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Article ; Online: Lung T

Malis, Vadim / Kassai, Yoshimori / Vucevic, Diana / Bae, Won C / Ohno, Yoshiharu / Yen, Andrew / Miyazaki, Mitsue

2023 Volume 90, Issue 5, Page(s) 2001–2010

Abstract: Purpose: To develop 3D ultrashort-TE (UTE) sequences with tight TE intervals (δTE), allowing for accurate : Methods: We have implemented a four-echo UTE sequence with δTE (< 0.5 ms). A Monte-Carlo simulation was performed to identify an optimal ... ...

Abstract	Purpose: To develop 3D ultrashort-TE (UTE) sequences with tight TE intervals (δTE), allowing for accurate Methods: We have implemented a four-echo UTE sequence with δTE (< 0.5 ms). A Monte-Carlo simulation was performed to identify an optimal number of echoes that would result in a significant improvement in the accuracy of the Results: The simulation for the proposed 10-echo acquisition predicted over 2-fold improvement in the accuracy of estimating the short Conclusion: A UTE sequence using δTE was implemented and validated on short
MeSH term(s)	Adult ; Humans ; Imaging, Three-Dimensional/methods ; Magnetic Resonance Imaging/methods ; Phantoms, Imaging ; Image Interpretation, Computer-Assisted/methods ; Lung/diagnostic imaging
Language	English
Publishing date	2023-06-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	605774-3
ISSN	1522-2594 ; 0740-3194
ISSN (online)	1522-2594
ISSN	0740-3194
DOI	10.1002/mrm.29756
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Article ; Online: Salvage Therapies including Retreatment with BCMA-directed Approaches Following BCMA CAR-T Relapses for Multiple Myeloma.

Reyes, Kevin Robert / Liu, Yen-Chun / Huang, Chiung-Yu / Banerjee, Rahul / Martin, Thomas / Wong, Sandy W / Wolf, Jeffrey Lee / Arora, Shagun / Shah, Nina / Chari, Ajai / Chung, Alfred

Blood advances

2024

Abstract: ... maturation antigen (BCMA)-directed chimeric antigen receptor T-cell therapies (CAR-T), optimal salvage ... treatment strategies remain unclear. BCMA-directed CAR-T and bispecific antibodies (BsAb) are now ... We performed a retrospective analysis of 68 patients with relapsed disease after BCMA-directed CAR-T ...

Abstract	For patients with relapsed/refractory multiple myeloma (RRMM) with relapse following B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell therapies (CAR-T), optimal salvage treatment strategies remain unclear. BCMA-directed CAR-T and bispecific antibodies (BsAb) are now commercially available, and the outcomes for retreatment with BCMA-directed approaches are not well-studied. We performed a retrospective analysis of 68 patients with relapsed disease after BCMA-directed CAR-T to evaluate outcomes and responses to salvage therapies. With a median follow-up of 13.5 months, median overall survival from time of relapse until death was 18 months (95% confidence interval (CI): 13.2 months-not reached (NR)). 58 patients received subsequent myeloma-directed therapies, with a total of 265 lines-of-therapy (LOTs). The overall response rate for first-line salvage therapy was 41% (CI: 28-55%). Among all LOTs, high response rates were observed among those receiving another BCMA-directed CAR-T (89%), BCMA-directed BsAb (60%), CD38-directed combinations (80% when combined with BsAb; 50% when combined with immunomodulatory drugs and/or proteasome inhibitors), and alkylator-combinations (50% overall; 69% with high-dose alkylators). Thirty-four patients received at least one line of salvage BCMA-directed therapy; median PFS was 8.3 months (CI: 7.9 months-NR), 3.6 months (CI: 1.4 months-NR), and 1 month (CI: 0.9 months-NR) with median duration of response (DOR) of 8 months, 4.4 months, and 2.8 months for subsequent BCMA-directed CAR-T, BsAb, and belantamab mafadotin, respectively. Retreatment with BCMA-directed CAR-T and BsAb can be effective salvage options post-BCMA-directed CAR-T relapse; however, DORs appear limited and further studies with new combinations and alternative targets are warranted.
Language	English
Publishing date	2024-03-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2023012066
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Article: Biologic and clinical features of childhood gamma delta T-ALL: identification of STAG2/LMO2 γδ T-ALL as an extremely high risk leukemia in the very young.

