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"Grace Lai-Hung Wong"

Original Articles

Normal-weight MASLD: reclassification, characteristics, and adverse liver outcomes across diverse populations
Sherlot Juan Song, Eileen Laureal Yoon, Vincent Wai-Sun Wong, Ae Jeong Jo, Grace Lai-Hung Wong, Jimmy Che-To Lai, Dae Won Jun, Terry Cheuk-Fung Yip
Received July 28, 2025  Accepted December 9, 2025  Published online December 12, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0851    [Accepted]
Background & Aims
Previous studies have identified a substantial degree of agreement between the non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) populations, but the same notion may not apply to normal-weight patients with a lower cardiometabolic risk burden. This study aims to investigate the CMRF distributions between normal-weight and overweight/obese MASLD, the agreement between historical NAFLD and MASLD, and to compare the risk of liver-related events (LREs) and all-cause mortality in normal-weight versus overweight or obese MASLD.
Methods
This study included participants with steatotic liver disease (SLD) from five cohorts in Hong Kong, South Korea, and the United States. Participants were recruited from settings including both hospitals and communities. Individuals were classified into normal-weight and overweight/obese groups.
Results
This study included 33,793 participants with SLD from five cohorts, of whom 20,893 and 20,701 patients met the diagnosis of NAFLD and MASLD, respectively. Normal-weight patients with NAFLD demonstrated a lower CMRF distribution compared to those with overweight/obese NAFLD. In the community-based cohorts, the proportions of 0 CMRF ranged from 9.0-26.7% among normal-weight NAFLD, representing the discrepancy between MASLD and NAFLD definitions. Compared with the overweight/obese MASLD, the normal-weight MASLD had increased all-cause mortality (normal-weight vs. overweight/obese, 23.44 and 13.80 per 1000 person-years; p<0.001) but not LREs (2.81 and 2.59 per 1000 person-years; p=0.54) in the HK CDARS cohort.
Conclusions
Normal-weight individuals with NAFLD demonstrated a lower distribution of CMRFs, resulting in the incomplete agreement between historical NAFLD and MASLD.
Ethical Compliance
For all involved cohorts, the study protocols conformed to the ethical guidelines of the 1975 Declaration of Helsinki and were approved by the appropriate clinical research ethics committee and/or institutional review board, which provided either written consent or a waiver of informed consent.
  • 719 View
  • 104 Download
Hypothyroidism and the risk of liver-related events in patients with metabolic dysfunction-associated steatotic liver disease
Xinrui Jin, Sherlot Juan Song, Jimmy Che-To Lai, Grace Lai-Hung Wong, Alice Pik-Shan Kong, Nana Peng, Xiang Xiao, Vincent Wai-Sun Wong, Terry Cheuk-Fung Yip
Clin Mol Hepatol 2026;32(1):353-367.
Published online December 1, 2025
DOI: https://doi.org/10.3350/cmh.2025.0860
Background/Aims
Previous studies suggest that hypothyroidism is associated with metabolic dysfunction-associated steatotic liver disease (MASLD) and its histological severity, but clinical outcome data are largely lacking. We aimed to study the impact of hypothyroidism on liver-related events (LREs).
Methods
Patients with MASLD were identified from a territory-wide registry in Hong Kong during 2000–2024. Thyroid status was determined using diagnosis codes and thyroid function tests. The primary outcome, LRE, was defined as a composite of hepatic decompensation, hepatocellular carcinoma, liver transplantation, and liver-related death.
Results
A total of 20,478 patients with MASLD were included in the final analysis (mean age 56.4±13.2 years; 43.9% male). At baseline, 18,178 (88.8%) patients were euthyroid, 598 (2.9%) were hyperthyroid, and 1,702 (8.3%) were hypothyroid. Compared with euthyroid patients, both hyperthyroidism and overt hypothyroidism were associated with cirrhosis. At a median follow-up of 4.8 years, 179 patients developed LREs, and 26 died from liver disease. Compared with patients with normal serum thyroid-stimulating hormone (TSH) levels of 0.4–4 mIU/L, those with subclinical (4–10 mIU/L; adjusted time-dependent cause-specific hazard ratio [aCSHR], 2.49; 95% CI, 1.51–4.13) and overt hypothyroidism (>10 mIU/L; aCSHR, 4.91; 95% CI, 1.56–15.47) had an increased risk of LREs. Time-dependent, but not baseline, TSH and thyroid status were associated with LRE risk.
Conclusions
Subclinical and overt hypothyroidism are associated with an increased risk of LREs in a dose-dependent manner. The association with time-dependent but not baseline thyroid status underscores the importance of thyroid monitoring and suggests that correction of hypothyroidism may mitigate LRE risk.
  • 830 View
  • 114 Download
Histological severity and hepatic outcomes in patients with metabolic dysfunction-associated steatotic liver disease and discrepant FIB-4 and liver stiffness measurement
Joseph Rabbat, Boyu Yang, Hye Won Lee, Huapeng Lin, Emmanuel Tsochatzis, Salvatore Petta, Elisabetta Bugianesi, Masato Yoneda, Ming-Hua Zheng, Hannes Hagström, Jérôme Boursier, José Luis Calleja, George Boon-Bee Goh, Wah-Kheong Chan, Rocio Gallego-Durán, Arun J. Sanyal, Victor de Lédinghen, Philip N Newsome, Jian-Gao Fan, Laurent Castéra, Michelle Lai, Céline Fournier-Poizat, Grace Lai-Hung Wong, Mirko Zoncape, Grazia Pennisi, Angelo Armandi, Atsushi Nakajima, Wen-Yue Liu, Ying Shang, Marc de Saint-Loup, Elba Llop, Kevin Kim Jun Teh, Carmen Lara-Romero, Amon Asgharpour, Sara Mahgoub, Mandy Sau-Wai Chan, Clemence M Canivet, Manuel Romero-Gomez, Vincent Wai-Sun Wong, Seung Up Kim, Terry Cheuk-Fung Yip
Clin Mol Hepatol 2026;32(1):289-304.
Published online November 11, 2025
DOI: https://doi.org/10.3350/cmh.2025.0888
Background/Aims
Current guidelines recommend a 2-step approach for identifying advanced fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD), using Fibrosis-4 index (FIB-4) followed by liver stiffness measurement (LSM) via vibration-controlled transient elastography (VCTE). However, some patients may exhibit discordant results. This study evaluates the histological severity and outcomes in patients with discordant FIB-4 and LSM results.
Methods
This secondary analysis of the VCTE-Prognosis study included 12,950 patients evaluated for MASLD at 16 tertiary centers, of whom 2,915 underwent liver biopsy. Patients were categorized into four groups based on established FIB-4 (1.3) and LSM (8 kPa) cutoffs.
Results
F3–F4 fibrosis was observed in 6.4%, 13.7%, 30.6%, and 62.4% in low-FIB-4-low-LSM (n=6,403), high-FIB-4-low-LSM (n=3,017), low-FIB-4-high-LSM (n=1,363), and high-FIB-4-high-LSM (n=2,167) groups, respectively. During a median follow-up of 47.4 months, 248 patients experienced hepatic decompensation, hepatocellular carcinoma, liver transplantation, or liver-related death. The incidence rates of liver-related events (LREs) were 0.67, 1.19, 2.58, and 21.30 per 1,000 person-years, respectively. Compared to low-FIB-4-low-LSM patients, those with low-FIB-4-high-LSM (adjusted subdistribution hazard ratio [aSHR] 4.12) and high-FIB-4-high-LSM (aSHR 21.38) had a significantly higher risk of LREs, while high-FIB-4-low-LSM patients did not. Similar findings were observed when hepatic decompensation and hepatocellular carcinoma were analyzed separately.
Conclusions
Approximately 30% of patients in tertiary centers exhibit discordant FIB-4 and LSM results, with LSM more likely reflecting true severity. While some patients with discordant results may have advanced fibrosis, the overall incidence of LREs remains low.
  • 1,786 View
  • 217 Download

