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Shin H, Hur MH, Song BG, Park SY, Kim GA, Choi G, Nam JY, Kim MA, Park Y, Ko Y, Park J, Lee HA, Chung SW, Choi NR, Park MK, Lee YB, Sinn DH, Kim SU, Kim HY, Kim JM, Park SJ, Lee HC, Lee DH, Chung JW, Kim YJ, Yoon JH, Lee JH. AI model using CT-based imaging biomarkers to predict hepatocellular carcinoma in patients with chronic hepatitis B. J Hepatol 2025; 82:1080-1088. [PMID: 39710148 DOI: 10.1016/j.jhep.2024.12.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 11/12/2024] [Accepted: 12/07/2024] [Indexed: 12/24/2024]
Abstract
BACKGROUND & AIMS Various hepatocellular carcinoma (HCC) prediction models have been proposed for patients with chronic hepatitis B (CHB) using clinical variables. We aimed to develop an artificial intelligence (AI)-based HCC prediction model by incorporating imaging biomarkers derived from abdominal computed tomography (CT) images along with clinical variables. METHODS An AI prediction model employing a gradient-boosting machine algorithm was developed utilizing imaging biomarkers extracted by DeepFore, a deep learning-based CT auto-segmentation software. The derivation cohort (n = 5,585) was randomly divided into the training and internal validation sets at a 3:1 ratio. The external validation cohort included 2,883 patients. Six imaging biomarkers (i.e. abdominal visceral fat-total fat volume ratio, total fat-trunk volume ratio, spleen volume, liver volume, liver-spleen Hounsfield unit ratio, and muscle Hounsfield unit) and eight clinical variables were selected as the main variables of our model, PLAN-B-DF. RESULTS In the internal validation set (median follow-up duration = 7.4 years), PLAN-B-DF demonstrated an excellent predictive performance with a c-index of 0.91 and good calibration function (p = 0.78 by the Hosmer-Lemeshow test). In the external validation cohort (median follow-up duration = 4.6 years), PLAN-B-DF showed a significantly better discrimination function compared to previous models, including PLAN-B, PAGE-B, modified PAGE-B, and CU-HCC (c-index, 0.89 vs. 0.65-0.78; all p <0.001), and maintained a good calibration function (p = 0.42 by the Hosmer-Lemeshow test). When patients were classified into four groups according to the risk probability calculated by PLAN-B-DF, the 10-year cumulative HCC incidence was 0.0%, 0.4%, 16.0%, and 46.2% in the minimal-, low-, intermediate-, and high-risk groups, respectively. CONCLUSION This AI prediction model, integrating deep learning-based auto-segmentation of CT images, offers improved performance in predicting HCC risk among patients with CHB compared to previous models. IMPACT AND IMPLICATIONS The novel predictive model PLAN-B-DF, employing an automated computed tomography segmentation algorithm, significantly improves predictive accuracy and risk stratification for hepatocellular carcinoma in patients with chronic hepatitis B (CHB). Using a gradient-boosting algorithm and computed tomography metrics, such as visceral fat volume and myosteatosis, PLAN-B-DF outperforms previous models based solely on clinical and demographic data. This model not only shows a higher c-index compared to previous models, but also effectively classifies patients with CHB into different risk groups. This model uses machine learning to analyze the complex relationships among various risk factors contributing to hepatocellular carcinoma occurrence, thereby enabling more personalized surveillance for patients with CHB.
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Affiliation(s)
- Hyunjae Shin
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Gyeonggi-do, Korea
| | - Moon Haeng Hur
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Byeong Geun Song
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Gi-Ae Kim
- Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, Kyung Hee University Hospital, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Gwanghyeon Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Gyeonggi-do, Korea
| | | | - Minseok Albert Kim
- Department of Internal Medicine, ABC Hospital, Hwaseong, Gyeonggi-do, Korea
| | - Youngsu Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Yunmi Ko
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jeayeon Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea
| | - Sung Won Chung
- Division of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Na Ryung Choi
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | - Min Kyung Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Gyeonggi-do, Korea
| | - Yun Bin Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hwi Young Kim
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | | | - Sang Joon Park
- AI Center, MedicalIP. Co. Ltd., Seoul, Korea; Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Hyung-Chul Lee
- Department of Anesthesiology, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Ho Lee
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Jin Wook Chung
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea; Inocras Inc., San Diego, CA, USA.
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Li MP, Luo KZ. The outcomes and mechanisms of chronic hepatitis B complicated by metabolic dysfunction-associated steatotic liver disease. Hepatobiliary Pancreat Dis Int 2025:S1499-3872(25)00087-6. [PMID: 40355317 DOI: 10.1016/j.hbpd.2025.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Accepted: 04/24/2025] [Indexed: 05/14/2025]
Abstract
BACKGROUND In recent years, the rising prevalence of obesity and metabolic syndrome has led to an increased number of individuals developing metabolic dysfunction-associated steatotic liver disease (MASLD). Furthermore, given the substantial global prevalence of chronic hepatitis B (CHB), instances of MASLD coexisting with CHB are becoming increasingly commonplace in clinical scenarios. Both conditions can lead to liver fibrosis, cirrhosis, and potentially hepatocellular carcinoma (HCC). However, the intricacies of the dual etiology, consequential outcomes, and associated risks of CHB concurrent with MASLD are still not fully understood. DATA SOURCES A literature search was conducted on PubMed for articles published up to March 2024. The search keywords included nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, chronic hepatitis B, liver fibrosis, hepatocellular carcinoma, nuclear factor erythroid 2-related factor 2, and oxidative stress. RESULTS This review examined recent studies on the interplay between MASLD and CHB. The coexistence of these conditions may facilitate the clearance of hepatitis B surface antigen from the serum and impede hepatitis B virus (HBV) replication. Conversely, individuals with coexisting CHB tend to exhibit a lower rate of hypertriglyceridemia and reduced serum triglyceride levels compared with those only having NAFLD. Nevertheless, these observations do not necessarily indicate universally positive outcomes. Indeed, MASLD and CHB may synergistically act as "co-conspirators" to exacerbate clinical manifestations, particularly liver fibrosis and HCC. CONCLUSIONS As our understanding of the interaction between steatosis and HBV infection becomes clearer, we can better assess the risk of advanced liver disease in patients with concurrent CHB and MASLD. These insights will support the exploration of potential underlying mechanisms and may provide recommendations for improving patient outcomes.
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Affiliation(s)
- Mao-Ping Li
- Department of Infectious Diseases, the Second Xiangya Hospital of Central South University, Changsha 410011, China; Institute of Hepatology, Central South University, Changsha 410011, China; Furong Laboratory, Changsha 410078, China
| | - Kai-Zhong Luo
- Department of Infectious Diseases, the Second Xiangya Hospital of Central South University, Changsha 410011, China; Institute of Hepatology, Central South University, Changsha 410011, China; Furong Laboratory, Changsha 410078, China.
