Randomized controlled trials (RCTs) have been conducted to evaluate treatment efficacy for metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis. This study aimed to compare the effectiveness and safety of 11 promising targets among adults with MASLD.

PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, Scopus, and Embase were searched from inception to November 20, 2024. The primary outcomes were fibrosis improvement ≥1 stage without worsening of steatohepatitis and steatohepatitis resolution without worsening of fibrosis. Additional outcomes included reductions in liver fat content, liver enzymes, metabolic profiles, and selected safety outcomes. The surface under the cumulative ranking curve (SUCRA) was used to rank efficacy.

Of 11,584 articles screened, 44 eligible RCTs (11,410 participants, 33 medications) were included. For fibrosis improvement, d-(R)-pioglitazone (SUCRA: 79.3) and fibroblast growth factor (FGF) 21 analogs (SUCRA: 71.9) ranked higher. For steatohepatitis resolution, glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) dual receptor agonists (RAs) (SUCRA: 91.7) ranked higher. Co-agonists of GLP-1/GIP/GCG and GLP-1/GCG receptors ranked higher for relative and absolute changes in liver fat content, respectively. For liver enzymes and glucose improvement, the combination of a GLP-1 RA and an acetyl-coenzyme A carboxylase inhibitor ranked higher. GLP-1 RAs, peroxisome proliferator-activated RAs, and FGF21 analogs showed favorable effects on lipid profile improvement.

Incretin-based co-agonists and FGF21 analogs showed favorable profiles across key endpoints, while d-(R)-pioglitazone and GLP-1/GIP dual RAs ranked higher for fibrosis improvement and steatohepatitis resolution, respectively. SUCRA rankings should be interpreted in conjunction with effect sizes, uncertainty, and available safety data.

Hepatic sinusoidal obstruction syndrome (HSOS) is a life-threatening liver vascular disorder with limited treatment options. HSOS results from the activation and injury of liver sinusoidal endothelial cells (LSECs). Berberine (BBR) has been shown to protect endothelial cells in various diseases. However, whether BBR can alleviate liver injury and LSEC disruption in HSOS remains unclear. In this study, we aimed to evaluate the effect of BBR on HSOS.

Two mouse models of HSOS were established using monocrotaline or oxaliplatin. Mice in the treatment groups received a low dose (100 mg/kg) or a high dose (200 mg/kg) of BBR daily. Histology, scanning electron microscopy, immunofluorescence, and flow cytometry were used to evaluate the therapeutic effects of BBR. Cell co-culture, Transwell assays, qRT-PCR, and Western blotting were performed to investigate the molecular pathways involved.

BBR treatment dose-dependently reduced liver injury and disruption of LSECs in murine HSOS models. Moreover, BBR significantly reduced hepatic neutrophil infiltration, thereby attenuating neutrophil-mediated injury to LSECs. Additionally, BBR inhibited the effect of injured LSECs on neutrophil activation. Mechanistically, injured LSECs were identified as one of the major sources of CXCL1 in HSOS, and BBR downregulated CXCL1 expression in injured LSECs by inhibiting MAPK signaling.

In this study, we demonstrate that BBR ameliorates HSOS by inhibiting endothelial-mediated neutrophil recruitment and activation. BBR may be a promising therapeutic option for HSOS treatment.

The impact of baseline liver fibrosis severity on the effectiveness of pegylated interferon (Peg-IFN) combined with nucleos(t)ide analogs (NAs) in the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) has not been fully clarified. This study aimed to investigate whether the effectiveness of this combination therapy differed according to the severity of baseline liver fibrosis.

A total of 172 HBeAg-positive CHB patients receiving Peg-IFN plus NAs were stratified according to non-invasive fibrosis markers (aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 index [FIB-4]) into three groups: no significant fibrosis (n = 75), significant fibrosis (n = 70), and advanced fibrosis/cirrhosis (n = 27). The primary outcome was the HBeAg clearance rate at 24 months of treatment. Secondary outcomes included the hepatitis B surface antigen (HBsAg) clearance rate, the rate of HBsAg level decline > 1.0 log10, virological response, and improvement in non-invasive fibrosis indices.

At 24 months, HBsAg clearance and complete virological response rates were comparable across the three groups. Cumulative HBeAg clearance rates differed significantly (log-rank P = 0.027): 16.00%, 30.00%, and 40.74% in the three groups, respectively, with Group 3 higher than Groups 1 and 2. Multivariate analysis identified a significantly higher likelihood of HBeAg clearance in Group 3 versus Group 1 (adjusted odds ratio = 6.373, 95% confidence interval: 1.288–31.531, P = 0.023). Additionally, analysis of liver fibrosis outcomes showed that patients with more severe baseline fibrosis had a higher proportion of improvement in non-invasive fibrosis indices, with 95.00% in Group 3, while 42.98% of the overall cohort achieved fibrosis improvement.