Letter to the Editor

Hepatic neoplasm

Dipeptidyl peptidase-4 inhibitors are associated with improved survival of patients with diabetes mellitus and hepatocellular carcinoma receiving immunotherapy: Letter to the editor on “Statin and aspirin for chemoprevention of hepatocellular carcinoma: Time to use or wait further?”
Dorothy Cheuk-Yan Yiu, Huapeng Lin, Vincent Wai-Sun Wong, Grace Lai-Hung Wong, Ken Liu, Terry Cheuk-Fung Yip
Clin Mol Hepatol 2024;30(4):970-973.
Published online July 4, 2024
DOI: https://doi.org/10.3350/cmh.2024.0280

Citations

Citations to this article as recorded by  Crossref logo
  • CXCL12 as a Potential Hub Gene for N-Acetylcysteine Treatment of T1DM Liver Disease
    Menglong Zhao, Mingzheng Han, Shuaihao Guo, Zhaoxin Tang
    Biomolecules.2025; 15(2): 176.     CrossRef
  • Comparative Risk of Hepatitis B Virus Reactivation in Patients Receiving Immune Checkpoint Inhibitors or Tyrosine Kinase Inhibitors for Liver Cancer
    Dorothy Cheuk‐Yan Yiu, Jimmy Che‐To Lai, Landon Long Chan, Grace Lai‐Hung Wong, Mandy Sze‐Man Lai, Vincent Wai‐Sun Wong, Yee‐Kit Tse, Henry Lik‐Yuen Chan, Stephen Lam Chan, Terry Cheuk‐Fung Yip
    Alimentary Pharmacology & Therapeutics.2025;[Epub]     CrossRef
  • Prognostic Impact of DPP4 Inhibitors on Systemic Drug Therapy for Advanced Kidney Cancer Patients
    Shuhei Kamada, Sachi Kitayama, Ryosuke Yamase, Kazuhiro Ikeda, Wataru Sato, Tomokazu Sazuka, Hideki Takeshita, Shinichi Sakamoto, Akihiro Yano, Kuniko Horie, Tomohiko Ichikawa, Satoru Kawakami, Satoshi Inoue
    Cancer Science.2025;[Epub]     CrossRef
  • 4,508 View
  • 72 Download
  • 3 Web of Science
  • Crossref

