研究者詳細 - 伊藤　隆徳

Decreased appetite is associated with the presence of sarcopenia in patients with cirrhosis 査読有り

Ishizu Y., Ishigami M., Honda T., Imai N., Ito T., Yamamoto K., Yokoyama S., Ishikawa T., Kawashima H.

Nutrition 103-104 巻頁： 111807 2022年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nutrition

Objectives: To our knowledge, the relationship between appetite and sarcopenia in patients with cirrhosis is unknown. The aims of this study were to examine the factors associated with decreased appetite and to clarify the relationship between appetite and sarcopenia. Methods: This study included 61 patients with cirrhosis. The patients were asked to describe their appetite using a numerical rating scale (NRS) from 0 (none at all) to 10 (most), with ≤5 defined as decreased appetite. The clinical characteristics, gastrointestinal symptoms as assessed using the Gastrointestinal Symptom Rating Scale, handgrip strength, and skeletal muscle area at the third vertebra were collected retrospectively. Sarcopenia was diagnosed according to the criteria of the Japan Society of Hepatology. The differences in these factors between patients with and without decreased appetite, and the factors associated with the presence of sarcopenia were examined. Results: Alcoholic liver disease was the most common etiology. The median Model for End-Stage Liver Disease score was 8 (interquartile range = 7 - 10) and hepatocellular carcinoma was present in 35 patients. Overall, 36% of the patients with cirrhosis had decreased appetite. Patients with decreased appetite had a higher frequency of abdominal pain and acid reflux–related symptoms and significantly lower handgrip strength than patients without, among both men (P = 0.034) and women (P = 0.017). The multivariate analysis identified a decrease in appetite as a significant factor associated with the presence of sarcopenia (NRS one increase, odds ratio, 0.701; 95% confidence interval, 0.502–0.977; P = 0.036). Conclusion: Decreased appetite was associated with the presence of sarcopenia.

DOI： 10.1016/j.nut.2022.111807

Combined ultrasound and magnetic resonance elastography predict hepatocellular carcinoma after hepatitis C virus eradication 査読有り

Kumada T., Toyoda H., Yasuda S., Ogawa S., Gotoh T., Tada T., Ito T., Sumida Y., Tanaka J.

Hepatology Research 52 巻 ( 11 ) 頁： 957 - 967 2022年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Hepatology Research

Aim: Elastography is an established, noninvasive method for measuring liver stiffness using to 2-D shear-wave elastography (2D-SWE) or magnetic resonance elastography (MRE). The aim of this study was to determine the usefulness of combined measurement using 2D-SWE and MRE to stratify the risk of developing hepatocellular carcinoma (HCC) in patients who achieved hepatitis C virus eradication. Methods: Five hundred and twenty-five patients who underwent 2D-SWE and MRE before antiviral therapy and who achieved eradication were enrolled. The optimal 2D-SWE and MRE cutoff values were determined using time-dependent receiver operating characteristic (ROC) curves for predicting HCC development. Inverse probability of treatment weighting (IPTW) and a Cox proportional hazards model were used to adjust the cumulative incidence rate of HCC development for potential imbalances. Results: Time-dependent ROC analysis showed that the optimal cut-off values of 2D-SWE and MRE for predicting HCC development were 11.7 and 4.5 kPa, respectively. The IPTW-adjusted cumulative incidence rate of HCC development in patients with both an 2D-SWE value ≥ 11.7 kPa and an MRE value ≥ 4.5 kPa had a higher hazard ratio (28.080; 95% confidence interval, 5.527–132.600; p < 0.001) than those with either an 2D-SWE value < 11.7 kPa or an MRE value < 4.5 kPa. Conclusions: The combined measurement of 2D-SWE and MRE was very effective for identifying patients at high risk of HCC development. US-based elastography should be performed first, and if the 2D-SWE value is high, MRE should then be carried out to confirm the degree of liver stiffness.

