Alcohol-related diseases represent a major global public health concern, among which alcoholic liver disease and alcohol use disorder are the two most representative categories of alcohol-related health problems. The Asia-Pacific region is characterized by a large population, marked socioeconomic disparities, and diverse drinking cultures. In recent years, the burden of alcohol-related diseases in this region has exhibited significant regional heterogeneity. This article reviews the epidemiological trends, disease burden characteristics, contributing factors, and prevention and control strategies for alcohol-related liver disease in the Asia-Pacific region, with the aim of providing a reference for regionalized and stratified intervention approaches.
Objective:To compare the efficacy and safety profiles of heparin and heparin-free pre-flushing methods in patients with liver failure treated with a double plasma molecular adsorption system (DPMAS).Method:A prospective, single-center observational study was conducted. Patients with liver failure who received DPMAS treatment at the Liver Disease Center of Nanfang Hospital, Southern Medical University, between October 2024 and February 2025 were consecutively screened for inclusion. The choice of whether to use the heparin pre-flushing method was determined in accordance with the clinicians' clinical experience. Demographic characteristics, treatment-related variables (heparin pre-flush method, adverse events, and pressure parameters), and clinical indicators (liver biochemical parameters, coagulation parameters, and inflammatory markers) were collected before and 48 hours after treatment. Categorical variables were compared using the χ2 test. Inter-group comparisons of continuous variables were performed using t-tests or non-parametric tests. Result:Data from 128 patients with liver failure treated with DPMAS were included. The mean age was 44.5 years, with 115 males (89.8%) and 13 females (10.2%). The internal jugular vein was the primary vascular access in both groups. Baseline data showed that coagulation parameters were worse in the heparin-free group than in the heparin group ( P<0.05). After DPMAS treatment, changes were observed in both pre-flushing groups, including total bilirubin (heparin group pre-and post-treatment mean: 381.62 μmol/L vs. 337.36 μmol/L, P<0.001; heparin-free group pre-and post-treatment mean: 404 μmol/L vs. 379 μmol/L, P=0.022), albumin (heparin group pre-and post-treatment mean: 33.48 g/L vs. 33.49 g/L, P=0.056; heparin-free group pre- and post-treatment mean: 31.41 g/L vs. 32.42 g/L, P=0.052), prothrombin activity (heparin group pre-and post-treatment median: 41.5% vs. 42.0%, P=0.103; heparin-free group pre-and post-treatment median: 33.90% vs. 32.35%, P=0.022), C-reactive protein (heparin group pre-and post-treatment median: 13.17 mg/L vs. 13.32 mg/L, P=0.004; heparin-free group pre-and post-treatment median: 16.29 mg/L vs. 19.30 mg/L, P=0.415), and procalcitonin (heparin group pre-and post-treatment median: 0.783 ng/mL vs. 0.796 ng/mL, P=0.598; heparin-free group pre-and post-treatment median: 0.82 ng/mL vs. 1.15 ng/mL, P=0.172). Regarding treatment efficacy, there were no statistically significant differences in the magnitude of changes in total bilirubin and albumin before and after treatment between the two pre-flushing methods ( P=0.144, P=0.843). In terms of safety profile, there were no statistically significant differences in the magnitude of changes in prothrombin time, international normalized ratio, and prothrombin activity before and after treatment with the two pre-flushing methods ( P=0.395, P=0.474, P=0.965). Regarding adverse events, there were no statistically significant differences in abnormal treatment parameters, bleeding, circuit clotting, and hypotension during treatment between the two groups ( P>0.05). Conclusion:The heparin-free pre-flushing method can be safely and effectively applied during DPMAS treatment in patients with liver failure with relatively poor coagulation function and an increased risk of bleeding. The heparin-free pre-flush method may be more preferable from patient and nursing perspectives.