Review

Steatotic liver disease

Role of noninvasive tests in the prognostication of metabolic dysfunction-associated steatotic liver disease
Yue Wang, Sherlot Juan Song, Yichong Jiang, Jimmy Che-To Lai, Grace Lai-Hung Wong, Vincent Wai-Sun Wong, Terry Cheuk-Fung Yip
Clin Mol Hepatol 2025;31(Suppl):S51-S75.
Published online June 27, 2024
DOI: https://doi.org/10.3350/cmh.2024.0246
In managing metabolic dysfunction-associated steatotic liver disease, which affects over 30% of the general population, effective noninvasive biomarkers for assessing disease severity, monitoring disease progression, predicting the development of liver-related complications, and assessing treatment response are crucial. The advantage of simple fibrosis scores lies in their widespread accessibility through routinely performed blood tests and extensive validation in different clinical settings. They have shown reasonable accuracy in diagnosing advanced fibrosis and good performance in excluding the majority of patients with a low risk of liver-related complications. Among patients with elevated serum fibrosis scores, a more specific fibrosis and imaging biomarker has proved useful to accurately identify patients at risk of liver-related complications. Among specific fibrosis blood biomarkers, enhanced liver fibrosis is the most widely utilized and has been approved in the United States as a prognostic biomarker. For imaging biomarkers, the availability of vibration-controlled transient elastography has been largely improved over the past years, enabling the use of liver stiffness measurement (LSM) for accurate assessment of significant and advanced fibrosis, and cirrhosis. Combining LSM with other routinely available blood tests enhances the ability to diagnose at-risk metabolic dysfunction-associated steatohepatitis and predict liver-related complications, some reaching an accuracy comparable to that of liver biopsy. Magnetic resonance imaging-based modalities provide the most accurate quantification of liver fibrosis, though the current utilization is limited to research settings. Expanding their future use in clinical practice depends on factors such as cost and facility availability.

Citations

Citations to this article as recorded by  Crossref logo
  • Fe-Mn-IGF-AMD nanoparticles in accurate detection and treatment of liver cirrhosis via regulating relaxation coefficients and attenuating hepatocyte senescence
    Baihe Wang, Tingting Ji, Zihao Zhang, Yuyao Duan, Zhiqun Xing, Jiazhi Duan, Songbo Zhao, Yang Jia, Qian Wang
    Colloids and Surfaces B: Biointerfaces.2026; 257: 115182.     CrossRef
  • Stimuli-responsive nanomedicines for hepatic diseases: mechanism, design, recent advances, and clinical translation
    Leyi Wang, Xue Zhang, Yinggang Li, Min Zhao, Gang Xu, Zhenyu Duan, Qiyong Gong, Kui Luo
    Journal of Controlled Release.2026; 390: 114522.     CrossRef
  • Prediction of major liver-related events in the population using prognostic models
    Fredrik Åberg, Ville Männistö
    Gastroenterology Report.2025;[Epub]     CrossRef
  • Clinical and Economic Burden of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in a Spanish Mediterranean Region: A Population-Based Study
    Javier Díaz Carnicero, Inma Saurí-Ferrer, Josep Redon, Jorge Navarro, Gonzalo Fernández, Carlos Hurtado, Karine Ferreira, Carolina Alvarez-Ortega, Antón Gómez, Carlos J. Martos-Rodríguez, David Martí-Aguado, Desamparados Escudero, Marta Cedenilla
    Journal of Clinical Medicine.2025; 14(7): 2441.     CrossRef
  • Non-invasive risk-based surveillance of hepatocellular carcinoma in patients with metabolic dysfunction-associated steatotic liver disease
    Jimmy Che-To Lai, Boyu Yang, Hye Won Lee, Huapeng Lin, Emmanuel A Tsochatzis, Salvatore Petta, Elisabetta Bugianesi, Masato Yoneda, Ming-Hua Zheng, Hannes Hagström, Jerome Boursier, Jose Luis Calleja, George Boon-Bee Goh, Wah-Kheong Chan, Rocìo Gallego-Du
    Gut.2025; 74(12): 2050.     CrossRef
  • Effect of Antidiabetic Drug Classes on the Risk of Liver-Related Events in Individuals With T2D and MASLD
    Yu Shi, Seung Up Kim, Terry Cheuk-Fung Yip, Emmanuel Tsochatzis, Salvatore Petta, Atsushi Nakajima, Hannes Hagström, Elisabetta Bugianesi, Wah-Kheong Chan, Jérôme Boursier, Boon-Bee George Goh, Arun J. Sanyal, Manuel Romero-Gomez, José Luis Calleja, Victo
    Clinical Gastroenterology and Hepatology.2025;[Epub]     CrossRef
  • Risk stratification by noninvasive tests in patients with metabolic dysfunction-associated steatotic liver disease
    Hye Won Lee, Jae Seung Lee, Mi Na Kim, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Seung Up Kim
    Clinical and Molecular Hepatology.2025; 31(3): 1018.     CrossRef
  • Non-invasive tests of fibrosis in the management of MASLD: revolutionising diagnosis, progression and regression monitoring
    Gong Feng, Vincent Wai-Sun Wong, Giovanni Targher, Christopher D Byrne, Ming-Hua Zheng
    Gut.2025; 74(10): 1741.     CrossRef
  • Relative change rate of liver stiffness measurements predicts the risk of liver decompensation in compensated advanced chronic liver disease
    Yanqiu Li, Zihang Qiao, Jinze Li, Bingbing Zhu, Yu Lu, Ying Feng, Xianbo Wang
    Clinical and Experimental Medicine.2025;[Epub]     CrossRef
  • Correspondence to letter to the editor on “Risk Stratification of Metabolic Dysfunction-Associated Steatotic Liver Disease: The KASL Pathway
    Hye Won Lee, Seung Up Kim
    Clinical and Molecular Hepatology.2025;[Epub]     CrossRef
  • Endohepatology in the Management of Liver Diseases
    Thomas J. Wang, Ajaypal Singh
    Seminars in Liver Disease.2025; 45(04): 439.     CrossRef
  • Letter to the Editor: Are we overestimating LSM-based HCC risk in MASLD? Addressing immortal time bias
    Heechul Nam, Sung Won Lee
    Hepatology.2025;[Epub]     CrossRef
  • Liver stiffness measurement-based risk score for predicting liver decompensation risk: a single-center retrospective Chinese study
    Yanqiu Li, Zihang Qiao, Jinze Li, Yongqi Li, Ying Feng, Xianbo Wang
    Clinical and Experimental Medicine.2025;[Epub]     CrossRef
  • Liver Transplantation in the Era of Metabolic Dysfunction–Associated Fatty Liver Disease: Challenges, Ethical Dilemmas, and Future Directions
    Said A. Al-Busafi, Mohammed Eslam
    Transplantology.2025; 6(4): 35.     CrossRef
  • Preface
    Seung Up Kim
    Clinical and Molecular Hepatology.2024; 30(Suppl): S3.     CrossRef
  • 12,205 View
  • 296 Download
  • 13 Web of Science
  • Crossref

