Accurate, non-invasive liver fibrosis detection is essential for chronic liver disease management, particularly with rising metabolic dysfunction-associated liver disease (MASLD) and chronic hepatitis B (CHB). While the Fibrosis-4 (FIB-4) index is widely used, its performance for advanced fibrosis is limited. We develop Met-FIB using metabolomics and machine learning, integrating FIB-4 parameters (age, aspartate aminotransferase, alanine aminotransferase, and platelet count) with tyrosine and taurocholic acid identified in a CHB discovery cohort (n = 3,251). Validation includes one CHB cohort (n = 729) and two MASLD cohorts (n = 149, n = 155). Met-FIB outperforms FIB-4, FibroScan, and other serum markers across all fibrosis stages. In CHB, Met-FIB achieves 96.3% rule-out sensitivity and 85.4% rule-in specificity for significant fibrosis, with rule-in specificity reaching 98.6% and 98.8% for advanced fibrosis and cirrhosis. In MASLD, corresponding values are 93.9% and 90.2% for significant fibrosis, with >97.9% specificity for late-stage disease. Met-FIB demonstrates clinical utility for non-invasive fibrosis staging across diverse etiologies.

INTRODUCTION:Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disease, and liver biopsy remains the gold standard for diagnosis. However, a subset of patients diagnosed with MASLD by imaging paradoxically exhibit steatosis grade S0 on liver biopsy, posing a diagnostic challenge. This study investigated the outcomes and causes of steatosis 0. METHODS:Steatosis 0 was defined as imaging-detected MASLD with a biopsy-defined steatosis grade S0. We used global cohorts to evaluate outcomes, histologic progression by paired biopsies, and possible causes. The cause analysis included MRI-proton density fat fraction (MRI-PDFF) for fat distribution, pathologist consistency testing, and comparison of serial biopsy sections. RESULTS:In a follow-up cohort of 3,273 biopsy individuals from 16 centers, 123 (3.8%) exhibited steatosis 0. Of these, 29.3% of them had advanced fibrosis (burnt-out MASLD) and demonstrated a risk of liver-related events, whereas those without advanced fibrosis had no such events. In the paired-biopsy cohort of 1,865 patients, 74 (4.0%) individuals initially showed steatosis grade S0; among them, 93.2% retained no or mild steatosis on follow-up biopsy. MRI-PDFF assessments in 42 MASLD patients revealed heterogeneous hepatic fat distribution, with some segments showing steatosis grade S0 despite elevated average liver fat. Interpathologist variability and discrepancies across consecutive biopsy sections contributed to misclassification of steatosis grade. DISCUSSION:Steatosis 0 represents a potential diagnostic gray zone in MASLD. It may be caused by burnt-out MASLD, uneven liver fat distribution, or variability in pathological assessment. Understanding the causes and implications of steatosis 0 is critical for diagnosis and management.

The conventional biomarker discovery approach in metabolomics treats metabolites as isolated features, failing to capture their interdependencies. We applied a network-based method using Tabular Prior-Data Fitted Networks (TabPFN) integrated with SHapley Additive exPlanations (SHAP) to derive stage-specific metabolic networks capturing statistical metabolite co-contribution patterns and identify key metabolites. We analyzed 1312 participants across five stages (control, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC)), quantitatively profiling 160 metabolites, and externally validated the results in 721 samples. We compared three approaches: (1) TabPFN-SHAP, (2) conventional statistics with machine learning, and (3) TabPFN-SHAP integrated with literature-validated biomarkers. TabPFN-SHAP–based approaches outperformed the conventional pipeline, revealing distinct stage-specific metabolic signatures with overlapping metabolites between consecutive networks, marking consistently prioritized features. A five-metabolite HCC-screening panel (sebacic acid, alpha-linolenic acid, phenylalanyl-tryptophan, arachidonic acid, and glycocholic acid) was identified. At the screening-oriented cutoff, the panel achieved an AUROC of 0.979 (95% CI: 0.966–0.991) for Control vs HCC and 0.955 (95% CI: 0.936–0.977) for Fibrosis/Cirrhosis vs HCC, with sensitivity of 0.937, specificity ≥0.855, accuracy ≥0.897, and negative predictive value ≥ 0.981 across both clinical scenarios, outperforming all comparative approaches. TabPFN-SHAP provides an interpretable computational framework for metabolite-panel discovery, with demonstrated utility for HCC screening.