Objective:To investigate whether fibroblast growth factor 21 (FGF21) can improve alcoholic liver disease (ALD) by regulating gut microbiota.Methods:Male C57BL/6J wild-type (WTPF) and Fgf21 -/- (KO) mice were used and divided into control groups (fed with a control liquid diet), ALD model groups (fed with an ethanol-containing liquid diet for 8 weeks), and rhFGF21 treatment groups (administered intraperitoneal injections of rhFGF21 4 mg·kg -1·day -1 for 5 days before the end of ALD modeling), totaling six groups. Gut microbiota was analyzed using 16S rRNA sequencing to detect liver histopathology and serum lipopolysaccharide (LPS) levels. Statistical analysis was performed using one-way ANOVA or the Kruskal-Wallis test. Results:The KOPF group showed more severe liver damage and higher triglyceride accumulation compared to the WTPF group under ethanol exposure. Exogenous rhFGF21 administration significantly reduced intracellular liver triglyceride content and degree of liver injury in WTPF and KOPF groups ( P<0.05). Gut microbiota analysis showed that FGF21 significantly altered gut microbiota β-diversity in mice (adjusted P<0.05). The WTAF and KOAF groups had a lower abundance of Firmicutes compared to the control group, while the abundance of Proteobacteria, Bacteroidetes, and serum LPS levels was increased. The abundance of Proteobacteria, Bacteroidetes, and serum LPS levels decreased again, while the firmicutes abundance was restored following rhFGF21 administration ( P<0.05). Conclusion:FGF21 deficiency worsens gut microbiota dysbiosis in ALD mice, while exogenous rhFGF21 supplementation regulates gut microbiota, lowers serum LPS, and improves ALD.
目的:探讨2018-2022年中国丙型病毒性肝炎的流行特征及空间聚集性特征，为科学制定区域性疾病防控策略与干预措施提供理论依据。方法:依托国家人口健康科学数据共享平台-公共卫生科学数据中心及《中国卫生健康统计年鉴》，收集2018-2022年我国31个省、自治区、直辖市（不含港澳台地区）丙型病毒性肝炎发病相关数据；运用GeoDa9.5软件绘制丙型病毒性肝炎发病三维空间趋势图，分析其地区分布变化趋势，并采用空间自相关分析方法，系统探究近年来我国丙型病毒性肝炎的空间聚集特征。对发病率采用 χ2检验。 结果:2018-2022全国31个省份（自治区、直辖市）累计报告丙型肝炎病例1 021 233例，年平均发病率为14.44/10万。报告发病率从2018年的15.79/10万下降到2022年的12.20/10万（ χ2=14.90，df=1，Z＝3.86， P＜0.05）。2018-2022年，我国丙型病毒性肝炎发病呈现出稳定且显著的地区聚集性特征（Moran's I＞0， P＜0.05），地区分布总体表现为“东西向强梯度、南北向弱波动”，西北、华中及华南等地区是我国丙型肝炎发病的高-高聚集区域。 结论:目前我国丙型病毒性肝炎仍维持较高的发病水平，且发病存在稳定显著的空间聚集性特征。针对丙型肝炎发病呈高-高聚集的区域，应适度加大卫生资源配置力度，强化健康宣教工作，科学制定区域化丙型肝炎防控策略，有效遏制丙型肝炎发病热点区域的扩散蔓延。
Portal hypertension (PH) is generally considered a complication of advanced liver fibrosis and cirrhosis in chronic liver disease and is closely associated with poor prognosis. Metabolic-associated fatty liver disease (MAFLD) may develop PH even during the non-cirrhotic stages, suggesting that mechanisms beyond cirrhosis exist that contribute to PH. However, prior research has primarily focused on the characteristics and pathophysiological mechanisms of PH in cirrhosis, while systematic discussions on the occurrence of PH in the non-cirrhotic stage of MAFLD are still not expounded. This article takes the metabolic characteristics as an entry point to systematically analyze the roles and mechanisms of the metabolic microenvironment in the development of PH, providing a basis for effectively preventing the progression of PH in MAFLD.
