228 results on '"Hirooka M."'
Search Results
2. Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib
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Rimini, M., Kudo, M., Tada, T., Shigeo, S., Kang, W., Suda, G., Jefremow, A., Burgio, V., Iavarone, M., Tortora, R., Marra, F., Lonardi, S., Tamburini, E., Piscaglia, F., Masi, G., Cabibbo, G., Foschi, F.G., Silletta, M., Kumada, T., Iwamoto, H., Aoki, T., Goh, M.J., Sakamoto, N., Siebler, J., Hiraoka, A., Niizeki, T., Ueshima, K., Sho, T., Atsukawa, M., Hirooka, M., Tsuji, K., Ishikawa, T., Takaguchi, K., Kariyama, K., Itobayashi, E., Tajiri, K., Shimada, N., Shibata, H., Ochi, H., Yasuda, S., Toyoda, H., Fukunishi, S., Ohama, H., Kawata, K., Tani, J., Nakamura, S., Nouso, K., Tsutsui, A., Nagano, T., Takaaki, T., Itokawa, N., Okubo, T., Arai, T., Imai, M., Joko, K., Koizumi, Y., Hiasa, Y., Cucchetti, A., Ratti, F., Aldrighetti, L., Cascinu, S., and Casadei-Gardini, A.
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- 2021
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3. A validation study of combined resection and ablation therapy for multiple hepatocellular carcinoma
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Tada, T., primary, Kumada, T., additional, Toyoda, H., additional, Nakamura, S., additional, Endo, Y., additional, Kaneoka, Y., additional, Hiraoka, A., additional, Joko, K., additional, Hirooka, M., additional, and Hiasa, Y., additional
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- 2022
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4. Phase of radiation from stimulated emission
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Hirooka, M., primary
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- 2017
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5. Nonalcoholic fatty liver with hepatic arterial buffer response strongly caused metabolic diseases, while bright pancreas was not associated with metabolic diseases – 5 years’ cohort
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Hirooka, M., primary, Koizumi, Y., additional, Miyake, T., additional, Yukimoto, A., additional, Nakamura, Y., additional, Imai, Y., additional, Watanabe, T., additional, Yoshida, O., additional, Tokumoto, Y., additional, Abe, M., additional, and Hiasa, Y., additional
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- 2017
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6. Fontan-associated liver disease: diagnosis by elastography and laparoscopic liver biopsy
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Koizumi, Y., primary, Hirooka, M., additional, Yukimoto, A., additional, Imai, Y., additional, Nakamura, Y., additional, Watanabe, T., additional, Yoshida, O., additional, Tokumoto, Y., additional, Higaki, T., additional, Abe, M., additional, and Hiasa, Y., additional
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- 2017
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7. Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib
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T. Ishikawa, M. Imai, Noritomo Shimada, Kazuya Kariyama, Shinya Fukunishi, Akemi Tsutsui, Masashi Hirooka, Hideki Iwamoto, Norio Itokawa, Atsushi Hiraoka, Tomomi Okubo, Ei Itobayashi, Kazuhito Kawata, Joji Tani, Yoichi Hiasa, Kouji Joko, N. Sakamoto, F. Marra, Taeang Arai, Koichi Takaguchi, Francesco Giuseppe Foschi, Masanori Atsukawa, Yohei Koizumi, Marianna Silletta, Massimo Iavarone, Takuya Nagano, J. Siebler, Stefano Cascinu, T. Sho, Margherita Rimini, S. Shigeo, T. Aoki, L. Aldrighetti, Toshifumi Tada, G. Suda, A. Jefremow, V. Burgio, Takashi Niizeki, Hidenori Toyoda, Gianluca Masi, Sara Lonardi, Kazuto Tajiri, F. Ratti, Shinichiro Nakamura, W. Kang, A. Cucchetti, Takashi Kumada, Raffaella Tortora, E. Tamburini, Kunihiko Tsuji, Satoshi Yasuda, Fabio Piscaglia, Hiroshi Shibata, Kazuhiro Nouso, Giuseppe Cabibbo, K. Ueshima, Hironori Ochi, Andrea Casadei-Gardini, Hideko Ohama, T. Takaaki, M. Kudo, M.J. Goh, Rimini M., Kudo M., Tada T., Shigeo S., Kang W., Suda G., Jefremow A., Burgio V., Iavarone M., Tortora R., Marra F., Lonardi S., Tamburini E., Piscaglia F., Masi G., Cabibbo G., Foschi F.G., Silletta M., Kumada T., Iwamoto H., Aoki T., Goh M.J., Sakamoto N., Siebler J., Hiraoka A., Niizeki T., Ueshima K., Sho T., Atsukawa M., Hirooka M., Tsuji K., Ishikawa T., Takaguchi K., Kariyama K., Itobayashi E., Tajiri K., Shimada N., Shibata H., Ochi H., Yasuda S., Toyoda H., Fukunishi S., Ohama H., Kawata K., Tani J., Nakamura S., Nouso K., Tsutsui A., Nagano T., Takaaki T., Itokawa N., Okubo T., Arai T., Imai M., Joko K., Koizumi Y., Hiasa Y., Cucchetti A., Ratti F., Aldrighetti L., Cascinu S., Casadei-Gardini A., Rimini, M., Kudo, M., Tada, T., Shigeo, S., Kang, W., Suda, G., Jefremow, A., Burgio, V., Iavarone, M., Tortora, R., Marra, F., Lonardi, S., Tamburini, E., Piscaglia, F., Masi, G., Cabibbo, G., Foschi, F. G., Silletta, M., Kumada, T., Iwamoto, H., Aoki, T., Goh, M. J., Sakamoto, N., Siebler, J., Hiraoka, A., Niizeki, T., Ueshima, K., Sho, T., Atsukawa, M., Hirooka, M., Tsuji, K., Ishikawa, T., Takaguchi, K., Kariyama, K., Itobayashi, E., Tajiri, K., Shimada, N., Shibata, H., Ochi, H., Yasuda, S., Toyoda, H., Fukunishi, S., Ohama, H., Kawata, K., Tani, J., Nakamura, S., Nouso, K., Tsutsui, A., Nagano, T., Takaaki, T., Itokawa, N., Okubo, T., Arai, T., Imai, M., Joko, K., Koizumi, Y., Hiasa, Y., Cucchetti, A., Ratti, F., Aldrighetti, L., Cascinu, S., and Casadei-Gardini, A.
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Oncology ,Phenylurea Compound ,atezolizumab ,Cancer Research ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Quinoline ,lenvatinib ,bevacizumab ,chemistry.chemical_compound ,Liver disease ,Retrospective Studie ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Medicine ,Humans ,nonalcoholic steatohepatitis ,Original Research ,Retrospective Studies ,Univariate analysis ,Settore MED/12 - Gastroenterologia ,Performance status ,business.industry ,Phenylurea Compounds ,Hazard ratio ,Liver Neoplasms ,Retrospective cohort study ,Hepatitis C ,hepatocellular carcinoma ,medicine.disease ,Prognosis ,digestive system diseases ,advanced hepatocarcinoma ,hepatitis C ,immunotherapy ,sorafenib ,chemistry ,Liver Neoplasm ,Hepatocellular carcinoma ,nonalcoholic steatohepatiti ,Quinolines ,business ,Lenvatinib ,Human - Abstract
Background Hepatocellular carcinoma (HCC) treatment remains a big challenge in the field of oncology. The liver disease (viral or not viral) underlying HCC turned out to be crucial in determining the biologic behavior of the tumor, including its response to treatment. The aim of this analysis was to investigate the role of the etiology of the underlying liver disease in survival outcomes. Patients and methods We conducted a multicenter retrospective study on a large cohort of patients treated with lenvatinib as first-line therapy for advanced HCC from both Eastern and Western institutions. Univariate and multivariate analyses were performed. Results Among the 1232 lenvatinib-treated HCC patients, 453 (36.8%) were hepatitis C virus positive, 268 hepatitis B virus positive (21.8%), 236 nonalcoholic steatohepatitis (NASH) correlate (19.2%) and 275 had other etiologies (22.3%). The median progression-free survival (mPFS) was 6.2 months [95% confidence interval (CI) 5.9-6.7 months] and the median overall survival (mOS) was 15.8 months (95% CI 14.9-17.2 months). In the univariate analysis for OS NASH-HCC was associated with longer mOS [22.2 versus 15.1 months; hazard ratio (HR) 0.69; 95% CI 0.56-0.85; P = 0.0006]. In the univariate analysis for PFS NASH-HCC was associated with longer mPFS (7.5 versus 6.5 months; HR 0.84; 95% CI 0.71-0.99; P = 0.0436). The multivariate analysis confirmed NASH-HCC (HR 0.64; 95% CI 0.48-0.86; P = 0.0028) as an independent prognostic factor for OS, along with albumin–bilirubin (ALBI) grade, extrahepatic spread, neutrophil-to-lymphocyte ratio, portal vein thrombosis, Eastern Cooperative Oncology Group (ECOG) performance status and alpha-fetoprotein. An interaction test was performed between sorafenib and lenvatinib cohorts and the results highlighted the positive predictive role of NASH in favor of the lenvatinib arm (P = 0.0047). Conclusion NASH has been identified as an independent prognostic factor in a large cohort of patients with advanced HCC treated with lenvatinib, thereby suggesting the role of the etiology in the selection of patients for tyrosine kinase treatment. If validated, this result could provide new insights useful to improve the management of these patients., Highlights • Evidence supported the idea that etiology could sustain a crucial role in biological behavior. • NASH constitutes one of the more important risk factors for hepatocarcinoma, and its incidence is increasing very fast. • We performed an analysis in patients treated with lenvatinib as the first-line therapy. • NASH was found to be an independent prognostic factor.
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- 2021
8. Lenvatinib versus sorafenib in first-line treatment of unresectable hepatocellular carcinoma: An inverse probability of treatment weighting analysis
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Andrea Casadei‐Gardini, Mario Scartozzi, Toshifumi Tada, Changhoon Yoo, Shigeo Shimose, Gianluca Masi, Sara Lonardi, Luca Giovanni Frassineti, Silvestris Nicola, Fabio Piscaglia, Takashi Kumada, Hyung‐Don Kim, Hironori Koga, Caterina Vivaldi, Caterina Soldà, Atsushi Hiraoka, Yeonghak Bang, Masanori Atsukawa, Takuji Torimura, Kunihiko Tsuj, Ei Itobayashi, Hidenori Toyoda, Shinya Fukunishi, Lorenza Rimassa, Margherita Rimini, Stefano Cascinu, Alessandro Cucchetti, Shinichiro Nakamura, Kojiro Michitaka, Norio Itokawa, Korenobu Hayama, Masashi Hirooka, Yohei Koizumi, Yoichi Hiasa, Toru Ishikawa, Michitaka Imai, Koichi Takaguchi, Akemi Tsutsui, Takuya Nagano, Kazuya Kariyama, Kazuhiro Nouso, Kazuto Tajiri, Noritomo Shimada, Hiroshi Shibata, Hironori Ochi, Kouji Joko, Satoshi Yasuda, Hideko Ohama, Kazuhito Kawata, Casadei-Gardini A., Scartozzi M., Tada T., Yoo C., Shimose S., Masi G., Lonardi S., Frassineti L.G., Nicola S., Piscaglia F., Kumada T., Kim H.-D., Koga H., Vivaldi C., Solda C., Hiraoka A., Bang Y., Atsukawa M., Torimura T., Tsuj K., Itobayashi E., Toyoda H., Fukunishi S., Rimassa L., Rimini M., Cascinu S., Cucchetti A., Nakamura S., Michitaka K., Itokawa N., Hayama K., Hirooka M., Koizumi Y., Hiasa Y., Ishikawa T., Imai M., Takaguchi K., Tsutsui A., Nagano T., Kariyama K., Nouso K., Tajiri K., Shimada N., Shibata H., Ochi H., Joko K., Yasuda S., Ohama H., Kawata K., Casadei-Gardini, A., Scartozzi, M., Tada, T., Yoo, C., Shimose, S., Masi, G., Lonardi, S., Frassineti, L. G., Nicola, S., Piscaglia, F., Kumada, T., Kim, H. -D., Koga, H., Vivaldi, C., Solda, C., Hiraoka, A., Bang, Y., Atsukawa, M., Torimura, T., Tsuj, K., Itobayashi, E., Toyoda, H., Fukunishi, S., Rimassa, L., Rimini, M., Cascinu, S., Cucchetti, A., Nakamura, S., Michitaka, K., Itokawa, N., Hayama, K., Hirooka, M., Koizumi, Y., Hiasa, Y., Ishikawa, T., Imai, M., Takaguchi, K., Tsutsui, A., Nagano, T., Kariyama, K., Nouso, K., Tajiri, K., Shimada, N., Shibata, H., Ochi, H., Joko, K., Yasuda, S., Ohama, H., and Kawata, K.
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Sorafenib ,Oncology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Antineoplastic Agents ,lenvatinib ,survival ,trans-arterial chemoembolization ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Clinical endpoint ,performance status ,Humans ,Adverse effect ,Probability ,Hepatology ,Performance status ,business.industry ,Phenylurea Compounds ,Carcinoma ,Liver Neoplasms ,Hepatocellular ,medicine.disease ,extrahepatic disease ,sorafenib ,Quinolines ,chemistry ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Cohort ,030211 gastroenterology & hepatology ,Lenvatinib ,business ,medicine.drug ,performance statu - Abstract
Purpose Data from common clinical practice were used to generate balanced cohorts of patients receiving either sorafenib or lenvatinib, for unresectable hepatocellular carcinoma, with the final aim to investigate their declared equivalence. Methods Clinical features of lenvatinib and sorafenib patients were balanced through inverse probability of treatment weighting (IPTW) methodology, which weights patients' characteristics and measured outcomes of each patient in both treatment arms. Overall survival was the primary endpoint and occurrence of adverse events was the secondary. Results The analysis included 385 patients who received lenvatinib, and 555 patients who received sorafenib. In the unadjusted cohort, lenvatinib did not show a survival advantage over sorafenib (HR: 0.85, 95% CI 0.70-1.02). After IPTW adjustment, lenvatinib still not returned a survival advantage over sorafenib (HR: 0.82, 95% CI: 0.62-1.07) even in presence of balanced baseline characteristics. Lenvatinib provided longer survival than sorafenib in patients previously submitted to TACE (HR: 0.69), with PS of 0 (HR: 0.73) or without extrahepatic disease (HR: 0.69). Conclusion Present results confirmed randomized controlled trial in the real-life setting, but also suggests that in earlier stages some benefit can be expected.