Kimura, Shunsuke / Polonen, Petri / Montefiori, Lindsey / Park, Chun Shik / Iacobucci, Ilaria / Yeoh, Allen Ej / Attarbaschi, Andishe / Moore, Andrew S / Brown, Anthony / Manabe, Atsushi / Buldini, Barbara / Freeman, Burgess B / Chen, Chelsey / Cheng, Cheng / Kean Hui, Chiew / Li, Chi-Kong / Pui, Ching-Hon / Qu, Chunxu / Tomizawa, Daisuke /

Teachey, David T / Varotto, Elena / Paietta, Elisabeth M / Arnold, Elizabeth D / Locatelli, Franco / Escherich, Gabriele / Elisa Muhle, Hannah / Marquart, Hanne Vibeke / de Groot-Kruseman, Hester A / Rowe, Jacob M / Stary, Jan / Trka, Jan / Choi, John Kim / Meijerink, Jules P P / Yang, Jun J / Takita, Junko / Pawinska-Wasikowska, Katarzyna / Roberts, Kathryn G / Han, Katie / Caldwell, Kenneth J / Schmiegelow, Kjeld / Crews, Kristine R / Eguchi, Mariko / Schrappe, Martin / Zimmerman, Martin / Takagi, Masatoshi / Maybury, Mellissa / Svaton, Michael / Reiterova, Michaela / Kicinski, Michal / Prater, Mollie S / Kato, Motohiro / Reyes, Noemi / Spinelli, Orietta / Thomas, Paul / Mazilier, Pauline / Gao, Qingsong / Masetti, Riccardo / Kotecha, Rishi S / Pieters, Rob / Elitzur, Sarah / Luger, Selina M / Mitchell, Sharnise / Pruett-Miller, Shondra M / Shen, Shuhong / Jeha, Sima / Köhrer, Stefan / Kornblau, Steven M / Skoczeń, Szymon / Miyamura, Takako / Vincent, Tiffaney L / Imamura, Toshihiko / Conter, Valentino / Tang, Yanjing / Liu, Yen-Chun / Chang, Yunchao / Gu, Zhaohui / Cheng, Zhongshan / Yinmei, Zhou / Inaba, Hiroto / Mullighan, Charles G

medRxiv : the preprint server for health sciences

2023

Abstract: Purpose: Gamma delta T-cell receptor-positive acute lymphoblastic leukemia (γδ T-ALL) is a high ... risk but poorly characterized disease.: Methods: We studied clinical features of 200 pediatric γδ T ... ALL, and compared the prognosis of 93 cases to 1,067 protocol-matched non-γδ T-ALL. Genomic features were ...

