中华肝脏病杂志最新文献

Functional cure (i.e., clinical cure) of chronic hepatitis B (CHB) is a core research objective in the field of hepatology. With the revision of the Expert opinions on the technical guiding Principles for clinical trials of drugs in the treatment of chronic hepatitis B virus infection, this article concisely reviews the evolving concept of functional cure for hepatitis B, research progress on the dynamic trajectories and threshold of key serological markers (such as HBsAg/anti-HBs), strategies for safety evaluation of treatment discontinuation, and the importance of building a collaborative innovation ecosystem involving scientific research, industry, healthcare, policy, and societal forces. Through multidimensional technological breakthroughs and interdisciplinary collaboration, the functional cure rate of chronic hepatitis B infection is expected to improve significantly over the next 5-10 years, laying the foundation for achieving the World Health Organization (WHO)'s goal of eliminating viral hepatitis as a public health threat by 2030.

Objective: To analyze the causal relationship between circulating inflammatory proteins and the risk of liver cirrhosis by the two-sample Mendelian randomization (MR) method. Methods: Single nucleotide polymorphisms (SNP) strongly associated with 91 plasma inflammatory proteins in genome-wide association studies (GWAS) were used as instrumental variables, and liver cirrhosis was used as the outcome variable. Random-effects inverse variance-weighted (IVW), MR Egger regression, odds ratio (OR) and its 95% confidence interval were used to evaluate the causal relationship. Simultaneously, sensitivity analysis was performed using MR pleiotropy residuals and outliers (MR-PRESSO) and the Q-test. Results: The causal relationship between the expression of seven specific circulating inflammatory proteins and liver cirrhosis was confirmed by the inverse variance-weighted (IVW) method. The results showed that five plasma inflammatory proteins, including leukemia inhibitory factor [OR(CI)=0.66,P=9.73×10^-5], interleukin-18 [OR(CI)=0.76,P=0.013], tumor necrosis factor ligand superfamily member 12[OR(CI)=0.75,P=0.024], monocyte chemoattractant protein 2 [OR(CI)=0.89,P=0.036], and C-C motif chemokine 25 [OR(CI)=0.84,P=0.039], were negatively correlated with cirrhosis and were protective factors for cirrhosis. T cell surface glycoprotein CD5 [OR (CI)=1.29,P=0.035] and C-X-C motif chemokine 10 [OR(CI)=1.32,P=0.043] were positively correlated with cirrhosis and were risk factors for cirrhosis. The results of the MR-PRESSO, Q-test, MR-Egger intercept test, and leave-one-out method all showed the stability. Conclusion: The research results indicated that the increased levels of leukemia inhibitory factor, interleukin-18, tumor necrosis factor ligand superfamily member 12, monocyte chemoattractant protein-2, and C-C motif chemokine 25 were protective factors in the development of cirrhosis, while the increased levels of T cell surface glycoprotein CD5 and C-X-C motif chemokine 10 were risk factors for the development of cirrhosis based on genetic data.

Chronic hepatitis B virus (HBV) infection remains one of the major public health challenges facing our country. There are approximately seventy-five million chronic HBV-infected cases in our country, according to the latest epidemiological data. Current first-line antiviral drugs, including nucleos(t)ide analogs and interferons, can effectively suppress viral replication and delay disease progression, but they still struggle to provide a functional cure for chronic hepatitis B or completely eliminate HBV infection. This unmet clinical need has become the core driving force behind the development of new antiviral drugs for chronic HBV infection. In recent years, China's drug regulatory policy reform has continued to deepen, and the indications for antiviral treatment of HBV infection have been continuously broadened, creating a more favorable policy environment for innovative drug research and development. In this context, global drug development for HBV, especially in China, is accelerating, and new drugs with various mechanisms of action are entering the clinical research phase. In order to standardize and guide the rational design, efficient implementation, and accurate evaluation of clinical trials of new antiviral drugs for the treatment of chronic HBV infection, the expert group combined the latest research progress and clinical practice experience at home and abroad to systematically update key issues such as the research endpoints of clinical trials of new antiviral drugs, aiming to provide authoritative and practical technical guidance for new drug research and development.