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- 2021
9. Adverse events as potential predictive factors of activity in patients with advanced hepatocellular carcinoma treated with lenvatinib
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Joji Tani, Noritomo Shimada, Taeang Arai, Massimo Iavarone, Valentina Burgio, Koichi Takaguchi, Masanori Atsukawa, Marianna Silletta, Hideko Ohama, Takaaki Tanaka, Hironori Koga, Masashi Hirooka, Emiliano Tamburini, Stefano Cascinu, Ei Itobayashi, Luca Aldrighetti, Gianluca Masi, Takashi Kumada, Kazuhito Kawata, Yoichi Hiasa, Toshifumi Tada, Atsushi Hiraoka, Raffaella Tortora, Shinichiro Nakamura, Kouji Joko, Takuji Torimura, Sara Lonardi, Takuya Nagano, Hironori Ochi, Ilario Giovanni Rapposelli, Francesco Giuseppe Foschi, Akemi Tsutsui, Hideki Iwamoto, Shigeo Shimose, Satoshi Yasuda, Tomomi Okubo, Hiroshi Shibata, Takashi Niizeki, Hidenori Toyoda, Giuseppe Cabibbo, Margherita Rimini, Toru Ishikawa, Shinya Fukunishi, Claudia Campani, Kazuya Kariyama, Kazuto Tajiri, Kunihiko Tsuji, Fabio Piscaglia, Andrea Casadei-Gardini, Kazuhiro Nouso, Yohei Koizumi, Francesca Ratti, Norio Itokawa, Michitaka Imai, Rapposelli I.G., Tada T., Shimose S., Burgio V., Kumada T., Iwamoto H., Hiraoka A., Niizeki T., Atsukawa M., Koga H., Hirooka M., Torimura T., Iavarone M., Tortora R., Campani C., Lonardi S., Tamburini E., Piscaglia F., Masi G., Cabibbo G., Giuseppe Foschi F., Silletta M., Tsuji K., Ishikawa T., Takaguchi K., Kariyama K., Itobayashi E., Tajiri K., Shimada N., Shibata H., Ochi H., Yasuda S., Toyoda H., Fukunishi S., Ohama H., Kawata K., Tani J., Nakamura S., Nouso K., Tsutsui A., Nagano T., Tanaka T., Itokawa N., Okubo T., Arai T., Imai M., Joko K., Koizumi Y., Hiasa Y., Rimini M., Ratti F., Aldrighetti L., Cascinu S., Casadei-Gardini A., Rapposelli, I. G., Tada, T., Shimose, S., Burgio, V., Kumada, T., Iwamoto, H., Hiraoka, A., Niizeki, T., Atsukawa, M., Koga, H., Hirooka, M., Torimura, T., Iavarone, M., Tortora, R., Campani, C., Lonardi, S., Tamburini, E., Piscaglia, F., Masi, G., Cabibbo, G., Giuseppe Foschi, F., Silletta, M., Tsuji, K., Ishikawa, T., Takaguchi, K., Kariyama, K., Itobayashi, E., Tajiri, K., Shimada, N., Shibata, H., Ochi, H., Yasuda, S., Toyoda, H., Fukunishi, S., Ohama, H., Kawata, K., Tani, J., Nakamura, S., Nouso, K., Tsutsui, A., Nagano, T., Tanaka, T., Itokawa, N., Okubo, T., Arai, T., Imai, M., Joko, K., Koizumi, Y., Hiasa, Y., Rimini, M., Ratti, F., Aldrighetti, L., Cascinu, S., and Casadei-Gardini, A.
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Phenylurea Compound ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Multivariate analysis ,predictive factors ,adverse event ,lenvatinib ,Gastroenterology ,predictive factor ,chemistry.chemical_compound ,Quality of life ,Internal medicine ,medicine ,Humans ,Adverse effect ,Retrospective Studies ,adverse events ,hepatocellular carcinoma ,Settore MED/12 - Gastroenterologia ,Hepatology ,business.industry ,Phenylurea Compounds ,Liver Neoplasms ,Hazard ratio ,medicine.disease ,Confidence interval ,Discontinuation ,chemistry ,Liver Neoplasm ,Hepatocellular carcinoma ,Quality of Life ,Quinolines ,Lenvatinib ,business - Abstract
Background and Aim: Lenvatinib is a standard of care option in first-line therapy of advanced hepatocellular carcinoma (HCC). In the present study, we aim to identify, in patients with HCC treated with lenvatinib, a possible association between occurrence and grading of adverse events (AEs) and outcome. Methods: We performed a retrospective analysis of 606 Japanese and Italian patients treated with lenvatinib in first-line setting and investigated the possible correlation between the onset of AEs, toxicity grade (G) and outcome measures such as overall survival (OS) and progression-free survival (PFS). Results: The appearance of arterial hypertension G≥2 independently predicted prolonged OS [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.46–0.93, P=.0188], whereas decreased appetite G≥2 independently predicted decreased OS (HR 1.70, 95% CI 1.25–2.32, P=.0007) by multivariate analysis. Appearance of hand-foot skin reaction independently predicted prolonged PFS (HR 0.72, 95% CI 0.56–0.93, P=.0149), whereas decreased appetite G≥2 predicted decreased PFS (HR 1.36, 95% CI 1.04–1.77, P=.0277). Conclusions: Our main findings are that the occurrence of arterial hypertension G≥2 is a predictor of longer survival, whereas decreased appetite G≥2 predicts for a poor prognosis. A careful management of AEs under lenvatinib treatment for HCC is required, to improve patients’ quality of life, minimize the need for treatment discontinuation and achieve optimal outcome.
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- 2021
10. Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis
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M. Rimini, L. Rimassa, K. Ueshima, V. Burgio, S. Shigeo, T. Tada, G. Suda, C. Yoo, J. Cheon, D.J. Pinato, S. Lonardi, M. Scartozzi, M. Iavarone, G.G. Di Costanzo, F. Marra, C. Soldà, E. Tamburini, F. Piscaglia, G. Masi, G. Cabibbo, F.G. Foschi, M. Silletta, T. Pressiani, N. Nishida, H. Iwamoto, N. Sakamoto, B.-Y. Ryoo, H.J. Chon, F. Claudia, T. Niizeki, T. Sho, B. Kang, A. D’Alessio, T. Kumada, A. Hiraoka, M. Hirooka, K. Kariyama, J. Tani, M. Atsukawa, K. Takaguchi, E. Itobayashi, S. Fukunishi, K. Tsuji, T. Ishikawa, K. Tajiri, H. Ochi, S. Yasuda, H. Toyoda, C. Ogawa, T. Nishimur, T. Hatanaka, S. Kakizaki, N. Shimada, K. Kawata, T. Tanaka, H. Ohama, K. Nouso, A. Morishita, A. Tsutsui, T. Nagano, N. Itokawa, T. Okubo, T. Arai, M. Imai, A. Naganuma, Y. Koizumi, S. Nakamura, K. Joko, H. Iijima, Y. Hiasa, F. Pedica, F. De Cobelli, F. Ratti, L. Aldrighetti, M. Kudo, S. Cascinu, A. Casadei-Gardini, M Rimini , L Rimassa, K Ueshima, V Burgio, S Shigeo, T Tada, G Suda, C Yoo, J Cheon, D J Pinato, S Lonardi, M Scartozzi, M Iavarone, G G Di Costanzo, F Marra, C Soldà, E Tamburini, F Piscaglia, G Masi, G Cabibbo, F G Foschi, M Silletta, T Pressiani, N Nishida, H Iwamoto, N Sakamoto, B-Y Ryoo, H J Chon, F Claudia, T Niizeki, T Sho, B Kang, A D'Alessio, T Kumada, A Hiraoka, M Hirooka, K Kariyama, J Tani, M Atsukawa, K Takaguchi, E Itobayashi, S Fukunishi, K Tsuji, T Ishikawa, K Tajiri, H Ochi, S Yasuda, H Toyoda, C Ogawa, T Nishimur, T Hatanaka, S Kakizaki, N Shimada, K Kawata , T Tanaka, H Ohama, K Nouso, A Morishita, A Tsutsui, T Nagano, N Itokawa, T Okubo, T Arai, M Imai, A Naganuma, Y Koizumi, S Nakamura, K Joko, H Iijima, Y Hiasa, F Pedica, F De Cobelli, F Ratti, L Aldrighetti, M Kudo, S Cascinu, A Casadei-Gardini, Rimini M., Rimassa L., Ueshima K., Burgio V., Shigeo S., Tada T., Suda G., Yoo C., Cheon J., Pinato D.J., Lonardi S., Scartozzi M., Iavarone M., Di Costanzo G.G., Marra F., Solda C., Tamburini E., Piscaglia F., Masi G., Cabibbo G., Foschi F.G., Silletta M., Pressiani T., Nishida N., Iwamoto H., Sakamoto N., Ryoo B.-Y., Chon H.J., Claudia F., Niizeki T., Sho T., Kang B., D'Alessio A., Kumada T., Hiraoka A., Hirooka M., Kariyama K., Tani J., Atsukawa M., Takaguchi K., Itobayashi E., Fukunishi S., Tsuji K., Ishikawa T., Tajiri K., Ochi H., Yasuda S., Toyoda H., Ogawa C., Nishimur T., Hatanaka T., Kakizaki S., Shimada N., Kawata K., Tanaka T., Ohama H., Nouso K., Morishita A., Tsutsui A., Nagano T., Itokawa N., Okubo T., Arai T., Imai M., Naganuma A., Koizumi Y., Nakamura S., Joko K., Iijima H., Hiasa Y., Pedica F., De Cobelli F., Ratti F., Alrighetti L., Kudo M., Cascinu S., and Casadei-Gardini A.
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atezolizumab ,Cancer Research ,Settore MED/12 - Gastroenterologia ,Oncology ,sorafenib ,NAFLD ,NASH ,advanced HCC ,advanced HCC, NASH, NAFLD, lenvatinib, sorafenib, atezolizumab, bevacizumab ,lenvatinib ,bevacizumab - Abstract
Background: A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy. Materials and methods: We carried out a retrospective analysis of prospectively collected data from consecutive patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib, or sorafenib, in 36 centers in 4 countries (Italy, Japan, Republic of Korea, and UK). The primary endpoint was overall survival (OS) with atezolizumab plus bevacizumab versus lenvatinib. Secondary endpoints were progression-free survival (PFS) with atezolizumab plus bevacizumab versus lenvatinib, and OS and PFS with atezolizumab plus bevacizumab versus sorafenib. For the primary and secondary endpoints, we carried out the analysis on the whole population first, and then we divided the cohort into two groups: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) population and non-NAFLD/NASH population. Results: One hundred and ninety patients received atezolizumab plus bevacizumab, 569 patients received lenvatinib, and 210 patients received sorafenib. In the whole population, multivariate analysis showed that treatment with lenvatinib was associated with a longer OS [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.44-0.95; P = 0.0268] and PFS (HR 0.67; 95% CI 0.51-0.86; P = 0.002) compared to atezolizumab plus bevacizumab. In the NAFLD/NASH population, multivariate analysis confirmed that lenvatinib treatment was associated with a longer OS (HR 0.46; 95% CI 0.26-0.84; P = 0.0110) and PFS (HR 0.55; 95% CI 0.38-0.82; P = 0.031) compared to atezolizumab plus bevacizumab. In the subgroup of non-NAFLD/NASH patients, no difference in OS or PFS was observed between patients treated with lenvatinib and those treated with atezolizumab plus bevacizumab. All these results were confirmed following propensity score matching analysis. By comparing patients receiving atezolizumab plus bevacizumab versus sorafenib, no statistically significant difference in survival was observed. Conclusions: The present analysis conducted on a large number of advanced non-viral HCC patients showed for the first time that treatment with lenvatinib is associated with a significant survival benefit compared to atezolizumab plus bevacizumab, in particular in patients with NAFLD/NASH-related HCC.
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- 2022
11. Predictive factors and survival outcome of conversion therapy for unresectable hepatocellular carcinoma patients receiving atezolizumab and bevacizumab: Comparative analysis of conversion, partial response and complete response patients.
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Hatanaka T, Kakizaki S, Hiraoka A, Tada T, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Toyoda H, Ogawa C, Nishikawa H, Nishimura T, Kawata K, Kosaka H, Naganuma A, Yata Y, Ohama H, Kuroda H, Matono T, Aoki T, Kanayama Y, Tanaka K, Tada F, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Nakamura S, Enomoto H, Kaibori M, Hiasa Y, Kudo M, and Kumada T
- Abstract
Aim: This study aims to investigate the predictive factors for conversion therapy in patients with unresectable hepatocellular carcinoma (uHCC) and to evaluate the prognosis of conversion cases by comparing them with partial response (PR) and complete response (CR) cases., Methods: In this retrospective multicentre study, we included a total of 946 uHCC patients treated with atezolizumab and bevacizumab (Atez/Bev) from September 2020 to September 2023., Results: Out of the patients, 43 (4.5%) received conversion therapy following Atez/Bev treatment. The overall response rate was 65.1% and 23.7% in the conversion and non-conversion group, respectively, with a statistical significance (p < 0.001). Multivariate analyses identified that BCLC stage B or an earlier stage (p = 0.045), absence of macrovascular invasion and extrahepatic spread (p = 0.045), and a low value of neutrophil to lymphocyte ratio (p = 0.04) were significantly favourable predictive factors associated with conversion therapy. The conversion group showed significantly better survival compared to the non-conversion group (p < 0.001). In the landmark analysis at 6, 12 and 18 months, the conversion group exhibited better survival compared to PR patients in the non-conversion group (p = 0.04, 0.01 and 0.03, respectively) and there were no significant differences in the overall survival (OS) between the conversion group and patients who achieved a CR (p = 0.7, 1.0 and 0.3, respectively)., Conclusions: Patients with low tumour burden and low value of NLR were more likely to undergo conversion therapy. The OS of patients undergoing conversion therapy showed better survival compared to those achieving PR and was comparable to those with CR patients. Conversion therapy could be considered if feasible., (© 2024 John Wiley & Sons Ltd.)
