Efficacy and Safety of Durvalumab Plus Tremelimumab in Hepatocellular Carcinoma Patients With Portal Vein Thrombosis and High Tumor Burden: A Multicenter Retrospective Analysis.

Aims: This study aimed to evaluate the therapeutic efficacy of durvalumab and tremelimumab (Dur/Tre) in patients with hepatocellular carcinoma (HCC) who had a tumor thrombus in the main portal vein trunk (Vp4) or high tumor burden (HTB).

Methods: A total of 309 patients with BCLC stage B or C HCC who received Dur/Tre between March 2023 and October 2024 were included. HTB was defined as the presence of at least one of the following radiological findings: ≥ 50% liver involvement by HCC, bile duct invasion, or the presence of Vp4.

Potential role of Geriatric Nutritional Risk Index as a risk factor for immune-mediated adverse events during durvalumab plus tremelimumab therapy in unresectable hepatocellular carcinoma.

Background: Immune-mediated adverse events (imAEs) are a significant concern in patients with unresectable hepatocellular carcinoma (uHCC) undergoing combination immunotherapy with durvalumab and tremelimumab (Dur/Tre). This study aimed to investigate the potential association of risk factors, particularly nutrition and immune markers, associated with the development of imAEs.

Methods: Between November 2022 and December 2024, 312 patients with uHCC treated with Dur/Tre were enrolled and retrospectively analyzed.

Deep-Learning-Aided Quantification of Steatohepatitis-Associated Pathological Findings in Liver Specimens.

Background: Although semi-quantitative scoring is a common method for quantifying histopathological findings, semi-quantitative evaluation may lead to errors in objectivity and reproducibility depending on the histological findings. We developed a deep learning model to quantify steatohepatitis-associated pathological findings from liver specimens.

Methods: Eighteen liver specimens of steatohepatitis, and eight liver specimens of chronic hepatitis were used to train AI (convolutional neural network), and construct an AI to quantify steatohepatitis-associated pathological findings.

Limited Prognostic Impact of Sustained Virologic Response on Atezolizumab plus Bevacizumab Therapy for HCV-Related Unresectable Hepatocellular Carcinoma.

Aims: Sustained virological response (SVR) is a favorable prognostic factor for patients with hepatocellular carcinoma (HCC) caused by hepatitis C virus (HCV) treated curatively. This study aimed to evaluate the impact of SVR on atezolizumab plus bevacizumab (Atez/Bev) therapy for unresectable HCC (uHCC) caused by HCV.

Methods: A retrospective analysis of 364 uHCC patients treated with Atez/Bev (September 2020-April 2025) and divided into SVR (n = 284) and non-SVR (n = 80) groups was performed, with clinical characteristics, prognosis, and adverse events compared.

Safety and Efficacy of Durvalumab Plus Tremelimumab in Older Individuals With Unresectable Hepatocellular Carcinoma: A Multicenter Analysis.

Aim: To evaluate the safety and efficacy of durvalumab plus tremelimumab (Dur/Tre) in older adults with unresectable hepatocellular carcinoma (HCC).

Methods: A total of 345 patients with HCC who received Dur/Tre were included in this study. Using propensity score matching, we compared outcomes between older (aged ≥ 75 years; n = 120) and younger individuals (n = 120).

A Case of Nontuberculous Mycobacterial Pulmonary Disease Complicating Massive Pulmonary Embolism.

A 39-year-old man presented with fever and dyspnoea for 1 week. Imaging suggested bacterial pneumonia with infiltrates in the right lung. However, the symptoms persisted despite antibiotics.

Adenylosuccinate Mediates Imeglimin-Induced Proliferative and Antiapoptotic Effects in β-Cells.

Although imeglimin promotes β-cell proliferation and ameliorates β-cell apoptosis, the detailed metabolic changes induced by imeglimin in β-cells are unknown. Imeglimin increases adenylosuccinate (S-AMP), which is produced by adenylosuccinate synthase (ADSS) from inosine monophosphate and aspartate, and imeglimin also increases amino acid content, including aspartate, in mouse islets. Inhibition of S-AMP production by an ADSS inhibitor reduces the ability of imeglimin to increase β-cell proliferation and ameliorate β-cell apoptosis in mouse islets, human islets, porcine islets, and human pluripotent stem cell-derived β-cells.

Prognosis of Hepatectomy versus Systemic Chemotherapy Based on Oncological Resectability Criteria for Borderline Resectable Hepatocellular Carcinoma.

