Most ReadLiver fibrosis is a key pathological process in the transition from chronic liver disease to cirrhosis，especially in elderly patients with chronic hepatitis B，and this process is characterized by rapid progression and poor prognosis. T cell function gradually declines with aging，and T cell senescence is recognized as a key immunological mechanism accelerating the progression of liver fibrosis. Current studies have shown that senescent T cells promote the transition from liver fibrosis to liver cirrhosis by altering the liver inflammatory microenvironment，modulating the activity of fibrosis-related cells，and impairing immune surveillance function. This article systematically reviews the molecular mechanisms of T cell senescence and its role in the progression of liver fibrosis in elderly patients with chronic hepatitis B，as well as novel therapeutic approaches targeting immunosenescence with reference to the latest immunological findings and stem cell-based therapeutic strategies，so as to provide theoretical support for precise intervention for such patients.
Accurate traditional Chinese medicine （TCM） syndrome differentiation is an important prerequisite for TCM treatment； however，there is currently still a lack of unified standards and operable clinical tools for the diagnosis of TCM syndromes in primary liver cancer，posing great challenges to the promotion of clinical regimens and the rational use of Chinese patent drugs. In order to unify and standardize the diagnostic criteria for TCM syndromes in primary liver cancer，the consensus working group organized relevant experts in the fields of TCM，integrated traditional Chinese and Western medicine hepatology，and methodology to discuss and conduct expert consultation using the two-round Delphi method through a systematic review of the descriptions of TCM syndromes in existing guidelines，consensuses，and indications of Chinese patent medicines，with the mean，coefficient of variation，and full score rate as the criteria for item selection. This consensus establishes a syndrome diagnosis system covering 12 syndrome factors，11 composite syndromes，and their corresponding diagnostic items and constructs a quantitative model for syndrome diagnosis based on item weights，and develops an online quantitative tool that can support dynamic entry of syndrome and symptom scores and achieve the visualization of trends before and after treatment. In addition，this consensus systematically describes the construction method and content of the above diagnostic system and provides a quantitative and visualized tool for syndrome diagnosis and efficacy evaluation，in order to provide a methodological reference and an operable platform for the standardized promotion of TCM syndrome differentiation and to improve the consistency of clinical syndrome differentiation and the rationality of the use of Chinese patent drugs.
Metabolic dysfunction-associated fatty liver disease （MAFLD） is the most common chronic liver disease，and it has become a major global health issue. Excessive lipid accumulation in the liver is the core pathological event of MAFLD，which triggers lipotoxicity and leads to cell apoptosis，necrosis，and inflammatory cascades by mediating endoplasmic reticulum stress，oxidative stress，organelle dysfunction，and ferroptosis，thereby promoting the progression of simple hepatic steatosis to steatohepatitis and fibrosis. In this process，very-long-chain fatty acids （VLCFAs），as essential components of cell membranes and lipid metabolism，have attracted increasing attention for their role in lipotoxicity mechanisms. This article reviews the role of VLCFAs in lipid metabolism processes and lipotoxicity mechanisms，focusing on how VLCFAs participate in metabolic regulation through key proteins and disrupt cell membranes to induce oxidative stress，and how their metabolites and derivatives drive inflammatory responses，ultimately promoting the progression of MAFLD.
Chronic hepatitis B virus （HBV） infection is a major cause of hepatocellular carcinoma （HCC），with a population-attributable fraction of 57.1% for HCC globally and 76.1% for HCC in China. Identifying the early molecular mechanisms of HBV-driven hepatocarcinogenesis can facilitate precise HCC prevention. Persistent HBV replication，HBV mutation，HBV integration，and the synergistic interplay among them are the main mechanisms of HBV-driven hepatocarcinogenesis. HBV replication activates and sustains a chronic hepatic inflammatory microenvironment，providing conditions for accumulation of viral mutations； under the conditions of chronic inflammation，inflammatory factors cause the imbalance between apolipoprotein B messenger RNA editing enzyme catalytic polypeptide-like 3B and uracil-DNA glycosylase，which promotes HBV mutations and human genomic mutations and enhances the carcinogenic effect of HBV mutations，and the inflammatory microenvironment can promote dedifferentiation of mutated cells and acquisition of stemness； HBV genome integration can cause “gate-keeper” mutations including telomerase reverse transcriptase （TERT） promoter mutation，thereby triggering chromosomal instability and epigenetic reprogramming. The three events of HBV replication，mutation，and integration work synergistically under the evolutionary principle of “variation-selection-adaptation” and jointly drive the development and progression of HCC. The high-risk HBV mutation profile，circulating HBV integration fragments，and the TERT promoter mutations can be used to guide precision HCC prevention via antiviral prophylaxis and assist in early screening and monitoring of postoperative recurrence，which provides a scientific basis for refining stratified prevention and control strategies against HCC.
