Takuro Uchida

Background: Despite recent treatment advancements, the high recurrence rate of hepatocellular carcinoma (HCC) following curative therapy remains a significant challenge. Autotaxin (ATX) is a key biomarker in chronic liver disease that has a yet unclarified role in predicting HCC recurrence. This study examined whether precurative radiofrequency ablation (RFA) serum ATX level could serve as a predictor of HCC recurrence after treatment. Methods: Fifty‐six HCC patients (37 [66%] male; median age: 74 years) treated by curative RFA were retrospectively analyzed. Results: Twenty‐one patients experienced HCC recurrence during follow‐up. ATX demonstrated superior predictive performance for HCC recurrence after RFA, with an area under the receiver operating characteristic curve of 0.729, sensitivity of 0.857, and specificity of 0.629. Kaplan–Meier analysis revealed that patients with high ATX had a significantly higher incidence of HCC recurrence than those with low ATX ( p = 0.0006). In univariate analysis, the significant predictors of HCC recurrence included ATX (≥ 1.323 mg/L; hazard ratio [HR]: 6.49; 95% confidence interval [CI]: 1.90–22.13; p = 0.003), fibrosis‐4 index (≥ 3.524; HR: 2.75; 95% CI: 1.00–7.55; p = 0.050), and mac‐2 binding protein glycosylation isomer (≥ 3.85; HR: 2.12; 95% CI: 1.08–4.19; p = 0.030). According to multivariate Cox proportional hazards analysis with seven different models adjusting for age and various established biomarkers, ATX consistently emerged as the only significant independent predictor of HCC recurrence, with HR values ranging from 6.38 to 10.50 (all p < 0.05). Conclusion: Serum ATX is a promising biomarker for predicting HCC recurrence post‐RFA treatment that may outperform conventional markers.

Objectives: Pancreatic fluid collections (PFCs) are able to develop secondary to either fluid leakage or liquefaction of acute pancreatitis, chronic pancreatitis, pancreatic trauma, or after pancreatic surgery. While most PFCs resolve spontaneously, endoscopic procedures are sometimes necessary. Endoscopic ultrasound‐guided transluminal drainage (EUS‐TD) using lumen‐apposing metal stents (LAMS) is now widely performed for PFCs. This study investigated the incidence of complications and points to be considered during and after EUS‐TD using LAMS for the treatment of patients with PFCs. Methods: This three‐center retrospective study investigated patients who underwent EUS‐TD using LAMS or using a double‐pigtail plastic stent (DPS) for the treatment of PFCs at the University of Oita Hospital and affiliated institutions from December 2018 to June 2024. The primary outcome was the clinical success rate. Secondary outcomes included the technical success rate, endoscopic procedure time, LAMS indwell term, adverse events (AEs), and post‐LAMS placement course. Results: Twenty‐five patients (mean age, 67.5 ± 15.4 years; 76% male) underwent LAMS placement for PFCs. Median size of PFCs was 90 mm (range, 40–227 mm). A clinical success rate was achieved in 96%. The technical success rate was 96%, and the median endoscopic procedure time was 11 min (range, 5–32 min). Median LAMS indwell term was 46 days (range, 36‐60 days). AEs were bleeding and stent migration. Post‐LAMS placement course was good in 22 patients. No patients required re‐treatment after LAMS removal. Conclusions: EUS‐TD using LAMS is a simple procedure for the treatment of PFCs and appears clinically effective, highly safe, and efficient compared to conventional EUS‐TD using DPS.

While hepatocellular carcinoma (HCC) often invades the portal or hepatic vein to form tumor thrombus, tumor thrombus in the bile duct is rare. In such cases, differentiation from intrahepatic cholangiocarcinoma is difficult, and the tumor often appears as a smooth, yellowish‐white, polypoid mass within the bile duct lumen. We report herein a case of obstructive jaundice due to bile duct tumor thrombus of HCC diagnosed by peroral cholangioscopy (POCS). A 64‐year‐old man presented with epigastralgia and jaundice. Contrast‐enhanced computed tomography revealed an irregular mass with hypoenhancement in liver segment S8, along with dilatation of the right intrahepatic bile duct due to the invading tumor. The hepatic mass was poorly visualized on ultrasound, making percutaneous liver tumor biopsy difficult. POCS was performed after endoscopic retrograde cholangiopancreatography for biopsy of the intrahepatic bile duct tumor thrombus. POCS clearly revealed a smooth, yellowish‐white, polypoid tumor in the right intrahepatic bile duct, and a biopsy of the tumor was performed under POCS. Based on the pathological findings, HCC was diagnosed, and chemotherapy with atezolizumab and bevacizumab was initiated.