Editorial

Hepatic neoplasm

Unlocking the future: Machine learning sheds light on prognostication for early-stage hepatocellular carcinoma: Editorial on “Conventional and machine learning-based risk scores for patients with early-stage hepatocellular carcinoma”
Junlong Dai, Jimmy Che-To Lai, Grace Lai-Hung Wong, Terry Cheuk-Fung Yip
Clin Mol Hepatol 2024;30(4):698-701.
Published online May 7, 2024
DOI: https://doi.org/10.3350/cmh.2024.0327

Citations

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  • Artificial intelligence (AI)-enabled thermochemical risk modeling via self-attentive deep neural networks for predicting the SADT of organic peroxides
    Fanzhi Meng, Wei Xu, Yanan Qian, Feng Sun, Bing Sun, Zhe Yang
    Journal of Loss Prevention in the Process Industries.2026; 99: 105827.     CrossRef
  • Correspondence to letter to the editor 2 on “Conventional and machine learning-based risk scores for patients with early-stage hepatocellular carcinoma”
    Chun-Ting Ho, Elise Chia-Hui Tan, Chien-Wei Su
    Clinical and Molecular Hepatology.2025; 31(1): e101.     CrossRef
  • Prediction Model for Familial Aggregated HBV‐Associated Hepatocellular Carcinoma Based on Serum Biomarkers
    Linmei Zhong, Guole Nie, Qiaoping Wu, Honglong Zhang, Haiping Wang, Jun Yan
    Cancer Reports.2025;[Epub]     CrossRef
  • Correspondence to editorial on “Conventional and machine learning-based risk scores for patients with early-stage hepatocellular carcinoma”
    Chun-Ting Ho, Elise Chia-Hui Tan, Chien-Wei Su
    Clinical and Molecular Hepatology.2024; 30(4): 1016.     CrossRef
  • 5,240 View
  • 62 Download
  • 3 Web of Science
  • Crossref

Review

Steatotic liver disease

Non-invasive biomarkers for liver inflammation in non-alcoholic fatty liver disease: present and future
Terry Cheuk-Fung Yip, Fei Lyu, Huapeng Lin, Guanlin Li, Pong-Chi Yuen, Vincent Wai-Sun Wong, Grace Lai-Hung Wong
Clin Mol Hepatol 2023;29(Suppl):S171-S183.
Published online December 12, 2022
DOI: https://doi.org/10.3350/cmh.2022.0426
Inflammation is the key driver of liver fibrosis progression in non-alcoholic fatty liver disease (NAFLD). Unfortunately, it is often challenging to assess inflammation in NAFLD due to its dynamic nature and poor correlation with liver biochemical markers. Liver histology keeps its role as the standard tool, yet it is well-known for substantial sampling, intraobserver, and interobserver variability. Serum proinflammatory cytokines and apoptotic markers, namely cytokeratin-18, are well-studied with reasonable accuracy, whereas serum metabolomics and lipidomics have been adopted in some commercially available diagnostic models. Ultrasound and computed tomography imaging techniques are attractive due to their wide availability; yet their accuracies may not be comparable with magnetic resonance imaging-based tools. Machine learning and deep learning models, be they supervised or unsupervised learning, are promising tools to identify various subtypes of NAFLD, including those with dominating liver inflammation, contributing to sustainable care pathways for NAFLD.