DOI： 10.1111/hepr.13814

An improved method to assess skeletal muscle mass in patients with liver cirrhosis based on computed tomography images 査読有り

Additional survival follow-up of TACTICS-L: Transcatheter arterial chemoembolization therapy (TACE) in combination strategy with lenvatinib in (LEN) patients with unresectable hepatocellular carcinoma in Japan

Inaba Y., Ueshima K., Ishikawa T., Saeki I., Morimoto N., Aikata H., Tanabe N., Wada Y., Kondo Y., Tsuda M., Nakao K., Ikeda M., Moriguchi M., Ito T., Hosaka T., Koga H., Hino K., Kawamura Y., Yoshimura K., Kudo M.

ANNALS OF ONCOLOGY 33 巻頁： S1472 - S1472 2022年11月

Sugiyama Y., Ishizu Y., Ando Y., Yokoyama S., Yamamoto K., Ito T., Imai N., Nakamura M., Honda T., Kawashima H., Ishikawa T., Ishigami M.

Hepatology Research 52 巻 ( 11 ) 頁： 937 - 946 2022年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Hepatology Research

Aim: Conventionally, the skeletal muscle area with computed tomography (CT) attenuation ranging from −29 to +150 Hounsfield unit (HU) divided by height squared (the conventional skeletal muscle index [SMI]) was used as an index of skeletal muscle mass. However, it includes fat-infiltrated skeletal muscle, which is known to have poor function. This study aims to determine whether the low-fat SMI, which uses skeletal muscle mass with CT attenuation ranging from +30 to +150 HU, or conventional SMI appropriately reflects the function of skeletal muscle. Methods: We retrospectively analyzed 120 patients with cirrhosis whose handgrip strength was measured. Among them, 48 patients underwent a physical performance assessment such as liver frailty index (LFI) and short physical performance battery (SPPB), and 80 underwent quality of life (QOL) assessment. The relationships between each SMI and handgrip strength, LFI, SPPB, and QOL were evaluated. Results: Low-fat SMI was significantly correlated with handgrip strength (males, R = 0.393, p = 0.002; females, R = 0.423, p < 0.001) and LFI (males, R = −0.535, p = 0.035; females, R = −0.368, p = 0.039), whereas conventional SMI was not. When using low-fat SMI, patients with low skeletal muscle mass had significantly low handgrip strength, LFI, SPPB, and physical and social-related QOL score than those without. By contrast, no significant differences were found for any items when using conventional SMI. Conclusions: Low-fat SMI is a good index of skeletal muscle mass that appropriately reflects skeletal muscle function.

DOI： 10.1111/hepr.13820

Elevated TSH Level, TgAb, and Prior Use of Ramucirumab or TKIs as Risk Factors for Thyroid Dysfunction in PD-L1 Blockade 査読有り

Kobayashi T., Iwama S., Yamagami A., Yasuda Y., Okuji T., Ito M., Zhou X., Ando M., Onoue T., Miyata T., Sugiyama M., Hagiwara D., Suga H., Banno R., Hase T., Morise M., Ito T., Kikumori T., Inoue M., Ando Y., Masuda N., Kawashima H., Hashimoto N., Arima H.

Journal of Clinical Endocrinology and Metabolism 107 巻 ( 10 ) 頁： E4115 - E4123 2022年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Clinical Endocrinology and Metabolism