Background Metabolic dysfunction-associated steatotic liver disease (MASLD) often coexists with chronic hepatitis B (CHB), yet early diagnosis remains challenging, particularly in non-obese patients or those with subclinical features. This study aimed to identify metabolic signatures of CHB-related MASLD and construct a predictive model using untargeted metabolomics integrated with machine learning. Methods Serum metabolomics was performed on 160 subjects (80 CHB + MASLD and 80 healthy controls). Differential metabolites were identified and analyzed using KEGG enrichment and 4 machine learning algorithms (Random Forest, XGBoost, SVM, and LASSO). Metabolite-clinical correlations and diagnostic model performance were evaluated. Results A total of 924 differential metabolites were identified, with significant enrichment in pathways related to the TCA cycle, sphingolipid metabolism, and amino acid turnover. Machine learning prioritized six robust and biologically relevant metabolites: L-aspartic acid, succinic acid, caproic acid, sebacic acid, monomenthyl succinate, and glycolaldehyde, which consistently distinguished CHB + MASLD patients from controls (AUC > 0.75). These metabolites reflect key disruptions in mitochondrial function, lipid oxidation, and redox homeostasis. Integrated models combining metabolomics with clinical indices achieved perfect classification (AUC = 1.000). Conclusion CHB-associated MASLD is driven by systemic metabolic remodeling centered on mitochondrial overload, oxidative stress, and impaired amino acid metabolism. The identified metabolites provide mechanistic insights and hold promise for non-invasive MASLD screening in CHB patients. This study underscores the potential of multi-algorithmic metabolomics in advancing early diagnosis and personalized management of complex liver comorbidities.

BACKGROUND & AIMS:Fibrosis-4 Index (FIB-4) is a noninvasive tool for assessing liver fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). However, its role of dynamic FIB-4 for assessing fibrosis progression and predicting clinical outcomes remains unclear. The aim of this study was to examine the association between changes in FIB-4 and changes in liver stiffness, fibrosis progression, and outcomes in MASLD. METHODS:Three cohorts were analyzed: VCTE-Prognosis cohort (n = 10,203) for stiffness progression, Paired Liver Biopsy cohort (n = 1,145) for fibrosis progression, and Wenzhou Real-World (WRW) cohort (n = 41,105) for clinical outcomes. Stiffness progression was defined as an increase in liver stiffness measurement, and fibrosis progression by a 1-stage increase. Outcomes included all-cause mortality, cardiovascular events, and liver-related events (LREs). FIB-4 was dichotomized into low (<1.3) and high (≥1.3). Increases were defined as ≥20% rise and to ≥1.3 in the low FIB-4 group, and ≥20% rise in the high FIB-4 group. RESULTS:In the VCTE-Prognosis cohort, stiffness progression was more likely with increasing vs stable FIB-4 (adjusted odds ratio [OR], 2.36; P < .001) in those with low baseline FIB-4. In the high FIB-4 group, stiffness progression rates increased from stable to increasing FIB-4 (adjusted OR, 3.42; P < .001). In the Paired Liver Biopsy cohort, fibrosis progression was more frequent with increasing FIB-4 (adjusted OR, 2.20; P = .004 in low FIB-4; adjusted OR, 3.68; P < .001 in high FIB-4). In the WRW cohort, an increase in dynamic FIB-4 was linked to higher risks for all-cause mortality, cardiovascular events, and LREs (all P < .001). CONCLUSIONS:Dynamic FIB-4 monitoring tracks fibrosis and stiffness progression and predicts clinical outcomes in MASLD.

