Hepatology Research最新文献

Backgrounds: This study aimed to investigate the incidence and potential risk factors for hepatic encephalopathy (HE) recurrence following the initiation of rifaximin therapy in patients with liver cirrhosis.

Methods: We conducted a multicenter retrospective cohort study of cirrhotic patients who initiated rifaximin between December 2016 and December 2023. Patients with a prior episode of overt HE who received rifaximin for secondary prophylaxis were included. Clinical data, laboratory parameters, and concomitant medications were extracted from medical records. Factors associated with HE recurrence after rifaximin initiation were analyzed using univariate and multivariate analyses.

Results: A total of 145 patients were included (median age, 70 years; male, 52.4%). During a median observation period of 26.4 months (interquartile range: 11.4-48.9), 52 patients (35.9%) experienced HE recurrence. In multivariate analysis, the baseline aMAP risk scores the only independent predictor of HE recurrence (p = 0.041). Receiver operating characteristic (ROC) analysis identified a cutoff value of 70.843 for the aMAP risk score to predict HE recurrence. Patients with an aMAP risk score below 70.843 had significantly lower cumulative recurrence rates than those with scores ≥ 70.843 (p = 0.012).

Conclusions: Despite good tolerability, more than one-third of the patients experienced HE recurrence after rifaximin initiation. The aMAP risk score was useful for predicting the risk of recurrence, suggesting its potential clinical utility in the treatment of HE.

Background: Esophagogastric variceal (EGV) bleeding is a serious complication of pediatric-onset liver disease; however, evidence regarding endoscopic management and long-term outcomes remains limited. This study aimed to evaluate clinical outcomes following endoscopic therapy for pediatric EGV and to clarify challenges related to adherence and transitional care.

Methods: We retrospectively reviewed patients with pediatric-onset liver disease who underwent endoscopic treatment for EGV between 2012 and 2024. Patients were categorized into a childhood group (≤ 15 years) and a young adult group (> 15 years). Clinical characteristics, treatment outcomes, retreatment, survival, and adherence during the transition to adult care were analyzed.

Results: Emergency endoscopy for hematemesis was common in the childhood group. Despite frequent recurrence, endoscopic therapy was effective and no rebleeding or deaths occurred. In contrast, young adults showed significantly poorer survival (1-year 84.6%; 2-year 69.2%; and p = 0.045), primarily due to hepatic decompensation. Nearly half self-discontinued follow-up during the transition period, and nonadherence was associated with higher Child-Pugh and MELD scores and markedly reduced survival (5-year 33.3% and p = 0.038). Some young adults later developed alcohol-related liver disease, with significantly worse outcomes than the childhood group (p = 0.023).

Conclusions: Endoscopic therapy is effective and safe for pediatric EGV, although recurrence is common. In young adults, long-term outcomes are determined more by adherence and successful transitional care than by variceal severity. Structured transitional programs are essential for preventing loss to follow-up and improving survival in pediatric-onset portal hypertension.

Aim: The cystine/glutamate antiporter xCT facilitates cystine uptake and glutathione synthesis and suppresses ferroptosis. However, its role in hepatocellular carcinoma (HCC), particularly in glucose metabolism and disulfidptosis, remains unclear. We examined the prognostic value of xCT expression and tumor 18F-fluorodeoxyglucose (FDG) uptake as well as their association with tumor biology.

Methods: We retrospectively analyzed 345 patients with HCC who underwent hepatic resection. Immunohistochemical staining for xCT was performed in all 345 cases, and its associations with clinicopathological characteristics and survival were evaluated. Among these, 108 patients also underwent preoperative 18F-FDG positron emission tomography/computed tomography (PET/CT). In this subset, tumor FDG uptake was quantified and its relationship with xCT expression and patient prognosis was assessed.

Results: Patients with xCT-positive tumors had significantly worse overall survival compared with those with xCT-negative tumors (10-year, 42.6% vs. 75.2%; log-rank test, p < 0.0001). Among 108 patients with HCC who underwent PET/CT, xCT positivity was an independent predictor of poor prognosis in multivariate analysis (hazard ratio, 3.17; 95% confidence interval, 1.47-6.87; p = 0.0034). In addition, xCT expression correlated with FDG uptake (p = 0.0335). Importantly, tumors that were both xCT-positive and had high FDG uptake exhibited the poorest prognosis (log-rank test, p = 0.0405).

