Published Papers - Masuzaki Hiroaki

Two Cases of Plasmablastic Myeloma Mimicking Plasmablastic Lymphoma With In-Depth Review of Literature.

Kitamura S, Morichika K, Nakachi S, Hanashiro T, Miyagi R, Nakajima T, Nishi Y, Tamaki K, Fukushima T, Masuzaki H

Cancer reports (Hoboken, N.J.) ( Cancer Reports )  8 ( 2 ) e70094   2025.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Intramuscular abscess and multiple lymphadenitis due to <i>Nocardia asiatica</i> infection requiring differential diagnosis from smoldering adult T-cell leukemia/lymphoma

YAMASHIRO Mahito, NAKAJIMA Tomo, IREI Yuka, MIYAGI Riko, KITAMURA Sakiko, TAMAKI Keita, NISHI Yukiko, MORICHIKA Kazuho, NAKACHI Sawako, MAEHARA Hiroki, FUKUSHIMA Takuya, MASUZAKI Hiroaki

Rinsho Ketsueki ( The Japanese Society of Hematology )  66 ( 2 ) 121 - 126   2025 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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<p>A 72-year-old male engaged in horticulture developed a progressively enlarging painful mass in the left upper arm. The first biopsy revealed no malignancy or pathogenic bacteria. He completed an adequate course of antibiotics for infectious lymphadenitis, but showed no apparent improvement. Computed tomography demonstrated systemic lymphadenopathy, suggesting malignant lymphoma. Monoclonal integration of the HTLV-1 proviral genome in peripheral blood cells was confirmed by Southern blot analysis, but repeated lymph node biopsies identified no malignant cells. Based on these findings, a diagnosis of smoldering adult T-cell leukemia/lymphoma was made. After prolonged culture of the specimen, <i>Nocardia</i> sp. were detected and 16S rRNA sequencing confirmed infection by <i>Nocardia asiatica</i>. Combination therapy with sulfamethoxazole-trimethoprim and minocycline was started, and the systemic lymphadenopathy improved within 3 months. Although <i>Nocardia asiatica</i> infection manifesting as systemic lymphadenitis is extremely rare, it should be considered as a possibility in immunocompromised patients to ensure an accurate diagnosis.</p>

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A Rare Case of Autoimmune-Mediated Lecithin:Cholesterol Acyltransferase Insufficiency Manifesting as the Acute Onset of Extremely Hypo-High-Density Lipoprotein-Cholesterolemia and Spontaneous Improvement: A Case Report with a Review of the Literature.

Tamaki A, Kuroda M, Yonaha K, Ishiki Y, Uehara M, Nakayama Y, Honma KI, Chinen R, Uema T, Okamoto S, Miyoshi J, Kirinashizawa M, Sato K, Aohara T, Yamamoto M, Maezawa Y, Yokote K, Masuzaki H

Journal of atherosclerosis and thrombosis ( 一般社団法人 日本動脈硬化学会 )  advpub ( 0 )   2024.12 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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A 59-year-old Japanese woman was referred for an extremely low level of circulating high-density lipoprotein cholesterol (HDL-C). The serum HDL-C level had long been within the normal range but suddenly decreased asymptomatically to 7 mg/dL. She had no typical symptoms associated with familial lecithin, cholesterol acyltransferase deficiency (FLD), including proteinuria, anemia, and corneal opacity. The circulating level of ApoA-1 was also markedly decreased at 48 mg/dL, and the proportion of esterified cholesterol to free cholesterol was irregularly low at 26%. Whole-genome sequencing revealed no apparent pathological mutations in the LCAT gene. Notably, anti-LCAT antibodies were detected in the serum at 146±1.7 ng/mL, resulting in her being diagnosed with acquired LCAT insufficiency (ALCATI) caused by anti-LCAT antibodies. Five years after her HDL-C levels spontaneously decreased, they increased without any identifiable cause. To our knowledge, only six cases of ALCATI caused by anti-LCAT antibodies have been reported to date. In contrast to the present case, previously reported cases of ALCATI manifested proteinuria that improved with steroid therapy. The unique clinical course in the present case highlights the heterogeneity of ALCATI, warranting further research to clarify the molecular pathophysiology of FLD and ALCATI.

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Machine learning-based reproducible prediction of type 2 diabetes subtypes.

