Humans ; Ascites/etiology* ; Liver Cirrhosis/complications* ; Cholecystectomy/adverse effects*

OBJECTIVES: Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT). METHODS: This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored. RESULTS: Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910). CONCLUSIONS The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.
Humans ; Hepatitis B, Chronic/complications* ; Hepatitis B e Antigens/therapeutic use* ; Alkaline Phosphatase ; DNA, Viral ; Retrospective Studies ; Fibrosis ; Hepatitis B virus/genetics* ; Liver Cirrhosis/etiology* ; Inflammation/drug therapy* ; Antiviral Agents/therapeutic use* ; Alanine Transaminase

Hepatitis D virus (HDV) infection causes the most severe form of viral hepatitis with rapid progression to cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Although discovered > 40 years ago, little attention has been paid to this pathogen from both scientific and public communities. However, effectively combating hepatitis D requires advanced scientific knowledge and joint efforts from multi-stakeholders. In this review, we emphasized the recent advances in HDV virology, epidemiology, clinical feature, treatment, and prevention. We not only highlighted the remaining challenges but also the opportunities that can move the field forward.
Carcinoma, Hepatocellular/complications* ; Hepatitis B virus ; Hepatitis D/epidemiology* ; Hepatitis Delta Virus/genetics* ; Humans ; Liver Cirrhosis/etiology* ; Liver Neoplasms/complications*

Although the treatment strategy of esophageal and gastric varices bleeding in portal hypertension has been diversified and multidisciplinary now,the surgical treatment represented by pericardial devascularization operation will still play an important and irreplaceable role in China. In order to standardize the surgical procedure,guide clinical practice and improve the level of surgical treatment of portal hypertension,Chinese Society of Spleen and Portal Hypertension Surgery,Chinese Surgical Society,Chinese Medical Association organized Chinese experts to formulate this consensus. The main contents include:the position of surgical treatment,surgical indications and contraindications,preoperative evaluation,key points and precautions of surgical procedure,perioperative treatment,prevention and treatment of postoperative complications. The consensus emphasizes the standardization of surgical treatment of portal hypertension,pay attention to the prevention and treatment of postoperative portal vein thrombosis,and expect to provide surgeons with clinical guidance.
Consensus ; Esophageal and Gastric Varices ; Gastrointestinal Hemorrhage/etiology* ; Humans ; Hypertension, Portal/surgery* ; Liver Cirrhosis/complications* ; Retrospective Studies ; Splenectomy/adverse effects*

OBJECTIVE: To explore the role of 5-hydroxytryptamine (5-HT) in type 2 diabetes mellitus (T2DM)-related hepatic inflammation and fibrosis. METHODS: Male C57BL/6J mice were used to establish T2DM model by high-fat diet feeding combined with intraperitoneal injection of streptozotocin. Then, the mice with hyperglycemia were still fed with high-fat diet for nine weeks, and treated with or without 5-HT_2A receptor (5-HT_2AR) antagonist sarpogrelate hydrochloride (SH) and 5-HT synthesis inhibitor carbidopa (CDP) (alone or in combination). To observe the role of 5-HT in the myofibroblastization of hepa-tic stellate cells (HSCs), human HSCs LX-2 were exposed to high glucose, and were treated with or without SH, CDP or monoamine oxidase A (MAO-A) inhibitor clorgiline (CGL). Hematoxylin & eosin and Masson staining were used to detect the pathological lesions of liver tissue section, immunohistochemistry and Western blot were used to analyze protein expression, biochemical indicators were measured by ELISA or enzyme kits, and levels of intracellular reactive oxygen species (ROS) were detected by fluorescent probe. RESULTS: There were up-regulated expressions of 5-HT_2AR, 5-HT synthases and MAO-A, and elevated levels of 5-HT in the liver of the T2DM mice. In addition to reduction of the hepatic 5-HT levels and MAO-A expression, treatment with SH and CDP could effectively ameliorate liver lesions in the T2DM mice, both of which could ameliorate hepatic injury and steatosis, significantly inhibit the increase of hepatic ROS (H₂O₂) levels to alleviate oxidative stress, and markedly suppress the production of transforming growth factor β1 (TGF-β1) and the development of inflammation and fibrosis in liver. More importantly, there was a synergistic effect between SH and CDP. Studies on LX-2 cells showed that high glucose could induce up-regulation of 5-HT_2AR, 5-HT synthases and MAO-A expression, increase intracellular 5-HT level, increase the production of ROS, and lead to myofibroblastization of LX-2, resulting in the increase of TGF-β1 synthesis and production of inflammatory and fibrosis factors. The effects of high glucose could be significantly inhibited by 5-HT_2AR antagonist SH or be markedly abolished by mitochondrial 5-HT degradation inhibitor CGL. In addition, SH significantly suppressed the up-regulation of 5-HT synthases and MAO-A induced by high glucose in LX-2. CONCLUSION Hyperglycemia-induced myofibroblastization and TGF-β1 production of HSCs, which leads to hepatic inflammation and fibrosis in T2DM mice, is probably due to the up-regulation of 5-HT_2AR expression and increase of 5-HT synthesis and degradation, resulting in the increase of ROS production in mitochondria. Among them, 5-HT_2AR is involved in the regulation of 5-HT synthases and MAO-A expression.
Male ; Mice ; Humans ; Animals ; Hepatic Stellate Cells/pathology* ; Transforming Growth Factor beta1/pharmacology* ; Serotonin/metabolism* ; Reactive Oxygen Species/metabolism* ; Diabetes Mellitus, Type 2/complications* ; Hydrogen Peroxide/metabolism* ; Mice, Inbred C57BL ; Liver Cirrhosis/etiology* ; Hyperglycemia/pathology* ; Monoamine Oxidase/metabolism* ; Inflammation ; Glucose/metabolism* ; Cytidine Diphosphate/pharmacology*

