Publications by authors named "Tomokazu Kawaoka"

Purpose: Postsustained virologic response (SVR) screening following clinical guidelines does not address individual risk of hepatocellular carcinoma (HCC). Our aim is to provide tailored screening for patients using machine learning to predict HCC incidence after SVR.

Methods: Using clinical data from 1,028 SVR patients, we developed an HCC prediction model using a random survival forest (RSF).

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Background: This study aims to identify biomarkers for treatment response of atezolizumab plus bevacizumab (Atezo+Bev) in patients with hepatocellular carcinoma (HCC).

Methods: 96 patients who received Atezo+Bev or lenvatinib as a first-line systemic therapy were enrolled as the training group after propensity score matching (PSM), and 42 patients treated with Atezo+Bev were enrolled as the validation group. 17 serum cytokines were measured by Luminex multiplex assay at the start of treatment.

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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.

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Article Synopsis
  • Durvalumab plus tremelimumab (STRIDE) is a new treatment for unresectable hepatocellular carcinoma (uHCC), but real-world data on its effectiveness is limited.
  • A study assessed 21 patients treated with STRIDE, finding an objective response rate of 52.4% and a median progression-free survival of 6.8 months.
  • A high tumor-to-liver ratio on FDG-PET scans was linked to a better response, suggesting it could serve as a useful biomarker for patient outcomes.
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Background: We have been able to use molecular targeted agents for unresectable hepatocellular carcinoma since 2009, and immune checkpoint inhibitors have been approved in recent years. We assessed the efficacy of systemic therapy in Hiroshima University Hospital by each era.

Methods: A total of 357 patients who were treated with sorafenib, lenvatinib, atezolizumab plus bevacizumab combination therapy, or durvalumab plus tremeliumab combination therapy as first-line systemic therapy in our hospital from November 2009 to December 2023 were enrolled in this retrospective cohort study.

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A 58-year-old man visited an orthopedic clinic complaining of pain in his right lower back and numbness in his lower limbs for one month. Imaging tests revealed a tumorous lesion from the left side of the second lumbar vertebra to the paraspinal muscles. CT-guided biopsy of the tumor was performed, and immunostaining results diagnosed hepatocellular carcinoma (HCC).

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Article Synopsis
  • The study examined the effects of immune-checkpoint inhibitors (ICIs) in patients with unresectable hepatocellular carcinoma, specifically looking at switching between different ICI regimens.
  • Sixteen patients underwent treatment with atezolizumab-bevacizumab (Atezo+Bev) as first-line therapy and durvalumab-tremelimumab (Dur+Tre) as second-line therapy, with outcomes related to response rates and adverse events recorded.
  • Findings indicated that while Atezo+Bev had a higher overall response rate and a significant drop in liver function scores, Dur+Tre maintained relatively safe disease control, although it presented risks of worsening immune-related side effects, particularly colitis, in patients previously treated
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Article Synopsis
  • The study investigates the effectiveness of tumor markers in predicting the response to immune checkpoint inhibitors in cancer therapy, specifically looking at situations where tumors may initially swell before ultimately shrinking (pseudo-progression).
  • A group of 33 patients received a combination therapy of durvalumab and tremelimumab, with tumor markers measured before and during treatment at various intervals to assess their correlation with treatment response.
  • Results showed that changes in tumor markers, such as AFP and DCP, are more reliable indicators of treatment success than imaging tests alone, particularly noting a significant decrease in these markers among responders after 8 weeks of treatment.
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Background & Aims: In the global, phase III HIMALAYA study in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) improved overall survival (OS) vs. sorafenib; durvalumab was non-inferior to sorafenib. HBV is the predominant HCC aetiology in most of Asia vs.

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Article Synopsis
  • This study assessed the safety and effectiveness of ramucirumab as a second- and third-line treatment for advanced hepatocellular carcinoma (HCC) in a real-world setting, complementing findings from the REACH-2 trial.
  • Conducted in Japan with 19 enrolled patients, the study found a 6-month progression-free survival rate of 14.3%, with median progression-free survival and overall survival of 3.7 and 12.0 months, respectively.
  • The most common severe adverse events included hypertension (23.5%), proteinuria (17.6%), and neutropenia (11.8%), with 29.4% of patients discontinuing treatment due to these adverse effects.
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Aim: Shear wave (SW) elastography is used to evaluate metabolic dysfunction-associated steatotic liver disease (MASLD) pathophysiology. Increased elasticity due to fibrosis and increased viscosity due to necrosis and inflammation affect SW. Assessing fibrosis, the most prognostically relevant pathology, is critical.

