ABSTRACT Liver fibrosis is a common consequence of chronic liver injury and a major contributor to liver‐related mortality. Persistent hepatocellular injury promotes fibrosis initiation and progression through excessive extracellular matrix deposition. Hepatic stellate cells (HSCs), the principal source of extracellular matrix in the fibrotic liver, transition from a quiescent state to an activated myofibroblast‐like phenotype in response to profibrotic stimuli such as transforming growth factor‐beta. This transition is accompanied by transcriptional and epigenetic reprogramming involving DNA methylation, histone modifications, and regulation by non‐coding RNAs. Treating the underlying cause of liver disease, such as promoting weight loss in metabolic dysfunction‐associated steatohepatitis or eradicating viral hepatitis, remains the principal strategy for slowing or potentially reversing fibrosis. Despite substantial advances in understanding the cellular and molecular basis of liver fibrosis and HSC activation, most mechanism‐based therapeutic approaches have not yet demonstrated clinical efficacy. Further translational and clinical studies are therefore required. Recent advances in molecular biology have highlighted the potential relevance of epigenetic modifications to the diagnosis, treatment, and prognosis of chronic liver disease. In this review, we summarize the principal epigenetic changes involved in HSC activation, and initiation/progression of liver fibrosis. We also discuss recent interventions designed to modulate these epigenetic changes and evaluate their therapeutic potential in experimental models of liver fibrosis.
ABSTRACT Contrast‐enhanced ultrasonography (CEUS), enabled by microbubble‐based agents, provides a noninvasive alternative to the hepatic venous pressure gradient (HVPG) for assessing portal hypertension (PH) in cirrhosis. The HVPG is considered the “gold standard” for assessing portal vein pressure (PVP); however, its clinical application is limited by its invasive nature, high cost, and varying levels of detection technology. Therefore, there is a critical unmet need to develop a safe, reliable, convenient, and accessible noninvasive diagnostic method or means to diagnose and dynamically and accurately monitor PVP. Recently, with the rapid progress in digital technology and imaging modalities and the accessibility of microbubble‐based ultrasound contrast agents (UCAs), CEUS has shown great promise in the noninvasive assessment of PVP. Microbubble‐based UCAs not only perform well in the diagnosis and dynamic monitoring of PH but also have clinical significance in cirrhosis complications, monitoring the progression of PH, and identifying patients who respond to PH therapy. In this study, we summarize the principles, methods, diagnostic efficacy, and limitations of using microbubble‐based UCAs in CEUS for assessing PVP in patients with cirrhosis.
ABSTRACT Owing to the lack of suitable models, disease modeling and drug development and toxicity assessment for primary sclerosing cholangitis (PSC) face significant challenges. In recent years, major advances have been made in PSC disease modeling, rapid drug screening, and toxicity evaluation due to the development of organoid technology, gene editing, and bioengineering techniques. This review not only summarizes the pathogenesis and characteristics of PSC animal models but also details the latest progress in organoid models and engineered organoids. First, we introduce in vivo mouse models of PSC, which replicate bile stasis, biliary aging, and peribiliary inflammation, including gene‐edited mice (multidrug resistance‐related protein‐2 [ Mdr2 ]) and chemical models (3,5‐Diethoxycarbonyl‐1,4‐dihydroxyphenyl‐2,4,6‐collidine [DDC]‐fed). We subsequently discuss the characteristics and research progress of primary cholangiocytes, cell lines, cholangiocyte organoids, and engineered organoids. In summary, we emphasize the role of novel in vitro and in vivo models in simulating PSC disease progression, developing new drugs, and conducting toxicity assessments.
