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2. PPP1R15A-expressing monocytic MDSCs promote immunosuppressive liver microenvironment in fibrosis-associated hepatocellular carcinoma

Author

Liu, Xiaoyu, Liu, Man, Wu, Haoran, Tang, Wenshu, Yang, Weiqin, Chan, Thomas T.H., Zhang, Lingyun, Chen, Shufen, Xiong, Zhewen, Liang, Jianxin, Wai-Yiu Si-Tou, Willis, Shu, Ting, Li, Jingqing, Cao, Jianquan, Zhong, Chengpeng, Sun, Hanyong, Kwong, Tsz Tung, Leung, Howard H.W., Wong, John, Bo-San Lai, Paul, To, Ka-Fai, Xiang, Tingxiu, Jao-Yiu Sung, Joseph, Chan, Stephen Lam, Zhou, Jingying, and Sze-Lok Cheng, Alfred

Published
2024
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3. Safety analysis by treatment periods from EMERALD-1: A phase 3, randomized, placebo-controlled study of transarterial chemoembolization with durvalumab with/without bevacizumab in participants with embolization-eligible unresectable hepatocellular carcinoma.

Author

Kudo, Masatoshi, Chan, Stephen Lam, Sangro, Bruno, Erinjeri, Joseph P., Qin, Shukui, Ren, Zhenggang, Arai, Yasuaki, Breder, Valeriy Vladimirovich, Lin, Shi-Ming, Peron, Jean-Marie, Nguyen, Tien Quang, Yan, Lunan, Chiu, Chang-Fang, Santos, Florinda A., Veluvolu, Anil, Thungappa, Satheesh Chiradoni, Morgan, Claire, Parsons, Kerry, Xynos, Ioannis, and Lencioni, Riccardo

Published
2024
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6. Outcomes by transarterial chemoembolization (TACE) modality from participants (pts) with embolization-eligible hepatocellular carcinoma (HCC) treated with durvalumab (D) + bevacizumab (B) + TACE and placebos (PBO) + TACE: EMERALD-1 subgroup analysis.

Author

Heo, Jeong, Okusaka, Takuji, Yoon, Jung-Hwan, Sangro, Bruno, Chan, Stephen Lam, Erinjeri, Joseph P., Matos, Marco, Decaens, Thomas, Chen, Eric Xueyu, Beg, Muhammad S., Matilla, Ana Maria, Tuyet Phuong, Le Thi, Griffin, Rebecca, Udoye, Stephanie I., Indiviglio, Sandra, and Kudo, Masatoshi

Published
2025
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7. Patterns of radiological progression in participants (pts) with embolization-eligible hepatocellular carcinoma (HCC) treated with durvalumab (D) + bevacizumab (B) + transarterial chemoembolization (TACE) and placebos + TACE: EMERALD-1 post hoc analysis.

Author

Sangro, Bruno, Bouattour, Mohamed, Park, Joong-Won, Diaz, Dr. Consuelo, Erinjeri, Joseph P., Alves, Gustavo Vasconcelos, Gu, Shan-Zhi, Manikhas, Aleksei, Kuroda, Hidekatsu, Suksombooncharoen, Thatthan, Vo, Truc Hoi Trung, Ostwal, Vikas S., Eastgate, Melissa A., Vaccaro, Gina M., Griffin, Rebecca, Ali, Sajid, Balaji, Kavitha, and Chan, Stephen Lam

Published
2025
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10. The molecular mechanism underlying KRAS regulation on STK31 expression in pancreatic ductal adenocarcinoma.

Author

Liu, Yuting, Tang, Shing Chun, Li, Chi Han, To, Ka Fai, Li, Bo, Chan, Stephen Lam, Wong, Chi Hin, and Chen, Yangchao

Abstract

KRAS gene mutations are common in pancreatic ductal adenocarcinoma (PDAC), but targeting mutant KRAS is still challenging. Here, an endoribonuclease‐prepared small interfering RNA (esiRNA) library was used to screen new kinases that play critical roles in PDAC driven by KRAS gene mutations, and serine/threonine kinase 31 (STK31) was identified and characterized as a potential therapeutic target for KRAS‐mutant PDAC. Our results showed that STK31 was upregulated in KRAS‐mutant PDAC patients with poor survival and highly expressed in PDAC cell lines with KRASG12D mutation. Inhibition of STK31 in KRAS‐mutant cell lines significantly reduced PDAC cell growth in vitro and hindered tumor growth in vivo. Gain and loss of function experiments revealed that STK31 is a downstream target of KRAS in PDAC. A pharmacological inhibition assay showed MAPK/ERK signaling involved in STK31 regulation. The further mechanistic study validated that c‐Jun, regulated by KRAS/MAPK signaling, directly modulates the transcription level of STK31 by binding to its promoter region. Through RNA sequencing, we found that the cell cycle regulators CCNB1 and CDC25C are downstream targets of STK31. Taken together, our results indicate that STK31, which is the downstream target of the KRAS/MAPK/ERK/c‐Jun signaling pathway in KRAS‐mutant PDAC, promotes PDAC cell growth by modulating the expression of the cell cycle regulators CCNB1 and CDC25C. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Cell cycle-related kinase reprograms the liver immune microenvironment to promote cancer metastasis