Abstract	Purpose: Gamma delta T-cell receptor-positive acute lymphoblastic leukemia (γδ T-ALL) is a high-risk but poorly characterized disease. Methods: We studied clinical features of 200 pediatric γδ T-ALL, and compared the prognosis of 93 cases to 1,067 protocol-matched non-γδ T-ALL. Genomic features were defined by transcriptome and genome sequencing. Experimental modeling was used to examine the mechanistic impacts of genomic alterations. Therapeutic vulnerabilities were identified by high throughput drug screening of cell lines and xenografts. Results: γδ T-ALL in children under three was extremely high-risk with 5-year event-free survival (33% v. 70% [age 3-<10] and 73% [age ≥10], Conclusion: γδ T-ALL in children under the age of three is extremely high-risk and enriched for Support: The authors are supported by the American and Lebanese Syrian Associated Charities of St Jude Children's Research Hospital, NCI grants R35 CA197695, P50 CA021765 (C.G.M.), the Henry Schueler 41&9 Foundation (C.G.M.), and a St. Baldrick's Foundation Robert J. Arceci Innovation Award (C.G.M.), Gabriella Miller Kids First X01HD100702 (D.T.T and C.G.M.) and R03CA256550 (D.T.T. and C.G.M.), F32 5F32CA254140 (L.M.), and a Garwood Postdoctoral Fellowship of the Hematological Malignancies Program of the St Jude Children's Research Hospital Comprehensive Cancer Center (S.K.). This project was supported by the National Cancer Institute of the National Institutes of Health under the following award numbers: U10CA180820, UG1CA189859, U24CA114766, U10CA180899, U10CA180866 and U24CA196173. Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funding agencies were not directly involved in the design of the study, gathering, analysis and interpretation of the data, writing of the manuscript, or decision to submit the manuscript for publication.
Language	English
Publishing date	2023-11-08
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.11.06.23298028
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Article ; Online: Treatment outcomes of T and natural-killer/T-cell lymphoma with ifosfamide, carboplatin and etoposide chemotherapy.

Tay, Tricia / Somasundaram, Nagavalli / Lim, Cindy / Khoo, Lay Poh / Goh, Allan Zhi Kai / Lee, Yuh Shan / Liu, Xin / Tao, Miriam / Quek, Richard / Farid, Mohamad / Poon, Eileen / Chan, Jason Y S / Chang, Esther W Y / Yang, Valerie S W / Goh, Yeow Tee / Tan, Daryl / Diong, Colin / Grigoropoulos, Nicholas F / Nagarajan, Chandramouli /

Poon, Michelle / de Mel, Sanjay / Jeyasekharan, Anand / Chan, Esther H L / Lee, Joanne / Chee, Yen Lin / Lim, Soon Thye / Tang, Tiffany

Cancer reports (Hoboken, N.J.)

2022 Volume 5, Issue 9, Page(s) e1552

Abstract: Background: Contemporary data of peripheral T-cell lymphoma (PTCL) and natural-killer/T-cell ...

Abstract	Background: Contemporary data of peripheral T-cell lymphoma (PTCL) and natural-killer/T-cell lymphoma (NKTL) patients treated with ifosfamide, carboplatin and etoposide (ICE) are limited. Aims: We performed a retrospective analysis to estimate outcomes of ICE-treated PTCL and NKTL patients at three tertiary cancer centres in Singapore. Methods and results: Patients were identified through lymphoma databases from National Cancer Centre Singapore (NCCS), National University Hospital, Singapore (NUHS), and Singapore General Hospital (SGH). Responses and survival outcomes were determined from electronic medical records. A total of 75 patients with a median age of 50 were included. ICE was used as first-line treatment in 14 patients (19%) and as subsequent lines of treatment in 61 patients (81%). The overall response rates (ORR) for all patients was 63% (40% complete response [CR]). The ORR and CR in the first line were 86% and 64% respectively. At a median follow-up duration of 71.0 months, the median progression-free (PFS) and overall survival (OS) for all patients were 4.4 months (95%CI, 2.7-6.0) and 16 months (95%CI, 8.3-45.4) respectively. Conclusion: In summary, ICE showed high ORR but poor PFS in relapsed/refractory PTCL and NKTL. ORR of ICE in the first line setting appears better than real-world CHOP data and warrants further study.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols ; Carboplatin ; Etoposide ; Humans ; Ifosfamide/adverse effects ; Lymphoma ; Lymphoma, T-Cell/chemically induced ; Lymphoma, T-Cell/drug therapy ; Retrospective Studies ; Treatment Outcome
Chemical Substances	Etoposide (6PLQ3CP4P3) ; Carboplatin (BG3F62OND5) ; Ifosfamide (UM20QQM95Y)
Language	English
Publishing date	2022-04-28
Publishing country	United States
Document type	Journal Article
ISSN	2573-8348
ISSN (online)	2573-8348
DOI	10.1002/cnr2.1552
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Article ; Online: Concurrent peripheral T-cell lymphoma and T-cell lymphoblastic leukemia/lymphoma with identical

