Acute-on-chronic liver failure （ACLF） is an acute decompensation syndrome that develops on the background of chronic liver disease and is characterized by high mortality，rapid disease progression，complex clinical phenotypes，and a narrow window for reversibility. At present，there is still a lack of a unified standardized diagnostic system for ACLF globally，and there are significant differences between different diagnostic criteria in terms of liver failure，extrahepatic organ failure，and high-risk states within specific etiological contexts. To achieve individualized risk stratification of ACLF patients and optimize the allocation of clinical resources，it is urgently needed to establish a scientifically sound and precise classification system. Traditional static diagnostic models are confined only to baseline assessment and mortality prediction and fail to reflect dynamic disease evolution or effectively distinguish treatment response across different groups of patients. This article systematically reviews the major definitions and classification systems of ACLF at the current stage，analyzes the application value and limitations of various classification frameworks in clinical treatment decision-making，prognostic risk assessment，and clinical trial design，and proposes that the clinical classification system for ACLF should move beyond the single baseline evaluation approach toward a dynamic，treatment-oriented，and cross-etiology integrated assessment model，in order to provide a more precise theoretical basis for clinical diagnosis and treatment regarding artificial liver support，intensive care management，liver regeneration therapies，and determination of indications for liver transplantation.

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.

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.

Acute-on-chronic liver failure （ACLF） is a clinical syndrome characterized by rapid disease progression and extremely high short-term mortality，and the number and severity of complications are core factors contributing to poor prognosis. However，there is still a lack of systematic evaluations of the impact of single or multiple complications of ACLF on prognosis，as well as the clinical value of standardized complication management. This article systematically reviews the impact of common complications of ACLF on prognosis and related management strategies，in order to provide a reference for clinical practice.

Acute-on-chronic liver failure （ACLF） is a severe clinical syndrome characterized by acute decompensation of liver function，extrahepatic organ injury，and a high short-term mortality rate，with a complex pathogenesis that has not yet been fully clarified. Animal models of ACLF play a crucial role in disease research，since they not only provide a solid foundation for mechanistic studies，but also offer experimental evidence for clinical practice，thereby helping to promote advances in diagnosis and treatment. This article systematically reviews the commonly used animal models of ACLF，compares the establishment methods，pathophysiological characteristics，advantages，and limitations of different models，and discusses the latest research advances in animal models and innovative therapeutic strategies in the field，in order to provide a reference for further optimization，standardization，and application of animal models for ACLF.

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.

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.

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.

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.

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.