Author

Zeng, Xuezhen, Zhou, Jingying, Xiong, Zhewen, Sun, Hanyong, Yang, Weiqin, Mok, Myth T. S., Wang, Jing, Li, Jingqing, Liu, Man, Tang, Wenshu, Feng, Yu, Wang, Hector Kwong-Sang, Tsang, Shun-Wa, Chow, King-Lau, Yeung, Philip Chun, Wong, John, Lai, Paul Bo-San, Chan, Anthony Wing-Hung, To, Ka Fai, Chan, Stephen Lam, Xia, Qiang, Xue, Jing, Chen, Xiao, Yu, Jun, Peng, Sui, Sung, Joseph Jao-Yiu, Kuang, Ming, and Cheng, Alfred Sze-Lok

Published
2021
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17. Artificial intelligence-based pathology as a biomarker of sensitivity to atezolizumab–bevacizumab in patients with hepatocellular carcinoma: a multicentre retrospective study

Author

Zeng, Qinghe, primary, Klein, Christophe, additional, Caruso, Stefano, additional, Maille, Pascale, additional, Allende, Daniela S, additional, Mínguez, Beatriz, additional, Iavarone, Massimo, additional, Ningarhari, Massih, additional, Casadei-Gardini, Andrea, additional, Pedica, Federica, additional, Rimini, Margherita, additional, Perbellini, Riccardo, additional, Boulagnon-Rombi, Camille, additional, Heurgué, Alexandra, additional, Maggioni, Marco, additional, Rela, Mohamed, additional, Vij, Mukul, additional, Baulande, Sylvain, additional, Legoix, Patricia, additional, Lameiras, Sonia, additional, Amaddeo, Giuliana, additional, Argemi, Josepmaria, additional, Beaufrère, Aurélie, additional, Bermúdez-Ramos, María, additional, Boursier, Jérôme, additional, Bruges, Léa, additional, Calderaro, Julien, additional, Campani, Claudia, additional, Castano Garcia, Andres, additional, Chan, Stephen Lam, additional, D'Alessio, Antonio, additional, Di Tommaso, Luca, additional, Diaz, Alba, additional, Digklia, Antonia, additional, Dufour, Jean-François, additional, Garcia-Porrero, Guillermo, additional, Ghaffari Laleh, Narmin, additional, Gnemmi, Viviane, additional, Gopal, Purva, additional, Graham, Rondell P., additional, Iñarrairaegui, Mercedes, additional, Kather, Jakob Nikolas, additional, Labgaa, Ismail, additional, Lequoy, Marie, additional, Leung, Howard Ho-Wai, additional, Loménie, Nicolas, additional, Marín-Zuluaga, Juan Ignacio, additional, Mendoza-Pacas, Guillermo, additional, Michalak, Sophie, additional, El Nahhas, Omar S M, additional, Nault, Jean-Charles, additional, Navale, Pooja, additional, Paradis, Valérie, additional, Park, Young Nyun, additional, Pawlotsky, Jean-Michel, additional, Peter, Simon, additional, Pinato, David James, additional, Pinter, Matthias, additional, Radu, Pompilia, additional, Regnault, Hélène, additional, Reig, Maria, additional, Rhee, Hyungjin, additional, Rimassa, Lorenza, additional, Salcedo, María Teresa, additional, Sangro, Bruno, additional, Scheiner, Bernhard, additional, Sempoux, Christine, additional, Su, Tung-Hung, additional, Torres, Callie, additional, Tran, Nguyen H, additional, Trépo, Eric, additional, Varela, Maria, additional, Verset, Gontran, additional, Vogel, Arndt, additional, Wendum, Dominique, additional, Zeng, Qinghe, additional, and Ziol, Marianne, additional

Published
2023
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20. A liver stiffness-based etiology-independent machine learning algorithm to predict hepatocellular carcinoma

Author

Lin, Huapeng, primary, Li, Guanlin, additional, Delamarre, Adèle, additional, Ahn, Sang Hoon, additional, Zhang, Xinrong, additional, Kim, Beom Kyung, additional, Liang, Lilian Yan, additional, Lee, Hye Won, additional, Lai-Hung Wong, Grace, additional, Yuen, Pong-Chi, additional, Lik-Yuen Chan, Henry, additional, Chan, Stephen Lam, additional, Wai-Sun Wong, Vincent, additional, de Lédinghen, Victor, additional, Kim, Seung Up, additional, and Cheuk-Fung Yip, Terry, additional

Published
2023
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24. Baveno VII criteria identify varices needing treatment in patients with hepatocellular carcinoma of different Barcelona Clinic Liver Cancer stages

Author

Wu, Claudia Wing‐Kwan, primary, Wong, Grace Lai‐Hung, additional, Wong, Vincent Wai‐Sun, additional, Yam, Tsz‐Fai, additional, Yip, Terry Cheuk‐Fung, additional, Wong, Angus Chun‐Hei, additional, Chan, Brian Wai‐Nok, additional, Fong, Matthew Man‐Lok, additional, Lai, Jimmy Che‐To, additional, Tse, Yee‐Kit, additional, Lee, Kit‐Fai, additional, Mok, Tony Shu‐Kam, additional, Chan, Henry Lik‐Yuen, additional, Lui, Rashid Nok‐Shun, additional, Chan, Stephen Lam, additional, and Ng, Kelvin Kwok‐Chai, additional

