Hepatology Research最新文献

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.

Background: There are few reports on the factors that contribute to liver function at the time of disease progression after first-line systemic therapy for unresectable hepatocellular carcinoma (u-HCC). Therefore, our multicenter study investigated these factors in u-HCC patients treated with atezolizumab plus bevacizumab (ATZ/BEV).

Methods: We enrolled 101 patients with u-HCC who had preserved liver function, Child-Pugh (CP) Class A at baseline, and were treated with ATZ/BEV as the first-line systemic chemotherapy. All were evaluated for progressive disease (PD) during the observational period, and those who had Child-Pugh Class A at evaluation of PD were classified as Group A, with those who had Child-Pugh Class B at evaluation of PD being classified as Group B.

Results: Comparing the two groups, Group A had significantly higher platelet counts than Group B (p = 0.008). Receiver operating characteristic curve analysis for differentiating CP Class A versus B at the time of evaluation of PD, using platelet counts, showed that the area under the curve was 0.690 and the optimal cutoff value was 12.8 × 10⁴/μL. Multivariate analysis showed that only the low platelet count was associated with CP Class B at the time of evaluation of PD (< 12.8/≥ 12.8 × 10⁴/μL: OR 3.780, p = 0.022).

Conclusions: The data suggest that the platelet count can be used to predict liver function at the time of evaluation of PD after ATZ/BEV therapy in patients with u-HCC. Treatment strategies in u-HCC patients with low platelet counts should be conducted by taking into account deterioration of liver function after ATZ/BEV therapy.

Background: The Japan Liver Cancer Association and the Japanese Society of Hepato-Biliary-Pancreatic Surgery proposed oncological resectability criteria for hepatocellular carcinoma (HCC), classifying tumors as R, BR1, or BR2. However, serum tumor markers, such as alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP), despite their prognostic value, were not incorporated.

Methods: We retrospectively analyzed 803 patients undergoing curative liver resection for HCC. Significant tumor marker elevation (TM-high) was defined as AFP > 500 ng/mL or DCP > 1000 mAU/mL. Overall survival (OS) and relapse-free survival (RFS) were compared according to resectability status and tumor marker levels.

Results: TM-high status was observed in 171 patients with R (32.3%), 75 patients with BR1 (27.5%), and 46 patients with BR2 (70.1%). In the R group, TM-high patients had significantly worse outcomes than non-TM-high patients (median survival time [MST], RFS: 26.9 vs. 55.9 months, and p < 0.001; OS: 120.7 vs. 160.8 months and p = 0.008). No significant difference in the OS was observed between R/TM-high and BR1/non-TM-high patients (120.7 vs. 103.1 months and p = 0.159) or BR1/TM-high and BR2/non-TM-high patients (58.7 vs. 58.5 months and p = 0.657). Multivariate analyses confirmed that a TM-high status was an independent predictor for both the RFS (HR 1.36 and p < 0.003) and OS (HR 1.50 and p < 0.001).

Conclusion: AFP and DCP provide independent prognostic information beyond the oncological resectability criteria. Incorporating tumor markers may refine risk stratification and optimize multidisciplinary treatment strategies for HCC.

Aim: Curative resection is possible for hepatocellular carcinoma (HCC) if the disease is detected early. However, recurrence patterns are variable, and it is difficult to control recurrent lesions in some cases.

Methods: We identified patients with HCC who underwent curative resection as their initial treatment between January 2011 and December 2020 and divided them into three groups according to recurrence pattern. Treatment of recurrent lesions and patient outcomes were compared between groups, and predictors of recurrence beyond the Milan criteria were identified.

Results: Data for 351 patients were analyzed. During a median observation period of 69.0 months, 132 patients (37.6%) had no recurrence, 90 (25.6%) had recurrence within the Milan criteria, and 129 (36.8%) had recurrence beyond the Milan criteria. Patient outcomes were comparable between the group with recurrence within the Milan criteria and the group without recurrence (hazard ratio 1.019 and P = 0.95). However, outcomes were significantly worse in the group with recurrence beyond the Milan criteria than in the group without recurrence (hazard ratio 5.059 and p < 0.01). Male sex, alfa fetoprotein > 500 ng/mL, PIVKA-II > 400 mAU/mL, two or more tumors, portal vein invasion, and liver cirrhosis were identified as risk factors for recurrence beyond the Milan criteria after curative resection for HCC. Overall survival was stratified by number of risk factors.

Conclusions: This study suggests that the recurrence pattern determines the outcome after curative resection of HCC rather than recurrence itself. Further investigations are needed to develop perioperative treatment for patients with risk factors for recurrence beyond the Milan criteria.