ABSTRACT Metabolic dysfunction‐associated steatotic liver disease (MASLD) and intrapancreatic fat deposition (IPFD) are key manifestations of ectopic fat accumulation that share metabolic pathophysiological links, but differ sharply in clinical research and practice. As a highly prevalent and burdensome chronic liver disease, MASLD has a well‐established research framework. Its diagnostic criteria, risk factors, detection methods, pathophysiology and complications are well‐characterized, with a globally recognized consensus. Artificial intelligence (AI) can facilitate MASLD management, including screening, staging, and prognosis, and approved drugs have been shown to improve outcomes and slow disease progression. In contrast, in the context of IPFD, AI must first address the issue of pancreatic segmentation to meet the requirements for subsequent fat quantification. Owing to its retroperitoneal location, fat‐deposition heterogeneity, and limited understanding of its clinical impact, IPFD lacks universal diagnostic criteria, standardized assessments, and targeted therapies. This review summarizes the latest evidence on MASLD and IPFD, covering fat‐deposition pathology, diagnosis, risk factors, complications, and advances in AI applications and drug therapy; clarifies their similarities and differences; and urges the establishment of standardized diagnostics for IPFD. It also proposes “personalized therapy integrated with the liver‐pancreas axis” to balance disease‐specific traits and inter‐organ interactions, offering new insights for IPFD management.
A 60-year-old man presented with recurrent stomal bleeding for 3 years. He had undergone cystoprostatectomy with ileal conduit diversion for bladder cancer 7 years prior. Endoscopy revealed multiple protruding lesions (0.6-0.8 cm) inside the stoma, which were initially suspected to be ectopic varices given concomitant esophageal varices and splenomegaly. Baseline liver function, renal function and coagulation profiles were all normal. Hemodynamic assessments showed a normal hepatic venous pressure gradient of 4 mmHg but an elevated portal pressure gradient (PPG) of 15 mmHg. Portal vein stenosis, incomplete septal fibrosis, portal tract vascular congestion, and abnormal periportal vessels without pseudolobule formation were founded in liver biopsy, confirming the diagnosis of porto-sinusoidal vascular disorder (PSVD). Transjugular intrahepatic portosystemic shunt (TIPS) combined with variceal embolization was thereafter performed, reducing PPG to 5 mmHg. At 12-month follow-up, no stomal bleeding recurrence occurred, and the stent patency was maintained. This case suggests that PSVD needs to be considered in patients with non-cirrhotic portal hypertension, and ectopic varices merit attention in the setting of portal hypertension.
Aims Elastography is an important noninvasive method for diagnosing advanced fibrosis (AF); however, evidence remains insufficient, particularly for acoustic radiation force impulse (ARFI) techniques. This research aims to evaluate the diagnostic performance and the optimal cutoff values of four ultrasound-based elastography techniques for detecting AF in patients with chronic liver disease (CLD), and to assess the agreement among these methods in measuring liver stiffness (LS). Methods Adult inpatients with suspected or confirmed CLD who were scheduled for ultrasound-guided liver biopsy were prospectively and consecutively enrolled from the hepatology departments of four institutions in Nanjing, Changzhou, and Xuzhou. Agreement in LS measurements among the four elastography techniques was assessed using Bland-Altman analysis. Diagnostic performance for AF was evaluated using receiver-operating characteristic (ROC) curve analysis, and comparisons were made using Delong's test. Optimal cutoff values for AF detection were determined using Youden's index with the bootstrap resampling. Results A total of 209 patients with CLD were included, 148 in the main cohort and 61 in the external validation cohort. The main cohort had a median age of 52.0 years (interquartile range [IQR], 12.0) and a median body mass index (BMI) of 24.59 kg/m2 (IQR, 5.88). AF was diagnosed in 34 patients, corresponding to a prevalence of 23.0% (34/148). LS values measured by ARFI techniques were significantly lower than that obtained by vibration controlled transient elastography (VCTE). The mean differences were -3.82 kPa (95% confidence interval [CI], -4.59 to -3.04 kPa) for point shear wave elastography (pSWE), -3.68 kPa (95% CI, -4.52 to -2.83 kPa) for auto-pSWE, and -4.27 kPa (95% CI, -5.17 to -3.38 kPa) for two-dimensional shear wave elastography (2D-SWE). For the diagnosis of AF in the main cohort, VCTE demonstrated the highest diagnostic accuracy, with an area under the ROC curve of 0.842 (95% CI, 0.773-0.896), significantly outperforming all other ultrasound-based elastography techniques (0.713 [95% CI, 0.633-0.785] for pSWE, 0.685 [95% CI, 0.604-0.759] for auto-pSWE, and 0.728 [95% CI, 0.649-0.798] for 2D-SWE; all p < 0.05). The optimal cutoff values for diagnosing AF in the main cohort was >= 12.0 kPa for VCTE, >= 5.5 kPa for pSWE, >= 8.2 kPa for auto-pSWE, and >= 8.9 kPa for 2D-SWE. External validation and subgroup analysis confirmed the superior performance of VCTE for diagnosing AF in those with hepatic steatosis. Conclusion In this mixed-etiology cohort, VCTE exhibited superior diagnostic performance compared with pSWE, auto-pSWE, and 2D-SWE for the detection of AF in patients with CLD. Choice should also consider device availability, and patient factors.Trial Registration Chinese Clinical Trial Registry at https://www.chictr.org.cn/ (registration number ChiCTR2400090256).