Published
2023
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25. Duration of type 2 diabetes and liver-related events in nonalcoholic fatty liver disease: A landmark analysis

Author

Zhang, Xinrong, primary, Yip, Terry Cheuk-Fung, additional, Tse, Yee-Kit, additional, Hui, Vicki Wing-Ki, additional, Li, Guanlin, additional, Lin, Huapeng, additional, Liang, Lilian Yan, additional, Lai, Jimmy Che-To, additional, Chan, Henry Lik-Yuen, additional, Chan, Stephen Lam, additional, Kong, Alice Pik-Shan, additional, Wong, Grace Lai-Hung, additional, and Wong, Vincent Wai-Sun, additional

Published
2023
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26. Targeting PPAR-gamma counteracts tumour adaptation to immune-checkpoint blockade in hepatocellular carcinoma

Author

Xiong, Zhewen, primary, Chan, Stephen Lam, additional, Zhou, Jingying, additional, Vong, Joaquim S.L., additional, Kwong, Tsz Tung, additional, Zeng, Xuezhen, additional, Wu, Haoran, additional, Cao, Jianquan, additional, Tu, Yalin, additional, Feng, Yu, additional, Yang, Weiqin, additional, Wong, Patrick Pak-Chun, additional, Si-Tou, Willis Wai-Yiu, additional, Liu, Xiaoyu, additional, Wang, Jing, additional, Tang, Wenshu, additional, Liang, Zhixian, additional, Lu, Jiahuan, additional, Li, Ka Man, additional, Low, Jie-Ting, additional, Chan, Michael Wing-Yan, additional, Leung, Howard H.W., additional, Chan, Anthony W.H., additional, To, Ka-Fai, additional, Yip, Kevin Yuk-Lap, additional, Lo, Yuk Ming Dennis, additional, Sung, Joseph Jao-Yiu, additional, and Cheng, Alfred Sze-Lok, additional

Published
2023
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27. Trends in risk factor control and treatment among patients with non‐alcoholic fatty liver disease and type 2 diabetes between 2000 and 2020: A territory‐wide study

Author

Zhang, Xinrong, primary, Yip, Terry Cheuk‐Fung, additional, Tse, Yee‐Kit, additional, Hui, Vicki Wing‐Ki, additional, Li, Guanlin, additional, Lin, Huapeng, additional, Liang, Lilian Yan, additional, Lai, Jimmy Che‐To, additional, Lai, Mandy Sze‐Man, additional, Cheung, Johnny T. K., additional, Chan, Henry Lik‐Yuen, additional, Chan, Stephen Lam, additional, Kong, Alice Pik‐Shan, additional, Wong, Grace Lai‐Hung, additional, and Wong, Vincent Wai‐Sun, additional

Published
2023
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28. Pembrolizumab as Second-Line Therapy for Advanced Hepatocellular Carcinoma: Longer-Term Follow-Up From the Phase 3 KEYNOTE-240 Trial

Author

Merle, Philippe, primary, Kudo, Masatoshi, additional, Edeline, Julien, additional, Bouattour, Mohamed, additional, Cheng, Ann-Lii, additional, Chan, Stephen Lam, additional, Yau, Thomas, additional, Garrido, Marcelo, additional, Knox, Jennifer, additional, Daniele, Bruno, additional, Breder, Valeriy, additional, Lim, Ho Yeong, additional, Ogasawara, Sadahisa, additional, Cattan, Stéphane, additional, Chao, Yee, additional, Siegel, Abby B., additional, Martinez-Forero, Iván, additional, Wei, Ziwen, additional, Liu, Chih-Chin, additional, and Finn, Richard S., additional

Published
2023
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30. Achievement of cancer- and treatment-free status by atezolizumab plus bevacizumab combined with or without curative conversion in patients with transarterial chemoembolization-unsuitable, intermediate-stage hepatocellular carcinoma: A multicenter cohort study.

Author

Kudo, Masatoshi, primary, Aoki, Tomoko, additional, Ueshima, Kazuomi, additional, Tsuchiya, Kaoru, additional, Morita, Masahiro, additional, Hagiwara, Satoru, additional, Minami, Yasunori, additional, Ida, Hiroshi, additional, Nishida, Naoshi, additional, Ogawa, Chikara, additional, Tomonari, Tetsu, additional, Nakamura, Noriaki, additional, Kuroda, Hidekatsu, additional, Takebe, Atsushi, additional, Takeyama, Yoshifumi, additional, Hidaka, Masaaki, additional, Eguchi, Susumu, additional, Chan, Stephen Lam, additional, Kurosaki, Masayuki, additional, and Izumi, Namiki, additional

Published
2023
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31. Tebotelimab, a PD-1/LAG-3 bispecific antibody, in patients with advanced hepatocellular carcinoma who had failed prior targeted therapy and/or immunotherapy: An open-label, single-arm, phase 1/2 dose-escalation and expansion study.