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Kwak M, Kim HS, Jiang ZG, Yeo YH, Trivedi HD, Noureddin M, Yang JD. MASLD/MetALD and mortality in individuals with any cardio-metabolic risk factor: A population-based study with 26.7 years of follow-up. Hepatology 2025; 81:228-237. [PMID: 38739848 DOI: 10.1097/hep.0000000000000925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 03/24/2024] [Indexed: 05/16/2024]
Abstract
BACKGROUND AND AIMS A new term, metabolic dysfunction-associated steatotic liver disease (MASLD), has been proposed by a multi-society expert panel. However, it remains unclear whether hepatic steatosis per se in MASLD contributes to an increased risk of mortality in individuals with any cardio-metabolic risk factor (CMRF), which is also a significant risk factor for increased mortality. This study aimed to compare all-cause and cause-specific mortality between the "MASLD/MetALD" and "no steatotic liver disease (SLD)" groups in individuals with any CMRF. APPROACH AND RESULTS A population-based cohort study was conducted using 10,750 participants of the Third National Health and Nutrition Examination Survey. All-cause and cause-specific (cardiovascular, cancer, diabetes, and liver) mortality risks were compared between the "MASLD," "MetALD," and "no SLD" groups using the Cox proportional hazards model with complex survey design weights, adjusted for confounders. Over 26 years, the "MASLD" group did not show significantly increased all-cause (adjusted HR 1.04[95% CI: 0.95-1.14], p = 0.413), cardiovascular (0.88 [0.75-1.04], p = 0.139), or cancer (1.06[0.84-1.33], p = 0.635) mortality risk compared to the "no SLD" group in individuals with any CMRF. The MetALD group was associated with increased all-cause (1.41 [1.05-1.89], p = 0.022), cancer (2.35 [1.33-4.16], p = 0.004), and liver (15.04 [2.96-76.35], p = 0.002) mortality risk compared with the no SLD group. This trend was more pronounced in the MetALD group with advanced fibrosis assessed by Fibrosis-4 (FIB-4). CONCLUSIONS In individuals with CMRF, the presence of steatotic liver disease (MASLD) alone did not increase the risk of mortality, except in cases with more alcohol consumption (MetALD). Therefore controlling metabolic risk factors and reducing alcohol consumption in people with MASLD or MetALD will be crucial steps to improve long-term health outcomes.
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Affiliation(s)
- Minsun Kwak
- Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hyun-Seok Kim
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Zhenghui Gordon Jiang
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Yee Hui Yeo
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Hirsh D Trivedi
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Mazen Noureddin
- Houston Methodist Hospital, Houston, Texas, USA
- Department of Houston Research Institute, Houston, Texas, USA
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
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Oh KK, Yoon SJ, Song SH, Park JH, Kim JS, Kim MJ, Kim DJ, Suk KT. The unfolded features on the synchronized fashion of gut microbiota and Drynaria rhizome against obesity via integrated pharmacology. Food Chem 2024; 460:140616. [PMID: 39094340 DOI: 10.1016/j.foodchem.2024.140616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 06/30/2024] [Accepted: 07/22/2024] [Indexed: 08/04/2024]
Abstract
Drynaria rhizome (DR) is used as a natural remedy to ameliorate obesity (OB) in East Asia; in parallel, the gut microbiota (GM) might exert a positive impact on OB through their metabolites. This study elucidates the orchestrated effects of DR and GM on OB. DR-GM, - a key signaling pathway-target-metabolite (DGSTM) networks were used to unveil the relationship between DR and GM, and Molecular Docking Test (MDT) and Density Functional Theory (DFT) were adopted to underpin the uppermost molecules. The NR1H3 (target) - 3-Epicycloeucalenol (ligand), and PPARG (target) - Clionasterol (ligand) conjugates from DR, FABP3 (target) - Ursodeoxycholic acid, FABP4 (target) - Lithocholic acid (ligand) or Deoxycholic acid (ligand), PPARA (target) - Equol (ligand), and PPARD (target) - 2,3-Bis(3,4-dihydroxybenzyl)butyrolactone (ligand) conjugates from GM formed the most stable conformers via MDT and DFT. Overall, these findings suggest that DR-GM might be a promising ameliorator on PPAR signaling pathway against OB.
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Affiliation(s)
- Ki-Kwang Oh
- Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.
| | - Sang-Jun Yoon
- Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea
| | - Seol Hee Song
- Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea
| | - Jeong Ha Park
- Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea
| | - Jeong Su Kim
- Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea
| | - Min Ju Kim
- Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea
| | - Dong Joon Kim
- Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea
| | - Ki-Tae Suk
- Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.
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Fiehn F, Beisel C, Binder M. Hepatitis C virus and hepatocellular carcinoma: carcinogenesis in the era of direct-acting antivirals. Curr Opin Virol 2024; 67:101423. [PMID: 38925094 DOI: 10.1016/j.coviro.2024.101423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 05/31/2024] [Accepted: 06/02/2024] [Indexed: 06/28/2024]
Abstract
Chronic hepatitis C virus (HCV) infection is a major cause of hepatic fibrosis and cirrhosis, with a risk for the development of hepatocellular carcinoma (HCC). Although highly effective direct-acting antivirals (DAAs) are available, the incidence, morbidity, and mortality of HCV-associated HCC are still high. This article reviews the current knowledge of the mechanisms of HCV-induced carcinogenesis with a special focus on those processes that continue after virus clearance and outlines implications for patient surveillance after DAA treatment.
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Affiliation(s)
- Felix Fiehn
- Research Group "Dynamics of Early Viral Infection and the Innate Antiviral Response", Division Virus-Associated Carcinogenesis (D430), German Cancer Research Center (DKFZ), Heidelberg, Germany; Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany
| | - Claudia Beisel
- Department of Internal Medicine IV, Gastroenterology and Infectious Diseases, University Hospital Heidelberg, Heidelberg, Germany; German Center for Infection Research (DZIF), Partner Site Heidelberg, Heidelberg, Germany
| | - Marco Binder
- Research Group "Dynamics of Early Viral Infection and the Innate Antiviral Response", Division Virus-Associated Carcinogenesis (D430), German Cancer Research Center (DKFZ), Heidelberg, Germany.
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Chen X, Fu L, Zhu Z, Wang Y. Exploring the link: magnesium intake and hepatic steatosis in Americans. Front Nutr 2024; 11:1367174. [PMID: 38846544 PMCID: PMC11153825 DOI: 10.3389/fnut.2024.1367174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 04/26/2024] [Indexed: 06/09/2024] Open
Abstract
Purpose The connection between magnesium and hepatic steatosis has not been well-studied. This study aimed to explore the link between magnesium intake and hepatic steatosis, utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020. Materials and methods The analysis included 5,935 participants, excluding individuals with hepatitis infection or substantial alcohol consumption. Magnesium intake assessment was based on 24-h dietary recalls. Hepatic steatosis evaluation employed the controlled attenuation parameter (CAP), measured via transient elastography. Multivariate regression and subgroup analyses were conducted to scrutinize the relationship between magnesium intake and CAP values. Results A higher magnesium intake was associated with lower CAP values, after adjusting for potential confounders. Subgroup analyses indicated an inverted U-shaped correlation between magnesium intake and CAP in women, White people, and non-hypertensive individuals, with respective inflection points at 126, 124.5, and 125 mg/day, respectively. Below these thresholds, a higher magnesium intake correlated with increased CAP values, while above these points, it was associated with decreased CAP. Conclusion This extensive population-based study indicates an inverse relationship between magnesium intake and hepatic steatosis in Americans. This relationship displays an inverted U-curve, varying before and after specified inflection points in women, White people, and non-hypertensive individuals. These findings offer insights into tailored magnesium supplementation strategies for preventing and treating liver steatosis, based on gender and ethnicity.
