Reference Citation Analysis: Find an Article, Find a Category, Find a Journal, Find a Scholar

For: Tseng TC, Liu CJ, Su TH, Yang WT, Chen CL, Yang HC, Wang CC, Kuo SFT, Liu CH, Chen PJ, Chen DS, Kao JH. Fibrosis-4 Index Helps Identify HBV Carriers With the Lowest Risk of Hepatocellular Carcinoma. Am J Gastroenterol 2017;112:1564-1574. [PMID: 28853728 DOI: 10.1038/ajg.2017.254] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 07/14/2017] [Indexed: 12/11/2022]

For:	Tseng TC, Liu CJ, Su TH, Yang WT, Chen CL, Yang HC, Wang CC, Kuo SFT, Liu CH, Chen PJ, Chen DS, Kao JH. Fibrosis-4 Index Helps Identify HBV Carriers With the Lowest Risk of Hepatocellular Carcinoma. Am J Gastroenterol 2017;112:1564-1574. [PMID: 28853728 DOI: 10.1038/ajg.2017.254] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 07/14/2017] [Indexed: 12/11/2022]

Number

Cited by Other Article(s)

Zhang J, Lan Z, Zhu K, Yu S, Li S, Huang Y. Analysis of high-risk factors for hepatocellular carcinoma after sustained virological suppression of chronic hepatitis B. BMC Cancer 2025;25:635. [PMID: 40200195 PMCID: PMC11980259 DOI: 10.1186/s12885-025-14015-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 03/25/2025] [Indexed: 04/10/2025] Open

Cong X, Song S, Li Y, Song K, MacLeod C, Cheng Y, Lv J, Yu C, Sun D, Pei P, Yang L, Chen Y, Millwood I, Wu S, Yang X, Stevens R, Chen J, Chen Z, Li L, Kartsonaki C, Pang Y. Comparison of models to predict incident chronic liver disease: a systematic review and external validation in Chinese adults. BMC Med 2024;22:601. [PMID: 39736748 DOI: 10.1186/s12916-024-03754-9] [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: 02/06/2024] [Accepted: 11/05/2024] [Indexed: 01/01/2025] Open

Affiliation(s)

Xue Cong Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, China
Shuyao Song Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, China
Yingtao Li Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, China
Kaiyang Song Medical Sciences Division, University of Oxford, Oxford, OX3 9DU, UK
Cameron MacLeod Medical Sciences Division, University of Oxford, Oxford, OX3 9DU, UK
Yujie Cheng Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, China
Jun Lv Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, China Center for Public Health and Epidemic Preparedness & Response, Peking University, Beijing, 100191, China Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, 100191, China
Canqing Yu Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, China Center for Public Health and Epidemic Preparedness & Response, Peking University, Beijing, 100191, China Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, 100191, China
Dianjianyi Sun Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, China Center for Public Health and Epidemic Preparedness & Response, Peking University, Beijing, 100191, China Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, 100191, China
Pei Pei Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, China Center for Public Health and Epidemic Preparedness & Response, Peking University, Beijing, 100191, China
Ling Yang Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK Medical Research Council Population Health Research Unit at the University of Oxford, Oxford, OX3 7LF, UK
Yiping Chen Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK Medical Research Council Population Health Research Unit at the University of Oxford, Oxford, OX3 7LF, UK
Iona Millwood Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK Medical Research Council Population Health Research Unit at the University of Oxford, Oxford, OX3 7LF, UK
Shukuan Wu Meilan Center for Disease Control and Prevention, Haikou, 570100, China
Xiaoming Yang Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK
Rebecca Stevens Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK
Junshi Chen China National Center for Food Safety Risk Assessment, Beijing, 100022, China
Zhengming Chen Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK
Liming Li Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, China Center for Public Health and Epidemic Preparedness & Response, Peking University, Beijing, 100191, China Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, 100191, China
Christiana Kartsonaki Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK. Medical Research Council Population Health Research Unit at the University of Oxford, Oxford, OX3 7LF, UK.
Yuanjie Pang Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, China. Center for Public Health and Epidemic Preparedness & Response, Peking University, Beijing, 100191, China. Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, 100191, China.

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Chang SH, Su TH, Ling ZM, Lee MH, Liu CJ, Chen PJ, Yang HC, Liu CH, Chen CL, Tseng TC, Chen CH, Lee HS, Chen CJ, Kao JH. Fibrosis-4 index stratifies risks of hepatocellular carcinoma in patients with chronic hepatitis C. J Formos Med Assoc 2024;123:1154-1160. [PMID: 38944614 DOI: 10.1016/j.jfma.2024.06.008] [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: 01/04/2024] [Revised: 04/17/2024] [Accepted: 06/12/2024] [Indexed: 07/01/2024] Open

Affiliation(s)

Shan-Han Chang Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
Tung-Hung Su Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
Ze-Min Ling Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Mei-Hsuan Lee Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Chun-Jen Liu Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Pei-Jer Chen Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan
Hung-Chih Yang Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Chen-Hua Liu Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Chi-Ling Chen Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
Tai-Chung Tseng Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
Chien-Hung Chen National Taiwan University Cancer Center, Taipei, Taiwan
Hsuan-Shu Lee Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Chien-Jen Chen Genomics Research Center, Academia Sinica, Taipei, Taiwan
Jia-Horng Kao Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.

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Giangregorio F, Mosconi E, Debellis MG, Provini S, Esposito C, Garolfi M, Oraka S, Kaloudi O, Mustafazade G, Marín-Baselga R, Tung-Chen Y. A Systematic Review of Metabolic Syndrome: Key Correlated Pathologies and Non-Invasive Diagnostic Approaches. J Clin Med 2024;13:5880. [PMID: 39407941 PMCID: PMC11478146 DOI: 10.3390/jcm13195880] [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: 09/10/2024] [Revised: 09/26/2024] [Accepted: 09/27/2024] [Indexed: 10/20/2024] Open

Abstract

Background and Objectives: Metabolic syndrome (MetS) is a condition marked by a complex array of physiological, biochemical, and metabolic abnormalities, including central obesity, insulin resistance, high blood pressure, and dyslipidemia (characterized by elevated triglycerides and reduced levels of high-density lipoproteins). The pathogenesis develops from the accumulation of lipid droplets in the hepatocyte (steatosis). This accumulation, in genetically predisposed subjects and with other external stimuli (intestinal dysbiosis, high caloric diet, physical inactivity, stress), activates the production of pro-inflammatory molecules, alter autophagy, and turn on the activity of hepatic stellate cells (HSCs), provoking the low grade chronic inflammation and the fibrosis. This syndrome is associated with a significantly increased risk of developing type 2 diabetes mellitus (T2D), cardiovascular diseases (CVD), vascular, renal, pneumologic, rheumatological, sexual, cutaneous syndromes and overall mortality, with the risk rising five- to seven-fold for T2DM, three-fold for CVD, and one and a half-fold for all-cause mortality. The purpose of this narrative review is to examine metabolic syndrome as a "systemic disease" and its interaction with major internal medicine conditions such as CVD, diabetes, renal failure, and respiratory failure. It is essential for internal medicine practitioners to approach this widespread condition in a "holistic" rather than a fragmented manner, particularly in Western countries. Additionally, it is important to be aware of the non-invasive tools available for assessing this condition. Materials and Methods: We conducted an exhaustive search on PubMed up to July 2024, focusing on terms related to metabolic syndrome and other pathologies (heart, Lung (COPD, asthma, pulmonary hypertension, OSAS) and kidney failure, vascular, rheumatological (osteoarthritis, rheumatoid arthritis), endocrinological, sexual pathologies and neoplastic risks. The review was managed in accordance with the PRISMA statement. Finally, we selected 300 studies (233 papers for the first search strategy and 67 for the second one). Our review included studies that provided insights into metabolic syndrome and non-invasive techniques for evaluating liver fibrosis and steatosis. Studies that were not conducted on humans, were published in languages other than English, or did not assess changes related to heart failure were excluded. Results: The findings revealed a clear correlation between metabolic syndrome and all the pathologies above described, indicating that non-invasive assessments of hepatic fibrosis and steatosis could potentially serve as markers for the severity and progression of the diseases. Conclusions: Metabolic syndrome is a multisystem disorder that impacts organs beyond the liver and disrupts the functioning of various organs. Notably, it is linked to a higher incidence of cardiovascular diseases, independent of traditional cardiovascular risk factors. Non-invasive assessments of hepatic fibrosis and fibrosis allow clinicians to evaluate cardiovascular risk. Additionally, the ability to assess liver steatosis may open new diagnostic, therapeutic, and prognostic avenues for managing metabolic syndrome and its complications, particularly cardiovascular disease, which is the leading cause of death in these patients.

