In 2026， the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases jointly published a Delphi consensus statement on surrogate endpoints and real-world evidence in primary biliary cholangitis. This consensus proposes 16 statements and 42 recommendations centering on the following three most critical issues in the development of new drugs for primary biliary cholangitis： whether liver biochemical parameters and noninvasive assessments of liver fibrosis can be used as surrogate endpoints for clinical outcomes； how real-world data and real-world evidence can complement or support confirmatory studies in a manner compliant with regulatory requirements； how patient-reported outcomes can be standardized for the assessment of quality of life， pruritus， and fatigue. This article provides an excerpt and expert interpretation of the background， methodological framework， core statements， recommendations， and key figures and tables of this consensus， in order to provide a reference for the diagnosis and treatment of primary biliary cholangitis， drug evaluation， real-world study design， and the development of patient-centered clinical endpoints in China.

ObjectiveTo investigate the effect of SU056， an azo-podophyllotoxin derivative， on carbon tetrachloride （CCl₄）-induced liver fibrosis in mice and related mechanisms of action. MethodsA total of 12 mice were randomly divided into control group， model group （CCl₄+normal saline）， and treatment group （CCl₄+SU056）， with 4 mice in each group. Mice were given intraperitoneal injection of CCl₄ to establish a model of liver fibrosis， and during the middle stage of modeling， the mice in the treatment group were given daily intraperitoneal injection of SU056. Liver histopathological injury， collagen deposition， and liver function were assessed based on HE staining， Masson staining， Sirius Red staining， the content of hydroxyproline in liver tissue， and the serum levels of alanine aminotransferase and aspartate aminotransferase， and immunofluorescence assay was used to measure the expression levels of smooth muscle actin α （α-SMA）， collagen type Ⅰ， and Y-box binding protein 1 （YB1）. The human hepatic stellate cell （HSC） line LX-2 and primary mouse HSC were used， and CCK-8 assay was used to measure cell proliferation； Transwell assay was used to observe cell migration； quantitative reverse transcription-polymerase chain reaction and Western Blot were used to measure the expression levels of collagen type Ⅰ， collagen type Ⅲ， YB1， phosphorylated mammalian target of rapamycin （mTOR）， and phosphorylated S6K， so as to validate the function of the YB1/mTOR signaling axis. The one-way or two-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsIn the mouse model of liver fibrosis induced by CCl₄， compared with the model group， the treatment group had significant alleviation of inflammatory cell infiltration， collagen deposition， and pseudolobule formation in liver tissue and significant reductions in the serum levels of alanine aminotransferase and aspartate aminotransferase and the content of hydroxyproline in liver tissue （all P<0.01）. Immunofluorescence assay showed that SU056 significantly inhibited the abnormal high expression of α-SMA， collagen type I， and YB1 in liver tissue （all P<0.01）. In vitro experiments showed that SU056 inhibited the transforming growth factor-β1-induced proliferation of LX-2 cells （P<0.01）， the migration of LX-2 cells （P<0.05）， and the transcriptional up-regulation of collagen type Ⅰ and collagen type Ⅲ （all P<0.05） in a dose-dependent manner， and SU056 could inhibit the spontaneous activation of primary HSC in vitro. Mechanistic studies revealed that transforming growth factor-β1 simultaneously upregulated the expression levels of YB1， phosphorylated mTOR， and phosphorylated S6K in LX-2 cells， and treatment with SU056 （10 and 20 µmol/L） could downregulate the protein expression levels of collagen type I， YB1， phosphorylated mTOR， and phosphorylated S6K. Specific knockdown of YB1 or administration of the mTOR inhibitor rapamycin exerted a similar effect as SU056. SU056 also inhibited the co-upregulation of α-SMA and phosphorylated mTOR in liver tissue of model mice （P<0.01）. ConclusionSU056 can effectively inhibit HSC activation， proliferation， migration， and extracellular matrix production both in vivo and in vitro and thus delay the progression of liver fibrosis， by disrupting the YB1/mTOR positive feedback signaling axis.

Metabolic associated fatty liver disease （MAFLD） is a liver disease associated with metabolic disorders， and it is characterized by excessive fat deposition in hepatocytes and is closely associated with insulin resistance and genetic susceptibility. Aging is an important factor in the progression of MAFLD and is positively correlated with the mortality rate of patients with MAFLD. The pathophysiological mechanisms of MAFLD involve lipid metabolism disorders， insulin resistance， inflammation， and oxidative stress， and aging exacerbates the pathological process of MAFLD by further affecting these key mechanisms. Cell senescence is an important factor in organismal aging， and therapeutic strategies targeting senescent cells can reduce the number of senescent cells or inhibit the inflammatory factors secreted by such cells， thereby helping to slow down the progression of MAFLD. In addition， the screening of novel regulatory factors provides new targets for the development of new drugs for MAFLD treatment. Although several anti-aging therapies have entered clinical trials， further studies are needed to validate the specificity and potential liver damage of these therapies due to the complex mechanisms of aging on the liver. Transforming multisystem metabolic dysfunction therapies for MAFLD into specialized therapies for aging may provide new ideas for MAFLD drug development.

