Since 2020, the international community has successively proposed new nomenclatures for metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD). In 2024, the Chinese Society of Hepatology updated and published the Guideline for the prevention and treatment of metabolic dysfunction-associated (non-alcoholic) fatty liver disease (version 2024). This review deeply analyzes the differences between MASLD and MAFLD in terms of concept, definition framework, and clinical management. On this basis, it provides an in-depth interpretation of the updated highlights and features of the working definition in the 2024 updated Chinese guideline.

Inflammatory liver injury is the initiating factor for various chronic liver diseases.It can involve the whole body,and on the contrary,systemic diseases may also lead to liver injury.The diagnosis and treatment of liver disease should not only consider the liver disease itself,but also understand the interaction between various systemic diseases and inflammatory liver injury and related pathophysiological mechanisms.Therefore,the diagnosis and treatment of liver injury often require multidisciplinary discussions and joint decision-making.One of the important links in the treatment of liver disease is to protect and maintain the stability of liver function,and how to carry out anti-inflammatory and liver-protecting treatment should be considered during the development of treatment strategies.Bicyclol is a chemical agent independently developed by China and is used for the treatment of inflammatory liver injury.Bicyclol has a good clinical effect in the prevention and treatment of inflammatory liver injury due to various causes and has been registered and listed in nine countries along the Belt and Road.Therefore,we have organized domestic experts from relevant disciplines all over the country to summarize the advances in the multidisciplinary clinical application of bicyclol in the prevention and treatment of inflammatory liver injury based on related guidelines/consensus statements/clinical pathways and evidence-based medicine and with reference to the clinical practice in China,in order to improve the scientific and standard use of bicyclol in clinical practice and the prevention and treatment of inflammatory liver injury in each discipline.

Objective:To investigate the clinical and genetic characteristics and predictive role of the severe liver disease phenotype in patients with hepatolenticular degeneration (HLD).Methods:Inpatients with HLD confirmed at Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine from January 1989 to December 2022 were selected as the research subjects. Clinical classification was performed according to the affected organs. Patients with liver disease phenotypes were classified into the liver disease group and further divided into the severe liver disease group and the ordinary liver disease group. The clinical characteristics and genetic variations were compared in each group of patients. The predictive indicators of patients with severe liver disease were analyzed by multiple regression. Statistical analysis was performed using the t-test, Mann-Whitney U test, or χ2 test according to different data. Results:Of the 159 HLD cases, 142 were in the liver disease group (34 in the severe liver disease group and 108 in the ordinary liver disease group), and 17 were in the encephalopathy group. The median age of onset was statistically significantly different between the liver disease group and the encephalopathy group [12.6 (7.0, 13.3) years versus 16.9 (11.0, 21.5) years, P<0.01]. 156 ATP7B gene mutation sites were found in 83 cases with genetic testing results, of which 54 cases carried the p.Arg778Leu gene mutation (allele frequency 46.2%). Compared with patients with other types of gene mutations ( n=65), patients with homozygous p.Arg778Leu mutations ( n=18) had lower blood ceruloplasmin and albumin levels, a higher prognostic index, Child-Pugh score, an international normalized ratio, and prothrombin time ( P<0.05). Hemolytic anemia, corneal K-F ring, homozygous p.Arg778Leu mutation, and multiple laboratory indexes in the severe liver disease group were statistically significantly different from those in the ordinary liver disease group ( P<0.05). Multivariate logistic regression analysis showed that the predictive factors for severe liver disease were homozygous p.Arg778Leu mutation, total bilirubin, and bile acids ( ORs=16.512, 1.022, 1.021, 95% CI: 1.204-226.425, 1.005-1.039, and 1.006-1.037, respectively, P<0.05). The drawn ROC curve demonstrated a cutoff value of 0.215 3, an AUC of 0.953 2, and sensitivity and specificity of 90.91% and 92.42%, respectively. Conclusion:Liver disease phenotypes are common in HLD patients and have an early onset. Total bilirubin, bile acids, and the homozygous p.Arg778Leu mutation of ATP7B is related to the severity of liver disease in HLD patients, which aids in predicting the occurrence and risk of severe liver disease.