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Affiliation(s)
- Xingxing Chen
- Clinical Research Center, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, Zhejiang, China
| | - Liying Fu
- Voluntary Blood Donation Service Center of Xiaoshan District, Hangzhou, Zhejiang, China
| | - Zhongxin Zhu
- Clinical Research Center, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, Zhejiang, China
| | - Yunchao Wang
- Department of General Practice, The First People's Hospital of Xiaoshan District, Hangzhou, Zhejiang, China
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Kim KS, Hong S, Han K, Park CY. Association of non-alcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes mellitus: nationwide population based study. BMJ 2024; 384:e076388. [PMID: 38350680 PMCID: PMC10862140 DOI: 10.1136/bmj-2023-076388] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/02/2024] [Indexed: 02/15/2024]
Abstract
OBJECTIVE To investigate the risk of non-alcoholic fatty liver disease (NAFLD) for cardiovascular disease and all cause death in patients with type 2 diabetes mellitus (T2DM). DESIGN Nationwide population based study. SETTING Longitudinal cohort study in Korea. PARTICIPANTS 7 796 763 participants in the National Health Screening Programme in 2009 were divided into three groups based on NAFLD status: no NAFLD (fatty liver index<30); grade 1 NAFLD (30≤fatty liver index<60); and grade 2 NAFLD (fatty liver index≥60). Median follow-up was 8.13 years. MAIN OUTCOME MEASURES The primary outcome was incident cardiovascular disease (myocardial infarction, ischaemic stroke) or all cause death. RESULTS Of 7 796 763 participants, 6.49% (n=505 763) had T2DM. More patients with T2DM had grade 1 NAFLD (34.06%) and grade 2 NAFLD (26.73%) than those without T2DM (grade 1 NAFLD: 21.20%; grade 2 NAFLD: 10.02%). The incidence rate (per 1000 person years) of cardiovascular disease and all cause death increased in the order of no NAFLD, grade 1 NAFLD, and grade 2 NAFLD, and the incidence rates in patients with T2DM were higher than those in patients without T2DM. The five year absolute risk for cardiovascular disease and all cause death increased in the order of no NAFLD, grade 1 NAFLD, and grade 2 NAFLD in patients without and with T2DM (no NAFLD, without T2DM: 1.03, 95% confidence interval 1.02 to 1.04, and 1.25, 1.24 to 1.26, respectively; grade 1 NAFLD, without T2DM: 1.23, 1.22 to 1.25, and 1.50, 1.48 to 1.51, respectively; grade 2 NAFLD, without T2DM: 1.42, 1.40 to 1.45, and 2.09, 2.06 to 2.12, respectively; no NAFLD, with T2DM: 3.34, 3.27 to 3.41, and 3.68, 3.61 to 3.74, respectively; grade 1 NAFLD, with T2DM: 3.94, 3.87 to 4.02, and 4.25, 4.18 to 4.33, respectively; grade 2 NAFLD, with T2DM: 4.66, 4.54 to 4.78, and 5.91, 5.78 to 6.05, respectively). Patients with T2DM and without NAFLD had a higher five year absolute risk for cardiovascular disease and all cause death than those without T2DM and with grade 2 NAFLD. Risk differences for cardiovascular disease and all cause death between no NAFLD and grade 1 or grade 2 NAFLD were higher in patients with T2DM than in those without T2DM. CONCLUSIONS NAFLD in patients with T2DM seems to be associated with a higher risk of cardiovascular disease and all cause death, even in patients with mild NAFLD. Risk differences for cardiovascular disease and all cause death between the no NAFLD group and the grade 1 or grade 2 NAFLD groups were higher in patients with T2DM than in those without T2DM.
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Affiliation(s)
- Kyung-Soo Kim
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea
| | - Sangmo Hong
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Republic of Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Cheol-Young Park
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Lin CL, Kao JH. Precision Management of Patients with HBV Infection. CURRENT HEPATOLOGY REPORTS 2024; 23:22-31. [DOI: 10.1007/s11901-024-00632-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/02/2024] [Indexed: 01/03/2025]
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Ni W, Shi J, Li J. Epidemiology, natural history, and management of patients with CHB concurrent with MASLD. Clin Liver Dis (Hoboken) 2024; 23:e0171. [PMID: 38903875 PMCID: PMC11186830 DOI: 10.1097/cld.0000000000000171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Accepted: 03/06/2024] [Indexed: 06/22/2024] Open
Affiliation(s)
- Wenjing Ni
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Department of Infectious Disease, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Junping Shi
- Department of Infectious Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Jie Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Department of Infectious Disease, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
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Kountouras J, Kazakos E, Gatopoulou A, Polyzos SA, Touloumtzi M, Kyrailidi F, Mouratidou MC, Stogianni A, Vardaka E. Letter: Histological changes among asymptomatic chronic HBV carriers with normal alanine aminotransferase levels. Aliment Pharmacol Ther 2023; 58:1252-1253. [PMID: 37986592 DOI: 10.1111/apt.17760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2023]
Abstract
LINKED CONTENTThis article is linked to Li et al papers. To view these articles, visit https://doi.org/10.1111/apt.17718 and https://doi.org/10.1111/apt.17784
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Affiliation(s)
- Jannis Kountouras
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Evangelos Kazakos
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
- School of Healthcare Sciences, Midwifery Department, University of West Macedonia, Kozani, Macedonia, Greece
| | - Anthia Gatopoulou
- Second Department of Internal Medicine, General University Hospital of Alexandroupolis, Alexandroupolis, Greece
| | - Stergios A Polyzos
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Maria Touloumtzi
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Foteini Kyrailidi
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Maria C Mouratidou
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Aggeliki Stogianni
- Department of Radiology, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Elisabeth Vardaka
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
- Department of Nutritional Sciences and Dietetics, School of Health Sciences, International Hellenic University, Thessaloniki, Macedonia, Greece
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Kim BK, Ahn SH. Prediction model of hepatitis B virus-related hepatocellular carcinoma in patients receiving antiviral therapy. J Formos Med Assoc 2023; 122:1238-1246. [PMID: 37330305 DOI: 10.1016/j.jfma.2023.05.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 05/15/2023] [Accepted: 05/24/2023] [Indexed: 06/19/2023] Open
Abstract
Chronic hepatitis B virus (HBV) infection, which ultimately leads to liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC), remains a significant disease burden worldwide. Despite the use of antiviral therapy (AVT) using oral nucleos(t)ide analogs (NUCs) with high genetic barriers, the risk of HCC development cannot be completely eliminated. Therefore, bi-annual surveillance of HCC using abdominal ultrasonography with or without tumor markers is recommended for at-risk populations. For a more precise assessment of future HCC risk at the individual level, many HCC prediction models have been proposed in the era of potent AVT with promising results. It allows prognostication according to the risk of HCC development, for example, low-vs. intermediate-vs. high-risk groups. Most of these models have the advantage of high negative predictive values for HCC development, allowing exemption from biannual HCC screening. Recently, non-invasive surrogate markers for liver fibrosis, such as vibration-controlled transient elastography, have been introduced as integral components of the equations, providing better predictive performance in general. Furthermore, beyond the conventional statistical methods that primarily depend on multi-variable Cox regression analyses based on the previous literature, newer techniques using artificial intelligence have also been applied in the design of HCC prediction models. Here, we aimed to review the HCC risk prediction models that were developed in the era of potent AVT and validated among independent cohorts to address the clinical unmet needs, as well as comment on future direction to establish the individual HCC risk more precisely.