Background: Thyroid dysfunction is frequently caused by treatment with antiprogrammed cell death-1 ligand 1 antibodies (PD-L1-Abs) and anticancer drugs, including ramucirumab (RAM) and multitargeted tyrosine kinase inhibitors (multi-TKIs), which are often used prior to PD-L1-Ab treatment in cancer patients. Methods: A total of 148 patients treated with PD-L1-Abs were evaluated for antithyroid antibodies at baseline and for thyroid function every 6 weeks for 24 weeks after treatment initiation and then were observed until the visits stopped. Results: Of the 148 patients, 15 (10.1%) developed thyroid dysfunction after PD-L1-Ab treatment (destructive thyroiditis in 8 and hypothyroidism without preceding thyrotoxicosis in 7). The prevalence of an elevated thyroid-stimulating hormone (TSH) level at baseline (3/15 [20.0%] vs 4/133 [3.0%], P < .05), positive antithyroglobulin antibodies (TgAbs) at baseline (4/15 [26.7%] vs 5/133 [3.8%], P < .05) and prior treatment with RAM or multi-TKIs (3/15 [20.0%] vs 5/133 [3.8%], P < .05) were significantly higher in patients with vs without thyroid dysfunction. In a multivariate analysis, elevated TSH level at baseline, TgAb positivity at baseline, and prior treatment with RAM or multi-TKIs were significantly associated with the development of thyroid dysfunction, with ORs of 7.098 (95% CI 1.154-43.638), 11.927 (95% CI 2.526-56.316), and 8.476 (95% CI 1.592-45.115), respectively. Conclusion: The results of this real-world study suggest that the risk of thyroid dysfunction induced by PD-L1-Abs can be predicted by the TSH level at baseline, TgAb positivity at baseline, and prior treatment with RAM or multi-TKIs.

DOI： 10.1210/clinem/dgac467

Factors linked to hepatocellular carcinoma development beyond 10 years after viral eradication in patients with hepatitis C virus 査読有り

USEFULNESS OF MUTATIONS INDUCED IN THE CORE REGION BY INTERFERON-BASED THERAPY

Honda Takashi Honda, Ishigami Masatoshi, Kato Asuka, Yokoyama Shinya, Yamamoto Kenta, Ito Takanori, Imai Norihiro, Ishizu Yoji, Yasuda Satoshi, Toyoda Hidenori, Kumada Takashi, Ishikawa Tetsuya, Kawashima Hiroki

HEPATOLOGY 76 巻頁： S262 - S263 2022年10月

ANOREXIA IS ASSOCIATED WITH THE PRESENCE OF SARCOPENIA IN PATIENTS WITH CIRRHOSIS

Ishizu Yoji, Yokoyama Shinya, Yamamoto Kenta, Ito Takanori, Imai Norihiro, Honda Takashi Honda, Ishigami Masatoshi, Kawashima Hiroki

HEPATOLOGY 76 巻頁： S1181 - S1181 2022年10月

ANTIVIRAL THERAPY REDUCES HEPATOCELLULAR CARCINOMA RISK AMONG HBV PATIENTS IN THE INDETERMINATE PHASE

Huang Daniel, Tran Andrew Khoa, Yeh Ming-Lun, Tsai Pei-Chien, Chuang Wan-Long, Huang Chung-Feng, Dai Chia-Yen, Toyoda Hidenori, Yasuda Satoshi, Trinh Huy, Ogawa Eiichi, Ishigami Masatoshi, Ito Takanori, Kozuka Ritsuzo, Enomoto Masaru, Tanaka Yasuhito, Suzuki Takanori, Yoshimaru Yoko, Preda Carmen, Marin Raluca, Sandra Irina, Quek Sabrina, Khine Htet Htet Toe Wai, Itokawa Norio, Atsukawa Masanori, Uojima Haruki, Watanabe Tsunamasa, Takahashi Hirokazu, Inoue Kaori, Maeda Mayumi, Hoang Joseph, Trinh Lindsey, Cheung Ramsey, Lim Seng Gee, Yu Ming-Lung, Nguyen Mindie H.

HEPATOLOGY 76 巻頁： S34 - S35 2022年10月

CIRRHOSIS INCIDENCE AND LONG-TERM MORTALITY RATE AMONG LEAN, OVERWEIGHT, AND OBESE PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IN THE UNITED STATES

Nguyen Vy H., Ha Audrey, Park Jung Eun, Rouillard Nicholas, Le Richard H. X., Fong Ashley, Maeda Mayumi, Ito Takanori, Nguyen Mindie H.

