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1. Application of a deep learning algorithm for the diagnosis of HCC

Author

Yu, Philip Leung Ho, Chiu, Keith Wan-Hang, Lu, Jianliang, Lui, Gilbert C.S., Zhou, Jian, Cheng, Ho-Ming, Mao, Xianhua, Wu, Juan, Shen, Xin-Ping, Kwok, King Ming, Kan, Wai Kuen, Ho, Y.C., Chan, Hung Tat, Xiao, Peng, Mak, Lung-Yi, Tsui, Vivien W.M., Hui, Cynthia, Lam, Pui Mei, Deng, Zijie, Guo, Jiaqi, Ni, Li, Huang, Jinhua, Yu, Sarah, Peng, Chengzhi, Li, Wai Keung, Yuen, Man-Fung, and Seto, Wai-Kay

Published
2025
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4. Dual-Attention Enhanced BDense-UNet for Liver Lesion Segmentation

Author

Cao, Wenming, Yu, Philip L. H., Lui, Gilbert C. S., Chiu, Keith W. H., Cheng, Ho-Ming, Fang, Yanwen, Yuen, Man-Fung, and Seto, Wai-Kay

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition
Abstract

In this work, we propose a new segmentation network by integrating DenseUNet and bidirectional LSTM together with attention mechanism, termed as DA-BDense-UNet. DenseUNet allows learning enough diverse features and enhancing the representative power of networks by regulating the information flow. Bidirectional LSTM is responsible to explore the relationships between the encoded features and the up-sampled features in the encoding and decoding paths. Meanwhile, we introduce attention gates (AG) into DenseUNet to diminish responses of unrelated background regions and magnify responses of salient regions progressively. Besides, the attention in bidirectional LSTM takes into account the contribution differences of the encoded features and the up-sampled features in segmentation improvement, which can in turn adjust proper weights for these two kinds of features. We conduct experiments on liver CT image data sets collected from multiple hospitals by comparing them with state-of-the-art segmentation models. Experimental results indicate that our proposed method DA-BDense-UNet has achieved comparative performance in terms of dice coefficient, which demonstrates its effectiveness., Comment: 9 pages, 3 figures

Published
2021

5. Long-term open-label vebicorvir for chronic HBV infection: Safety and off-treatment responses

Author

Yuen, Man-Fung, Fung, Scott, Ma, Xiaoli, Nguyen, Tuan T., Hassanein, Tarek, Hann, Hie-Won, Elkhashab, Magdy, Nahass, Ronald G., Park, James S., Jacobson, Ira M., Ayoub, Walid S., Han, Steven-Huy, Gane, Edward J., Zomorodi, Katie, Yan, Ran, Ma, Julie, Knox, Steven J., Stamm, Luisa M., Bonacini, Maurizio, Weilert, Frank, Ramji, Alnoor, Bennett, Michael, Ravendhran, Natarajan, Chan, Sing, Dieterich, Douglas T., Kwo, Paul Yien, Schiff, Eugene R., Bae, Ho S., Lalezari, Jacob, Agarwal, Kosh, and Sulkowski, Mark S.

Published
2024
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9. HBV DNA and HBsAg Levels at 24 Weeks Off-Treatment Predict Clinical Relapse and HBsAg Loss in HBeAg-Negative Patients Who Discontinued Antiviral Therapy

Author

Sonneveld, Milan J., Chiu, Shao-Ming, Park, Jun Yong, Brakenhoff, Sylvia M., Kaewdech, Apichat, Seto, Wai-Kay, Tanaka, Yasuhito, Carey, Ivana, Papatheodoridi, Margarita, Colombatto, Piero, van Bömmel, Florian, Janssen, Harry L., Berg, Thomas, Zoulim, Fabien, Ahn, Sang Hoon, Dalekos, George N., Erler, Nicole S., Brunetto, Maurizia, Wedemeyer, Heiner, Cornberg, Markus, Yuen, Man-Fung, Agarwal, Kosh, Boonstra, Andre, Buti, Maria, Piratvisuth, Teerha, Papatheodoridis, George, Chen, Chien-Hung, and Maasoumy, Benjamin

Published
2024
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10. Lower pretreatment HBV DNA levels are associated with better off-treatment outcomes after nucleo(s)tide analogue withdrawal in patients with HBeAg-negative chronic hepatitis B: A multicentre cohort study

Author

Sonneveld, Milan J., Chiu, Shao-Ming, Park, Jun Yong, Brakenhoff, Sylvia M., Kaewdech, Apichat, Seto, Wai-Kay, Tanaka, Yasuhito, Carey, Ivana, Papatheodoridi, Margarita, Colombatto, Piero, van Bömmel, Florian, Berg, Thomas, Zoulim, Fabien, Ahn, Sang Hoon, Dalekos, George N., Erler, Nicole S., Brunetto, Maurizia, Wedemeyer, Heiner, Cornberg, Markus, Yuen, Man-Fung, Agarwal, Kosh, Boonstra, Andre, Buti, Maria, Piratvisuth, Teerha, Papatheodoridis, George, Chen, Chien-Hung, and Maasoumy, Benjamin

Published
2023
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11. Differential Relapse Patterns After Discontinuation of Entecavir vs Tenofovir Disoproxil Fumarate in Chronic Hepatitis B

Author

Choi, Hannah S.J., Hirode, Grishma, Chen, Chien-Hung, Su, Tung-Hung, Seto, Wai-Kay, Van Hees, Stijn, Papatheodoridi, Margarita, Lens, Sabela, Wong, Grace L.H., Brakenhoff, Sylvia M., Chien, Rong-Nan, Feld, Jordan J., Sonneveld, Milan J., Chan, Henry L.Y., Forns, Xavier, Papatheodoridis, George V., Vanwolleghem, Thomas, Yuen, Man-Fung, Hsu, Yao-Chun, Kao, Jia-Horng, Cornberg, Markus, Hansen, Bettina E., Jeng, Wen-Juei, and Janssen, Harry L.A.