Citations

Citations to this article as recorded by  Crossref logo
  • Association between neutrophil-albumin ratio and ultrasound-defined metabolic dysfunction-associated fatty liver disease in U.S. adults: evidence from NHANES 2017–2018
    Ming-yu He, Xin-jie Du, Yi-ming Liu
    BMC Gastroenterology.2025;[Epub]     CrossRef
  • Mitochondrial mt12361A>G increased risk of metabolic dysfunction-associated steatotic liver disease among non-diabetes
    Ming-Ying Lu, Yu-Ju Wei, Chih-Wen Wang, Po-Cheng Liang, Ming-Lun Yeh, Yi-Shan Tsai, Pei-Chien Tsai, Yu-Min Ko, Ching-Chih Lin, Kuan-Yu Chen, Yi-Hung Lin, Tyng-Yuan Jang, Ming-Yen Hsieh, Zu-Yau Lin, Chung-Feng Huang, Jee-Fu Huang, Chia-Yen Dai, Wan-Long Ch
    World Journal of Gastroenterology.2025;[Epub]     CrossRef
  • Validation of the diagnostic accuracy of the acFibroMASH index for at-risk MASH in patients with metabolic dysfunction-associated steatotic liver disease
    Yunfei Wu, Yan Han, Liming Zheng, Longgen Liu, Wenjian Li, Fan Zhang
    BMC Gastroenterology.2025;[Epub]     CrossRef
  • Diagnostic Value of Serum Cytokeratin 18 for the Staging of Liver Inflammation and Fibrosis: A Meta‐Analysis
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    Molecular Biomedicine.2025;[Epub]     CrossRef
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    Frontiers in Nutrition.2025;[Epub]     CrossRef
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  • Neither hepatic steatosis nor fibrosis is associated with clinical outcomes in patients with intestinal Behçet’s disease
    Hye Kyung Hyun, Jihye Park, Soo Jung Park, Jae Jun Park, Tae Il Kim, Jae Seung Lee, Hye Won Lee, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Seung Up Kim, Jae Hee Cheon
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  • Evolutive Models, Algorithms and Predictive Parameters for the Progression of Hepatic Steatosis
    Marinela Sînziana Tudor, Veronica Gheorman, Georgiana-Mihaela Simeanu, Adrian Dobrinescu, Vlad Pădureanu, Venera Cristina Dinescu, Mircea-Cătălin Forțofoiu
    Metabolites.2024; 14(4): 198.     CrossRef
  • Editorial: Inflammation and chronic disease
    Frank A. Orlando, Arch G. Mainous
    Frontiers in Medicine.2024;[Epub]     CrossRef
  • Advances in Noninvasive Molecular Imaging Probes for Liver Fibrosis Diagnosis
    Shaofang Chen, Danping Zhuang, Qingyun Jia, Bing Guo, Genwen Hu
    Biomaterials Research.2024;[Epub]     CrossRef
  • Serum Cytokeratin-18 levels as a prognostic biomarker in advanced liver disease: a comprehensive meta-analysis
    Xin Zhang, Jiangguo Li, Li Jiang, Yuexia Deng, Licheng Wei, Xing Li
    Clinical and Experimental Medicine.2024;[Epub]     CrossRef
  • The Metabolomic Footprint of Liver Fibrosis
    Diren Beyoğlu, Yury V. Popov, Jeffrey R. Idle
    Cells.2024; 13(16): 1333.     CrossRef
  • Machine learning based identification potential feature genes for prediction of drug efficacy in nonalcoholic steatohepatitis animal model
    Marwa Matboli, Ibrahim Abdelbaky, Abdelrahman Khaled, Radwa Khaled, Shaimaa Hamady, Laila M. Farid, Mariam B. Abouelkhair, Noha E. El-Attar, Mohamed Farag Fathallah, Manal S. Abd EL Hamid, Gena M. Elmakromy, Marwa Ali
    Lipids in Health and Disease.2024;[Epub]     CrossRef
  • Structure-function analysis of time-resolved immunological phases in metabolic dysfunction-associated fatty liver disease (MASH) comparing the NIF mouse model to human MASH
    Anja Schmidt-Christensen, Gustaw Eriksson, William M. Laprade, Behnaz Pirzamanbein, Maria Hörnberg, Kajsa Linde, Julia Nilsson, Mark Skarsfeldt, Diana J. Leeming, Rajmund Mokso, Mariana Verezhak, Anders Dahl, Vedrana Dahl, Kristina Önnerhag, Massoud Rezae
    Scientific Reports.2024;[Epub]     CrossRef
  • Polygala japonica Houtt.: A comprehensive review on its botany, traditional uses, phytochemistry, pharmacology, and pharmacokinetics
    Hai-Peng Tang, En-Lin Zhu, Qian-Xiang Bai, Shuang Wang, Zhi-Bin Wang, Meng Wang, Hai-Xue Kuang
    Fitoterapia.2024; 179: 106233.     CrossRef
  • Chondroitin Sulfate from Halaelurus burgeri Skin Inhibits Hepatic Endoplasmic Reticulum Stress and Inflammation, and Regulates Gut Microbiota
    Zhaocai Ren, Shang Gao, Shiwei Hu, Sichun Chen, Wei Jiang, Yaming Ge
    Molecular Nutrition & Food Research.2024;[Epub]     CrossRef
  • Serum Cytokeratin 18 Fragment Is an Indicator for Treating Metabolic Dysfunction-Associated Steatotic Liver Disease
    Miwa Kawanaka, Yoshihiro Kamada, Hirokazu Takahashi, Michihiro Iwaki, Ken Nishino, Wenli Zhao, Yuya Seko, Masato Yoneda, Yoshihito Kubotsu, Hideki Fujii, Yoshio Sumida, Hirofumi Kawamoto, Yoshito Itoh, Atsushi Nakajima, Takeshi Okanoue, Takumi Kawaguchi,
    Gastro Hep Advances.2024; 3(8): 1120.     CrossRef
  • Metabolomic Hallmarks of Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease
    Diren Beyoğlu, Yury V. Popov, Jeffrey R. Idle
    International Journal of Molecular Sciences.2024; 25(23): 12809.     CrossRef
  • MASLD: predictive value for liver-related events and extra-hepatic complications
    Mohamad Jamalinia, Amedeo Lonardo
    Expert Review of Gastroenterology & Hepatology.2024; 18(11): 685.     CrossRef
  • Baseline Tyrosine Level Is Associated with Dynamic Changes in FAST Score in NAFLD Patients under Lifestyle Modification
    Hwi Young Kim, Da Jung Kim, Hye Ah Lee, Joo-Youn Cho, Won Kim
    Metabolites.2023; 13(3): 444.     CrossRef
  • Prospective direct comparison of non‐invasive liver tests in outpatients with type 2 diabetes using intention‐to‐diagnose analysis
    Thierry Poynard, Olivier Deckmyn, Valentina Peta, Valérie Paradis, Jean‐Francois Gautier, Angélique Brzustowski, Pierre Bedossa, Laurent Castera, Stanislas Pol, Dominique Valla
    Alimentary Pharmacology & Therapeutics.2023; 58(9): 888.     CrossRef
  • 10,725 View
  • 341 Download
  • 28 Web of Science
  • Crossref