BACKGROUND:Non-invasive assessment of improvement in fibrotic metabolic dysfunction-associated steatohepatitis (MASH) is an important clinical problem. We aimed to develop and validate the fibrotic MASH resolutionVCTE index, a non-invasive tool for identifying fibrotic MASH resolution and predicting liver-related events (LREs). METHODS:We collected data from 2,017 individuals who had two liver biopsies, separated in time, across 40 centers in the first dataset. This dataset included two independent cohorts, which were used to develop and externally validate the tool (including the baseline and change in acFibroMASH index plus change in serum alanine aminotransferase levels). The second independent dataset, comprising 17,949 patients who underwent vibration-controlled transient elastography (VCTE) at 16 centers, was used to examine associations between the developed index and the risk of incident LREs. FINDINGS:After application of the inclusion and exclusion criteria, 252 and 8,752 patients were included in the first and second datasets, respectively. The fibrotic MASH resolutionVCTE index accurately identified fibrotic MASH resolution with an area under the receiver operating curve (AUROC) of 0.82 (95% CI 0.74-0.90) in the derivation cohort and 0.80 (95% CI 0.72-0.88) in the validation cohort. Patients with a fibrotic MASH resolutionVCTE index >0.61 had a substantially lower risk of incident LREs than those with an index <0.24 (adjusted-hazard ratio 0.043). The index achieved AUROCs of 0.86 and 0.87, respectively, for predicting the 5- and 10-year probability of not developing LREs. CONCLUSIONS:This global multicenter study suggests that the fibrotic MASH resolutionVCTE index may offer a non-invasive approach to estimate fibrotic MASH resolution and stratify long-term risk of LREs. FUNDING:National Natural Science Foundation.

BACKGROUND:Inhibition of liver fibrosis plays a crucial role in curbing the advancement of chronic disease to cirrhosis and even liver cancer. However, modern medicine currently lacks direct anti-fibrotic drugs. He-He-Shu-Yang formula (HHSY) is a renowned Chinese medicine for the treatment of liver fibrosis. However, its mechanism of action has not been fully unraveled. AIM:To explore the efficacy and mechanism of action of HHSY through in vitro and in vivo experiments. METHODS:A liver fibrosis rat model (carbon tetrachloride-induced) was treated with low- or high-dose HHSY (10.42 g/kg or 20.84 g/kg) or with colchicine (1 mg/kg) for 9 weeks. In vitro, LX-2 human hepatic stellate cells (HSCs) were activated using transforming growth factor-β1 and subsequently treated with HHSY-containing serum or a nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) inhibitor. Through high-performance liquid chromatography, histopathology (hematoxylin and eosin, Masson), immunohistochemistry, western blot, and quantitative reverse transcription polymerase chain reaction analyses, we demonstrated that HHSY inhibited HSC activation and suppressed the NOX4/reactive oxygen species (ROS)/nucleotide binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) pathway. RESULTS:In vivo, HHSY improved liver function and alleviated liver pathology, including reducing inflammatory cell infiltration, and liver fibrosis in carbon tetrachloride rats. with more significant effects at higher doses. Immunohistochemistry revealed that HHSY could decrease alpha-smooth muscle actin, NOX4, and NLRP3 expression, as well as serum ROS levels (O2 - and H2O2, P < 0.05). Western blot analysis confirmed HHSY also reduced NLRP3 protein levels (P < 0.05). In vitro, HHSY at 1.25% or 2.5% reduced the levels of ACTA2 mRNA, NOX4 protein and NOX4 mRNA, ROS production, and NLRP3 and IL-1β mRNA in activated LX-2 cells (P < 0.05). CONCLUSION:HHSY effectively treats liver fibrosis, likely by inhibiting HSC activation through the NOX4/ROS/NLRP3 pathway. This underscores HHSY's clinical relevance as a potential therapeutic option for liver fibrosis.