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is the endoscopic modality of choice for the treatment of biliary and pancreatic diseases. However, patients with cirrhosis, particularly those with decompensated cirrhosis, are believed to be at increased risk for complications associated with ERCP. There is a paucity of literature describing the outcomes of ERCP for patients with cirrhosis. This study aimed to investigate the outcomes of ERCP for cirrhosis patients, especially adverse events, and evaluated its safety and efficacy. METHODS: We performed a multicenter, retrospective study of all patients at Beijing Friendship Hospital affiliated to Capital Medical University, Xijing Hospital affiliated to Air Force Military Medical University, Beijing Youan Hospital affiliated to Capital Medical University, and the Fifth Medical Center of the People's Liberation Army General Hospital from June 2003 to August 2019. The adverse events of inpatient ERCP for patients with ( n  = 182) and without liver cirrhosis (controls; n  = 385) were compared. RESULTS: A total of 567 patients underwent ERCP between January 2003 and December 2019 were enrolled in this study. Compared to patients without cirrhosis, patients with cirrhosis were at higher risk for postoperative complications (odds ratio [OR], 4.172; 95% confidence interval [CI], 1.232-7.031; P  < 0.001) such as postoperative pancreatitis (OR, 2.026; 95% CI, 1.002-4.378; P  = 0.001) and cholangitis (OR, 3.903; 95% CI, 1.001-10.038; P  = 0.036). The main indications for ERCP for patients with cirrhosis in this study included choledocholithiasis (101 cases; 55.5%), benign bile duct strictures (46 cases; 25.3%), and malignant bile duct strictures (28 cases; 15.4%). Among them, 23 patients (12.6%) underwent balloon dilation and 79 patients (43.4%) underwent sphincterotomy. Of the patients with cirrhosis, delayed bleeding occurred in ten patients (5.5%), postoperative pancreatitis occurred in 80 patients (44.0%), and postoperative cholangitis occurred in 25 patients (13.7%). An additional multivariate analysis showed that the total bilirubin (TBIL) level (OR, 4.58; 95% CI, 2.37-6.70) and Child-Pugh score of C (OR, 3.11; 95% CI, 1.04-5.37) were risk factors for postoperative complications in patients with cirrhosis. CONCLUSIONS Compared with the general population of patients undergoing ERCP, patients with cirrhosis were more prone to postoperative pancreatitis and cholangitis. TBIL levels and Child-Pugh scores were risk factors for postoperative complications in patients with cirrhosis.
Humans ; Cholangiopancreatography, Endoscopic Retrograde/adverse effects* ; Retrospective Studies ; Constriction, Pathologic ; Risk Factors ; Liver Cirrhosis/complications* ; Pancreatitis/etiology* ; Postoperative Complications/epidemiology* ; Cholangitis

