To evaluate the diagnostic utility of T1ρ mapping for assessing hepatic fibrosis in patients with chronic liver disease (CLD), including steatotic liver disease (SLD). In this prospective study (September 2024 to May 2025), consecutive patients with CLD underwent liver MRI, including MR-elastography, PDFF, T1, extracellular volume fraction (ECV), and T1ρ mapping. MRE-based liver stiffness was used as the reference to assess the diagnostic performance of the MRI-derived mapping parameters. MR-elastography-based liver stiffness thresholds for significant fibrosis (≥ F2) were set at > 3.66 kPa for participants without hepatic steatosis (PDFF ≤ 5%), and > 3.14 kPa for participants with hepatic steatosis (PDFF > 5%). The t-test, Spearman's correlation, and the ROC analysis were applied. One hundred twelve CLD participants were included (mean age, 48 ± 16 years; 53 participants with hepatic steatosis). All assessed quantitative mapping parameters were significantly increased in participants with significant fibrosis than in those without (e.g., T1ρ: 110 ± 15 vs 92 ± 6 ms, p < 0.001). T1ρ revealed a moderate to strong correlation with MR-elastography-based stiffness, superior to T1 and ECV (entire cohort: r = 0.75 [T1ρ] vs 0.49 [native T1] vs 0.68 [ECV]; participants with hepatic steatosis: r = 0.67 [T1ρ] vs 0.32 [native T1] vs 0.62 [ECV]; p < 0.05 in each case, respectively). T1ρ provided the highest diagnostic performance for diagnosing significant fibrosis (in the entire cohort: AUC 0.90 [T1ρ] vs 0.73, p < 0.001 [native T1], vs 0.81, p = 0.05 [ECV]; in participants with hepatic steatosis: AUC 0.87 [T1ρ] vs 0.67, p = 0.03 [native T1], vs 0.79, p = 0.047 [ECV], p values are given vs T1ρ). Hepatic T1ρ might be a more accurate marker of hepatic fibrosis in CLD, including SLD, compared to hepatic native T1 and ECV mapping. Question Accurate non-invasive assessment of hepatic fibrosis remains challenging, particularly in the presence of steatosis, where MRI biomarkers such as native T1 and ECV fraction are limited. Findings T1ρ mapping outperformed native T1 and ECV for identifying significant fibrosis and maintained robust accuracy in the presence of hepatic steatosis. Clinical relevance T1ρ mapping offers a robust, non-invasive MRI biomarker for assessing hepatic fibrosis across the full spectrum of CLD, including SLD, with superior accuracy to native T1 and ECV and reduced influence from hepatic fat infiltration.

Microbiome-gut-liver axis in chronic inflammation and cancer immunotherapy: Multi-omics Insights and a translational roadmap toward personalized medicine.

Inflammatory dysregulation and tissue homeostatic imbalance are the fundamental pathological mechanisms underlying the progression of various types of chronic disease, and identifying key regulatory molecules is important for achieving effective anti‑inflammatory therapeutic goals. Stabilin‑1, an immunoregulatory scavenger receptor, regulates inflammation and tissue homeostasis in multiple ways. In the field of innate immunity, Stabilin‑1 acts as a monocyte‑recruiting factor through the interaction of fibronectin with its extracellular fasciclin domain and mediates the polarization of macrophages to M2‑type cells. In addition, its extracellular epidermal growth factor‑like domain can recognize and interact with phosphatidylserine on the surface of apoptotic cells, and bind to its corresponding Gulp1 adapter molecules, activating downstream signalling pathways and making the clearance of these apoptotic cells possible. It can also specifically recognize and take up oxidative stress products, such as oxidized low‑density lipoprotein and lipopolysaccharide, inhibiting the activation of any proinflammatory signal transduction pathway. In adaptive immune regulation, Stabilin‑1 can inhibit the T‑helper cell (Th)1 type immune response and regulate the Th2 type immune response. The inflammatory microenvironment induces the synthesis of Stabilin‑1 and its surface localization on blood and lymphatic endothelial cells, mediating the transendothelial migration of immune cells such as regulatory T cells and B cells to regulate the intensity of immune responses. Stabilin‑1 has regulatory functions in different diseases, such as atherosclerosis, chronic liver disease, viral myocarditis, infection, sepsis and tumours. The present review discusses the role of Stabilin‑1 as an immunomodulatory scavenger receptor in inflammatory microenvironments and tissue homeostasis, providing novel theoretical support and potential therapeutic targets for the targeted treatment of inflammation‑related diseases.