Author

Ren, Zhenggang, primary, Guo, Yabing, additional, Bai, Yuxian, additional, Ying, Jieer, additional, Meng, Zhiqiang, additional, Chen, Zhendong, additional, Gu, Shanzhi, additional, Zhang, Jingdong, additional, Liang, Jun, additional, Hou, Xinfang, additional, Li, Wei, additional, Xu, Aibing, additional, Hao, Chunyi, additional, Zhang, Jian, additional, Xing, Ruijun, additional, Zhang, Xinyu, additional, Zhang, Dan, additional, and Chan, Stephen Lam, additional

Published
2023
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33. Utility of Combining PIVKA-II and AFP in the Surveillance and Monitoring of Hepatocellular Carcinoma in the Asia-Pacific Region

Author

KIM, Do-Young, primary, TOAN, Bao Nguyen, additional, TAN, Chee-Kiat, additional, HASAN, Irsan, additional, SETIAWAN, Lyana, additional, YU, Ming-Lung, additional, IZUMI, Namiki, additional, HUYEN, Nguyen Nguyen, additional, CHOW, Pierce Kah-Hoe, additional, MOHAMED, Rosmawati, additional, CHAN, Stephen Lam, additional, TANWANDEE, Tawesak, additional, LEE, Teng-Yu, additional, HAI, Thi Thanh Nguyen, additional, YANG, Tian, additional, LEE, Woo-Chang, additional, and CHAN, Henry Lik Yuen, additional

Published
2023
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34. Targeting PPAR-gamma counteracts tumour adaptation to immune-checkpoint blockade in hepatocellular carcinoma.

Author

Zhewen Xiong, Chan, Stephen Lam, Jingying Zhou, Vong, Joaquim S. L., Tsz Tung Kwong, Xuezhen Zeng, Haoran Wu, Jianquan Cao, Yalin Tu, Yu Feng, Weiqin Yang, Pak-Chun Wong, Patrick, Willis Wai-Yiu Si-Tou, Xiaoyu Liu, Jing Wang, Wenshu Tang, Zhixian Liang, Jiahuan Lu, Ka Man Li, and Jie-Ting Low

Subjects
HEPATOCELLULAR carcinoma, GASTROINTESTINAL hemorrhage, MONONUCLEAR leukocytes, CYTOTOXIC T cells
Published
2023
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35. Real-World Study of Systemic Treatment after First-Line Atezolizumab plus Bevacizumab for Hepatocellular Carcinoma in Asia-Pacific Countries

Author

Lee, Choong-kun, Yoo, Changhoon, Hong, Jung Yong, Park, Se Jun, Kim, Jin Won, Tai, David Wai Meng, Kim, Hyeyeong, Korphaisarn, Krittiya, Tanasanvimon, Suebpong, Chen, San-Chi, Kim, Ju Won, Kim, Ilhwan, Kim, Moonho, Choo, Joan, Oh, Sang-Bo, Chen, Ching-Tso, Bae, Woo Kyun, Kim, Hongsik, Huh, Seok Jae, Yen, Chia-Jui, Park, Sejung, Lee, Dong Ki, Chan, Landon Long, Kang, Beodeul, Kang, Minsu, Sundar, Raghav, Choi, Hye Jin, Chan, Stephen Lam, Chon, Hong Jae, and Lee, Myung-Ah

Abstract

Introduction:Atezolizumab plus bevacizumab is a commonly used first-line regimen for advanced hepatocellular carcinoma (HCC) treatment owing to its superior outcomes compared to sorafenib. However, optimal subsequent treatment options for patients with HCC who progressed on first-line atezolizumab plus bevacizumab remain unclear. Methods:This multinational, multi-institutional, retrospective study included patients with HCC from 22 centers in five Asia-Pacific countries who were treated with first-line atezolizumab plus bevacizumab, which was discontinued for any reason. The endpoints included progression-free survival (PFS) and overall survival (OS) according to patient characteristics and second-line regimens. Results:Between June 2016 and May 2023, 1,141 patients were treated with first-line atezolizumab plus bevacizumab, of whom 629 (55.1%) received subsequent treatment. Sorafenib and lenvatinib were the most commonly administered second-line regimens (53.9% and 25.6%, respectively). Overall, the median PFS and OS were 2.9 and 8.0 months, respectively. Lenvatinib had longer PFS (4.0 vs. 2.3 months) and OS (8.0 vs. 6.3 months) than sorafenib. Patients treated with tyrosine kinase inhibitor (TKI) plus immune checkpoint inhibitor (ICI) (n= 50, 8.3%) showed PFS and OS of 5.4 and 12.6 months, respectively. Lower tumor burden and lenvatinib or TKI plus ICI use were associated with longer second-line PFS. Preserved liver function was associated with improved OS. Conclusions:In patients with HCC who progressed on first-line atezolizumab plus bevacizumab, sorafenib and lenvatinib were the most commonly used second-line regimens in Asia-Pacific countries, with lenvatinib resulting in longer OS than sorafenib. The second-line TKI plus ICI combination exhibited promising efficacy, suggesting the potential role of continuing ICIs beyond disease progression.