Aims Conventional fixed-caliber transjugular intrahepatic portosystemic shunt (TIPS) stents may limit individualized portal decompression and lead to over- or under-shunting. We therefore aimed to evaluate the safety and performance of a novel controlled-expansion expanded polytetrafluoroethylene (ePTFE)-covered TIPS stent, which is designed for precise placement, secure anchoring, and on-demand diameter adjustment. Methods Eleven healthy swine (40-50 kg) underwent TIPS with a self-expanding nitinol stent-graft comprising a covered intrahepatic segment and an uncovered portal segment, with balloon-calibrated diameter adjustment across 6.0-10.0 mm; all stents were post-dilated to a fixed 8.0-mm functional diameter. Animals were assigned to 1- (n = 3), 3- (n = 3), or 6-month (n = 5) endpoints. Patency was defined as < 50% diameter stenosis without angiographic occlusion. Patency and integrity were assessed by digital subtraction angiography with quantitative vascular angiography (QVA). Systemic and local responses were evaluated by clinical monitoring, hematology/serum biochemistry, comprehensive necropsy, and blinded histopathology. Results Technical success rate was 100% in all 11 cases, with no intraoperative complications; all animals survived to endpoint. Deployment, visibility, and handling were consistently excellent. Follow-up angiography showed patent shunts without migration, thrombosis, or fracture; no collapse, kinking, or ePTFE delamination. QVA demonstrated mild luminal loss: mean diameter stenosis was 4.88 (3.13-7.19)% at 1 month, 9.93 (7.30-14.09)% at 3 months, and 13.41 (12.05-16.05)% at 6 months; all shunts showed < 30% stenosis. Laboratory values remained within or returned to normal limits. Necropsy confirmed well-incorporated tracts without device-related pathology. Histology showed complete endothelialization, a thin neointima with minimal inflammation, and absence of thrombosis at all time points. Conclusions In healthy swine, this stent demonstrated favorable safety and patency; performance in portal hypertension remains to be established. This adjustable-caliber design may help overcome some limitations of fixed-diameter stents and supports further evaluation in disease models and humans.
Aims Esophagogastric variceal bleeding (EGVB) is a life-threatening complication associated with cirrhosis and portal hypertension. Although endoscopic treatment is central to EGVB management, evidence of its effectiveness in acute-on-chronic liver failure (ACLF) remains limited because of severe coagulation and multi-organ dysfunction. This study aims to evaluate the efficacy of endoscopic treatment in ACLF patients with EGVB and identify prognostic factors associated with 6-week rebleeding and mortality.Methods In this single-center retrospective cohort study, we analyzed 106 patients with ACLF experiencing an EGVB episode between January 1, 2021, and June 30, 2024. Patients were categorized into endoscopic and non-endoscopic treatment groups. Endoscopic treatment was performed within 12 to 24 h after admission once hemodynamic stability was achieved. The primary outcomes were 6-week rebleeding rate and 6-week all-cause mortality, and the secondary outcome was bleeding-related mortality. Multivariable logistic regression was used to identify risk factors for early rebleeding (72 h to 6 weeks), 6-week mortality, and hemorrhage-related death.Results Early rebleeding occurred in 36.8% (39/106) of patients. Moderate-to-severe ascites independently predicted early rebleeding (odds ratio [OR] = 3.379, 95% confidence interval [CI], 1.376-8.300, p = 0.008). By contrast, endoscopic treatment was a protective factor (OR = 0.266, 95% CI, 0.108-0.657, p = 0.004). The early rebleeding rate was significantly lower in the endoscopic group (26.8%, 19/71) compared to the non-endoscopic group (57.1%, 20/35; p = 0.002). The 6-week mortality was 46.2% (49/106) and was associated with moderate-to-severe ascites (OR = 2.587, 95% CI, 1.043-6.418, p = 0.040) and elevated total bilirubin level (OR = 1.004, 95% CI, 1.001-1.008, p = 0.012). First