Tanabe H, Sato M, Miyake A, Shimajiri Y, Ojima T, Narita A, Saito H, Tanaka K, Masuzaki H, Kazama JJ, Katagiri H, Tamiya G, Kawakami E, Shimabukuro M

Diabetologia ( Diabetologia )  67 ( 11 ) 2446 - 2458   2024.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Young-onset type 2 diabetes mellitus enhances proteinuria, but not glomerular filtration rate decline: A Japanese cohort study.

Saito H, Tanabe H, Hirai H, Higa M, Tanaka K, Yamaguchi S, Maimaituxun G, Masuzaki H, Kazama JJ, Shimabukuro M

Journal of diabetes investigation ( Journal of Diabetes Investigation )  15 ( 10 ) 1444 - 1456   2024.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Gut microbiota-based prediction for the transition from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) in a remote island cohort study.

Uema T, Tsukita M, Okamoto S, Uehara M, Honma KI, Nakayama Y, Tamaki A, Miyazato M, Ashikari A, Maeda S, Imamura M, Matsushita M, Nakamura K, Masuzaki H

Diabetes research and clinical practice ( Diabetes Research and Clinical Practice )  213   111747 - 111747   2024.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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AIM: The present cohort study explored whether specific gut microbiota (GM) profile would predict the development of impaired glucose tolerance (IGT) in individuals with normal glucose tolerance (NGT). METHODS: A total of 114 study subjects with NGT in Kumejima island, Japan participated in the present study and underwent 75 g oral glucose tolerance tests at baseline and one year later. We compared the profile of GM at baseline between individuals who consistently maintained NGT (NRN, n = 108) and those who transitioned from NGT to IGT (NTI, n = 6). RESULTS: Within-individual bacterial richness and evenness as well as inter-individual bacterial composition showed no significant differences between NRN and NTI. Of note, however, partial least squares discriminant analyses revealed distinct compositions of GM between groups, with no overlap in their 95 % confidence interval ellipses. Multi-factor analyses at the genus level demonstrated that the proportions of CF231, Corynebacterium, Succinivibrio, and Geobacillus were significantly elevated in NTI compared to NRN (p < 0.005, FDR < 0.1, respectively) after adjusting for age, sex, HbA1c level, and BMI. CONCLUSIONS: Our data suggest that increased proportion of specific GM is linked to the future deterioration of glucose tolerance, thereby serving as a promising predictive marker for type 2 diabetes mellitus.

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Impact of the transition from radioimmunoassay (RIA) to chemiluminescent enzyme immunoassay (CLEIA) for the measurement of plasma aldosterone concentration (PAC) on the diagnosis of primary aldosteronism (PA) via retrospective analyses in Okinawa, Japan.

Honma KI, Nakayama Y, Tamaki A, Uehara M, Teruya T, Yabiku T, Ishiki Y, Yonaha K, Chinen R, Uema T, Okamoto S, Masuzaki H

Endocrine journal ( 一般社団法人 日本内分泌学会 )  advpub ( 0 ) 895 - 906   2024.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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In Japan, the traditional method for measuring plasma aldosterone concentration (PAC) was radioimmunoassay (RIA), which had several challenges, including poor traceability of certified reference materials and reduced detection sensitivity at low concentrations. To overcome these issues, a chemiluminescent enzyme immunoassay (CLEIA) for PAC measurement was introduced in April 2021 and the Japan Endocrine Society published new guidelines for primary aldosteronism (PA). This study aimed to evaluate the impact of the transition from RIA to CLEIA for PAC measurement on PA diagnosis. Data from 190 patients admitted to the Second Department of Internal Medicine, University of the Ryukyus Hospital, between April 2012 and March 2021 were analyzed. Patients who were diagnosed with PA underwent adrenal venous sampling. The PAC measured by RIA (PAC(RIA)) was converted to the estimated PAC measured by CLEIA (ePAC(CLEIA)) using a conversion formula. The present study evaluated the discordance rates in diagnoses based on screening (SC), captopril challenge test (CCT), saline infusion test (SIT), and diagnosis of PA between results judged by PAC(RIA) according to the previous guidelines and those judged by ePAC(CLEIA) according to the new guidelines. The results revealed discordant diagnosis rates of 6.4% for SC and 10.1% for CCT, with no discordance for SIT. The discordant diagnosis rate for PA was 3.7%. Our study reveals the challenges in establishing appropriate diagnostic criteria for PA using PAC(CLEIA) and highlights the demand for further research on provisionally positive categories.