BACKGROUND: Hepatitis B is a viral infection that attacks the liver and can cause both potentially life-threatening acute and chronic liver disease. China has the world's largest burden of hepatitis B and is considered to be a major contributor toward the goal of World Health Organization (WHO) of eliminating hepatitis B virus (HBV) as a global health threat by 2030. This study aimed to analyze data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to determine the trends in mortality of liver disease due to hepatitis B in China between 1990 and 2019 and the gap with the WHO's goal. METHODS: Annual deaths and age-standardized mortality rates (ASMRs) of liver disease due to hepatitis B in China between 1990 and 2019 were collected from GBD 2019. We calculated the percentage changes in deaths and estimated annual percentage changes (EAPCs) of ASMRs of liver disease due to hepatitis B. RESULTS: In China, deaths of total liver disease due to hepatitis B decreased by 29.13% from 229 thousand in 2016 to 162 thousand in 2019, and ASMR decreased by an average of 4.92% (95% confidence interval [CI]: 4.45-5.39%) per year in this period. For the spectrum of liver disease due to hepatitis B, deaths decreased by 74.83%, 34.71%, and 23.34% for acute hepatitis, cirrhosis and other chronic liver diseases, and liver cancer from 1990 to 2019, respectively, and ASMRs of acute hepatitis (EAPC = -7.63; 95% CI: -8.25, -7.00), cirrhosis and other chronic liver diseases (EAPC = -4.15; 95% CI: -4.66, -3.65), and liver cancer (EAPC = -5.17; 95% CI: -6.00, -4.33) decreased between 1990 and 2019. The proportions of older adults aged ≥70 years among all deaths of the spectrum of liver disease due to hepatitis B increased from 1990 to 2019. Deaths of liver cancer due to hepatitis B increased by 7.05% from 2015 to 2019. CONCLUSIONS Although a favorable trend in the mortality of liver disease due to hepatitis B was observed between 1990 and 2019, China still faces challenges in achieving the WHO's goal of eliminating HBV as a public threat by 2030. Therefore, efforts to increase the coverage of diagnosis and treatment of liver disease due to hepatitis B, especially of liver cancer due to hepatitis B, are warranted in China.
Humans ; Aged ; Global Burden of Disease ; Hepatitis B/complications* ; Hepatitis B virus ; Liver Cirrhosis/complications* ; China/epidemiology* ; Liver Neoplasms/etiology*

Liver cirrhosis is a major global health burden worldwide due to its high risk of morbidity and mortality. Role of terlipressin for the management of liver cirrhosis related complications has been recognized during recent years. This paper aims to develop evidence-based clinical practice guidance on the use of terlipressin for liver cirrhosis related complications. Hepatobiliary Study Group of Chinese Society of Gastroenterology of Chinese Medical Association and Hepatology Committee of Chinese Research Hospital Association have invited gastroenterologists, hepatologists, infectious disease specialists, surgeons, and clinical pharmacists to formulate the clinical practice guidance based on comprehensive literature review and experts' clinical experiences. Overall, 10 major statements regarding efficacy and safety of terlipressin in liver cirrhosis were proposed. Terlipressin can be beneficial for the management of cirrhotic patients with acute variceal bleeding and hepatorenal syndrome (HRS). However, the evidence regarding the use of terlipressin in cirrhotic patients with ascites, post-paracentesis circulatory dysfunction, and bacterial infections and in those undergoing hepatic resection and liver transplantation remains insufficient. Terlipressin-related adverse events, mainly including gastrointestinal symptoms, electrolyte disturbance, and cardiovascular and respiratory adverse events, should be closely monitored. The current clinical practice guidance supports the use of terlipressin for gastroesophageal variceal bleeding and HRS in liver cirrhosis. High-quality studies are needed to further clarify its potential effects in other liver cirrhosis related complications.
Electrolytes ; Esophageal and Gastric Varices/drug therapy* ; Gastrointestinal Hemorrhage/etiology* ; Hepatorenal Syndrome/etiology* ; Humans ; Liver Cirrhosis/drug therapy* ; Lypressin/adverse effects* ; Terlipressin/adverse effects* ; Vasoconstrictor Agents/adverse effects*