Published
2024
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36. First-Line Systemic Therapies for Advanced Hepatocellular Carcinoma: A Systematic Review and Patient-Level Network Meta-Analysis

Author

Fong, Khi Yung, Zhao, Joseph Jonathan, Sultana, Rehena, Lee, Joycelyn Jie Xin, Lee, Suat Ying, Chan, Stephen Lam, Yau, Thomas, Tai, David Wai Meng, Sundar, Raghav, and Too, Chow Wei

Abstract

Introduction:Sorafenib was historically the standard of care for advanced hepatocellular carcinoma (aHCC) until it was superseded by the combination of atezolizumab and bevacizumab. Thereafter, several novel first-line combination therapies have demonstrated favorable outcomes. The efficacies of these treatments in relation to current and previous standards of care are unknown, necessitating an overarching evaluation. Methods:A systematic literature search was conducted on PubMed, EMBASE, Scopus, and the Cochrane Controlled Register of Trials for phase III randomized controlled trials investigating first-line systemic therapies for aHCC. Kaplan-Meier curves for overall survival (OS) and progression-free survival (PFS) were graphically reconstructed to retrieve individual patient-level data. Derived hazard ratios (HRs) for each study were pooled in a random-effects network meta-analysis (NMA). NMAs were also conducted using study-level HRs for various subgroups, according to viral etiology, Barcelona Clinic Liver Cancer (BCLC) staging, alpha-fetoprotein (AFP) levels, macrovascular invasion, and extrahepatic spread. Treatment strategies were ranked using pscores. Results:Among 4,321 articles identified, 12 trials and 9,589 patients were included for analysis. Only two therapies showed OS benefit over sorafenib: combined anti-programmed-death and anti-VEGF pathway inhibitor monoclonal antibodies (Anti-PD-(L)1/VEGF Ab), including atezolizumab-bevacizumab and sintilimab-bevacizumab biosimilar (HR = 0.63, 95% CI = 0.53–0.76) and tremelimumab-durvalumab (HR = 0.78, 95% CI = 0.66–0.92). Anti-PD-(L)1/VEGF Ab showed OS benefit over all other therapies except tremelimumab-durvalumab. Low heterogeneity (I2 = 0%) and inconsistency (Cochran’s Q= 0.52, p= 0.773) was observed. pscores for OS ranked Anti-PD-(L)1/VEGF Ab as the best treatment in all subgroups, except hepatitis B where atezolizumab-cabozantinib ranked highest for both OS and PFS, as well as nonviral HCC and AFP ≥400 μg/L where tremelimumab-durvalumab ranked highest for OS. Conclusion:This NMA supports Anti-PD-(L)1/VEGF Ab as the first-line therapy for aHCC and demonstrates a comparable benefit for tremelimumab-durvalumab which also extends to certain subgroups. Results of the subgroup analysis may guide treatment according to baseline characteristics, while pending further studies.

Published
2023
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37. Isoformic PD-1-mediated immunosuppression underlies resistance to PD-1 blockade in hepatocellular carcinoma patients

Author

Tan, Zhiwu, primary, Chiu, Mei Sum, additional, Yang, Xinxiang, additional, Yue, Ming, additional, Cheung, Tan To, additional, Zhou, Dongyan, additional, Wang, Yuewen, additional, Chan, Anthony Wing-Hung, additional, Yan, Chi Wing, additional, Kwan, Ka Yi, additional, Wong, Yik Chun, additional, Li, Xin, additional, Zhou, Jingying, additional, To, Ka Fai, additional, Zhu, Jiye, additional, Lo, Chung Mau, additional, Cheng, Alfred Sze-Lok, additional, Chan, Stephen Lam, additional, Liu, Li, additional, Song, You-Qiang, additional, Man, Kwan, additional, and Chen, Zhiwei, additional

Published
2022
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38. IDDF2022-ABS-0103 A selective class I HDAC inhibitor recovers intratumoral interferon signaling to overcome immune-checkpoint blockade resistance in hepatocellular carcinoma

Author

Tu, Yalin, primary, Xiong, Zhewen, additional, Zhong, Chengpeng, additional, Wu, Haoran, additional, Wang, Jing, additional, Wong, Patrick Pak-Chun, additional, Yang, Weiqin, additional, Zhou, Jingying, additional, To, Ka-Fai, additional, Sung, Joseph, additional, Chan, Stephen Lam, additional, Kerr, David, additional, Thangue, Nick La, additional, and Cheng, Alfred Sze-Lok, additional

Published
2022
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39. Isoformic PD-1-mediated immunosuppression underlies resistance to PD-1 blockade in hepatocellular carcinoma patients.

