中华肝脏病杂志最新文献

Objective: To investigate the efficacy and safety of tenofovir amibufenamide in patients over 65 years old with chronic hepatitis B and liver cirrhosis. Methods: We recruited 45 patients in Linyi People's Hospital with chronic hepatitis B and liver cirrhosis who were treated with TMF antiviral therapy for 48 weeks, compared the virologic response rate and HBV DNA decrease level at 12, 24 and 48 weeks, and the changes in hepatitis B surface antigen, alanine aminotransferase, glomerular filtration rate, creatinine, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, serum phosphorus and blood lipids, and the changes in ALT normalization rate at 48 weeks. P<0.05 was statistically significant. Results: The age of the enrolled patients was 69.0 (67.0, 72.5) years. At 12, 24, and 48 weeks of treatment, the complete virological response rates were 32.4% (12/37), 70.0% (28/40), and 84.6% (33/39) respectively, and the level of HBV DNA decreased from baseline (P＜0.05). After 48 weeks of treatment, the level of HBsAg decreased (P<0.05), and there was no negative HBsAg conversion and seroconversion. After 48 weeks of treatment, the level of ALT decreased (P<0.05). At 48 weeks of treatment, the rates of ALT reverted to normality were 88.9% (16/18) and 70.4% (19/27), respectively. There was no significant difference in the levels of glomerular filtration rate, creatinine, phosphorus, triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol estimated at baseline before and after treatment (P＞0.05), and no serious adverse events were observed. Conclusions: For patients over 65 years old with chronic hepatitis B and liver cirrhosis, TMF can significantly inhibit HBV DNA replication, and the ALT normalization rate is high and well tolerated.

Objective: To explore the independent risk factors for bleeding in patients following percutaneous liver biopsy examination. Methods: The clinicopathological data of patients who underwent percutaneous liver biopsy examination at Nanjing Second Hospital from January 2012 to December 2021 were retrospectively collected. Univariate and multivariate logistic regression analysis were used to investigate the effect of age, gender, lesion type (diffuse liver parenchymal lesions, focal liver lesions), number of biopsies, tissue length, presence or absence of cirrhosis, presence or absence of portosystemic shunt, erythrocytes, white blood cells, hemoglobin, platelets, prothrombin time, fibrinogen, international normalized ratio, and liver biochemical indicators on bleeding following liver biopsy, as well as to screen independent risk factors. Results: A total of 3 331 patients were examined by percutaneous liver biopsy, and 3 060 cases were actually included by excluding 271 cases who took consultation from other hospitals. The overall postoperative hemorrhagic rate was 1.6% (49/3 060). Of which, forty-four cases (1.4%) had overt bleeding (hemodynamic changes or hemoglobin decreased by more than 20 g/L), five cases (0.2%) had minor bleeding, three cases had subcapsular hepatic hemaotma, and two cases had local bleeding from liver biopsy. Among the overt bleeding cases, two cases were in the off-label group (platelet<50×10⁹/L or international normalized ratio>1.5), and the rest were in the non-off-label group. The results of univariate analysis showed that factors such as focal liver lesions, portosystemic shunt, prolonged prothrombin time, increased international normalized ratio, bilirubin, and alkaline phosphatase were associated with bleeding after liver biopsy in the non-off-label group. The multivariate collinearity diagnosis revealed statistically significant differences for the indicators. Multivariate logistic regression analysis finally included factors such as lesion type, portosystemic shunt, international normalized ratio, total bilirubin, and alkaline phosphatase. The results showed that patients with focal liver lesions were more prone to bleed after surgery than patients with diffuse liver parenchymal lesions (OR=3.396, P=0.002, 95%CI: 1.596-7.228). Patients with portosystemic shunt were more prone to bleed than those without portosystemic shunt (OR=3.301, P=0.018, 95%CI: 1.232-8.845). Patients were more likely to experience bleeding following liver biopsy when their total bilirubin levels were elevated (OR=1.006, P<0.001, 95%CI:1.003-1.008). Conclusion: Focal liver lesions, portosystemic shunts, and elevated total bilirubin are independent risk factors for bleeding after percutaneous liver biopsy.

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.

Thrombocytopenia is one of the common complications with the hematologic system in patients with chronic liver disease, which often causes poor quality of life and high risk of bleeding, thereby affecting their diagnosis, treatment, and prognosis. Platelet transfusion can improve the patient's declining platelet count to a certain extent, but it has problems such as high price and being easy to cause immune rejection. Thrombopoietin (TPO), as an important cytokine that affects platelet production, can bind to TPO receptors and activate megakaryocytes to produce platelets. Lusutrombopag is a newly developed small-molecule TPO receptor agonist that can induce bone marrow progenitor cells to differentiate into megakaryocytes and increase platelet production, posing characteristics of oral convenience, safety and effectiveness; thus, it has been used in many countries and regions for the treatment of patients with chronic liver diseases concurrent with thrombocytopenia. Herein, the pharmacological features and clinical research are reviewed.