Published
2023
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12. Characterization of Hepatitis B Virus Transcripts in Chronically HBV-Infected Chimpanzees and Patients Treated with ARC-520 siRNA Demonstrates Transcriptional Silencing of cccDNA.

Author

Wooddell, Christine I., Sanders, Dean, Xu, Zhao, Mak, Lung-Yi, Schluep, Thomas, Seto, Wai-Kay, Given, Bruce D., and Yuen, Man-Fung

Subjects
RNA interference, CHRONIC hepatitis B, SMALL interfering RNA, GENETIC transcription, CHIMPANZEES, HEPATITIS B virus
Abstract

Full-length hepatitis B virus (HBV) transcripts of chimpanzees and patients treated with multidose (MD) HBV siRNA ARC-520 and entecavir (ETV) were characterized by single-molecule real-time (SMRT) sequencing, identifying multiple types of transcripts with the potential to encode HBx, HBsAg, HBeAg, core, and polymerase, as well as transcripts likely to be derived from dimers of dslDNA, and these differed between HBeAg-positive (HBeAg+) and HBeAg-negative (HBeAg−) individuals. HBV transcripts from the last follow-up ~30 months post-ARC-520 treatment were categorized from one HBeAg+ (one of two previously highly viremic patients that became HBeAg− upon treatment and had greatly reduced cccDNA products) and four HBeAg− patients. The previously HBeAg+ patient received a biopsy that revealed that he had 3.4 copies/cell cccDNA (two to three orders of magnitude more cccDNA than HBeAg− chimpanzees) but expressed primarily truncated X and HBsAg from iDNA, like two patients that were HBeAg− at the start of the study and had one copy/cell cccDNA. No HBV transcripts were detected in two other HBeAg− patients that had ~0.3 copies/cell cccDNA, one of which had seroconverted for HBsAg. The paucity of cccDNA-derived transcripts in the presence of high cccDNA demonstrates the transcriptional silencing of HBV following MD siRNA treatment with ETV. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Glycaemic control is a modifiable risk factor for hepatocellular carcinoma and liver‐related mortality in patients with diabetes.

Author

Mao, Xianhua, Cheung, Ka‐Shing, Tan, Jing‐Tong, Mak, Lung‐Yi, Lee, Chi‐Ho, Chiang, Chi‐Leung, Cheng, Ho‐Ming, Hui, Rex Wan‐Hin, Leung, Wai K., Yuen, Man‐Fung, and Seto, Wai‐Kay

Subjects
GLYCEMIC control, PROPENSITY score matching, FATTY liver, DIABETES, HEPATOCELLULAR carcinoma
Abstract

Summary: Background: Optimal glycaemic control has well‐established health benefits in patients with diabetes mellitus (DM). It is uncertain whether optimal glycaemic control can benefit liver‐related outcomes. Aims: To examine the association of optimal glycaemic control with hepatocellular carcinoma (HCC) and liver‐related mortality. Methods: In a population‐based cohort, we identified patients with newly diagnosed DM between 2001 and 2016 in Hong Kong. Optimal glycaemic control was defined as mean haemoglobin A1c (HbA1c) <7% during the 3‐year lead‐in period after DM diagnosis. By applying propensity score matching to balance covariates, we analysed glycaemic control via competing risk models with outcomes of interest being HCC and liver‐related mortality. Results: We identified 146,430 patients (52.2% males, mean age 61.4 ± 11.8 years). During a median follow‐up duration of 7.0 years, 1099 (0.8%) and 978 (0.7%) patients developed HCC and liver‐related deaths. Optimal glycaemic control, when compared to suboptimal glycaemic control, was associated with reduced risk of HCC (subdistribution hazard ratio [SHR] 0.70, 95% CI 0.61–0.79). The risk of HCC increased with incremental HbA1c increases beyond >7% (SHR 1.29–1.71). Significant associations with HCC were also found irrespective of age (SHR 0.54–0.80), sex (SHR 0.68–0.69), BMI <25 or ≥25 kg/m2 (SHR 0.63–0.75), smoking (SHR 0.61–0.72), hepatic steatosis (SHR 0.67–0.68) and aspirin/statin/metformin use (SHR 0.67–0.75). A lower risk of liver‐related mortality in relation to optimal glycaemic control was also observed (SHR 0.70, 95% CI 0.61–0.80). Conclusions: Glycaemic control is an independent risk factor for HCC and liver‐related mortality, and should be incorporated into oncoprotective strategies in the general DM population. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Progression Rates by Age, Sex, Treatment, and Disease Activity by AASLD and EASL Criteria: Data for Precision Medicine

