Wilson disease （WD） is a disorder of copper metabolism caused by mutations in the ATP7B gene. Traditional diagnosis mainly relies on the Leipzig scoring system， while copper chelators and zinc preparations are mainly used for treatment. In recent years， the continuous emergence of various techniques has provided additional tools for the early detection and disease assessment of WD， such as novel assays targeting non-ceruloplasmin-bound copper， immunohistochemistry for metallothionein in liver tissue， and ⁶⁴Cu positron emission tomography-computed tomography imaging. Meanwhile， the new formulation trientine tetrahydrochloride and the potential novel agent methanobactin provide new drugs for safe and efficient copper removal， and gene therapy has brought new hope for clinical cure of WD. This article systematically reviews the recent advances in the diagnosis and treatment of WD， discusses their advantages and limitations in a real-world setting， and proposes new ideas for future clinical practice and research.

Among chronic hepatitis B patients undergoing long-term treatment with nucleos（t）ide analogues （NAs）， approximately 10%—20% can achieve a low level of <100 IU/mL for hepatitis B surface antigen （HBsAg）. These patients have the advantage to achieve clinical cure （HBsAg clearance） and are currently a key focus for treatment discontinuation and combination treatment strategies. As for the selection of clinical management strategies， the NAs discontinuation strategy， based on the “immune reactivation” hypothesis， may lead to HBsAg clearance in some patients， especially among Caucasians， but the risk of recurrence after discontinuation cannot be neglected. The treatment strategies based on pegylated interferon-α exhibit a higher potential for active HBsAg clearance， and some novel immunomodulators have also shown preliminary efficacy. Overall， for patients with HBsAg <100 IU/mL previously treated with NAs， treatment discontinuation or active combination treatment should be carefully assessed based on individual risk-benefit profiles. In the future， it is essential to incorporate more refined biomarkers for precise stratification and explore novel combination regimens with finite treatment courses that are safe and highly effective， in order to help more patients achieve clinical cure and reduce long-term risks of liver disease.

The incidence of juvenile Hereditary Hemochromatosis caused by HAMP gene mutation is low, which is rarely reported in China. This patient took abnormal liver function as the first symptom, and was finally diagnosed by genetic testing and hepatic histopathology, and treated by venous bloodletting.

Gilbert's syndrome is a type of hereditary disease caused by mutations in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene, which leads to decreased UGT1A1 activity. Clinically, it is mainly characterized by increased unconjugated bilirubin and is often considered a benign disease. The incidence rate of Gilbert's syndrome is as high as 5%-10% in the population, and its interaction with commonly used clinical drugs deserves attention. On the one hand, some drugs can enhance or reduce UGT1A1 activity, causing bilirubin levels to decrease or increase. On the other hand, the decrease of UGT1A1 activity can also change part of drug metabolism, increase or reduce drug efficacy, and may cause adverse reactions and even endanger the patient's life in severe conditions. This article summarizes the interactions between common drug metabolism and precautions for drug usage in Gilbert syndrome.

Genetic cholestatic liver disease is a type of disease caused by several different gene mutations, with cholestasis as the main manifestation, and is usually rare. Although these diseases differ in pathophysiology, clinical manifestations, and prognosis, they all possess the common feature of cholestasis. To this end, the European Association for the Study of the Liver published the EASL Clinical Practice Guidelines for Genetic Cholestatic Liver Disease in 2024, which provide a general approach to the management of cholestatic pruritus, detailed information on the diagnosis and treatment method of certain hereditary cholestatic liver diseases, and put forward recommendations on diagnosis and treatment with the aim to assist hepatologists (pediatric and adult) in implementing the latest diagnostic and management strategies.

Hepatolenticular degeneration, also known as Wilson disease (WD), is a type of copper metabolism disorder caused by an ATP7B gene variant, which is manifested by the abnormal accumulation of copper in the liver and other organs, resulting in multisystem damage. This article summarizes the latest research progress, with an emphasis on clinical characteristics, analysis of the optimization of diagnostic technology, and the clinical application of novel copper chelator therapy, as well as the development status and future prospects of gene therapy for WD. Future research should focus on the in-depth analysis of the mechanism, the application of multidimensional precision diagnosis technology, the development of individualized treatment plans, and the development of multicenter clinical trials in order to improve the comprehensive treatment effects and quality of life for patients with WD.