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Affiliation(s)

Francesco Giangregorio Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
Emilio Mosconi Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
Maria Grazia Debellis Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
Stella Provini Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
Ciro Esposito Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
Matteo Garolfi Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
Simona Oraka Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
Olga Kaloudi Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
Gunel Mustafazade Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
Raquel Marín-Baselga Department of Internal Medicine, Hospital Universitario La Paz, Paseo Castellana 241, 28046 Madrid, Spain;
Yale Tung-Chen Department of Internal Medicine, Hospital Universitario La Paz, Paseo Castellana 241, 28046 Madrid, Spain;

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Inoue J, Akahane T, Kobayashi T, Kimura O, Sato K, Ninomiya M, Iwata T, Takai S, Kisara N, Sato T, Nagasaki F, Miura M, Nakamura T, Umetsu T, Sano A, Tsuruoka M, Onuki M, Sawahashi S, Niitsuma H, Masamune A. Usefulness of the Fibrosis-4 index and alanine aminotransferase at 1 year of nucleos(t)ide analog treatment for prediction of hepatocellular carcinoma in chronic hepatitis B patients. Hepatol Res 2024;54:131-141. [PMID: 37621201 DOI: 10.1111/hepr.13957] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 08/08/2023] [Accepted: 08/11/2023] [Indexed: 08/26/2023]

Affiliation(s)

Jun Inoue Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
Takehiro Akahane Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Japan
Tomoo Kobayashi Department of Hepatology, Tohoku Rosai Hospital, Sendai, Japan
Osamu Kimura Department of Gastroenterology, South Miyagi Medical Center, Ogawara, Japan
Kosuke Sato Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
Masashi Ninomiya Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
Tomoaki Iwata Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
Satoshi Takai Department of Gastroenterology, Iwaki City Medical Center, Iwaki, Japan
Norihiro Kisara Department of Gastroenterology, Japan Community Health Care Organization Sendai South Hospital, Sendai, Japan
Toshihiro Sato LC Clinic, Sendai, Japan
Futoshi Nagasaki Department of Gastroenterology, Sendai City Hospital, Sendai, Japan
Masahito Miura Department of Gastroenterology, Omagari Kousei Medical Center, Daisen, Japan
Takuya Nakamura Department of Gastroenterology, Yamagata City Hospital Saiseikan, Yamagata, Japan
Teruyuki Umetsu Department of Internal Medicine, Kesennuma City Hospital, Kesennuma, Japan
Akitoshi Sano Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
Mio Tsuruoka Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
Masazumi Onuki Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
Satoko Sawahashi Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
Hirofumi Niitsuma Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
Atsushi Masamune Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan

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Arai J, Ito K. Deciphering the dual nature of the Fibrosis-4 index in predicting hepatocellular carcinoma risk among hepatitis B patients undergoing nucleos(t)ide analog therapy. Hepatol Res 2024;54:120-121. [PMID: 38126190 DOI: 10.1111/hepr.13997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2023]

Gao TM, Jin SJ, Fang F, Qian JJ, Zhang C, Zhou BH, Bai DS, Jiang GQ. Novel Preoperative Type IV Collagen to Predict the Risk of Hepatocellular Carcinoma in Patients with Hepatitis B Virus-Related Cirrhotic Portal Hypertension After Laparoscopic Splenectomy and Azygoportal Disconnection. J Hepatocell Carcinoma 2024;10:2411-2420. [PMID: 38260186 PMCID: PMC10801173 DOI: 10.2147/jhc.s425814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 08/15/2023] [Indexed: 01/24/2024] Open

Abstract

Purpose

Although laparoscopic splenectomy and azygoportal disconnection (LSD) can significantly decrease portal vein pressure and even the incidence of hepatocellular carcinoma (HCC) in patients with cirrhotic portal hypertension (CPH), postoperative HCC inevitably occurs in certain patients. The purpose of this study was to seek a novel preoperative non-invasive predictive indicator to predict the occurrence of postoperative HCC.

Patients and Methods

From April 2012 to April 2022, we collected clinical data of 178 hepatitis B virus (HBV)-related CPH patients. Based on inverse treatment probability weighting, candidate variables for predicting postoperative HCC were determined by means analysis. Then, a novel preoperative non-invasive prediction indicator (ie, type IV collagen-alpha fetoprotein-fibrosis-4 score [IVAF-FIB-4]) was established based on candidate variables, and its predictive ability was explored.

Results

Postoperative HCC occurred in 9 (5.1%) patients. Correlation analyses showed that the IVAF-FIB-4 had a significant positive correlation with HCC (r = 0.835, P < 0.001). IVAF-FIB-4 showed a high accuracy (the area under the receiver operating characteristic curve: 0.939, 95% confidence interval [CI]: 0.818-1.000; sensitivity: 88.9%; specificity: 93.5%). At the end of follow-up, the incidence density of HCC in patients with IVAF-FIB-4 (1) was significant higher than that in patients with IVAF-FIB-4 (0) (138.1/1000 vs 1.1/1000 person-years; rate ratio: 130.475, 95% CI: 16.318-1043.227). In logistic regression, IVAF-FIB-4 was an independent risk factor for HCC (odds ratio: 668.000, 95% CI: 53.895-8279.541; P < 0.001).

Conclusion

IVAF-FIB-4 is a novel preoperative noninvasive predictive indicator for predicting postoperative HCC in HBV-related CPH patients after LSD, with satisfactory predictive ability.

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Tseng TC, Hosaka T, Liu CJ, Suzuki F, Chiang C, Hong CM, Kumada H, Yang WT, Su TH, Yang HC, Liu CH, Chen PJ, Kao JH. HBcrAg-based risk score performs better than the HBV DNA-based scores for HCC prediction in grey zone patients who are HBeAg-negative. JHEP Rep 2024;6:100956. [PMID: 38089551 PMCID: PMC10714239 DOI: 10.1016/j.jhepr.2023.100956] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Accepted: 09/26/2023] [Indexed: 04/16/2025] Open

Abstract

BACKGROUND & AIMS

Risk scores have been designed to predict the development of hepatocellular carcinoma (HCC) in treatment-naive patients with chronic hepatitis B (CHB). However, little is known about their predictive accuracy in HBeAg-negative patients in the grey zone (GZ). We aimed to develop a HBcrAg-based HCC risk score and explore whether it outperforms other risk scores in GZ patients.