Author

Park, Jiyoon, Le, An K., Tseng, Tai-Chung, Yeh, Ming-Lun, Jun, Dae Won, Trinh, Huy, Wong, Grace L.H., Chen, Chien-Hung, Peng, Cheng-Yuan, Kim, Sung Eun, Oh, Hyunwoo, Kwak, Min-Sun, Cheung, Ka Shing, Toyoda, Hidenori, Hsu, Yao-Chun, Jeong, Jae Yoon, Yoon, Eileen L., Ungtrakul, Teerapat, Zhang, Jian, Xie, Qing, Ahn, Sang Bong, Enomoto, Masaru, Shim, Jae-Jun, Cunningham, Chris, Jeong, Soung Won, Cho, Yong Kyun, Ogawa, Eiichi, Huang, Rui, Lee, Dong-Hyun, Takahashi, Hirokazu, Tsai, Pei-Chien, Huang, Chung-Feng, Dai, Chia-Yen, Tseng, Cheng-Hao, Yasuda, Satoshi, Kozuka, Ritsuzo, Li, Jiayi, Wong, Christopher, Wong, Clifford C., Zhao, Changqing, Hoang, Joseph, Eguchi, Yuichiro, Wu, Chao, Tanaka, Yasuhito, Gane, Ed, Tanwandee, Tawesak, Cheung, Ramsey, Yuen, Man-Fung, Lee, Hyo-Suk, Yu, Ming-Lung, Kao, Jia-Horng, Yang, Hwai-I, and Nguyen, Mindie H.

Published
2022
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15. Prediction of Sustained Response After Nucleo(s)tide Analogue Cessation Using HBsAg and HBcrAg Levels: A Multicenter Study (CREATE)

Author

Sonneveld, Milan J., Park, Jun Yong, Kaewdech, Apichat, Seto, Wai-Kay, Tanaka, Yasuhito, Carey, Ivana, Papatheodoridi, Margarita, van Bömmel, Florian, Berg, Thomas, Zoulim, Fabien, Ahn, Sang Hoon, Dalekos, George N., Erler, Nicole S., Höner zu Siederdissen, Christoph, Wedemeyer, Heiner, Cornberg, Markus, Yuen, Man-Fung, Agarwal, Kosh, Boonstra, Andre, Buti, Maria, Piratvisuth, Teerha, Papatheodoridis, George, and Maasoumy, Benjamin

Published
2022
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16. Off-Therapy Response After Nucleos(t)ide Analogue Withdrawal in Patients With Chronic Hepatitis B: An International, Multicenter, Multiethnic Cohort (RETRACT-B Study)

Author

Hirode, Grishma, Choi, Hannah S.J., Chen, Chien-Hung, Su, Tung-Hung, Seto, Wai-Kay, Van Hees, Stijn, Papatheodoridi, Margarita, Lens, Sabela, Wong, Grace, Brakenhoff, Sylvia M., Chien, Rong-Nan, Feld, Jordan, Sonneveld, Milan J., Chan, Henry L.Y., Forns, Xavier, Papatheodoridis, George V., Vanwolleghem, Thomas, Yuen, Man-Fung, Hsu, Yao-Chun, Kao, Jia-Horng, Cornberg, Markus, Hansen, Bettina E., Jeng, Wen-Juei, and Janssen, Harry L.A.

Published
2022
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18. Therapeutic vaccine BRII-179 restores HBV-specific immune responses in patients with chronic HBV in a phase Ib/IIa study

Author

Ma, Haiyan, Lim, Tien Huey, Leerapun, Apinya, Weltman, Martin, Jia, Jidong, Lim, Young-suk, Tangkijvanich, Pisit, Sukeepaisarnjaroen, Wattana, Ji, Yun, Le Bert, Nina, Li, Dong, Zhang, Yao, Hamatake, Robert, Tan, Nicole, Li, Chunming, Strasser, Simone I., Ding, Huiguo, Yoon, Jung-Hwan, Stace, Nigel H., Ahmed, Tanvir, Anderson, Dave E., Yan, Li, Bertoletti, Antonio, Zhu, Qing, and Yuen, Man-Fung

Published
2021
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19. Safety, tolerability and antiviral activity of the antisense oligonucleotide bepirovirsen in patients with chronic hepatitis B: a phase 2 randomized controlled trial

Author

Yuen, Man-Fung, Heo, Jeong, Jang, Jeong-Won, Yoon, Jung-Hwan, Kweon, Young-Oh, Park, Sung-Jae, and Tami, Yvonne

Subjects
Antisense nucleic acids -- Testing, Hepatitis B -- Diagnosis -- Care and treatment, Viral proteins -- Analysis, Biological sciences, Health
Abstract