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- 2024
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12. Diagnostic performance of shear wave measurement in the detection of hepatic fibrosis: A multicenter prospective study.
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Kumada T, Toyoda H, Ogawa S, Gotoh T, Yoshida Y, Yamahira M, Hirooka M, Koizumi Y, Hiasa Y, Tamai T, Kuromatsu R, Matsuzaki T, Suehiro T, Kamada Y, Sumida Y, Tanaka J, and Shimizu M
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Aim: This study aimed to establish the shear wave measurement (SWM) cut-off value for each fibrosis stage using magnetic resonance (MR) elastography values as a reference standard., Methods: We prospectively analyzed 594 patients with chronic liver disease who underwent SWM and MR elastography. Correlation coefficients (were analyzed, and the diagnostic value was evaluated by the area under the receiver operating characteristic curve. Liver stiffness was categorized by MR elastography as F0 (<2.61 kPa), F1 (≥2.61 kPa, <2.97 kPa, any fibrosis), F2 (≥2.97 kPa, <3.62 kPa, significant fibrosis), F3 (≥3.62 kPa, <4.62 kPa, advanced fibrosis), or F4 (≥4.62 kPa, cirrhosis)., Results: The median SWM values increased significantly with increasing fibrosis stage (p < 0.001). The correlation coefficient between SWM and MR elastography values was 0.793 (95% confidence interval 0.761-0.821). The correlation coefficients between SWM and MR elastography values significantly decreased with increasing body mass index and skin-capsular distance; skin-capsular distance values were associated with significant differences in sensitivity, specificity, accuracy, or positive predictive value, whereas body mass index values were not. The best cut-off values for any fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis were 6.18, 7.09, 8.05, and 10.89 kPa, respectively., Conclusions: This multicenter study in a large number of patients established SWM cut-off values for different degrees of fibrosis in chronic liver diseases using MR elastography as a reference standard. It is expected that these cut-off values will be applied to liver diseases in the future., (© 2024 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)
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- 2024
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13. Association between serum remnant cholesterol level and metabolic dysfunction-associated steatotic liver histology.
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Miyake T, Furukawa S, Matsuura B, Yoshida O, Kanamoto A, Miyazaki M, Shiomi A, Nakaguchi H, Okazaki Y, Nakamura Y, Imai Y, Koizumi M, Watanabe T, Yamamoto Y, Koizumi Y, Tokumoto Y, Hirooka M, Kumagi T, Abe M, and Hiasa Y
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Context: Estimated remnant cholesterol (Rem-C) level, a risk factor for cardiovascular disease (CVD), is associated with metabolic dysfunction-associated steatotic liver disease (MASLD) diagnosed via ultrasonography. However, the relationship between accurate serum Rem-C level measurements and histological findings of MASLD remains unclear., Objective: We aimed to elucidate the relationship between accurately measured serum Rem-C levels and histological findings of MASLD., Design: Cross-sectional single-center observational study., Methods: We assessed 222 patients (94 men and 128 women; age 20-80) who were diagnosed with MASLD via liver biopsy with available medical history, physical examination, and biochemical measurement data. Serum ester-type cholesterol and free cholesterol contents in the remnant lipoproteins were measured using an enzymatic method., Results: Serum Rem-C levels were significantly higher in patients with NAFLD activity score (NAS) 5-8, >66% steatosis grade, lobular inflammation with ≥5 foci, and many cells/prominent ballooning cells (a contiguous patch of hepatocytes showing prominent ballooning injury) than in patients with NAS 1-4, <33% steatosis grade, lobular inflammation with <2 foci, and few ballooning cells (several scattered balloon cells), respectively. While univariate analysis revealed no significant association between Rem-C levels and advanced fibrosis, a significant association between Rem-C levels and NAS was evident. This relationship remained significant in multivariate analysis adjusted for confounders. Furthermore, in the analysis by sex, these relationships were significant for men but not for women., Conclusion: High serum Rem-C levels were associated with high NAS, but not with fibrosis stage, particularly in men. Controlling serum Rem-C level may improve MASLD activity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)
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- 2024
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14. Changes in characteristics of gastroenterology center inpatients in Japan because of rapidly aging society.
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Fukunishi Y, Hiraoka A, Tada F, Fukumoto M, Matsuda T, Matsuoka K, Nakatani K, Yanagihara E, Saneto H, Izumoto H, Murakami T, Onishi K, Kitahata S, Kanemitsu-Okada K, Kawamura T, Kuroda T, Miyata H, Tsubouchi E, Hanaoka J, Watanabe J, Ohtani H, Yoshida O, Hirooka M, Abe M, Matsuura B, Ninomiya T, and Hiasa Y
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- Humans, Japan epidemiology, Aged, Retrospective Studies, Male, Female, Aged, 80 and over, Middle Aged, Aging, Liver Diseases epidemiology, Liver Diseases therapy, Liver Diseases diagnosis, Biliary Tract Diseases epidemiology, Biliary Tract Diseases therapy, Gastrointestinal Diseases epidemiology, Gastrointestinal Diseases therapy, Gastrointestinal Diseases diagnosis, Hospitalization statistics & numerical data, Time Factors, Age Factors, Adult, Pancreatic Diseases epidemiology, Pancreatic Diseases therapy, Inpatients statistics & numerical data, Gastroenterology statistics & numerical data, Gastroenterology trends
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Background and Aim: Rapidly aging societies have become a major issue worldwide including Japan. This study aimed to elucidate relative changes in the characteristics of inpatients in Japan related to this issue., Methods: A total of 23 835 Japanese inpatients treated from 2010 to 2021 were enrolled (2010-2013, period I; 2014-2017, period II; 2018-2021, period III). Changes in clinical features were retrospectively analyzed based on ICD-10 diagnosis data., Results: The percentage of patients aged over 75 years increased over time (period I, 38.0%; II, 39.5%, III, 41.4%). Emergency admissions comprised 27.5% of all in period I, which increased to 43.2% in period II and again to 44.5% in period III (P < 0.001). In period I, gastrointestinal disease, liver disease, pancreatic-biliary disease, and other disease types were noted in 47.4%, 29.5%, 19.2%, and 3.9%, respectively, while those values were 44.0%, 18.0%, 33.9%, and 4.1%, respectively, in period III (P < 0.001). The frequency of liver disease decreased by approximately 0.6-fold from periods I to III, while that of biliary-pancreatic disease increased by approximately 1.8-fold during that time. Both percentage and actual numbers of patients with biliary-pancreatic disease increased during the examined periods. Analysis of changes in the proportion of organs affected by malignancy during periods I, II, and III showed a marked increase in cases of biliary-pancreatic malignancy (11.6%, 19.5%, 26.6%, respectively) (P < 0.001)., Conclusion: In association with the rapidly aging Japanese society, there has been an increasing frequency of biliary-pancreatic disease cases requiring hospitalization for treatment in the west Japan region of Shikoku., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)
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- 2024
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15. Correction to: A Novel SAVE Score to Stratify Decompensation Risk in Compensated Advanced Chronic Liver Disease (CHESS2102): An International Multicenter Cohort Study.
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Liu C, Cao Z, Yan H, Wong YJ, Xie Q, Hirooka M, Enomoto H, Kim TH, Hanafy AS, Liu Y, Huang Y, Li X, Kang N, Koizumi Y, Hiasa Y, Nishimura T, Iijima H, Jung YK, Yim HJ, Guo Y, Zhang L, Ma J, Kumar M, Jindal A, Teh KB, Sarin SK, and Qi X
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- Humans, Risk Assessment, Chronic Disease, Liver Cirrhosis complications, Cohort Studies, Liver Diseases complications, Severity of Illness Index
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- 2024
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16. Diagnostic accuracy of non-invasive tests to screen for at-risk MASH-An individual participant data meta-analysis.
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Mózes FE, Lee JA, Vali Y, Selvaraj EA, Jayaswal ANA, Boursier J, de Lédinghen V, Lupșor-Platon M, Yilmaz Y, Chan WK, Mahadeva S, Karlas T, Wiegand J, Shalimar, Tsochatzis E, Liguori A, Wong VW, Lee DH, Holleboom AG, van Dijk AM, Mak AL, Hagström H, Akbari C, Hirooka M, Lee DH, Kim W, Okanoue T, Shima T, Nakajima A, Yoneda M, Thuluvath PJ, Li F, Berzigotti A, Mendoza YP, Noureddin M, Truong E, Fournier-Poizat C, Geier A, Tuthill T, Yunis C, Anstee QM, Harrison SA, Bossuyt PM, and Pavlides M
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- Humans, ROC Curve, Liver pathology, Liver diagnostic imaging, Liver Cirrhosis diagnosis, Biopsy, Mass Screening methods, Elasticity Imaging Techniques methods, Non-alcoholic Fatty Liver Disease diagnosis, Non-alcoholic Fatty Liver Disease diagnostic imaging
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Background & Aims: There is a need to reduce the screen failure rate (SFR) in metabolic dysfunction-associated steatohepatitis (MASH) clinical trials (MASH+F2-3; MASH+F4) and identify people with high-risk MASH (MASH+F2-4) in clinical practice. We aimed to evaluate non-invasive tests (NITs) screening approaches for these target conditions., Methods: This was an individual participant data meta-analysis for the performance of NITs against liver biopsy for MASH+F2-4, MASH+F2-3 and MASH+F4. Index tests were the FibroScan-AST (FAST) score, liver stiffness measured using vibration-controlled transient elastography (LSM-VCTE), the fibrosis-4 score (FIB-4) and the NAFLD fibrosis score (NFS). Area under the receiver operating characteristics curve (AUROC) and thresholds including those that achieved 34% SFR were reported., Results: We included 2281 unique cases. The prevalence of MASH+F2-4, MASH+F2-3 and MASH+F4 was 31%, 24% and 7%, respectively. Area under the receiver operating characteristics curves for MASH+F2-4 were .78, .75, .68 and .57 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F2-3 were .73, .67, .60, .58 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F4 were .79, .84, .81, .76 for FAST, LSM-VCTE, FIB-4 and NFS. The sequential combination of FIB-4 and LSM-VCTE for the detection of MASH+F2-3 with threshold of .7 and 3.48, and 5.9 and 20 kPa achieved SFR of 67% and sensitivity of 60%, detecting 15 true positive cases from a theoretical group of 100 participants at the prevalence of 24%., Conclusions: Sequential combinations of NITs do not compromise diagnostic performance and may reduce resource utilisation through the need of fewer LSM-VCTE examinations., (© 2024 The Authors. Liver International published by John Wiley & Sons Ltd.)
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- 2024
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17. Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306).
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Liu C, You H, Zeng QL, Wong YJ, Wang B, Grgurevic I, Liu C, Yim HJ, Gou W, Dong B, Ju S, Guo Y, Yu Q, Hirooka M, Enomoto H, Hanafy AS, Cao Z, Dong X, Lv J, Kim TH, Koizumi Y, Hiasa Y, Nishimura T, Iijima H, Xu C, Dai E, Lan X, Lai C, Liu S, Wang F, Guo Y, Lv J, Zhang L, Wang Y, Xie Q, Shao C, Liu Z, Ravaioli L, Colecchia A, Li J, Teng GJ, and Qi X
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Background & Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model., Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvedilol-treating cohort., Results: In the meta-analysis with six studies (n = 819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new "CSPH risk" model. In the HVPG cohort (n = 151), the new model accurately predicted CSPH with cutoff values of 0 and -0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n = 1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <-0.68 (low-risk), -0.68 to 0 (medium-risk), and >0 (high-risk). In the carvedilol-treated cohort, patients with high-risk CSPH treated with carvedilol (n = 81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n = 613 before propensity score matching [PSM], n = 162 after PSM)., Conclusions: Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.
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- 2024
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18. Correction: Clinical features of patients with hepatocellular carcinoma treated with radiofrequency ablation therapy: developing a simple score to determine the need for immune-adjuvant therapy.
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Tada F, Hiraoka A, Nakatani K, Matsuoka K, Fukumoto M, Matsuda T, Yanagihara E, Saneto H, Murakami T, Onishi K, Izumoto H, Kitahata S, Kanemitsu-Okada K, Kawamura T, Kuroda T, Hanaoka J, Watanabe J, Ohtani H, Yoshida O, Hirooka M, Miyata H, Tsubouchi E, Abe M, Matsuura B, Ninomiya T, and Hiasa Y
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- 2024
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19. Outcomes of patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab in real-world clinical practice who met or did not meet the inclusion criteria for the phase 3 IMbrave150 trial.
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Tada T, Kumada T, Hiraoka A, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Nishikawa H, Tsuji K, Ishikawa T, Tajiri K, Koshiyama Y, Toyoda H, Ogawa C, Hatanaka T, Kakizaki S, Kawata K, Ohama H, Tada F, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Nishimura T, Imai M, Kosaka H, Naganuma A, Matono T, Aoki T, Kuroda H, Yata Y, Koizumi Y, Nakamura S, Enomoto H, Kaibori M, Hiasa Y, and Kudo M
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- Humans, Male, Female, Middle Aged, Aged, Treatment Outcome, Progression-Free Survival, Adult, Liver Neoplasms drug therapy, Liver Neoplasms mortality, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular mortality, Bevacizumab therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use
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Background: Atezolizumab plus bevacizumab (Atezo/Bev) is frequently selected as the primary systemic therapy for hepatocellular carcinoma (HCC)., Aims: To investigate the outcomes of patients with HCC treated with Atezo/Bev in a real-world setting based on whether they met the inclusion criteria for the phase 3 IMbrave150 trial., Methods: A total of 936 patients were enrolled. There were 404 patients who met the inclusion criteria of the phase 3 IMbrave150 trial (IMbrave150 group) and 532 who did not (non-IMbrave150 group)., Results: Median progression-free survival (PFS) in the IMbrave150 and non-IMbrave150 groups was 7.4 months and 5.6 months (p = 0.002). Multivariable analysis revealed that non-B, non-C HCC aetiology (hazard ratio [HR], 1.173), α-fetoprotein ≥100 ng/mL (HR, 1.472), Barcelona Clinic Liver Cancer stage ≥ C (HR, 1.318), and modified albumin-bilirubin (mALBI) grade 2b or 3 (HR, 1.476) are independently associated with PFS. Median overall survival (OS) in the IMbrave150 and non-Imbrave150 groups was 26.5 and 18.8 months (p < 0.001). Multivariable analysis revealed that Eastern Cooperative Oncology Group performance status ≥2 (HR, 1.986), α-fetoprotein ≥100 ng/mL (HR, 1.481), and mALBI grade 2b or 3 (HR, 2.037) are independently associated with OS. In subgroup analysis, there were no significant differences in PFS or OS between these groups among patients with mALBI grade 1 or 2a., Conclusions: Patients who are treated with Atezo/Bev and meet the inclusion criteria for the phase 3 IMbrave150 trial, as well as those who do not meet the inclusion criteria but have good liver function, have a good prognosis for survival., (© 2024 John Wiley & Sons Ltd.)