METHODS

Two retrospective cohorts of HBeAg-negative patients with American Association for the Study of Liver Diseases-defined GZ were established for derivation and validation (Taiwanese, N = 911; Japanese, N = 806). All of them were non-cirrhotic at baseline and remained treatment-naive during the follow-up. The primary endpoint was HCC development.

RESULTS

In a median follow-up period of 15.5 years, 85 patients developed HCC in the derivation cohort. We found that age, sex, alanine aminotransferase, platelet count, and HBcrAg, but not HBV DNA levels, were independent predictors and a 20-point GZ-HCC score was developed accordingly. The 10-year and 15-year area under the ROC curve (AUROC) ranged from 0.83 to 0.86, which outperformed the HBV DNA-based HCC risk scores, including REACH-B and GAG-HCC scores (AUROC ranging from 0.66 to 0.74). The better performance was also validated in EASL- and Asian Pacific Association for the Study of the Liver-defined GZ patients. These findings remained consistent in the validation cohort. Finally, the low-risk and high-risk GZ patients (stratified by a score of 8) had an HCC risk close to inactive CHB and immune-active CHB patients, respectively, in both cohorts.

CONCLUSIONS

The HBcrAg-based GZ-HCC score predicts HCC better than other HBV DNA-based risk scores in GZ patients who are HBeAg-negative patients, which may help optimise their clinical management.

IMPACT AND IMPLICATIONS

We have developed a risk score based on HBcrAg, which has shown better predictive ability for HCC compared with other risk scores based on HBV DNA. Using a score of 8, GZ patients can be classified into low- and high-risk groups, which can guide follow up and early treatment, respectively. This validated risk score is a valuable tool for optimising the management of GZ patients who are HBeAg-negative.

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Affiliation(s)

Tai-Chung Tseng Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
Tetsuya Hosaka Department of Hepatology, Toranomon Hospital, Tokyo, Japan
Chun-Jen Liu Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine Taipei, Taiwan
Fumitaka Suzuki Department of Hepatology, Toranomon Hospital, Tokyo, Japan
Chieh Chiang Department of Mathematics, Tamkang University, New Taipei City, Taiwan
Chun-Ming Hong Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Hiromitsu Kumada Department of Hepatology, Toranomon Hospital, Tokyo, Japan
Wan-Ting Yang Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Tung-Hung Su Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Hung-Chih Yang Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine Taipei, Taiwan Department of Microbiology, National Taiwan University College of Medicine Taipei, Taiwan
Chen-Hua Liu Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Pei-Jer Chen Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine Taipei, Taiwan
Jia-Horng Kao Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine Taipei, Taiwan

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Tseng TC, Chiang C, Liu CJ, Hong CM, Su TH, Yang HC, Yang WT, Liu CH, Chen PJ, Kao JH. Low Hepatitis B Core-Related Antigen Levels Correlate Higher Spontaneous Seroclearance of Hepatitis B Surface Antigen in Chronic Hepatitis B Patients With High Hepatitis B Surface Antigen Levels. Gastroenterology 2023;164:669-679.e6. [PMID: 36642151 DOI: 10.1053/j.gastro.2023.01.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 11/07/2022] [Accepted: 01/03/2023] [Indexed: 01/17/2023]

Abstract

BACKGROUND & AIMS

Seroclearance of hepatitis B surface antigen (HBsAg) indicates functional cure for hepatitis B virus (HBV) infection. Low HBsAg levels can predict HBsAg seroclearance over time. However, little is known about the association between hepatitis B core-related antigen (HBcrAg) levels and spontaneous seroclearance of HBsAg.

METHODS

We conducted a retrospective cohort study including 2614 treatment-naïve patients with chronic HBV infection who received long-term follow-up at the National Taiwan University Hospital. The primary end point was spontaneous HBsAg seroclearance. We aimed to explore whether HBcrAg levels could predict HBsAg seroclearance, especially for patients with HBsAg levels >1000 IU/mL.

RESULTS

There were 465 patients who cleared HBsAg with 32,414.72 person-years of follow-up, with a mean clearance rate of 1.43% per year. We found that lower HBcrAg levels at baseline were associated with an increased likelihood of HBsAg seroclearance (log rank P < .001). When restricting the study population to 1539 patients with HBsAg levels >1000 IU/mL, only HBcrAg <10,000 U/mL (vs ≥100,000 U/mL) served as an independent viral predictor for HBsAg seroclearance, with adjusted hazard ratio of 1.95 (95% CI, 1.16-3.27). In contrast to the late decline of HBsAg levels (5-9 years before HBsAg seroclearance), HBcrAg levels became undetectable 10-14 years before HBsAg seroclearance. This finding was confirmed by the different annual HBsAg seroclearance rates in the first and second decades of follow-up (0.97% vs 3.75%; P < .001) in patients achieving undetectable HBcrAg levels.

CONCLUSIONS

Lower serum HBcrAg levels were associated with increased probability of HBsAg seroclearance over time. In patients with HBsAg levels >1000 IU/mL, clearing HBcrAg may serve as an early biomarker for HBsAg seroclearance.

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Affiliation(s)

Tai-Chung Tseng Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
Chieh Chiang Department of Mathematics, Tamkang University, New Taipei City, Taiwan
Chun-Jen Liu Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
Chun-Ming Hong Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Tung-Hung Su Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Hung-Chih Yang Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan
Wan-Ting Yang Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Chen-Hua Liu Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Pei-Jer Chen Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
Jia-Horng Kao Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.

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Inoue T, Tanaka Y. Noninvasive assessments of liver disease severity based on biomarkers. COMPREHENSIVE GUIDE TO HEPATITIS ADVANCES 2023:31-60. [DOI: 10.1016/b978-0-323-98368-6.00009-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]

Sono S, Sae-Chan J, Kaewdech A, Chamroonkul N, Sripongpun P. HBV seroprevalence and liver fibrosis status among population born before national immunization in Southern Thailand: Findings from a health check-up program. PLoS One 2022;17:e0270458. [PMID: 35749545 PMCID: PMC9231792 DOI: 10.1371/journal.pone.0270458] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 06/12/2022] [Indexed: 11/18/2022] Open

Zhao D, Zhang X, Tang Y, Guo P, Ai R, Hou M, Wang Y, Yuan X, Cui L, Zhang Y, Zhao S, Li W, Wang Y, Sun X, Liu L, Dong S, Li L, Zhao W, Nan Y. Identification and Validation of Novel Biomarkers for Hepatocellular Carcinoma, Liver Fibrosis/Cirrhosis and Chronic Hepatitis B via Transcriptome Sequencing Technology. J Hepatocell Carcinoma 2022;9:389-403. [PMID: 35592243 PMCID: PMC9112460 DOI: 10.2147/jhc.s357380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 04/27/2022] [Indexed: 11/27/2022] Open

Abstract

Purpose

The aim of this study was to identify and validate novel biomarkers for distinguishing among hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), liver fibrosis/liver cirrhosis (LF/LC) and chronic hepatitis B (CHB).