Chronic infection with hepatitis B virus (HBV) leads to an increased risk of death from cirrhosis and hepatocellular carcinoma. Functional cure rates are low with current treatment options (nucleos(t)ide analogs (NAs) and pegylated interferons). Bepirovirsen is an antisense oligonucleotide targeting all HBV messenger RNAs; in cell culture and animal models, bepirovirsen leads to reductions in HBV-derived RNAs, HBV DNA and viral proteins. This phase 2 double-blinded, randomized, placebo-controlled trial is the first evaluation of the safety and activity of an antisense oligonucleotide targeting HBV RNA in both treatment-naïve and virally suppressed individuals with chronic HBV infection. The primary objective was to assess the safety and tolerability of bepirovirsen in individuals with chronic hepatitis B (CHB) (NCT02981602). The secondary objective was to assess antiviral activity, including the change from baseline to day 29 in serum hepatitis B surface antigen (HBsAg) concentration. Participants with CHB infection [greater than or equal to]6 months and serum HBsAg [greater than or equal to]50 IU ml.sup.-1 were enrolled from seven centers across Hong Kong and the Republic of Korea and randomized (3:1 within each dose cohort) to receive bepirovirsen or placebo via subcutaneous injection twice weekly during weeks 1 and 2 (days 1, 4, 8 and 11) and once weekly during weeks 3 and 4 (days 15 and 22). Participants were then followed for 26 weeks. Twenty-four participants were treatment-naïve and seven were receiving stable NA therapy. Treatment-emergent adverse events were mostly mild/moderate (most commonly injection site reactions). Eleven (61.1%) and three (50.0%) treatment-naïve participants experienced one or more treatment-emergent adverse event in the bepirovirsen and placebo groups, respectively. In participants receiving NA therapy, the corresponding numbers were three (60.0%) and one (50.0%). Transient, self-resolving alanine aminotransferase flares ([greater than or equal to]2× upper limit of normal) were observed in eight treatment-naïve participants and three participants on stable NA regimens in the bepirovirsen treatment arms. HBsAg reductions were observed and were significant versus placebo for treatment-naïve participants receiving bepirovirsen 300 mg (P = 0.001), but not for the bepirovirsen 150 mg group (P = 0.245) or participants receiving stable NA therapy (P = 0.762). Two participants in each of the 300 mg dose groups achieved HBsAg levels below the lower limit of quantitation by day 29 (n = 3) or day 36 (n = 1). Bepirovirsen had a favorable safety profile. These preliminary observations warrant further investigation of the safety and activity of bepirovirsen in a larger CHB patient population. A first-in-human study of an antisense oligonucleotide targeting hepatitis B virus (HBV) RNA provides initial insights into this potential new therapeutic modality for individuals with chronic HBV infection., Author(s): Man-Fung Yuen [sup.1] , Jeong Heo [sup.2] , Jeong-Won Jang [sup.3] , Jung-Hwan Yoon [sup.4] , Young-Oh Kweon [sup.5] , Sung-Jae Park [sup.6] , Yvonne Tami [sup.7] , Shihyun [...]

Published
2021
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20. Hepatitis B Core-Related Antigen to Indicate High Viral Load: Systematic Review and Meta-Analysis of 10,397 Individual Participants

Author

Yoshida, Kyoko, Desbiolles, Alice, Feldman, Sarah F., Ahn, Sang Hoon, Alidjinou, Enagnon K., Atsukawa, Masanori, Bocket, Laurence, Brunetto, Maurizia R., Buti, Maria, Carey, Ivana, Caviglia, Gian Paolo, Chen, En-Qiang, Cornberg, Markus, Enomoto, Masaru, Honda, Masao, Zu Siederdissen, Christoph Höner, Ishigami, Masatoshi, Janssen, Harry L.A., Maasoumy, Benjamin, Matsui, Takeshi, Matsumoto, Akihiro, Nishiguchi, Shuhei, Riveiro-Barciela, Mar, Takaki, Akinobu, Tangkijvanich, Pisit, Toyoda, Hidenori, van Campenhout, Margo J.H., Wang, Bo, Wei, Lai, Yang, Hwai-I, Yano, Yoshihiko, Yatsuhashi, Hiroshi, Yuen, Man-Fung, Tanaka, Eiji, Lemoine, Maud, Tanaka, Yasuhito, and Shimakawa, Yusuke

Published
2021
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23. Efficacy, safety, and pharmacokinetics of capsid assembly modulator linvencorvir plus standard of care in chronic hepatitis B patients

Author

Hou, Jinlin, primary, Gane, Edward, additional, Balabanska, Rozalina, additional, Zhang, Wenhong, additional, Zhang, Jiming, additional, Lim, Tien Huey, additional, Xie, Qing, additional, Yeh, Chau-Ting, additional, Yang, Sheng-Shun, additional, Liang, Xieer, additional, Komolmit, Piyawat, additional, Leerapun, Apinya, additional, Xue, Zenghui, additional, Chen, Ethan, additional, Zhang, Yuchen, additional, Xie, Qiaoqiao, additional, Chang, Ting-Tsung, additional, Hu, Tsung-Hui, additional, Lim, Seng Gee, additional, Chuang, Wan-Long, additional, Leggett, Barbara, additional, Bo, Qingyan, additional, Zhou, Xue, additional, Triyatni, Miriam, additional, Zhang, Wen, additional, and Yuen, Man-Fung, additional

Published
2024
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24. Phase 1 Trial of the Safety, Pharmacokinetics, and Antiviral Activity of EDP-514 in Untreated Viremic Chronic Hepatitis B Patients

Author

Yuen, Man-Fung, primary, Chuang, Wan-Long, additional, Peng, Cheng-Yuan, additional, Jeng, Wen-Juei, additional, Su, Wei-Wen, additional, Chang, Ting-Tsung, additional, Chen, Chi-Yi, additional, Hsu, Yao-Chun, additional, De La Rosa, Guy, additional, Ahmad, Alaa, additional, Luo, Ed, additional, and Conery, Annie L., additional

Published
2024
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25. Effects of SARS-CoV-2 infection on incidence and treatment strategies of hepatocellular carcinoma in people with chronic liver disease

Author

Mak, Lung-Yi, primary, Chung, Matthew Shing Hin, additional, Li, Xue, additional, Lai, Francisco Tsz Tsun, additional, Wan, Eric Yuk Fai, additional, Chui, Celine Sze Ling, additional, Cheng, Franco Wing Tak, additional, Chan, Esther Wai Yin, additional, Cheung, Ching Lung, additional, Au, Ivan Chi Ho, additional, Xiong, Xi, additional, Seto, Wai-Kay, additional, Yuen, Man-Fung, additional, Wong, Carlos King Ho, additional, and Wong, Ian Chi Kei, additional

