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MATSUURA TakanoriGraduate School of Medicine / Faculty of Medical SciencesAssistant Professor
Research activity information
■ Paper- Jul. 2025, Communications MedicineScientific journal
- AIMS: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy; however, they are associated with ICI-induced liver injury (ICI-LI), which manifests as hepatocellular, mixed, or cholestatic patterns with variable treatment responses. This study aimed to develop and validate a predictive model to identify ICI-LI type using clinical data available at ICI initiation. METHODS: A retrospective analysis of 297 patients with ICI-LI was conducted. Baseline clinical data were analyzed using univariate and multivariate logistic regression to predict ICI-LI types in the training and validation cohorts. A predictive model was developed and validated using receiver operating characteristic (ROC) curve analysis. RESULTS: Multivariate analysis in the training cohort identified male sex (odds ratio [OR]: 3.33, 95% confidence interval [CI]: 1.57-7.06, p = 0.002), serum albumin levels (OR: 0.42, 95% CI: 0.19-0.91, p = 0.027), and serum alanine aminotransferase (ALT) levels (OR: 0.97, 95% CI: 0.94-0.99, p = 0.015) as significant predictors, along with ICI regimen types selected using the Akaike information criterion. The logistic regression model, expressed as p = 1/{1 + (-(5.02 + 1.20 × (sex [F:0, M:1])) - 0.87 × albumin [g/dL] - 0.03 × ALT [U/L] - 0.9 × (drug [non-anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) related regimen:0, anti-CTLA-4 related regimen:1]))}, achieved an area under the ROC (AUROC) of 0.73 (95% CI: 0.63-0.82) in the training cohort. At a cut-off of 0.86, the sensitivity was 60.3%, specificity 74.4%, positive predictive value 92.3%, and negative predictive value 26.9%. In the validation cohort, the AUROC was 0.752 (95% CI: 0.476-1.00). CONCLUSION: This predictive model demonstrates its utility in classifying ICI-LI types.Apr. 2025, JGH open : an open access journal of gastroenterology and hepatology, 9(4) (4), e70147, English, International magazineScientific journal
- Background/Objectives: Although immunotherapy is the primary treatment option for intermediate-stage hepatocellular carcinoma (HCC), its efficacy varies. This study aimed to identify non-invasive imaging biomarkers predictive of the immunoscore linked to dynamic contrast-enhanced computed tomography (CECT). Methods: We performed immunohistochemical staining with CD3+ and CD8+ antibodies and counted the positive cells in the invasive margin (IM) and central tumor (CT), converting them to an immunoscore of 0 to 4 points. We assessed the dynamic CECT findings obtained from 96 patients who underwent hepatectomy for HCC and evaluated the relationship between dynamic CECT findings and immunoscores. For validation, we assessed the treatment effects on 81 nodules using the Response Evaluation Criteria in Solid Tumors in another cohort of 41 patients who received combined immunotherapy with atezolizumab and bevacizumab (n = 27) and durvalumab and tremelizumab (n = 14). Results: HCCs with peritumoral enhancement in the arterial phase (p < 0.001) and rim APHE (p = 0.009) were associated with the immunoscore in univariate linear regression analysis and peritumoral enhancement in the arterial phase (p = 0.004) in multivariate linear regression analysis. The time to nodular progression in HCCs with peritumoral enhancement in the arterial phase was significantly longer than that in HCCs without this feature (p < 0.001). Conclusions: We identified HCCs with peritumoral enhancement in the arterial phase as a noninvasive imaging biomarker to predict immune-inflamed HCC with a high immunoscore tendency. These HCCs were most likely to respond to combined immunotherapy.Mar. 2025, Cancers, 17(6) (6), English, International magazineScientific journal
- PURPOSE: The prognosis of patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) in the first-order or main trunk/contralateral branches (Vp3/4) is poor. The present study aimed to clarify the real-world data of atezolizumab plus bevacizumab treatment (Ate/bev) for HCC patients with Vp3/4 PVTT. METHODS: The subjects of this study were 22 consecutive HCC patients with Vp3/4 PVTT, who were treated with Ate/bev. Survival rates and radiological responses were evaluated based on the modified albumin-bilirubin (mALBI) grade [mALBI 1 + 2a (1/2a) versus 2b + 3 (2b/3)] using the modified Response Evaluation Criteria in Solid Tumors. RESULTS: The median survival time of the 22 patients was 15.0 months, with 1- and 2-year survival rates of 62.7% and 49.3%, respectively. The objective response (OR) rates of patients with mALBI 1/2a and 2b/3 were 91.7% (11/12) and 10.0% (1/10), respectively, with a significant difference (p < 0.001). The 2-year survival rates of patients with mALBI 1/2a and 2b/3 were 78.6% and 20.0%, respectively, with a significant difference (p = 0.0041). CONCLUSION: Ate/bev was effective for treating HCC patients with Vp3/4 PVTT. OR rate and MST were favorable, particularly for patients with preserved liver function (mALBI 1/2a), suggesting its great potential for the treatment of HCC in patients with Vp3/4 PVTT.Feb. 2025, Surgery today, English, Domestic magazineScientific journal