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Article Synopsis
  • * Of the 15,517 cases studied, ALD accounted for 35.4%, while the prevalence of hepatitis C and B virus-associated LC decreased significantly, indicating changing trends in liver disease causation.
  • * The study concluded that the emerging trends suggest a transition in Japan’s liver health landscape, with an increasing number of cases linked to nonviral conditions like ALD and nonalcoholic steatohepatitis (NASH).
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The therapeutic benefits of the immunotherapeutic combination of atezolizumab and bevacizumab (Atez/Bev) in hepatocellular carcinoma (HCC) vary. Therapeutic biomarkers might help improve outcomes for HCC patients receiving Atez/Bev therapy. The role of systemic immune profiles in HCC progression also remains unclear.

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Aim: Autotaxin (ATX) is a newly identified liver fibrosis biomarker; however, its clinical usefulness remains unclear. Therefore, we analyzed the changes in patients with chronic hepatitis B virus infection treated with nucleos(t)ide analogs (NAs) to evaluate its usefulness. We also investigated the predictors of hepatocellular carcinoma development, including ATX, in patients with chronic hepatitis B based on their clinical characteristics.

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Aim: Atezolizumab plus bevacizumab combination therapy (Atezo + Beva) is used as the first-line therapy for unresectable hepatocellular carcinoma (u-HCC). Serious adverse events (AEs), including rupture of esophagogastric varices, have been seen during treatment. Therefore, the relationships of efficacy, safety, and portal hypertension (PH) were analyzed.

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Background: This study aimed to clarify the population in whom the presence of metabolic dysfunction-associated fatty liver disease (MAFLD) especially contributes to recurrence after liver resection for non-B, non-C hepatocellular carcinoma (NBNC-HCC).

Methods: Of the 199 patients who underwent liver resection for NBNC-HCC, those who exceeded Milan criteria and with pathologically proven vascular invasion, intrahepatic metastasis, and positive resection margins were excluded, and the remaining 94 were eligible for this study. We explored factors contributing to postoperative recurrence in populations with and without advanced liver fibrosis.

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Background: Zoledronic acid reduces the risk of bone metastasis, but denosumab is a better option for treating bone metastases. However, few studies have evaluated the use of denosumab to treat bone metastasis originating from hepatocellular carcinoma. This study aimed to assess the clinical outcomes of switching from zoledronic acid to denosumab for treating bone metastasis in patients with hepatocellular carcinoma.

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Article Synopsis
  • * Among 50 patients with progressive disease post-treatment, those who were later given lenvatinib had a median OS of 15.3 months and a PFS of 4.0 months, with response rates of 33.3% to 54.2% depending on evaluation criteria.
  • * Key factors associated with better OS included lower Child-Pugh class and minimal intrahepatic tumor occupancy, while
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Background/aim: This study aimed to evaluate the outcomes of patients who underwent resection for oligometastasis from hepatocellular carcinoma (HCC) and identify the prognostic factors associated with poor survival.

Patients And Methods: Patients who underwent resection for oligometastasis from HCC between January 2000 and April 2021 were retrospectively investigated. Oligometastasis was defined as 1-5 single organ metastases that were detected preoperatively in this study.

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Introduction: Small liver tumours are difficult to identify during hepatectomy, which prevents curative tumour excision. Preoperative marking is a standard practice for small, deep-seated tumours in other solid organs; however, its effectiveness for liver tumours has not been validated. The objective of this study is to evaluate the effectiveness of preoperative markings for curative resection of small liver tumours.

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Background: Lenvatinib, a multiple receptor tyrosine kinase inhibitor, might exert antitumor effects via tumor immune modulation. However, changes in the tumor immune microenvironment induced by lenvatinib are poorly understood. We investigated the effect of lenvatinib on immune features in clinical samples from patients with hepatocellular carcinoma.

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Introduction: The feasibility and efficacy of surgical resection following systemic therapy for intermediate-stage hepatocellular carcinoma (HCC) beyond the Up-to-7 criteria is unclear. The combination of lenvatinib (LEN) and transcatheter arterial chemoembolisation (TACE), termed LEN-TACE sequential therapy, has shown a high response rate and survival benefit in patients with intermediate-stage HCC. This trial aims to evaluate the efficacy and safety of LEN-TACE sequential therapy and the feasibility of surgical resection for intermediate-stage HCC beyond the Up-to-7 criteria.

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Introduction: Systemic therapy is recommended for patients with Child-Pugh A in hepatocellular carcinoma (HCC). We analyzed the outcomes of a cohort of patients with HCC who received either sorafenib (Sor), lenvatinib (Len) or atezolizumab plus bevacizumab (Atezo + Bev) as first-line systemic therapy for HCC, with the aim of identifying prognostic factors for survival.

Methods: A total of 825 patients with advanced HCC and Child-Pugh A or B received either Sor, Len or Atezo + Bev as first-line systemic therapy.

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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).

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