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- 2024
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20. Adverse Events as Potential Predictive Factors of Activity in Patients with Advanced HCC Treated with Atezolizumab Plus Bevacizumab.
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Persano M, Rimini M, Tada T, Suda G, Shimose S, Kudo M, Rossari F, Yoo C, Cheon J, Finkelmeier F, Lim HY, Presa J, Masi G, Bergamo F, Amadeo E, Vitiello F, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Chon HJ, Himmelsbach V, Iavarone MA, Cabibbo G, Montes M, Foschi FG, Vivaldi C, Soldà C, Sho T, Niizeki T, Nishida N, Steup C, Bruccoleri M, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Hiraoka A, Tada F, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Imai M, Kosaka H, Naganuma A, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, Foti S, Camera S, Piscaglia F, Scartozzi M, Cascinu S, and Casadei-Gardini A
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- Humans, Male, Female, Retrospective Studies, Aged, Middle Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols pharmacology, Aged, 80 and over, Adult, Prognosis, Bevacizumab therapeutic use, Bevacizumab pharmacology, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized pharmacology, Antibodies, Monoclonal, Humanized adverse effects, Liver Neoplasms drug therapy, Liver Neoplasms pathology, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular pathology
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Background: In the context of patients with hepatocellular carcinoma (HCC) treated with systemic therapy, the correlation between the appearance of adverse events (AEs) and reported efficacy outcomes is well-known and widely investigated. From other pathological settings, we are aware of the prognostic and predictive value of the occurrence of immune-related AEs in patients treated with immune-checkpoint inhibitors., Objective: This retrospective multicenter real-world study aims to investigate the potential prognostic value of AEs in patients with HCC treated with atezolizumab plus bevacizumab in the first-line setting., Patients and Methods: The study population consisted of 823 patients from five countries (Italy, Germany, Portugal, Japan, and the Republic of Korea)., Results: Of the patients, 73.3% presented at least one AE during the study period. The most common AEs were proteinuria (29.6%), arterial hypertension (27.2%), and fatigue (26.0%). In all, 17.3% of the AEs were grade (G) 3. One death due to bleeding was reported. The multivariate analysis confirmed the appearance of decreased appetite G < 2 [versus G ≥ 2; hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.13-0.90; p < 0.01] and immunotoxicity G < 2 (versus G ≥ 2; HR: 0.70; 95% CI 0.24-0.99; p = 0.04) as independent prognostic factors for overall survival, and the appearance of decreased appetite G < 2 (versus G ≥ 2; HR: 0.73; 95% CI 0.43-0.95; p = 0.01), diarrhea (yes versus no; HR: 0.57, 95% CI 0.38-0.85; p = 0.01), fatigue (yes versus no; HR: 0.82, 95% CI 0.65-0.95; p < 0.01), arterial hypertension G < 2 (versus G ≥ 2; HR: 0.68, 95% CI 0.52-0.87; p < 0.01), and proteinuria (yes versus no; HR: 0.79, 95% CI 0.64-0.98; p = 0.03) as independent prognostic factors for progression-free survival., Conclusions: As demonstrated for other therapies, there is also a correlation between the occurrence of AEs and outcomes for patients with HCC for the combination of atezolizumab plus bevacizumab., (© 2024. The Author(s).)
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- 2024
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21. Diagnostic accuracy of ultrasound-derived fat fraction for the detection and quantification of hepatic steatosis in patients with liver biopsy.
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Nakamura Y, Hirooka M, Koizumi Y, Yano R, Imai Y, Watanabe T, Yoshida O, Tokumoto Y, Abe M, and Hiasa Y
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Purpose: This retrospective study was conducted to investigate the diagnostic accuracy of ultrasound-derived fat fraction (UDFF) for grading hepatic steatosis using liver histology as the reference standard., Methods: Seventy-three patients with liver disease were assessed using UDFF and liver biopsy. Pearson's test and the Bland-Altman plot were used to assess the correlation between UDFF and histological fat content in liver sections. The UDFF cutoff values for histologically proven steatosis grades were determined using the area under the receiver operating characteristic curve (AUROC)., Results: The median age of the patients was 66 (interquartile range 54-74) years, and 33 (45%) were females. The UDFF values showed a stepwise increase with increasing steatosis grade (p < .001) and were strongly correlated with the histological fat content (r = .7736, p < .001). The Bland-Altman plot revealed a mean bias of 2.384% (95% limit of agreement, - 6.582 to 11.351%) between them. Univariate regression analysis revealed no significant predictors of divergence. The AUROCs for distinguishing steatosis grades of ≥ 1, ≥2, and 3 were 0.956 (95% confidence interval [CI], 0.910-1.00), 0.926 (95% CI, 0.860-0.993), and 0.971 (95% CI, 0.929-1.000), respectively. The UDFF cutoff value of > 6% had a sensitivity and specificity of 94.8% and 82.3%, respectively, for diagnosing steatosis grade ≥ 1. There was no association between UDFF and the fibrosis stage., Conclusion: UDFF shows strong agreement with the histological fat content and excellent diagnostic accuracy for grading steatosis. UDFF is a promising tool for detecting and quantifying hepatic steatosis in clinical practice., (© 2024. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)
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- 2024
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22. Clinical features of patients with hepatocellular carcinoma treated with radiofrequency ablation therapy: developing a simple score to determine the need for immune-adjuvant therapy.
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Tada F, Hiraoka A, Nakatani K, Matsuoka K, Fukumoto M, Matsuda T, Yanagihara E, Saneto H, Murakami T, Onishi K, Izumoto H, Kitahata S, Kanemitsu-Okada K, Kawamura T, Kuroda T, Hanaoka J, Watanabe J, Ohtani H, Yoshida O, Hirooka M, Miyata H, Tsubouchi E, Abe M, Matsuura B, Ninomiya T, and Hiasa Y
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- Humans, Male, Female, Aged, Retrospective Studies, Middle Aged, Chemotherapy, Adjuvant, Risk Factors, Aged, 80 and over, Carcinoma, Hepatocellular therapy, Carcinoma, Hepatocellular surgery, Carcinoma, Hepatocellular pathology, Liver Neoplasms therapy, Liver Neoplasms pathology, Liver Neoplasms surgery, Neoplasm Recurrence, Local, Radiofrequency Ablation
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Background/aim: Unresectable recurrence after curative treatments for hepatocellular carcinoma (HCC) is a life-limited event. Although the IMbrave050 trial (IM050) showed a favorable reduction in recurrence with adjuvant immune-combination chemotherapy, inclusion criteria of the radiofrequency ablation (RFA) group were lower risk than that of the resection group. This study aimed to elucidate the clinical features of patients treated with RFA, which really need adjuvant-chemotherapy., Methods: From 2000 to 2022, 528 patients with Child-Pugh A and HCC within the Milan criteria (MC), who met the IM050 criteria for RFA and undergone resection or RFA, were enrolled (71 years, HCV:HBV:HBV/HCV:alcohol:others = 337:44:5:53:89, multi-tumor = 138, RFA:resection = 309:219). Unresectable recurrence was defined as beyond the MC. Risk factors for recurrence beyond the MC were retrospectively evaluated., Results: Multivariate Cox-hazard analysis showed HCV-positive (HR 1.49), AFP-L3 > 10% (HR 1.75), and DCP > 100 mAU/mL (HR1.80) as significant prognostic factors for recurrence beyond the MC (each P < 0.05). Summing of positive factors (1 point for each) was used for scoring (AD-ON score), which showed increased positive rates for micro-hepatic vein invasion (score 0:1:2:3 = 0%:1.1%:6.6%:15.8%), micro-portal vein invasion (0:1:2:3 = 2.0%:12.1%:14.1%:31.6%), and poor differentiation (0:1:2:3 = 6.0%:6.7%:15.3%:15.8%) in the resection group associated with a greater score (each P < 0.01). In patients treated with RFA, those with greater AD-ON scores showed shorter time to recurrence beyond the MC, recurrence-free time, and overall survival (score 0:1:2:3 = no-estimation:97:66:23 months, 35:27:20:12 months, and 91:82:67:52 months, respectively, each P < 0.05)., Conclusion: HCC patients treated by RFA and with a high AD-ON score (≧2) should be considered for aggressive adjuvant-chemotherapy to prolong the period of recurrence beyond the MC., (© 2024. Japanese Society of Gastroenterology.)
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- 2024
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23. iATT liver fat quantification for steatosis grading by referring to MRI proton density fat fraction: a multicenter study.
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Hirooka M, Ogawa S, Koizumi Y, Yoshida Y, Goto T, Yasuda S, Yamahira M, Tamai T, Kuromatsu R, Matsuzaki T, Suehiro T, Kamada Y, Sumida Y, Hiasa Y, Toyoda H, and Kumada T
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- Humans, Female, Male, Middle Aged, Prospective Studies, Reproducibility of Results, Adult, Aged, ROC Curve, Non-alcoholic Fatty Liver Disease diagnostic imaging, Non-alcoholic Fatty Liver Disease pathology, Severity of Illness Index, Adipose Tissue diagnostic imaging, Adipose Tissue pathology, Magnetic Resonance Imaging methods, Ultrasonography methods, Fatty Liver diagnostic imaging, Fatty Liver pathology, Liver diagnostic imaging, Liver pathology
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Background: Several preliminary reports have suggested the utility of ultrasound attenuation coefficient measurements based on B-mode ultrasound, such as iATT, for diagnosing steatotic liver disease. Nonetheless, evidence supporting such utility is lacking. This prospective study aimed to investigate whether iATT is highly concordant with magnetic resonance imaging (MRI)-based proton density fat fraction (MRI-PDFF) and could well distinguish between steatosis grades., Methods: A cohort of 846 individuals underwent both iATT and MRI-PDFF assessments. Steatosis grade was defined as grade 0 with MRI-PDFF < 5.2%, grade 1 with 5.2% MRI-PDFF < 11.3%, grade 2 with 11.3% MRI-PDFF < 17.1%, and grade 3 with MRI-PDFF of 17.1%. The reproducibility of iATT and MRI-PDFF was evaluated using the Bland-Altman analysis and intraclass correlation coefficients, whereas the diagnostic performance of each steatosis grade was examined using receiver operating characteristic analysis., Results: The Bland-Altman analysis indicated excellent reproducibility with minimal fixed bias between iATT and MRI-PDFF. The area under the curve for distinguishing steatosis grades 1, 2, and 3 were 0.887, 0.882, and 0.867, respectively. A skin-to-capsula distance of ≥ 25 mm was identified as the only significant factor causing the discrepancy. No interaction between MRI-logPDFF and MRE-LSM on iATT values was observed., Conclusions: Compared to MRI-PDFF, iATT showed excellent diagnostic accuracy in grading steatosis. iATT could be used as a diagnostic tool instead of MRI in clinical practice and trials. Trial registration This study was registered in the UMIN Clinical Trials Registry (UMIN000047411)., (© 2024. The Author(s).)
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- 2024
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24. Glycemic Control Is Associated with Histological Findings of Nonalcoholic Fatty Liver Disease.
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Miyake T, Furukawa S, Matsuura B, Yoshida O, Miyazaki M, Shiomi A, Kanamoto A, Nakaguchi H, Nakamura Y, Imai Y, Koizumi M, Watanabe T, Yamamoto Y, Koizumi Y, Tokumoto Y, Hirooka M, Kumagi T, Takesita E, Ikeda Y, Abe M, and Hiasa Y
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- Humans, Male, Female, Middle Aged, Adult, Blood Glucose analysis, Disease Progression, Aged, Body Mass Index, Biopsy, Non-alcoholic Fatty Liver Disease blood, Non-alcoholic Fatty Liver Disease pathology, Glycated Hemoglobin analysis, Glycemic Control, Liver Cirrhosis blood, Liver pathology
- Abstract
Backgruound: Poor lifestyle habits may worsen nonalcoholic fatty liver disease (NAFLD), with progression to nonalcoholic steatohepatitis (NASH) and cirrhosis. This study investigated the association between glycemic control status and hepatic histological findings to elucidate the effect of glycemic control on NAFLD., Methods: This observational study included 331 patients diagnosed with NAFLD by liver biopsy. Effects of the glycemic control status on histological findings of NAFLD were evaluated by comparing the following four glycemic status groups defined by the glycosylated hemoglobin (HbA1c) level at the time of NAFLD diagnosis: ≤5.4%, 5.5%-6.4%, 6.5%-7.4%, and ≥7.5%., Results: Compared with the lowest HbA1c group (≤5.4%), the higher HbA1c groups (5.5%-6.4%, 6.5%-7.4%, and ≥7.5%) were associated with advanced liver fibrosis and high NAFLD activity score (NAS). On multivariate analysis, an HbA1c level of 6.5%- 7.4% group was significantly associated with advanced fibrosis compared with the lowest HbA1c group after adjusting for age, sex, hemoglobin, alanine aminotransferase, and creatinine levels. When further controlling for body mass index and uric acid, total cholesterol, and triglyceride levels, the higher HbA1c groups were significantly associated with advanced fibrosis compared with the lowest HbA1c group. On the other hand, compared with the lowest HbA1c group, the higher HbA1c groups were also associated with a high NAS in both multivariate analyses., Conclusion: Glycemic control is associated with NAFLD exacerbation, with even a mild deterioration in glycemic control, especially a HbA1c level of 6.5%-7.4%, contributing to NAFLD progression.
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- 2024
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25. Impact of body mass index on the prognosis of unresectable HCC patients receiving first-line Lenvatinib or atezolizumab plus bevacizumab.