BACKGROUND & AIMS:Hypertension is common in metabolic dysfunction-associated steatotic liver disease (MASLD), but its impact on long-term clinical outcomes and disease progression remains unclear. This study investigated the association of hypertension with the risk of adverse clinical outcomes and progression of liver stiffness/fibrosis in MASLD. METHODS:Three multicenter large cohorts were analyzed: the UK Biobank (UKBB) cohort to assess the risk of adverse clinical outcomes, the VCTE-Prognosis cohort to assess liver stiffness/fibrosis progression, and the Paired Liver Biopsy cohort to assess histologic liver fibrosis progression. Adverse clinical outcomes were defined as all-cause mortality, cardiovascular events, and/or liver-related events. Liver stiffness progression was defined as an increase in liver stiffness measurement from <10 kPa to ≥10 kPa or an increase of ≥20% for baseline liver stiffness measurement ≥10 kPa. Liver fibrosis progression was defined as a 1-stage fibrosis stage increase. Cox regression and Kaplan-Meier analyses were used to evaluate the impact of baseline hypertension on outcomes. RESULTS:A total of 107,316 adults from the UKBB cohort, 8,169 from the VCTE-Prognosis cohort, and 1,670 from the Paired Liver Biopsy cohort were included. The prevalence of hypertension was 37.1%, 33.4%, and 48.9%, respectively. In the UKBB cohort, hypertension was associated with long-term adverse clinical outcomes (adjusted hazard ratio [HR] 1.30, 95% CI 1.26-1.33, p <0.001). In the VCTE-Prognosis cohort, hypertension was associated with a higher risk of liver stiffness progression (adjusted HR 1.57, 95% CI 1.30-1.90, p <0.001), while in the Paired Liver Biopsy cohort, hypertension was associated with a greater risk of histologic liver fibrosis progression (adjusted HR 1.41, 95% CI 1.12-1.78, p = 0.004). Subgroup and sensitivity analyses supported these findings. CONCLUSIONS:Hypertension is a modifiable risk factor that increases the risk of adverse clinical outcomes and progression of liver stiffness and fibrosis in MASLD. IMPACT AND IMPLICATIONS:This study provides robust evidence from three large multicenter cohorts demonstrating that hypertension is independently associated with increased risks of adverse clinical outcomes and liver fibrosis progression in individuals with MASLD. These findings reveal that hypertension, traditionally managed from a cardiovascular perspective, also plays a critical and underrecognized role in liver disease progression, making them highly relevant for hepatologists, cardiologists, and primary care providers. Incorporating non-invasive fibrosis assessments into routine care for patients with MASLD and hypertension may facilitate early risk stratification and support targeted interventions to reduce both hepatic and cardiovascular complications.

Background: The aim of this study was to evaluate the accuracy of LiveBoost™, a gradient boosting (GB)-based prediction system based on standard biochemical values (AST, ALT, platelet count) and age, in Chinese patients with chronic hepatitis B (CHB) and compare its performance with FIB-4 (fibrosis-4 score) and APRI (the aspartate transaminase to platelet ratio index). Methods: This retrospective trial enrolled 454 participants, including 279 CHB patients who underwent liver biopsy and 175 normal controls from 3 centers in China. All participants underwent laboratory blood testing. LiveBoost was constructed using GB and FIB-4 and APRI were calculated from laboratory data. Results: LiveBoost outperformed APRI and FIB-4 in predicting hepatic fibrosis and cirrhosis. The GB model had an AUROC of 0.977 for CHB diagnosis, 0.804 for early and advanced fibrosis, and 0.836 for non-cirrhosis and cirrhosis, compared to AUROC of 0.554, 0.673 and 0.720 for FIB-4, AUROC of 0.977, 0.652 and 0.654 for APRI. Conclusions: LiveBoost is a more reliable and cost-effective method than APRI and FIB-4 for assessing liver fibrosis in Chinese patients with CHB.