Objective:To investigate and evaluate the incidence rate, time distribution, related factors, and prediction model discriminative ability for recompensation in patients with hepatitis B-related decompensated cirrhosis.Methods:Four hundred and five patients hospitalized for the first time due to hepatitis B-related decompensated cirrhosis were retrospectively enrolled, using the date of initial hospitalization for decompensation as the follow-up initial point. Recompensation was defined as the resolution condition of decompensation complications, lasting for at least 12 months without specific maintenance therapy, with reference to the Baveno Ⅶ consensus in combination with real-world clinical practice. A statistical analysis was performed on the recompensation occurrence time in patients who achieved recompensation. Patients followed up for≥12 months ( n=382) were included, with 12 months as the cutoff. Univariate and multivariate logistic regression analyses were used to analyze related factors, with recompensation (primary event time of occurrence >12 months) as the endpoint. A recompensation prediction model was constructed based on key variables. The discriminative ability was evaluated using the area under the receiver operating characteristic curve (AUC), and tertile risk stratification was performed. The baseline and recompensated indicators were compared pairwise for patients with recompensation. Results:Recompensation occurred in 94 out of 405 cases, with an overall incidence of 23.2%. The recompensation incidence was 22.7% (92/405) when "time to recompensation >12 months" was used as the primary event criterion. The median time to recompensation was 22.9 (16.0, 35.4) months, mainly concentrated between 12 and <24 months. Multivariate logistic regression showed that persistent virological suppression was independently associated with recompensation ( OR=2.387, 95% CI 1.395-4.082, P=0.001). The independent adverse factors for recompensation were initial decompensated complications ≥2( OR=0.525, 95% CI 0.288-0.957, P=0.036) and portal vein thrombosis ( OR=0.296, 95% CI 0.108-0.806, P=0.017). There was no statistically significant difference in the composition of the initial decompensation complication types, but the complication burden was closely related to recompensation, with a significantly lower recompensation rate in patients with ≥2 complications [18.2% (25/137) vs. 28.2% (69/245), P=0.031]. The model for end-stage liver disease (MELD), complication burden, portal vein thrombosis, sustained virological suppression, and non-selective β receptor blockers had better discrimination in Model B than Model A (AUC 0.670 vs. 0.532). The actual recompensation rates following tripartite risk stratification were 15.4% (18/117), 19.7% (23/117), and 35.9% (42/117), respectively. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and MELD and Maddrey discriminant function (MDF) scores were decreased, while albumin levels were increased, and the infection rate decreased from 25.5% (24/94) to 12.8% (12/94) ( P<0.05) at the time of recompensation assessment. Conclusion:Recompensation is not uncommon in patients with hepatitis B-related decompensated cirrhosis, and it often occurs more than 12 months after the initial decompensation. Sustained virologic suppression is an independent favorable factor for recompensation, while a severe complication burden and portal vein thrombosis suggest a lower likelihood of recompensation. The predictive models have a certain discriminative ability and can be used for risk stratification and as a reference for follow-up and comprehensive management based on key clinical variables.
