1.Analysis of the association between chronic liver disease and depressive disorder and the mediating effect of nocturnal sleep duration
Panshili HAN ; Yue FENG ; Yanhang GAO
Journal of Clinical Hepatology 2026;42(4):890-899
ObjectiveTo investigate the association between chronic liver disease (CLD) and depression and the mediating role of nocturnal sleep duration, as well as the consistency of this association between Chinese and American populations. MethodsThe data from two databases were integrated, i.e., China Health and Retirement Longitudinal Study (CHARLS) (n=14 225) in China and National Health and Nutrition Examination Survey (NHANES) (n=11 353) in the United States, and the subjects were divided into CLD group and non-CLD group. A stepwise Logistic regression model was used to assess the independent association between CLD and depression. Bootstrap resampling (1 000 times) was used to quantify the proportion of the mediating effect of nocturnal sleep duration, and interaction effects were evaluated through stratified analyses based on the factors including registered residence/race and income. The independent-samples t test was used for comparison of continuous data between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data; a multivariate Logistic regression model analysis was used to investigate the association of different types of CLD with depression. ResultsAfter multivariate adjustment, CLD was significantly associated with the increased risk of depression (CHARLS: odds ratio [OR]=1.76, 95% confidence interval [CI]: 1.46 — 2.12, P<0.001; NHANES: OR=1.87, 95%CI: 1.50 — 2.35, P<0.001). Nocturnal sleep duration played a partial mediating role in the association between CLD and depression, with a mediating effect accounted for 12.41% in CHARLS and 2.16% in NHANES (P<0.05). The interaction analysis showed that in CHARLS, the association between CLD and depression was more significant in the residents with agricultural registered permanent residence (OR=2.07, 95%CI: 1.67 — 2.57, P<0.001), and in NHANES, this association was more significant in the population with moderate poverty income ratio (OR=2.66, 95% CI: 1.92 — 3.69, P<0.001). The subtype analysis showed that autoimmune hepatitis (OR=3.63, 95%CI: 1.49 — 8.88, P=0.005), liver cirrhosis (OR=2.46, 95%CI: 1.32 — 4.60, P=0.005), and fatty liver disease (OR=1.75, 95%CI: 1.27 — 2.39, P=0.001) significantly increased the risk of depression, while no statistical significance was observed for viral hepatitis or other liver diseases (P>0.05). ConclusionThis study reveals the significant association between CLD and depression at the population level and suggests that nocturnal sleep duration may play a partial mediating role, which is consistent between the Chinese and American populations. These research findings provide quantitative evidence-based support for understanding the underlying mechanism of CLD-related depression and points out the potential significance of sleep issues in CLD management.
2.Multidimensional diagnostic biomarkers for functional cure of chronic hepatitis B
Heming SUN ; Fei KONG ; Xingyu WANG ; Junqi NIU ; Yanhang GAO
Journal of Clinical Hepatology 2026;42(7):1532-1540
Chronic hepatitis B (CHB) is a significant public health issue worldwide. The persistent presence of covalently closed circular DNA of the hepatitis B virus (HBV) and the integration of the viral genome are the main obstacles limiting the achievement of virological cure in CHB. Functional cure has now become an important goal in antiviral therapy for CHB, and its accurate determination and efficacy prediction rely on a comprehensive assessment of multidimensional diagnostic markers. This article systematically reviews the research advances in diagnostic markers associated with functional cure in CHB, focusing on the clinical value of serological and virological indicators (HBsAg quantification and HBV DNA), genomic, transcriptomic, proteomic, and metabolomic markers, and indicators associated with host innate immunity and adaptive immunity. Furthermore, it discusses future research directions such as the establishment of unified detection standards and the construction of predictive models combining multiple markers, in order to promote the precise assessment and individualized management of functional cure in CHB.
3.Alcohol-related liver disease-associated acute-on-chronic liver failure: Mechanisms, dynamic assessment, and precise management
Na AI ; Huaining CUI ; Xiaohui FANG ; Tao LIU ; Yanhang GAO
Journal of Clinical Hepatology 2026;42(8):1755-1760
Acute-on-chronic liver failure (ACLF) is a high-mortality syndrome that develops during the acute deterioration of chronic liver disease and is characterized by multiple organ dysfunction driven by systemic inflammation. Due to gut microbiota dysbiosis, endotoxin translocation, and amplified inflammatory responses, alcohol-related liver disease-associated ACLF (ALD-ACLF) is more pronounced and is often accompanied by a high risk of secondary infection and extrahepatic organ involvement, thereby exhibiting distinct etiological and clinical characteristics. This article systematically reviews the advances in the definitional boundaries, pathophysiological mechanisms, dynamic early warning, and prognostic assessment of ALD-ACLF, elaborates on risk stratification and key issues in clinical management, and discusses the potential impact of the dual-hit phenotype of metabolic dysfunction and alcohol-related liver disease on risk stratification in ALD-ACLF. This article also highlights the need to further strengthen etiology-oriented early identification, dynamic stratification, control of predisposing factors, and earlier intervention, in order to provide a reference for the precise assessment and individualized intervention of these patients.