HEPATOLOGY 76 巻頁： S742 - S743 2022年10月

CLINICAL COURSE AND PROGNOSIS OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH HEMOPHILIA

Imai Norihiro, Ishigami Masatoshi, Matsuda Noritaka, Yokoyama Shinya, Yamamoto Kenta, Ito Takanori, Ishizu Yoji, Honda Takashi Honda, Kawashima Hiroki

HEPATOLOGY 76 巻頁： S1330 - S1330 2022年10月

Kumada T., Toyoda H., Yasuda S., Ito T., Tsuji K., Fujioka S., Hiraoka A., Kariyama K., Nouso K., Ishikawa T., Tamai T., Tada T., Tanaka J.

Journal of Viral Hepatitis 29 巻 ( 10 ) 頁： 919 - 929 2022年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Viral Hepatitis

The risk factors for hepatocellular carcinoma (HCC) development in patients whose duration of sustained virological response (SVR) is over 10 years are not fully understood. We compared the incidence of HCC development within and beyond 10 years after SVR. A total of 1384 patients who achieved SVR (714, interferon-based therapy; 670, direct-acting antiviral therapy) were enrolled. Factors associated with HCC development were analysed within and beyond 10 years after SVR by Cox proportional hazards models. The annual incidence rates of HCC development were 0.568% within 10 years after SVR and 0.190% beyond 10 years, and there was a significant difference in the incidence of HCC development between the 2 periods (p = 0.0242, log-rank test). Male gender (adjusted hazard ratio [aHR] 2.930; 95% confidence interval [CI] 1.508–5.693, p = 0.0015), fibrosis-4 (FIB-4) score > 3.25 (aHR 4.364; 95%CI 2.206–8.633, p < 0.0001) and alpha-fetoprotein ≥5.0 ng/ml (aHR 2.381; 95%CI 1.325–4.280, p = 0.0037) were independently associated with HCC development within 10 years after SVR. Male gender (aHR 4.702; 95%CI 1.366–16.190, p = 0.0141), presence of diabetes mellitus (aHR 2.933; 95%CI 1.240–6.935, p = 0.0143) and gamma-glutamyl transpeptidase (GGT) ≥ 56 U/l (aHR 4.157; 95%CI 1.400–12.350, p = 0.0103) were independently associated with HCC development beyond 10 years after SVR. The incidence of HCC development beyond 10 years after SVR was very low, and the associated factors were mainly extrahepatic, including DM and elevated GGT. Annual routine check-ups with abdominal ultrasound may be sufficient for such patients. (242 words).

DOI： 10.1111/jvh.13728

GLOBAL INCIDENCE OF NON-ALCOHOLIC FATTY LIVER DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS

Le Michael, Le David M., Baez Thomas, Wu Yuankai, Lee Eunice Y., Ito Takanori, Nguyen Mindie H.

HEPATOLOGY 76 巻頁： S850 - S850 2022年10月

HIGHER HEPATOCELLULAR CARCINOMA (HCC) INCIDENCE IN CHRONIC HEPATITIS C (CHC) PATIENTS AFTER HEPATITIS C VIRUS (HCV) CURE COMPARED TO TREATED CHRONIC HEPATITIS B (CHB): RESULTS FROM A MULTINATIONAL REAL-WORLD COHORT OF PATIENTS WITH CIRRHOSIS