Author

Zhiwu Tan, Mei Sum Chiu, Xinxiang Yang, Ming Yue, Tan To Cheung, Dongyan Zhou, Yuewen Wang, Wing-Hung Chan, Anthony, Chi Wing Yan, Ka Yi Kwan, Yik Chun Wong, Xin Li, Jingying Zhou, Ka Fai To, Jiye Zhu, Chung Mau Lo, Cheng, Alfred Sze-Lok, Chan, Stephen Lam, Li Liu, and You-Qiang Song

Subjects
FATTY liver, HEPATOCELLULAR carcinoma, CYTOTOXIC T cells, MONONUCLEAR leukocytes, PROGRAMMED cell death 1 receptors, IMMUNE checkpoint proteins
Published
2023
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43. Age and the relative importance of liver‐related deaths in nonalcoholic fatty liver disease

Author

Lin, Huapeng, primary, Yip, Terry Cheuk‐Fung, additional, Zhang, Xinrong, additional, Li, Guanlin, additional, Tse, Yee‐Kit, additional, Hui, Vicki Wing‐Ki, additional, Liang, Lilian Yan, additional, Lai, Jimmy Che‐To, additional, Chan, Stephen Lam, additional, Chan, Henry Lik‐Yuen, additional, Wong, Grace Lai‐Hung, additional, and Wong, Vincent Wai‐Sun, additional

Published
2022
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45. Pembrolizumab Monotherapy for Previously Untreated Advanced Hepatocellular Carcinoma: Data from the Open-Label, Phase II KEYNOTE-224 Trial

Author

Verset, Gontran, Borbath, Ivan, Karwal, Mark, Verslype, Chris, Van Vlierberghe, Hans, Kardosh, Adel, Zagonel, Vittorina, Stal, Per, Sarker, Debashis, Palmer, Daniel D.H., Vogel, Arndt, Edeline, Julien, Cattan, Stéphane, Kudo, Masatoshi, Cheng, Ann Lii, Ogasawara, Sadahisa, Daniele, Bruno, Chan, Stephen Lam, Knox, Jennifer, Qin, Shukui, Siegel, Abby A.B., Chisamore, Michael, Hatogai, Ken, Wang, Anran, Finn, Richard R.S., Zhu, Andrew Xiuxuan, Verset, Gontran, Borbath, Ivan, Karwal, Mark, Verslype, Chris, Van Vlierberghe, Hans, Kardosh, Adel, Zagonel, Vittorina, Stal, Per, Sarker, Debashis, Palmer, Daniel D.H., Vogel, Arndt, Edeline, Julien, Cattan, Stéphane, Kudo, Masatoshi, Cheng, Ann Lii, Ogasawara, Sadahisa, Daniele, Bruno, Chan, Stephen Lam, Knox, Jennifer, Qin, Shukui, Siegel, Abby A.B., Chisamore, Michael, Hatogai, Ken, Wang, Anran, Finn, Richard R.S., and Zhu, Andrew Xiuxuan

Abstract

Purpose: KEYNOTE-224 cohort 1 demonstrated that pembrolizumab was efficacious and tolerable in patients with advanced hepatocellular carcinoma (HCC) previously treated with sorafenib. We report results from KEYNOTE-224 (NCT02702414) cohort 2, which enrolled patients with advanced HCC and no prior systemic therapy. Patients and Methods: KEYNOTE-224 was an open-label, multicountry phase II trial. Eligible patients in cohort 2 had advanced HCC not amenable or refractory to locoregional therapy and not previously treated with systemic therapy. Patients received pembrolizumab 200 mg intravenously every 3 weeks for ≤2 years. Primary endpoint was objective response rate (ORR) by central imaging review per RECIST v1.1. Secondary endpoints included duration of response (DOR), disease control rate (DCR), time to progression (TTP), progression-free survival (PFS), overall survival (OS), and safety/tolerability. Results: Between September 4, 2018, and February 20, 2019, 51 patients were allocated in cohort 2. The median time from the first dose to data cutoff (January 19, 2021) was 27 months (range, 23-29). ORR was 16% [95% confidence interval (CI), 7-29] and was similar across key subgroups. Median DOR was 16 months (range, 3-24+), and DCR was 57%. The median PFS was 4 months (95% CI, 2-8), and median TTP was 4 months (95% CI, 3-9). Median OS was 17 months (95% CI, 8-23). Grade ≥3 treatment-related adverse events occurred in 16% of patients. Conclusions: In patients with advanced HCC with no prior systemic therapy, pembrolizumab provided durable antitumor activity, promising OS, and had a safety profile consistent with previous observations. These findings support further evaluation of pembrolizumab-based regimens for HCC., SCOPUS: re.j, info:eu-repo/semantics/published

Published
2022

46. Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312): a multicentre, open-label, randomised, phase 3 trial

Author

Kelley, Robin Kate, Rimassa, Lorenza, Cheng, Ann Lii, Kaseb, Ahmed, Qin, Shukui, Zhu, Andrew Xiuxuan, Chan, Stephen Lam, Melkadze, Tamar, Sukeepaisarnjaroen, Wattana, Breder, Valery, Verset, Gontran, Gane, Edward, Borbath, Ivan, Rangel, Jose David Gomez, Ryoo, Baek Yeol, Makharadze, Tamta, Merle, Philippe, Benzaghou, Fawzi, Banerjee, Kamalika, Hazra, Saswati, Fawcett, Jonathan, Yau, Thomas, Kelley, Robin Kate, Rimassa, Lorenza, Cheng, Ann Lii, Kaseb, Ahmed, Qin, Shukui, Zhu, Andrew Xiuxuan, Chan, Stephen Lam, Melkadze, Tamar, Sukeepaisarnjaroen, Wattana, Breder, Valery, Verset, Gontran, Gane, Edward, Borbath, Ivan, Rangel, Jose David Gomez, Ryoo, Baek Yeol, Makharadze, Tamta, Merle, Philippe, Benzaghou, Fawzi, Banerjee, Kamalika, Hazra, Saswati, Fawcett, Jonathan, and Yau, Thomas