Drug-induced liver injury (DILI) is an important adverse drug reaction with diverse clinical manifestations. Drug-induced autoimmune-like hepatitis (DI-ALH) is a special type of DILI possessing clinical, serological, and histological features similar to autoimmune hepatitis (AIH). However, there are significant differences between DI-ALH and AIH in terms of treatment plan, course of disease, and prognosis; therefore, differential diagnosis between DI-ALH and AIH is crucial. This article summarizes the epidemiology, pathogenesis, clinical characteristics, diagnosis and differential diagnosis, treatment, and prognosis of DI-ALH and analyzes the existing problems in order to provide guidance for the diagnosis, treatment, and future research direction.

Cholestatic liver disease(CLD)is a group of hepatobiliary disorders caused by impaired bile production,secretion,or excretion.With the application of liquid biopsy,multi-parameter radiological examination,and genomics technology,significant progress has been made in the diagnosis and prognostic evaluation of CLD.At present,the therapeutic principles for CLD mainly focus on addressing the underlying causes and managing cholestasis,and commonly used drugs include ursodeoxycholic acid,S-adenosylmethionine,cholestyramine,fibrates,and obeticholic acid.Based on the latest clinical consensus statements and research advances in CLD,this article systematically elaborates on the clinical management strategies for CLD from the aspects of diagnosis,treatment,and prognostic evaluation.

Liver cirrhosis as the terminal stage of chronic liver disease has seen many new insights and advances in its treatment strategies and perspectives in recent years. However, there are still many controversies about cirrhotic portal hypertension management, prevention, therapy, and complications. This article summarizes the main key controversial points in the current treatment of liver cirrhosis from an evidence-based medicine perspective, including the use of non-selective β-blockers during decompensated stages, exploration of precise strategies for albumin, re-evaluation of the risks of statins, weighing the pros and cons of proton pump inhibitors, new understandings of anticoagulation therapy, breakthroughs in targeting gut microbiota, and nutritional support management. In addition, it combines the latest research data and guideline recommendations to explore future development directions so as to provide clinical practice reference.

Liver fibrosis is a common pathological process in various chronic liver diseases. Early-stage and accurate diagnosis, as well as assessment of the degree of liver fibrosis, is crucial for the management of chronic liver diseases. Conventional imaging techniques for liver fibrosis (elastography and magnetic resonance elastography) still have the drawback of low sensitivity in detecting early-stage fibrosis. In recent years, emerging imaging omics based on ultrasound and magnetic resonance have improved the diagnostic accuracy and visualization stage of liver fibrosis. The emergence of artificial intelligence technology has also provided more options for the technological advancement of liver fibrosis imaging. This article aims to review the emerging liver fibrosis imaging technologies in recent years and compare their diagnostic performance with ultrasound elastography, shear wave elastography, and magnetic resonance elastography recommended by the current domestic and international guidelines and to pinpoint simultaneously the limitations and challenges that still exist in liver fibrosis imaging while reflecting the technological advances.

Portal hypertensive biliopathy is a secondary condition of intrahepatic and extrahepatic bile duct abnormalities caused by portal hypertension, especially in extrahepatic portal venous obstruction. Most patients may remain asymptomatic for a long time, while a few may present with symptomatic portal hypertensive biliopathy, such as obstructive jaundice, cholelithiasis with or without cholangitis, gastrointestinal bleeding, and others. Such disease is rare in clinical practice and is prone to misdiagnosis and missed diagnosis. Improper treatment can lead to serious adverse consequences. We report a case of unexpected discovery of bile duct dilation due to abdominal pain, which was ultimately diagnosed as portal hypertensive biliopathy based on the medical history, manifestations of portal hypertension, and imaging examinations, especially intraductal ultrasonography.

Metabolic associated fatty liver disease (MAFLD) has replaced non-alcoholic fatty liver disease (NAFLD), emphasizing the core role of metabolic dysfunctions and necessitating a multidisciplinary (MDT) approach for diagnosis and treatment to concurrently manage liver disease and metabolic disorders.Downplaying the non-alcohol label while focusing more on metabolic driving factors allows it to coexist with other liver diseases. The gastroenterology and hepatology department is the initial assessment department, and MDT, which includes endocrinology, nutrition, sports medicine, surgery, and psychology, develops individualized treatment plans. With the aim of halting the progression of the disease (steatosis → fibrosis → cirrhosis) and eventually improving patient prognosis, MAFLD management must be based on metabolic intervention and accomplish "liver disease metabolic co-treatment" through multidisciplinary integration.

Cholestatic liver disease(CLD)is a group of hepatobiliary disorders caused by impaired bile production,secretion,or excretion.With the application of liquid biopsy,multi-parameter radiological examination,and genomics technology,significant progress has been made in the diagnosis and prognostic evaluation of CLD.At present,the therapeutic principles for CLD mainly focus on addressing the underlying causes and managing cholestasis,and commonly used drugs include ursodeoxycholic acid,S-adenosylmethionine,cholestyramine,fibrates,and obeticholic acid.Based on the latest clinical consensus statements and research advances in CLD,this article systematically elaborates on the clinical management strategies for CLD from the aspects of diagnosis,treatment,and prognostic evaluation.