4.Targeting functional cure of hepatitis B and establishing a China-specific evaluation benchmark for novel hepatitis B drugs: Interpretation of Q&A Document for the technical guidance for clinical trials of therapeutic drugs for chronic hepatitis B virus infection
Xie’er LIANG ; Yanhang GAO ; Junqi NIU ; Jinlin HOU
Journal of Clinical Hepatology 2026;42(8):1778-1781
Achieving the functional cure (clinical cure) of hepatitis B is the primary goal of current clinical hepatology and novel drug research and development. In 2023, the Center for Drug Evaluation, National Medical Products Administration, issued Technical guidance for clinical trials of therapeutic drugs for chronic hepatitis B virus infection to establish a top-level regulatory framework. Supporting Q&A documents for public consultation were released in July 2026 to provide practical policy guidance for the research and development of novel hepatitis B drugs, which has far-reaching implications for clinical investigators, innovative pharmaceutical enterprises, and the development of hepatology.
5.Noninvasive diagnosis of anti-mitochondrial antibody-negative primary biliary cholangitis
Jia ZHOU ; Jingyuan ZHOU ; Yanhang GAO
Journal of Clinical Hepatology 2025;41(9):1896-1901
Primary biliary cholangitis (PBC) is an autoimmune disease characterized by cholestasis of the intrahepatic bile ducts. Anti-mitochondrial antibody (AMA) is currently the key serum marker for the diagnosis of PBC, and however, there are still 5%—10% of patients with PBC who have undetectable AMA in their serum and need liver biopsy to make a confirmed diagnosis. Noninvasive diagnosis remains a challenge in AMA-negative PBC patients. This article reviews the research advances in specific serum markers other than AMA, summarizes the advantages and disadvantages of these serum markers in the diagnosis of AMA-negative PBC, and analyzes the types of new biomarkers that may be used in the noninvasive diagnosis of patients with AMA-negative PBC, in order to provide new ideas for identifying serum markers with higher sensitivities.
6.The development and application of genetically engineered human serum albumin
Journal of Clinical Hepatology 2025;41(3):415-419
Human serum albumin (HSA) is the most abundant protein in plasma and has many biological functions and clinical applications. An adequate and stable supply of functional HSA molecules that are easy to store and have a long half-life is still an unmet clinical need. Therefore, it is extremely necessary to develop alternative methods for large-scale production of HSA. Genetic engineering techniques can clone the HSA gene into microorganism, animal, and plant hosts for efficient expression, which provides new possibilities for the large-scale production of HSA. This article reviews the advances in recombinant HSA (rHSA) in different expression systems and the production of rHSA by xenogeneic animals such as pigs and cattle, in order to draw attention to the application potential of genetic engineering techniques in HSA production and the importance of rHSA in the biomedical field in future.
7.Metabolic and alcohol-associated liver disease: A novel liver disease entity
Yue FENG ; Hongqin XU ; Panshili HAN ; Tao LIU ; Yanhang GAO
Journal of Clinical Hepatology 2025;41(11):2235-2239
The term “metabolic and alcohol-related liver disease (MetALD)” recently proposed emphasizes the synergistic role of metabolic dysfunction and alcohol exposure in the progression of liver injury. Although this theoretical framework improves the understanding of the multifactorial and complex nature of liver disease, its clinical application still faces numerous new challenges in diagnosis and treatment. This article summarizes the latest evidence for the prevalence, potential pathogenesis, clinical diagnostic markers, and treatment of MetALD and particularly emphasizes the urgency to develop reliable preclinical models that can accurately simulate the intricate pathophysiology of this disease due to various factors. This article also provides a systematic evaluation of emerging therapies including fecal microbiota transplantation and nutritional interventions and proposes the future directions for drug innovation in MetALD.
8.Effectiveness of increasing alcohol excise taxes in the management of alcohol-associated liver disease in China
Feiyu ZHANG ; Peng XIAO ; Yali LIU ; Tao LIU ; Yanhang GAO
Journal of Clinical Hepatology 2023;39(7):1703-1707
Increasing alcohol excise taxes has been confirmed by the World Health Organization as the most cost-effective public policy for reducing alcohol consumption at the population level. In recent years, studies in foreign countries have believed that increasing alcohol excise taxes can improve the burden of alcohol-associated liver disease (ALD), but it is still unclear whether this policy is applicable to ALD management in China. Therefore, with reference to related research evidence in China and globally, this article analyzes the key factors influencing the effectiveness of the policy of increasing alcohol excise taxes from the perspective of ALD management in China, including tax shifting, price elasticity of demand, and unrecorded alcohol, and introduces other public policies that help curb ALD. We think that increasing alcohol excise taxes is currently a useful but not effective policy for improving the burden of ALD in China.
9.Copper homeostasis dysregulation promoting cell damage and the association with liver diseases.
Tao LIU ; Yali LIU ; Feiyu ZHANG ; Yanhang GAO
Chinese Medical Journal 2023;136(14):1653-1662
Copper plays an important role in many metabolic activities in the human body. Copper level in the human body is in a state of dynamic equilibrium. Recent research on copper metabolism has revealed that copper dyshomeostasis can cause cell damage and induce or aggravate some diseases by affecting oxidative stress, proteasome, cuprotosis, and angiogenesis. The liver plays a central role in copper metabolism in the human body. Research conducted in recent years has unraveled the relationship between copper homeostasis and liver diseases. In this paper, we review the available evidence of the mechanism by which copper dyshomeostasis promotes cell damage and the development of liver diseases, and identify the future research priorities.
Humans
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Copper/metabolism*
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Homeostasis
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Oxidative Stress
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Liver Diseases

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