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Affiliation(s)
- Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea.
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12
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Nasr P, Jönsson C, Ekstedt M, Kechagias S. Non-metabolic causes of steatotic liver disease. METABOLISM AND TARGET ORGAN DAMAGE 2023; 3. [DOI: 10.20517/mtod.2023.20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Hepatic steatosis is caused by exaggerated hepatic lipid accumulation and is a common histological and radiological finding. Non-alcoholic fatty liver disease (NAFLD), or metabolic dysfunction associated steatotic liver disease (MASLD), is highly associated with metabolic syndrome and represents the most common cause of hepatic steatosis. However, since several comorbidities, lifestyle factors, and drugs can cause hepatic steatosis, MASLD is, to some extent, a diagnosis of exclusion. Nevertheless, initiatives have been taken to encompass positive (instead of negative) criteria for diagnosis - such as the presence of cardiometabolic risk factors together with hepatic steatosis. Nonetheless, before confirming a patient with MASLD, it is essential to map and evaluate other causes of fatty liver disease or steatotic liver disease. Several causes of hepatic steatosis have been identified in studies; however, the study cohorts are scarce and often anecdotal. Additionally, many studies have shown correlation without proving causation, and many are retrospective without reporting relevant patient characteristics and comorbidities - making it difficult to draw conclusions regarding the underlying etiology or present comorbidity of hepatic steatosis. In this narrative review, we aimed to identify and summarize present studies evaluating the impact of the most common and often suggested causes of hepatic steatosis.
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13
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Yoon EL, Jun DW. Waiting for the changes after the adoption of steatotic liver disease. Clin Mol Hepatol 2023; 29:844-850. [PMID: 37670441 PMCID: PMC10577335 DOI: 10.3350/cmh.2023.0291] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 08/30/2023] [Accepted: 09/04/2023] [Indexed: 09/07/2023] Open
Abstract
Steatotic liver disease was suggested as an overarching term encompassing various etiologies of hepatic steatosis. Experts from multinational liver societies went through the Delphi process, including four rounds of surveys, and consented to adopt a new nomenclature and definition instead of the conventional nonalcoholic fatty liver disease (NAFLD). This was to improve the understanding of the patients and primary care physicians, with an explanation of the pathophysiology in the name of the disease. Also, it could minimize the stigmatization of patients by using the histological neutral term "steatosis" instead of "fatty". Herein, we will discuss the changes and continuity between the two nomenclatures, metabolic dysfunction-associated steatotic liver disease (MASLD) and NAFLD, as well as the challenges to MASLD which need to be addressed in future.
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Affiliation(s)
- Eileen L. Yoon
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
- Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
- Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul, Korea
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14
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Song BG, Choi SC, Goh MJ, Kang W, Sinn DH, Gwak GY, Paik YH, Choi MS, Lee JH, Paik SW. Metabolic dysfunction-associated fatty liver disease and the risk of hepatocellular carcinoma. JHEP Rep 2023; 5:100810. [PMID: 37538246 PMCID: PMC10393797 DOI: 10.1016/j.jhepr.2023.100810] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 03/23/2023] [Accepted: 05/18/2023] [Indexed: 08/05/2023] Open
Abstract
Background & Aims The metabolic dysfunction-associated fatty liver disease (MAFLD) is a new inclusive term proposed to replace non-alcoholic fatty liver disease (NAFLD). We analysed whether hepatocellular carcinoma (HCC) risk differs by MAFLD or NAFLD status in a large sample of asymptomatic adults. Methods A cohort comprising 73,691 adults were followed up for the development of HCC. NAFLD was diagnosed among participants without other liver diseases (n = 65,992). Results Participants with MAFLD showed higher incidence of HCC than those without MAFLD (0.37 and 0.24 per 1,000 person-years, respectively; p = 0.006). However, MAFLD was not an independent factor associated with HCC in multivariable adjusted analysis (hazard ratio [HR] 1.21; 95% CI 0.92-1.60). When stratified according to presence of other liver diseases, MAFLD was not associated with HCC in participants with other liver diseases. In participants without other liver diseases, both MAFLD (adjusted HR 1.84; 95% CI 1.09-3.11) and NAFLD (adjusted HR 1.71; 95% CI 1.01-2.90) were independent factors associated with HCC. When stratified according to NAFLD and MAFLD status, there was no HCC development among participants with NAFLD only during 8,936 person-years of follow-up, but this NAFLD-only group comprised 3.4%, and the majority of participants with hepatic steatosis fulfilled both NAFLD and MAFLD criteria. Conclusions In patients with other chronic liver diseases, the presence of MAFLD is not independently associated with an increased risk of HCC. For those without other chronic liver diseases, MAFLD largely overlaps with NAFLD and is associated with an increased risk of HCC. Impact and Implications This study investigated the usefulness of newly proposed nomenclature, metabolic dysfunction-associated fatty liver disease (MAFLD), over non-alcoholic fatty liver disease (NAFLD), in terms of predicting hepatocellular carcinoma. In patients with other chronic liver diseases, the presence of MAFLD is not independently associated with an increased risk of HCC. However, for those without chronic liver disease, MAFLD largely overlaps with NAFLD and is associated with an increased risk of HCC.