Khanlari, Mahsa / Wang, Wei / Liu, Yen-Chun / Wang, Lu / Rubnitz, Jeffrey E / Dixon, Stephanie / Orr, Brent A / Anelo, Obianuju M / Cheng, Zhongshan / Balagopal, Vidya / Klco, Jeffery M

Haematologica

2024 Volume 109, Issue 3, Page(s) 994–999

MeSH term(s)	Humans ; Intracellular Signaling Peptides and Proteins ; Lymphoma, T-Cell ; Lymphoma, T-Cell, Peripheral/diagnosis ; Lymphoma, T-Cell, Peripheral/genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; T-Cell Acute Lymphocytic Leukemia Protein 1 ; T-Lymphocytes
Chemical Substances	Intracellular Signaling Peptides and Proteins ; STIL protein, human ; T-Cell Acute Lymphocytic Leukemia Protein 1 ; TAL1 protein, human (135471-20-4)
Language	English
Publishing date	2024-03-01
Publishing country	Italy
Document type	Case Reports ; Journal Article
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2023.283585
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Article ; Online: T1 relaxation time of ISMRM/NIST T1 phantom spheres at 7 T.

Yen, Yi-Fen / Stupic, Karl F / Janicke, Michael T / Greve, Douglas N / Mareyam, Azma / Stockmann, Jason / Polimeni, Jonathan R / van der Kouwe, Andre / Keenan, Kathryn E

NMR in biomedicine

2022 Volume 36, Issue 5, Page(s) e4873

Abstract: ... are reported at 7 T. T1 values of six of the 14 T1 spheres at 7 T (with T1 > 270 ms) have been ... reported previously, but, to the best of our knowledge, not all of the T1s of the 14 T1 spheres at 7 T have ... been reported before. Given the increasing number of 7-T MRI systems in clinical settings and ...

Abstract	T1 relaxation times of the 14 T1 phantom spheres that make up the standard International Society for Magnetic Resonance in Medicine (ISMRM)/National Institute of Standards and Technology (NIST) system phantom are reported at 7 T. T1 values of six of the 14 T1 spheres at 7 T (with T1 > 270 ms) have been reported previously, but, to the best of our knowledge, not all of the T1s of the 14 T1 spheres at 7 T have been reported before. Given the increasing number of 7-T MRI systems in clinical settings and the increasing need for T1 phantoms that cover a wide range of T1 relaxation times to evaluate rapid T1 mapping techniques at 7 T, it is of high interest to obtain accurate T1 values for all the ISMRM/NIST T1 spheres at 7 T. In this work, T1 relaxation time was measured on a 7-T MRI scanner using an inversion-recovery spin-echo pulse sequence and derived by curve fitting to a signal equation that exhibits insensitivity to
MeSH term(s)	Reproducibility of Results ; Magnetic Resonance Imaging/methods ; Neuroimaging ; Phantoms, Imaging ; Reference Values
Language	English
Publishing date	2022-11-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1000976-0
ISSN	1099-1492 ; 0952-3480
ISSN (online)	1099-1492
ISSN	0952-3480
DOI	10.1002/nbm.4873
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Article ; Online: Clonal germinal center B cells function as a niche for T-cell lymphoma.

Blood

2022 Volume 140, Issue 18, Page(s) 1937–1950

Abstract: Angioimmunoblastic T-cell lymphoma (AITL) is proposed to be initiated by age-related clonal ... promotes the development of T follicular helper (TFH)-like tumor cells. Here, we investigated the mechanism ... in the T cells (Cd4-Cre × Tet2flox/flox × G17V RHOA transgenic mice) did not. Therefore, Tet2-deficient ...