- BACKGROUND AND AIMS: Tremelimumab plus durvalumab (Dur/Tre) combination therapy is now a first-line systemic therapy for advanced hepatocellular carcinoma (HCC). Because systemic therapy is not effective in some patients, it is clinically important to identify factors that could predict the response to treatment at an early stage. We investigated the factors associated with the response to Dur/Tre for advanced HCC in a clinical setting. METHODS: Seventy patients (median age 74 years; 61 men) who received Dur/Tre between March 2023 and September 2024 were analyzed. We examined the factors associated with the treatment response, including pretreatment factors and factors early in treatment. RESULTS: The median treatment duration was 77.5 (interquartile range [IQR] 28-187) days. The overall response and disease control rates were 25.8% and 58.1%, respectively. The median (IQR) progression-free survival (PFS) and overall survival (OS) were 82 (61-133) and 415 (337-NA) days, respectively. Multivariable analysis revealed that higher absolute lymphocyte count (ALC) and lower des-γ-carboxyprothrombin (DCP) levels were significantly associated with PFS. Receiver operating characteristic curve analysis showed that the cutoff value for ALC after 4 weeks of treatment in relation to clinical efficacy was 1125/mm3. A log-rank test using the Kaplan-Meier method showed that OS was significantly longer in patients with ALC above the cutoff and in patients whose DCP levels decreased after starting treatment. CONCLUSION: Higher ALC and lower DCP levels after treatment initiation were associated with the clinical efficacy of Dur/Tre for advanced HCC.Feb. 2025, JGH open : an open access journal of gastroenterology and hepatology, 9(2) (2), e70123, English, International magazineScientific journal
- BACKGROUND/AIM: Atezolizumab plus bevacizumab (AteBev) is widely used as a first-line treatment for advanced hepatocellular carcinoma (HCC). However, evidence regarding the optimal drug sequence following AteBev treatment is limited. This study aimed to compare the treatment outcomes between tyrosine kinase inhibitors (TKIs) and durvalumab plus tremelimumab (DurTre) following AteBev treatment. PATIENTS AND METHODS: Overall, 134 consecutive patients who received AteBev for advanced HCC were enrolled in this study. Treatment outcomes were retrospectively compared between TKIs (AteBev→TKI group) and DurTre (AteBev→DurTre group). RESULTS: The AteBev→TKI and Ate→DurTre groups included 46 and 7 patients, respectively. The AteBev→TKI group had significantly longer median progression-free survival after second-line treatment (3.6 vs. 0.94 months, p<0.001). The disease control rate was significantly higher in the AteBev→TKI group (p=0.020). The serum alpha-fetoprotein levels significantly decreased at one month in the AteBev→TKI group (0.909 vs. 1.435, p=0.035), whereas the albumin-bilirubin score significantly decreased at one month in the AteBev→TKI group (0.875 vs. 0.952, p=0.017). Each group reported no new unmanageable adverse events. CONCLUSION: TKIs may be a more optimal drug sequence than DurTre after AteBev treatment from an oncological perspective. TKIs following AteBev treatment require careful monitoring for deteriorating liver function.Jan. 2025, Anticancer research, 45(1) (1), 251 - 260, English, International magazineScientific journal
- With the widespread use of immune checkpoint inhibitors (ICIs), liver injury (ICI-induced liver injury) as an immune-related adverse event has become a major concern in clinical practice. Because severe cases of liver injury require administration of corticosteroids, a comprehensive evaluation is crucial, including clinical course, blood and imaging tests, and if necessary, pathological examination through liver biopsy. As with liver injury induced by other drugs, classification of injury type by R-value is useful in deciding treatment strategies for ICI-induced liver injury. Histologically, the most representative feature is an acute hepatitis-like hepatocellular injury, characterized by diffuse lobular inflammation accompanied by CD8-positive T lymphocytes. Another condition that can cause liver injury during ICI treatment is cholangitis accompanied by non-obstructive bile duct dilatation and bile duct wall thickening. Many cases of ICI-induced cholangitis are classified as non-hepatocellular injury type, and they have been reported to respond poorly to corticosteroids. It is essential that gastroenterologists/hepatologists and doctors in various departments work in cooperation to develop a system that achieves early diagnosis and appropriate treatment of ICI-induced liver injury.Aug. 2024, Hepatology research : the official journal of the Japan Society of Hepatology, 54(8) (8), 719 - 726, English, International magazineScientific journal