Introduction: Oncological resectability criteria for hepatocellular carcinoma have been defined (resectable [R]/borderline resectable 1 [BR1]/borderline resectable 2 [BR2]); however, their validation is necessary.

Methods: A total of 1,469 patients who underwent hepatectomy and 525 patients who received systemic chemotherapy, including lenvatinib, atezolizumab plus bevacizumab, and durvalumab plus tremelimumab, as first-line treatment were analyzed.

Results: In the BR1 group, the median survival times (MSTs) of patients who underwent hepatectomy and systemic chemotherapy were 52.

Vascular Invasion Within the Resectability Criteria Is a Prognostic Factor in Patients Treated With Atezolizumab and Bevacizumab.

Background And Aims: To assess the outcomes of patients with hepatocellular carcinoma (HCC) who were treated with atezolizumab plus bevacizumab (Atezo/Bev), categorised by oncological resectability criteria, which reflect tumour burden and extent of disease.

Methods: A cohort of 467 HCC patients who received Atezo/Bev was enrolled. Patients were classified into two groups based on oncological resectability criteria: BR (borderline resectable) 1 (n = 153) and BR2 (n = 314).

Clinical Impact of Serum CRP Levels on Advanced HCC Treated With Durvalumab and Tremelimumab: A Multicentre Study.

Aim: This study aimed to evaluate the therapeutic efficacy and prognostic significance of C-reactive protein (CRP) in patients with advanced hepatocellular carcinoma (HCC) receiving durvalumab and tremelimumab (Dur/Tre).

Methods: A total of 167 patients treated with Dur/Tre between March 2023 and March 2024 in Japanese hospitals were included in this retrospective multicentre study. Patients were divided into two groups based on pre-treatment serum CRP levels: the low-CRP group (< 1 mg/dL, n = 106) and the high-CRP group (≥ 1 mg/dL, n = 61).

Evaluation of Anti-VEGFR2 Specific Photoimmunotherapy for Targeted Regression of Neovascularization in an AMD Model.

Purpose: This study aimed to evaluate the efficacy of photoimmunotherapy (PIT) targeting VEGFR2 for the treatment of neovascular AMD and to investigate its potential as a novel therapeutic strategy.

Methods: DC101-IR700, a conjugate of the anti-mouse VEGFR2 monoclonal antibody DC101 and the photosensitizer IR700, was investigated both in vitro and in vivo. VEGFR2 expression in endothelial cells was confirmed via qPCR and immunocytochemistry.

Neutrophil-Lymphocyte Ratio Predicts Overall Survival in Patients With HCC Treated With Durvalumab Plus Tremelimumab.

Aim: To investigate the prognostic impact of the neutrophil-to-lymphocyte ratio (NLR) on outcomes in patients with hepatocellular carcinoma (HCC) treated with durvalumab plus tremelimumab (Dur/Tre).

Methods: A total of 182 patients with HCC who received Dur/Tre were included in the analysis. Univariate and multivariate survival analyses were conducted.

Prognostic Significance of the BALAD Serological Model in Systemic Therapies for Hepatocellular Carcinoma: A Personalized Approach to the Prediction of Survival Benefit.

Purpose: The BALAD model, a scoring system for staging hepatocellular carcinoma (HCC), is based on five serum markers: bilirubin, albumin, agglutinin-reactive alpha-fetoprotein [AFP], AFP, and des-gamma-carboxy prothrombin. It has shown good ability to predict survival in patients with HCC irrespective of stage and treatment, a high BALAD value being associated with a poor prognosis. However, its prognostic significance is unclear in patients with advanced unresectable HCC (uHCC) who undergo systemic therapies.

Impact of time-of-day atezolizumab plus bevacizumab combination therapy infusion for unresectable hepatocellular carcinoma: A retrospective multicenter study.

Aim: This study aimed to evaluate the impact of infusion timing of time-of-day on clinical outcomes in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab combination therapy.

Methods: A retrospective analysis was conducted using data from 751 unresectable HCC patients treated with atezolizumab plus bevacizumab between September 2020 and April 2024. Patients were categorized into morning (AM; n = 351) and afternoon (PM; n = 400) groups based on infusion timing of time-of-day.

Phase separation of the PRPP amidotransferase into dynamic condensates promotes de novo purine synthesis in yeast.

De novo purine synthesis (DPS) is up-regulated under conditions of high purine demand to ensure the production of genetic materials and chemical energy, thereby supporting cell proliferation. However, the regulatory mechanisms governing DPS remain unclear. We herein show that PRPP amidotransferase (PPAT), the rate-limiting enzyme in DPS, forms dynamic and motile condensates in Saccharomyces cerevisiae cells under a purine-depleted environment.