Published
2024
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26. Impact of hepatic steatosis on risk of acute liver injury in people with chronic hepatitis B and SARS ‐CoV‐2 infection

Author

Chung, Matthew S. H., Wong, Carlos K. H., Li, Xue, Lai, Francisco T. T., Wan, Eric Y. F., Chui, Celine S. L., Cheng, Franco W. T., Chan, Esther W., Cheung, Ching Lung, Xiong, Xi, Li, Lanlan, Seto, Wai Kay, Yuen, Man‐Fung, Mak, Lung‐Yi, Wong, Ian C. K., Chung, Matthew S. H., Wong, Carlos K. H., Li, Xue, Lai, Francisco T. T., Wan, Eric Y. F., Chui, Celine S. L., Cheng, Franco W. T., Chan, Esther W., Cheung, Ching Lung, Xiong, Xi, Li, Lanlan, Seto, Wai Kay, Yuen, Man‐Fung, Mak, Lung‐Yi, and Wong, Ian C. K.

Abstract

Background: SARS‐CoV‐2 infection was known to be associated with higher risk of liver impairment in people with chronic hepatitis B infection (CHB). However, evidence regarding the impact of concomitant hepatic steatosis (HS) on the risk of liver disease among people with CHB and SARS‐CoV‐2 infection is lacking. We investigated the impact of concomitant HS on people with CHB suffering from SARS‐CoV‐2 infection. Methods: This retrospective cohort study was performed using an electronic health database for people in Hong Kong with CHB and confirmed SARS‐CoV‐2 infection between 21 January 2020 and 31 January 2023. People with HS diagnosis (HS + CHB + COVID‐19) were identified and matched 1:1 by propensity score with those without (CHB + COVID‐19). Each person was followed up until death, outcome event, or 31st January 2023. Study outcome was incidence of acute liver injury (ALI) within first 28 days since COVID‐19 diagnosis. Severity of ALI and comparison of ALI risk stratified by the presence of CHB infection and HS were also analysed. Incidence rate ratios (IRRs) were estimated by Poisson regression models. Results: Of 52 259 COVID‐19 patients with CHB infection in the cohort, 15 391 people with HS + CHB + COVID‐19 and 15 391 people with CHB + COVID‐19 were included after matching. HS + CHB + COVID‐19 was associated with increased risk of ALI (IRR: 1.41, 95% CI:1.05–1.90, p = 0.023), compared to CHB + COVID‐19. Over 99% ALI cases were mild to moderate severity, and there were no differences in the severity of ALI between HS + CHB + COVID‐19 and CHB + COVID‐19 (p = 0.127). Conclusions: Concomitant HS was associated with increased risk of ALI among people with CHB infection suffering from SARS‐CoV‐2 infection.

Published
2024

30. Factors Associated With Rates of HBsAg Seroclearance in Adults With Chronic HBV Infection: A Systematic Review and Meta-analysis

Author

Yeo, Yee Hui, Ho, Hsiu J., Yang, Hwai-I, Tseng, Tai-Chung, Hosaka, Tetsuya, Trinh, Huy N., Kwak, Min-Sun, Park, Young Min, Fung, James Yan Yue, Buti, Maria, Rodríguez, Manuel, Treeprasertsuk, Sombat, Preda, Carmen Monica, Ungtrakul, Teerapat, Charatcharoenwitthaya, Phunchai, Li, Xiangyong, Li, Jiayi, Zhang, Jian, Le, Michael Huan, Wei, Bin, Zou, Biyao, Le, An, Jeong, Donghak, Chien, Nicholas, Kam, Leslie, Lee, Chiao-Chin, Riveiro-Barciela, Mar, Istratescu, Doina, Sriprayoon, Tassanee, Chong, Yutian, Tanwandee, Tawesak, Kobayashi, Mariko, Suzuki, Fumitaka, Yuen, Man-Fung, Lee, Hyo-Suk, Kao, Jia-Horng, Lok, Anna S., Wu, Chun-Ying, and Nguyen, Mindie H.

Published
2019
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32. Range of Normal Liver Stiffness and Factors Associated With Increased Stiffness Measurements in Apparently Healthy Individuals

Author

Bazerbachi, Fateh, Haffar, Samir, Wang, Zhen, Cabezas, Joaquín, Arias-Loste, Maria Teresa, Crespo, Javier, Darwish-Murad, Sarwa, Ikram, M. Arfan, Olynyk, John K., Gan, Eng, Petta, Salvatore, Berzuini, Alessandra, Prati, Daniele, de Lédinghen, Victor, Wong, Vincent W., Del Poggio, Paolo, Chávez-Tapia, Norberto C., Chen, Yong-Peng, Cheng, Pin-Nan, Yuen, Man-Fung, Das, Kausik, Chowdhury, Abhijit, Caballeria, Llorenç, Fabrellas, Núria, Ginès, Pere, Kumar, Manoj, Sarin, Shiv Kumar, Conti, Fabio, Andreone, Pietro, Sirli, Roxana, Cortez-Pinto, Helena, Carvalhana, Sofia, Sugihara, Takaaki, Kim, Seung Up, Parikh, Pathik, Chayama, Kazuaki, Corpechot, Christophe, Kim, Kang Mo, Papatheodoridis, George, Alsebaey, Ayman, Kamath, Patrick S., Murad, M. Hassan, and Watt, Kymberly D.