目的:探索丙氨酸转氨酶（ALT）正常的不确定期慢性乙型肝炎病毒（HBV）感染者的抗病毒方案。方法:选取2024-01-01至2025-08-01来院治疗的ALT正常不确定期慢性HBV感染者，根据患者意愿分为含聚乙二醇干扰素α-2b（PEG-IFN α-2b）治疗的试验组和单纯口服核苷（酸）类似物（NAs）的对照组；试验组可单用PEG-IFNα-2b或联合NAs，两组各入组50例，治疗48周。统计两组患者乙型肝炎表面抗原（HBsAg）转阴率、HBsAg水平下降幅度、乙型肝炎e抗原（HBeAg）转阴率、完全病毒学应答（CVR）率，并进一步对比分析不同NAs对HBsAg下降的影响。计量资料组间数据比较采用 t检验、方差分析或秩和检验；计数资料组间数据比较采用 χ2检验或Fisher's精确概率法。 结果:基线HBsAg水平，试验组为126.70（7.33，978.58）IU/mL，对照组为205.47（48.50，1 647.34）IU/mL；基线HBV DNA水平，试验组为914.0（200.2，999.0）IU/mL，对照组为1 032.5（365.7，2 474.5）IU/mL，两组间基线水平差异无统计学意义。试验组患者治疗48周的HBsAg转阴率是54.0%（27/50），HBsAg水平降幅是105.81（7.25，804.14）IU/mL，CVR率是94.0%（47/50），HBeAg转阴率是66.7%（2/3）。单纯使用PEG-IFNα-2b的HBsAg转阴率是50.0%（5/10）。与试验组对比，单纯NAs（对照组）治疗48周后HBsAg转阴率为0（ P<0.001）；HBsAg水平降幅是9.56（0，155.63）IU/ml（ Z=-3.151， P=0.002）；CVR率是94.0%（47/50； χ2=0， P=1）；HBeAg转阴率是50.0%（1/2； P=1）。PEG-IFNα-2b联合NAs中富马酸丙酚替诺福韦治疗后HBsAg转阴率较高；单纯不同NAs治疗中，艾米替诺福韦的HBsAg水平降幅较大。 结论:ALT正常的HBeAg阴性不确定期慢性HBV感染者抗病毒采用含PEG-IFNα-2b治疗方案时，HBsAg转阴率较高，联合NAs治疗时选择富马酸丙酚替诺福韦或艾米替诺福韦可能有更大的获益。
Objective:To investigate the association between steatotic liver disease (SLD) and its clinical subtypes with metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), hypertension (HTN), chronic kidney disease (CKD), cardiovascular disease (CVD), and extrahepatic malignancies, as well as the impact of cardiovascular health scores on these aforementioned comorbidities.Methods:A cross-sectional analysis was conducted within a subcohort of the Malignancy Occurrence Risk Epidemiology Study, based on baseline data from the Shanghai Chongming Town Community Residents Cohort (March-November, 2011) among Chinese patients with type 2 diabetes mellitus. Sonographically diagnosed SLD was classified into metabolic-associated fatty liver disease (MASLD), metabolic and alcohol-associated fatty liver disease (MetALD), alcoholic liver disease (ALD), and SLD of other causes according to metabolic cardiovascular risk factors and alcohol consumption. Cardiovascular health status was assessed using the LE8 (Life's Essential 8) score. Intergroup differences were compared using appropriate parametric or nonparametric tests. The association between the prevalence of extrahepatic comorbidities and LE8 scores was analyzed using a multivariate logistic regression models.Results:The prevalence rates of SLD and its subtypes, MASLD, MetALD, and ALD were 42.15% (4 122/9 779), 39.00% (3 814/9 779), 1.48% (145/9 779), and 1.57% (154/9 779), respectively, among 9 779 subjects aged 40 -70 years. The prevalence rates of T2DM, HTN, CKD, and CVD were significantly higher in the high-risk liver fibrosis index-4 group (FIB-4>2.67) than in the non-high-risk group ( P<0.05). The prevalence rates of T2DM, HTN, CKD, and CVD metabolic disorders were significantly higher in patients with SLD than patients with non-SLD ( P<0.05). MetALD and ALD patients had higher prevalence rates of HTN than patients with MASLD ( P<0.05). All ALD patients had combined metabolic cardiovascular risk factors, with the prevalence rates of MetS, T2DM, HTN, and CVD showing an increasing trend from MASLD to MetALD to ALD. However, no significant differences were observed in the history of extrahepatic malignancies between SLD and non-SLD groups or among subgroups. Multivariate logistic regression analysis revealed that the LE8 score was significantly negatively correlated with T2DM and HTN prevalence rates in the overall population, validating a preventive impact in groups of patients with SLD and non-SLD as well as MASLD ( P<0.05). Conclusion:Cardiovascular-renal-metabolic diseases impose a substantial burden on patients with SLD, while metabolic disorders are more pronounced among patients with ALD. The development of extrahepatic comorbidities is jointly driven by overnutrition and harmful alcohol consumption in patients with MetALD and ALD. LE8 is beneficial for multidimensional risk assessment and interventions targeting for T2DM and HTN in patients with SLD.
