Hepatology Research最新文献

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.

Acute-on-chronic liver failure (ACLF) represents a distinct clinical syndrome characterized by acute deterioration of chronic liver disease with systemic inflammation, organ failures, and high short-term mortality. Multiple diagnostic frameworks exist globally, including those proposed by the Asian Pacific Association for the Study of the Liver (APASL), the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) consortium, and the North American Consortium for the Study of End-Stage Liver Disease (NACSELD). Liver transplantation (LT) remains the only curative therapy for ACLF, offering substantial survival benefit. Posttransplant outcomes are strongly influenced by disease severity and timing of intervention, with ACLF grade 3 patients representing challenging population. Dynamic prognostic models, including the CLIF-C ACLF, and AARC scores, enable sequential assessment during the critical first week of illness, identifying patients likely to benefit from urgent transplantation versus those who may recover with medical management. The concept of a "golden window" for transplantation refers to the optimal timeframe within the first week when intervention offers maximal benefit. Living-donor liver transplantation (LDLT) predominates in Asia, whereas deceased donor liver transplantation (DDLT) remains the standard in Western countries. Emerging futility models, such as the TAM score, help identify patients too critically ill to benefit from LT. The ongoing CHANCE study, a global prospective registry, aims to clarify transplant benefit, waitlist attrition, and futility thresholds across diverse populations. Given the heterogeneity of diagnostic criteria, determining transplant candidacy in ACLF is inherently complex and requires individualized patient-specific (n = 1) assessment that integrates multiple frameworks including APASL and EASL-CLIF criteria.

Background & aim: Classic hepatic glycogen storage disease IV (GSD-IV) is widely regarded as an irreversible disorder that causes fatal cirrhosis by the age of 5 years unless liver transplantation is performed. We describe the first patient with biopsy-proven classic hepatic GSD-IV who survived into middle adulthood without transplantation and showed histological reversal of cirrhosis.

Case: We followed an infant diagnosed at 11 months with hepatosplenomegaly, severe aminotransferase elevation, and near-absent erythrocyte branching enzyme activity. Liver biopsies at ages 4 and 12 years confirmed polyglucosan-laden METAVIR F4 cirrhosis, and two episodes of variceal bleeding were controlled endoscopically and surgically. Thereafter, without disease-specific therapy, the aminotransferase level, platelet count, and portal hemodynamics gradually normalized. A third biopsy at age 43 showed complete disappearance of polyglucosan bodies and regression of fibrosis to F0, despite persistently minimal enzyme activity and compound heterozygous GBE1 variants in trans: c.137A > C p.(Gln46Pro) and the novel c.1340T > C p.(Leu447Pro).

Conclusions: This unprecedented case demonstrates that biochemical and histological remission is possible in classic hepatic GSD-IV despite persistently deficient branching-enzyme activity. Early, aggressive management of portal hypertension may therefore permit long-term survival and full histological recovery, challenging the transplant-first paradigm and supporting individualized, transplant-sparing care.

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease characterized by diverse clinical and histological manifestations. Accurate histopathological evaluation plays a critical role in determining disease activity, guiding treatment strategies, and predicting prognosis. However, due to its broad histological spectrum, AIH can resemble other liver disorders such as drug-induced liver injury (DILI) and viral hepatitis, making differential diagnosis challenging. In particular, acute-onset AIH often lacks typical serological markers, further complicating timely diagnosis. Liver biopsy provides essential information that cannot be obtained through serological or imaging studies alone, such as the distribution and pattern of hepatic injury and the presence of bile duct involvement. Furthermore, with the increasing prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), distinguishing AIH from overlapping or coexisting liver diseases has become increasingly important. This review highlights the characteristic histological features of AIH, discusses key differential diagnoses, and addresses current limitations in the diagnostic approach.

Aim: Hepatocellular carcinoma (HCC), a major cause of cancer death, highlights the need for biomarkers predicting early progressive disease (PD) under atezolizumab/bevacizumab (Atezo/Bev) therapy. We used the proximity extension assay (PEA) to identify plasma biomarkers linked to early PD.

Methods: This study included 47 patients with unresectable HCC treated with Atezo/Bev, divided into derivation (n = 27) and validation (n = 20) cohorts. To identify plasma biomarkers for early PD, 92 cytokines were measured by PEA; enzyme-linked immunosorbent assays (ELISA) were then used to determine key protein cutoffs in derivation. Cutoff validity was confirmed in validation.

Results: PEA showed vascular endothelial growth factor (VEGF)-A, angiopoietin-2 (ANGPT2), and Tie-2 were elevated in early PD cases. ELISA confirmed significantly higher levels in early PD versus nonearly PD (VEGF-A: 78.3 pg/mL vs. 53.2 pg/mL and p = 0.002; ANGPT2: 18.4 ng/mL vs. 12.7 ng/mL and p = 0.007; and Tie-2: 24.5 ng/mL vs. 17.6 ng/mL and p = 0.009). After establishing cutoff values for each protein, multivariate logistic regression analysis incorporating clinical background identified VEGF-A as the sole independent predictor of early PD (cutoff: 73.9 pg/mL, OR: 40.00, and p = 0.006). The predictive value of VEGF-A for early PD was evaluated in the validation cohort. With a cutoff of 73.9 pg/mL, early PD occurred in 21.4% and 83.3% of the low (n = 14) and high VEGF-A groups (n = 6), respectively (p = 0.018).

Conclusions: Plasma VEGF-A levels were identified as a significant biomarker for early PD in individuals with HCC receiving Atezo/Bev therapy.