Park Jiyoon, Tran Sally, Ogawa Eiichi, Huang Chung-Feng, Toyoda Hidenori, Chen Chien Hung, Yeh Ming-Lun, Tseng Cheng-Hao, Hsu Yao-Chun, Kawashima Keigo, Preda Carmen, Istratescu Doina, Yasuda Satoshi, Nozaki Akito, Chuma Makoto, Oh Hyunwoo, Shim Jae-Jun, Jeong Soung Won, An Jihyun, Ahn Sang Bong, Kim Sung Eun, Yoon Eileen, Lee Han Ah, Kim Hyoung Su, Cho Yong Kyun, Uojima Haruki, Trinh Huy, Atsukawa Masanori, Itokawa Norio, Okubo Tomomi, Abe Hiroshi, Lee Dong Hyun, Jun Mi Jung, Landis Charles, Liu Joanne, Enomoto Masaru, Watanabe Tsunamasa, Ji Fanpu, Wang Wenjun, Yu Li, Xie Qing, Fukunishi Shinya, Asai Akira, Yokohama Keisuke, Ishikawa Toru, Liu Li, Li Junyi, Takahashi Hirokazu, Inoue Kaori, Eguchi Yuichiro, Ishigami Masatoshi, Ito Takanori, Huang Daniel, Wong Grace L., Wong Vincent, Lu Chengzhen, Zang Wenqian, Li Jia, Ueno Yoshiyuki, Haga Hiroaki, Marciano Sebastian, Jing Liang, Ye Qing, Lam Carla, Ho Dang Kh, Do Son T., Huang Rui, Takaguchi Koichi, Senoh Tomonori, Chien Nicholas, Maeda Mayumi, Kudaravalli Sahith, Henry Linda, Chuang Wan-Long, Dai Chia-Yen, Huang Jee-Fu, Gadano Adrian C., Yuen Man-Fung, Lim Seng Gee, Cheung Ramsey, Tanaka Yasuhito, Jun Dae Won, Yu Ming-Lung, Nguyen Mindie H.

HEPATOLOGY 76 巻頁： S377 - S379 2022年10月

Liver Stiffness Measurements by 2D Shear-Wave Elastography: Effect of Steatosis on Fibrosis Evaluation 査読有り

Kumada T., Toyoda H., Yasuda S., Ogawa S., Gotoh T., Ito T., Tada T., Tanaka J.

American Journal of Roentgenology 219 巻 ( 4 ) 頁： 604 - 613 2022年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：American Journal of Roentgenology

BACKGROUND. Hepatic steatosis has been found not to affect liver stiffness measurements (LSM) from MR elastography (MRE). However, the effect of steatosis on LSM from 2D shear-wave elastography (SWE) remains controversial. OBJECTIVE. The purpose of this study was to evaluate the effect of hepatic steatosis on the diagnostic performance of LSM from 2D SWE (LSM2D SWE) for evaluation of liver fibrosis with LSM from MRE (LSMMRE) as the reference standard. METHODS. This retrospective study included 888 patients (442 women, 446 men; median age, 67 years) with chronic liver disease who underwent LSM by both 2D SWE and MRE within a 3-month window. Steatosis was also assessed on ultrasound examinations by ultrasound-guided attenuation parameter (UGAP) and on MRI examinations by proton density fat fraction (PDFF). Fibrosis stages and steatosis grades were classified according to previously established thresholds. The effect of steatosis on LSM2D SWE was evaluated by Kruskal-Wallis tests with post hoc tests and ROC analysis. RESULTS. LSM2D SWE were significantly higher in patients with severe steatosis than those without steatosis by MRI PDFF among patients with F0 fibrosis (5.5 kPa [IQR, 4.7–6.0 kPa] vs 4.7 kPa [IQR, 4.2–5.5 kPa], p = .009) and F1 fibrosis (6.3 kPa [IQR, 6.0–7.2 kPa] vs 5.9 kPa [IQR, 5.0–6.6 kPa], p = .009). LSM2D SWE were significantly higher in patients with severe steatosis than those without steatosis by UGAP among patients with F1 fibrosis (6.6 kPa [IQR, 5.9–7.3 kPa] vs 5.9 kPa [IQR, 5.1–6.5 kPa], p = .008). Otherwise, LSM2D SWE did not vary significantly across steatosis grades at a given fibrosis stage (all p > .05). Sensitivity and specificity for ≥ F1 fibrosis were 63.8% and 91.5% in patients without versus 60.4% and 80.9% in patients with severe steatosis by MRI PDFF and were 62.4% and 91.5% in patients without versus 72.1% and 78.3% in patients with severe steatosis by UGAP. CONCLUSION. Severe hepatic steatosis may result in overestimation of LSM2D SWE in patients without or with mild steatosis, reducing the specificity of liver fibrosis detection. CLINICAL IMPACT. Assessment of UGAP at 2D SWE may help identify patients in whom LSM2D SWE should be assessed with caution. In patients with no or mild steatosis by 2D SWE and severe steatosis by UGAP, MRE helps provide a more reliable measure of liver fibrosis.