Alcohol liver disease (ALD) represents a major health challenge worldwide, with particularly high mortality in severe alcohol-associated hepatitis. Inflammation plays a central role in ALD progression, and immune cells along with their inflammatory mediators contribute to disease development through actions in both the liver and extrahepatic organs. Currently, there is a lack of targeted therapies that can effectively block chronic ALD progression or intervene in alcohol-related acute liver failure. This article elucidates the core mechanisms by which immune heterogeneity drives the development and progression of ALD and influences treatment responses, summarizes current clinical research progress in anti-inflammatory therapies, and highlights promising future directions, particularly biomarker-guided precision therapy.
Objective:To explore the likelihood of metabolic-associated fatty liver disease (MAFLD)based on metabolic characteristics and to provide a reference for identifying potential causative factors in patients with cryptogenic cirrhosis.Methods:A total of 2,190 patients with cirrhosis admitted to the Department of Hepatology, Beijing Friendship Hospital, Capital Medical University, from January 2022 to December 2024 were retrospectively analyzed. 163 patients with cryptogenic cirrhosis following screening by exclusion criteria were finally included. According to the Liver Forum consensus, patients were classified into three groups based on metabolic characteristics: "very likely" MAFLD-related cirrhosis, "possibly" MAFLD-related cirrhosis, and "other" cryptogenic cirrhosis. 151 patients with MAFLD-related cirrhosis served as the control group and were admitted during the same period. Clinical data and prognostic scores were collected and compared among the groups. Logistic regression analysis was used to assess the impact of MAFLD as a potential etiology for prognostic score categories. Normally distributed continuous variables were compared using one-way ANOVA, while non-normally distributed continuous variables were compared using non-parametric tests for overall intergroup analysis. Categorical variables were analyzed using chi-square tests or Fisher's exact tests. Post-hoc pairwise comparisons were conducted when the overall differences were statistically significant. Multiple comparisons were performed for type 1 error control. The Bonferroni correction method was applied to control for type I error in multiple comparisons and p-values.Results:Among 163 patients with cryptogenic cirrhosis, 57(35.0%) were "very likely" MAFLD-related cirrhosis, and 31(19.0%) were "possibly" MAFLD-related cirrhosis, both groups totaling 88(54.0%). Compared with the definitive diagnosis group, the "very likely" and "possibly" groups showed no statistically significant differences in the prevalence rate of overweight/obesity (86.4% vs. 90.7%), type 2 diabetes mellitus (53.4% vs. 59.6%), and hyperlipidemia (10.2% vs. 20.5%) (adjusted P>0.05), with only a lower prevalence of hypertension (40.9% vs. 56.3%, adjusted P=0.044). However, the former group exhibited significantly lower lipid levels at presentation (adjusted P<0.05), with no significant difference in fasting blood glucose levels (adjusted P=1.000). Additionally, a higher proportion of patients were in decompensated stages (81.8% vs. 60.9%, adjusted P=0.002), with worse liver function and higher risks of adverse prognosis. Conclusion:Metabolic factors were associated with more than half of the cases of cryptogenic cirrhosis at our hospital. However, lipid and blood glucose abnormalities at the time of consultation were often unremarkable, as these patients had already progressed to the decompensated stage. Therefore, the assessment of current and past metabolic factors should be prioritized for patients with cryptogenic cirrhosis in clinical practice.