The World Federation for Ultrasound in Medicine and Biology (WFUMB) guidance update 2024 proposed a 'rule-of-4' using ARFI liver stiffness measurement (LSM) to stratify the risk of decompensation events. This rule identifies advanced chronic liver disease (ACLD) at a threshold of ≥ 13 kPa and indicates a high probability of clinically significant portal hypertension (CSPH) above 21 kPa. We prospectively enrolled 187 patients undergoing same-day SSI-2D-LSM (Aixplorer SuperSonic Imagine) and hepatic venous pressure gradient (HVPG) measurement. Patients were stratified into three LSM groups < 13 kPa, 13-21 kPa and > 21 kPa and followed for decompensation events for 1 year (Y1). The cohort comprised 31 (16.6%) patients with LSM < 13 kPa (non-ACLD); 33 (17.6%) LSM 13-21 kPa (ACLD) and 123 (65.8%) LSM > 21 kPa (high CSPH probability). The corresponding median HVPG values were 5 [IQR: 3-7] vs. 10 [7-14] vs. 17 [13-21] mmHg, respectively, and the corresponding CSPH prevalence was 6.5%, 54.5% and 91.9%. In ROC analysis to predict CSPH, SSI-2D-LSM demonstrated high accuracy (AUC: 0.83). Validating the new WFUMB extension of the 'rule-of-4', the recommended > 21 kPa threshold identified CSPH with a specificity of 80.0% and a PPV of 83.1%. In competing risk analysis, the Y1-decompensation rate was 0%, 10% and 24.7% of patients in the < 13 kPa, 13-21 kPa and > 21 kPa groups, respectively. For prediction of Y1-decompensation risk in the compensated ACLD (cACLD) subgroup, HVPG demonstrated the highest predictive accuracy (AUC: 0.92), while SSI-2D-LSM (AUC: 0.75) performed similarly to vibration-controlled transient elastography (VCTE: AUC: 0.77; AUC-comparison: p = 0.837). The WFUMB 'rule-of-4' for ARFI-LSM allows for accurate and point-of-care non-invasive risk stratification of patients with liver disease. Specifically, the short-term risk of decompensation starts at SSI-2D-LSM ≥ 13 kPa and becomes considerable at SSI-2D-LSM > 21 kPa (indicating high CSPH probability). These findings support the broader implementation of ARFI-LSM for risk assessment in clinical routine.

AISF practice guidance on pharmacological treatment of metabolic-dysfunction associated steatotic liver disease and steatohepatitis (MASLD/MASH): A 2026 Update.

Cirrhosis is the irreversible architectural endpoint of chronic liver disease and is the greatest risk factor for hepatocellular carcinoma (HCC). Despite its centrality in HCC management algorithms, there are no standardised morphologic criteria for diagnosing cirrhosis on cross-sectional imaging. Criteria used in clinical studies and clinical practice guidelines have not been reviewed systematically. We aim to assess cross-sectional imaging criteria in clinical practice guidelines and clinical studies. We appraised clinical practice guidelines from major hepatology or radiological associations and conducted a systematic review of MEDLINE and EMBASE to identify original studies using ultrasound, CT, and MRI to diagnose liver cirrhosis from 1 January 2015 to 5 November 2025. Studies were classified as having clear, indirect, or no definition. Bias for diagnostic accuracy studies was assessed using QUADAS-2. Among 18 clinical practice guidelines, only 3 specified explicit imaging-based criteria for diagnosing cirrhosis in at-risk populations. From 6859 records screened, 73 studies (n = 41,417 patients) met inclusion criteria. Only 4 (5%) studies provided a clear definition, 55 (75%) provided indirect definition, and 14 (19%) provided no imaging criteria. Diagnostic performance of imaging features for cirrhosis varied across modalities. While CT and MRI offered higher specificity for certain features (e.g., regenerative nodules), no single modality or feature was sufficient, highlighting the need for standardised morphological-based criteria applicable for several modalities. Despite the widespread use of cross-sectional imaging in cirrhosis, there is no consensus-based, standardised imaging definition. This highlights the urgent need for a standardised, morphology-based definition of cirrhosis.