Patients and Methods

Transcriptomic sequencing was conducted on the liver tissues of 5 patients with HCC, 5 patients with LF/LC, 5 patients with CHB, and 4 healthy controls. The expression levels of selected mRNAs and proteins were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical (IHC) staining, and were verified in validation set (n=200) and testing set (n=400) via enzyme-linked immunosorbent assay (ELISA).

Results

A total of 9 hub mRNAs were identified by short time-series expression miner and weighted gene co-expression network analysis. Of note, the results of qRT-PCR and IHC staining demonstrated that SHC adaptor protein 1 (SHC1), SLAM family member 8 (SLAMF8), and interleukin-32 (IL-32) exhibited gradually increasing trends in the four groups. Subsequent ELISA tests on the validation cohort indicated that the plasma levels of SHC1, SLAMF8 and IL-32 also gradually increased. Furthermore, a diagnostic model APFSSI (age, PLT, ferritin, SHC1, SLAMF8 and IL-32) was established to distinguish among CHB, LF/LC and HCC. The performance of APFSSI model for discriminating CHB from healthy subjects (AUC=0.966) was much greater compared to SHC1 (AUC=0.900), SLAMF8 (AUC=0.744) and IL-32 (AUC=0.821). When distinguishing LF/LC from CHB, APFSSI was the most outstanding diagnostic parameter (AUC=0.924), which was superior to SHC1, SLAMF8 and IL-32 (AUC=0.812, 0.684 and 0.741, respectively). Likewise, APFSSI model with the greatest AUC value displayed an excellent performance for differentiating between HCC and LF/LC than other variables (SHC1, SLAMF8 and IL-32) via ROC analysis. Finally, the results in the test set were consistent with those in the validation set.

Conclusion

SHC1, SLAMF8 and IL-32 can differentiate among patients with HCC, LF/LC, CHB and healthy controls. More importantly, the APFSSI model greatly improves the diagnostic accuracy of HBV-associated liver diseases.

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Affiliation(s)

Dandan Zhao Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, People’s Republic of China
Xiaoxiao Zhang Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, People’s Republic of China
Yuhui Tang Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, People’s Republic of China
Peilin Guo Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, People’s Republic of China
Rong Ai Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, People’s Republic of China
Mengmeng Hou Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, People’s Republic of China
Yiqi Wang Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, People’s Republic of China
Xiwei Yuan Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, People’s Republic of China
Luyao Cui Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, People’s Republic of China
Yuguo Zhang Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, People’s Republic of China
Suxian Zhao Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, People’s Republic of China
Wencong Li Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, People’s Republic of China
Yang Wang Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, People’s Republic of China
Xiaoye Sun Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, People’s Republic of China
Lingdi Liu Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, People’s Republic of China
Shiming Dong Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, People’s Republic of China
Lu Li Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, People’s Republic of China
Wen Zhao Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, People’s Republic of China
Yuemin Nan Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, People’s Republic of China Correspondence: Yuemin Nan, Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang, Hebei Province, 050051, People’s Republic of China, Tel +86 311-66781227, Fax +86 311-66781289, Email

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Hepatitis B Core-Related Antigen Stratifies the Risk of Liver Cancer in HBeAg-Negative Patients With Indeterminate Phase. Am J Gastroenterol 2022;117:748-757. [PMID: 35191399 DOI: 10.14309/ajg.0000000000001691] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 02/10/2022] [Indexed: 12/11/2022]

Zhao D, Yu S, Guo P, Zhang X, Tang Y, Dong C, Zhao S, Li L, Al‐Dhamin Z, Ai R, Xue N, Dong S, Nan Y. Identification of potential plasma markers for hepatitis B virus related chronic hepatitis and liver fibrosis/cirrhosis. J Med Virol 2022;94:3900-3910. [PMID: 35420168 DOI: 10.1002/jmv.27761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 03/08/2022] [Accepted: 04/02/2022] [Indexed: 11/11/2022]

Affiliation(s)

Dandan Zhao Department of Traditional and Western Medical HepatologyThird Hospital of Hebei Medical University050051ShijiazhuangChina Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver DiseasesChina
Songhao Yu Department of Traditional and Western Medical HepatologyThird Hospital of Hebei Medical University050051ShijiazhuangChina Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver DiseasesChina
Peilin Guo Department of Traditional and Western Medical HepatologyThird Hospital of Hebei Medical University050051ShijiazhuangChina Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver DiseasesChina
Xiaoxiao Zhang Department of Traditional and Western Medical HepatologyThird Hospital of Hebei Medical University050051ShijiazhuangChina Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver DiseasesChina
Yuhui Tang Department of Traditional and Western Medical HepatologyThird Hospital of Hebei Medical University050051ShijiazhuangChina Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver DiseasesChina
Chen Dong Department of Traditional and Western Medical HepatologyThird Hospital of Hebei Medical University050051ShijiazhuangChina Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver DiseasesChina
Suxian Zhao Department of Traditional and Western Medical HepatologyThird Hospital of Hebei Medical University050051ShijiazhuangChina Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver DiseasesChina
Lu Li Department of Traditional and Western Medical HepatologyThird Hospital of Hebei Medical University050051ShijiazhuangChina Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver DiseasesChina
Zaid Al‐Dhamin Department of Traditional and Western Medical HepatologyThird Hospital of Hebei Medical University050051ShijiazhuangChina Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver DiseasesChina
Rong Ai Department of Traditional and Western Medical HepatologyThird Hospital of Hebei Medical University050051ShijiazhuangChina Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver DiseasesChina
Ningning Xue Department of Traditional and Western Medical HepatologyThird Hospital of Hebei Medical University050051ShijiazhuangChina Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver DiseasesChina
Shiming Dong Department of Traditional and Western Medical HepatologyThird Hospital of Hebei Medical University050051ShijiazhuangChina Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver DiseasesChina
Yuemin Nan Department of Traditional and Western Medical HepatologyThird Hospital of Hebei Medical University050051ShijiazhuangChina Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver DiseasesChina

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Sohn W, Chang Y, Cho YK, Hong YS, Shin H, Ryu S. Liver fibrosis scores and risk of liver-related mortality in young adults with chronic hepatitis B: A cohort study. J Viral Hepat 2022;29:69-77. [PMID: 34582599 DOI: 10.1111/jvh.13618] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 09/21/2021] [Accepted: 09/23/2021] [Indexed: 12/14/2022]

Goh MJ, Kang W, Kim KM, Sinn DH, Gwak GY, Paik YH, Choi MS, Lee JH, Koh KC, Paik SW. Incidence and risk factors for development of hepatocellular carcinoma at young age in patients with chronic hepatitis B. Scand J Gastroenterol 2022;57:70-77. [PMID: 34731072 DOI: 10.1080/00365521.2021.1988700] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]

Zhang X, Guan L, Tian H, Zeng Z, Chen J, Huang D, Sun J, Guo J, Cui H, Li Y. Risk Factors and Prevention of Viral Hepatitis-Related Hepatocellular Carcinoma. Front Oncol 2021;11:686962. [PMID: 34568017 PMCID: PMC8458967 DOI: 10.3389/fonc.2021.686962] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Accepted: 08/20/2021] [Indexed: 12/11/2022] Open