Metabolic and alcohol-related liver disease (MetALD) is a key subtype within the new classification system of fatty liver disease, and its diagnosis relies on three core elements: hepatic steatosis, metabolic dysfunction, and alcohol consumption. However, the applicability of current diagnostic criteria is limited in patients with cirrhosis and liver transplant recipients due to structural destruction of the liver, remodeling of metabolic status, and difficulties in accurately assessing alcohol intake. This article systematically reviews the current application of MetALD diagnostic criteria in the above special populations, focusing on the key limitations in clinical evaluation, and explores precision diagnostic strategies including combined biomarker detection and optimization of imaging techniques, aiming to provide a basis for stratified management and prognostic assessment in these patients.
The Asia-Pacific region has the heavy burden of chronic hepatitis B. In 2026, the Asia-Pacific Association for the Study of the Liver (APASL) updated its clinical practice guidelines for the management of chronic hepatitis B. The recommendations in this version of the guideline are formulated around focusing 13 core areas: vaccination and universal screening strategies, an established system of progressive treatment goals, pathways for stratified assessment of liver fibrosis based on resource availability, expansion of antiviral therapy indications, and advocacy of proactive treatment strategies. Incorporating metabolic risk factors into long-term care and managing co-existing metabolic dysfunction-associated fatty liver disease at the same time emphasizes shared decision-making between patients and clinicians and the use of new technologies in risk assessment, which optimizes the link between diagnosis and treatment and improves long-term clinical outcomes for patients.
Long-term and excessive alcohol consumption is metabolized in the liver while simultaneously causing liver injury, ultimately leading to alcoholic liver disease (ALD). With the increasing consumption of alcoholic beverages among the general population, ALD has become one of the major liver diseases in China. The progression of ALD encompasses stages including hepatic steatosis, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. In the absence of effective pharmacotherapies for ALD, current management strategies should prioritize early diagnosis and timely reinforcement of alcohol abstinence to prevent disease progression to cirrhosis and hepatocellular carcinoma. Overlooked drinking history frequently results in missed diagnosis of ALD; therefore, greater attention should be paid to the systematic collection of long-term drinking history in clinical practice. ALD is closely associated with lifestyle factors, and its prevention and control require not only professional medical guidance and governmental public health support, but also rely on public dissemination of medical knowledge and gradual shifts in drinking culture. Furthermore, existing research achievements in ALD should be accelerated in their translation into clinical diagnostic and therapeutic strategies as well as related health industry applications, so as to promote disease prevention, early recognition, and standardized management.
The global incidence of alcohol-associated liver disease(ALD) is rising. Beyond glucocorticoids, effective pharmacological therapies for severe ALD remain limited. With the introduction of the novel concept of "metabolic and alcohol-associated liver disease (MetALD) ", it has emerged as a distinct clinical condition characterized by synergistic liver injury resulting from the interplay between metabolic dysfunction and alcohol consumption. In contrast to the substantial progress in drug development for metabolic associated steatotic liver disease (MASLD), clinical research on ALD and MetALD has advanced slowly. Worldwide, only a limited number of clinical trials for ALD have been registered, and ongoing studies frequently encounter challenges such as patient recruitment difficulties and high attrition rates. Given its recent classification, MetALD currently lacks specific clinical trial guidance from regulatory agencies. These hurdles are compounded by additional challenges, including etiological heterogeneity, stigma related to alcohol use, and suboptimal treatment adherence, which collectively impede therapeutic development. Stratification of study populations according to cardiometabolic risk profiles and stages of liver fibrosis represents a critical strategy to optimize trial design and identify patient subgroups most likely to benefit. This article delineates key challenges in clinical trial design for novel ALD and MetALD therapeutics, summarizes the current research landscape and its core limitations, and proposes future directions focused on the selection of hard clinical endpoints, dual-pathway benefit assessment, and investigator-initiated trials.
Currently, there are clinically limited therapeutic options for metabolic-associated fatty liver disease (MAFLD), and the treatment effect is not optimistic. Mesenchymal stem cell (MSC) therapy for MAFLD shows good application prospects but also possesses certain potential treatment risks. Mesenchymal stem cells can secrete various functional exosomes, which not only retain the therapeutic efficacy of mesenchymal stem cells but also significantly mitigate their associated treatment risks. Mesenchymal stem cell-derived exosomes can play a hepatoprotective, antioxidant, or drug-sensitizing role in liver diseases, with advantages of low immunogenicity and high biocompatibility. Therefore, mesenchymal stem cell-derived exosomes are expected to offer novel therapeutic strategies for the treatment of metabolic-associated fatty liver disease.