3,3'-diindolylmethane ameliorates non-alcoholic fatty liver disease by inhibiting the FMO3-TMAO axis in mice.

Glycoursodeoxycholic acid regulates peritoneal monocytic myeloid-derived suppressor cells to alleviate systemic inflammation in decompensated cirrhosis.

Hedyotis diffusa Willd. extract alleviates CCl4-induced liver fibrosis via modulation of the gut microbiota and FXR/SHP/CYP7A1-mediated bile acid metabolism.

Xiayuxue decoction alleviates MASH by regulating gut microbiota, bile acid metabolism, and m6A modification.

The integration of the multitude of ultrasound techniques into a "one-stop" liver clinic model will revolutionize the management of liver diseases. This approach streamlines patient care by providing immediate imaging assessment, facilitating prompt diagnosis, and expediting treatment plans. The traditional ultrasound methods of B-mode imaging and Doppler techniques have been supplemented by the newer techniques of tissue elastography, fat quantification, and contrast-enhanced ultrasound-termed multiparametric ultrasound. The deployment of these techniques to establish in more detail the underlying status of liver disease has been profound. The encompassing ultrasound techniques have allowed the ultrasound practitioner to establish a comprehensive assessment of liver disease, allowing further accurate management, and negating the need for additional, often more expensive, imaging to establish the diagnosis. This paper explores the implementation, benefits, and challenges of ultrasound-based one-stop liver clinics, emphasizing their impact on patient outcomes and healthcare efficiency. A detailed assessment of the techniques and their position in the diagnostic armamentarium is reviewed with a comprehensive overview established. CRITICAL RELEVANCE STATEMENT: Multiparametric liver ultrasound integrating B-mode, Doppler, CEUS, elastography and fat quantification provides a practical, low-cost one-stop pathway for staging chronic liver disease, assessing portal hypertension surrogates and characterizing incidental lesions, thereby speeding up treatment. KEY POINTS: Ultrasound is the first-line imaging investigation for liver disease, with established criteria on B-mode imaging for steatosis and cirrhosis. Multiparametric ultrasound integrates morphology, hemodynamics, fibrosis, steatosis, and lesion assessment. A one-stop liver ultrasound clinic accelerates decisions and reduces additional imaging.

BACKGROUND Hepatic cirrhosis is a chronic condition often associated with malnutrition and sarcopenia, both of which negatively affect patient prognosis. Early identification of sarcopenia is essential for effective interventions. AIM To evaluate the strength, assistance with walking, rising from a chair, climbing stairs and falls (SARC-F) questionnaire as an indirect predictor of sarcopenia risk in patients with chronic liver disease (CLD). METHODS This was a pilot, prospective, cross-sectional study including 45 patients with hepatic cirrhosis undergoing clinical follow-up at the Gastroenterology Outpatient Clinic of the Hospital Complex of the Irmandade Santa Casa de Misericórdia de Porto Alegre. The following tools were used: Phase angle, five times sit-to-stand test, handgrip strength (HGS), and the SARC-F questionnaire. RESULTS Among the 45 patients evaluated (mean age: 61 years, slight male predominance), the SARC-F questionnaire identified only eight suspected cases of sarcopenia. In contrast, objective strength tests identified 15 cases by HGS and 21 by the sit-to-stand test. Cross-tabulation analysis showed that SARC-F did not identify any true positives and demonstrated low specificity and negative predictive value, compromising its effectiveness as a screening tool. CONCLUSION Despite its ease of application and low cost, the SARC-F demonstrated limited sensitivity and a high rate of false-positive results, compromising its accuracy as a standalone screening tool for sarcopenia in patients with hepatic cirrhosis.