bleeding was a protective factor (OR = 0.304, 95% CI, 0.120-0.772, p = 0.012). Endoscopic treatment did not significantly affect overall survival (p = 0.734) but reduced hemorrhage-related mortality (OR = 0.186, 95% CI, 0.040-0.857, p = 0.031). Among the 49 deaths, 20 were attributed to gastrointestinal hemorrhage and 29 to other causes, primarily severe infections (n = 12), hepatic encephalopathy (n = 7), and renal failure (n = 7). Portal vein thrombosis (PVT) was independently associated with bleeding-related death regardless of whether endoscopic treatment was performed (OR = 8.262, 95% CI, 1.514-45.092, p = 0.015).Conclusion In ACLF patients with EGVB, moderate-to-severe ascites was the key predictor of early rebleeding and 6-week mortality. Endoscopic therapy reduced early rebleeding and hemorrhage-related death but did not improve overall survival; higher total bilirubin levels, prior bleeding, and PVT may further identify high-risk patients.
ABSTRACT The global landscape of liver cirrhosis has undergone a significant transformation with the widespread implementation of viral vaccines, and metabolic dysfunction‐associated steatotic liver disease (MASLD) cirrhosis has emerged as a predominant etiology. Given the differences in the pathogenic mechanisms between viral and MASLD cirrhosis, conventional diagnostic and therapeutic strategies for viral cirrhosis have demonstrated limited applicability in MASLD cirrhosis. The pathogenesis of MASLD cirrhosis involves multifaceted interactions between metabolic dysregulation, inflammatory responses, immune dysregulation, and gut–liver axis disruption, presenting substantial challenges in clinical management. Although liver biopsy remains the gold standard for diagnosis, complications, including hemorrhage, infection, pain, and pneumothorax, lead to suboptimal patient compliance, thereby prompting the development of various noninvasive diagnostic tools. Current therapeutic approaches primarily target key pathological mechanisms through metabolic regulation of glucose and lipid homeostasis, inflammation control, and microbial balance restoration. This review summarized the epidemiological transition from viral to MASLD cirrhosis and aimed to provide a conceptual framework for optimizing diagnostic and therapeutic strategies in the MASLD era.
ABSTRACT Metabolic dysfunction‐associated steatotic liver disease (MASLD) is a leading cause of liver‐related morbidity and mortality worldwide. Hyperuricemia, characterized by elevated levels of uric acid, is increasingly recognized as a key mediator linking metabolic dysfunction to liver and systemic complications. Elevated uric acid levels have been frequently observed in patients with MASLD, and there is growing evidence that hyperuricemia is not merely a byproduct but also an active factor involved in the pathogenesis of MASLD and its associated comorbidities. Recent studies have shown a significant correlation between elevated uric acid levels and the severity of liver disease in patients with MASLD, with higher uric acid levels associated with increased liver fat content and more severe histological features. Moreover, hyperuricemia has been identified as an independent predictor of adverse outcomes in MASLD, including the development of hepatocellular carcinoma (HCC) and liver‐related mortality. The relationship between uric acid and MASLD is multifaceted and involves several pathophysiological pathways, including inflammation and oxidative stress, which are critical factors in the development of liver steatosis and fibrosis. Therefore, in this study, we review the relevant progress in MASLD research, outline the concept and epidemiology of MASLD, discuss the correlation between changes in uric acid levels and the prognosis of patients with MASLD and the potential underlying mechanism, and consider future improvements in its clinical diagnosis and treatment. The goal of this review is to provide a reference for scientific research and clinical practice to promote a more in‐depth understanding of the disease and more effective clinical management.