Objective: To investigate the correlation between serum serine levels and the degree of severity of primary biliary cholangitis (PBC) so as to elucidate the protective effect and molecular mechanism of serine supplementation in cholestatic liver disease. Methods: Serum serine levels were measured in 62 cases with PBC patients diagnosed at Tianjin Medical University General Hospital from January 2021 to June 2023, and their correlation with serological indicators and liver pathological scores was analyzed. A C57BL/6J mouse model of cholestatic liver injury was established by inducing a 0.1% dimethylnitrosamine (DDC) diet. Serum biochemical indicators, hepatic inflammatory factor mRNA expression, liver histopathological changes, macrophage M1 polarization marker (CD86), and protein expression in the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway were intervened through dietary serine supplementation. In vitro experiments were conducted by stimulating RAW264.7 macrophages with lipopolysaccharide (LPS) to observe the effects of serine on inflammatory factors, M1 polarization, and the AKT/mTOR pathway. Intergroup comparisons for measurement data were performed using independent sample t-tests or Wilcoxon rank-sum tests. Correlations between serum serine levels and the above serological indicators and liver pathological scores were analyzed using Pearson or Spearman methods. Results: Serum serine levels were significantly negatively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (γ-glutamyltransferase), total bilirubin, immunoglobulin G, and liver pathological scores in patients with PBC (P<0.05). Dietary serine supplementation significantly improved cholestasis in DDC mice, inhibited the expression of hepatic tumor necrosis factor-α, interleukin-1β, and interleukin-6 mRNA (P<0.05), reduced portal inflammatory infiltration, and decreased CD86⁺M1 macrophage infiltration and p-AKT/p-mTOR co-localization (P<0.05). In vitro experiments showed that serine intervention inhibited lipopolysaccharide-induced macrophage M1 polarization and inflammatory cytokine expression and downregulated p-AKT/p-mTOR protein expression (P<0.05). Conclusion: Reduced serum serine levels are associated with the degree of severity of PBC. Dietary serine supplementation can inhibit the hepatic macrophage AKT/mTOR signaling pathway and block M1 polarization and inflammatory responses, thereby improving cholestatic liver injury.
The research system and clinical decision-making pathways have been systematically reshaped as the application of artificial intelligence (AI) in the field of ultrasonically has become increasingly mature recently for liver disease imaging. Research focus has shifted at the clinical level from low-dimensional classification and diagnostic tasks to high-dimensional, task-driven intelligent diagnosis and treatment. The underlying algorithms are undergoing a profound transition at the technological level from single-modality to multi-modal collaboration and from isolated feature extraction to spatiotemporal sequential reasoning. Therefore, to provide a forward-looking analysis and reflection on future development trends and existing challenges, this article systematically reviews the latest research progress of AI in the field of liver disease in terms of four aspects of ultrasonography: early-stage screening, precise diagnosis, personalized treatment, and prognostic monitoring.