Published
2019
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37. Pretreatment gamma‐glutamyl transferase predicts mortality in patients with chronic hepatitis B treated with nucleotide/nucleoside analogs

Author

Jang, Tyng‐Yuan, primary, Liang, Po‐Cheng, additional, Jun, Dae Won, additional, Jung, Jang Han, additional, Toyoda, Hidenori, additional, Wang, Chih‐Wen, additional, Yuen, Man‐Fung, additional, Cheung, Ka Shing, additional, Yasuda, Satoshi, additional, Kim, Sung Eun, additional, Yoon, Eileen L., additional, An, Jihyun, additional, Enomoto, Masaru, additional, Kozuka, Ritsuzo, additional, Chuma, Makoto, additional, Nozaki, Akito, additional, Ishikawa, Toru, additional, Watanabe, Tsunamasa, additional, Atsukawa, Masanori, additional, Arai, Taeang, additional, Hayama, Korenobu, additional, Ishigami, Masatoshi, additional, Cho, Yong Kyun, additional, Ogawa, Eiichi, additional, Kim, Hyoung Su, additional, Shim, Jae‐Jun, additional, Uojima, Haruki, additional, Jeong, Soung Won, additional, Ahn, Sang Bong, additional, Takaguchi, Koichi, additional, Senoh, Tomonori, additional, Buti, Maria, additional, Vargas‐Accarino, Elena, additional, Abe, Hiroshi, additional, Takahashi, Hirokazu, additional, Inoue, Kaori, additional, Huang, Jee‐Fu, additional, Chuang, Wan‐Long, additional, Yeh, Ming‐Lun, additional, Dai, Chia‐Yen, additional, Huang, Chung‐Feng, additional, Nguyen, Mindie H., additional, and Yu, Ming‐Lung, additional

Published
2023
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39. Pretreatment gamma‐glutamyl transferase predicts mortality in patients with chronic hepatitis B treated with nucleotide/nucleoside analogs.

Author

Jang, Tyng‐Yuan, Liang, Po‐Cheng, Jun, Dae Won, Jung, Jang Han, Toyoda, Hidenori, Wang, Chih‐Wen, Yuen, Man‐Fung, Cheung, Ka Shing, Yasuda, Satoshi, Kim, Sung Eun, Yoon, Eileen L., An, Jihyun, Enomoto, Masaru, Kozuka, Ritsuzo, Chuma, Makoto, Nozaki, Akito, Ishikawa, Toru, Watanabe, Tsunamasa, Atsukawa, Masanori, and Arai, Taeang

Subjects
CHRONIC hepatitis B, FATTY liver, ALANINE aminotransferase, MORTALITY, ALCOHOL drinking
Abstract

Elevated serum gamma‐glutamyl transferase (GGT) levels are associated with chronic hepatitis B (CHB)‐related hepatocellular carcinoma. However, their role in predicting mortality in patients with CHB treated with nucleotide/nucleoside analogs (NAs) remains elusive. Altogether, 2843 patients with CHB treated with NAs were recruited from a multinational cohort. Serum GGT levels before and 6 months (Month‐6) after initiating NAs were measured to explore their association with all‐cause, liver‐related, and non‐liver‐related mortality. The annual incidence of all‐cause mortality was 0.9/100 person‐years over a follow‐up period of 17,436.3 person‐years. Compared with patients who survived, those who died had a significantly higher pretreatment (89.3 vs. 67.4 U/L, p = 0.002) and Month‐6‐GGT levels (62.1 vs. 38.4 U/L, p < 0.001). The factors associated with all‐cause mortality included cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 2.66/1.92–3.70, p < 0.001), pretreatment GGT levels (HR/CI: 1.004/1.003–1.006, p < 0.001), alanine aminotransferase level (HR/CI: 0.996/0.994–0.998, p = 0.001), and age (HR/CI: 1.06/1.04–1.07, p < 0.001). Regarding liver‐related mortality, the independent factors included cirrhosis (HR/CI: 4.36/2.79–6.89, p < 0.001), pretreatment GGT levels (HR/CI: 1.006/1.004–1.008, p < 0.001), alanine aminotransferase level (HR/CI: 0.993/0.990–0.997, p = 0.001), age (HR/CI: 1.03/1.01–1.05, p < 0.001), and fatty liver disease (HR/CI: 0.30/0.15–0.59, p = 0.001). Pretreatment GGT levels were also independently predictive of non‐liver‐related mortality (HR/CI: 1.003/1.000–1.005, p = 0.03). The results remained consistent after excluding the patients with a history of alcohol use. A dose‐dependent manner of <25, 25–75, and >75 percentile of pretreatment GGT levels was observed with respect to the all‐cause mortality (trend p < 0.001). Pretreatment serum GGT levels predicted all‐cause, liver‐related, and non‐liver‐related mortality in patients with CHB treated with NAs. [ABSTRACT FROM AUTHOR]

Published
2024
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41. Incidence, Factors, and Patient-Level Data for Spontaneous HBsAg Seroclearance: A Cohort Study of 11,264 Patients

Author

Yeo, Yee Hui, Tseng, Tai-Chung, Hosaka, Tetsuya, Cunningham, Chris, Fung, James Yan Yue, Ho, Hsiu J., Kwak, Min-Sun, Trinh, Huy N., Ungtrakul, Teerapat, Yu, Ming-Lung, Kobayashi, Mariko, Le, An K., Henry, Linda, Li, Jiayi, Zhang, Jian, Sriprayoon, Tassanee, Jeong, Donghak, Tanwandee, Tawesak, Gane, Ed, Cheung, Ramsey C., Wu, Chun-Ying, Lok, Anna S., Lee, Hyo-Suk, Suzuki, Fumitaka, Yuen, Man-Fung, Kao, Jia-Horng, Yang, Hwai-I, and Nguyen, Mindie H.

