Hepatology Research最新文献

Aim: In patients with decompensated liver cirrhosis, water retention often leads to complications such as acute kidney injury and poor prognosis. Soluble CD14 (sCD14), a marker of bacterial translocation, may have clinical relevance in this setting. Therefore, we aimed to investigate the prognostic value of sCD14 in patients with decompensated liver cirrhosis and water retention, and to determine its association with diuretic responsiveness, acute kidney injury development, and short-term mortality.

Methods: We retrospectively analyzed 134 patients with decompensated liver cirrhosis and refractory fluid retention treated with tolvaptan. Associations between serum sCD14 levels and diuretic response, acute kidney injury development, and liver-related mortality were evaluated. sCD14 was compared with other bacterial translocation markers (soluble CD163 and mannose receptor) in a subset excluding patients with advanced hepatocellular carcinoma.

Results: Lower sCD14 levels were associated with improved short- and long-term diuretic responses and a lower acute kidney injury incidence. Patients with sCD14 ≤ 2340 pg/mL had significantly better liver-related survival than those with higher levels (median survival time: 24.5 vs. 4.8 months, respectively; p < 0.01). In the multivariate analysis, sCD14 > 2340 pg/mL independently predicted liver-related mortality (hazard ratio = 2.71, p < 0.01). Compared with sCD163 and mannose receptor, sCD14 demonstrated superior prognostic value. Concomitant rifaximin use was significantly associated with lower sCD14 levels.

Conclusions: sCD14 is a potential biomarker for predicting prognosis, diuretic response, and acute kidney injury development in patients with decompensated liver cirrhosis and water retention. Its predictive capacity surpasses that of other bacterial translocation markers and may be influenced by administering therapeutic interventions, including rifaximin.

Background: A substantial proportion of chronic hepatitis B (CHB) patients with indeterminate phase have significant liver injury, yet only a small proportion of these patients receive liver biopsy. We compared the clinical characteristics of indeterminate CHB patients with and without liver biopsy.

Methods: A total of 2928 untreated CHB patients with indeterminate phases were retrospectively included. The indeterminate phase was identified and classified based on the AASLD 2018 guidance.

Results: The median age of patients was 39.0 years and male accounted for 65.0%. A total of 288 (9.8%) CHB patients with the indeterminate phase underwent liver biopsy. Patients with liver biopsy were older (42.0 vs. 39.0 years, p < 0.001) and had higher HBV DNA (3.4 log₁₀IU/mL vs. 2.7 log₁₀IU/mL, p < 0.001), APRI (0.42 vs. 0.36, p < 0.001), FIB-4 (1.18 vs. 0.99, p < 0.001), and liver stiffness values (9.9 vs. 6.6 kPa, p < 0.001), whereas lower platelets (169.0 × 10⁹/L vs. 192.0 × 10⁹/L, p < 0.001) than those without liver biopsy. Patients with PLT< 150.0 × 10⁹/L (OR 1.587, 95% CI 1.207-2.085, p < 0.001) and high HBV DNA (OR 1.458, 95% CI 1.298-1.637, p < 0.001) were more likely to receive liver biopsy in the indeterminate phase.

Conclusion: Only 9.8% of indeterminate CHB patients underwent liver biopsy in our cohort. These patients exhibited higher values on noninvasive fibrosis tests. Hepatic histologic findings from biopsied patients should be interpreted with caution and should not be generalized to all patients in the indeterminate phase.

Background: Liver fibrosis is central to chronic liver disease prognosis, including metabolic dysfunction-associated steatotic liver disease (MASLD). Mac-2 binding protein glycan isomer (M2BPGi) is a recognized liver fibrosis marker, but lacks an established reference range in healthy populations, thereby limiting clinical use.

Methods: This cross-sectional study analyzed 3623 Japanese adults undergoing routine health checks (2020-2021), excluding those with hepatitis B or C. Participants had physical and laboratory assessments, including serum M2BPGi, metabolic parameters, and liver indices. The fatty liver index (FLI) and Fibrosis-4 (FIB-4) index assessed hepatic steatosis and fibrosis. Multiple regression identified independent determinants of M2BPGi, and a normal reference range was established from participants with all metabolic and liver factors within normal limits.