Infection is not only a common predisposing factor for acute-on-chronic liver failure （ACLF），but also a critical complication of ACLF，and it is closely associated with multiple organ failure and high mortality. This article systematically reviews the recent advances in the epidemiology，clinical and etiological features，pathogenesis，and diagnosis and treatment strategies of ACLF with infection，in order to provide guidance for further optimizing clinical decision-making and exploring novel diagnostic and treatment methods for such patients.
To assess the performance of preoperative serum Golgi protein 73 （GP73） in diagnosing liver fibrosis degree in patients with resectable hepatocellular carcinoma （HCC），to investigate its value in predicting postoperative survival，and to provide a basis for risk stratification and individualized decision-making in this population.
A total of 631 patients with HCC who underwent liver resection at The First Hospital of Jilin University from March 1，2009 to December 31，2022 were enrolled. The demographic，pathological，and serological features of the patients were collected，and the serum level of GP73 was measured before surgery. Scheuer score determined by liver biopsy was used as the gold standard for diagnosing liver fibrosis； the Spearman correlation analysis was used to investigate the correlation between GP73 and liver fibrosis； the receiver operating characteristic （ROC） curve and the area under the ROC curve （AUC） were used to assess the value of serum GP73 and compound serological markers in the diagnosis of liver fibrosis，and the Delong test was used for comparison of AUC. With all-cause mortality as the outcome，X-Tile 3.6.1 software was used to determine the optimal cut-off value of GP73； the univariate and multivariate Cox regression analyses were used to identify independent influencing factors for prognosis，and a nomogram model was constructed. Ten-fold cross-validation was used for internal validation； index of concordance （C-index），integrated discrimination improvement （IDI） index，and net reclassification improvement （NRI） index were calculated； calibration curve and decision curve analysis were used to assess the predictive performance of the model.
The serum level of GP73 was positively correlated with Scheuer liver fibrosis stage （rs=0.255，P<0.001）. Serum GP73 had a significantly higher AUC than gamma-glutamyl transferase-to-platelet ratio （0.704 vs 0.634，Z=2.00，P=0.046） and S index （0.704 vs 0.637，Z=1.98，P=0.048） in the diagnosis of significant liver fibrosis，with no significant difference compared with aspartate aminotransferase-to-platelet ratio index （AUC=0.722） and fibrosis-4 index （AUC=0.695） （both P>0.05）. During a median follow-up time of 48.66 months，239 patients （37.9%） died. GP73 had an optimal cut-off value of 65 ng/mL in predicting postoperative mortality in patients with resectable HCC，and high GP73 expression （≥65 ng/mL） alone achieved a C-index of 0.617 for predicting the prognosis of HCC patients，which was better than the C-index of 0.551 for Barcelona Clinic Liver Cancer （BCLC） stage （P<0.001）. The multivariate Cox regression analysis showed that serum GP73 （hazard ratio ［HR］=2.56，95% confidence interval ［CI］：1.86 — 3.52，P<0.001），sex （HR=1.58，95%CI：1.10 — 2.28，P=0.014），vascular invasion （HR=1.69，95%CI：1.30 — 2.21，P<0.001），total bilirubin （HR=1.49，95%CI：1.16 — 1.93，P=0.002），and maximum tumor diameter （HR=1.07，95%CI：1.04 — 1.11，P<0.001） were independent risk factors for all-cause mortality after hepatectomy in patients with HCC. In order to assess whether the addition of GP73 to the other four variables could further improve model performance，the model based on GP73，sex，vascular invasion，total bilirubin，and maximum tumor diameter was defined as the GP73-included model，and the model based on all five variables except GP73 was defined as the GP73-excluded model. The GP73-included model achieved an AUC of 0.704 （95%CI：0.656 — 0.753） for predicting 5-year survival rate after surgery，and ten-fold cross-validation showed that this model had a mean C-index of 0.716 （95%CI：0.682 — 0.750），which was higher than the C-index of the GP73-excluded model （C-index=0.682，95%CI：0.645 — 0.719，P=0.008） and BCLC stage （C-index=0.551，95%CI：0.523 — 0.580，P<0.001）. Compared with the GP73-excluded model，the GP73-included model yielded an IDI index of 0.039 （95%CI：0.016 — 0.069，P<0.001） and an NRI index of 0.259 （95%CI：0.179 — 0.335，P<0.001），and compared with BCLC stage，the GP73-included model had an IDI index of 0.112 （95%CI：0.069 — 0.163，P<0.001） and an NRI index of 0.272 （95%CI：0.169 — 0.380，P<0.001）. Calibration curve and decision curve analyses showed that the GP73-included model had good calibration and net clinical benefit.