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Post-traumatic pituitary stalk transection syndrome (PSTS) expeditiously manifested after a fall from a height combined with acute traumatic spinal cord injury: a rare case report with review of literature.

Ishiki Y, Tamaki A, Honma KI, Yonaha K, Yabiku T, Teruya T, Uehara M, Nakayama Y, Chinen R, Uema T, Nakachi S, Okamoto S, Masuzaki H

Endocrine journal ( 一般社団法人 日本内分泌学会 )  advpub ( 0 ) 817 - 824   2024.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Post-traumatic pituitary stalk transection syndrome (PSTS) is an extremely rare cause of combined pituitary hormone deficiency (CPHD), affecting approximately 9 per 100,000 cases of traumatic brain injury. In contrast, pituitary stalk interruption syndrome (PSIS) is also a rare cause of CPHD. Importantly, these conditions are often confused due to their similar names and resembling findings on magnetic resonance imaging (MRI). PSIS has been thought to be a prenatal developmental event resulting from a couple of genetic aberrations. In typical PSIS, anterior pituitary hormone deficiencies are restricted to growth hormone (GH) and gonadotropin during the pediatric age, gradually and generally progressing to panhypopituitarism in most cases. In contrast, global deficiencies of the anterior pituitary hormones in PSTS are temporally associated with trauma. To the best of our knowledge, no case reports of PSTS combined with acute traumatic spinal cord injury have been reported. A 34-year-old female was transferred to our hospital after jumping from the fourth building floor. She was diagnosed as an acute traumatic spinal cord injury and underwent the operation of elective posterior spinal fusion. On postoperative day 7, the blood tests revealed considerable hyperkalemia, hyponatremia and eosinophilia. Notably, menstruation stopped after falling from a height. Pituitary function tests revealed GH deficiency, hypogonadism, hypothyroidism and hypoadrenocorticism. MRI revealed loss of the pituitary stalk, whilst the hyperintense signal from distal axon of hypothalamus was still identified. Based on these findings, she was diagnosed as PSTS. Our case highlights endocrinological landscape of transection of the pituitary stalk by acute trauma.

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Role of perirenal adiposity in renal dysfunction among CKD individuals with or without diabetes: a Japanese cross-sectional study.

Kono T, Maimaituxun G, Tanabe H, Higa M, Saito H, Tanaka K, Masuzaki H, Sata M, Kazama JJ, Shimabukuro M

BMJ open diabetes research & care ( BMJ Open Diabetes Research and Care )  12 ( 2 )   2024.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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INTRODUCTION: It remains unclear whether increased perirenal fat (PRF) accumulation is equally related to renal involvement in patients with and without diabetes mellitus (DM). We evaluated the association between PRF volume (PRFV) and low glomerular filtration rate (GFR) and proteinuria in people with or without type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: We performed a cross-sectional analysis of 473 individuals without T2DM (non-DM, n=202) and with T2DM (DM, n=271). PRFV (cm3), obtained from non-contrast CT, was indexed as PRF index (PRFV/body surface area, cm3/m2). Multivariate-adjusted models were used to determine the ORs of PRFV and PRFV index for detecting estimated GFR (eGFR) decrease of <60 mL/min/1.73 m2 proteinuria onset, or both. RESULTS: Although body mass index (BMI), visceral fat area, and waist circumference were comparable between the non-DM and DM groups, kidney volume, PRFV, and PRFV index were higher in individuals with T2DM than in those without T2DM. In the multivariate analysis, after adjusting for age, sex, BMI, hypertension, smoking history, and visceral fat area ≥100 cm2, the cut-off values of PRFV index were associated with an eGFR<60 in individuals with DM (OR 6.01, 95% CI 2.20 to 16.4, p<0.001) but not in those without DM. CONCLUSIONS: PRFV is associated with low eGFR in patients with T2DM but not in those without T2DM. This suggests that PRF accumulation is more closely related to the onset and progression of diabetic kidney disease (DKD) than non-DKD. Clarifying the mechanisms through which PRF influences DKD development could pave the way for novel prevention and treatment strategies.