- Immune checkpoint inhibitor (ICI)-induced liver injury (LI) is a common adverse event, but the clinical characteristics based on the classification of hepatocellular injury and cholestatic types are not fully evaluated. This study aims to analyze risk factors and histological findings in relation to the classification of ICI-induced LI. In total, 254 ICI-induced LI patients among 1086 treated with ICIs between September 2014 and March 2022 were classified according to the diagnostic criteria for drug-induced LI (DILI), and their risk factors and outcomes were evaluated. Kaplan-Meier analyses showed that overall survival in patients with hepatocellular-injury-type LI was significantly longer than others (p < 0.05). Regarding pre-treatment factors, the lymphocyte count was significantly higher in patients with ICI-induced LI, especially in hepatocellular-injury-type LI. Gamma glutamyl transferase (γGTP) and alkaline phosphatase (ALP) were also significantly lower in patients with ICI-induced LI (p < 0.05). Multivariate analyses revealed that malignant melanoma, high lymphocyte count, and low ALP levels were extracted as factors contributing to hepatocellular-injury-type LI. The histological findings among 37 patients diagnosed as ICI-induced LI via liver biopsy also revealed that the spotty/focal necrosis was significantly frequent in hepatocellular-injury-type LI, whereas ductular reactions were frequently observed in cholestatic-type LI. It is suggested that the histological inflammation pattern in patients with LI is closely correlated with the type of DILI.Apr. 2024, Diagnostics (Basel, Switzerland), 14(8) (8), English, International magazineScientific journal
- Currently, hepatitis B virus (HBV) core antibody (anti-HBc antibody) and HBV core-related antigen (HBcrAg) are widely used as serum markers for diagnosis based on the HBV core region. This review focused on anti-HBc antibodies and HBcrAg and aimed to summarize the clinical significance of currently used assay systems and the issues involved. While anti-HBc is very significant for clinical diagnosis, the clinical significance of quantitative assay of anti-HBc antibody has been reevaluated with improvements in diagnostic performance, including its association with clinical stage and prediction of carcinogenesis and reactivation. In addition, concerning the new HBcrAg, a high-sensitivity assay method has recently been established, and its diagnostic significance, including the prediction of reactivation, is being reevaluated. On the other hand, the quantitative level of anti-HBc antibody expressed in different units among assay systems complicates the interpretation of the results. However, it is difficult to standardize assay systems as they vary in advantages, and caution is needed in interpreting the assay results. In conclusion, with the development of highly sensitive HBcrAg and anti-HBc antibody, a rapid and sensitive detection assay system has been developed and used in clinical practice. In the future, it is hoped that a global standard will be created based on the many clinical findings.Mar. 2024, Diagnostics (Basel, Switzerland), 14(7) (7), English, International magazineScientific journal
- BACKGROUND: Although genome duplication, or polyploidization, is believed to drive cancer evolution and affect tumor features, its significance in hepatocellular carcinoma (HCC) is unclear. We aimed to determine the characteristics of polyploid HCCs by evaluating chromosome duplication and to discover surrogate markers to discriminate polyploid HCCs. METHODS: The ploidy in human HCC was assessed by fluorescence in situ hybridization for multiple chromosomes. Clinicopathological and expression features were compared between polyploid and near-diploid HCCs. Markers indicating polyploid HCC were explored by transcriptome analysis of cultured HCC cells. RESULTS: Polyploidy was detected in 36% (20/56) of HCCs and discriminated an aggressive subset of HCC that typically showed high serum alpha-fetoprotein, poor differentiation, and poor prognosis compared to near-diploid