, the new variants were predicted the deleteriousness and protein structure using relevant software to evaluate their pathogenicity.Results:Among the 11 PFIC3 children, 8 were boys and 3 were girls. The age of onset was 3.1 (0.2, 15.6) years. The main complaint of onset was different in the 11 patients;5 of them were abnormal liver function, 3 of them were liver and spleen enlargement, 2 of them were abdominal distension, and 1 of them was jaundice. Alanine aminotransferase, asparate aminotransferase and γ-glutamyltransferase increased in all the patients, which were(113±40), (150±44) and (270±156) U/L respectively. Moreover, direct bilirubin increased in 9 patients, and cholestasis was showed in 8 patients. All patients showed liver fibrosis on imaging, and 8 patients had cirrhosis. The pathological features of 8 cases by liver biopsy were as follows: 8 cases of fibrosis in the portal area, 7 cases of small bile duct hyperplasia, 4 cases of positive copper staining, and 5 cases of cirrhosis. A total of 17 ABCB4 gene variants were detected, including 9 new variants: c.589C>T(p.Q197X), c.1230+1G>A(Splicing), c.2914G>A(P.D972N), c.1058G>A(p.C353Y), c.956G>T(p.G319V), c.473T>A(p.L158Q), c.164T>C(p.L55S), c.2493G>C(p.R831S), and c.1150G>C(p.G384R). All 11 patients were treated with ursodeoxycholic acid and followed up for 5.1(0.6, 7.4) years. Among them, 4 cases of cirrhosis progressed continuously, 3 cases had liver transplantations, and the remaining 4 cases were stable after medical treatment.Conclusions:Children with PFIC3 have early onset, diverse clinical manifestations, rapid progression of fibrotic and cholestasis, as well as poor prognosis. Genetic testing helps to confirm the diagnosis.

Objective:To investigate the role of serum hepatitis B virus RNA (HBV RNA) in predicting HBeAg serological conversion in children with chronic hepatitis B.Methods:175 children aged 1~17 years with chronic hepatitis B who received interferon α (IFNα) for 48 weeks were selected. Patients were divided into HBeAg seroconversion and non-conversion based on whether HBeAg seroconversion occurred at 48 weeks of treatment.T-test and Mann-Whitney U test were used to compare between groups; chisquare test or Fisher exact probability method was used to compare the frequency between groups of classified variables; and Pearson correlation was used to analyze the correlation between indicators. Univariate and multivariate logistic regression analyses were used to identify influencing factors associated with HBeAg serological conversion. The predictive effect of HBV RNA, HBV DNA, and HBsAg on HBeAg serological conversion was compared and analyzed by the receiver operating characteristic curve (ROC).Results:The seroconversion rate of HBeAg at 48 weeks was 36.0% (63/175). The reduction in HBVRNA levels from baseline to the 12th, 24th, 36th, and 48th weeks of antiviral therapy was significantly greater in the HBeAg serological conversion group than that in the non-conversion group, and the difference was statistically significant between the two groups (P < 0.05). Univariate and multivariate regression analyses showed that age and a decline in HBV RNA levels at week 12 were independent predictors of HBeAg serological conversion. The area under the ROC curve (AUROC) of HBV RNA decline at week 12 was 0.677(95% CI∶0.549-0.806, P = 0.012), which was significantly better than the same period of AUROC of HBV DNA (0.657, 95% CI∶0.527-0.788, P = 0.025) and HBsAg (0.660, 95% CI∶0.526-0.795, P = 0.023) decline. HBV RNA levels decreased (>1.385 log10 copies/ml) at week 12, with a positive predictive value of 53.2%, a negative predictive value of 72.2%, a sensitivity of 77.4%, and a specificity of 57.9% for HBeAg seroconversion. Conclusion:HBV RNA level lowering during the 12th week of antiviral therapy can serve as an early predictor marker for HBeAg serological conversion in children with chronic hepatitis B.