Cross-sectional analyses using liver tissue from chronic hepatitis B patients make it difficult to exclude the influence of host immune responses. In this study, we performed next-generation sequencing using the livers of hepatitis B virus (HBV)-infected uPA/SCID mice with humanized livers before and after antiviral therapy (AVT) with entecavir and pegylated interferon, and then performed a comparative transcriptome analysis of gene expression alteration. After HBV infection, the expression of genes involved in multiple pathways was significantly altered in the HBV-infected livers. After AVT, the levels of 37 out of 89 genes downregulated by HBV infection were restored, and 54 of 157 genes upregulated by HBV infection were suppressed. Interestingly, genes associated with hypoxia and KRAS signaling were included among the 54 genes upregulated by HBV infection and downregulated by AVT. Several genes associated with cell growth or carcinogenesis via hypoxia and KRAS signaling were significantly downregulated by AVT, with a potential application for the suppression of hepato-carcinogenesis.

It has been reported that high intensity in the hepatobiliary (HB) phase of Gd-EOB-DTPA-enhanced MRI (EOB-MRI) is associated with an immune-cold microenvironment in HCC. The aim of this study is to reveal whether non-high-intensity HCCs are homogeneous with respect to the immune microenvironment and to investigate the predictive ability of EOB-MRI for the response to atezolizumab + bevacizumab therapy (Atezo/Bev). The association between differences in stepwise signal intensity of HB phase and molecular subtypes and somatic mutations associated with the immune microenvironment was investigated in 65 HCC patients (cohort 1). The association between EOB-MRI and the therapeutic effect of Atezo/Bev was evaluated in the Atezo/Bev cohort (60 patients in cohort 2). The proportion of HCCs having CTNNB1 mutations and classified as Chiang CTNNB1 and Hoshida S3 was high in the high-intensity HB-phase group. Infiltration of tumor-associated macrophages (TAM) and regulatory T-lymphocytes (Treg) was characteristic of the high-intensity and low-intensity groups, respectively. Although EOB-MRI could not predict the response to Atezo/Bev treatment, our results demonstrate that EOB-MRI could serve as a surrogate marker predicting the immune microenvironment. This suggests that Atezo/Bev treatment can be selected regardless of signal intensity in the EOB-MRI HB phase.

Background and Aim: The prognosis of acute liver failure (ALF) remains poor, and liver transplantation is an alternative treatment option. Assessing the prognosis of ALF is important in determining treatment strategies. Here, we investigated clinical factors including serum pro‐inflammatory cytokine levels that are associated with the prognosis of ALF.Methods: Sixty‐six patients who developed ALF were enrolled in this study. Serum concentrations of 12 pro‐inflammatory cytokines were measured on admission. The prognosis and factors associated with survival and development of hepatic coma were analyzed.Results: Of 66 patients, 4 patients underwent liver transplantation, and 49 patients were rescued without liver transplantation, while the remaining 13 patients died. Serum concentrations of interleukin (IL)‐1β, IL‐4, IL‐6, IL‐8, IL‐13, TNF, IFN ‐γ, IP‐10, and G‐CSF were significantly elevated in ALF patients. IL‐4 and IL‐8 levels were higher in patients who underwent liver transplantation or died than in rescued patients. Multivariable analysis identified age ≥ 55 years and IL‐4 ≥ 1.2 pg/mL on admission as independent factors for mortality. Serum IL‐8 levels were higher in patients with hepatic coma, and prothrombin‐international normalized ratio ≥ 3.5 and IL‐8 ≥ 77.2 pg/mL on admission were associated with development of hepatic coma after admission.Conclusion: Serum levels of several pro‐inflammatory cytokines were elevated in ALF patients. IL‐4 and IL‐8 were correlated with survival and development of hepatic coma after admission, respectively. Measurement of serum pro‐inflammatory cytokines seems to be useful for the management of ALF.

Introduction: Measurements of body composition, such as the skeletal muscle index (SMI), are useful for predicting prognosis in hepatocellular carcinoma (HCC). This study aimed to analyze the relationship between skeletal muscle changes during therapy with atezolizumab plus bevacizumab (Atezo + Beva) or lenvatinib (Len) and the association between SMI and prognosis. Methods: Patients with advanced HCC and Child-Pugh A status received Atezo + Beva or Len as first-line systemic chemotherapy. We assessed prognosis and body composition obtained by bioelectrical impedance analysis. Results: A total of 109 patients received treatment (Atezo + Beva, n = 47; Len, n = 62). During treatment, the arm SMI was reduced in the Len group and maintained in the Atezo + Beva group. The extracellular water to total body water ratio (ECW/TBW) increased significantly in both groups during treatment. In the Atezo + Beva group, no factor was associated with prognosis. Multivariate analysis showed that in the Len group, the arm SMI (hazard ratio [HR], 0.5; 95% CI: 0.26–0.89; p = 0.02), ECW/TBW (HR: 2.7; 95% CI: 1.21–6.01; p = 0.01), and Child-Pugh score (HR: 2.3; 95% CI: 1.31–6.13; p = 0.004) were associated with progression-free survival. Conclusion: Assessing body composition with BIA before Atezo + Beva and Len treatment may be useful.