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, as well as a growing public health concern. Erectile dysfunction (ED) is one of the most common sexual dysfunctions in men. Currently, clinical research on the relationship between NAFLD and ED is limited. AIM To systematically review and narrative synthesize the existing evidence on the association between NAFLD and ED, and to elucidate potential underlying mechanisms. METHODS We conducted a comprehensive search of various electronic databases to identify original observational studies investigating the association between NAFLD and ED. However, due to significant heterogeneity among the included studies and the limited number of eligible investigations, we opted for a narrative synthesis instead of a meta-analysis. RESULTS A total of seven observational studies, involving 4442 participants (2043 of whom had NAFLD), were included in the analysis. The evidence consistently indicates a significant positive association between NAFLD and ED. Key influencing factors identified across the studies included age, components of metabolic syndrome, insulin resistance, serum testosterone levels, and psychological factors such as anxiety. CONCLUSION Existing evidence indicates a strong correlation between NAFLD and ED. The strength of this association is influenced by various factors, including age, insulin resistance, testosterone levels, and anxiety. NAFLD is an important risk factor for ED. Further high-quality studies are needed to confirm this relationship and explain its underlying mechanisms.

Accurate mortality data for American Indian and Alaska Native (AI/AN) people are critical for describing health disparities and program planning needs. We describe the rates of leading causes of death among non-Hispanic AI/AN as compared with non-Hispanic White populations living in the same area, by sex and Indian Health Service (IHS) Area in 2020. We used the 2020 US Cancer Statistics AI/AN Mortality Database and SEER*Stat software to calculate sex-specific age-adjusted death rates (per 100 000 population) for the 15 leading causes of death among non-Hispanic AI/AN and non-Hispanic White people in the United States overall (all areas combined), by IHS Area, and by age group. We restricted analyses to non-Hispanic AI/AN and non-Hispanic White people living in Purchased/Referred Care Delivery Area counties. Death rates were higher among non-Hispanic AI/AN people than among non-Hispanic White people in the United States overall (rate ratio = 1.90) and in every IHS Area (rate ratio range = 1.11-2.78). Death rates also varied by sex and age. Death rates were nearly 4 times higher among non-Hispanic AI/AN people than among non-Hispanic White people in the 25- to 44-year age group. Leading causes of death among non-Hispanic AI/AN males and females included COVID-19, heart disease, unintentional injury, cancer, and chronic liver disease. Death rates differed between non-Hispanic AI/AN and non-Hispanic White people by IHS Area, sex, and age when data corrected for racial misclassification were used. Our findings have important implications for guiding future public health practice to address disparities in mortality, particularly in the context of public health emergencies.

There is a common chronic liver disease among adolescents, called non-alcoholic fatty liver disease. It is common among teenagers all over the world. This kind of liver disease is difficult to detect in the early stage, and the symptoms are not obvious, but long-term development will lead to liver evolution. And this liver disease can lead to insulin resistance and metabolic complications. However, the current medical direction is mainly targeted at adults, and there is still a lack of research on the causes and prevention mechanisms of adolescents. In fact, the liver metabolism of adolescents is very active, which will also lead to the immaturity of intestinal flora, so the mechanism of liver disease in adolescents is worth studying. This paper systematically introduced the prevalence of nonalcoholic fatty liver disease in adolescents and the data of high fructose intake, explained the relationship between high fructose intake and the incidence of nonalcoholic fatty liver disease, proposed intervention strategies at different levels for different age groups, analyzed the implementation problems faced by implementing these measures in reality, and summarized the possible research directions and prevention prospects in the future.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide and a major contributor to the global cardiometabolic burden. Early identification of patients at risk of metabolic dysfunction-associated steatohepatitis (MASH) and advanced fibrosis is essential to prevent liver-related and cardiovascular complications. In Spain, the burden of MASLD is increasing, yet information on routine clinical management by gastroenterologists remains limited. Methods: A nationwide cross-sectional online survey was conducted among members of the Spanish Society of Digestive Diseases (SEPD). The questionnaire explored five domains: MASLD knowledge, use of non-invasive biomarkers and imaging, awareness and implementation of clinical guidelines, cardiometabolic and alcohol-related risk assessment, and coordination with primary care. Results: A total of 429 specialists responded, 33.1% reported more than 20 years of practice and most worked in public hospitals, including 29.2% in large tertiary centers. Awareness of the MASLD definition was high, and 91.2% identified fibrosis as the main prognostic determinant. Non-invasive fibrosis biomarkers were widely used, whereas steatosis biomarkers were less frequently applied. Elastography was available to 96.1%. Guideline knowledge was reported by 80.4%, although implementation was lower. Cardiovascular risk evaluation varied: 75.1% reported systematic screening. Alcohol consumption was usually assessed. Coordination with primary care was limited: 91.1% expressed concerns regarding physicians’ familiarity with MASLD classification, and only 31.1% reported shared protocols. Conclusions: Spanish gastroenterologists show high awareness of MASLD and broad access to non-invasive diagnostic tools. However, important gaps remain in cardiovascular and alcohol risk assessment, guideline implementation, and coordination with primary care.