Objective:To explore the effect of tenofovir disoproxil fumarate (TDF) treatment on renal function for preventing mother-to-infant transmission of hepatitis B virus (HBV) in pregnant women during the second and third trimester of pregnancy.Methods:The subjects were selected from pregnant women with HBV infection who were registered in Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University and delivered between January and December 2021. The pregnant women who had HBV DNA ≥2.0×10 5 IU/ml and took TDF at 24-28 weeks of gestation were included in treatment group, and the pregnant women who had HBV DNA <2.0×10 5 IU/ml and did not use anti-HBV drugs during pregnancy were included in control group. The medical records data of pregnant women in the 2 groups were collected, including urine routine examination, liver function, renal function, estimated glomerular filtration rate (eGFR), blood phosphorus, serum markers of hepatitis B, HBV DNA, ect. at 24-28 weeks of gestation (baseline data), renal function, eGFR, serum phosphorus at 36-37 weeks of gestation, delivery, and 42 days postpartum, and adverse events related to renal tubular injury. Serum creatinine (Scr), blood urea nitrogen, eGFR, and blood phosphorus at baseline level, 36-37 weeks, delivery and 42 days postpartum, and changes of Scr and blood phosphorus before and after treatment between the 2 groups were compared, and adverse events related to renal tubular injury in the treatment group were recorded. Results:A total of 189 pregnant women were entered in the analysis, including 106 in the treatment group and 83 in the control group. The differences in age, proportion of primipara, baseline level of alanine aminotransferase, Scr, blood urea nitrogen, eGFR and blood phosphorus between the 2 groups were not statistically significant (all P>0.05), but the proportion of HBeAg-positive women and HBV DNA level in the treatment group were significantly higher than those in the control group (all P<0.05). The differences in Scr, blood urea nitrogen, eGFR, and blood phosphorus between the treatment group and the control group at 36-37 weeks of gestation, delivery and 42 days postpartum were not statistically significant (all P>0.05). The trends of changes in Scr, blood urea nitrogen, eGFR, and blood phosphorus from baseline level to 42 days postpartum were similar between 2 groups (all P>0.05). None of the pregnant women in the treatment group had adverse events related to renal tubular injury, such as hypophosphatemia, elevated Scr, renal hypouricemia, β2-microglobulinuria, non-diabetic glycosuria, metabolic acidosis, etc. Conclusion:TDF is safe for the kidney in the second and third trimester of pregnancy to strengthen the blocking of mother-to-infant transmission of HBV.

Objective:To explore the effect of tenofovir disoproxil fumarate (TDF) treatment on renal function for preventing mother-to-infant transmission of hepatitis B virus (HBV) in pregnant women during the second and third trimester of pregnancy.Methods:The subjects were selected from pregnant women with HBV infection who were registered in Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University and delivered between January and December 2021. The pregnant women who had HBV DNA ≥2.0×10 5 IU/ml and took TDF at 24-28 weeks of gestation were included in treatment group, and the pregnant women who had HBV DNA <2.0×10 5 IU/ml and did not use anti-HBV drugs during pregnancy were included in control group. The medical records data of pregnant women in the 2 groups were collected, including urine routine examination, liver function, renal function, estimated glomerular filtration rate (eGFR), blood phosphorus, serum markers of hepatitis B, HBV DNA, ect. at 24-28 weeks of gestation (baseline data), renal function, eGFR, serum phosphorus at 36-37 weeks of gestation, delivery, and 42 days postpartum, and adverse events related to renal tubular injury. Serum creatinine (Scr), blood urea nitrogen, eGFR, and blood phosphorus at baseline level, 36-37 weeks, delivery and 42 days postpartum, and changes of Scr and blood phosphorus before and after treatment between the 2 groups were compared, and adverse events related to renal tubular injury in the treatment group were recorded. Results:A total of 189 pregnant women were entered in the analysis, including 106 in the treatment group and 83 in the control group. The differences in age, proportion of primipara, baseline level of alanine aminotransferase, Scr, blood urea nitrogen, eGFR and blood phosphorus between the 2 groups were not statistically significant (all P>0.05), but the proportion of HBeAg-positive women and HBV DNA level in the treatment group were significantly higher than those in the control group (all P<0.05). The differences in Scr, blood urea nitrogen, eGFR, and blood phosphorus between the treatment group and the control group at 36-37 weeks of gestation, delivery and 42 days postpartum were not statistically significant (all P>0.05). The trends of changes in Scr, blood urea nitrogen, eGFR, and blood phosphorus from baseline level to 42 days postpartum were similar between 2 groups (all P>0.05). None of the pregnant women in the treatment group had adverse events related to renal tubular injury, such as hypophosphatemia, elevated Scr, renal hypouricemia, β2-microglobulinuria, non-diabetic glycosuria, metabolic acidosis, etc. Conclusion:TDF is safe for the kidney in the second and third trimester of pregnancy to strengthen the blocking of mother-to-infant transmission of HBV.