The grade of histological severity is a determining factor to evaluate the prognosis and survival rate in primary biliary cholangitis (PBC). However, liver biopsy is limited by sampling error, invasiveness, high cost, and poor compliance. Therefore, in order to overcome the limitations of liver biopsy, some non-invasive evaluation methods have been studied and applied to evaluate the progression of liver fibrosis in PBC. The prognostic score can be calculated using routine laboratory test results obtained at the time of diagnosis, which are characterized by their simplicity, affordability, ease of acquisition, and superior reproducibility. Recent studies have reported that the prognostic score can be employed as a non-invasive liver fibrosis model to diagnose the liver fibrosis stage in PBC and predict the transplant-free survival rate, in addition to being used to evaluate the patient prognosis and transplant-free survival (TFS). This paper reviews, summarizes, and explores the research progress of different prognostic scores as non-invasive liver fibrosis models via their diagnostic performance and predictive accuracy for PBC.

Hepatitis B surface antigen (HBsAg) seroclearance, or s-loss, has traditionally been regarded as a key indicator of hepatitis B virus (HBV) functional cure. However, growing insights into HBV pathogenesis and treatment strategies have reshaped our understanding of the relationship between s-loss and functional cure. While an HBsAg level below 100 IU/mL is often used to define partial cure, it primarily reflects a therapeutic milestone that facilitates eventual s-loss rather than a definitive endpoint. New biomarkers such as serum HBV RNA and hepatitis B core-related antigen are promising but, due to limitations in sensitivity, are not yet adequate substitutes for s-loss in defining functional cure. Importantly, achieving s-loss alone does not guarantee functional cure. Other factors-such as HBeAg seroclearance, the durability of s-loss, and whether single timepoint of rebound ("Blips") are permissible-must be considered in evaluating functional cure. These evolving perspectives underscore the importance of consolidation therapy. Further researches are needed to elucidate the mechanisms between different therapies induced s-loss, the implications of lower detection limits for HBsAg, and the role of hepatitis B surface antibodies in seeking functional cure.

Objective: To investigate the correlation between serum NOD-like receptor protein 3 (NLRP3) levels and serum lipids in metabolic-associated fatty liver disease (MAFLD) before and after a single high-fat meal. Methods: A retrospective cohort study was conducted. Sixty-three MAFLD patients (MAFLD group) and fifty-four healthy subjects (CON group) recruited from February 2019 to December 2019 at Hebei Provincial People's Hospital were included. The baseline data were compared between the two groups, and a single high-fat meal trial was conducted. The levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and NLRP3 were measured at 2 h, 4 h, and 6 h after fasting and a high-fat meal. Multiple linear regression analysis was used to evaluate the influencing factors of area under the operating curve (AUC_NLRP3) of serum NLRP3 subjects. Logistic regression analysis was used to evaluate the correlation between serum AUC_NLRP3 and the risk of MAFLD. Results: The levels of TC, TG, LDL-C, and NLRP3 were significantly higher in the fasting group than the CON group at 2 h, 4 h, and 6 h after a meal [TC (mmol/L), fasting: (5.29±1.01) vs. (4.28±0.62), 2 h: (5.24±0.98) vs. (4.25±0.62), 4 h: (5.38±1.04) vs. (4.26±0.63), 6 h: (5.54±1.07) vs. (4.41±0.65); TG (mmol/L), fasting: (2.67±0.96) vs. (0.92±0.33), 2 h: (3.91±1.35) vs. (1.69±0.59), 4 h: (5.09±1.7) vs. (1.91±0.93), 6 h: (5.36±2.27) vs. (1.75±1.03); LDL-C (mmol/L), fasting: (3.47±0.74) vs. (2.65±0.49), 2 h: (3.36±0.71) vs. (2.58±0.49), 4 h: (3.30±0.71) vs. (2.55±0.47), 6 h: (3.36±0.74) vs. (2.63±0.48); NLRP3 (ng/L), fasting: (84.63±12.96) vs. (56.71±11.37), 2 h: (106.06±17.76) vs. (69.12±14.92), 4 h: (89.78±15.98) vs. (57.74±12.34), 6 h: (80.03±13.61) vs. (54.06±10.35); P<0.001], while the HDL-C level was significantly lower than the CON group [HDL-C (mmol/L), fasting: (1.14±0.24) vs. (1.33±0.29), 2 h: (1.14±0.24) vs. (1.33±0.29), 4 h: (1.09±0.24) vs. (1.27±0.28), and 6 h: (1.05±0.26) vs. (1.29±0.30); P<0.001]. Serum AUC_NLRP3 was significantly correlated with AUC_TG and AUC_LDL-C (AUC_TG: B=7.391, 95%CI:5.662-9.12; AUC_LDL-C: B=6.559, 95%CI:3.052-10.065; P<0.001) after adjusting for confounding factors, and it was identified as an independent influencing factor for MAFLD (OR=1.039, 95%CI:1.007-1.071;P=0.015). Conclusion: The serum NLRP3 levels before and after a single high-fat meal are significantly associated with elevated TG and LDL-C levels, and may influence the progression of MAFLD.

