Faculty Profiles - ITO Takanori

Effect of illness uncertainty on alanine transaminase levels and aspartate aminotransferase levels in patients with nonalcoholic fatty liver disease. Open Access

Decreased appetite is associated with the presence of sarcopenia in patients with cirrhosis. Open Access

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

Nutrition (Burbank, Los Angeles County, Calif.) Vol. 103-104 page： 111807 2022.11

Language：English Publishing type：Research paper (scientific journal) Publisher：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

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 Open Access

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 Vol. 33 page： S1472 - S1472 2022.11

Ozawa N, Sato K, Sugimura A, Maki S, Tanaka T, Yamamoto K, Ito T, Ishizu Y, Kuzuya T, Honda T, Ishigami M, Fujishiro M, Ishikawa T, Ando S

Nagoya journal of medical science Vol. 84 ( 4 ) page： 857 - 864 2022.11

Language：English Publishing type：Research paper (scientific journal) Publisher：Nagoya Journal of Medical Science

Patients with nonalcoholic fatty liver disease (NAFLD) have illness uncertainty. The purpose of this longitudinal study was to investigate the effect of the degree of illness uncertainty in patients with NAFLD on liver function values. We conducted a questionnaire survey and collected blood samples from outpatients with NAFLD. The items in the questionnaire were measured for illness uncertainty using the Japanese version of the Mishel Uncertainty in Illness Scale-Community (MUIS-C). Blood samples were collected at baseline and after 1 year. We divided the patients into two groups: one with high illness uncertainty and the other with low illness uncertainty. We then compared changes in alanine transaminase (ALT) and aspartate aminotransferase (AST) levels over time from baseline using multiple regression analysis. This study analyzed 148 patients with NAFLD; 75 were male and 73 were female, with a mean age of 58.4 ± 12.3 years. The group with higher illness uncertainty had significantly higher ALT and AST levels at 1 year (b =.185 and.183, respectively) than the group with lower illness uncertainty. High illness uncertainty in patients with NAFLD can lead to higher ALT and AST levels. Healthcare providers must focus on reducing illness uncertainty in patients with NAFLD.

DOI： 10.18999/nagjms.84.4.857

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

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

AJR. American journal of roentgenology Vol. 219 ( 4 ) page： 604 - 612 2022.10

Language：English Publishing type：Research paper (scientific journal) Publisher：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 (LSM<inf>2D SWE</inf>) for evaluation of liver fibrosis with LSM from MRE (LSM<inf>MRE</inf>) 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 LSM<inf>2D SWE</inf> was evaluated by Kruskal-Wallis tests with post hoc tests and ROC analysis. RESULTS. LSM<inf>2D SWE</inf> 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). LSM<inf>2D SWE</inf> 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, LSM<inf>2D SWE</inf> 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 LSM<inf>2D SWE</inf> 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 LSM<inf>2D SWE</inf> 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

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

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 Vol. 76 page： S262 - S263 2022.10

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 Vol. 76 page： S377 - S379 2022.10

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 Vol. 76 page： S1181 - S1181 2022.10

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 Vol. 76 page： S34 - S35 2022.10

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 Vol. 76 page： S742 - S743 2022.10

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 Vol. 76 page： S1330 - S1330 2022.10

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 Vol. 29 ( 10 ) page： 919 - 929 2022.10

Language：English Publishing type：Research paper (scientific journal) Publisher：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

Elevated TSH Level, TgAb, and Prior Use of Ramucirumab or TKIs as Risk Factors for Thyroid Dysfunction in PD-L1 Blockade. Open Access

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 Vol. 76 page： S850 - S850 2022.10

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

The Journal of clinical endocrinology and metabolism Vol. 107 ( 10 ) page： e4115 - e4123 2022.9

Language：English Publishing type：Research paper (scientific journal) Publisher：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

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

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

Ultrasound in medicine & biology Vol. 48 ( 8 ) page： 1537 - 1546 2022.8

Language：English Publishing type：Research paper (scientific journal) Publisher：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. Open Access

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

Anticancer research Vol. 42 ( 8 ) page： 3947 - 3951 2022.8

Language：English Publishing type：Research paper (scientific journal) Publisher：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 Vol. 23 ( 7 ) page： 404 - 409 2022.7

Metabolic abnormalities play a crucial role in non-obese people suffering from non-alcoholic fatty liver disease (NAFLD). Reviewed International coauthorship Open Access

Ye Q, Ito T, Henry L, Nguyen MH

Hepatobiliary surgery and nutrition Vol. 11 ( 2 ) page： 333 - 334 2022.4

Increased Risk of Thyroid Dysfunction by PD-1 and CTLA-4 Blockade in Patients Without Thyroid Autoantibodies at Baseline. Open Access

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

The Journal of clinical endocrinology and metabolism Vol. 107 ( 4 ) page： e1620 - e1630 2022.3

Language：English Publishing type：Research paper (scientific journal) Publisher：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