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Rimini M, Stefanini B, Tada T, Suda G, Shimose S, Kudo M, Finkelmeier F, Yoo C, Presa J, Amadeo E, Genovesi V, De Grandis MC, Iavarone M, Marra F, Foschi F, Tamburini E, Rossari F, Vitiello F, Bartalini L, Soldà C, Tovoli F, Vivaldi C, Lonardi S, Silletta M, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Himmelsbach V, Montes M, Hiraoka A, Sho T, Niizeki T, Nishida N, Steup C, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Tada F, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Kosaka H, Naganuma A, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, Persano M, Camera S, Foti S, Aldrighetti L, Cascinu S, Casadei-Gardini A, and Piscaglia F
- Subjects
- Humans, Bevacizumab therapeutic use, Body Mass Index, Overweight, Prognosis, Thinness, Antibodies, Monoclonal, Humanized therapeutic use, Carcinoma, Hepatocellular, Liver Neoplasms, Phenylurea Compounds therapeutic use, Quinolines therapeutic use
- Abstract
Introduction: Overweight is a negative prognostic factor in the general population in the long term. However, the role of body mass index (BMI) in the short-mid term in advanced tumours is unclear. The present analysis investigates the role of BMI weight classes in a large sample of patients affected by HCC and receiving atezolizumab plus bevacizumab or lenvatinib as first-line treatment., Methods and Material: The cohort included consecutive patients affected by BCLC-c and BCLC-B HCC patients from a multicenter international study group who received atezolizumab plus bevacizumab or lenvatinib as first-line therapy. Population was stratified according to the BMI in under-, over- and normal-weight according to the conventional thresholds. The primary objective of the study was to evaluate the prognostic and predictive impact of BMI in patients affected by advanced or intermediate HCC. Survival curves were estimated using the product-limit method of Kaplan-Meier. The role of stratification factors was analysed with log-rank tests., Results: 1292 consecutive patients with HCC were analysed. 466 (36%) patients were treated with lenvatinib and 826 (64%) patients were treated with atezolizumab plus bevacizumab. In the atezolizumab plus bevacizumab arm, 510 (62%) patients were normal-weight, 52 (6%) underweight and 264 (32%) overweight. At the univariate analysis for OS, underweight patients had significantly shorter OS compared to normal-weight patients, whereas no differences were found between normal-weight versus overweight. Multivariate analysis confirmed that underweight patients had significantly shorter OS compared to normal-weight patients (HR: 1.7; 95% CI: 1.0-2.8; p = .0323). In the lenvatinib arm, 26 patients (5.6%) were categorized as underweight, 256 (54.9%) as normal-weight, and 184 (39.5%) as overweight. At the univariate analysis for OS, no significant differences were found between normal-weight versus underweight and between normal-weight versus overweight, which was confirmed at multivariate analysis., Conclusion: Our analysis highlighted a prognostic role of BMI in a cohort of patients with advanced HCC who received atezolizumab plus bevacizumab, while no prognostic role for low BMI was apparent in patients who received lenvatinib., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2024
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26. Combined effect of histological findings and diabetes mellitus on liver-related events in patients with metabolic dysfunction-associated steatotic liver disease.
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Shiomi A, Miyake T, Furukawa S, Matsuura B, Yoshida O, Watanabe T, Kanamoto A, Miyazaki M, Nakaguchi H, Tokumoto Y, Hirooka M, Abe M, and Hiasa Y
- Abstract
Aim: Advanced fibrosis has a strong influence on the occurrence of liver-related events in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while diabetes mellitus (DM), which is often complicated by MASLD, is associated with the progression of MASLD. We stratified patients with MASLD according to the severity of liver pathological findings and the presence of DM, aiming to examine whether these indices could be used to accurately assess the risk of developing liver-related events., Methods: A total of 282 patients with liver biopsy-proven MASLD were included. Liver-related events were defined as the occurrence of hepatocellular carcinoma (HCC) and complications of liver cirrhosis, such as ascites, hepatic encephalopathy, Child-Pugh class B and C, as well as treatment-eligible esophageal and gastric varices., Results: Multivariate analysis adjusted for age, sex, body mass index, alanine aminotransferase, creatinine, hemoglobin A1c, smoking habits, dyslipidemia, hypertension, nonalcoholic fatty liver disease activity score (NAS), or fibrosis stage showed that advanced fibrosis with or without DM was a risk factor for liver-related events. The combined effect of DM and advanced fibrosis increased the risk of HCC onset. However, DM alone or in combination with NAS did not affect the development of liver-related events, including the occurrence of HCC and complications of liver cirrhosis., Conclusions: While the assessment of fibrosis in patients with MASLD is important for evaluating the risk of developing liver-related events, combining the assessment of DM may be possible to stratify groups at higher risk of developing HCC., (© 2024 Japan Society of Hepatology.)
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- 2024
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27. Correction to: Deep attenuation transducer to measure liver stiffness in obese patients with liver disease.
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Hirooka M, Koizumi Y, Nakamura Y, Yano R, Hirooka K, Morita M, Imai Y, Tokumoto Y, Abe M, and Hiasa Y
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- 2024
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28. Comparative analysis of the therapeutic outcomes of atezolizumab plus bevacizumab and lenvatinib for hepatocellular carcinoma patients aged 80 years and older: Multicenter study.
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Hatanaka T, Kakizaki S, Hiraoka A, Tada T, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Yokohama K, Nishikawa H, Nishimura T, Shimada N, Kawata K, Kosaka H, Naganuma A, Yata Y, Ohama H, Kuroda H, Aoki T, Tanaka K, Tanaka T, Tada F, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, Kudo M, and Kumada T
- Abstract
Aim: Elderly patients are believed to have a reduced immune capacity, which may make immunotherapy less effective. The aim of this study was to compare the therapeutic outcome of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) for advanced hepatocellular carcinoma (HCC) in patients aged 80 years and older., Methods: From March 2018 to July 2022, 170 and 92 elderly patients who received LEN and Atez/Bev as first-line treatment, respectively, were retrospectively analyzed., Results: The median ages of the Atez/Bev and LEN groups were 83.0 (8.01-86.0) and 83.0 (82.0-86.0) years (p = 0.3), respectively. Men accounted for approximately 70% of the patients in both groups. The objective response rate was 35.9% in the LEN group and 33.7% in the Atez/Bev group (p = 0.8), whereas the disease control rates in the LEN and Atez/Bev groups were 62.9% and 63.0%, respectively (p = 1.0). The median progression-free survival (PFS) in the LEN and Atez/Bev groups was 6.3 and 7.2 months, respectively, which were not significantly different (p = 0.2). The median overall survival (OS) was 17.9 months in the LEN group and 14.0 months in the Atez/Bev group. This difference was not statistically significant (p = 0.7). In multivariate analyses, the choice of treatment (LEN vs. Atez/Bev) showed no association with PFS or OS. The Atez/Bev group had a significantly higher rate of postprogression treatment (59.0% vs. 35.7%, p = 0.01) and a lower rate of discontinuation due to adverse events (69 [40.6%] vs. 19 [20.7%], p < 0.001) compared to the LEN group., Conclusions: Atezolizumab plus bevacizumab showed comparable effectiveness to LEN in HCC patients aged 80 years and older. Given the results of postprogression treatment and discontinuation due to adverse events, Atez/Bev could serve as a first-line treatment even for elderly HCC patients., (© 2023 Japan Society of Hepatology.)
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- 2024
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29. A case of hepatocellular carcinoma with pseudoaneurysm formation upon lenvatinib administration.
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Yano R, Hirooka M, Nakamura Y, Imai Y, Koizumi Y, Watanabe T, Yoshida O, Tokumoto Y, Abe M, and Hiasa Y
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- Male, Humans, Aged, Bevacizumab, Carcinoma, Hepatocellular drug therapy, Aneurysm, False chemically induced, Aneurysm, False diagnostic imaging, Spinal Neoplasms, Liver Neoplasms drug therapy, Phenylurea Compounds, Quinolines
- Abstract
A 79-year-old man received treatment for multiple intrahepatic hepatocellular carcinoma with atezolizumab + bevacizumab. However, he developed lower back pain attributed to spinal metastases upon tumor enlargement; thus, he was admitted to our hospital for a change from atezolizumab + bevacizumab to lenvatinib and radiation therapy for the spinal metastases. On the 11th day after starting lenvatinib treatment, a pulsatile aneurysm appeared in the tumor, detected using abdominal ultrasonography Micro B-flow imaging, which visualized blood flow at a high frame rate; this was diagnosed as a pseudoaneurysm. The patient refused treatment for the pseudoaneurysm; therefore, he was carefully followed up. Fortunately, the pseudoaneurysm disappeared on the 17th day. One month later, the tumor had become completely necrotic. Lenvatinib demonstrated effectiveness in inhibiting angiogenesis in the tumor, as evidenced by a decrease in tumor blood flow. This case report suggests that pseudoaneurysm formation within the tumor occurs early after the administration of lenvatinib; thus, clinicians must be aware of the potential risk of pseudoaneurysm rupture., (© 2024. Japanese Society of Gastroenterology.)
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- 2024
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30. Clinical usefulness of newly developed prognostic predictive score for atezolizumab plus bevacizumab for hepatocellular carcinoma.
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Ohama H, Hiraoka A, Tada T, Hirooka M, Kariyama K, Hatanaka T, Tani J, Takaguchi K, Atsukawa M, Itobayashi E, Nishimura T, Tsuji K, Tajiri K, Ishikawa T, Yasuda S, Toyoda H, Fukunishi S, Ogawa C, Kakizaki S, Shimada N, Naganuma A, Kawata K, Kosaka H, Kuroda H, Matono T, Yata Y, Ochi H, Tada F, Nouso K, Morishita A, Itokawa N, Okubo T, Arai T, Tsutsui A, Nagano T, Yokohama K, Nishikawa H, Imai M, Koizumi Y, Nakamura S, Iijima H, Kaibori M, Hiasa Y, and Kumada T
- Subjects
- Male, Humans, Aged, Bevacizumab, Prognosis, Retrospective Studies, alpha-Fetoproteins, Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Antibodies, Monoclonal, Humanized
- Abstract
Aims: The aim of the present study was to elucidate detailed parameters for prediction of prognosis for patients with unresectable hepatocellular carcinoma (uHCC) receiving atezolizumab plus bevacizumab (Atez/Bev) treatment., Methods: A total of 719 patients (males 577, median age 74 years) treated with Atez/Bev between September 2020 and January 2023 were enrolled. Factors related to overall survival (OS) were extracted and a prognostic scoring system based on hazard ratio (HR) was created. OS and progression-free survival (PFS) were retrospectively examined, and the prognostic ability of the newly developed system was compared to CRAFITY score using concordance index (c-index) and Akaike information criterion (AIC) results., Results: Cox-hazards multivariate analysis showed BCLC classification C/D (HR 1.4; 1 point), AFP ≥100 ng/mL (HR 1.4; 1 point), mALBI 2a (HR 1.7; 1 point), mALBI 2b/3 (HR 2.8; 2 points), and DCP ≥100 mAU/mL (HR 1.6; 1 point) as significant factors. The assigned points were added and used to develop the IMmunotherapy with AFP, BCLC staging, mALBI, and DCP evaluation (IMABALI-De) scoring system. For IMABALI-De scores of 0, 1, 2, 3, 4, and 5, OS was not applicable (NA), NA, 26.11, 18.79, 14.07, and 8.32 months, respectively (p < .001; AIC 2788.67, c-index 0.699), while for CRAFITY scores of 0, 1, and 2, OS was 26.11, 20.29, and 11.32 months, respectively (p < .001; AIC 2864.54, c-index 0.606). PFS periods for those IMABALI-De scores were 21.75, 12.89, 9.18, 8.0, 5.0, and 3.75 months, respectively (p < .001; AIC 5203.32, c-index 0.623) and for the CRAFITY scores were 10.32, 7.68, and 3.57 months, respectively (p < .001; AIC 5246.61, c-index 0.574). As compared with CRAFITY score, IMABALI-De score had better AIC and c-index results for both OS and PFS., Conclusion: The present results indicated that the proposed IMABALI-De score may be favorable for predicting prognosis of uHCC patients receiving Atez/Bev therapy., (© 2024 The Authors. Cancer Reports published by Wiley Periodicals LLC.)
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- 2024
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31. α-FAtE: A new predictive score of response to atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma.
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Rossari F, Tada T, Suda G, Shimose S, Kudo M, Yoo C, Cheon J, Finkelmeier F, Lim HY, Presa J, Masi G, Bergamo F, Amadeo E, Vitiello F, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Chon HJ, Himmelsbach V, Iavarone M, Cabibbo G, Montes M, Foschi FG, Vivaldi C, Soldà C, Sho T, Niizeki T, Nishida N, Steup C, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Hiraoka A, Tada F, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Imai M, Kosaka H, Naganuma A, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, Persano M, Burgio V, Piscaglia F, Scartozzi M, Cascinu S, Casadei-Gardini A, and Rimini M
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- Humans, Bevacizumab therapeutic use, Prospective Studies, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Phenylurea Compounds, Quinolines, Antibodies, Monoclonal, Humanized
- Abstract
Atezolizumab plus bevacizumab (AB) and lenvatinib can be alternatively used as first-line systemic treatment of unresectable hepatocellular carcinoma (HCC). However, no direct comparison of the two regimens has been performed in randomized clinical trials, making the identification of baseline differential predictors of response of major relevance to tailor the best therapeutic option to each patient. Baseline clinical and laboratory characteristics of real-world AB-treated HCC patients were analyzed in uni- and multivariate analyses to find potential prognostic factors of overall survival (OS). Significant variables were incorporated in a composite score (α-FAtE) and it was tested for specificity and sensitivity in receiver operating characteristic (ROC) curve and in multivariate analysis for OS. The score was applied in uni- and multivariate analyses for OS of a comparable lenvatinib-treated HCC population. Finally, comparison between treatments was performed in patients with low and high α-FAtE scores and predictivity estimated by interaction analysis. Time-to-progression (TTP) was a secondary endpoint. OS of AB-treated HCC patients was statistically longer in those with α-fetoprotein <400 ng/mL (HR 0.62, p = .0407), alkaline phosphatase (ALP) <125 IU/L (HR 0.52, p = .0189) and eosinophil count ≥70/μL (HR 0.46, p = .0013). The α-FAtE score was generated by the sum of single points attributed to each variable among the above reported. In ROC curve analysis, superior sensitivity and specificity were achieved by the score compared to individual variables (AUC 0.794, p < .02). Patients with high score had longer OS (HR 0.44, p = .0009) and TTP (HR 0.34, p < .0001) compared to low score if treated with AB, but not with lenvatinib. Overall, AB was superior to lenvatinib in high score patients (HR 0.55, p = .0043) and inferior in low score ones (HR 1.75, p = .0227). At interaction test, low α-FAtE score resulted as negative predictive factor of response to AB (p = .0004). In conclusion, α-FAtE is a novel prognostic and predictive score of response to first-line AB for HCC patients that, if validated in prospective studies, could drive therapeutic choice between lenvatinib and AB., (© 2023 UICC.)