Objective: To explore the predictive value of hepatitis B surface antibody (HBsAb) quantitative level for achieving hepatitis B surface antigen (HBsAg) seroclearance and serological conversion in patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogs (NAs) or interferon (IFN). Methods: A two-center prospective cohort study was conducted, including CHB patients from Nanfang Hospital Southern Medical University and Eastern Theater General Hospital treated with NAs and IFN. All patients were followed up once every three to six months. Basic clinical information and test results were collected at each follow-up. The presence or absence of HBsAg seroclearance and serological conversion rate was evaluated. HBsAg serological conversion was defined as HBsAg quantification continuously below the detection limit (<0.05 IU/mL) at two detection time points at least six months apart. HBsAg serological conversion was defined as HBsAb positivity (≥10 IU/L) at the same time as the first HBsAg seroclearance. The Kruskal-Wallis test was used to compare the quantitative data of multiple groups, and the Wilcoxon rank-sum test was used to compare the data between groups. The chi-square test was used for the count data, and the Fisher exact test was used when the chi-square test was not met. Univariate and multivariate Cox analysis was used to determine the predictors of the study endpoints, and stepwise regression was used for variable screening. Results: A total of 2 266 CHB cases were included, of which 86.5% (1 959/2 266) were NA antiviral-received population. The median treatment duration before baseline was 10.5 (2.5, 37.6) months, and the baseline HBsAg quantification was 3.1 (2.6, 3.5) log₁₀ IU/mL. A total of 68 cases (3.0%) had HBsAg seroclearance, and 44 cases (1.9%) achieved serological conversion after 85.0 (62.7, 97.3) months of prospective follow-up. The level and positivity rate of HBsAb showed a progressive increase 36 months before and significantly after HBsAg seroclearance. Cox regression analysis results showed that baseline HBsAb level was an independent predictor of HBsAg serological conversion (HR=2.26, P=0.002) in the overall population, especially in the subgroup with HBsAg between 100 and 1 000 IU/mL, suggesting HBsAb level had important predictive value. In addition, the serological conversion development rate was significantly higher in the GOLDEN model favourable patients than in the unfavourable patients (11.5% vs. 0, P<0.001). Conclusion: The baseline HBsAb quantitative level can predict HBsAg seroclearance and serological conversion for patients with CHB receiving antiviral treatment, which is of significant value in long-term treatment monitoring.

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.

Hepatitis B virus infection is a global public health issue, and there exist many controversies about the antiviral treatment strategies for patients with low-level hepatitis B surface antigen. This article reviews the definition, clinical significance, and current controversial focus of treatment strategies for low-level hepatitis B surface antigen, including treatment timing, drug selection, treatment course determination, and other aspects, while also suggesting future research directions.