Abstract	Angioimmunoblastic T-cell lymphoma (AITL) is proposed to be initiated by age-related clonal hematopoiesis (ACH) with TET2 mutations, whereas the G17V RHOA mutation in immature cells with TET2 mutations promotes the development of T follicular helper (TFH)-like tumor cells. Here, we investigated the mechanism by which TET2-mutant immune cells enable AITL development using mouse models and human samples. Among the 2 mouse models, mice lacking Tet2 in all the blood cells (Mx-Cre × Tet2flox/flox × G17V RHOA transgenic mice) spontaneously developed AITL for approximately up to a year, while mice lacking Tet2 only in the T cells (Cd4-Cre × Tet2flox/flox × G17V RHOA transgenic mice) did not. Therefore, Tet2-deficient immune cells function as a niche for AITL development. Single-cell RNA-sequencing (scRNA-seq) of >50 000 cells from mouse and human AITL samples revealed significant expansion of aberrant B cells, exhibiting properties of activating light zone (LZ)-like and proliferative dark zone (DZ)-like germinal center B (GCB) cells. The GCB cells in AITL clonally evolved with recurrent mutations in genes related to core histones. In silico network analysis using scRNA-seq data identified Cd40-Cd40lg as a possible mediator of GCB and tumor cell cluster interactions. Treatment of AITL model mice with anti-Cd40lg inhibitory antibody prolonged survival. The genes expressed in aberrantly expanded GCB cells in murine tumors were also broadly expressed in the B-lineage cells of TET2-mutant human AITL. Therefore, ACH-derived GCB cells could undergo independent clonal evolution and support the tumorigenesis in AITL via the CD40-CD40LG axis.
MeSH term(s)	Humans ; Mice ; Animals ; T-Lymphocytes, Helper-Inducer ; Immunoblastic Lymphadenopathy/genetics ; Lymphoma, T-Cell/pathology ; Germinal Center/pathology ; Mice, Transgenic
Language	English
Publishing date	2022-08-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2022015451
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Article ; Online: CD28-CAR-T cell activation through FYN kinase signaling rather than LCK enhances therapeutic performance.

Wu, Ling / Brzostek, Joanna / Sakthi Vale, Previtha Dawn / Wei, Qianru / Koh, Clara K T / Ong, June Xu Hui / Wu, Liang-Zhe / Tan, Jia Chi / Chua, Yen Leong / Yap, Jiawei / Song, Yuan / Tan, Vivian Jia Yi / Tan, Triscilla Y Y / Lai, Junyun / MacAry, Paul A / Gascoigne, Nicholas R J

Cell reports. Medicine

2023 Volume 4, Issue 2, Page(s) 100917

Abstract: ... on the activity of the SRC family kinase (SFK) LCK, as is the case with T cell receptor (TCR) signaling. Here ... the related SFK FYN and a CD28 intracellular domain within the CAR. LCK-deficient CAR-T cells are strongly ... to lead to exhaustion. This non-canonical signaling of CAR-T cells provides insight into the initiation ...

Abstract	Signal transduction induced by chimeric antigen receptors (CARs) is generally believed to rely on the activity of the SRC family kinase (SFK) LCK, as is the case with T cell receptor (TCR) signaling. Here, we show that CAR signaling occurs in the absence of LCK. This LCK-independent signaling requires the related SFK FYN and a CD28 intracellular domain within the CAR. LCK-deficient CAR-T cells are strongly signaled through CAR and have better in vivo efficacy with reduced exhaustion phenotype and enhanced induction of memory and proliferation. These distinctions can be attributed to the fact that FYN signaling tends to promote proliferation and survival, whereas LCK signaling promotes strong signaling that tends to lead to exhaustion. This non-canonical signaling of CAR-T cells provides insight into the initiation of both TCR and CAR signaling and has important clinical implications for improvement of CAR function.
MeSH term(s)	Receptors, Chimeric Antigen ; Proto-Oncogene Proteins/metabolism ; CD28 Antigens ; Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism ; T-Lymphocytes ; Receptors, Antigen, T-Cell ; Proto-Oncogene Proteins c-fyn ; Signal Transduction
Chemical Substances	Receptors, Chimeric Antigen ; Proto-Oncogene Proteins ; CD28 Antigens ; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) (EC 2.7.10.2) ; Receptors, Antigen, T-Cell ; Proto-Oncogene Proteins c-fyn (EC 2.7.10.2)
Language	English
Publishing date	2023-01-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2023.100917
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Article ; Online: Bioconjugated liquid-like solid enhances characterization of solid tumor - chimeric antigen receptor T cell interactions.