Background: The combined effect of hepatitis B virus infection and metabolic dysfunction-associated steatotic liver disease (MASLD) on hepatocellular carcinoma (HCC) risk remains unclear. The current study sought to elucidate the impact of MASLD on HCC progression in chronic hepatitis B (CHB) patients.Method: This retrospective cohort study included CHB patients who had undergone liver biopsy and abdominal imaging at the Guangdong Provincial Hospital of Chinese Medicine between 2013 and 2019. We investigated the correlation between MASLD and HCC risk, and inverse probability treatment weighting (IPTW) was used to adjust for patient characteristics.Results: A total of 1,613 patients were included, and 483 (29.9%) were diagnosed with MASLD. Over a median follow-up period of 5.02 years, 36 (2.2%) developed HCC, comprising 4.8% (23/483) of those with MASLD and 1.2% (13/1,130) of those without. Those with MASLD had a significantly higher cumulative incidence of HCC than those without (p < 0.001). The presence of MASLD was associated with a higher risk of HCC (adjusted hazard ratio [HR], 3.996; 95% confidence interval [CI], 2.007–7.959; p < 0.001). After adjustment using IPTW, the patients with MASLD retained a higher cumulative incidence of HCC (p < 0.001). Moreover, MASLD was found to be an independent risk factor for the development of HCC (adjusted HR, 10.191; 95% CI, 4.327–24.002; p < 0.001). However, among patients with MASLD, there were no significant differences in the cumulative risk of HCC between patients with and without overweight, between those with <2 and ≥2 cardiometabolic risk factors (CMRFs), between those with <3 and ≥3 CMRFs, or between those with <4 and ≥4 CMRFs (p = 0.110, p = 0.087, p = 0.066, and p = 0.490, respectively).Conclusion: The presence of MASLD is associated with a higher risk of HCC in patients with CHB. Notably, this higher risk is present in patients with MASLD, irrespective of the presence or absence of overweight or the number of CMRFs they have.

Abstract Objectives To explore the impact of hepatic steatosis measured by MRI-proton density fat fraction (MRI-PDFF) on liver stiffness measurement (LSM) value and its diagnostic performance for staging liver fibrosis in patients with chronic hepatitis B (CHB). Methods A total of 914 patients with CHB who underwent liver biopsy and MRI-PDFF were retrospectively reviewed. The influence of MRI-PDFF on LSM value was assessed using univariate and multivariate linear analyses. To assess the influence of liver steatosis on the diagnostic performance of LSM, a series of ROC analyses were performed and compared by stratifying patients into non-steatosis (PDFF < 5%) and steatosis (PDFF ≥ 5%) groups according to MRI-PDFF values. The effects of different LSM cut-off values on the false-positive rate in the steatosis cohort were compared using McNemar’s test. Results LSM values were significantly affected by MRI-PDFF in the entire cohort (B-coefficient: 0.003, p < 0.001), F1 cohort (B-coefficient: 0.005, p < 0.001), and F2 cohort (B-coefficient: 0.003, p = 0.002). Hepatic steatosis was not observed to have a significant influence on the ROC curve of LSM for staging liver fibrosis. Compared with using the cut-off values for the CHB cohort, using relatively higher cut-off values for hepatic steatosis significantly improved the false-positive rate of LSM in the steatosis cohort. Conclusion Steatosis significantly influenced LSM, with a higher value in the early stage of liver fibrosis but did not affect the diagnostic efficiency of LSM for staging liver fibrosis. Moreover, using relatively high cut-off values significantly improved the false-positive rate of LSM in CHB patients with steatosis. Clinical relevance statement The identified correlation between MRI-PDFF and VCTE-measured LSM is not clinically relevant since the diagnostic performance of LSM in staging liver fibrosis is not affected by steatosis. A higher cut-off should be applied in CHB patients with steatosis to improve the false-positive rate. Key Points Steatosis can affect liver stiff measurement (LSM) values in the early stage of liver fibrosis. The diagnostic performance of LSM in staging liver fibrosis is not affected by steatosis. LSM’s cutoffs should be increased in patients with steatosis to improve the false-positive rate. Graphical Abstract