ABSTRACT Aims Accurate noninvasive fibrosis staging is essential in chronic liver disease (CLD). Although both FibroTouch and FibroScan are widely used, differences in technical design may affect measurement consistency. Whether their diagnostic thresholds for liver fibrosis are interchangeable remains unclear. The study aims to compare their diagnostic performance and threshold agreement in a biopsy‐confirmed CLD cohort. Methods This single‐center, cross‐sectional study included 339 patients with biopsy‐confirmed CLD from February 2014 to March 2019, all of whom underwent biochemical testing, FibroTouch, and FibroScan. Diagnostic performance was evaluated using the area under the receiver operating characteristic curves (AUROCs). Univariable and multivariable linear models were used to identify factors associated with inter‐device liver stiffness measurement (LSM) differences. Misclassification was calculated using manufacturer‐recommended thresholds. Subgroup analysis was conducted among patients with metabolic dysfunction–associated fatty liver disease (MAFLD). Results Both devices showed excellent diagnostic performance for detecting fibrosis ≥ F2, ≥ F3, and F4, with AUROCs exceeding 0.900, outperforming the fibrosis‐4 index (FIB‐4) and aspartate aminotransferase‐to‐platelet ratio index (APRI) in the entire cohort (FIB‐4 AUROCs: 0.775, 0.801, and 0.815; APRI AUROCs: 0.771, 0.754, and 0.749; all p < 0.001). FibroTouch required higher LSM thresholds than FibroScan at ≥ F2 (9.8 vs. 8.5 kPa) and ≥ F3 (13.1 vs 11.5 kPa). Cirrhosis (β: −4.144, p = 0.001), Grade 4 hepatic inflammation (β: −6.257, p = 0.001), and elevated alkaline phosphatase (β: −0.004, p = 0.007) were independently associated with inter‐device discordance. Misclassification rates were 36.9% (125/339) for FibroTouch and 32.2% (109/339) for FibroScan, primarily due to overestimation. In the MAFLD subgroup (n = 113), diagnostic accuracy remained high (AUROCs > 0.910), but threshold gaps widened further. Conclusion FibroTouch and FibroScan provide comparable diagnostic accuracy for fibrosis staging in CLD. However, they are not interchangeable, and the use of device‐specific thresholds is mandatory to reduce misclassification, especially in patients with MAFLD.
ABSTRACT Aims Thrombocytopenia and antiangiogenic agents increase bleeding risk in hepatocellular carcinoma (HCC). We aimed to identify a baseline platelet threshold for bleeding risk stratification. Methods This single‐center retrospective cohort included 489 HCC patients treated with antiangiogenic agents from January 2018 to June 2022 without prophylactic platelet‐increasing interventions. Bleeding events were defined using International Society on Thrombosis and Hemostasis criteria. Fine and Gray competing‐risk models were used to explore platelet‐count cutoffs associated with bleeding. Associations were assessed with logistic regression and Chi‐square/Fisher's exact tests, adjusting for key confounders including high‐risk esophageal and gastric varices (EGV). Severe thrombocytopenia was defined as baseline platelets < 50 × 109/L. Results The bleeding rate was 11.0% (54/489). Baseline platelet counts were lower in patients with bleeding than in those without (median 116 × 109/L vs. 140 × 109/L; p = 0.015). Bleeding was more frequent with severe thrombocytopenia (< 50 × 109/L) than with platelet counts ≥ 50 × 109/L (22.9% [8/35] vs. 10.1% [46/454]; p = 0.021). Although platelet count < 50 × 109/L was associated with bleeding in univariable analyses, it was not independently predictive after multivariable adjustment; high‐risk EGV remained the dominant independent risk factor. Conclusion Baseline platelets < 50 × 109/L is a useful risk‐stratification marker (not an independent predictive biomarker) for bleeding during antiangiogenic therapy in HCC, and this threshold should be interpreted alongside variceal risk assessment, particularly in patients with high‐risk EGV.