Conclusions: High xCT expression combined with elevated FDG uptake may identify a subset of patients with HCC who have poor prognoses and dual resistance to ferroptosis and disulfidptosis. These findings highlight the potential of xCT as both a prognostic biomarker and therapeutic target for aggressive HCC.

Background: Attenuation imaging (ATI) is used for the noninvasive diagnosis of hepatic steatosis (HS) based on the ultrasound system. However, the clinical utility of ATI has not yet been sufficiently evaluated. In this study, we used the magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) as a reference standard to investigate the usefulness of ATI in diagnosing HS.

Methods: We conducted a prospective multicenter study that included 1059 patients with chronic liver disease who underwent ATI and MRI-PDFF. We defined the degree of steatosis as follows: S0, MRI-PDFF < 5.2%; S1, 5.2% ≤ MRI-PDFF < 11.3%; S2, 11.3% ≤ MRI-PDFF < 17.1%; and S3, MRI-PDFF ≥ 17.1%, based on previously published studies.

Results: Because the MRI-PDFF data were not normally distributed, log-transformed data (log MRI-PDFF) were used for the analyses. The correlation coefficient between ATI values and log MRI-PDFF was high (r = 0.779). A Bland-Altman analysis revealed that ATI values and log MRI-PDFF showed good consistency with a mean bias of 0.000 and a narrow range of agreement (95% confidence interval [CI], -0.519-0.519). The areas under the receiver operating characteristic curve (95% CI) and cutoff values for ATI were 0.910 (0.893-0.928) and 0.65 dB/cm/MHz for ≥ S1 steatosis, 0.928 (0.913-0.944) and 0.69 dB/cm/MHz for ≥ S2 steatosis, and 0.913 (0.894-0.931) and 0.72 dB/cm/MHz for ≥ S3 steatosis, respectively.

Conclusions: ATI is an excellent and beneficial noninvasive technique for the evaluation of HS.

Trial registration: UMIN Clinical Trials Registry (UMIN000048672).

Aim: Serum autotaxin (ATX) has emerged as a promising biomarker for liver fibrosis, despite known sex-related variability. In addition to the conventional enzyme immunoassay (EIA-ATX), newer methods have been developed: a chemiluminescent enzyme immunoassay (CL-ATX), which enables rapid measurement with smaller sample volumes, and an enzyme assay (E-ATX), compatible with routine clinical chemistry analyzers, thereby enhancing accessibility. This study aimed to evaluate the diagnostic performance of ATX in comparison with other noninvasive tests for liver fibrosis.

Methods: A total of 357 patients with chronic liver disease who underwent liver biopsy and had measurements of serum MAC-2 binding protein glycosylation isomer (M2BPGi) and shear wave measurement (SWM) were analyzed. ATX levels were measured using stored serum samples with both EIA-ATX and CL-ATX. Additionally, in 317 of these patients, ATX was also measured using the E-ATX method.

Results: In male patients, the area under the receiver operating characteristic curve (AUROC) values for predicting significant fibrosis (≥ fibrosis Stage 2) were 0.862 for SWM, 0.836 for M2BPGi, 0.814 for the fibrosis-4 index, 0.758 for platelet count, 0.800 for EIA-ATX, 0.790 for CL-ATX, and 0.783 for E-ATX. In female patients, the corresponding AUROC values were 0.834, 0.828, 0.857, 0.786, 0.805, 0.804, and 0.805, respectively. No significant differences were observed in AUROC values between ATX and other noninvasive liver fibrosis tests, nor among the different ATX measurement methods.

Conclusions: ATX demonstrated acceptable diagnostic performance for significant fibrosis, comparable to established noninvasive tests. The availability of E-ATX on routine chemistry analyzers highlights its potential as a practical biomarker for primary care and health checkups.

Aim: The COVID-19 pandemic markedly affected lifestyle behaviors and metabolic health worldwide. Patients with chronic liver disease (CLD) are particularly vulnerable to such disruptions; however, how these effects changed after daily life returned to normal remains unclear. This study examined changes in body composition, hepatic steatosis, and liver fibrosis during the with-COVID-19 and after-COVID-19 periods, with a focus on potential sex-specific differences.