Editorial

Viral hepatitis

Moving toward hepatitis B virus functional cure - the impact of on-treatment kinetics of serum viral markers
Lilian Yan Liang, Vincent Wai-Sun Wong, Grace Lai-Hung Wong, Terry Cheuk-Fung Yip
Clin Mol Hepatol 2023;29(1):113-117.
Published online October 31, 2022
DOI: https://doi.org/10.3350/cmh.2022.0333

Citations

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  • Hepatocellular carcinoma surveillance after HBsAg seroclearance
    Jimmy Che-To Lai, Vicki Wing-Ki Hui, Grace Lai-Hung Wong, Vincent Wai-Sun Wong, Terry Cheuk-Fung Yip
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    Leeor Hershkovich, Louis Shekhtman, Michel Bazinet, Victor Pântea, Gheorge Placinta, Scott J. Cotler, Andrew Vaillant, Harel Dahari
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  • Correspondence on Editorial regarding “HBV pgRNA and HBcrAg reductions at week 4 predict favourable HBsAg response upon long-term nucleos(t)ide analogue in CHB”
    Lung-Yi Mak, Wai-Kay Seto, Man-Fung Yuen
    Clinical and Molecular Hepatology.2023; 29(1): 191.     CrossRef
  • Hepatitis B and Hepatitis D Viruses: A Comprehensive Update with an Immunological Focus
    Daniel G. Sausen, Oren Shechter, William Bietsch, Zhenzhen Shi, Samantha M. Miller, Elisa S. Gallo, Harel Dahari, Ronen Borenstein
    International Journal of Molecular Sciences.2022; 23(24): 15973.     CrossRef
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Original Articles