Accurate differentiation between benign and malignant focal liver lesions (FLLs) remains a major diagnostic challenge. Vasomics, an emerging discipline, classifies vascular phenotypes into anatomical, biomechanical, biochemical, pathophysiological, and composite categories. Sono-Vasomics, the ultrasound-based subset, leverages super-resolution contrast-enhanced ultrasound (SR-CEUS) for real-time microvascular phenotyping. A 32-year-old male patient presented to our hospital with multiple large hepatic masses for ultrasound examination. On B-mode ultrasound, the lesion appeared as multiple large, well-defined hypoechoic masses with heterogeneous echogenicity. SR-CEUS revealed thick, straight, non-tortuous vessels with regular branching and homogeneous perfusion. Quantitative Sono-Vasomics based on SR-CEUS demonstrated vessel density 21.74%, flow-weighted density 10.55, fractal dimension 1.51, velocity variance 172.98, direction variance 2672.52, and perfusion index 4.48. Mapping these values to vasomics categories identified benign anatomical and biomechanical vascular phenotypes, excluding malignancy and suggesting hepatic adenoma. Based on the gene sequencing results confirming glycogen storage disease type Ia (GSD Ia), together with the clinical and laboratory findings of fasting hypoglycemia, hyperuricemia, hyperlactatemia, and hypertriglyceridemia, as well as a history of hepatomegaly, the patient was ultimately diagnosed with hepatic adenoma. In this case, quantitative vascular phenotyping helped accurately characterize hepatic adenoma and may reduce misdiagnosis. By aligning imaging-derived vascular phenotypes with the vasomics framework, Sono-Vasomics provides a clinically feasible implementation of vasomics and suggests the potential value of integrating imaging and genomics in hepatology.
Metabolic dysfunction-associated steatotic liver disease（MASLD）has become one of the leading causes of chronic liver diseases in China and even globally. Early non-invasive diagnosis and grading MASLD，along with timely intervention，are crucial for assessing the disease condition and slowing the disease progression. In recent years，non-invasive techniques for assessing liver steatosis content based on ultrasound have attracted significant attention. The ultrasound derived fat fraction（UDFF）is an emerging quantitative technique for liver fat assessment using ultrasound，which calculates the percentage value of the fat content by analyzing the radiofrequency signals reflected from the liver tissue，thereby quantifying the degree of liver steatosis. UDFF shows significant potential in assessing liver steatosis. However，the current application guidelines based on this technology do not yet fully meet the clinical needs. To further standardize its clinical application，institutions such as the Ultrasound Medicine Branch of the Chinese Medical Association，the National Clinical Research Center for Aging and Medicine，and the Institute of Ultrasound Medicine and Engineering of Fudan University，together with multidisciplinary experts ultrasound，endocrinology，radiology，and hepatology from across China have formulated this "Chinese expert consensus on the use of ultrasound derived fat fraction in the assessment of metabolic dysfunction-associated steatotic liver disease（2025 edition）" based on the lastest clinical application advances of the UDFF technology. This consensus standardizes the clinical scope of application and scenarios of this technology. It optimizes the technical operation process in various aspects，including pre- examination preparation，the operation process，quality control，the number of measurements，result presentation format，and influencing factors as well. Meanwhile，it summarizes current clinical research results，aiming to ensure the standardization of the UDFF technology in clinical applications.
Primary liver cancer remains a significant global public health challenge, characterized by persistently high incidence and mortality. This review synthesizes current epidemiological data to analyze trends and etiological shifts, with particular emphasis on China, which bears over 40% of the global burden. Findings highlight a transition in dominant risk factors from viral hepatitis to metabolic dysfunction-associated steatotic liver disease (MASLD), alongside persistent threats from aflatoxin exposure and lifestyle behaviors. Evidence-based prevention strategies, including universal hepatitis B virus (HBV) vaccination, antiviral therapy expansion, aflatoxin control, and early metabolic intervention, are critical to reducing disease burden. The integration of artificial intelligence into screening and management represents a promising advancement. A multi-faceted approach combining vaccination, surveillance, lifestyle modification, and technological innovation is essential for effective global liver cancer control.
ABSTRACT Liver cirrhosis is the end stage of various chronic liver diseases, which is mainly divided into compensated stage and decompensated stage. Portal hypertension (PH) is a key factor leading to the progression from compensated to decompensated liver cirrhosis. Non‐selective beta‐blockers (NSBBs), as the cornerstone drugs for reducing portal vein pressure, have been widely used in the prevention and management of liver cirrhosis and PH‐related complications in recent years. This review summarizes the mechanisms, clinical efficacy, and controversies of NSBBs in the prevention of variceal bleeding, the management of ascites, and the prophylaxis of hepatocellular carcinoma. Further efforts are needed to optimize the indications for NSBBs and develop individualized treatment strategies.