Objective:To evaluate the efficacy and safety of direct antiviral drugs based on sofosbuvir in the treatment of chronic hepatitis C in children.Methods:Data of children diagnosed with chronic hepatitis C from May 2017 to December 2019 and received sofosbuvir (SOF, body weight ≥ 17 kg 200 mg/d, <17 kg 150 mg/d)/ledipasvir (LDV, body mass ≥ 17 kg 45 mg/d, <17 kg 33.75 mg/d) or velpatasvir (VEL, body weight ≥ 17 kg 50 mg/d), were collected. The patients were treated with ribavirin (RBV, 15 mg/kg·d) for 12 weeks and followed up for 12 weeks. The main outcome measures were sustained virological response (SVR) at 12 weeks follow-up after drug discontinuation, and the occurrence of adverse events during the treatment period was observed to evaluate the safety of the drug.Results:HCV RNA turned negative in 10 of the 13 children (76.92%), within 2 weeks after antiviral treatment, in 2 cases (15.38%) HCV RNA turned negative in 2-4 weeks, in 1 case (7.69%) RBV was added when HCV RNA did not turn negative in 8 weeks, but turned negative at 10 weeks. At 12 and 24 weeks after discontinuation of antiviral drugs (SVR12), HCV RNA continued to be negative, and at 24 weeks (SVR24), it was also negative. Adverse reactions: headache occurred in 2 cases (15.38%), fatigue in 3 cases (23.08%), no serious adverse reactions occurred in any of the patients.Conclusions:The efficacy and safety of direct antiviral drugs based on SOF in the treatment of children with chronic hepatitis C were good.

Objective:To explore the status of HBV infection, immune response to hepatitis B vaccine and its influencing factors of one-year old children born to HBV infected mothers in real world.Methods:In this cross-sectional study, eligible mothers infected with chronic HBV and children who completed standard vaccination against hepatitis B vaccine and hepatitis B immunoglobulin injection were selected. Clinical biochemical, virological measurements, data of antiviral therapy and complications during pregnancy and childbirth were collected by HIS(Hospital Information System)system and LIS (Laboratoty Information Management System) system. At one year of age, the children were tested for HBsAg, HBsAb and HBV DNA in venous blood specimens.Results:A total of 1 302 eligible mothers and children were collected, including 600 in high viral load group (mothers’ HBV DNA≥2×10 5 IU/ml) and 702 in low viral load group (mothers’ HBV DNA<2×10 5 IU/ml). In high viral load group, 587 patients received antiviral drugs in the middle or late trimester (Treated group) and 13 patients did not receive antiviral drugs (Untreated group). No chronic HBV infection occurred in children of low viral load group, and in 5 cases (0.83%) the infection occurred in high viral load group. In the five HBV infected children, 3 cases (0.51%) were in the treated group, and 2 cases (15.38%) in untreated group. The failure rate of mother-to-child blocking in low viral load group was significantly lower than that in high viral load group ( χ2=5.87, P=0.015), and it was significantly lower in treated group than that in untreated group ( χ2=29.195, P=0.001). The percentages of HBsAb level <10 mIU/ml, 10- <100 mIU/ml and ≥100 mIU/ml in 1 297 children without HBV infection were 1.15%, 15.65% and 83.19%, respectively. Univariate and multivariate logistic regression analysis showed that maternal total bilirubin level and hypothyroidism during pregnancy were correlated with HBsAb level at 1 year of age ( χ2=29.003, P <0.05). Conclusions:Antiviral drugs taken during pregnancy by pregnant women with high HBV viral load can significantly reduce mother-to-child transmission of HBV. Follow-up on the response of children born to HBV-infected mothers to hepatitis B vaccine should be enhanced after birth.