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- 2024
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32. Hepatocellular Carcinoma Showing Tumor Shrinkage Due to an Abscopal Effect.
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Yano R, Hirooka M, Morita M, Okazaki Y, Nakamura Y, Imai Y, Watanabe T, Koizumi Y, Yoshida O, Tokumoto Y, Abe M, and Hiasa Y
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- Male, Humans, Middle Aged, Bevacizumab, Immunotherapy, Pain, Carcinoma, Hepatocellular diagnostic imaging, Carcinoma, Hepatocellular therapy, Liver Neoplasms diagnostic imaging, Liver Neoplasms therapy
- Abstract
We herein report a 63-year-old man who presented with left lower jaw pain and was diagnosed with hepatocellular carcinoma with bone metastases post-examination. All tumors grew after immunotherapy with atezolizumab and bevacizumab, and his jaw pain worsened. After palliative radiation therapy, however, the tumors shrank markedly, with no recurrence seen after stopping immunotherapy. To our knowledge, this is the first case in which a radiotherapy- and immunotherapy-mediated abscopal effect facilitated tumor shrinkage and immunotherapy discontinuation.
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- 2024
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33. Comparison of prognostic impact of atezolizumab plus bevacizumab versus lenvatinib in patients with intermediate-stage hepatocellular carcinoma.
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Tada T, Kumada T, Hiraoka A, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Tada F, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Kosaka H, Naganuma A, Matono T, Aoki T, Kuroda H, Yata Y, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, and Kudo M
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- Humans, Prognosis, Bevacizumab therapeutic use, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Antineoplastic Agents therapeutic use
- Abstract
Background & Aims: The study goal was to compare the outcomes of patients with intermediate-stage (Barcelona Clinic Liver Cancer [BCLC]-B) hepatocellular carcinoma (HCC) who received atezolizumab plus bevacizumab (Atezo/Bev) or lenvatinib (LEN) as first-line systemic therapy., Methods: A total of 358 patients with BCLC-B HCC treated with Atezo/Bev (n = 177) or LEN (n = 181) as first-line systemic therapy were included., Results: The median progression-free survival (PFS) times in the Atezo/Bev and LEN groups were 10.8 months (95% confidence interval [CI], 7.8-12.6) and 7.3 months (95% CI, 6.3-8.5), respectively (p = .019). In the propensity score-matched cohort, the median PFS times in the Atezo/Bev (n = 151) and LEN (n = 151) groups were 10.2 months (95% CI, 7.0-12.3) and 6.9 months (95% CI, 5.9-8.1), respectively (p = .020). Restricted mean survival times of PFS were significantly higher in the Atezo/Bev group than in the LEN group at landmarks of 12 and 18 months (p = .031 and .012, respectively). In a subgroup analysis of patients with HCC beyond the up-to-seven criteria, the median PFS times in the Atezo/Bev (n = 134) and LEN (n = 117) groups were 10.5 months (95% CI, 7.0-11.8) and 6.3 months (95% CI, 5.5-7.3), respectively (p = .044)., Conclusions: The use of Atezo/Bev as first-line systemic therapy in patients with BCLC-B HCC is expected to result in good PFS., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2024
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34. Safety and Efficacy of Lenvatinib in Very Old Patients with Unresectable Hepatocellular Carcinoma.
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Camera S, Rimini M, Rossari F, Tada T, Suda G, Shimose S, Kudo M, Yoo C, Cheon J, Finkelmeier F, Lim HY, Presa J, Masi G, Bergamo F, Salani F, Marseglia M, Amadeo E, Vitiello F, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Chon HJ, Himmelsbach V, Iavarone M, Cabibbo G, Montes M, Foschi FG, Vivaldi C, Lonardi S, Sho T, Niizeki T, Nishida N, Steup C, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Hiraoka A, Tada F, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Imai M, Kosaka H, Naganuma A, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, Persano M, Foti S, Piscaglia F, Scartozzi M, Cascinu S, and Casadei-Gardini A
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- Humans, Aged, 80 and over, Phenylurea Compounds adverse effects, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Quinolines pharmacology, Quinolines therapeutic use
- Abstract
Background: Data concerning the use of lenvatinib in very old patients (≥ 80 years) are limited, although the incidence of hepatocellular carcinoma (HCC) in this patient population is constantly increasing., Objective: This analysis aimed to evaluate the efficacy and safety of lenvatinib in a large cohort of very old patients (≥ 80 years) with unresectable HCC., Patients and Methods: The study was conducted on a cohort of 1325 patients from 46 centers in four Western and Eastern countries (Italy, Germany, Japan, and the Republic of Korea) who were undergoing first-line treatment with lenvatinib between July 2010 and February 2022. Patients were stratified according to age as very old (≥ 80 years) and not very old (< 80 years)., Results: The median overall survival (OS) was 15.7 months for patients < 80 years old and 18.4 months for patients ≥ 80 years old [hazard ratio (HR) = 1.02, 95% confidence interval (CI) 0.84-1.25, p = 0.8281]. Median progression free survival (PFS) was 6.3 months for patients < 80 years old and 6.5 months for patients ≥ 80 years old (HR = 1.07, 95% CI 0.91-1.25, p = 0.3954). No differences between the two study groups were found in terms of disease control rate (DCR; 80.8% versus 78.8%; p = 0.44) and response rate (RR; 38.2% versus 37.9%; p = 0.88). Patients < 80 years old experienced significantly more hand-foot skin reaction (HFSR) grade ≥ 2 and decreased appetite grade ≥ 2. Conversely, patients ≥ 80 years old experienced significantly more fatigue grade ≥ 2. In the very old group, parameters associated with prognosis were AFP, albumin-bilirubin (ALBI) grade, Barcelona Clinic Liver Cancer (BCLC), and Child-Pugh score. BCLC stage was the only independent predictor of overall survival (OS; HR = 1.59, 95% CI 1.11-2.29, p = 0.01115)., Conclusions: Our study highlights the same efficacy and safety of lenvatinib between very old and not very old patients., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
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- 2024
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35. Simple Scoring System for Esophagogastric Varices Prediction in Hepatocellular Carcinoma Patients without Liver Stiffness Evaluation.
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Hiraoka A, Tada F, Ohama H, Fukumoto M, Matsuoka K, Matsuda T, Nakatani K, Yanagihara E, Saneto H, Izumoto H, Murakami T, Onishi K, Kitahata S, Kanemitsu-Okada K, Kawamura T, Kuroda T, Miyata H, Tsubouchi E, Hirooka M, Abe M, Matsuura B, Ninomiya T, and Hiasa Y
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- Humans, Retrospective Studies, Liver Cirrhosis, Carcinoma, Hepatocellular diagnostic imaging, Carcinoma, Hepatocellular therapy, Liver Neoplasms diagnostic imaging, Liver Neoplasms therapy, Esophageal and Gastric Varices diagnostic imaging, Esophageal and Gastric Varices etiology, Varicose Veins
- Abstract
Introduction: For predicting esophagogastric varices (EGVs), the Virtual Baveno VII Consensus Workshop has proposed a combination of liver stiffness determination and platelet count measurement using a FibroScan®. However, FibroScan® is not available at all institutions. The present study aimed to develop a simple method to predict development of EGV using only general blood examination results., Materials and Methods: A total of 1,090 hepatocellular carcinoma patients were enrolled, after excluding 956 with major portal vein tumor thrombus (Vp3/Vp4) or without upper gastrointestinal endoscopy examination results available. Those with EGV (≥ grade F2) or a history of treatment for the condition were defined as positive for significant EGV, and then clinical factors were retrospectively evaluated to determine indicators of occurrence., Results: Logistic multivariate analysis showed platelet count (≤12 × 104/μL) (odds ratio [OR] 3.79, p < 0.001), mALBI grade 2a (OR 1.52, p = 0.036), and mALBI 2b or 3 (OR 3.46, p < 0.001) as significant predictive factors. Based on the OR values, platelet count (≤12 × 104/μL) and mALBI grade 2b/3 were each assigned 2 points and mALBI 2a was given 1 point, with the result termed recommendation for EGV screening (REGS) score. Significant EGV occurrence was noted in 2.9% (9/311) of the patients with a REGS score 0, 11.0% (13/118) with a score 1, 19.3% (53/274) with a score 2, 29.5% (39/132) with a score 3, and 38.0% (97/255) with a score 4 (p < 0.001)., Conclusion: The findings indicate that REGS score can provide useful predictive information for development of significant EGV without the need for special equipment such as a FibroScan®., (© 2023 S. Karger AG, Basel.)
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- 2024
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36. Clinical and Pathological Features of Immune Checkpoint Inhibitor-induced Liver Injury in Comparison with Drug-induced Liver Injury and Autoimmune Hepatitis.
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Sunago K, Abe M, Yoshida O, Watanabe T, Nakamura Y, Imai Y, Koizumi Y, Hirooka M, Tokumoto Y, and Hiasa Y
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- Humans, Immune Checkpoint Inhibitors, Liver pathology, Hepatitis, Autoimmune diagnosis, Hepatitis, Autoimmune etiology, Hepatitis, Autoimmune pathology, Chemical and Drug Induced Liver Injury, Chronic pathology, Chemical and Drug Induced Liver Injury diagnosis, Chemical and Drug Induced Liver Injury etiology, Chemical and Drug Induced Liver Injury pathology
- Abstract
Background and Aims: Immune checkpoint inhibitors may cause various types of organ damage as immune-related adverse events, of which, liver damage is the most common. Herein, we evaluated the clinicopathological features of immune checkpoint inhibitor-related liver injury and investigated the differences between immune checkpoint inhibitor-related liver injury and drug-induced liver injury or autoimmune hepatitis., Methods: We selected patients with ≥ grade 3 liver injury who were diagnosed with immune checkpoint inhibitor-related liver injury (n=15). Liver biopsies were performed in 10 of the 15 cases. We also selected cases in which a liver biopsy was performed and drug-induced liver injury (n=7) or autoimmune hepatitis [n=21: acute exacerbation (n=13) was diagnosed and cases of acute onset (n=8), in which liver function test results corresponded to ≥ grade 3]., Results: Portal fibrosis and periportal activity scores were significantly higher in the acute exacerbation autoimmune hepatitis group than in the other groups. Portal and lobular activity were not different between the groups. Plasma cell infiltration showed a higher trend in the autoimmune hepatitis group than in the other groups. Granuloma formations were seen in 90% of immune checkpoint inhibitor-related liver injury cases. The CD4/8 ratio was significantly lower in the immune checkpoint inhibitor-related liver injury group than in the other groups. Patients with bile duct injury had poorer response to corticosteroid therapy than those without., Conclusions: There are some obvious differences among immune checkpoint inhibitor-related liver injury, drug-induced liver injury, and autoimmune hepatitis in liver histology. Liver biopsy is helpful for the diagnosis and severity evaluation of liver injury.
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- 2023
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37. Lymphatic drainage dysfunction via narrowing of the lumen of cisterna chyli and thoracic duct after luminal dilation.
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Yano R, Hirooka M, Koizumi Y, Nakamura Y, Imai Y, Morita M, Okazaki Y, Watanabe T, Yoshida O, Tokumoto Y, Abe M, and Hiasa Y
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- Humans, Thoracic Duct diagnostic imaging, Thoracic Duct pathology, Cross-Sectional Studies, Dilatation, Prospective Studies, Liver Cirrhosis pathology, Esophageal and Gastric Varices pathology, Hypertension, Portal diagnostic imaging, Hypertension, Portal pathology
- Abstract
Background: The chronological pattern of extrahepatic lymphatic vessel progression in the course of chronic liver disease has not been clarified. This study aimed to clarify the chronological changes in lymphatic vessels with liver disease progression., Methods: This was a prospective cross-sectional study that enrolled a total of 199 patients. The maximum diameter of the cisterna chyli (CC) or terminal thoracic duct (tTD) was measured using computed tomography or ultrasonography, respectively. Changes in the maximum diameters of the CC and tTD were evaluated with patients with chronic liver disease as the pilot set (n = 138). Subsequently, we examined whether CC/tTD could be used to re-allocate unclassified patients by the Baveno-VII criteria to appropriately diagnose clinically significant portal hypertension (CSPH) in the pilot and validation sets., Results: In the pilot set, a scatter-plot showed that both CC and tTD were narrowed as terminal features in chronic liver disease after dilation. Because there was a significant correlation between the CC diameter and hepatic venous pressure gradient (r = 0.724) in unclassified patients, the diagnostic value of CC and tTD for CSPH was good (AUC: 0.961 and 0.913, respectively). After re-allocation, 68 and 27 unclassified patients were reduced to 4 and 5 in the pilot and validation sets, respectively., Conclusion: Both the CC and tTD narrow in the course of liver disease after dilation. Moreover, the maximum diameter of the CC and tTD can be used to re-allocate patients who are unclassified according to the Baveno-VII criteria., Clinical Trial Number: UMIN trial no. 000044857., (© 2023. Asian Pacific Association for the Study of the Liver.)
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- 2023
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38. Comparing the impact of atezolizumab plus bevacizumab and lenvatinib on the liver function in hepatocellular carcinoma patients: A mixed-effects regression model approach.