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Affiliation(s)
- Byeong Geun Song
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sung Chul Choi
- Center for Health Promotion, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea
| | - Myung Ji Goh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Wonseok Kang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Yong-Han Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Moon Seok Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Joon Hyeok Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Seung Woon Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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15
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Martín-Escolano R, Virseda-Berdices A, Berenguer J, González-García J, Brochado-Kith O, Fernández-Rodríguez A, Díez C, Hontañon V, Resino S, Jiménez-Sousa MÁ. Predictive plasma biomarkers of long-term increase in hepatic steatosis index after HCV eradication in HIV/HCV-coinfected patients. Biomed Pharmacother 2023; 164:114913. [PMID: 37216704 DOI: 10.1016/j.biopha.2023.114913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 05/17/2023] [Accepted: 05/18/2023] [Indexed: 05/24/2023] Open
Abstract
Hepatic steatosis is a common condition found in the liver of hepatitis C virus (HCV)-infected patients, contributing to more severe forms of liver disease. In addition, the human immunodeficiency virus (HIV) may accelerate this process. Alternatively, several immune checkpoint proteins have been reported to be upregulated and correlated with disease progression during HCV and HIV infections. In steatosis, a detrimental immune system activation has been established; however, the role of the immune checkpoints has not been addressed so far. Thus, this study aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before antiviral therapy) with hepatic steatosis index (HSI) increase at the end of follow-up (∼ five years after sustained virologic response (SVR)). We performed a multicenter retrospective study in 62 patients coinfected with HIV/HCV who started antiviral therapy. Immune checkpoint proteins were analyzed at baseline using a Luminex 200TM analyzer. The statistical association analysis was carried out using Generalized Linear Models (GLM) and Partial Least Squares Discriminant Analysis (PLS-DA). Fifty-three percent of the patients showed HSI increase from baseline to the end of follow-up. Higher immune checkpoint protein levels of BTLA, CD137(4-1BB), CD80, GITR, LAG-3, and PD-L1 before HCV therapy were associated with a long-term increase in HSI after successful HCV therapy, suggesting a potential predictive role for early detection of progression towards steatosis in HIV/HCV-coinfected patients.
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Affiliation(s)
- Rubén Martín-Escolano
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain
| | - Ana Virseda-Berdices
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain; Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Juan Berenguer
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Unidad de Enfermedades Infecciosas/VIH; Hospital General Universitario "Gregorio Marañón", Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Juan González-García
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Servicio de Medicina Interna-Unidad de VIH. Hospital Universitario La Paz. Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPAZ). Madrid, Spain
| | - Oscar Brochado-Kith
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain; Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Amanda Fernández-Rodríguez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain; Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Cristina Díez
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Unidad de Enfermedades Infecciosas/VIH; Hospital General Universitario "Gregorio Marañón", Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Victor Hontañon
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Servicio de Medicina Interna-Unidad de VIH. Hospital Universitario La Paz. Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPAZ). Madrid, Spain
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain; Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
| | - María Ángeles Jiménez-Sousa
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain; Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
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16
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Guarnizo-Ortiz M, Vilar-Gomez E. Editorial: first-degree relatives of Mexican Americans with HCC are at increased risk of significant fibrosis. Aliment Pharmacol Ther 2023; 57:1036-1037. [PMID: 37053484 DOI: 10.1111/apt.17447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/15/2023]
Affiliation(s)
- Maria Guarnizo-Ortiz
- Department of Internal Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Eduardo Vilar-Gomez
- Department of Internal Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
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17
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Han CL, Tian BW, Yang CC, Yang YF, Ma YL, Ding ZN, Yan LJ, Liu H, Dong ZR, Chen ZQ, Hong JG, Wang DX, Li T. The association of fatty liver and risk of hepatocellular carcinoma in HBV or HCV infected individuals: a systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol 2023; 17:189-198. [PMID: 36625022 DOI: 10.1080/17474124.2023.2166930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND Fatty liver (FL) is reportedly a risk factor for hepatocellular carcinoma (HCC) in individuals affected with Hepatitis C (HCV) or B (HBV) virus. However, the results are contradictory, necessitating a meta-analysis. RESEARCH DESIGN AND METHODS Sixteen relevant studies involving 88,618 individuals were retrieved from the Cochrane Library, PubMed, MEDLINE, Embase, and Scopus databases from their inception to 10 December 2022. The hazard ratios (HR) and 95% confidence intervals (CI) were analyzed. RESULTS Liver biopsy-proven FL may be a significant risk factor for HCC in individuals affected with HBV (univariate analyses: HR = 3.13, 95% CI = 1.69-5.79; multivariate analyses: HR = 3.42, 95% CI = 0.83-14.09) as well as HCV (univariate analyses: HR = 1.64, 95% CI = 0.93-2.90; multivariate analyses: HR = 1.75, 95% CI = 1.02-3.00). However, the presence of FL confirmed using reasonable methods other than liver biopsy may not indicate a risk for HCC in HBV-infected individuals (univariate analyses: HR = 0.90, 95% CI = 0.44-1.81; multivariate analyses: HR = 0.69, 95% CI = 0.45-1.08). CONCLUSIONS Biopsy-proven FL may be a significant risk factor for HCC in HCV/HBV-infected individuals. Thus, such individuals should receive suitable interventions to prevent HCC formation or at least attenuate the risk of HCC.
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Affiliation(s)
- Cheng-Long Han
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Bao-Wen Tian
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Chun-Cheng Yang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Ya-Fei Yang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Yun-Long Ma
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zi-Niu Ding
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Lun-Jie Yan
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Hui Liu
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zhao-Ru Dong
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zhi-Qiang Chen
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Jian-Guo Hong
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Dong-Xu Wang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Tao Li
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China.,Department of Hepatobiliary Surgery, the Second Hospital of Shandong University, Jinan, P.R. China
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18
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Tan Y, Wang J. Letter: ductular reaction is a risk factor for prognosis of chronic hepatitis B complicated with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2023; 57:446-447. [PMID: 36710539 DOI: 10.1111/apt.17383] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 12/29/2022] [Accepted: 12/29/2022] [Indexed: 01/31/2023]
Affiliation(s)
- Youwen Tan
- Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang, China
| | - Jiaming Wang
- Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang, China
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19
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Muthiah M, Ng CH, Chan KE, Fu CE, Lim WH, Tan DJH, Nah B, Kong G, Xiao J, Yong JN, Tan B, Syn N, Wang JW, Sayed N, Tan E, Chew NW, Dan YY, Siddiqui MS, Sanyal AJ, Noureddin M. Type 2 diabetes mellitus in metabolic-associated fatty liver disease vs. type 2 diabetes mellitus non-alcoholic fatty liver disease: a longitudinal cohort analysis. Ann Hepatol 2023; 28:100762. [PMID: 36182031 DOI: 10.1016/j.aohep.2022.100762] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Revised: 08/30/2022] [Accepted: 09/10/2022] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Type 2 Diabetes Mellitus (T2DM) is comorbidity commonly presenting with fatty liver. A recently proposed definition of "metabolic associated fatty liver disease" (MAFLD) is thought to replace non-alcoholic fatty liver disease (NAFLD). Yet, despite the significant prevalence of T2DM among fatty liver, there remains limited evidence on the impact of the change in the definition of T2DM. MATERIALS AND METHODS The current study uses data from the United States National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Survival analysis was conducted with a cox regression and sub-distribution hazard ratio for competing risk events. RESULTS 6727 patients had a diagnosis of T2DM. 4982 individuals with T2DM had MAFLD and 2032 were MAFLD(+)/NAFLD(-), while 2950 patients were MAFLD(+)/NAFLD(+). The new definition increased fatty liver diagnosis by 68.89%. Patients who were classified as MAFLD(+)/NAFLD(-) were at a higher risk of major adverse cardiovascular events, advanced fibrosis, all-cause and cardiovascular-related mortality compared to MAFLD(+)/NAFLD(+). In MAFLD(+)/NAFLD(-), viral hepatitis significantly increases the odds of advanced fibrosis (OR: 6.77, CI: 3.92 to 11.7, p < 0.001) and all-cause mortality (HR: 1.75, CI: 1.29 to 2.40, p < 0.001). CONCLUSIONS The identification and treatment of NAFLD in patients with T2DM is a major concern and the premature change to MAFLD results in an over-diagnosis of fatty liver, exaggerated mortality, and morbidity in patients with T2DM. The definition of MAFLD causes further heterogeneity in fatty liver disease/NAFLD.