With the prevalence of obesity and metabolic syndrome,non-alcoholic fatty liver disease(NAFLD)has replaced chronic hepatitis B as the leading chronic liver disease in China.In recent years,continuous exploration of the epidemiology and natural history of this disease,proposals for renaming,rapid advancements in diagnostic techniques,and continuous updates in treatment methods have propelled significant progress in the related diagnostic and therapeutic fields.Recently,experts in the Chinese Society of Hepatology revised the"Guidelines for the Prevention and Treatment of Non-Al-coholic Fatty Liver Disease(2018 Updated Version)"and published the"Guidelines for the Prevention and Treatment of Metabolic Dysfunction-associated(Non-alcoholic)Fatty Liver Disease(Version 2024)".The updated guideline provides guiding recommendations on important clinical issues such as renaming and sorting,screening and monitoring,diagnosis and assessment,treatment,and follow-up for this disease.This article aims to interpret the key updates in this guideline to help clinical practitioners gain a more comprehensive understanding and apply them to guide clinical practice.

Metabolic dysfunction-associated steatotic liver disease (MASLD), also called non-alcoholic fatty liver disease, is the most epidemic chronic liver disease worldwide. Metabolic dysfunction-associated steatohepatitis (MASH) is the critical stage of MASLD, and early diagnosis and treatment of MASH are crucial for reducing the incidence of intrahepatic and extrahepatic complications. So far, pharmacotherapeutics for the treatment of MASH are still a major challenge, because of the complexity of the pathogenesis and heterogeneity of MASH. Many agents under investigation have shown impressive therapeutic effects by targeting different key pathways, including the attenuation of steatohepatitis or fibrosis or both. It is notable that thyroid hormone receptor-β agonist, resmetirom has become the first officially approved drug for treating MASH with fibrosis. Other agents such as peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 analogs, and fibroblast growth factor 21 analogs are awaiting approval. This review focuses on the current status of drug therapy for MASH and summarizes the latest results of new medications that have completed phase 2 or 3 clinical trials, and presents the future directions and difficulties of new drug research for MASH.

BACKGROUND: Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH. METHODS: Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) ≥5 with a score of ≥1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS ≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL). RESULTS: A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference [SMD]: 0.87 [0.69-1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension ( P  < 0.001, P  = 0.026 and P  = 0.049, respectively). CK-18 M30 levels were positively associated with histological NAS in most centers. The area under the receiver operating characteristics (AUROC) for NASH was 0.750 (95% confidence intervals: 0.714-0.787), and CK-18 M30 at Youden's index maximum was 275.7 U/L. Both sensitivity (55% [52%-59%]) and positive predictive value (59%) were not ideal. CONCLUSION This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.
Humans ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Keratin-18 ; Biomarkers ; Biopsy ; Hepatocytes/pathology* ; Apoptosis ; Liver/pathology*

Hepatolenticular degeneration is an autosomal recessive genetic disease caused by mutations in the ATP7B gene. More than 800 mutations have been identified in the ATP7B gene so far, with significant differences in clinical phenotypes among different mutation sites. Totally different clinical phenotypic mutations can even exist in the same gene. Although copper accumulation due to gene mutation is the basis of the pathogenesis of hepatolenticular degeneration, more and more evidence demonstrates that it is difficult to explain the diversity of clinical manifestations solely from the perspective of gene mutation. Therefore, this article reviews the research progress on the factors influencing genotype, modifier genes, epigenetics, age, gender, diet, and other factors on the phenotype of patients with hepatolenticular degeneration.

Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic stress liver injury due to chronic malnutrition in genetically susceptible individuals. With the prevalence of obesity, diabetes, and metabolic syndrome, NAFLD has become the world's number one chronic liver disease, and the flaws of forty years of exclusive disease diagnostic criteria and stigmatized disease terminology are becoming increasingly prominent. To this end, in the past three years, the international consensus group and the three major hepatology societies have suggested that NAFLD be renamed metabolism-associated fatty liver disease (MAFLD) and metabolism-associated steatosis liver disease (MASLD). Here is a description of the background of naming NAFLD, MAFLD, and MASLD, the similarities and differences of the three terms, the existing disputes, and our country’s coping strategies.

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in the world and seriously threatens human health. So far, change in unhealthy lifestyle is still the most important treatment method for NAFLD. However, traditional lifestyle intervention depends on hospital visits and follow-up, and patients tend to have poor execution and compliance. With the help of the Internet technology, digital therapeutics overcome these disadvantages and has achieved a certain clinical effect in NAFLD patients. This article reviews the application of digital therapeutics in medicine and NAFLD treatment, so as to provide a reference for the treatment of NAFLD.