The role of fibrosis index FIB-4 in predicting liver fibrosis stage and clinical prognosis: A diagnostic or screening tool? J Formos Med Assoc 2021;121:454-466. [PMID: 34325952 DOI: 10.1016/j.jfma.2021.07.013] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 04/09/2021] [Accepted: 07/12/2021] [Indexed: 12/14/2022] Open

Shin SK, Yim HJ, Kim JH, Lee CU, Yeon JE, Suh SJ, Jung YK, Kim YS, Kim JH, Kwon OS. Partial Virological Response after 2 Years of Entecavir Therapy Increases the Risk of Hepatocellular Carcinoma in Patients with Hepatitis B Virus-Associated Cirrhosis. Gut Liver 2021;15:430-439. [PMID: 33115966 PMCID: PMC8129658 DOI: 10.5009/gnl20074] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 05/28/2020] [Accepted: 06/08/2020] [Indexed: 12/17/2022] Open

The FIB-4 Index Is a Useful Predictor for the Development of Hepatocellular Carcinoma in Patients with Coexisting Nonalcoholic Fatty Liver Disease and Chronic Hepatitis B. Cancers (Basel) 2021;13:cancers13102301. [PMID: 34064988 PMCID: PMC8151791 DOI: 10.3390/cancers13102301] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 05/03/2021] [Accepted: 05/05/2021] [Indexed: 02/07/2023] Open

Abstract

Simple Summary

This retrospective study analyzed 237 consecutive patients with coexisting nonalcoholic fatty liver disease and chronic hepatitis B (NAFLD-CHB) with long observation period (median follow-up duration, 13 years). The optimal cutoff for the FIB-4 index of 1.77 was calculated based on the maximum Youden index value, and the value was 1.77 with an AUC of 0.70. The significant higher risk of developing hepatocellular carcinoma (HCC) in patients with a high FIB-4 index (≥1.77) than the patients with a low FIB-4 index (<1.77) (adjusted hazard ratio, 4.35; 95% CI, 1.42–13.24; log-rank test, p = 0.006) were found among the NAFLD-CHB patients whose baseline characteristics were balanced by propensity score matching. The FIB-4 index might be a useful predictor of the development of HCC among NAFLD–CHB patients.

Abstract

Background: The FIB-4 index, a noninvasive tool (FIB-4 index = age × aspartate transaminase (AST)/(platelet count × √alanine aminotransferase (ALT)), is a useful assessment for liver fibrosis. Patients with a high FIB-4 index were reported to have a high risk of developing hepatocellular carcinoma (HCC). This study analyzed the clinical association of the FIB-4 index with HCC development in patients with coexisting nonalcoholic fatty liver disease and chronic hepatitis B (NAFLD–CHB). Methods: This retrospective study analyzed 237 consecutive patients with NAFLD–CHB between January 2006 and December 2010 at the National Police Hospital in Korea. Patients with HCC at baseline and those diagnosed with HCC within 6 months from baseline were excluded. Propensity score matching analysis (PSM) was adopted to balance the baseline characteristics between patients with low and high FIB-4 index values. The cumulative rates of HCC development were compared between the two groups using the Kaplan–Meier method in the matched population. Results: The median follow-up duration was 13 years (interquartile range, 8.2–15.7). The optimal cutoff for the FIB-4 index of 1.77 was calculated based on the maximum Youden index value, with an AUC of 0.70. Among a total of 237 patients with NAFLD–CHB, HCC developed in 20 patients (8.4%) (14 of the 90 patients with a high FIB-4 index vs. 6 of the 147 patients (4.1%) with a low FIB-4 index; log-rank p = 0.003). Patients with a high FIB-4 index had a significantly and independently higher risk of HCC than those with a low FIB-4 index (adjusted hazard ratio, 4.35; 95%; confidence interval, 1.42–13.24; log-rank test, p = 0.006). Conclusion: A high FIB-4 index (≥1.77) might be a useful marker for predicting the development of HCC in patients with NAFLD–CHB.

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Jeon MY, Kim BK, Lee JS, Lee HW, Park JY, Kim DY, Ahn SH, Han KH, Kim SU. Negligible risks of hepatocellular carcinoma during biomarker-defined immune-tolerant phase for patients with chronic hepatitis B. Clin Mol Hepatol 2021;27:295-304. [PMID: 33317247 PMCID: PMC8046628 DOI: 10.3350/cmh.2020.0216] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Revised: 11/24/2020] [Accepted: 11/25/2020] [Indexed: 12/12/2022] Open

Affiliation(s)

Mi Young Jeon Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea Yonsei Liver Center, Severance Hospital, Seoul, Korea
Beom Kyung Kim Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea Yonsei Liver Center, Severance Hospital, Seoul, Korea Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Jae Seung Lee Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea Yonsei Liver Center, Severance Hospital, Seoul, Korea Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Hye Won Lee Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea Yonsei Liver Center, Severance Hospital, Seoul, Korea Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Jun Yong Park Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea Yonsei Liver Center, Severance Hospital, Seoul, Korea Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Do Young Kim Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea Yonsei Liver Center, Severance Hospital, Seoul, Korea Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Sang Hoon Ahn Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea Yonsei Liver Center, Severance Hospital, Seoul, Korea Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Kwang-Hyub Han Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea Yonsei Liver Center, Severance Hospital, Seoul, Korea Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Seung Up Kim Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea Yonsei Liver Center, Severance Hospital, Seoul, Korea Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea

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Liu Y, Mo Y, Wu A. Additional more factors should be included in predicting risk of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. J Viral Hepat 2021;28:573. [PMID: 33264447 DOI: 10.1111/jvh.13448] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 11/17/2020] [Indexed: 12/09/2022]

Sumida Y, Yoneda M, Tokushige K, Kawanaka M, Fujii H, Yoneda M, Imajo K, Takahashi H, Eguchi Y, Ono M, Nozaki Y, Hyogo H, Koseki M, Yoshida Y, Kawaguchi T, Kamada Y, Okanoue T, Nakajima A. FIB-4 First in the Diagnostic Algorithm of Metabolic-Dysfunction-Associated Fatty Liver Disease in the Era of the Global Metabodemic. Life (Basel) 2021;11:143. [PMID: 33672864 PMCID: PMC7917687 DOI: 10.3390/life11020143] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Revised: 01/22/2021] [Accepted: 01/25/2021] [Indexed: 12/16/2022] Open

Affiliation(s)