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Hatanaka T, Kakizaki S, Hiraoka A, Tada T, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Yokohama K, Nishikawa H, Nishimura T, Shimada N, Kawata K, Kosaka H, Naganuma A, Yata Y, Ohama H, Kuroda H, Tanaka K, Tanaka T, Tada F, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, Kudo M, and Kumada T
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- Humans, Bevacizumab adverse effects, Retrospective Studies, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy
- Abstract
Aim: This retrospective study compared the impact of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) on the liver function in patients with hepatocellular carcinoma., Methods: We included 526 patients who received Atez/Bev and 731 who received LEN March 2018 and July 2022 in this study. We conducted a 1:1 propensity-score-matched analysis and identified 324 patients in each group for inclusion in the present analysis. Nonlinear mixed-effects regression models were employed, allowing for the evaluation and inclusion of cases where treatment was interrupted due to disease progression, adverse events, or loss to follow-up. These models were used to compare the ALBI score between the Atez/Bev and LEN groups., Results: Following propensity score matching, the mean ALBI scores in the Atez/Bev and LEN groups were -2.41 ± 0.40 and -2.44 ± 0.42 at baseline, and -2.17 ± 0.56 and -2.19 ± 0.58 at 12 weeks, respectively. Although the ALBI score significantly worsened during treatment in both groups (p < 0.001), there was no significant difference in the rate of ALBI score deterioration between the groups (p = 0.06). Subgroup analyses showed that LEN-treated patients with BCLC advanced stage (p = 0.02) and those who initially received the full dose (p < 0.001) had a significantly greater worsening of ALBI score compared to Atez/Bev., Conclusions: Using a nonlinear mixed-effects regression approach, which allowed for the inclusion of cases with treatment interruption, we found no significant difference in the trend of liver function deterioration between the Atez/Bev and LEN groups. Caution should be exercised for LEN-treated patients with BCLC advanced stage or those receiving the full dose of LEN., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2023
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39. Survival Improvements in Advanced Hepatocellular Carcinoma with Sequential Therapy by Era.
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Nakamura Y, Hirooka M, Hiraoka A, Koizumi Y, Yano R, Morita M, Okazaki Y, Imai Y, Ohama H, Hirooka K, Watanabe T, Tada F, Yoshida O, Tokumoto Y, Abe M, and Hiasa Y
- Abstract
Treatment modalities for advanced hepatocellular carcinoma (HCC) have changed dramatically, with systemic therapy as the primary option. However, the effect of sequential treatment on prognosis remains unclear. This retrospective study included patients who began systemic therapy between 2009 and 2022. The patients were separated into three groups according to systemic therapy commencement. The number of therapy lines, treatment efficacy, and overall survival (OS) were compared. Multivariate analyses of the prognostic factors were analyzed using the Cox proportional hazards model. Overall, 336 patients were included (period 1: 2009-2013, n = 86; period 2: 2014-2018, n = 132; period 3: 2019-2022, n = 118). A significant etiological trend was observed with decreasing viral hepatitis-related HCC and increasing non-viral hepatitis-related HCC. Across periods 1-3, the proportion of patients who were administered >2 lines progressively increased (1.2%, 12.9%, and 17.0%, respectively; p < 0.001) and the median OS was significantly prolonged (14.3, 16.8, and 31.0 months; p < 0.001). The use of <3 lines, the non-complete and partial response of the first line, modified albumin-bilirubin at grade 2b or 3, an intrahepatic tumor number ≥ 5, extrahepatic metastasis, and alpha-fetoprotein at ≥400 ng/mL were the strongest factors associated with shorter OS. Sequential therapies have contributed to significant improvements in HCC prognosis, suggesting that sequential treatment post-progression is worthwhile for better survival.
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- 2023
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40. Efficacy and safety of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma patients with esophageal-gastric varices.
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Tada F, Hiraoka A, Tada T, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Naganuma A, Kosaka H, Matono T, Kuroda H, Yata Y, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Yokohama K, Nishikawa H, Imai M, Koizumi Y, Nakamura S, Iijima H, Kaibori M, Hiasa Y, and Kumada T
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Background: Bevacizumab inhibits vascular endothelial growth factor-A (VEGF-A), though is known to increase bleeding risk as an adverse event (AE). This study examined whether atezolizumab/bevacizumab (Atez/Bev) for unresectable hepatocellular carcinoma (uHCC) can be used for patients with esophageal-gastric varices (EGV)., Methods: From October 2020 to December 2022, 506 uHCC patients (median 74 years) underwent an upper gastrointestinal endoscopy examination were enrolled, after exclusion of those with portal vein tumor thrombus (PVTT). Patients with EGV (≧ F1) were defined as EGV positive, and the cohort was divided into non-EGV (n = 355) and EGV (n = 151). Before introducing Atez/Bev, endoscopic treatment was performed, when necessary. Prognosis was evaluated, retrospectively., Results: The EGV group had significantly worse hepatic function, lower platelet count, elevated alpha-fetoprotein, and lower rate of extrahepatic metastasis, and lower rate of first-line use (each P < 0.05) than the other. However, progression-free survival (PFS) was also not a significantly difference between the EGV and non-EGV groups in analyses with (PFS rate at 6/12/18 months: 60%/38%/30% vs. 65%/46%/34%, P = 0.29) or without inverse probability weighting adjustment [median: 10.6 months (95% CI 8.3-14.0) vs. 10.5 months (95% CI 7.8-13.7), P = 0.79]. As for AEs, diarrhea was more frequent in the EGV group (≧ G3: 2.0% vs. 0.3%, P = 0.036), while no significant difference was noted for EGV hemorrhage (≧ G3: 1.3% vs. 0.6%, P = 0.345). Of 28 patients who underwent endoscopic treatments before introducing Atez/Bev, none showed EGV-associated hemorrhage., Conclusions: Atez/Bev might be an effective therapeutic option in patients with EGV, when appropriate endoscopic treatment for EGV is performed., (© 2023. Japanese Society of Gastroenterology.)
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- 2023
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41. B-mode shear wave elastography can be an alternative method to vibration-controlled transient elastography according to a moderate-scale population study.
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Hirooka M, Koizumi Y, Nakamura Y, Yano R, Hirooka K, Morita M, Imai Y, Tokumoto Y, Abe M, and Hiasa Y
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- Humans, Reproducibility of Results, Vibration, Liver Cirrhosis diagnostic imaging, Liver diagnostic imaging, Elasticity Imaging Techniques methods
- Abstract
Purpose: We aimed to compare vibration-controlled transient elastography (VCTE) with shear wave elastography (SWE) without previous analysis and generate regression equations between VCTE and new point SWE using combination-elastography., Methods: Overall, 829 patients with chronic liver disease were enrolled in this study. Patients with a skin-liver capsule distance > 25 mm were excluded. The reproducibility of VCTE and SWE was confirmed in a phantom study and a clinical study. Considering that combination-elastography allows measurement based on strain elastography, a similar analysis was performed for the liver fibrosis index (LFI), which is a quantitative value for evaluation of liver fibrosis calculated using strain elastography image features. Regression equations between the VCTE and SWE values were obtained based on linear regression analysis., Results: In the phantom study and clinical study, there was a strong correlation between VCTE and SWE [r = 0.995 (p < 0.001) and r = 0.747 (p < 0.001), respectively). The regression equation between VCTE and SWE was VCTE (kPa) = 1.09 × point SWE (kPa) - 0.17. The Bland-Altman plots revealed no statistically significant bias. Meanwhile, there was no correlation between VCTE and LFI (r = 0.279). There was a statistically significant bias between VCTE and LFI in the Bland-Altman plots. The inter-operator reliability showed a good intraclass correlation coefficient of 0.760 (95% confidence interval: 0.720-0.779)., Conclusion: Liver stiffness measured using point SWE was comparable to that measured using VCTE., (© 2023. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)
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- 2023
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42. Geriatric nutritional risk index as an easy-to-use assessment tool for nutritional status in hepatocellular carcinoma treated with atezolizumab plus bevacizumab.
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Hiraoka A, Kumada T, Tada T, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Naganuma A, Kosaka H, Matono T, Kuroda H, Yata Y, Ohama H, Tada F, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Koizumi Y, Nakamura S, Iijima H, Kaibori M, and Hiasa Y
- Abstract
Aim: The present study focused on Geriatric Nutritional Risk Index (GNRI), which is based on bodyweight and serum albumin, and known as an easy-to-use nutritional assessment tool in clinical settings, to elucidate the prognostic predictive ability of GNRI in patients treated with atezolizumab plus bevacizumab (Atez/Bev) for hepatocellular carcinoma (HCC)., Methods: A total of 525 HCC patients treated with Atez/Bev, based on their classification of unsuitable status for curative treatments and/or transarterial catheter chemoembolization, were enrolled (Child-Pugh A:B:C = 484:40:1, Barcelona Clinic Liver Cancer stage 0:A:B:C:D = 7:25:192:283:18). Prognosis was evaluated retrospectively using GNRI., Results: Atez/Bev was used in 338 of the present cohort as first-line systemic chemotherapy (64.4%). Median progression-free survival based on GNRI indicating normal, mild decline, moderate decline, and severe decline was 8.3, 6.7, 5.3, and 2.4 months, respectively, whereas median overall survival was 21.4, 17.0, 11.5. and 7.3 months, respectively (both p < 0.001). The concordance index (c-index) values of GNRI for predicting prognosis (progression-free survival/overall survival) were superior to those of Child-Pugh class and albumin-bilirubin grade (0.574/0.632 vs. 0.527/0.570 vs. 0.565/0.629). As a subanalysis, muscle volume loss was observed in 37.5% of 256 patients with computed tomography data available. Along with GNRI decline, frequency of muscle volume loss became progressively larger (normal vs. mild vs. moderate vs. severe = 17.6% vs. 29.2% vs. 41.2% vs. 57.9%, p < 0.001), and a GNRI value of 97.8 was predictive of its occurrence (AUC 0.715, 95% CI 0.649-0.781; specificity/sensitivity = 0.644/0.688)., Conclusion: These findings indicate that GNRI is an effective nutritional prognostic tool for predicting prognosis and muscle volume loss complication in HCC patients treated with Atez/Bev., (© 2023 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)
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- 2023
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43. Intranasal HBsAg/HBcAg-Containing Vaccine Induces Neutralizing Anti-HBs Production in Hepatitis B Vaccine Non-Responders.
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Shiraishi K, Yoshida O, Imai Y, Akbar SMF, Sanada T, Kohara M, Miyazaki T, Kamishita T, Miyake T, Hirooka M, Tokumoto Y, Abe M, Rubido JCA, Nieto GG, and Hiasa Y
- Abstract
Hepatitis B vaccine induces the production of antibodies against hepatitis B surface antigen (anti-HBs) and prevents hepatitis B virus (HBV) infection. However, 5-10% of individuals cannot develop anti-HBs even after multiple vaccinations (HB vaccine non-responders). We developed an intranasal vaccine containing both HBs antigen (HBsAg) and HB core antigen (HBcAg) and mixed it with a viscosity enhancer, carboxyl vinyl polymer (CVP-NASVAC). Here, we investigated the prophylactic capacity of CVP-NASVAC in HB vaccine non-responders. Thirty-four HB vaccine non-responders were administered three doses of intranasal CVP-NASVAC. The prophylactic capacity of CVP-NASVAC was assessed by evaluating the induction of anti-HBs and anti-HBc (IgA and IgG) production, HBV-neutralization activity of sera, and induction of HBs- and HBc-specific cytotoxic T lymphocytes (CTLs). After CVP-NASVAC administration, anti-HBs and anti-HBc production were induced in 31/34 and 27/34 patients, respectively. IgA anti-HBs and anti-HBc titers significantly increased after CVP-NASVAC vaccination. HBV-neutralizing activity in vitro was confirmed in the sera of 26/29 CVP-NASVAC-administered participants. HBs- and HBc-specific CTL counts substantially increased after the CVP-NASVAC administration. Mild adverse events were observed in 9/34 participants; no serious adverse events were reported. Thus, CVP-NASVAC could be a beneficial vaccine for HB vaccine non-responders.
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- 2023
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44. Accuracy of spleen stiffness measurement for the diagnosis of clinically significant portal hypertension in patients with compensated advanced chronic liver disease: a systematic review and individual patient data meta-analysis.