Methods: A total of 187 patients with CLD underwent FibroScan and bioelectrical impedance analysis at three time points: before COVID-19 (2019-2020), during the pandemic (2020-2021), and after the disease was reclassified as Category V in Japan (2023-2024). Changes in obesity, hepatic steatosis, and skeletal muscle mass, as well as their associations with liver stiffness, were evaluated using univariate and multivariate analyses.

Results: Obesity and hepatic steatosis worsened during the pandemic but improved in the after-COVID-19 period, particularly in men. Overall skeletal muscle mass remained stable, whereas lower-limb muscle mass increased in women. The skeletal muscle index-to-BMI ratio increased in both sexes, showing relative preservation of muscle mass. In univariate analyses, changes in liver stiffness (ΔLSM) were associated with muscle mass parameters only in women; however, these associations did not remain significant as independent predictors after multivariate adjustment.

Conclusions: As lifestyles normalized after the pandemic, patients with CLD showed improvements in obesity and hepatic steatosis. Women demonstrated recovery of lower-limb muscle mass, suggesting greater susceptibility to pandemic-related lifestyle changes. Although muscle mass changes were not independently associated with liver stiffness in multivariate analyses, these findings should be interpreted cautiously; nonetheless, they suggest that sex-specific factors may warrant consideration when supporting comprehensive health management in patients with CLD.

Aim: The usefulness of the animal naming test (ANT) in identifying covert hepatic encephalopathy (CHE) is limited because adjustments for age and educational level are necessary. This study aimed to validate the ANT in Japanese patients with cirrhosis and to clarify whether such adjustments affect diagnostic performance.

Methods: This multicenter cross-sectional study included Japanese patients with cirrhosis and healthy controls. Independent CHE factors were assessed using a logistic regression model, and the discriminative ability of the ANT alone versus an adjusted model was compared using the area under the receiver-operating characteristic curve (AUC).

Results: Among the 152 patients with cirrhosis and 56 controls, propensity score matching identified 43 individuals in each group. Patients with CHE had the lowest ANT scores, followed by those without CHE and healthy controls (14 vs. 17 vs. 19). A multivariable analysis showed that the ANT was an independent factor for identifying CHE (odds ratio, 0.88; 95% confidence interval, 0.80-0.97; p = 0.009), whereas age and educational level were not. The AUC for the ANT alone in CHE diagnosis was comparable to that for the adjusted model using age and educational level (0.68 vs. 0.71; p = 0.350). ANT performance was not influenced by age or educational level among those with CHE. The ANT's optimal, rule-out, and rule-in cut-off values for identifying CHE were 15, 20, and 11, respectively.

Conclusions: The ANT can identify CHE in Japanese patients with cirrhosis, and adjustment for age and educational level has a limited influence on its diagnostic performance.

Trial registration: This study was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000046313).

Objectives: Acute pediatric liver failure (ALF) is a rare but life-threatening condition. This nationwide retrospective study aimed to characterize the clinical features, etiologies, management strategies, and outcomes of pediatric noncomatose and comatose ALF in Japan and to evaluate the utility of an early liver transplantation (LT) indication scoring system in this population.

Methods: We reviewed pediatric cases of noncomatose and comatose ALF reported in a national registry between 2016 and 2021. Based on the Japanese criteria, patients were classified into noncomatose and comatose ALF groups. Subgroup analyses were carried out based on age, etiology, and outcomes.

Results: A total of 136 patients (median age, 15.8 months) were included. Among the 136 patients, 48 (35.3%) were classified as noncomatose ALF and 88 (64.7%) as comatose ALF. Transplant-free survival was significantly higher in noncomatose ALF (66.7%) than in comatose ALF (28.4%) (p < 0.001). Patients with circulatory failure had a markedly worse prognosis, a high mortality rate (55.2%), and did not undergo LT. Infants had significantly lower transplant-free survival rates than older children (31.6% vs. 49.4% and p = 0.052). Survivors (n = 57) had higher platelet counts, lower bilirubin levels, and less liver atrophy patients who died or underwent LT (n = 79). The prognostic score correlated with outcomes and demonstrated a strong discriminative ability for predicting transplant-free survival (AUC 0.729; sensitivity 32.5% and specificity 92.9%).

Conclusion: Age, etiology, and early prognostic scoring may appropriately guide clinical decisions. These findings underscore the need for pediatric-specific prognostic tools and support the refinement of pediatric LT selection criteria.