HCCs. Molecular subtyping revealed that polyploid HCCs highly expressed alpha-fetoprotein but did not necessarily show progenitor features. Histological examination revealed abundant polyploid giant cancer cells (PGCCs) with a distinct appearance and frequent macrotrabecular-massive architecture in polyploid HCCs. Notably, the abundance of PGCCs and overexpression of ubiquitin-conjugating enzymes 2C indicated polyploidy in HCC and efficiently predicted poor prognosis in combination. CONCLUSIONS: Histological diagnosis of polyploidy using surrogate markers discriminates an aggressive subset of HCC, apart from known HCC subgroups, and predict poor prognosis in HCC.Oct. 2023, British journal of cancer, 129(8) (8), 1251 - 1260, English, International magazineScientific journal
- Aug. 2023, Internal medicine (Tokyo, Japan), 62(15) (15), 2285 - 2286, English, Domestic magazineScientific journal
- BACKGROUND AND AIM: The purpose of this study was to analyze factors associated with the overall survival (OS) of atezolizumab/bevacizumab combination therapy for advanced hepatocellular carcinoma (aHCC). We also assessed the OS of patients with ineffective therapy and those who discontinued treatment owing to adverse events (AEs). METHODS: This retrospective multicenter study involved 139 patients with aHCC who received atezolizumab/bevacizumab combination therapy between November 2020 and September 2022. RESULTS: The median duration of treatment was 136.5 days, and the median observation period was 316 days. The overall response rate was 40%, and the disease control rate was 78% according to mRECIST criteria. Grade ≥2 AEs occurred in 63 patients (43%) and led to treatment discontinuation in 16 patients. Multivariate analysis revealed that treatment response and occurrence of grade ≥2 AEs after therapy, as well as low level of albumin-bilirubin (ALBI) grade and low level of des-gamma carboxy prothrombin (DCP) before therapy, were extracted as factors that contributed to OS. Log-rank tests with the Kaplan-Meier method showed significant differences in OS among these factors. The OS of patients who discontinued owing to AEs was significantly shorter than that of other patients. CONCLUSION: Not only factors before therapy but also treatment response and the appearance of AEs are involved in OS for atezolizumab/bevacizumab combination therapy. Although the development of AEs also contributed to OS, appropriate management of AEs is important to avoid discontinuing treatment with this combination.Jul. 2023, JGH open : an open access journal of gastroenterology and hepatology, 7(7) (7), 476 - 481, English, International magazineScientific journal
- Nov. 2022, Endoscopy, 54(11) (11), E662-E663, English, International magazineScientific journal
- BACKGROUND AND AIM: Molecular-targeted therapies such as sorafenib and lenvatinib have long been used as first-line treatment for advanced hepatocellular carcinoma (aHCC). However, adverse events or limited therapeutic effects may necessitate the change to another therapeutic option, known as post-progression therapy. To investigate the significance of post-progression therapy, we analyzed the outcomes of aHCC patients following first-line molecular-targeted therapy in a real-world study. METHODS: This retrospective, multicenter study involved patients with aHCC who received sorafenib or lenvatinib as first-line therapy between January 2011 and September 2021. RESULTS: In total, 513 patients were analyzed: 309 treated with sorafenib and 204 with lenvatinib. The overall response and disease control rates were 15 and 50%, respectively, in the sorafenib group and 30 and 75%, respectively, in the lenvatinib group (P < 0.001). Kaplan-Meier analysis revealed no significant differences in progression-free survival and overall survival (OS) between the two treatments. Multivariate analysis revealed that fibrosis-4 index, disease control rate, post-progression therapy, and use of an immune checkpoint inhibitor (ICI) were significantly associated with OS. OS was significantly longer in patients who received post-progression therapy than in those who did not (log-rank P < 0.001). Most patients who received an ICI as post-progression therapy had previously received lenvatinib. Among lenvatinib-treated patients, OS was significantly longer in patients who received an ICI than in patients received another or no post-progression therapy (P = 0.004). CONCLUSION: The introduction of newer drugs for post-progression therapy is expected to prolong survival. ICI-based regimens appear to be effective after lenvatinib.Jun. 2022, JGH open : an open access journal of gastroenterology and hepatology, 6(6) (6), 427 - 433, English, International magazineScientific journal