Published
2020
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42. Small Extracellular Vesicle‐Derived vWF Induces a Positive Feedback Loop between Tumor and Endothelial Cells to Promote Angiogenesis and Metastasis in Hepatocellular Carcinoma

Author

Wong, Samuel Wan Ki, primary, Tey, Sze Keong, additional, Mao, Xiaowen, additional, Fung, Hiu Ling, additional, Xiao, Zhi‐Jie, additional, Wong, Danny Ka Ho, additional, Mak, Lung‐Yi, additional, Yuen, Man‐Fung, additional, Ng, Irene Oi‐Lin, additional, Yun, Jing Ping, additional, Gao, Yi, additional, and Yam, Judy Wai Ping, additional

Published
2023
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46. Incidence of Hepatic Decompensation After Nucleos(t)ide Analog Withdrawal:Results From a Large, International, Multiethnic Cohort of Patients With Chronic Hepatitis B (RETRACT-B Study)

Author

Hirode, Grishma, Hansen, Bettina E., Chen, Chien Hung, Su, Tung Hung, Wong, Grace, Seto, Wai Kay, Van Hees, Stijn, Papatheodoridi, Margarita, Brakenhoff, Sylvia M., Lens, Sabela, Choi, Hannah S.J., Chien, Rong Nan, Feld, Jordan J., Forns, Xavier, Sonneveld, Milan J., Papatheodoridis, George V., Vanwolleghem, Thomas, Yuen, Man Fung, Chan, Henry L.Y., Kao, Jia Horng, Hsu, Yao Chun, Cornberg, Markus, Jeng, Wen Juei, Janssen, Harry L.A., Hirode, Grishma, Hansen, Bettina E., Chen, Chien Hung, Su, Tung Hung, Wong, Grace, Seto, Wai Kay, Van Hees, Stijn, Papatheodoridi, Margarita, Brakenhoff, Sylvia M., Lens, Sabela, Choi, Hannah S.J., Chien, Rong Nan, Feld, Jordan J., Forns, Xavier, Sonneveld, Milan J., Papatheodoridis, George V., Vanwolleghem, Thomas, Yuen, Man Fung, Chan, Henry L.Y., Kao, Jia Horng, Hsu, Yao Chun, Cornberg, Markus, Jeng, Wen Juei, and Janssen, Harry L.A.

Abstract

INTRODUCTION: Despite improvements in the management of chronic hepatitis B (CHB), risk of cirrhosis and hepatocellular carcinoma remains. While hepatitis B surface antigen loss is the optimal end point, safe discontinuation of nucleos(t)ide analog (NA) therapy is controversial because of the possibility of severe or fatal reactivation flares.METHODS: This is a multicenter cohort study of virally suppressed, end-of-therapy (EOT) hepatitis B e antigen (HBeAg)-negative CHB patients who stopped NA therapy (n = 1,557). Survival analysis techniques were used to analyze off-therapy rates of hepatic decompensation and differences by patient characteristics. We also examined a subgroup of noncirrhotic patients with consolidation therapy of ≥12 months before cessation (n = 1,289). Hepatic decompensation was considered related to therapy cessation if diagnosed off therapy or within 6 months of starting retreatment. RESULTS: Among the total cohort (11.8% diagnosed with cirrhosis, 84.2% start-of-therapy HBeAg-negative), 20 developed hepatic decompensation after NA cessation; 10 events were among the subgroup. The cumulative incidence of hepatic decompensation at 60 months off therapy among the total cohort and subgroup was 1.8% and 1.1%, respectively. The hepatic decompensation rate was higher among patients with cirrhosis (hazard ratio [HR] 5.08, P < 0.001) and start-of-therapy HBeAg-positive patients (HR 5.23, P < 0.001). This association between start-of-therapy HBeAg status and hepatic decompensation remained significant even among the subgroup (HR 10.5, P < 0.001). DISCUSSION: Patients with cirrhosis and start-of-therapy HBeAg-positive patients should be carefully assessed before stopping NAs to prevent hepatic decompensation. Frequent monitoring of viral and host kinetics after cessation is crucial to determine patient outcome.

Published
2023

47. Lower pretreatment HBV DNA levels are associated with better off-treatment outcomes after nucleo(s)tide analogue withdrawal in patients with HBeAg-neegative chronic hepatitis B:A multicentre cohort study

Author

Sonneveld, Milan J., Chiu, Shao Ming, Park, Jun Yong, Brakenhoff, Sylvia M., Kaewdech, Apichat, Seto, Wai Kay, Tanaka, Yasuhito, Carey, Ivana, Papatheodoridi, Margarita, Colombatto, Piero, van Bömmel, Florian, Berg, Thomas, Zoulim, Fabien, Ahn, Sang Hoon, Dalekos, George N., Erler, Nicole S., Brunetto, Maurizia, Wedemeyer, Heiner, Cornberg, Markus, Yuen, Man Fung, Agarwal, Kosh, Boonstra, Andre, Buti, Maria, Piratvisuth, Teerha, Papatheodoridis, George, Chen, Chien Hung, Maasoumy, Benjamin, Sonneveld, Milan J., Chiu, Shao Ming, Park, Jun Yong, Brakenhoff, Sylvia M., Kaewdech, Apichat, Seto, Wai Kay, Tanaka, Yasuhito, Carey, Ivana, Papatheodoridi, Margarita, Colombatto, Piero, van Bömmel, Florian, Berg, Thomas, Zoulim, Fabien, Ahn, Sang Hoon, Dalekos, George N., Erler, Nicole S., Brunetto, Maurizia, Wedemeyer, Heiner, Cornberg, Markus, Yuen, Man Fung, Agarwal, Kosh, Boonstra, Andre, Buti, Maria, Piratvisuth, Teerha, Papatheodoridis, George, Chen, Chien Hung, and Maasoumy, Benjamin