Abstract Background and aims Numerous HBeAg-positive chronic hepatitis B (CHB) patients with persistently normal ALT have significant liver histopathology. It is imperative to identify true “immune tolerant” patients. We aimed to evaluate the liver histopathology features of HBeAg-positive CHB patients with normal ALT and the incidence of liver cirrhosis and HCC in CHB patients during follow-up. Methods 179 HBeAg-positive CHB patients with normal ALT who performed liver biopsy from 2009 to 2018 were retrospectively analyzed. Liver necroinflammation ≥ G2 and/or liver fibrosis ≥ S2 was defined as significant liver histopathological change. Results 57.5% patients were in the indeterminate phase with significant liver histological changes. The proportion of the patients with evident liver necroinflammation was higher in the high-normal ALT group (21-40U/L) when compared with the low-normal ALT group (≤ 20 U/L) (51.3% vs. 30.0%, p < 0.05), and patients aged ≥ 40 years had a higher proportion of significant fibrosis than those aged < 40 years (64.5% vs. 39.9%, p < 0.05). The percentages of patients with ≥ S2 and ≥ G2/S2 in the HBV DNA < 107 IU/mL group were higher than those in the HBV DNA ≥ 107 IU/mL group (72.7% vs. 40.1%, p < 0.01; 81.8% vs. 54.1%, p < 0.05). During follow-up, two of immune tolerant patients and four of indeterminate patients developed into cirrhosis, and one of immune tolerant patients and one of indeterminate patients developed into HCC, respectively. Conclusions HBeAg-positive CHB patients with high-normal ALT or HBV DNA < 107 IU/mL were tend to be indeterminate. Liver biopsy or noninvasive approaches are recommended to evaluate liver histopathology, and antiviral therapy is recommended for patients with significant liver histopathology.

Background or Purpose Although human umbilical cord blood-derived mesenchymal stem cell transplantation (HUCB-MSCT) resulted in a good short-term therapeutic effect on patients with decompensated liver cirrhosis (DLC), the long-term survival remained unclear. This study aimed to evaluate the impact of HUCB-MSCT on long-term outcomes in patients with DLC. Methods This retrospective cohort study included hospitalized patients with decompensated cirrhosis in Liuzhou Hospital of Traditional Chinese Medicine between November 2010 and February 2013. The primary outcome was overall survival (OS). The secondary outcomes were 3-year and 5-year survival rates and the occurrence rate of hepatocellular carcinoma (HCC). Results A total of 201 subjects were enrolled, including 36 patients who underwent HUCB-MSCT (SCT group) and 165 patients who did not (non-SCT group). After PSM (1:2), there were 36 patients in the SCT group and 72 patients in non-SCT group. The 3-year and 5-year survival rates of the two groups were 83.3% vs. 61.8% and 63.9% vs. 43.6%, and median OS time was 92.50 and 50.80 months, respectively. HUCB-MSCT treatment was found to be an independent beneficial factor for patient OS (hazard ratio = 0.47; 95% CI: 0.29–0.76; P = 0.002). There was no significant difference in the occurrence rate of HCC between the two groups ( P = 0.410). Discussion or Conclusions HUCB-MSCT may improve long-term OS without increasing the occurrence of HCC in patients with DLC. Trial Registration The Chinese Clinical Trial Registry (ChiCTR2100047550).