Abstract

Background: Cabozantinib has shown clinical activity in combination with checkpoint inhibitors in solid tumours. The COSMIC-312 trial assessed cabozantinib plus atezolizumab versus sorafenib as first-line systemic treatment for advanced hepatocellular carcinoma. Methods: COSMIC-312 is an open-label, randomised, phase 3 trial that enrolled patients aged 18 years or older with advanced hepatocellular carcinoma not amenable to curative or locoregional therapy and previously untreated with systemic anticancer therapy at 178 centres in 32 countries. Patients with fibrolamellar carcinoma, sarcomatoid hepatocellular carcinoma, or combined hepatocellular cholangiocarcinoma were not eligible. Tumours involving major blood vessels, including the main portal vein, were permitted. Patients were required to have measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), Barcelona Clinic Liver Cancer stage B or C disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, adequate organ and marrow function, and Child-Pugh class A. Previous resection, tumour ablation, radiotherapy, or arterial chemotherapy was allowed if more than 28 days before randomisation. Patients were randomly assigned (2:1:1) via a web-based interactive response system to cabozantinib 40 mg orally once daily plus atezolizumab 1200 mg intravenously every 3 weeks, sorafenib 400 mg orally twice daily, or single-agent cabozantinib 60 mg orally once daily. Randomisation was stratified by disease aetiology, geographical region, and presence of extrahepatic disease or macrovascular invasion. Dual primary endpoints were progression-free survival per RECIST 1.1 as assessed by a blinded independent radiology committee in the first 372 patients randomly assigned to the combination treatment of cabozantinib plus atezolizumab or sorafenib (progression-free survival intention-to-treat [ITT] population), and overall survival in all patients randomly assigned to cabozanti, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2022

47. Updated efficacy and safety of KEYNOTE-224: a phase II study of pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib

Author

Kudo, Masatoshi, Finn, Richard R.S., Edeline, Julien, Cattan, Stéphane, Ogasawara, Sadahisa, Palmer, Daniel D.H., Verslype, Chris, Zagonel, Vittorina, Fartoux, Laetitia, Vogel, Arndt, Sarker, Debashis, Verset, Gontran, Chan, Stephen Lam, Knox, Jennifer, Daniele, Bruno, Yau, Thomas, Gurary, Ellen E.B., Siegel, Abby A.B., Wang, Anran, Cheng, Ann Lii, Zhu, Andrew Xiuxuan, Kudo, Masatoshi, Finn, Richard R.S., Edeline, Julien, Cattan, Stéphane, Ogasawara, Sadahisa, Palmer, Daniel D.H., Verslype, Chris, Zagonel, Vittorina, Fartoux, Laetitia, Vogel, Arndt, Sarker, Debashis, Verset, Gontran, Chan, Stephen Lam, Knox, Jennifer, Daniele, Bruno, Yau, Thomas, Gurary, Ellen E.B., Siegel, Abby A.B., Wang, Anran, Cheng, Ann Lii, and Zhu, Andrew Xiuxuan

Abstract

Objective: Pembrolizumab, a PD-1 inhibitor, demonstrated anti-tumour activity and tolerability in patients treated with sorafenib and with advanced hepatocellular carcinoma in KEYNOTE-224. Longer-term efficacy and safety after ∼2.5 years of additional follow-up are reported. Patients and methods: Adults with confirmed hepatocellular carcinoma who experienced progression after or intolerance to sorafenib treatment received pembrolizumab 200 mg every 3 weeks for ≤35 cycles or until confirmed progression, unacceptable toxicity, withdrawal of consent or investigator decision. The primary end-point was objective response rate assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumours v1.1. The secondary end-points included duration of response, disease control rate, time to progression, progression-free survival, overall survival and adverse events. Results: Efficacy and safety were assessed in 104 patients. The median time from first dose to data cutoff was 45.1 months (range, 41.3–49.3). Objective response rate was 18.3% (95% CI: 11.4–27.1), and median duration of response was 21.0 months (range, 3.1 to 39.5+). Disease control rate was 61.5%, and median time to progression was 4.8 months (95% CI: 3.9–7.0). Median progression-free survival was 4.9 months (95% CI: 3.5–6.7) and median overall survival was 13.2 months (95% CI: 9.7–15.3). Of 104 patients, 76 (73.1%) patients reported treatment-related adverse events; most were low grade in severity (grade 3–4, n = 26 [25.0%]; grade 5, n = 1 [1.0%]). Immune-mediated hepatitis occurred in 3 patients (all grade 3). No viral-induced hepatitis flares occurred. Conclusions: After ∼2.5 years of additional follow-up, pembrolizumab continued to provide durable anti-tumour activity and no new safety concerns were identified. ClinicalTrials.gov identifier: NCT02702414., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2022

48. Trends in risk factor control and treatment among patients with non-alcoholic fatty liver disease and type 2 diabetes between 2000 and 2020: A territory-wide study.