Acta biomaterialia

2023 Volume 172, Page(s) 466–479

Abstract: Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable success ... of research. However, limited trafficking and mobility of T cells within the tumor microenvironment (TME ... present challenges for CAR T cell therapy in solid tumors. To gain a better understanding of CAR T cell ...

Abstract	Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable success as an immunotherapy for hematological malignancies, and its potential for treating solid tumors is an active area of research. However, limited trafficking and mobility of T cells within the tumor microenvironment (TME) present challenges for CAR T cell therapy in solid tumors. To gain a better understanding of CAR T cell function in solid tumors, we subjected CD70-specific CAR T cells to a challenge by evaluating their immune trafficking and infiltration through a confined 3D microchannel network in a bio-conjugated liquid-like solid (LLS) medium. Our results demonstrated successful CAR T cell migration and anti-tumor activity against CD70-expressing glioblastoma and osteosarcoma tumors. Through comprehensive analysis of cytokines and chemokines, combined with in situ imaging, we elucidated that immune recruitment occurred via chemotaxis, and the effector-to-target ratio plays an important role in overall antitumor function. Furthermore, through single-cell collection and transcriptomic profiling, we identified differential gene expression among the immune subpopulations. Our findings provide valuable insights into the complex dynamics of CAR T cell function in solid tumors, informing future research and development in this promising cancer treatment approach. STATEMENT OF SIGNIFICANCE: The use of specialized immune cells named CAR T cells to combat cancers has demonstrated remarkable success against blood cancers. However, this success is not replicated in solid tumors, such as brain or bone cancers, mainly due to the physical barriers of these solid tumors. Currently, preclinical technologies do not allow for reliable evaluation of tumor-immune cell interactions. To better study these specialized CAR T cells, we have developed an innovative in vitro three-dimensional model that promises to dissect the interactions between tumors and CAR T cells at the single-cell level. Our findings provide valuable insights into the complex dynamics of CAR T cell function in solid tumors, informing future research and development in this promising cancer treatment approach.
MeSH term(s)	Humans ; Receptors, Chimeric Antigen/genetics ; T-Lymphocytes ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/metabolism ; Antigens, Neoplasm ; Neoplasms/metabolism ; Bone Neoplasms/metabolism ; Cell Communication ; Tumor Microenvironment
Chemical Substances	Receptors, Chimeric Antigen ; Receptors, Antigen, T-Cell ; Antigens, Neoplasm
Language	English
Publishing date	2023-10-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2023.09.042
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Article ; Online: Sex Differences in Treatment Response to Nucleos(t)ide Therapy in Chronic Hepatitis B: A Multicenter Longitudinal Study.