Abstract Background and Aims: Numerous HBeAg-positive chronic hepatitis B(CHB) patients with persistently normal ALT have significant liver histopathology,it is imperative to identify true "immune tolerant" patients.We aimed to evaluate the liver histopathology features of HBeAg-positive CHBpatients with normalALT, and the incidence of liver cirrhosis and HCC in CHB patients during follow-up. Methods:179 HBeAg-positiveCHB patients with normalALT whoperformed liver biopsy from 2009 to 2018 were retrospectively analyzed.Liver necroinflammation ≥ G2 and/or liver fibrosis ≥ S2was defined as significant liver histopathological change. Results:57.5% patients were in the indeterminate phase with significant liver histological changes. The proportion of the patients with evident livernecroinflammation was higher in thehigh-normal ALT group (21-40U/L) when compared with the low-normal ALT group (≤ 20 U/L) (51.3% vs 30.0%, p < 0.05),and patients aged ≥ 40 years had a higher proportion of significant fibrosis than those aged < 40 years (64.5% vs 39.9%, p < 0.05).The percentage of patients with ≥ S2and ≥ G2/S2in the HBV DNA < 107 IU/mL group were higher than those in the HBV DNA ≥ 107 IU/mL group (72.7% vs 40.1%, p < 0.01; 81.8% vs 54.1%, p < 0.05). During follow-up, two of immune tolerant patients and four of indeterminate patients developed into cirrhosis, and one of immune tolerant patients and one of indeterminate patients developed into HCC, respectively. Conclusions:HBeAg-positive CHBpatients with high-normal ALT or HBV DNA < 107 IU/mL were tend to be indeterminate, liver biopsy or noninvasive approaches are recommended to evaluateliver histopathology, and antiviral therapyare recommendedfor patients with significant liver histopathology.

Background:There is an unmet need for accurate non-invasive methods to diagnose non-alcoholic steatohepatitis (NASH). Since impedance-based measurements of body composition are simple, repeatable and have a strong association with non-alcoholic fatty liver disease (NAFLD) severity, we aimed to develop a novel and fully automatic machine learning algorithm, consisting of a deep neural network based on impedance-based measurements of body composition to identify NASH [the bioeLectrical impEdance Analysis foR Nash (LEARN) algorithm].Methods:A total of 1,259 consecutive subjects with suspected NAFLD were screened from six medical centers across China, of which 766 patients with biopsy-proven NAFLD were included in final analysis. These patients were randomly subdivided into the training and validation groups, in a ratio of 4:1. The LEARN algorithm was developed in the training group to identify NASH, and subsequently, tested in the validation group.Results:The LEARN algorithm utilizing impedance-based measurements of body composition along with age, sex, pre-existing hypertension and diabetes, was able to predict the likelihood of having NASH. This algorithm showed good discriminatory ability for identifying NASH in both the training and validation groups [area under the receiver operating characteristics (AUROC): 0.81, 95% CI: 0.77-0.84 and AUROC: 0.80, 95% CI: 0.73-0.87, respectively]. This algorithm also performed better than serum cytokeratin-18 neoepitope M30 (CK-18 M30) level or other non-invasive NASH scores (including HAIR, ION, NICE) for identifying NASH (P value <0.001). Additionally, the LEARN algorithm performed well in identifying NASH in different patient subgroups, as well as in subjects with partial missing body composition data.Conclusions:The LEARN algorithm, utilizing simple easily obtained measures, provides a fully automated, simple, non-invasive method for identifying NASH.

肝纤维化是慢性乙型肝炎发展至肝硬化、肝癌的必经中间过程.近年来,中医药防治慢性乙型肝炎肝纤维化的研究取得突破性进展.以提高临床疗效为目的,多学科联合开展产学研研究,阐释慢性乙型肝炎肝纤维化中医证候生物学基础、建立与研发中医特色无创诊断模型,优化中医/中西医结合治疗方案并阐释中医治疗的科学内涵能够帮助中医药防治肝纤维化走向国际.