Abstract

Background & Aims: Pretreatment predictors of finite nucleo(s)tide analogue (NUC) therapy remain elusive. We studied the association between pretreatment HBV DNA levels and outcomes after therapy cessation. Methods: Patients with chronic hepatitis B who were HBeAg negative at the start of NUC treatment were enrolled from sites in Asia and Europe. We studied the association between pretreatment HBV DNA levels and (1) clinical relapse (defined as HBV DNA >2,000 IU/ml + alanine aminotransferase >2 × the upper limit of normal or retreatment) and (2) HBsAg loss after NUC withdrawal. Results: We enrolled 757 patients, 88% Asian, 57% treated with entecavir, with a median duration of treatment of 159 (IQR 156–262) weeks. Mean pretreatment HBV DNA levels were 5.70 (SD 1.5) log IU/ml and were low (<20,000 IU/ml) in 150 (20%) and high (>20,000 IU/ml) in 607 (80%). The cumulative risk of clinical relapse at 144 weeks after therapy cessation was 22% among patients with pretreatment HBV DNA levels <20,000 IU/ml vs. 60% among patients with pretreatment HBV DNA levels >20,000 IU/ml, whereas the cumulative probabilities of HBsAg loss were 17.5% vs. 5% (p <0.001). In multivariable analysis, pretreatment HBV DNA levels <20,000 IU/ml were independently associated with a reduced likelihood of clinical relapse (adjusted hazard ratio 0.379, p <0.001) and with an increased chance of HBsAg loss (adjusted hazard ratio 2.872, p <0.001). Conclusions: Lower pretreatment HBV DNA levels are associated with a lower risk of clinical relapse and a higher chance of HBsAg loss after cessation of NUC therapy, independent of end-of-treatment viral antigen levels. Further studies are needed to confirm these findings in non-Asian populations. Impact and Implications: A subgroup of patients with chronic hepatitis B may not require retreatment after stopping antiviral therapy. In this study, comprising 757 patients with chronic hepatitis B from Europe and Asia, we found

Published
2023

48. Portable electrical impedance tomography (EIT) system stages non-alcoholic fatty liver disease for potential screening and monitoring at home

Author

Li, Ho Wa, Touboul, Adrien, Zouari, Fedi, Cheung, Pak To, Wei, Ellie, Wong, Eddie C., Zhou, Iris Y., Yuen, Man-Fung, Seto, Wai-Kay, Mak, Lung-Yi, Chan, Russell W., Li, Ho Wa, Touboul, Adrien, Zouari, Fedi, Cheung, Pak To, Wei, Ellie, Wong, Eddie C., Zhou, Iris Y., Yuen, Man-Fung, Seto, Wai-Kay, Mak, Lung-Yi, and Chan, Russell W.

Abstract

This study demonstrates the feasibility of predicting NAFLD using multi-spectral electrical impedance tomography (EIT), group source separation, constant reference EIT and anthropometric measures. Vibration-controlled Transient Elastography (VCTE) Controlled Attenuated Parameter (CAP; n = 121) and magnetic resonance imaging-proton density fat fraction (MRI-PDFF; n = 34) achieved a sensitivity of 70.9% and specificity of 73.8% with our CAP predicting model and sensitivity of 77.8% and specificity of 80.0% with our MRI-PDFF predicting model. In summary, a portable EIT can be a cost-effective and self-administrable alternative for widespread home-based and community-based diagnostic screening and treatment monitoring of NAFLD.Clinical Relevance - Portable multi-spectral EIT system has the sensitivity and specificity to potentially unlock biomedical imaging in telemedicine for home-based and community-based screening, staging and monitoring for NAFLD. © 2023 IEEE.

Published
2023

49. Sex Differences in Association Between Gut Microbiome and Essential Hypertension Based on Ambulatory Blood Pressure Monitoring

Author

Virwani, Preeti Dinesh, primary, Qian, Gordon, additional, Hsu, Matthew S.S., additional, Pijarnvanit, Tommy K.K.T.S., additional, Cheung, Carman Nga-Man, additional, Chow, Yick Hin, additional, Tang, Lok Kan, additional, Tse, Yiu-Hei, additional, Xian, Jia-Wen, additional, Lam, Shirley Sau-Wing, additional, Lee, Crystal P.I., additional, Lo, Chelsea C.W., additional, Liu, Roxanna K.C., additional, Ho, Tsi Lok, additional, Chow, Bak Yue, additional, Leung, Kin Sum, additional, Tsang, Hing Wai, additional, Lo, Emily K.K., additional, Tung, Keith T.S., additional, Chung, Sookja Kim, additional, Yuen, Man-Fung, additional, Leung, Suet Yi, additional, Ip, Patrick, additional, Hung, Ivan Fan-Ngai, additional, Louie, Jimmy Chun Yu, additional, El-Nezami, Hani, additional, Ho, Joshua Wing Kei, additional, and Lau, Kui Kai, additional

Published
2023
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