Wilson disease (WD), also known as hepatolenticular degeneration, is an autosomal recessive inherited disorder of copper metabolism that primarily affects the liver, brain, and other organs. The diagnostic criteria include clinical features, biochemical tests (plasma ceruloplasmin, 24-hour urinary copper, liver copper content), and molecular genetic analysis. The Leipzig scoring system, supplemented by the use of exchangeable copper, is recommended for diagnosis. Pharmacotherapy mainly includes chelating agents (such as penicillamine and trientine) and zinc salts. Chelating agent therapy is recommended only for patients with severe liver disease. Patient monitoring is primarily based on clinical symptoms, liver biochemical indices, and copper metabolism parameters (such as 24-hour urinary copper and exchangeable copper) to identify poor adherence as well as over-treatment or under-treatment situations. The diagnosis and treatment of acute liver failure with WD is extremely challenging, as the diagnosis is difficult and medical treatment cannot save life. The role of liver transplantation has been clearly recognized in the treatment of acute liver failure with WD, and it may also be considered in cases with neurological involvement.

Copper, as a kind of trace element, is crucial for the physiological functions of various key enzymes in the body, and the liver plays a central role in maintaining copper metabolism. Theoretically, dysfunction in the body’s metabolic processes, such as copper absorption, transportation, and excretion, can lead to copper deposition or deficiency in various organs. Wilson’s disease’s characteristic pathological manifestation is deposition of copper in liver. However, during liver pathological examinations, it has been found in clinical practice that certain patients with non-Wilson's disease and inherited metabolic liver disease may also have copper deposition. This review summarizes the inherited metabolic liver diseases that can cause liver copper deposition, their related pathogenesis, and the differential diagnosis approach from the perspectives of clinical and pathological characteristics.

Objective:To analyze the liver histological characteristics and clinically related factors in inactive hepatitis B surface antigen (HBsAg) carriers (IHC), and also explore whether antiviral treatment is necessary for IHC, as defined in the 2022 version of the hepatitis B prevention and treatment guidelines.Methods:A multicenter, retrospective cohort study was conducted. Two hundred and thirty-one IHC cases who underwent liver biopsy histopathological examination in nine medical institutions, including Beijing Youan Hospital affiliated with Capital Medical University, from January 2018 to December 2023 were included. General informative data, clinical serological markers, and transient elastography (TE) examination results were collected. Patients were divided into a positive (148 cases) and a negative group (83 cases) according to the results of hepatitis B virus (HBV) DNA detection. The differences in liver pathological inflammatory activity (G) and liver fibrosis stage (S) were analyzed between the two groups to explore the correlation between liver tissue conditions and clinically related factors. Comparsions of normally distributed continwous data, skeukd continuous data, and categorical data between groups are performed using t tests, Mann-Whitney U tests and χ2 tests, respectively. Results:The age of 231 IHC cases was 43 (38, 51) years old, with 95.2% (220/231) aged ≥30 years, and males accounted for 64.9% (150/231). HBsAg and HBV DNA levels were 131.9 (20.8, 400.9) IU/mL and 94.0 (0, 448.5) IU/mL, respectively, of which 35.9% (83/231) were HBV DNA negative (<20 IU/mL). The remarkable proportions of G≥2, S≥2, and liver injury (G≥2 and/or S≥2) in liver tissue were 16.5% (38/231), 29% (67/231), and 35.9% (83/231), respectively. The S≥2 proportion was significantly higher in the HBV DNA-negative group than the positive group (42.2% vs. 21.6%, P<0.001), and it mainly occurred in the population cohort over 30 years old (44.9% vs. 31.0%, P=0.04). The liver stiffness measurement (LSM), aspartate transaminase to platelet ratio index (APRI), and platelet (PLT) were significantly higher in the S≥2 group than the S<2 group ( P<0.05). Conclusion:Clinicians can comprehensively evaluate the degree of liver fibrosis in IHC based on clinical factors such as age, PLT, APRI, and LSM, even if the liver histological results are lacking. The China 2022 version guidelines define that nearly half of IHC has histological indications for antiviral therapy, and liver biopsy and prompt treatment can be recommended.

Objective: To investigate the application of antigen avoidance pattern for compatible platelets matching. Methods: Samples from two patients with immune-mediated platelet transfusion refractoriness were screened for platelet antibodies using solid-phase red blood cell adhesion assay (SPRCA). The genotypes of HLA-A, -B loci were determined via ploymerase chain reaction sequence. The specificity of HLA class I antibodies was detected using Luminex technology. Results: Platelet antibody screening via SPRCA yielded positive results in both samples. Antibody specificity testing showed the presence of antibodies against HLA-B65, A80, B13, as well as antibodies against HLA-A11, B52, A24 respectively, with both patients exhibiting 80 kinds of positive antibodies. The antibody avoidance pattern successfully selected compatible platelets for transfusion. The bleeding symptoms of two patients were improved after compatible platelets transfusion. Conclusion: For blood stations with limited platelet gene bank resources, antibody avoidance pattern for compatible platelets matching represents an effective strategy for immune-mediated platelet transfusion refractoriness.