ABSTRACT Aims Metabolic dysfunction‐associated steatotic liver disease (MASLD) is a chronic liver disease closely associated with metabolic dysfunction. Research into a feasible, rapid, and effective assessment method is crucial for evaluating the therapeutic effects of semaglutide in MASLD. This study aims to explore the fast quantitative evaluation of the amelioration effect in MASLD during semaglutide therapy using ultrasound‐derived fat fraction (UDFF) and fat‐to‐muscle ratio (FMR). Methods This prospective study enrolled patients diagnosed with MASLD who were planned to be treated with subcutaneous injection of semaglutide. All patients underwent UDFF measurements (six acquisitions for each patient) using the Acuson Sequoia ultrasound system (Siemens Healthineers, Mountain View, USA) to assess hepatic steatosis before and 14 ± 2 weeks after treatment. Body composition (body weight, visceral fat area, percent body fat, waist circumference, waist‐to‐hip ratio, skeletal muscle mass index, and FMR) was analyzed by phase‐sensitive bio‐impedance. FMR was obtained to evaluate the ratio of fat mass to skeletal muscle mass. The Spearman correlation was performed to compare clinical, ultrasound parameters, and serum biomarkers. Results From July 2023 to June 2024, 22 patients (77.3% female) were included, with a median body mass index of 32.6 kg/m2. Semaglutide treatment resulted in a median weight loss of 7.5 kg from baseline. Most patients (19/22, 86.3%) achieved a significant weight reduction (weight loss ≥ 5%). Specifically, four patients had a weight loss of ≥ 5% and < 7%, nine patients had a weight loss of ≥ 7% and < 10%, and six patients had a weight loss of ≥ 10%. UDFF values were significantly decreased at follow‐up compared with those at baseline (9.4% vs. 21.8%; p < 0.001) and reached the highest reduction (49.4%). UDFF values were positively correlated with body composition at baseline (r = 0.33–0.54) and follow‐up (r = 0.30–0.65). The reduction of FMR (13.1%) was the second highest among body composition measures, after that of visceral fat area (17.3%). FMR values had a high correlation with visceral fat area at both baseline and follow‐up (r = 0.70 and r = 0.80, respectively, both p < 0.001). Conclusion UDFF and FMR values could be used as fast quantitative tools for assessing hepatic steatosis and myosteatosis in MASLD during semaglutide therapy.
ABSTRACT Aims Metabolic dysfunction‐associated steatotic liver disease (MASLD) is common among morbidly obese patients, but data on non‐invasive tests (NITs)' accuracy for liver fibrosis assessment are limited. We aimed to validate NITs for predicting liver fibrosis and post‐bariatric surgery outcomes. Methods This single‐tertiary‐center retrospective cross‐sectional study with longitudinal follow‐up included morbidly obese adults with biopsy‐proven MASLD undergoing bariatric surgery (laparoscopic Roux‐en‐Y gastric bypass [LRYGB] or laparoscopic sleeve gastrectomy [LSG]) between January 2011 and December 2022. Follow‐up exceeded 1 year. The primary outcome was NITs' performance in predicting liver fibrosis, including liver stiffness measurement (LSM), fibrosis‐4 (FIB‐4), non‐alcoholic fatty liver disease (NAFLD) fibrosis score (NFS), aspartate aminotransferase (AST) to platelet ratio index (APRI), and body mass index (BMI), AST/alanine aminotransferase (ALT) ratio and diabetes (BARD) scores. Secondary outcomes included biochemical and anthropometric changes. Data were compared using χ2 test, t‐test, or Wilcoxon tests as appropriate. The predictive performance of NITs was evaluated using receiver‐operating characteristics curve, and changes during follow‐up were assessed with paired tests. Results Among 193 patients (103 [53.4%] female, mean age 36.3 ± 10.9 years, mean BMI 47.70 ± 14.40 kg/m2, 78 [40.4%] with diabetes), 58 (30.1%) had liver fibrosis (≥ F1), and 10 (5.2%) had significant fibrosis (≥ F2). NITs showed low diagnostic accuracy for liver fibrosis (area under the receiver‐operating characteristics curve [AUROC]s: LSM 0.38, FIB‐4 0.59, NFS 0.53, APRI 0.50, BARD 0.51). After a median follow‐up of 1.9 years, LSM significantly decreased post‐surgery (7.80 to 5.50 kPa, p < 0.001). APRI and NFS improved (0.21 to 0.18, –0.773 to –1.395, p < 0.001), while FIB‐4 and BARD scores increased (0.52 to 0.60, 2 to 3, p < 0.001) over a median follow‐up of 2.9 years. Anthropometrically, over a median postoperative follow‐up of 2.9 years, BMI decreased significantly (47.70 to 35.05 kg/m2, p < 0.001). LRYGB had a higher percentage of total weight loss (%TWL) than LSG (30.8% vs. 28.5%, p = 0.040). Biochemical parameters (AST, ALT, platelets, glycated hemoglobin [HbA1C], low density lipoprotein [LDL]‐cholesterol, and triglycerides) improved significantly post‐surgery (all p < 0.001). Subgroup analysis (n = 27) showed LSM improvement of > 20% correlated with %TWL > 30% (p = 0.041). Conclusion Bariatric surgery improved long‐term clinical/biological outcomes, although NITs demonstrated poor diagnostic accuracy for baseline liver fibrosis. Research is needed to assess new NITs for monitoring liver fibrosis in morbidly obese patients.
ABSTRACT Aims The tolerance of patients with compensated hepatitis B cirrhosis to interferon (IFN) therapy remains controversial. Therefore, this study aimed to evaluate the safety of pegylated interferon‐alpha in chronic hepatitis B (CHB) patients with compensatory cirrhosis. Methods Data from two prospective cohorts (the OASIS Project and CHESS 2306) from January 2018 to January 2024 were synthesized and analyzed. Patients with Child‐Pugh Class A hepatitis B cirrhosis who received IFN‐based therapy (n = 920) were included. The control groups included patients with compensated hepatitis B receiving nucleos(t)ide analog (Nuc) monotherapy (n = 714) and patients without cirrhosis receiving IFN‐based therapy (n = 4111), respectively. Propensity score matching was used to control for confounding factors; 566 versus 566 cases were analyzed among patients with cirrhosis treated with IFN‐based therapy or Nuc monotherapy, and 785 versus 785 cases were analyzed among patients with and without cirrhosis treated with IFN‐based therapy. Primary outcomes included decompensation events, and secondary outcomes included severe adverse events, overall adverse events, and treatment‐related hospitalizations or deaths. Results In patients with hepatitis B virus‐related cirrhosis, the incidence of decompensation events was similar between IFN‐based therapy and Nuc monotherapy (6/566 [1.1%] vs. 3/566 [0.5%], p = 0.506). No hospitalizations or deaths were associated with adverse events during the observation period (48 weeks). The incidences of severe adverse events were similar in patients with cirrhosis under IFN‐based therapy or Nuc monotherapy (severe neutropenia: 1/450 [0.2%] vs. 0/378 [0], p = 0.999; severe thrombocytopenia: 4/435 [0.9%] vs. 0/296 [0], p = 0.153; severe alanine aminotransferase level elevation: 1/523 [0.2%] vs. 1/458 [0.2%], p = 0.999; and severe total bilirubin [TBIL] level elevation: 5/419 [1.2%] vs. 3/385 [0.8%], p = 0.727). The incidences of severe adverse events were similar between patients with and without cirrhosis receiving IFN‐based therapy, except that severe TBIL level elevation was more frequent in patients with cirrhosis who already had mildly to moderately elevated TBIL levels at baseline than in those without (6/153 [3.9%] vs. 0/118 [0], p = 0.040). Conclusion IFN‐based therapy demonstrates favorable safety in Child‐Pugh A compensated cirrhosis. It did not increase decompensation events or severe adverse events compared to Nuc monotherapy, and adverse event profiles were largely similar between cirrhotic and non‐cirrhotic patients, except for a higher risk of severe hyperbilirubinemia in those with pre‐existing TBIL elevation. ClinicalTrials.gov identifier: NCT04896255. Chinese Clinical Trial Registry number: ChiCTR2500107592.