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Dajti E, Ravaioli F, Zykus R, Rautou PE, Elkrief L, Grgurevic I, Stefanescu H, Hirooka M, Fraquelli M, Rosselli M, Chang PEJ, Piscaglia F, Reiberger T, Llop E, Mueller S, Marasco G, Berzigotti A, Colli A, Festi D, and Colecchia A
- Abstract
Background: The diagnosis of clinically significant portal hypertension is crucial for prognosis and treatment guidance in patients with compensated advanced chronic liver disease (ACLD). Spleen stiffness measurement (SSM) might improve the non-invasive diagnosis of clinically significant portal hypertension, but previous studies have reported heterogeneous SSM cutoffs. We aimed to evaluate the accuracy of SSM and SSM-based algorithms in this setting., Methods: In this systematic review and individual patient data meta-analysis, we searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library from database inception to Dec 31, 2022, for articles, abstracts, and letters, with no restrictions on language. Cross-sectional studies reporting hepatic venous pressure gradient and SSM by different techniques (transient elastography; two-dimensional shear-wave elastography [2D-SWE]; point shear-wave elastography [p-SWE]) in adults (≥18 years) with compensated ACLD were eligible for inclusion. The main outcome was the diagnostic performance of two SSM-based algorithms, with the Baveno VII model as a reference, evaluating sensitivity and specificity, as well as summary negative predictive values (NPVs) and positive predictive values (PPVs). In the Baveno VII model, clinically significant portal hypertension was ruled out if patients had a liver stiffness measurement (LSM) of 15 kPa or less and a platelet count of 150 × 10
9 platelets per L or higher and ruled in if they had an LSM of greater than 25 kPa. The two SSM-based models combined these same cutoffs with additional criteria. In the Baveno VII-SSM single cutoff model, clinically significant portal hypertension was ruled out if at least two of the following were present: LSM of 15 kPa or less, platelet count of 150 × 109 platelets per L or higher, and SSM of 40 kPa or less; and ruled in if at least two were present: LSM of greater than 25 kPa, platelet count of less than 150 × 109 platelets per L, and SSM of greater than 40 kPa. The Baveno VII-SSM dual cutoff model used the same criteria, but with a cutoff of SSM of less than 21 kPa to rule out, and greater than 50 kPa to rule in, clinically significant portal hypertension. This study is registered with PROSPERO, CRD42019127164., Findings: Of the 44 records assessed for eligibility, 17 studies (with 1245 patients) were included in the meta-analysis. In the transient elastography cohort (n=600), the Baveno VII algorithm was validated for both ruling out (NPV 100%, 95% CI 64-100; sensitivity 100%, 95% CI 70-100) and ruling in (PPV 95%, 85-98; specificity 94%, 95% CI 87-97) clinically significant portal hypertension, but the proportion of patients with indeterminate results (grey zone) was 48% (95% CI 44-52); 57% (95% CI 52-62) of patients with clinically significant portal hypertension were included in the rule-in zone. The Baveno VII-SSM dual cutoff model had adequate NPV (98%, 95% CI 58-100; sensitivity 100%, 95% CI 91-100) and PPV (93%, 95% CI 84-97; specificity 89%, 95% CI 84-93), with 32% (95% CI 28-36) of patients in the grey zone; 76% (95% CI 72-80) of the patients with clinically significant portal hypertension were in the rule-in zone. The Baveno VII-SSM single cutoff model had a sensitivity of 93% (95% CI 85-97) and a NPV of 85% (95% CI 60-96) for ruling out, and a specificity of 86% (95% CI 80-91) and a PPV of 92% (95% CI 83-95) for ruling in, clinically significant portal hypertension. 88% (95% CI 84-91) of patients with clinically significant portal hypertension were included in the rule-in zone and 9% (95% CI 7-12) of patients were in the grey zone. In the 2D-SWE cohort (n=225), all three algorithms could safely rule in clinically significant portal hypertension with adequate PPV (≥90%), but NPV was inadequate for ruling out clinically significant portal hypertension. Insufficient data were available to evaluate the performance of SSM assessed by p-SWE. Heterogeneity was low (I2 <25%) for most estimates., Interpretation: Algorithms combining Baveno VII criteria with SSM showed good performance and reduced the diagnostic grey zone for clinically significant portal hypertension compared with Baveno VII criteria alone. Future studies should evaluate whether SSM-based diagnosis allows for the identification of patients who would benefit from non-selective β-blocker treatment., Funding: None., Competing Interests: Declaration of interests P-ER has received research funding from Terrafirma; acted as a consultant for Hemostod, Mursla, Genfit, Boehringer Ingelheim, and Abbelight; and received speaker fees from Tillotts Pharma and AbbVie. TR received grant support from AbbVie, Boehringer Ingelheim, Gilead, Gore, Intercept, MSD, Myr Pharmaceuticals, Philips Healthcare, Pliant, and Siemens; speaking honoraria from AbbVie, Gilead, Gore, Intercept, Roche, and MSD; consulting or advisory board fees from AbbVie, Bayer, Boehringer Ingelheim, Gilead, Intercept, MSD, and Siemens; and travel support from AbbVie, Boehringer Ingelheim, Gilead, and Roche. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)- Published
- 2023
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45. Effect of butyrate-producing enterobacteria on advanced hepatocellular carcinoma treatment with atezolizumab and bevacizumab.
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Nouso K, Shiota S, Fujita R, Wakuta A, Kariyama K, Hiraoka A, Atsukawa M, Tani J, Tada T, Nakamura S, Tajiri K, Kaibori M, Hirooka M, Itobayashi E, Kakizaki S, Naganuma A, Ishikawa T, Hatanaka T, Fukunishi S, Tsuji K, Kawata K, Takaguchi K, Tsutsui A, Ogawa C, Ochi H, Yata Y, Kuroda H, Iijima H, Matono T, Shimada N, Yasuda S, Toyoda H, and Kumada T
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- Humans, Bevacizumab adverse effects, Butyric Acid, Enterobacteriaceae, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Drug-Related Side Effects and Adverse Reactions
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Aim: Multiple studies have revealed the correlation between gut microbiome and the response to checkpoint inhibitors (CPIs) in patients with cancer, and oral administration of butyrate-producing enterobacteria has been reported to enhance the efficacy of CPIs. However, the effects of enterobacteria on patients with hepatocellular carcinoma (HCC) are not well understood., Methods: In this retrospective multicenter study, we enrolled 747 patients with advanced HCC, treated with atezolizumab and bevacizumab combination therapy. Tumor response, survival, and adverse effects were compared between 99 patients who ingested drugs containing butyric acid-producing enterobacteria (butyric acid group) and the remaining patients (control group)., Results: Objective response and disease control rates in butyric acid group (29.7% and 77.8%, respectively) were higher than those in the control group (26.4% and 72.7%, respectively). However, the differences were not statistically significant (p = 0.543 and p = 0.222, respectively). No difference in median survival time was observed between the two groups (20.0 months and 21.4 months, respectively; p = 0.789), even after matching the backgrounds of the patients with propensity scores (p = 0.714). No adverse effects occurred upon the administration of butyrate-producing bacteria. However, proteinuria (41.4% vs. 30.9%; p = 0.041), fever (17.2% vs. 10.2%, p = 0.036), and diarrhea (15.2% vs. 6.2%; p = 0.001) occurred more frequently in the butyric acid group., Conclusion: Butyrate-producing bacteria does not enhance the efficacy of atezolizumab-bevacizumab combination therapy in patients with HCC., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2023
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46. Thread and Streak Sign at Microvascular Flow Imaging and Contrast-enhanced US.
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Hirooka M and Hiasa Y
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- Humans, Diagnostic Imaging, Software
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- 2023
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47. Association of abnormal glucose tolerance with liver-related disease and cardiovascular diseases in patients with chronic hepatitis C.
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Konishi F, Miyake T, Watanabe T, Tokumoto Y, Furukawa S, Matsuura B, Yoshida O, Miyazaki M, Shiomi A, Kanzaki S, Nakaguchi H, Nakamura Y, Imai Y, Koizumi M, Yamamoto Y, Koizumi Y, Hirooka M, Takeshita E, Kumagi T, Ikeda Y, Abe M, and Hiasa Y
- Abstract
Aim: Hepatitis C complicated by diabetes mellitus (DM) is considered a risk factor for the progression of fibrosis and development of hepatocellular carcinoma (HCC) and cardiovascular diseases. However, several studies may have lacked appropriate diagnosis of glucose intolerance. We aimed to examine the risk associated with abnormal glucose intolerance in the development of liver-related diseases, including HCC and complications of liver cirrhosis, such as ascites, esophageal and gastric varices, and hepatic encephalopathy, and cardiovascular diseases in patients with hepatitis C accurately diagnosed with impaired glucose tolerance., Methods: This longitudinal retrospective study included 365 patients with chronic hepatitis C admitted to Ehime University Hospital for anti-hepatitis C therapy between September 1991 and January 2015. Patients were classified into normal glucose tolerance (NGT), prediabetes, and DM groups based on 75-g oral glucose tolerance test results., Results: Both univariate and multivariate (adjusted for potential confounders) analyses revealed a significantly higher risk of developing HCC and cardiovascular events in the DM group than in the NGT group. However, in multivariate analysis, liver-related events, particularly liver cirrhosis complications, revealed no significant association. In addition, the prediabetes group had no significant risk of any outcome., Conclusions: Patients with hepatitis C complicated by DM, compared with patients with hepatitis C with NGT or complicated with prediabetes, have a higher risk of HCC and cardiovascular disease events, but not liver-related events, particularly in not developing liver cirrhosis complications. Therefore, appropriate follow-up is required for patients with hepatitis C based on their glucose tolerance status., (© 2023 Japan Society of Hepatology.)
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- 2023
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48. Usefulness of Tumor Marker Score for Predicting the Prognosis of Hepatocellular Carcinoma Patients Treated with Atezolizumab Plus Bevacizumab: A Multicenter Retrospective Study.
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Tanaka K, Tsuji K, Hiraoka A, Tada T, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Ishikawa T, Tajiri K, Ochi H, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Naganuma A, Kosaka H, Matono T, Kuroda H, Yata Y, Ohama H, Tada F, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Yokohama K, Nishikawa H, Imai M, Koizumi Y, Nakamura S, Iijima H, Kaibori M, Hiasa Y, and Kumada T
- Abstract
Aim: This study aimed to evaluate the ability of a previously reported tumor marker (TM) score involving alpha-fetoprotein (AFP), fucosylated AFP (AFP-L3), and des gamma-carboxy prothrombin (DCP) as TMs in predicting the prognosis and therapeutic efficacy in hepatocellular carcinoma (HCC) patients administered atezolizumab plus bevacizumab (Atez/Bev) as first-line treatment., Materials/methods: The study period covered September 2020 to December 2022 and involved 371 HCC patients treated with Atez/Bev. The values of the TMs AFP, AFP-L3, and DCP were measured upon introducing Atez/Bev. Elevations in the values of AFP (≥100 ng/mL), AFP-L3 (≥10%), and DCP (≥100 mAU/mL) were considered to indicate a positive TM. The number of positive TMs was summed up and used as the TM score, as previously proposed. Hepatic reserve function was assessed using the modified albumin-bilirubin grade (mALBI). Predictive values for prognosis were evaluated retrospectively., Results: A TM score of 0 was shown in 81 HCC patients (21.8%), 1 in 110 (29.6%), 2 in 112 (29.9%), and 3 in 68 (18.3%). The median overall survival (OS) times for TM scores 0, 1, 2, and 3 were not applicable [NA] (95% CI NA-NA), 24.0 months (95% CI 17.8-NA), 16.7 months (95% CI 17.8-NA), and NA (95% CI 8.3-NA), respectively ( p < 0.001). The median progression-free survival (PFS) times for TM scores 0, 1, 2, and 3 were 16.5 months (95% CI 8.0-not applicable [NA]), 13.8 months (95% CI 10.6-21.3), 7.7 months (95% CI 5.3-8.9), and 5.8 months (95% CI 3.0-7.6), respectively ( p < 0.001). OS was well stratified in mALBI 1/2a and mALBI 2a/2b. PFS was well stratified in mALBI 2a/2b, but not in mALBI 1/2a., Conclusions: The TM score involving AFP, AFP-L3, and DCP as TMs was useful in predicting the prognosis and therapeutic efficacy in terms of OS and PFS in HCC patients administered Atez/Bev as first-line treatment.
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- 2023
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49. Association of proton pump inhibitor and antibiotic use with the clinical outcomes of hepatocellular carcinoma patients receiving atezolizumab and bevacizumab: A multicenter analysis.
- Author
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Hatanaka T, Kakizaki S, Hiraoka A, Tada T, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Shimada N, Kawata K, Kosaka H, Naganuma A, Yata Y, Tanaka T, Ohama H, Tada F, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, and Kumada T
- Abstract
Aim: This retrospective study aimed to investigate the impact of proton pump inhibitor treatment (PPI) and antibiotic treatment on the therapeutic outcomes of hepatocellular carcinoma (HCC) patients receiving atezolizumab and bevacizumab (Atez/Bev)., Methods: The present study included a total of 441 HCC patients who were treated with Atez/Bev in 20 Japanese institutions from September 2020 to April 2022. We adopted the inverse probability of treatment weight to adjust for imbalance in the baseline characteristics of patients with and without PPI treatment as well as patients with and without antibiotic treatment., Results: The progression-free survival (PFS) and overall survival (OS) of patients with and without PPI treatment did not differ to a statistically significant extent. In the weighted cohort, the difference in PFS and OS between the patients with and without PPI did not reach statistical significance (median PFS, 7.0 vs. 6.5 months, p = 0.07; 1-year survival rate 66.3% and 73.8%, p = 0.9). The PFS and OS in patients with antibiotic treatment were worse in comparison to patients without antibiotic treatment (median PFS, 3.8 vs. 7.0 months, p = 0.007; 1-year survival rate 58.8% and 70.3%, p = 0.01). In the weighted cohort, the PFS and OS of the two groups did not differ to a statistically significant extent (median PFS, 3.8 vs. 6.7 months, p = 0.2; 1-year survival rate, 61.8% and 71.0%, p = 0.6)., Conclusions: The therapeutic outcomes of Atez/Bev in HCC patients did not differ between patients with and without PPI treatment or between patients with and without antibiotic treatment., (© 2023 Japan Society of Hepatology.)
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- 2023
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50. Impact of first-line systemic therapy with atezolizumab plus bevacizumab in patients with hepatocellular carcinoma.
- Author
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Tada T, Kumada T, Hiraoka A, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Tada F, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Kosaka H, Naganuma A, Matono T, Koizumi Y, Nakamura S, Kaibori M, Iijima H, and Hiasa Y
- Subjects
- Humans, Bevacizumab adverse effects, Ambulatory Care Facilities, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy
- Abstract
Background and Aim: The study goal was to compare the outcomes of patients with unresectable hepatocellular carcinoma (HCC) who received atezolizumab plus bevacizumab (Atezo/Bev) as either first- or later-line systemic therapy., Methods: A total of 430 patients with HCC treated with Atezo/Bev at 22 institutions in Japan were included. Patients treated with Atezo/Bev as first-line therapy for HCC were defined as the first-line group (n = 268) while those treated with Atezo/Bev as second- or later-line therapy were defined as the later-line group (n = 162)., Results: The median progression-free survival times in the first- and later-line groups were 7.7 months (95% confidence interval [CI], 6.7-9.2) and 6.2 months (95% CI, 5.0-7.7) (P = 0.021). Regarding treatment-related adverse events, hypertension of any grade was more common in the first-line group than in the later-line group (P = 0.025). Analysis adjusted by inverse probability weighting, including patient and HCC characteristics, showed that the later-line group (hazard ratio, 1.304; 95% CI, 1.006-1.690; P = 0.045) was significantly associated with progression-free survival. In patients with Barcelona Clinic Liver Cancer stage B, the median progression-free survival times in the first- and later-line groups were 10.5 months (95% CI, 6.8-13.8) and 6.8 months (95% CI, 5.0-9.4) (P = 0.021). Among patients with a history of lenvatinib therapy, the median progression-free survival times in the first- and later-line groups were 7.7 months (95% CI, 6.3-9.2) and 6.2 months (95% CI, 5.0-7.7) (P = 0.022)., Conclusion: The use of Atezo/Bev as first-line systemic therapy in patients with HCC is expected to prolong survival., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)
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- 2023
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