Baseline fibrosis severity is associated with higher HBeAg clearance and greater improvement in non-invasive fibrosis indices during Peg-IFN plus NAs therapy in HBeAg-positive CHB.

Nitric oxide (NO) is a crucial regulator of hepatic and systemic vascular tone. Abnormal distribution of NO in various anatomical locations is a pathogenetic characteristic of portal hypertension. Under normal portal pressure conditions, liver sinusoidal endothelial cells produce NO, which promotes both vasodilation and hepatic stellate cell relaxation. In portal hypertension, endothelial dysfunction, imbalance of asymmetric dimethylarginine levels, and production of superoxide result in impaired intrahepatic NO availability, leading to activation and contraction of hepatic stellate cells and worsening portal hypertension. Excess extrahepatic NO levels in the splanchnic vasculature result in systemic vasodilation, hyperdynamic circulation, and collateral vascular formation, worsening portal pressure. Abnormal clearance and production of NO can lead to extrahepatic complications, including hepatorenal syndrome and hepatopulmonary syndrome. Therapies including statins, phosphodiesterase-5 inhibitors, and midodrine have been developed to restore NO homeostasis but have achieved only partial success in modulating NO production, bioavailability, and distribution. The aim of this review is to update the understanding of the mechanisms and effects of NO dysregulation in cirrhosis as they relate to current and future therapeutic options.

In contemporary practice, elevated 24-hour urinary copper excretion (24-h UCE) often triggers referral for suspected Wilson disease (WD). In this hypercupriuric referral setting, interpretation of 24-h UCE may be distorted by spectrum effects. In this study, we aimed to compare conventional copper biomarkers in hypercupriuric referrals and evaluate whether a Leipzig-aligned ceruloplasmin (Cp) framework could provide a clinically useful triage approach.

We retrospectively studied consecutive, untreated patients evaluated for suspected WD with hypercupriuria between February 2017 and February 2025. The final diagnosis was established using a prespecified Leipzig-based algorithm, with ATP7B testing when indicated. Diagnostic performance of Cp and 24-h UCE was compared. A prespecified Cp three-zone framework was evaluated using <0.10 g/L, 0.10–0.20 g/L, and >0.20 g/L as high-probability, indeterminate, and low-probability zones, respectively.

Among 541 untreated hypercupriuric patients, 65 had WD and 476 had adjudicated non-WD liver disease. Cp outperformed 24-h UCE for diagnosing WD (AUROC, 0.988 vs. 0.762). The optimal Cp cutoff was 0.15 g/L, with 90.8% sensitivity and 97.7% specificity. Cp < 0.10 g/L defined a high-probability zone with 98.0% WD prevalence, whereas Cp > 0.20 g/L defined a low-probability zone with 0.5% WD prevalence. Among non-WD controls, higher urinary copper was independently associated with higher bilirubin, prolonged international normalized ratio, and lower albumin.

In hypercupriuric referrals for suspected WD, Cp retained strong diagnostic performance and outperformed 24-h UCE. A Leipzig-aligned Cp three-zone framework may support probability-based triage in contemporary referral practice.

Non-motor symptoms of Parkinson’s disease, including sleep disturbance, cognitive impairment, depression, and anxiety, are common and often undertreated, yet their responsiveness to mind-body exercises remains unclear. This scoping review evaluated the currently available evidence on the effects of Tai Chi and Qigong interventions on non-motor symptoms in patients with Parkinson’s disease.

We searched six databases (PubMed, Google Scholar, EMBASE, CINAHL, Web of Science, and PEDro) through February 28, 2026, for randomized controlled trials (RCTs). We included English-language RCTs that evaluated the effects of Qigong and Tai Chi interventions on non-motor outcomes in Parkinson’s disease and excluded non-RCTs, review articles, and protocol articles. We were predominantly interested in the following non-motor outcome measures: cognition, depression, anxiety, fatigue, and sleep quality.

This review identified 18 RCTs that met the inclusion criteria, including nine Tai Chi studies and nine Qigong studies. Most of the reviewed studies were of high quality according to the PEDro scale, but the small sample sizes limited our analysis to identifying trends in outcomes. A strong trend toward a beneficial effect was found for sleep quality and cognition, a moderate trend toward improvement was found in depression, anxiety and quality of life, and weak or unclear effects were found for other non-motor symptoms such as fatigue. Several studies also had high dropout rates.

Although these studies suggest that Tai Chi and Qigong may improve sleep quality and cognition, the evidence supporting their benefits in alleviating other non-motor symptoms is generally weak, primarily because of small sample sizes. The heterogeneity in methodologies across the reviewed studies and high dropout rates in some studies are significant limitations of previous RCTs.