Yoshio Sumida Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan;
Masashi Yoneda Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan;
Katsutoshi Tokushige Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo 162-8666, Japan;
Miwa Kawanaka Department of General Internal Medicine2, Kawasaki Medical School, Okayama 700-8505, Japan;
Hideki Fujii Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka 558-8585, Japan;
Masato Yoneda Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan; (M.Y.); (K.I.); (A.N.)
Kento Imajo Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan; (M.Y.); (K.I.); (A.N.)
Hirokazu Takahashi Department of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 840-8502, Japan;
Yuichiro Eguchi Loco Medical General Institute, Saga 840-8502, Japan;
Masafumi Ono Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokyo Women’s Medical University Medical Center East, Tokyo 116-8567, Japan;
Yuichi Nozaki Department of Gastroenterology, National Center for Global Health and Medicine, Tokyo 162-8655, Japan;
Hideyuki Hyogo Department of Gastroenterology, JA Hiroshima General Hospital, Hiroshima 738-8503, Japan;
Masahiro Koseki Division of Cardiovascular Medicine, Department of Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan;
Yuichi Yoshida Department of Gastroenterology and Hepatology, Suita Municipal Hospital, Osaka 564-8567, Japan;
Takumi Kawaguchi Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan;
Yoshihiro Kamada Department of Advanced Gastroenterology & Hepatology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan;
Takeshi Okanoue Hepatology Center, Saiseikai Suita Hospital, Osaka 564-0013, Japan;
Atsushi Nakajima Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan; (M.Y.); (K.I.); (A.N.)
Japan Study Group of NAFLD (JSG-NAFLD) Japan Strategic Medical Administration Research Center (J-SMARC), Nagoya, Aichi 460-0011, Japan

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Huang SC, Liao SH, Su TH, Jeng YM, Kao JH. Clinical manifestations and outcomes of patients with scirrhous hepatocellular carcinoma. Hepatol Int 2021;15:472-481. [PMID: 33544314 DOI: 10.1007/s12072-021-10146-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 01/17/2021] [Indexed: 11/26/2022]

Tseng TC, Choi J, Nguyen MH, Peng CY, Siakavellas S, Papatheodoridis G, Wang CC, Lim YS, Lai HC, Trinh HN, Wong C, Wong C, Zhang J, Li J, Kao JH. One-year Fibrosis-4 index helps identify minimal HCC risk in non-cirrhotic chronic hepatitis B patients with antiviral treatment. Hepatol Int 2021;15:105-113. [PMID: 33547557 PMCID: PMC7863859 DOI: 10.1007/s12072-020-10124-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Accepted: 12/15/2020] [Indexed: 12/15/2022]

Affiliation(s)

Tai-Chung Tseng Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te St, Taipei, 10002, Taiwan Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
Jonggi Choi Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
Mindie H Nguyen Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
Cheng-Yuan Peng School of Medicine, China Medical University, Taizhong, Taiwan Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taizhong, Taiwan
Spyros Siakavellas Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
George Papatheodoridis Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
Chia-Chi Wang Division of Gastroenterology, Department of Internal Medicine, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, New Taipei City, Taiwan School of Medicine, Tzu Chi University, Hualien, Taiwan
Young-Suk Lim Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
Hsueh-Chou Lai School of Medicine, China Medical University, Taizhong, Taiwan
Huy N Trinh San Jose Gastroenterology, San Jose, CA, USA
Christopher Wong Wong Clinics, San Francisco, CA, USA
Clifford Wong Wong Clinics, San Francisco, CA, USA
Jian Zhang Chinese Hospital, San Francisco, CA, USA
Jiayi Li Gastroenterology, Palo Alto Medical Foundation, Mountain View, CA, USA
Jia-Horng Kao Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te St, Taipei, 10002, Taiwan. Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan. Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.

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Liu TW, Huang CF, Yeh ML, Tsai PC, Jang TY, Huang JF, Dai CY, Chuang WL, Yu ML. Less liver fibrosis marker increment in overweight chronic hepatitis B patients observed by age-adjusted Fibrosis-4 Index. BMJ Open Gastroenterol 2020;7:bmjgast-2020-000543. [PMID: 33323472 PMCID: PMC7745320 DOI: 10.1136/bmjgast-2020-000543] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 11/23/2020] [Accepted: 11/24/2020] [Indexed: 12/22/2022] Open

Affiliation(s)

Ta-Wei Liu College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.,Internal Medicine, Pingtung Hospital, Ministry of Health and Welfare, Pingtung, Taiwan.,Hepatitis Center, Kaohsiung Medical University Chung Ho Memorial Hospital, Kaohsiung, Taiwan.,Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
Chung-Feng Huang College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Hepatitis Center, Kaohsiung Medical University Chung Ho Memorial Hospital, Kaohsiung, Taiwan.,Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
Ming-Lun Yeh College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Hepatitis Center, Kaohsiung Medical University Chung Ho Memorial Hospital, Kaohsiung, Taiwan.,Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
Pei-Chien Tsai College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Hepatitis Center, Kaohsiung Medical University Chung Ho Memorial Hospital, Kaohsiung, Taiwan.,Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
Tyng-Yuan Jang Internal Medicine, Pingtung Hospital, Ministry of Health and Welfare, Pingtung, Taiwan.,Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
Jee-Fu Huang College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.,Hepatitis Center, Kaohsiung Medical University Chung Ho Memorial Hospital, Kaohsiung, Taiwan.,Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
Chia-Yen Dai College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Hepatitis Center, Kaohsiung Medical University Chung Ho Memorial Hospital, Kaohsiung, Taiwan.,Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
Wan-Long Chuang College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Hepatitis Center, Kaohsiung Medical University Chung Ho Memorial Hospital, Kaohsiung, Taiwan.,Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
Ming-Lung Yu College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan .,Hepatitis Center, Kaohsiung Medical University Chung Ho Memorial Hospital, Kaohsiung, Taiwan.,Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

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Yuan TH, Chen JL, Shie RH, Yeh YP, Chen YH, Chan CC. Liver fibrosis associated with potential vinyl chloride and ethylene dichloride exposure from the petrochemical industry. THE SCIENCE OF THE TOTAL ENVIRONMENT 2020;739:139920. [PMID: 32534314 DOI: 10.1016/j.scitotenv.2020.139920] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 05/31/2020] [Accepted: 06/01/2020] [Indexed: 06/11/2023]

Abstract

BACKGROUND

The understanding of the relationship between exposure to carcinogenic vinyl chloride (VCM) and ethylene dichloride (EDC) and liver fibrosis is limited.

OBJECTIVE

This study aimed to investigate the associations between the urinary metabolite levels of VCM and EDC and the risk of liver fibrosis in residents living near a petrochemical complex.

METHODS

Our study comprised 447 adult residents of two townships with questionnaire survey and health examination near the largest petrochemical complex in central Taiwan. The urinary levels of thiodiglycolic acid (TdGA), the metabolite of VCM and EDC, were detected in study subjects. We utilized fibrosis-4 (FIB-4) as the noninvasive liver fibrosis index. Adjusted linear model was applied to evaluate the associations between the distance from the complex and the urinary TdGA levels. Adjusted logistic regression model was applied to evaluate the associations between the urinary TdGA levels and the risk of liver fibrosis.

RESULTS

The study subjects living in the closer township had significant higher urinary TdGA levels than those living in the more distant township (269.6 ± 200.7 vs. 199.2 ± 164.7 μg/g creatinine) (p < 0.001). It showed that urinary TdGA levels were decreased 0.53-fold when the distances from the complex were increased 1-fold after adjusting for confounding factors. It demonstrated that the study subjects with the highest TdGA levels (>343.3 μg/g creatinine) had a higher risk of FIB-4>1.29 (OR = 2.09; 95% CI: 1.17, 3.78), and those with higher TdGA levels (232.7 to 343.3 μg/g creatinine) had a marginally higher risk of FIB-4>1.29 (OR = 1.65; 95% CI: 0.94, 2.90).