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Affiliation(s)
- Mark Muthiah
- MBBS Programme, Yong Loo Lin School of Medicine, National University of Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Cheng Han Ng
- MBBS Programme, Yong Loo Lin School of Medicine, National University of Singapore.
| | - Kai En Chan
- MBBS Programme, Yong Loo Lin School of Medicine, National University of Singapore
| | - Clarissa Elysia Fu
- MBBS Programme, Yong Loo Lin School of Medicine, National University of Singapore
| | - Wen Hui Lim
- MBBS Programme, Yong Loo Lin School of Medicine, National University of Singapore
| | - Darren Jun Hao Tan
- MBBS Programme, Yong Loo Lin School of Medicine, National University of Singapore
| | - Benjamin Nah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Gwyneth Kong
- MBBS Programme, Yong Loo Lin School of Medicine, National University of Singapore
| | - Jieling Xiao
- MBBS Programme, Yong Loo Lin School of Medicine, National University of Singapore
| | - Jie Ning Yong
- MBBS Programme, Yong Loo Lin School of Medicine, National University of Singapore
| | - Bryan Tan
- MBBS Programme, Yong Loo Lin School of Medicine, National University of Singapore
| | - Nicholas Syn
- MBBS Programme, Yong Loo Lin School of Medicine, National University of Singapore
| | - Jiong-Wei Wang
- Department of Surgery, Cardiovascular Research Institute (CVRI), National University Heart Centre Singapore; Nanomedicine Translational Research Programme, Centre for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Nilofer Sayed
- Department of Surgery, Cardiovascular Research Institute (CVRI), National University Heart Centre Singapore; Nanomedicine Translational Research Programme, Centre for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Eunice Tan
- MBBS Programme, Yong Loo Lin School of Medicine, National University of Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Nicholas Ws Chew
- MBBS Programme, Yong Loo Lin School of Medicine, National University of Singapore; Department of Cardiology, National University Heart Centre, National University Hospital, Singapore
| | - Yock Young Dan
- MBBS Programme, Yong Loo Lin School of Medicine, National University of Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia
| | - Arun J Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia
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20
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Ayonrinde O, Goodheart R. Editorial: chronic hepatitis C with metabolic dysfunction-associated fatty liver disease - a model for adoption of Sustainable Development Goal 3. Aliment Pharmacol Ther 2023; 57:270-271. [PMID: 36468204 DOI: 10.1111/apt.17270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Oyekoya Ayonrinde
- Department of Gastro and Hepatology, Fiona Stanley Hospital, Muroch, Western Australia, Australia
| | - Richard Goodheart
- Department of Gastro and Hepatology, Fiona Stanley Hospital, Muroch, Western Australia, Australia
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21
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Lee JS, Lim TS, Lee HW, Kim SU, Park JY, Kim DY, Ahn SH, Lee HW, Lee JI, Kim JK, Min IK, Kim BK. Suboptimal Performance of Hepatocellular Carcinoma Prediction Models in Patients with Hepatitis B Virus-Related Cirrhosis. Diagnostics (Basel) 2022; 13:3. [PMID: 36611295 PMCID: PMC9818663 DOI: 10.3390/diagnostics13010003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 12/14/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022] Open
Abstract
This study aimed to evaluate the predictive performance of pre-existing well-validated hepatocellular carcinoma (HCC) prediction models, established in patients with HBV-related cirrhosis who started potent antiviral therapy (AVT). We retrospectively reviewed the cases of 1339 treatment-naïve patients with HBV-related cirrhosis who started AVT (median period, 56.8 months). The scores of the pre-existing HCC risk prediction models were calculated at the time of AVT initiation. HCC developed in 211 patients (15.1%), and the cumulative probability of HCC development at 5 years was 14.6%. Multivariate Cox regression analysis revealed that older age (adjusted hazard ratio [aHR], 1.023), lower platelet count (aHR, 0.997), lower serum albumin level (aHR, 0.578), and greater LS value (aHR, 1.012) were associated with HCC development. Harrell’s c-indices of the PAGE-B, modified PAGE-B, modified REACH-B, CAMD, aMAP, HCC-RESCUE, AASL-HCC, Toronto HCC Risk Index, PLAN-B, APA-B, CAGE-B, and SAGE-B models were suboptimal in patients with HBV-related cirrhosis, ranging from 0.565 to 0.667. Nevertheless, almost all patients were well stratified into low-, intermediate-, or high-risk groups according to each model (all log-rank p < 0.05), except for HCC-RESCUE (p = 0.080). Since all low-risk patients had cirrhosis at baseline, they had unneglectable cumulative incidence of HCC development (5-year incidence, 4.9−7.5%). Pre-existing risk prediction models for patients with chronic hepatitis B showed suboptimal predictive performances for the assessment of HCC development in patients with HBV-related cirrhosis.