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4. Conclusion

Masuzaki Hiroaki

Nihon Naika Gakkai Zasshi ( The Japanese Society of Internal Medicine )  113 ( 3 ) 402 - 403   2024.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Impact of coronavirus disease 2019 on medical practice in endocrine and metabolic diseases in Japan: a nationwide surveillance study conducted by the Japan Endocrine Society.

Manaka K, Kato S, Sakamoto R, Yamakage H, Uema T, Kawai S, Shibata M, Hiratsuka I, Nakachi S, Onoue T, Tsuchiya T, Fukui M, Hashimoto K, Suzuki A, Makita N, Ogawa Y, Arima H, Satoh-Asahara N, Masuzaki H

Endocrine journal ( 一般社団法人 日本内分泌学会 )  advpub ( 0 ) 499 - 514   2024.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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<p>We investigated the impact of the Coronavirus disease 2019 (COVID-19) pandemic on the management of endocrine and metabolic disorders in Japan. We conducted a cross-sectional nationwide questionnaire survey targeting board-certified endocrinologists under the auspices of the Japan Endocrine Society. The questionnaire consisted of multiple-choice questions and open-ended responses. Out of approximately 2,700 specialists, 528 (19.5%) opted to participate, suggesting a high level of interest in COVID-19 management among endocrinologists. The study found that almost half of participants had encountered cases of endocrine and metabolic disorders following COVID-19 infection or vaccination. Conditions related to thyroid diseases, glucose metabolism disorders/diabetes, and hypothalamic-pituitary disorders were particularly prevalent. Diabetes and obesity were identified as having high rates of severe cases or fatalities due to COVID-19. The study also highlighted challenges in routine diagnosis and treatment, emphasizing the potential benefits of combining remote consultations with in-person visits to optimize the frequency of examinations and check-ups during infectious disease outbreak which disrupts access to healthcare providers. The insights obtained from this survey are expected to contribute to ensuring appropriate healthcare provision for patients with endocrine and metabolic disorders by using flexible consultation formats, particularly even in the conditions where medical access may be limited due to future outbreaks of emerging or re-emerging infectious diseases.</p>

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Sex differences in the association between epicardial adipose tissue volume and left atrial volume index.

Yamaguchi S, Maeda M, Oba K, Maimaituxun G, Arasaki O, Yagi S, Kusunose K, Soeki T, Yamada H, Fukuda D, Masuzaki H, Sata M, Shimabukuro M

BMC cardiovascular disorders ( BMC Cardiovascular Disorders )  24 ( 1 ) 46 - 46   2024.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: Sex disparities in the association between epicardial adipose tissue volume (EATV) and cardiovascular disease have been reported. The sex-dependent effects of EATV on left atrial (LA) size have not been elucidated. METHODS: Consecutive 247 subjects (median 65 [interquartile range 57, 75] years; 67% of men) who underwent multi-detector computed tomography without significant coronary artery disease or moderate to severe valvular disease were divided into two groups: patients with sinus rhythm (SR) or atrial fibrillation (AF). Sex differences in the association between the EATV index (EATVI) (mL/m2) and LA volume index (LAVI) in 63 SR (28 men and 35 women) and 184 AF (137 men and 47 women) patients were evaluated using univariate and multivariate regression analyses. RESULTS: In overall that includes both men and women, the relationship between EATVI and LAVI was not significantly correlated for patients with SR and AF. The relationship between EATVI and LAVI differed between men and women in both SR and AF groups. In SR patients, there was a positive relationship between EATVI and LAVI in men, but not in women. In contrast, in patients with AF, a negative relationship was found between EATVI and LAVI in women, whereas no association was found in men. CONCLUSIONS: We evaluated sex differences in the association between EATVI and LAVI in patients with either SR or AF, and found a positive relationship in men with SR and a negative relationship in women with AF. This is the first report to evaluate sex differences in the relationship between EATVI and LAVI, suggesting that EAT may play a role, at least in part, in sex differences in the etiology of AF.