GP73 can be used as a serological biomarker for diagnosing liver fibrosis in patients with resectable HCC，and preoperative GP73 level has a certain value in predicting the survival of these patients after hepatectomy. The integrated prognostic model incorporating GP73 can help to optimize postoperative risk stratification，thereby providing a basis for decision-making in precise treatment of HCC.
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.
China bears a substantial disease burden of chronic hepatitis B （CHB）. Under current clinical management regimens for CHB，achieving functional cure （also termed clinical cure） is the core goal for the treatment of patients meeting treatment indications. To achieve the goal of functional cure，drug regulatory authorities in China and globally have successively issued technical criteria to provide guidance for the overall design and scientific evaluation of clinical trials for innovative drugs. However，the rapid development in scientific research，clinical practice，and new drug research and development in this field has brought new challenges，especially those concerning the assessment of the clinical value of investigational drugs. This article reviews the current status of clinical research and development of new drugs for achieving the functional cure of CHB worldwide，analyzes the characteristics of available clinical trial data，and focuses on key aspects of pivotal clinical trials for CHB functional cure drugs，including target populations （baseline HBsAg level），HBsAg seroclearance response，HBsAg seroreversion after drug withdrawal，and clinically meaningful target threshold of functional cure response rate，in order to provide a reference for further refinement of related technical criteria.
Metabolic dysfunction-associated fatty liver disease （MAFLD） is a chronic liver condition closely associated with dysregulated lipid metabolism，with the central pathological event of mitochondrial dysfunction in hepatocytes. The mitochondrial calcium uniporter （MCU） complex is a key molecular apparatus regulating mitochondrial calcium （mtCa2+） homeostasis，and mtCa2+ overload due to its dysfunction plays a critical role in the progression of MAFLD. This article systematically elaborates on the pathogenesis of MAFLD，with a particular focus on how the central signaling axis of “MCU complex dysfunction-mtCa2+ overload” drives the disease progression of MAFLD by disrupting energy metabolism，activating the adenosine monophosphate-activated protein kinase signaling pathway，triggering the NOD-like receptor protein 3 inflammasome，and inducing cell death. It also points out that traditional Chinese medicine can exert an interventional effect on multiple downstream pathways through various targets and has shown unique advantages and a significant potential in alleviating MAFLD by maintaining mitochondrial homeostasis and targeting the MCU complex，and therefore，it is expected to provide new strategies for the prevention and treatment of MAFLD.
Acute-on-chronic liver failure （ACLF） is characterized by marked heterogeneity and potential reversibility and thus requires refined clinical classification to achieve precise diagnosis and treatment. Establishing a scientific，standardized，simple，and practical clinical classification system is of great importance for disease assessment，prognostic evaluation，therapeutic decision-making，and stratified management. Based on the actual needs of the clinical diagnosis and treatment of ACLF in China and with reference to related guidelines，evidence-based medical evidence，and expert opinion in China and globally，this consensus summarizes the methods for ACLF classification and their application in clinical practice，in order to improve clinical identification and stratified diagnosis and treatment，promote precise diagnosis and treatment，and ultimately improve the prognosis of patients.
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