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Affiliation(s)
- Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Tae Seop Lim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Division of Gastroenterology, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University Health System, Gyeonggi-do, Seoul 03722, Republic of Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Hyun Woong Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University Health System, Seoul 06273, Republic of Korea
| | - Jung Il Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University Health System, Seoul 06273, Republic of Korea
| | - Ja Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Division of Gastroenterology, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University Health System, Gyeonggi-do, Seoul 03722, Republic of Korea
| | - In Kyung Min
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
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22
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Yun B, Ahn SH, Oh J, Yoon JH, Kim BK. Effect of metabolic dysfunction-associated fatty liver disease on liver cancer risk in a population with chronic hepatitis B virus infection: A nationwide study. Hepatol Res 2022; 52:975-984. [PMID: 35976670 DOI: 10.1111/hepr.13830] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 07/28/2022] [Accepted: 08/16/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND The association between metabolic dysfunction-associated fatty liver disease (MAFLD) and hepatocellular carcinoma (HCC) lacks clinical validation in at-risk populations. We assessed this relationship among chronic hepatitis B (CHB) patients. METHODS Data was collected from the National Health Insurance System database in South Korea. Chronic hepatitis B patients aged over 40 years receiving health examinations between 2011 and 2012 were recruited. The primary outcome was HCC. Metabolic dysfunction-associated fatty liver disease was defined as hepatic steatosis in combination with at least one of the following: (i) overweight, (ii) diabetes, or (iii) lean/normal weight with two or more metabolic components. Multivariable Cox regression analysis was used to estimate adjusted hazard ratios (aHRs). RESULTS Of 197 346 participants, 66 149 had MAFLD; 19 149, 44 475, and 2525 fulfilled diabetes (regardless of overweight), overweight alone, and lean/normal weight with two or more metabolic components, respectively. During follow-up (median 7 years), 13 771 developed HCC. Metabolic dysfunction-associated fatty liver disease was independently associated with increased risk of HCC, with aHR of 1.36 (p < 0.001). Propensity score matching confirmed the same phenomena, with aHR of 1.37 (p < 0.001). Furthermore, when stratified by liver cirrhosis and/or antiviral therapy, independent significances of MAFLD for HCC risk were maintained (all p < 0.001). Compared with the persistent non-MAFLD subgroup during the entire follow-up, diagnosis of MAFLD from at least one health examination significantly increased HCC risk with aHRs of 1.41, 1.37, and 1.14 among subgroups with persistent MAFLD, MAFLD to non-MAFLD, and non-MAFLD to MAFLD, respectively (all p < 0.05). CONCLUSIONS Metabolic dysfunction-associated fatty liver disease consistently increases HCC risk among CHB patients. Further studies are needed to develop an effective preventive strategy through control of metabolic health.
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Affiliation(s)
- Byungyoon Yun
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
| | - Juyeon Oh
- Department of Public Health, Graduate School, Yonsei University, Seoul, Korea
| | - Jin-Ha Yoon
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea.,Department of Occupational Health, Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
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23
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Yun B, Ahn SH, Oh J, Yoon JH, Kim BK. Prognostic Impact of MAFLD Following Surgical Resection of Hepatitis B Virus-Related Hepatocellular Carcinoma: A Nationwide Cohort Study. Cancers (Basel) 2022; 14:5002. [PMID: 36291786 PMCID: PMC9599346 DOI: 10.3390/cancers14205002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 10/12/2022] [Accepted: 10/12/2022] [Indexed: 11/16/2022] Open
Abstract
The association between the metabolic effects of hepatic steatosis as a part of postoperative outcomes of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) has rarely been studied. This study aimed to assess the relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and patients’ prognoses following curative resection of HBV-related HCC. Patients who underwent surgical resection for HBV-related HCC between 2009 and 2015 were recruited. The study endpoints were postoperative hepatocellular carcinoma (HCC) recurrence and all-cause mortality. Adjusted hazard ratios (aHRs) for the outcomes were estimated using multivariate Cox regression models. The mean age of the 2032 enrolled patients was 55.0 years, and 77.9% were men. During follow-up (median 5.3 years), HCC recurrence and all-cause mortality occurred in 954 (47.0%) and 422 (20.8%) patients, respectively. HCC recurrence and all-cause mortality were significantly associated with MAFLD, with aHRs of 1.22 (p = 0.003) and 1.44 (p < 0.001), respectively. Propensity score matching and inverse probability treatment weighting analyses confirmed similar results (p < 0.05). MAFLD was associated with significantly poor prognoses in terms of HCC recurrence and all-cause mortality following surgical resection of HBV-related HCC. Further studies are needed to develop an effective preventive strategy through the management of metabolic health.
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Affiliation(s)
- Byungyoon Yun
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Centre, Severance Hospital, Yonsei University Health System, Seoul 03722, Korea
| | - Juyeon Oh
- Department of Public Health, Yonsei University Graduate School, Seoul 03722, Korea
| | - Jin-Ha Yoon
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
- The Institute for Occupational Health, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Centre, Severance Hospital, Yonsei University Health System, Seoul 03722, Korea
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24
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Ng CH, Huang DQ, Nguyen MH. Nonalcoholic fatty liver disease versus metabolic-associated fatty liver disease: Prevalence, outcomes and implications of a change in name. Clin Mol Hepatol 2022; 28:790-801. [PMID: 35545437 PMCID: PMC9597238 DOI: 10.3350/cmh.2022.0070] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Accepted: 05/10/2022] [Indexed: 01/05/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) affects about a third of the world's adult population and is a major public health concern. NAFLD is defined by the presence of hepatic steatosis and the absence of other causes of liver disease. As NAFLD is closely associated with the presence of the metabolic syndrome, several experts have called for a change in nomenclature from NAFLD to metabolic-associated fatty liver disease (MAFLD) to better reflect the underlying pathophysiology of NAFLD as a metabolically driven disease and shift to a "positive" diagnostic criteria rather than one of exclusion. Recent studies have suggested that the global prevalence of MAFLD is higher than that of NAFLD, and patients with MAFLD have more metabolic comorbidities compared to those with NAFLD. Emerging data also suggest that all-cause and cardiovascular mortality may be higher in MAFLD compared with NAFLD. In this synopsis, we discuss differences in clinical features, prevalence and clinical outcomes between NAFLD and MAFLD. In addition, we highlight the advantages and disadvantages of a name change from NAFLD to MAFLD from the perspective of the scientific community, care providers and patients.
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Affiliation(s)
- Cheng Han Ng
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Daniel Q. Huang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore,Division of Gastroenterology and Hepatology, National University Health System, Singapore
| | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA,Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA,Corresponding author : Mindie H. Nguyen Division of Gastroenterology and Hepatology, Stanford University Medical Center, 780 Welch Road, Palo Alto, CA 94304, USA Tel: +1-650-498-6081, Fax: +1-650-721-8710, E-mail:
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25
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Response to Liao et al. Am J Gastroenterol 2022; 117:1718. [PMID: 36194050 DOI: 10.14309/ajg.0000000000001908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 07/11/2022] [Indexed: 12/11/2022]
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26
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Mao X, Cheung KS, Peng C, Mak LY, Cheng HM, Fung J, Peleg N, Leung HHW, Kumar R, Lee JH, Shlomai A, Yuen MF, Seto WK. Steatosis, HBV-related HCC, cirrhosis, and HBsAg seroclearance: A systematic review and meta-analysis. Hepatology 2022; 77:1735-1745. [PMID: 36111362 DOI: 10.1002/hep.32792] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 08/22/2022] [Accepted: 09/13/2022] [Indexed: 01/05/2023]
Abstract
BACKGROUND AND AIMS NAFLD and chronic hepatitis B (CHB) infection are common etiologies of HCC. The impact of hepatic steatosis on HCC in CHB, as well as its relationship with the development of cirrhosis, fibrosis, and HBsAg seroclearance, remains controversial. APPROACH AND RESULTS Data from observational studies were collected through PubMed, EMBASE, and the Cochrane Library from inception to February 1, 2022. Outcomes of interest included the association of hepatic steatosis with HCC, cirrhosis, advanced fibrosis, and HBsAg seroclearance, expressed in terms of pooled ORs. Additional subgroup and sensitivity analyses were performed to validate the robustness of findings. A total of 34 studies with 68,268 patients with CHB were included. Hepatic steatosis was associated with higher odds of HCC (OR, 1.59; 95% CI, 1.12-2.26; I2 = 72.5%), with the association remaining consistent in Asia (OR, 1.56; 95% CI, 1.08-2.25), studies with a median follow-up duration of ≥5 years (OR, 2.82; 95% CI, 1.57-5.08), exclusion of alcohol use (OR, 1.71; 95% CI, 1.01-2.91), and biopsy-proven steatosis (OR, 2.86; 95% CI, 1.61-5.06), although no significant association was noted among nucleos(t)ide analogue-treated patients (OR, 1.05; 95% CI, 0.62-1.77). Steatosis was associated with the development of cirrhosis (OR, 1.52; 95% CI, 1.07-2.16; I2 = 0%) and HBsAg seroclearance (OR, 2.22; 95% CI, 1.58-3.10; I2 = 49.0%). CONCLUSIONS Hepatic steatosis was associated with an increased risk of HCC and cirrhosis among patients with CHB but with a higher chance of achieving a functional cure, highlighting the importance of identifying concomitant steatosis in CHB.