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Impact of treatment cessation on incidence and progression of retinopathy in Japanese patients with type 2 diabetes mellitus: a retrospective cohort study

Yukiko Shinzato, Yoshiro Nakayama, Shiki Okamoto, Jasmine F. Millman, Tsugumi Uema, Ken-ichiro Honma, Atsuko Tamaki, Moriyuki Uehara, Taiki Teruya, Takamitsu Yabiku, Yohei Ishiki, Ken Yonaha, Ko-ichiro Arakaki, Moritake Higa, Hideki Koizumi, Koshi Nakamura, Michio Shimabukuro, Hiroaki Masuzaki

Diabetology International ( Springer Science and Business Media LLC )  15 ( 3 ) 535 - 543   2024 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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肺原発節外性NK/T細胞リンパ腫の一例

宮城 理子, 仲地 佐和子, 上間 道仁, 横田 雄太郎, 中島 知, 北村 紗希子, 玉城 啓太, 森近 一穂, 西 由希子, 森島 聡子, 福島 卓也, 益崎 裕章

日本血液学会学術集会 ( (一社)日本血液学会 )  85回   1165 - 1165   2023.10

Type of publication: Research paper (other science council materials etc.)

遺伝子異常を伴わないPAI-1欠乏症が疑われた1例

森島 聡子, 岩城 孝行, 浦野 哲盟, 宮城 理子, 中島 知, 北村 紗希子, 花城 多恵子, 西 由希子, 玉城 啓太, 森近 一穂, 仲地 佐和子, 益崎 裕章

日本血液学会学術集会 ( (一社)日本血液学会 )  85回   609 - 609   2023.10

Type of publication: Research paper (other science council materials etc.)

A Foreword to the Special Issue

Masuzaki Hiroaki

Journal of the Japan Diabetes Society ( THE JAPAN DIABETES SOCIETY )  66 ( 6 ) 459 - 459   2023.06

Type of publication: Research paper (scientific journal)

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Effect of dapagliflozin on 24-hour glycemic variables in Japanese patients with type 2 diabetes mellitus receiving basal insulin supported oral therapy (DBOT): a multicenter, randomized, open-label, parallel-group study.

Kudo A, Machii N, Ono T, Saito H, Oshiro Y, Takahashi R, Oshiro K, Taneda Y, Higa M, Nakachi K, Yagi S, Masuzaki H, Sata M, Shimabukuro M

BMJ open diabetes research & care ( BMJ Open Diabetes Research and Care )  11 ( 2 )   2023.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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INTRODUCTION: This study aimed to evaluate the impacts of dapagliflozin on 24-hour glucose variability and diabetes-related biochemical variables in Japanese patients with type 2 diabetes who had received basal insulin supported oral therapy (BOT). RESEARCH DESIGN AND METHODS: Changes in mean daily blood glucose level before and after 48-72 hours of add-on or no add-on of dapagliflozin (primary end point) and diabetes-related biochemical variables and major safety variables during the 12 weeks (secondary end point) were evaluated in the multicenter, randomized, two-arm, open-label, parallel-group comparison study. RESULTS: Among 36 participants, 18 were included in the no add-on group and 18 were included in the dapagliflozin add-on group. Age, gender, and body mass index were comparable between the groups. There were no changes in continuous glucose monitoring metrics in the no add-on group. In the dapagliflozin add-on group, mean glucose (183-156 mg/dL, p=0.001), maximum glucose (300-253, p<0.01), and SD glucose (57-45, p<0.05) decreased. Time in range increased (p<0.05), while time above the range decreased in the dapagliflozin add-on group but not in the no add-on group. After 12-week treatment with dapagliflozin add-on, 8-hydroxy-2'-deoxyguanosine (8OHdG), as well as hemoglobin A1c (HbA1c), decreased. CONCLUSIONS: This study showed that the mean daily blood glucose and other daily glucose profiles were amended after 48-72 hours of dapagliflozin add-on in Japanese patients with type 2 diabetes who received BOT. The diabetes-related biochemical variables such as HbA1c and urinary 8OHdG were also obtained during the 12 weeks of dapagliflozin add-on without major adverse events. A preferable 24-hour glucose profile in 'time in ranges' and an improvement in reactive oxygen species by dapagliflozin warrant us to evaluate these benefits in larger clinical studies. TRIAL REGISTRATION NUMBER: UMIN000019457.

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A Comprehensive Study of the Immunophenotype and its Clinicopathological Significance in Adult T-cell Leukemia/Lymphoma.