Introduction Fatty liver is a leading cause of chronic liver disease in children, most often due to metabolic dysfunction-associated steatotic liver disease (MASLD). Fatty liver in lean or younger children may indicate underlying metabolic or genetic disorders, such as familial hypobetalipoproteinemia (FHBL). We examined the importance of considering familial hypobetalipoproteinemia (FHBL) in children presenting with fatty liver. Methods This case series includes seven patients with FHBL from three families, treated at two medical centers. Clinical, laboratory, imaging, and genetic data were collected from the medical records. Results Four patients were male. The mean age at diagnosis was 15.3 years (range: 4–38). All the index patients were children or adolescents presenting with fatty liver. Genetic evaluation revealed biallelic variants in the microsomal triglyceride transfer protein ( MTTP ) gene in two siblings and heterozygous variants in the apolipoprotein B ( APOB ) gene in five patients. The mean body mass index was 27 kg/m 2 , and two patients had a BMI above 30 kg/m 2 . The median follow-up (FU) time was 12 months (interquartile range [IQR]: 1–57 months). Liver enzymes were elevated in three patients (range: 50–300 IU/L); median aspartate aminotransferase and alanine aminotransferase levels were 30 IU/L (IQR: 26–40.75) and 32 IU/L (IQR: 24.5–74), respectively. The median triglyceride, low-density lipoprotein, and apolipoprotein B levels were 74 mg/dL (IQR: 62–125), 55.3 mg/dL (IQR: 30–84.5), and 39.5 mg/dL (IQR: 35.2–43), respectively. Conclusion FHBL should be considered a potential diagnosis in children with fatty liver and may coexist with other contributing etiologies such as obesity.

ABSTRACT Background Bulevirtide (BLV) blocks hepatitis D virus (HDV) entry by targeting the sodium taurocholate co‐transporting polypeptide (NTCP). This study assessed the relationship between bile acid (BA) levels and antiviral response to BLV. Methods Serum BA levels were monitored in HDV‐infected patients pre‐, under, and post BLV treatment. Virologic response (VR) was defined by ≥ 2log 10 decline in HDV‐RNA and discriminated versus virologic non‐response (VNR). Delta BA levels (ΔBA) were calculated and analysed in relation to HDV‐RNA dynamics. Finally, the effect of BLV treatment cessation on BA was investigated. Results Twenty five patients (48% male; advanced chronic liver disease [ACLD]: 92.0%, 17 patients with VR at W48) were included. Median baseline BA levels were significantly higher in patients with ACLD and portal hypertension ( n = 10; 19.2 vs. 5.1 μmol/L; p = 0.015). No difference in median on‐treatment BA levels was detected between patients achieving VR or VNR at W24 (VR: 25.4 vs. VNR: 22.7 μmol/L; p = 1.000) and W48 (VR: 25.4 vs. VNR: 20.8 μmol/L; p = 1.000). Additionally, ΔBA from baseline to W48 did not differ between VR and VNR ( p = 0.534). No significant association between ΔBA and HDV‐RNA dynamics at W48 was detected. After BLV discontinuation, median BA levels significantly dropped to normal ranges (18.9 μmol/L at last on‐BLV assessment to 7.6 μmol/L after discontinuation; p = 0.028). On‐treatment BA levels did neither associate with self‐reported compliance nor with treatment‐related adverse events. Conclusion Bulevirtide increases bile acid levels in most patients, but ΔBA does not predict virologic response or adverse events, nor does it reflect compliance to therapy. Bile acid level monitoring during and following bulevirtide treatment is thus, not advised for clinical practise.