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Affiliation(s)
- Xianhua Mao
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong
| | - Ka Shing Cheung
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong.,Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Chengzhi Peng
- Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Lung-Yi Mak
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong.,State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong
| | - Ho Ming Cheng
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong
| | - James Fung
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong.,State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong
| | - Noam Peleg
- Division of Gastroenterology, Rabin Medical Center, Petach Tikva, Israel.,Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Howard H-W Leung
- Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong
| | - Rajneesh Kumar
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore.,Duke-NUS Graduate Medical School, Singapore
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Amir Shlomai
- Department of Medicine D and The Liver Institute, Rabin Medical Center, Beilinson Hospital, Petah-Tikva and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Man-Fung Yuen
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong.,State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong
| | - Wai-Kay Seto
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong.,Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.,State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong
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27
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Xue J, Wang QX, Xiao HM, Shi MJ, Xie YB, Li S, Lin M, Chi XL. Impact of Metabolic Dysfunction Associated Fatty Liver Disease on the Prognosis of Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma Based on Propensity Score Matching Analysis. Cancer Manag Res 2022; 14:2193-2202. [PMID: 35859711 PMCID: PMC9293246 DOI: 10.2147/cmar.s368366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 06/25/2022] [Indexed: 11/23/2022] Open
Abstract
Purpose Both metabolic dysfunction-associated fatty liver disease (MAFLD) and hepatitis B virus (HBV) are risk factors for hepatocellular carcinoma (HCC). Although concurrent MAFLD is common in patients with HBV-related HCC, whether MAFLD increases the risk of poor prognosis in patients with HBV-related HCC remains unclear. This study aimed to investigate the impact of MAFLD on prognosis in patients with HBV-related HCC. Patients and Methods In this retrospective cohort study, 549 patients with HBV-related HCC were enrolled from January 2010 to April 2020 in Guangdong Provincial Hospital of Chinese Medicine, including 169 patients with MAFLD (MAFLD group) and 380 patients without MAFLD (Non-MAFLD group). Propensity score matching (PSM) analysis was performed to balance the baseline characteristics. Kaplan–Meier survival curves were performed to compare the prognosis between the two matched groups. A multivariate Cox proportional hazards model was used to determine the risk factors for poor prognosis. Results The median follow-up time for all patients was 20 (interquartile range 8–40) months. We found concurrent MAFLD was associated with a significantly decreased PFS rate before and after PSM analysis. The 1-year, 2-year, and 3-year PFS rates for the MAFLD and Non-MAFLD groups after PSM were 61.3% and 70.8%, 43.9% and 54.5%, 31.1% and 41.8%, respectively. Cox multivariable analysis showed that concurrent MAFLD was an independent risk factor for poor prognosis (death or progression) (HR = 1.49, P = 0.001). More interestingly, the risk of poor prognosis was significantly higher in the MAFLD subtype with metabolic components ≥2 compared to those with metabolic components <2 (HR = 1.97, P < 0.001). Conclusion Concurrent MAFLD was associated with a higher risk of poor prognosis in patients with HBV-related HCC, especially MAFLD with metabolic components ≥2.
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Affiliation(s)
- Jiao Xue
- The Second School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People's Republic of China
| | - Qing-Xia Wang
- The Second School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People's Republic of China
| | - Huan-Ming Xiao
- Department of Hepatology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, People's Republic of China
| | - Mei-Jie Shi
- Department of Hepatology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, People's Republic of China
| | - Yu-Bao Xie
- Department of Hepatology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, People's Republic of China
| | - Sheng Li
- Department of Hepatology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, People's Republic of China
| | - Ming Lin
- Department of Hepatology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, People's Republic of China
| | - Xiao-Ling Chi
- Department of Hepatology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, People's Republic of China
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28
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Clinical impact and mechanisms of hepatitis B virus infection concurrent with non-alcoholic fatty liver disease. Chin Med J (Engl) 2022; 135:1653-1663. [PMID: 35940901 PMCID: PMC9509100 DOI: 10.1097/cm9.0000000000002310] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
ABSTRACT Chronic hepatitis B (CHB) virus infection is an important threat to global health despite the administration of vaccines and the use of antiviral treatments. In recent years, as the prevalence of obesity and metabolic syndrome has increased, non-alcoholic fatty liver disease (NAFLD) in patients with CHB has become more common. Both diseases can lead to liver fibrosis and even hepatocellular carcinoma, but the risk of dual etiology, outcome, and CHB combined with NAFLD is not fully elucidated. In this review, we assess the overlapping prevalence of NAFLD and CHB, summarize recent studies of clinical and basic research related to potential interactions, and evaluate the progressive changes of treatments for CHB patients with NAFLD. This review increases the understanding of the relationship and mechanisms of interaction between steatosis and hepatitis B virus infection, and it provides new strategies for the future clinical management and treatment of CHB combined with NAFLD.
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29
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Wang J, Pillai AA. Editorial: concurrent fatty liver and chronic viral hepatitis: a dual calamity leading to increased risk of hepatocellular carcinoma? Aliment Pharmacol Ther 2022; 55:479-480. [PMID: 35092049 DOI: 10.1111/apt.16732] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- Jennifer Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Anjana A Pillai
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Chicago Medicine, Chicago, IL, USA
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30
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Kim MN, Ahn SH. Editorial: concurrent fatty liver and chronic viral hepatitis: a dual calamity leading to increased risk of hepatocellular carcinoma? Authors' reply. Aliment Pharmacol Ther 2022; 55:481-482. [PMID: 35092057 DOI: 10.1111/apt.16765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Accepted: 12/28/2021] [Indexed: 12/09/2022]
Affiliation(s)
- Mi Na Kim
- Division of Gastroenterology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
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