DOI： 10.2214/AJR.22.27656

Intra-individual Comparisons of the Ultrasound-Guided Attenuation Parameter and the Magnetic Resonance Imaging–Based Proton Density Fat Fraction Using Bias and Precision Statistics 査読有り

Kumada T., Ogawa S., Goto T., Toyoda H., Yasuda S., Ito T., Yasuda E., Akita T., Tanaka J.

Ultrasound in Medicine and Biology 48 巻 ( 8 ) 頁： 1537 - 1546 2022年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Ultrasound in Medicine and Biology

Ultrasound-based techniques using the attenuation coefficient, including the ultrasound-guided attenuation parameter (UGAP), have been developed for the quantification of hepatic steatosis. The magnetic resonance imaging–based proton density fat fraction (MRI-PDFF) is considered to be more accurate than liver biopsy for liver fat quantification. The aim of this study was to perform intra-individual comparisons of UGAP and MRI-PDFF for determining hepatic steatosis grade. The study enrolled 309 patients who underwent UGAP and MRI-PDFF measurements. Bland–Altman analysis was conducted after transforming MRI-PDFF values to a normal distribution and converted to a common set of units using linear regression analysis for differing scales. The expected limits of agreement (LOA) was defined as the square root of the sum of the squares of UGAP and MRI-PDFF precision. A Bland–Altman plot revealed that the bias and upper and lower LOAs (ULOA and LLOA) were −0.0047, 0.1160 and −0.1255, respectively. The percentage difference indicated that the mean, ULOA and LLOA were −1.1434%, 18.1723% and −20.4590%, respectively. The calculated expected LOA was 18.5449%, and 283 of 309 patients (91.6%) had a percentage difference within 18.5449%. Bland–Altman analysis revealed that UGAP and MRI-PDFF were interchangeable within a clinically acceptable range.

DOI： 10.1016/j.ultrasmedbio.2022.03.019

Effectiveness of Porous Glass Membrane Pumping Emulsification Device in Transarterial Chemoembolization for Solitary Hepatocellular Carcinoma 査読有り

Imai N., Ishigami M., Oie Y., Kumagai M., Inukai Y., Yokoyama S., Yamamoto K., Ito T., Ishizu Y., Honda T., Kawashima H.

Anticancer Research 42 巻 ( 8 ) 頁： 3947 - 3951 2022年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Anticancer Research

Background/Aim: A porous glass membrane-pumping emulsification device (GMD) enables the formation of a high-percentage water-in-oil emulsion with homogeneous and stable droplets. Although GMD is expected to improve the locoregional therapeutic effects of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC), its effectiveness in the management of solitary HCC remains unclear. Patients and Methods: Patients treated for solitary HCCs (<5 cm) were retrospectively reviewed. A total of 46 patients who could not undergo liver resection and were unsuitable for radiofrequency ablation were included in this study. Among these, 22 patients underwent TACE using a GMD (GMD-TACE group) and 24 underwent stereotactic body radiotherapy (SBRT) using a robotic radiosurgery system (SBRT group). Local control rates were compared between the two groups. Results: The median HCC tumour size was 24 mm (range=12-50 mm) and 22 mm (range=8-39 mm) in the GMD-TACE and SBRT groups, respectively; however, the difference between the groups was not significant. Age, liver function test results, or Child-Pugh scores were not significantly different between the two groups. The rate of local control at 6 months after treatment was 100% in both groups. Although the 1-year local control rate was higher in the SBRT group (92.3%) than in the GMD-TACE group (81.8%), there was no significant difference in the log-rank test (p=0.654). No major treatment-related complications occurred in either group during the observation period. Conclusion: TACE with GMD could be considered an effective treatment option for the management of solitary HCC.