Results: Participants' mean age was 42.3 years (90.5% male). Median M2BPGi was 0.44 COI (IQR: 0.32-0.60). Higher M2BPGi correlated with increased BMI, waist circumference, glucose, lipid levels, liver enzymes, FLI and FIB-4. Regression analysis identified age, sex, BMI, waist, AST, GGT, HDL-C, fasting glucose, and FIB-4 as independent predictors of M2BPGi; alcohol intake was not significant. Females displayed significantly higher M2BPGi than males. Among 1350 participants with completely normal parameters, the reference M2BPGi was 0.41-0.43 COI in male and 0.46-0.54 COI in female.

Conclusions: M2BPGi levels are independently influenced by metabolic factors and sex, and the study establishes sex-specific normal reference ranges in healthy Japanese adults. M2BPGi above these limits should prompt further metabolic and hepatic evaluation.

Aim: Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by inflammation and fibrosis. We aimed to elucidate the antifibrotic advantage of Sacubitril/Valsartan (Sac/Val) and molecular mechanisms using a rat MASH model and cells.

Methods: A connexin 32 dominant negative transgenic rat MASH model was induced using a high-fat diet plus dimethylnitrosamine and treated with Val (5 mg/kg/day) or Sac/Val (10 mg/kg/day) for 17 weeks. Histological evaluation, immunohistochemistry, RT-PCR, western blot, and RNA sequencing were performed to assess steatohepatitis, fibrosis, hepatocarcinogenesis, and signaling pathways. Direct modulatory effects were analyzed using a rat hepatic stellate cell (HSC) line.

Results: Sac/Val significantly reduced steatohepatitis and hepatic fibrosis histologically compared with Val alone, with fewer α-smooth muscle actin (SMA)-positive activated HSCs. Hepatic preneoplastic lesions were also reduced. Sac/Val suppressed Nlrp3, reactive oxygen species levels, and phosphorylated p38 mitogen-activated protein kinase, and cleaved gasdermin D, mitigating oxidative stress and inflammasome signaling. RNA sequencing revealed integrin alpha 8 (Itga8), a key regulator of HSC activation, was downregulated by Sac/Val compared with Val, correlating with HSC activation and fibrosis. Immunohistochemistry revealed decreased Itga8 protein expression in fibrotic regions with Sac/Val treatment. Sac/Val inhibited transforming growth factor (TGF)-β1-induced HSC activation, proliferation, and collagen production, further supporting its direct antifibrotic effects. Conversely, stable Itga8 overexpression in HSC enhanced proliferation and upregulated Tgfb1 and α-SMA, supporting the role of Itga8 in HSC activation.

Conclusions: Sac/Val attenuated fibrosis and inflammation in MASH, potentially through suppression of Itga8 expression, oxidative stress, and inflammasome signaling, highlighting Sac/Val as a promising MASH therapy.

Aim: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease, yet its underlying mechanisms remain incompletely understood. Beyond hemostasis, platelets actively participate in inflammation, fibrosis, and vascular remodeling. This study investigated platelet proteomic alterations across MASLD stages to explore their potential contribution to disease progression.

Methods: We analyzed 25 MASLD patients undergoing hepatic catheterization and 21 viral-hepatitis controls. Platelets were isolated from sinusoidal and peripheral blood and profiled using high-throughput, mass spectrometry-based proteomics. Differential-abundance and pathway analyses were performed with appropriate statistical correction and exploratory evaluation.

Results: A total of 1052 platelet proteins were identified. Several proteins showed large effect sizes and are reported as putative markers: histidine-rich glycoprotein and ADP-ribosylation factor-like protein 8B were less abundant in MASLD than in controls. In advanced disease, perforin-1 and macro-H2A1 were increased in sinusoidal blood, suggesting immune activation and endothelial injury. Docking protein 1 and TGF-β-induced protein IG-H3 were enriched in patients with perisinusoidal fibrosis and obliterative venopathy.

Conclusions: Putative platelet-derived proteins associated with immune regulation, vascular remodeling, and metabolic dysfunction were identified in MASLD. These exploratory findings will be validated in a prospective, metabolically matched cohort to confirm disease specificity.