Chau, Angela / Yeh, Ming-Lun / Tsai, Pei-Chien / Huang, Daniel Q / Kim, Sung Eun / Trinh, Huy / Yoon, Eileen L / Oh, Hyunwoo / Jeong, Jae Yoon / Ahn, Sang Bong / An, Jihyun / Tseng, Cheng-Hao / Hsu, Yao-Chun / Jeong, Soung Won / Cho, Yong Kyun / Shim, Jae-Jun / Kim, Hyoung Su / Ito, Takanori / Marciano, Sebastián /

Kawashima, Keigo / Suzuki, Takanori / Watanabe, Tsunamasa / Nozaki, Akito / Ishikawa, Toru / Inoue, Kaori / Eguchi, Yuichiro / Uojima, Haruki / Abe, Hiroshi / Takahashi, Hirokazu / Chuma, Makoto / Ishigami, Masatoshi / Hoang, Joseph K / Maeda, Mayumi / Huang, Chung-Feng / Gadano, Adrian / Dai, Chia-Yen / Huang, Jee-Fu / Tanaka, Yasuhito / Chuang, Wan-Long / Lim, Seng Gee / Cheung, Ramsey / Yu, Ming-Lung / Jun, Dae-Won / Nguyen, Mindie H

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

2023 Volume 22, Issue 3, Page(s) 572–580.e5

Abstract: Background & aims: It is unclear if there may be sex differences in response to nucleos(t)ide ... hepatocellular carcinoma (HCC) incidence among hepatitis B patients. We compared nucleos(t)ide analog treatment outcomes ...

Abstract	Background & aims: It is unclear if there may be sex differences in response to nucleos(t)ide analogs including virologic response (VR), biochemical response (BR), complete response (CR), and hepatocellular carcinoma (HCC) incidence among hepatitis B patients. We compared nucleos(t)ide analog treatment outcomes by sex. Methods: We performed a retrospective cohort study of 3388 treatment-naïve adult hepatitis B patients (1250 female, 2138 male) from the Real-World Evidence from the Global Alliance for the Study of Hepatitis B Virus consortium who initiated therapy with either entecavir or tenofovir from 22 sites (Argentina, Korea, Japan, Taiwan, and the United States). We used propensity-score matching to balance background characteristics of the male and female groups and competing-risks analysis to estimate the incidence and subdistribution hazard ratios (SHRs) of VR, BR, CR, and HCC. Results: Females (vs males) were older (52.0 vs 48.6 y); less likely to be overweight/obese (49.3% vs 65.7%), diabetic (9.9% vs 13.1%), or cirrhotic (27.9% vs 33.0%); and had a lower HBV DNA level (5.9 vs 6.0 log10 IU/mL) and alanine aminotransferase level (91 vs 102 IU/L) (all P < .01). However, after propensity-score matching, relevant background characteristics were balanced between the 2 groups. Females (vs males) had similar 5-year cumulative VR (91.3% vs 90.3%; P = .40) and HCC incidence rates (5.1% vs 4.4%; P = .64), but lower BR (84.0% vs 90.9%; P < .001) and CR (78.8% vs 83.4%; P = .016). Males were more likely to achieve BR (SHR, 1.31; 95% CI, 1.17-1.46; P < .001) and CR (SHR, 1.16; 95% CI, 1.03-1.31; P = .016), but VR and HCC risks were similar. Conclusions: Sex differences exist for treatment outcomes among hepatitis B patients. Male sex was associated with a 16% higher likelihood of clinical remission and a 31% higher likelihood of biochemical response than females, while virologic response and HCC incidence were similar between the 2 groups.
MeSH term(s)	Adult ; Humans ; Female ; Male ; Hepatitis B, Chronic/complications ; Carcinoma, Hepatocellular/epidemiology ; Carcinoma, Hepatocellular/drug therapy ; Antiviral Agents ; Retrospective Studies ; Longitudinal Studies ; Sex Characteristics ; Liver Neoplasms/epidemiology ; Liver Neoplasms/drug therapy ; Hepatitis B virus/genetics ; Treatment Outcome ; Pathologic Complete Response
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2023-09-19
Publishing country	United States
Document type	Multicenter Study ; Journal Article
ZDB-ID	2119789-1
ISSN	1542-7714 ; 1542-3565
ISSN (online)	1542-7714
ISSN	1542-3565
DOI	10.1016/j.cgh.2023.09.002
Database	MEDical Literature Analysis and Retrieval System OnLINE

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