The effect of serum albumin levels before IMPELLA insertion on mortality risk in patients with cardiogenic shock.

Despite advances in the treatment of cardiogenic shock (CS), the 30-day mortality rate remains high. While some biomarkers predict outcomes in CS, none have been identified for prognostic prediction in IMPELLA patients. Patients with IMPELLA support due to CS were prospectively enrolled in the Japanese Registry for Percutaneous Ventricular Assist Devices.

The efficacy and safety of FOLFOX therapy for advanced esophageal squamous cell carcinoma.

Cisplatin-based chemotherapy is the standard advanced esophageal squamous cell carcinoma (ESCC) treatment. However, the 5-fluorouracil plus L-leucovorin and oxaliplatin (FOLFOX) regimen is available in Japan as an alternative to cisplatin-based chemotherapy, but its efficacy and safety remain unclear. Hence, we aimed to evaluate patients with advanced ESCC who received FOLFOX therapy retrospectively.

Diagnostic performance of attenuation imaging versus controlled attenuation parameter for hepatic steatosis with MRI-based proton density fat fraction as the reference standard: a prospective multicenter study.

Background: Attenuation Imaging (ATI) and controlled attenuation parameter (CAP) are non-invasive ultrasound-based methods for diagnosing hepatic steatosis. However, reports on the clinical usefulness of ATI are limited. We aimed to compare the ability of ATI and CAP to diagnose hepatic steatosis with magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) as the reference standard.

Possible Use of Body Surface Area Value for Estimating Skeletal Muscle Mass in Chronic Liver Disease.

Sarcopenia is an important clinical feature of patients with chronic liver disease (CLD). However, special devices are required to determine skeletal muscle mass. We evaluated the usefulness of body surface area (BSA) for estimating muscle mass and diagnosing sarcopenia in patients with CLD.

Serum PKCδ is a useful biomarker to distinguish hepatocellular carcinoma from other gastrointestinal cancers.

Protein kinase C delta (PKCδ) is a leaderless protein generally localized in the cytoplasm and nucleus; however, its extracellular unconventional protein secretion occurs exclusively in hepatocellular carcinoma (HCC) cells (but not in normal and non-cancerous hepatocytes or other gastrointestinal cancer cells) via an autophagy mechanism, despite the lack of a secretory signal. Therefore, PKCδ is detectable in the peripheral blood of HCC patients. Serum PKCδ indicates cancer-related unconventional protein secretion of an inactive form of cytosolic PKCδ and can be a unique biomarker independent of conventional markers.

The Current Status of Tumor Markers as Biomarkers in the Era of Immunotherapy for Hepatocellular Carcinoma: Alpha-Fetoprotein Alone Is Not Sufficient.

Introduction: Rapid development of systemic treatments has resulted in improved prognosis for unresectable hepatocellular carcinoma (uHCC) patients. Since immune therapy shows a favorable therapeutic efficacy, use of tumor markers as biomarkers for monitoring treatment response is necessary. This study aimed to elucidate changes in positive rates of 3 available tumor markers in Japan, including alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and lens culinaris agglutinin-reactive AFP (AFP-L3) in uHCC patients treated with systemic therapies over time.

Survival Outcomes Associated With Radiological Progressive Disease Subtypes in Patients With Atezolizumab and Bevacizumab-Treated HCC.

Background And Aim: To assess the relationship between survival outcomes and subtypes of radiological progressive disease (PD) in patients with hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Atezo/Bev).

Methods: A total of 462 patients with Atezo/Bev-treated HCC diagnosed with radiological PD during follow-up were enrolled. PD was classified into three categories: progression or emergence of intrahepatic lesions (PD-IH), macroscopic vascular invasion (PD-MVI), and extrahepatic spread lesions (PD-EHS).

Evaluation of Treatment Outcomes Using dNLR and GNRI in Combination Therapy With Atezolizumab and Bevacizumab for Hepatocellular Carcinoma.

Aim: This study aims to investigate the clinical utility of the derived neutrophil-to-lymphocyte ratio (dNLR) and the Geriatric Nutritional Risk Index (GNRI) in predicting treatment outcomes for patients with unresectable hepatocellular carcinoma (HCC) undergoing combination therapy with atezolizumab and bevacizumab (Atez/Bev).

Methods: A retrospective analysis was conducted on 310 patients. The dNLR, NLR, and GNRI were calculated, and their impact on progression-free survival (PFS) and overall survival (OS) was assessed.