CONCLUSION

The residents living closer to the VCM/PVC plant in the petrochemical complex had higher urinary TdGA levels, which were associated with an increased risk of fibrosis. This confirmed that the EDC and VCM potentially emitted from the petrochemical industry may have an impact on the liver health of nearby residents.

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Lim TS, Lee HW, Lee JI, Kim IH, Lee CH, Jang BK, Chung WJ, Yim HJ, Suh SJ, Seo YS, Lee HA, Yu JH, Lee JW, Kim SG, Kim YS, Park SY, Tak WY, Kim SS, Cheong JY, Jeong SW, Jang JY, Rou WS, Lee BS, Kim SU. Predictive score for hepatocellular carcinoma after hepatitis B e antigen loss in patients treated with entecavir or tenofovir. J Viral Hepat 2020;27:1052-1060. [PMID: 32383246 DOI: 10.1111/jvh.13316] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2019] [Revised: 02/28/2020] [Accepted: 04/14/2020] [Indexed: 12/13/2022]

Affiliation(s)

Tae Seop Lim Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
Hyun Woong Lee Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
Jung Il Lee Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
In Hee Kim Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea
Chang Hun Lee Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea
Byoung Kuk Jang Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
Woo Jin Chung Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
Hyung Joon Yim Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
Sang Jun Suh Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
Yeon Seok Seo Departments of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
Han Ah Lee Departments of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
Jung Hwan Yu Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea
Jin-Woo Lee Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea
Sang Gyune Kim Department of Internal Medicine, Soonchunhyang University College of Medicine Bucheon Hospital, Bucheon, Korea
Young Seok Kim Department of Internal Medicine, Soonchunhyang University College of Medicine Bucheon Hospital, Bucheon, Korea
Soo Young Park Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
Won Young Tak Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
Soon Sun Kim Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
Jae Youn Cheong Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
Soung Won Jeong Department of Internal Medicine, Soonchunhyang University College of Medicine Seoul Hospital, Seoul, Korea
Jae Young Jang Department of Internal Medicine, Soonchunhyang University College of Medicine Seoul Hospital, Seoul, Korea
Woo Sun Rou Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea
Byung Seok Lee Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea
Seung Up Kim Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

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Su TH, Peng CY, Tseng TC, Yang HC, Liu CJ, Liu CH, Chen PJ, Chen DS, Kao JH. Serum Mac-2-Binding Protein Glycosylation Isomer at Virological Remission Predicts Hepatocellular Carcinoma and Death in Chronic Hepatitis B-Related Cirrhosis. J Infect Dis 2020;221:589-597. [PMID: 31574141 DOI: 10.1093/infdis/jiz496] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 09/27/2019] [Indexed: 02/07/2023] Open

Affiliation(s)

Tung-Hung Su Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Cheng-Yuan Peng School of Medicine, China Medical University, Taichung, Taiwan.,Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
Tai-Chung Tseng Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Hung-Chih Yang Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Chun-Jen Liu Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Chen-Hua Liu Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Pei-Jer Chen Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
Ding-Shinn Chen Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Genomics Research Center, Academia Sinica, Taipei, Taiwan
Jia-Horng Kao Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan

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Marasco G, Colecchia A, Silva G, Rossini B, Eusebi LH, Ravaioli F, Dajti E, Alemanni LV, Colecchia L, Renzulli M, Golfieri R, Festi D. Non-invasive tests for the prediction of primary hepatocellular carcinoma. World J Gastroenterol 2020;26:3326-3343. [PMID: 32655261 PMCID: PMC7327793 DOI: 10.3748/wjg.v26.i24.3326] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 04/08/2020] [Accepted: 06/12/2020] [Indexed: 02/06/2023] Open

Tseng TC, Liu CJ, Chang CT, Su TH, Yang WT, Tsai CH, Chen CL, Yang HC, Liu CH, Chen PJ, Chen DS, Kao JH. HEV superinfection accelerates disease progression in patients with chronic HBV infection and increases mortality in those with cirrhosis. J Hepatol 2020;72:1105-1111. [PMID: 32006586 DOI: 10.1016/j.jhep.2020.01.012] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2019] [Revised: 12/27/2019] [Accepted: 01/06/2020] [Indexed: 02/08/2023]

Abstract

BACKGROUND & AIMS

Acute HEV infection causes varying degrees of liver damage. Although liver-related death due to HEV infection alone is rare in healthy individuals, it is unclear whether HEV superinfection is associated with worse outcomes in patients with chronic HBV infection. Thus, we explored whether HEV superinfection was associated with increased incidence of liver-related death, cirrhosis, and hepatocellular carcinoma (HCC).

METHODS

Serum and data were collected from 2 independent retrospective cohorts of patients with chronic HBV infection, comprising 2,123 patients without cirrhosis and 414 with cirrhosis at baseline, respectively. All the patients were negative for HEV-IgG at enrolment and HEV superinfection was defined by the presence of HEV-IgG seroconversion.

RESULTS

In the non-cirrhotic cohort, 46 of 2,123 patients developed HEV superinfection. Though HEV superinfection was only associated with increased incidence of liver-related death in the overall cohort, it was a risk factor for all 3 endpoints (liver-related death, cirrhosis, and HCC) in a subgroup of 723 HBeAg-negative patients with chronic HBV infection. In addition, the 1-year mortality rate after HEV superinfection was higher in 4 patients who developed cirrhosis during the follow-up than in those who did not (50% vs. 2.4%, p = 0.001). To elucidate the perceived relationship between HEV superinfection and risk of mortality, an independent cohort of cirrhotic patients (n = 414) was further analyzed to control for the inherent increase in mortality risk due to cirrhosis. The 10 cirrhotic patients with HEV superinfection had a higher 1-year mortality rate than those without (30% vs. 0%, p <0.001).

CONCLUSIONS

In both cohorts of patients with chronic HBV infection, acute HEV superinfection increases the risk of liver-related death, especially in those with cirrhosis.

LAY SUMMARY

The mortality caused by acute hepatitis E virus infection is usually low in the healthy population, but it is unclear how it affects patients with chronic hepatitis B virus infection, as they already have compromised liver function. Our data show that the 1-year mortality rate is 35.7% in patients with hepatitis B-related cirrhosis who contract hepatitis E virus. Hepatitis E may accelerate disease progression in patients with chronic hepatitis B.

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Affiliation(s)

Tai-Chung Tseng Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Chun-Jen Liu Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine Taipei, Taiwan
Crystal T Chang Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Tung-Hung Su Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Wan-Ting Yang Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Cheng-Hsueh Tsai Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Chi-Ling Chen Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine Taipei, Taiwan
Hung-Chih Yang Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine Taipei, Taiwan; Department of Microbiology, National Taiwan University College of Medicine Taipei, Taiwan
Chen-Hua Liu Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Pei-Jer Chen Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine Taipei, Taiwan
Ding-Shinn Chen Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taiwan
Jia-Horng Kao Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine Taipei, Taiwan.