DOI： 10.21873/anticanres.15889

A case of antiprogrammed death-ligand 1 antibody-induced multisystem immune-related adverse events with pancreatitis and steroid-resistant sclerosing cholangitis.

Yamamoto T, Ito T, Mizuno K, Shinya Y, Yamamoto K, Imai N, Ishizu Y, Honda T, Kawashima H, Matsui T, Hase T, Hashimoto N, Ishigami M

Journal of digestive diseases 23 巻 ( 7 ) 頁： 404 - 409 2022年7月

Increased Risk of Thyroid Dysfunction by PD-1 and CTLA-4 Blockade in Patients Without Thyroid Autoantibodies at Baseline 査読有り

Iwama S., Kobayashi T., Yasuda Y., Okuji T., Ito M., Ando M., Zhou X., Yamagami A., Onoue T., Kawaguchi Y., Miyata T., Sugiyama M., Takagi H., Hagiwara D., Suga H., Banno R., Hase T., Morise M., Wakahara K., Yokota K., Kato M., Nishio N., Tanaka C., Miyata K., Ogura A., Ito T., Sawada T., Shimokata T., Niimi K., Ohka F., Ishigami M., Gotoh M., Hashimoto N., Saito R., Kiyoi H., Kajiyama H., Ando Y., Hibi H., Sone M., Akiyama M., Kodera Y., Arima H.

Journal of Clinical Endocrinology and Metabolism 107 巻 ( 4 ) 頁： E1620 - E1630 2022年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Clinical Endocrinology and Metabolism

Background: Previous studies showed that although the risk of thyroid dysfunction [thyroid immune-related adverse events (irAEs)] induced by anti-programmed cell death-1 antibodies (PD-1-Ab) was as low as 2% to 7% in patients negative for anti-thyroid antibodies (ATAs) at baseline, it was much higher (30%-50%) in patients positive for ATAs. However, whether a similar increase occurs with combination therapy using PD-1-Ab plus anti-cytotoxic T-lymphocyte antigen-4 antibody (CTLA-4-Ab) is unknown. Methods: A total of 451 patients with malignancies treated with PD-1-Ab, CTLA-4-Ab, or a combination of PD-1-Ab and CTLA-4-Ab (PD-1/CTLA-4-Abs) were evaluated for ATAs at baseline and for thyroid function every 6 weeks for 24 weeks after treatment initiation and then observed until the last clinical visit. Results: Of the 451 patients, 51 developed thyroid irAEs after immunotherapy [41 of 416 (9.9%) treated with PD-1-Ab, 0 of 8 (0%) treated with CTLA-4-Ab, and 10 of 27 (37.0%) treated with PD-1/CTLA-4-Abs]. The cumulative incidence of thyroid irAEs was significantly higher in patients who were positive vs negative for ATAs at baseline after both PD-1-Ab [28/87 (32.2%) vs 13/329 (4.0%), P < 0.001] and PD-1/CTLA-4-Abs [6/10 (60.0%) vs 4/17 (23.5%), P < 0.05] treatments. The risk of thyroid irAEs induced by PD-1/CTLA-4Abs, which was significantly higher than that induced by PD-1-Ab, in patients negative for ATAs at baseline was not statistically different from that induced by PD-1-Ab in patients positive for ATAs at baseline. Conclusions: This study showed that the incidence of thyroid irAEs was high and not negligible after PD-1/CTLA-4-Abs treatment even in patients negative for ATAs at baseline.

DOI： 10.1210/clinem/dgab829