This article presented an overview of the therapeutic effects of Chinese medicine (CM) preparations for promoting blood circulation and removing blood stasis for patients with portal vein thrombosis (PVT) after splenectomy. Based on published clinical researches of CM preparations for PVT after splenectomy in patients with cirrhotic portal hypertension (CPH), this paper evaluated the incidence of PVT, and explored potential active components and mechanisms of CM preparations. Safflower Yellow Injection, Danshen Injection () Danhong Injection (), and Compound Danshen Dropping Pill () achieved good curative effect alone or combined with anticoagulant therapy. In addition, Compound Biejia Ruangan Tablet () and Anluo Huaxian Pill () can also significantly improve the hemodynamic disorders of portal vein system in patients with cirrhosis. Considering the role of CM preparations in ameliorating the incidence of PVT after splenectomy in patients with CPH, we suggested that future research should provide more attention to CM alone or CM combined with anticoagulant for cirrhosis with PVT.
Anticoagulants/therapeutic use* ; Humans ; Hypertension, Portal/drug therapy* ; Liver Cirrhosis/surgery* ; Medicine, Chinese Traditional/adverse effects* ; Portal Vein ; Risk Factors ; Splenectomy/adverse effects* ; Venous Thrombosis/etiology*

Objective: To investigate the effects of plasma lipopolysaccharide (LPS) concentration changes on platelet release of vascular endothelial growth factor (VEGF) and thrombospondin (TSP)-1 in patients with decompensated cirrhotic portal hypertension after transjugular intrahepatic portosystemic shunt (TIPS) procedure. Methods: 169 cases with cirrhotic portal hypertension were enrolled, of which 81 cases received TIPS treatment. LPS, VEGF, and TSP-1 concentrations with different Child-Pugh class in peripheral blood plasma of patients were measured. After pre-incubation of normal human platelets with different concentrations of LPS and stimulated by collagen in vitro, platelet PAC-1 expression rate, VEGF, and TSP-1 concentrations were detected. PAC-1 expression rate and the concentrations of LPS, VEGF and TSP-1 in peripheral blood plasma of patients before and after TIPS procedure were detected. The relationship between plasma LPS, VEGF and TSP-1 concentrations and Child-Pugh score changes in patients after TIPS procedure was analyzed. Statistical analysis was performed by t-test, one-way ANOVA or Pearson's rho according to different data. Results: Plasma LPS and TSP-1 concentrations were significantly higher in Child-Pugh class C patients than class A and B, but the concentration of plasma VEGF was significantly lower than class A and B (P < 0.01). In vitro experiments showed that concentration of LPS, TSP-1, and platelet PAC-1 expression rate was higher in the supernatant, but the difference in the concentration of VEGF in the supernatant was not statistically significant. Portal vein pressure and platelet activation were significantly decreased (P < 0.01) in patients after TIPS procedure. Portal venous pressure, platelet activation, plasma LPS, and TSP-1 levels were significantly decreased continuously, while VEGF levels were significantly increased continuously after TIPS procedure. Plasma LPS concentration was positively correlated with TSP-1 concentration (r = 0.506, P < 0.001), and negatively correlated with VEGF concentration (r = -0.167, P = 0.010). Child-Pugh score change range was negatively correlated with change range of plasma VEGF concentration (r = -0.297, P = 0.016), and positively correlated with change range of plasma TSP-1 concentration (r = 0.145, P = 0.031) after TIPS. Conclusion: Portal venous pressure gradient, plasma LPS concentration and corresponding platelet activation was decreased in cirrhotic portal hypertension after TIPS procedure, and with TSP-1 reduction and VEGF elevation it is possible to reduce the liver function injury caused by portal venous shunt.
Blood Platelets ; Humans ; Hypertension, Portal/etiology* ; Lipopolysaccharides ; Liver Cirrhosis/complications* ; Plasma ; Portasystemic Shunt, Transjugular Intrahepatic/adverse effects* ; Vascular Endothelial Growth Factor A