Primary liver cancer (represented by hepatocellular carcinoma and intrahepatic cholangiocarcinoma) is a common clinical malignant liver tumor with a high mortality burden. The disease has high heterogeneity, and diagnosis stratification and efficacy evaluation heavily rely on imaging. Among imaging modalities, ultrasound, with its advantages of real-time imaging, gradually improving resolution, and dynamic assessment of multi-parameter information such as blood flow perfusion, is continuously expanding its application scenarios in the liver cancer diagnosis and treatment chain along with the rapid development of a series of new technologies. In recent years, technologies such as microvascular blood flow ultrasound, super-resolution ultrasound, three-dimensional multi-parameter contrast-enhanced ultrasound, viscoelasticity, and dispersive imaging have developed rapidly, enabling more refined acquisition of blood flow, perfusion, and mechanical information related to liver cancer. Simultaneously, workflow technologies such as integrated navigation and artificial intelligence-assisted procedures have promoted more precise and visual positioning, quantification, and evaluation during interventional procedures and provided a foundation for the further introduction of closed-loop simulation and decision support frameworks represented by digital twins. This article focuses on the two key aspects of liver cancer diagnosis and treatment, systematically reviews the above-mentioned ultrasound technologies' new clinical value and applicable scenarios and limitations, and looks forward to directions such as standardization, multi-center validation, and workflow integration, with the aim of providing a reference for clinical practice and research design.
Objective:Hepatocellular carcinoma has a poor prognosis, and microvascular invasion (MVI) is an important indicator for guiding surgical decisions and influencing long-term survival. This study aims to explore the application value of habitat imaging combined with peritumoral radiomics in the preoperative assessment of MVI based on contrast-enhanced ultrasound (CEUS) images in hepatocellular carcinoma.Methods:The contrast-enhanced ultrasound images and clinical data of 186 patients with pathologically confirmed hepatocellular carcinoma at the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed and randomly divided into a training group ( n=130) and a test group ( n=56) in a 7∶3 ratio. Eleven clinical indicators, such as patient age and alpha-fetoprotein (AFP) were extracted. Microvascular invasion (MVI)-independent risk factors were screened to construct clinical prediction models for tumors. Peritumoral and intratumoral regions of interest (ROIs) were depicted at 5 mm and 10 mm on arterial and delayed CEUS phase images. Traditional radiomic features were extracted. Corresponding prediction models were constructed. The above-mentioned depicted intratumoral regions of interest were concurrently applied using K-means clustering to divide the tumor habitat subregions, habitat features, and establish an intratumoral habitat model. Furthermore, a combined model was constructed by integrating a habitat with 5 mm peritumoral features. The predictive efficacy of each model was comprehensively evaluated using indicators such as the area under the receiver operating characteristic (AUC), calibration curve, and decision curve. Results:The clinical model had poorly performed predictions for MVI (training set AUC=0.762; validation set AUC=0.668). The 5 mm peritumoral radiomics model showed better generalization ability and stability than the 10 mm peritumoral and intratumoral models (training set AUC=0.785 vs. 0.786, 0.802; validation set AUC=0.727 vs. 0.672, 0.708). The intratumoral habitat model (training set AUC=0.824; validation set AUC=0.753) was more effective in predicting MVI than both the clinical and the traditional radiomics models in hepatocellular carcinoma. Furthermore, the predictive efficacy of MVI with the selection of a constructed intratumoral habitat combined with 5 mm peritumoral was improved (training set AUC=0.888; test set AUC=0.843), with accuracy, sensitivity, specificity, and clinical net benefit all significantly higher than those of other models. The classification ability had a positive improvement effect. Conclusion:Intratumoral habitat analysis can effectively assess the MVI status based on contrast-enhanced ultrasound in patients with hepatocellular carcinoma. In addition, the combined 5-mm peritumoral radiomics model can more accurately assess the MVI status in patients with hepatocellular carcinoma.
Chronic liver disease and its complications impose a heavy burden，and the limits of liver biopsy tests have rendered non-invasive assessment an urgent clinical need. Multiple novel parameters，such as elasticity，viscosity，fat quantification，and micro-flow imaging，have been established as reliable methods for staging liver fibrosis，monitoring inflammatory activity，and quantifying steatosis，providing considerable potential for diagnosis，disease monitoring，and prognostic management of chronic liver diseases via ultrasonically technology at an early stage. Challenges such as the non-universal nature of diagnostic thresholds，interference from confounding factors，and a lack of technical standardization remain，despite the considerable value of each technology. Therefore，the integration of multiple parameters and artificial intelligence models may be a breakthrough direction in the future.