Liver fibrosis, cirrhosis, and portal hypertension

U-shaped relationship between urea level and hepatic decompensation in chronic liver diseases
Huapeng Lin, Grace Lai-Hung Wong, Xinrong Zhang, Terry Cheuk-Fung Yip, Ken Liu, Yee Kit Tse, Vicki Wing-Ki Hui, Jimmy Che-To Lai, Henry Lik-Yuen Chan, Vincent Wai-Sun Wong
Clin Mol Hepatol 2022;28(1):77-90.
Published online November 5, 2021
DOI: https://doi.org/10.3350/cmh.2021.0188
Background/Aims
We aimed to determine the association between blood urea level and incident cirrhosis, hepatic decompensation, and hepatocellular carcinoma in chronic liver disease (CLD) patients.
Methods
The association between blood urea level and liver fibrosis/liver-related events were evaluated on continuous scale with restricted cubic spline curves based on generalized additive model or Cox proportional hazards models. Then, the above associations were evaluated by urea level within intervals.
Results
Among 4,282 patients who had undergone liver stiffness measurement (LSM) by transient elastography, baseline urea level had a U-shaped association with LSM and hepatic decompensation development after a median follow-up of 5.5 years. Compared to patients with urea of 3.6–9.9 mmol/L, those with urea ≤3.5 mmol/L (adjusted hazard ratio [aHR], 4.15; 95% confidence interval [CI], 1.68–10.24) and ≥10 mmol/L (aHR, 5.22; 95% CI, 1.86–14.67) had higher risk of hepatic decompensation. Patients with urea ≤3.5 mmol/L also had higher risk of incident cirrhosis (aHR, 3.24; 95% CI, 1.50–6.98). The association between low urea level and incident cirrhosis and hepatic decompensation was consistently observed in subgroups by age, gender, albumin level, and comorbidities. The U-shaped relationship between urea level and LSM was validated in another population screening study (n=917). Likewise, urea ≤3.5 mmol/L was associated with a higher risk of incident cirrhosis in a territory-wide cohort of 12,476 patients with nonalcoholic fatty liver disease at a median follow-up of 9.9 years (aHR, 1.27; 95% CI, 1.03–1.57).
Conclusions
We identified a U-shaped relationship between the urea level and liver fibrosis/incident cirrhosis/hepatic decompensation in patients with CLD.

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Hepatic neoplasm

Serum fibrosis index-based risk score predicts hepatocellular carcinoma in untreated patients with chronic hepatitis B
Lilian Yan Liang, Hye Won Lee, Vincent Wai-Sun Wong, Terry Cheuk-Fung Yip, Yee-Kit Tse, Vicki Wing-Ki Hui, Grace Chung-Yan Lui, Henry Lik-Yuen Chan, Grace Lai-Hung Wong
Clin Mol Hepatol 2021;27(3):499-509.
Published online February 26, 2021
DOI: https://doi.org/10.3350/cmh.2020.0333
Background/Aims
Serum fibrosis scores comprised of common laboratory tests have high utility to assess severity of liver fibrosis. We aimed to derive and validate a hepatocellular carcinoma (HCC) risk score based on serum fibrosis scores to predict HCC in treatment-naïve chronic hepatitis B (CHB) patients.
Methods
Fifteen thousand one hundred eighty-seven treatment-naïve adult CHB patients were identified to form the training cohort in this retrospective study. Individual fibrosis score was included to construct a new HCC prediction score. The score was externally validated in an independent treatment-naïve Korean CHB cohort.
Results
180/15,187 patients (1.2%) in training cohort and 47/4,286 patients (1.1%) in validation cohort developed HCC during a mean follow-up of 52 and 50 months, respectively. The newly developed HCC risk score, Liang score, is composed of gender, age, hepatitis B virus DNA, fibrosis-4 (FIB-4) index, and ranges from 0 to 22. Area under the time-dependent receiver operating characteristic curve of Liang score was 0.79 (95% confidence interval, 0.70–0.89). A cutoff value of nine provided an extremely high negative predictive value of 99.9% and high sensitivity of 90.0% at 5 years in the validation cohort. Patients with Liang score ≤9 had HCC incidence <0.2% per year in both training and validation cohorts, in whom HCC surveillance might be exempted.
Conclusion
A novel HCC risk score, Liang score, based on FIB-4 index, is applicable and accurate to identify treatment-naïve CHB patients with very low risk of HCC to be exempted from HCC surveillance.

Citations

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Editorials

Negligible risk of hepatocellular carcinoma in chronic hepatitis B patients in immune-tolerant phase: Myth or fact
Terry Cheuk-Fung Yip, Grace Lai-Hung Wong, Vincent Wai-Sun Wong
Clin Mol Hepatol 2021;27(2):273-277.
Published online February 1, 2021
DOI: https://doi.org/10.3350/cmh.2021.0019

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Viral hepatitis

Drug-drug interactions with direct-acting antivirals — less is more
Grace Lai-Hung Wong
Clin Mol Hepatol 2021;27(1):81-82.
Published online December 3, 2020
DOI: https://doi.org/10.3350/cmh.2020.0278

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Reviews

Steatotic liver disease

Application of transient elastography in nonalcoholic fatty liver disease
Xinrong Zhang, Grace Lai-Hung Wong, Vincent Wai-Sun Wong
Clin Mol Hepatol 2020;26(2):128-141.
Published online November 8, 2019
DOI: https://doi.org/10.3350/cmh.2019.0001n
Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide. Although it has become one of the leading causes of cirrhosis and hepatocellular carcinoma in the Western world, the proportion of NAFLD patients developing these complications is rather small. Therefore, current guidelines recommend noninvasive tests for the initial assessment of NAFLD. Among the available non-invasive tests, transient elastography by FibroScan® (Echosens, Paris, France) is commonly used by hepatologists in Europe and Asia, and the machine has been introduced to the United States in 2013 with rapid adoption. Transient elastography measures liver stiffness and the controlled attenuation parameter simultaneously and can serve as a one-stop examination for both liver steatosis and fibrosis. Liver stiffness measurement also correlates with clinical outcomes and can be used to select patients for varices screening. Although obesity is a common reason for measurement failures, the development of the XL probe allows successful measurements in the majority of obese patients. This article reviews the performance and limitations of transient elastography in NAFLD and highlights its clinical applications. We also discuss the reliability criteria for transient elastography examination and factors associated with false-positive liver stiffness measurements.