Decompensated cirrhosis carries a significant health burden with high mortality. The aim of this study was to assess incidence of further decompensation and survival in patients with cirrhosis following hospitalization with initial decompensation. Adult patients with cirrhosis at three Australian state-wide liver transplant centres from 2006 to 2025, admitted to hospital with a first decompensating event (ascites, hepatic encephalopathy, variceal bleeding) and followed until further decompensation requiring hospitalisation, liver-related death (LRD), non-liver related death, or liver transplant (LT). A total of 542 patients were followed from first decompensation for a median of 24 (IQR 9-48) months, with alcohol-related liver disease the most common etiology (52%). Cumulative incidence of further decompensation at 5-years was 65.1% (95% CI 60.3-69.5), and incidence of LRD or LT was 39.2% (95% CI 34.1-44.2). Following further decompensation, cumulative incidence of LRD or LT was higher compared to first decompensation at 55.5% (sHR 3.45, 95% CI 2.31-5.16, p < 0.001). Ascites was the most common type of further decompensation (35.6%, 95% CI 31-40.2). Etiological treatment of the underlying CLD was protective for further decompensation and LRD/LT (sub hazard ratio [sHR] 0.58 and 0.65 respectively, p < 0.05), as was treatment with a non-selective beta blocker (sHR 0.40 and 0.60, p < 0.01). This multi-centre study describes the trajectory of patients after a first episode of decompensation for the first time in the Australian context. It highlights high morbidity and poor prognosis associated with further decompensation with over 50% dying or requiring LT within 5 years.

Liver fibrosis, a common consequence of chronic liver diseases, currently lacks effective pharmacological interventions. Saikosaponin B1 (S-B1), a bioactive triterpenoid saponin isolated from Bupleurum chinense, has been shown to exhibit anti-inflammatory and hepatoprotective activities. This study aimed to evaluate the therapeutic potential of S-B1 in carbon tetrachloride (CCl4)-induced hepatic fibrosis and to elucidate its underlying mechanisms. A mouse model of liver fibrosis was established through sequential administration of diethylnitrosamine (DEN) and CCl4, followed by 2weeks of S-B1 treatment. Our results demonstrate that S-B1 significantly ameliorates liver injury, as evidenced by reduced serum ALT and AST levels, improved oxidative stress parameters, and restoration of hepatic histology with attenuated collagen deposition. Moreover, S-B1 downregulates the expression of key fibrogenic genes (Col1a1, Col4a4, TGF-β1, TIMP1), suppresses hepatic stellate cell (HSCs) activation, and reduces inflammatory cell infiltration and cytokine production. In vitro studies using TGF-β1-stimulated LX-2 cells confirm that S-B1 directly inhibits HSC activation, proliferation, and pro-inflammatory responses. Mechanistically, we identify a novel pathway mediating S-B1's anti-fibrotic effects: direct targeting of lactate dehydrogenase A (LDHA) to inhibit lactate production, coupled with concurrent downregulation of the lactate transporters monocarboxylate transporters 1 and monocarboxylate transporters 4. Genetic validation confirms LDHA as an essential target, as LDHA knockdown abrogates S-B1's anti-fibrotic efficacy. In conclusion, S-B1 effectively alleviates hepatic fibrosis by directly targeting HSCs and disrupting a central lactate-driven profibrogenic axis, highlighting its promise as a therapeutic candidate for liver fibrosis.