目的 探讨代谢相关性脂肪性肝病(MAFLD)合并慢性乙型病毒性肝炎(CHB)患者的肾脏功能状况,并对影响肾小球滤过率(eGFR)的相关因素进行分析.方法 分别收集 MAFLD 组(n =141)和CHB-MAFLD组(n=144)患者的肝脏生化、肾脏生化等临床资料,利用eGFR对两组患者的肾脏功能进行评价,采用多因素logistic回归分析探讨肾功能受损的影响因素.结果 在符合纳入标准和排除标准的 285 例患者中,与MAFLD组对比,CHB-MAFLD组三酰甘油(TG)、总胆固醇(TC)、谷氨酰转肽酶(GGT)、血肌酐(SCr)、eGFR、大量饮酒史之间的差异有统计学意义(P＜0.05);CHB-MAFLD组出现SCr异常升高(16.67％vs 3.55％,x2 =13.418,P＜0.001)及肾功能受损(40.97％vs 12.77％,x2 =28.745,P＜0.001)的比例明显高于MAFLD组;多因素logistic回归分析提示性别、年龄、尿酸、合并糖尿病、合并高血压、合并CHB是影响患者肾功能的独立影响因素.结论 CHB-MAFLD患者存在亚临床型肾功能受损,可能比单纯MAFLD患者更易发生、发展早期肾功能受损.对于CHB-MAFLD患者,更应严格控制相关危险因素,预防慢性肾病的发生.

Objective To investigate the value of traditional noninvasive fibrosis models in the diagnosis of significant liver fibrosis inpatients with chronic hepatitis B（CHB）and metabolic associated fatty liver disease（MAFLD）. Methods A total of 499 patients who underwent liver pathological examination in Department of Hepatology，Guangdong Provincial Hospital of Traditional Chinese Medicine，from September 2014 to December 2020 and met the diagnostic criteria for CHB and MAFLD were enrolled in this study.The Scheuer scoring system was used to evaluate the degree of liver fibrosis. The Mann－Whitney U test was used for comparison of normally distributed continuous data between groups. A Spearman correlation analysis was used to investigate the correlation of each noninvasive diagnostic method with the degree of liver fibrosis；the receiver operating characteristic（ROC）curve was plotted to investigate the value of FibroScan，gamma－glutamyl transpeptidase－to－platelet ratio（GPR）， aspartate aminotransferase－to-platelet ratio index（APRI），fibrosis－4（FIB－4），and liver stiffness measurement－to－platelet ratio index（LPRI）in the diagnosis of CHB with MAFLD；a binary Logistic regression analysis was used to construct a combined model，and the area under the ROC curve（AUC）was compared between the combined model and the five indicators used alone. The DeLong method was used for comparison ofAUC between any two noninvasive diagnostic methods. Results There were 198 patients in the group with no or mild liver fibrosis（S0－S1）and 301 patients in the group with significant liver fibrosis（S≥2）. The S≥2 group had higher clinical indicators than the S0－S1 group，with significant differences between the two groups in alanine aminotransferase，aspartate aminotransferase， gamma－glutamyl transpeptidase，total bilirubin，GPR，FIB－4，APRI，LPRI，and liver stiffness measurement（LSM）（ all P< 0.05）. The Spearman correlation analysis showed that GPR，FIB－4，APRI，LSM，and LPRI were positively correlated with the stage of liver fibrosis（r = 0.393，0.414，0.449，0.553，and 0.580，all P<0.001）. The ROC curve analysis showed that GPR，FIB-4，APRI，LSM，and LPRI used alone had an AUC of 0.704，0.715，0.740，0.787，and 0.802，respectively，in the diagnosis of significant liver fibrosis. The binary Logistic regression analysis was used to construct a combined LGAF model of GPR，FIB－4， APRI，and LSM，which had an AUC of 0.814 in the diagnosis of significant liver fibrosis. LGAF was compared with GPR，FIB－4， APRI，LSM，and LPRI，respectively，in terms of AUC，and the results showed that there was a significant difference between LGAF and all five indicators except LPRI（Z=5.184，4.884，4.117，and 2.120，all P<0.05）. Conclusion The five data models of FibroScan，GPR，APRI，FIB－4，and LPRI have a similar value in the diagnosis of significant liver fibrosis in CHB with MAFLDcompared with the combined LGAF model，which provides reference and guidance for the application of noninvasive assessment of liver fibrosis in clinical practice.