Chronic hepatitis D is a kind of severe viral hepatitis caused by co-infection with hepatitis D virus (HDV) and hepatitis B virus (HBV) or infection with HDV on the ground of HBV infection. Patients with hepatitis D who are infected with HBV often have faster disease progression and a worse prognosis. However, the public and clinicians have always paid little attention to chronic hepatitis D. Coupled with the limitations of detection methods and the absence of a screening system, the HDV screening rate in various regions of the world is at a low level. Consequently, the enthusiasm for screening, diagnosis, and treatment has been further reduced by the inadequate effectiveness of previous treatment methods. In recent years, progress has been made in the research and development of anti-HDV drugs, and a variety of drugs have already entered the clinical trial stage, and some have already been approved for commercialization in specific parts of the world. In this context, the world is also actively exploring effective ways to increase the HDV screening rate. The reflex test model can effectively raise the HDV screening rate and serve as a reference for HDV screening in other countries and regions, as demonstrated by studies conducted in the United Kingdom, France, and Spain, among others. This article will review the detection methods, screening, diagnosis, and treatment current status, as well as the progress in drug research and development, in order to help clinical physicians understand chronic HDV diagnosis and treatment.

Hepatocellular carcinoma is one of the most common malignant tumors in the world, which is a serious threat to human health. HBV infection is one of the most common causes of hepatocellular carcinoma.The diagnosis of most hepatocellular carcinoma has progressed to the middle and late stage, and the prognosis is poor. Early detection, diagnosis and treatment are important supports to improve the clinical outcome of hepatocellular carcinoma. In recent years, scholars at home and abroad have established various hepatocellular carcinoma risk prediction models, which are conducive to improving the early diagnosis rate of hepatocellular carcinoma and reducing the mortality rate. This article reviews the risk factors and risk prediction models of chronic hepatitis B associated hepatocellular carcinoma, in order to provide reference for HBV-associated liver cancer risk monitoring and management decision.

Wilson's disease (WD) is a kind of inherited metabolic liver disease in which most patients need lifelong medication to maintain copper homeostasis in the body. Zinc is one of the most commonly used drugs for WD treatment. However, there are currently few high-quality, large-sample, and prospective clinical trials on zinc agent-treated WD. The selection and application of zinc agents are mainly based on patients' clinical phenotype, tolerance to zinc agents, and physicians' experience in treating WD. This article summarizes the application of zinc agents in WD.

Wilson's disease, also known as hepatolenticular degeneration, is an inherited disorder of copper metabolism caused by homozygous or compound heterozygous variants in the ATP7B gene, which is mainly clinically manifested as liver disease and/or neurological/psychological disorders, and Kayser-Fleischer ring in the peripheral cornea. Patients with Wilson's disease are currently treated with lifelong use of chelating agents that promote copper ion excretion and/or zinc agents that reduce copper absorption, but there is still an unmet clinical need because some patients who receive treatment have poor efficacy, disease progression, or serious adverse drug reactions. In recent years, new therapeutic drugs have been developed rapidly. This article will summarize the advances in drug treatment of Wilson's disease, shedding new light on the treatment of Wilson's disease.

Objective: To construct an individualized nomogram prediction model for predicting the risk of the occurrence of covert hepatic encephalopathy (CHE) in patients with liver cirrhosis. Methods: 325 cases of liver cirrhosis admitted from January 2020 to December 2022 were selected as the study subjects. Patients were divided into training (n=213) and validation (n=112) sets using a cluster randomization method. The risk factors for CHE occurrence in patients with cirrhosis in the training set were analyzed by univariate and multivariate logistic regression. A prediction model related to the nomogram was established. Results: Independent risk factors for the occurrence of CHE in patients with cirrhosis were a history of hepatic encephalopathy, co-infection, gastrointestinal bleeding, severe ascites, prothrombin time ≥16 seconds, high total bilirubin, and high blood ammonia levels (P<0.05). Nomogram model validation results: The model had a net benefit for the training and validation sets, with C-indices of 0.830 (95%CI: 0.802-0.858) and 0.807 (95%CI: 0.877-0.837), respectively, within the range of 0-96%. The calibration curves of both sets were evenly close to the ideal curves. The AUCs for the ROC curves in both sets were 0.827 (95%CI: 0.796-0.858) and 0.811 (95%CI: 0.787-0.836), respectively. Conclusion: Patients with cirrhosis have many risk factors for CHE occurrence. The nomogram model constructed based on these risk factors possesses a good predictive value for assessing CHE occurrence in cirrhotic patients.