Author

Xinrong Zhang, Yip, Terry Cheuk-Fung, Yee-Kit Tse, Hui, Vicki Wing-Ki, Guanlin Li, Huapeng Lin, Liang, Lilian Yan, Lai, Jimmy Che-To, Lai, Mandy Sze-Man, Cheung, Johnny T. K., Chan, Henry Lik-Yuen, Chan, Stephen Lam, Kong, Alice Pik-Shan, Wong, Grace Lai-Hung, and Wong, Vincent Wai-Sun

Subjects
NON-alcoholic fatty liver disease, TYPE 2 diabetes, BLOOD pressure, GLYCEMIC control, HYPOGLYCEMIC agents
Abstract

Background & Aims: We aimed to determine the trends in risk factor control and treatment among patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) in 2000-2020. Methods: We conducted a territory-wide cohort study of adult patients with NAFLD and T2D diagnosed between 1 January 2000 and 31 July 2021 in Hong Kong. T2D was defined by use of any anti-diabetic agents, laboratory tests and/or diagnosis codes. Results: This study included 16,084 patients with NAFLD and T2D (mean age, 54.8 ± 12.0 years; 7124 male [44.3%]). The percentage of patients achieving individualised haemoglobin A1c (HbA1c) targets increased from 44.5% (95% confidence interval [CI], 42.9-46.1) to 64.8% (95% CI, 64.1-65.5), and percentage of patients achieving individualised low-density lipoprotein-cholesterol (LDL-C) targets increased from 23.3% (95% CI, 21.9-24.7) to 54.3% (95% CI, 53.5-55.1) from 2000-2005 to 2016-2020, whereas percentage of patients achieving blood pressure control (<140/90 mm Hg) remained static at 53.1-57.2%. Combination therapy for diabetes increased, especially among those with poor glycaemic control, but there was no increase in combination therapy for hypertension. Fewer cirrhotic patients achieved blood pressure control and individualised LDL-C targets, but they were more likely to achieve individualised HbA1c targets than non-cirrhotics. Metformin and statins were underused in cirrhotic patients. Younger patients (18-44 years) were less likely to achieve individualised HbA1c targets than middle-aged (45-64 years) and older ones (=65 years). Conclusions: From 2000 to 2020, glycaemic and lipid control improved significantly, whereas blood pressure control remained static among patients with NAFLD and T2D. [ABSTRACT FROM AUTHOR]

Published
2023
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49. Baveno VII Criteria Is an Accurate Risk Stratification Tool to Predict High-Risk Varices Requiring Intervention and Hepatic Events in Patients with Advanced Hepatocellular Carcinoma.

Author

Wu, Claudia Wing-Kwan, Lui, Rashid Nok-Shun, Wong, Vincent Wai-Sun, Yam, Tsz-Fai, Yip, Terry Cheuk-Fung, Liu, Ken, Lai, Jimmy Che-To, Tse, Yee-Kit, Mok, Tony Shu-Kam, Chan, Henry Lik-Yuen, Ng, Kelvin Kwok-Chai, Wong, Grace Lai-Hung, and Chan, Stephen Lam

Subjects
ENDOSCOPIC surgery, ESOPHAGEAL varices, CIRRHOSIS of the liver, RISK assessment, LIVER diseases, PORTAL vein, HEPATOCELLULAR carcinoma, ENDOSCOPY, HEMORRHAGE
Abstract

Simple Summary: Patient with hepatocellular carcinoma are at an increased risk of variceal haemorrhage, and often require endoscopic workup to look for the presence of high-risk varices prior to starting systemic therapy. The Baveno VII criteria has been a well-validated non-invasive risk stratification tool in predicting high-risk varices for patients with liver cirrhosis, but data on its use in the hepatocellular carcinoma population is lacking. In this study, we successfully validated the Baveno VII criteria as a safe and accurate modality in predicting high-risk varices and hepatic events in patients with hepatocellular carcinoma. The Baveno VII criteria are used in patients with liver cirrhosis to predict high-risk varices in patients with liver cirrhosis. Yet its use in patients with advanced hepatocellular carcinoma (HCC) has not been validated. HCC alone is accompanied with a higher variceal bleeding risk due to its association with liver cirrhosis and portal vein thrombosis. The use of systemic therapy in advanced HCC has been thought to further augment this risk. Upper endoscopy is commonly used to evaluate for the presence of varices before initiation of treatment with systemic therapy. Yet it is associated with procedural risks, waiting time and limited availability in some localities which may delay the commencement of systemic therapy. Our study successfully validated the Baveno VI criteria with a 3.5% varices needing treatment (VNT) missed rate, also with acceptable <5% VNT missed rates when considering alternative liver stiffness (LSM) and platelet cut-offs. The Baveno VII clinically significant portal hypertension rule-out criteria (LSM < 15 kPa and platelet >150 × 109/L) also revealed a low frequency (2%) of hepatic events, whilst the rule-in criteria (LSM > 25 kPa) was predictive of a higher proportion of hepatic events (14%). Therefore, our study has successfully validated the Baveno VII criteria as a non-invasive stratification of the risk of variceal bleeding and hepatic decompensation in the HCC population. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
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