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Viral hepatitis

Unmet need in chronic hepatitis B management
Lilian Yan Liang, Grace Lai-Hung Wong
Clin Mol Hepatol 2019;25(2):172-180.
Published online February 12, 2019
DOI: https://doi.org/10.3350/cmh.2018.0106
Despite all these exciting developments, there remain some unmet needs in the management for patients with chronic hepatitis B (CHB). As majority of CHB patients are going to use oral nucleos(t)ide analogues (NAs) for decades, Safety profile of NAs is of no doubt an important issue. The newest nucleotide analogue tenofovir alafenamide is potent in terms of viral suppression, together with favourable renal and bone safety profile. Biochemical response as reflected by alanine aminotransferase (ALT) normalization is recently found to be prognostically important. Patients who achieved ALT normalization have reduced the risk of hepatic events by 49%. Functional cure as reflected by hepatitis B surface antigen seroclearance not only implies patients may stop NA treatment, it also confers to a reduced risk of hepatocellular carcinoma and other hepatic events. Hence functional cure should be the ultimate treatment goal in CHB patients. Preemptive antiviral treatment may reduce mother-to-child transmission of hepatitis B virus, especially if birth dose of vaccination cannot be given in the first two hours after delivery. Lastly, despite the currently first-line NAs have high-genetic barrier to drug resistance mutations, there are still are many patients who were previously treated with low barrier of resistance including lamivudine, telbivudine or adefovir dipivoxil which could lead to antiviral resistance and affecting the choice of NAs.

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Viral hepatitis

Management of chronic hepatitis B patients in immunetolerant phase: what latest guidelines recommend
Grace Lai-Hung Wong
Clin Mol Hepatol 2018;24(2):108-113.
Published online January 22, 2018
DOI: https://doi.org/10.3350/cmh.2017.0068
The natural history of chronic hepatitis B (CHB) is complex and may run through different immune phases that may overlap. In particulars, the immune-tolerant phase is the most interesting and not as well understood as we thought. The concept of true immune tolerance have been under challenged from immunology points of view. The major international guidelines have not yet reached a consensus on the definition of the immune-tolerant phase. While positive hepatitis B e antigen (HBeAg), high serum hepatitis B virus (HBV) DNA and normal serum alanine aminotransferase (ALT) levels are the three key features of this phase, some guidelines also put age into consideration. A new nomenclature, Phase 1 or HBeAg-positive chronic HBV infection, is given by the latest European Association for the Study of the Liver (EASL) published in April 2017. While current guidelines advise against starting antiviral treatment for immune-tolerant CHB patients, some new data suggest treating such patients may reduce the risk of liver fibrosis progression and hepatocellular carcinoma.

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Liver fibrosis, cirrhosis, and portal hypertension

Personalized management of cirrhosis by non-invasive tests of liver fibrosis
Grace Lai-Hung Wong, Wendell Zaragoza Espinosa, Vicnent Wai-Sun Wong
Clin Mol Hepatol 2015;21(3):200-211.
Published online September 30, 2015
DOI: https://doi.org/10.3350/cmh.2015.21.3.200

Owing to the high prevalence of various chronic liver diseases, cirrhosis is one of the leading causes of morbidity and mortality worldwide. In recent years, the development of non-invasive tests of fibrosis allows accurate diagnosis of cirrhosis and reduces the need for liver biopsy. In this review, we discuss the application of these non-invasive tests beyond the diagnosis of cirrhosis. In particular, their role in the selection of patients for hepatocellular carcinoma surveillance and varices screening is highlighted.

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Viral hepatitis

Prediction of fibrosis progression in chronic viral hepatitis
Grace Lai-Hung Wong
Clin Mol Hepatol 2014;20(3):228-236.
Published online September 25, 2014
DOI: https://doi.org/10.3350/cmh.2014.20.3.228

Prediction of liver fibrosis progression has a key role in the management of chronic viral hepatitis, as it will be translated into the future risk of cirrhosis and its various complications including hepatocellular carcinoma. Both hepatitis B and C viruses mainly lead to fibrogenesis induced by chronic inflammation and a continuous wound healing response. At the same time direct and indirect profibrogenic responses are also elicited by the viral infection. There are a handful of well-established risk factors for fibrosis progression including older age, male gender, alcohol use, high viral load and co-infection with other viruses. Metabolic syndrome is an evolving risk factor of fibrosis progression. The new notion of regression of advanced fibrosis or even cirrhosis is now strongly supported various clinical studies. Even liver biopsy retains its important role in the assessment of fibrosis progression, various non-invasive assessments have been adopted widely because of their non-invasiveness, which facilitates serial applications in large cohorts of subjects. Transient elastography is one of the most validated tools which has both diagnostic and prognostic role. As there is no single perfect test for liver fibrosis assessment, algorithms combining the most validated noninvasive methods should be considered as initial screening tools.

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    Korean Journal of Radiology.2016; 17(5): 750.     CrossRef
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