Tamaki T, Karube K, Sakihama S, Tsuruta Y, Awazawa R, Hayashi M, Nakada N, Matsumoto H, Yagi N, Ohshiro K, Nakazato I, Kitamura S, Nishi Y, Miyagi T, Yamaguchi S, Nakachi S, Morishima S, Masuzaki H, Takahashi K, Fukushima T, Wada N

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc ( Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc )  36 ( 8 ) 100169 - 100169   2023.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell tumor caused by human T-lymphotropic virus type 1 (HTLV-1). The typical ATLL immunophenotypes are described in the 2017 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues (positive: CD2, CD3, CD5, CD4, and CD25; negative: CD7, CD8, and cytotoxic markers; and partially positive: CD30, CCR4, and FOXP3). However, limited studies are available on the expression of these markers, and their mutual relationship remains unknown. Furthermore, the expression status of novel markers associated with T-cell lymphomas, including Th1 markers (T-bet and CXCR3), Th2 markers (GATA3 and CCR4), T follicular helper markers (BCL6, PD1, and ICOS), and T-cell receptor (TCR) markers, and their clinicopathologic significance is unclear. In this study, we performed >20 immunohistochemical stains in 117 ATLL cases to determine the comprehensive immunophenotypic profile of ATLL, which were compared on the basis of clinicopathologic factors, including morphologic variants (pleomorphic vs anaplastic), biopsy locations, treatments, Shimoyama classification-based clinical subtype, and overall survival. CD3+/CD4+/CD25+/CCR4+ was considered a typical immunophenotype of ATLL, but approximately 20% of cases did not conform to this pattern. Simultaneously, the following new findings were obtained: (1) most cases were negative for TCR-β and TCR-δ (104 cases, 88.9%), indicating the usefulness of negative conversion of TCR expression to provide differentiation from other T-cell tumors; (2) the positivity of CD30 and CD15 and the negativity of FOXP3 and CD3 were significantly associated with anaplastic morphology; and (3) atypical cases, such as T follicular helper marker-positive (12 cases, 10.3%) and cytotoxic molecule-positive cases (3 cases, 2.6%), were identified. No single markers could predict the overall survival among patients with acute/lymphoma subtypes of ATLL. The results of this study illustrate the diversity of ATLL phenotypes. In T-cell tumors occurring in HTLV-1 carriers, the possibility of ATLL should not be eliminated even when the tumor exhibits an atypical phenotype, and the confirmation of HTLV-1 in the tissue is recommended.

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Markers for obese and non-obese Type 2 diabetes identified using whole blood metabolomics.

Teruya T, Sunagawa S, Mori A, Masuzaki H, Yanagida M

Scientific reports ( Scientific Reports )  13 ( 1 ) 2460   2023.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Fatal acquired coagulation factor V deficiency after hepatectomy for advanced hepatocellular carcinoma as a possible immune checkpoint inhibitor-related adverse event: a case report.

Arakaki S, Ono S, Kawamata F, Ishino S, Uesato Y, Nakajima T, Nishi Y, Morishima S, Arakaki S, Maeshiro T, Souri M, Ichinose A, Masuzaki H, Takatsuki M

Surgical case reports ( SpringerOpen )  9 ( 1 ) 16 - 7   2023.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background Atezolizumab plus bevacizumab therapy was recently introduced as the first line for unresectable advanced hepatocellular carcinoma (HCC), but immune-related adverse events (IrAEs) due to atezolizumab are a great concern. Here, we report the case of a patient who developed fatal acquired coagulation factor deficiency after hepatectomy for HCC, treated with atezolizumab and bevacizumab before surgery. Case presentation A 70-year-old man received right trisegmentectomy of the liver with hepaticojejunostomy for advanced HCC with bile duct invasion, after atezolizumab and bevacizumab therapy. The patient suffered the sudden onset of severe multiple coagulation factor deficiency (II, V, VII, VIII, IX, X, XI and XII) immediately following reoperation for anastomotic leakage of hepaticojejunostomy, 7 days after hepatectomy. The coagulation factor deficiency did not reverse even with intensive treatment, and the patient died of uncontrollable bleeding 32 days after hepatectomy. An IrAE due to atezolizumab was suspected because the patient had developed the possible IrAE of enthesitis of the right gastrocnemius muscle before surgery, and specific inhibitors against factor V and anti-factor V autoantibodies were detected, leading to an ultimate diagnosis of autoimmune FV/5 deficiency (AiF5D). Conclusion Severe acquired coagulopathy should be recognized as a possible life-threatening IrAE when using atezolizumab and bevacizumab for HCC.

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