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Wang HW, Lai HC, Hu TH, Su WP, Lu SN, Lin CH, Hung CH, Chuang PH, Wang JH, Lee MH, Chen CH, Peng CY. On-Treatment Changes in FIB-4 and 1-Year FIB-4 Values Help Identify Patients with Chronic Hepatitis B Receiving Entecavir Therapy Who Have the Lowest Risk of Hepatocellular Carcinoma. Cancers (Basel) 2020;12:cancers12051177. [PMID: 32392752 PMCID: PMC7281667 DOI: 10.3390/cancers12051177] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Accepted: 05/05/2020] [Indexed: 02/08/2023] Open

Affiliation(s)

Hung-Wei Wang Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung 404, Taiwan; (H.-W.W.); (H.-C.L.); (W.-P.S.); (C.-H.L.); (P.-H.C.)
Hsueh-Chou Lai Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung 404, Taiwan; (H.-W.W.); (H.-C.L.); (W.-P.S.); (C.-H.L.); (P.-H.C.) School of Chinese Medicine, China Medical University, Taichung 404, Taiwan
Tsung-Hui Hu Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (T.-H.H.); (S.-N.L.); (C.-H.H.); (J.-H.W.)
Wen-Pang Su Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung 404, Taiwan; (H.-W.W.); (H.-C.L.); (W.-P.S.); (C.-H.L.); (P.-H.C.)
Sheng-Nan Lu Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (T.-H.H.); (S.-N.L.); (C.-H.H.); (J.-H.W.)
Chia-Hsin Lin Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung 404, Taiwan; (H.-W.W.); (H.-C.L.); (W.-P.S.); (C.-H.L.); (P.-H.C.)
Chao-Hung Hung Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (T.-H.H.); (S.-N.L.); (C.-H.H.); (J.-H.W.)
Po-Heng Chuang Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung 404, Taiwan; (H.-W.W.); (H.-C.L.); (W.-P.S.); (C.-H.L.); (P.-H.C.)
Jing-Houng Wang Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (T.-H.H.); (S.-N.L.); (C.-H.H.); (J.-H.W.)
Mei-Hsuan Lee Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan;
Chien-Hung Chen Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (T.-H.H.); (S.-N.L.); (C.-H.H.); (J.-H.W.) Correspondence: (C.-H.C.); (C.-Y.P.); Tel.: +886-4-2205-2121 (ext. 2260) (C.-Y.P.)
Cheng-Yuan Peng Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung 404, Taiwan; (H.-W.W.); (H.-C.L.); (W.-P.S.); (C.-H.L.); (P.-H.C.) School of Medicine, China Medical University, Taichung 404, Taiwan Correspondence: (C.-H.C.); (C.-Y.P.); Tel.: +886-4-2205-2121 (ext. 2260) (C.-Y.P.)

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Tseng TC, Peng CY, Hsu YC, Su TH, Wang CC, Liu CJ, Yang HC, Yang WT, Lin CH, Yu ML, Lai HC, Tanaka Y, Nguyen MH, Liu CH, Chen PJ, Chen DS, Kao JH. Baseline Mac-2 Binding Protein Glycosylation Isomer Level Stratifies Risks of Hepatocellular Carcinoma in Chronic Hepatitis B Patients with Oral Antiviral Therapy. Liver Cancer 2020;9:207-220. [PMID: 32399434 PMCID: PMC7206589 DOI: 10.1159/000504650] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Accepted: 11/08/2019] [Indexed: 02/04/2023] Open

Affiliation(s)

Tai-Chung Tseng Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Cheng-Yuan Peng School of Medicine, China Medical University, Taichung, Taiwan,Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
Yao-Chun Hsu Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
Tung-Hung Su Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Chia-Chi Wang Division of Gastroenterology, Department of Internal Medicine, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taipei, Taiwan,School of Medicine, Tzu Chi University, Hualien, Taiwan
Chun-Jen Liu Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
Hung-Chih Yang Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan,Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan
Wan-Ting Yang Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Chia-Hsin Lin Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
Ming-Lung Yu Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Hsueh-Chou Lai Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
Yasuhito Tanaka Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Mindie H. Nguyen Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
Chen-Hua Liu Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Pei-Jer Chen Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
Ding-Shinn Chen Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan,Genomics Research Center Academia Sinica, Taipei, Taiwan
Jia-Horng Kao Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan,Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan,*Prof. Jia-Horng Kao, National Chair Professor, Ministry of Education and Distinguished Professor, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te Street, Taipei 10002 (Taiwan), E-Mail

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Tseng TC, Liu CJ, Hsu CY, Hong CM, Su TH, Yang WT, Chen CL, Yang HC, Huang YT, Fang-Tzu Kuo S, Liu CH, Chen PJ, Chen DS, Kao JH. High Level of Hepatitis B Core-Related Antigen Associated With Increased Risk of Hepatocellular Carcinoma in Patients With Chronic HBV Infection of Intermediate Viral Load. Gastroenterology 2019;157:1518-1529.e3. [PMID: 31470004 DOI: 10.1053/j.gastro.2019.08.028] [Citation(s) in RCA: 92] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2018] [Revised: 08/18/2019] [Accepted: 08/20/2019] [Indexed: 02/07/2023]

Abstract

BACKGROUND & AIMS

Chronic hepatitis B virus (HBV) infection is a risk factor for hepatocellular carcinoma (HCC). Serum levels of HB core-related antigen (HBcrAg) have been associated with active replication of HBV. We investigated whether HBcrAg levels are associated with development of HCC, especially in patients who do not require antiviral treatment.

METHODS

We collected data from 2666 adults positive for hepatitis B surface antigen (HBsAg), infected with HBV genotypes B or C, and without liver cirrhosis, who had long-term follow-up at the National Taiwan University Hospital from 1985 through 2000. None of the patients received antiviral treatment during the follow-up. Baseline levels of HBV DNA, HBsAg, and HBcrAg were determined retrospectively and participants were followed for a mean of 15.95 years. The primary end point was an association between serum level of HBcrAg and HCC development.

RESULTS

HCC developed in 209 patients in the cohort (incidence rate, 4.91 cases/1000 person-years). We found a positive association between baseline level of HBcrAg and HCC development; HBcrAg level was an independent risk factor in multivariable analysis. In the subgroup of hepatitis B e antigen-negative patients with HBV DNA levels from 2000 to 19,999 IU/mL (intermediate viral load [IVL]) and normal levels of alanine aminotransferase, HBcrAg levels of 10 KU/mL or more identified patients at increased risk of HCC (hazard ratio, 6.29; confidence interval, 2.27-17.48). Patients with an IVL and a high level of HBcrAg had a risk for HCC that did not differ significantly from that of patients with a high viral load (≥20,000 IU/mL). Patients with an IVL but a low level of HBcrAg had a low risk of HCC, with an annual incidence rate of 0.10% (95% confidence interval, 0.04%-0.24%).

CONCLUSIONS

In a long-term follow-up study of 2666 patients with chronic HBV infection (genotypes B or C), level of HBcrAg is an independent risk factor of HCC. Moreover, HBcrAg level of 10 KU/mL identifies patients with an IVL who are at high risk for HCC.

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Affiliation(s)

Tai-Chung Tseng Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Chun-Jen Liu Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
Chen-Yang Hsu Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
Chun-Ming Hong Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Tung-Hung Su Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Wan-Ting Yang Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Chi-Ling Chen Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
Hung-Chih Yang Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan
Yen-Tsung Huang Institute of Statistical Science, Academia Sinica, Taipei, Taiwan
Stephanie Fang-Tzu Kuo Royal Hobart Hospital, Hobart, Australia
Chen-Hua Liu Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Pei-Jer Chen Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
Ding-Shinn Chen Genomics Research Center, Academia Sinica, Taipei, Taiwan
Jia-Horng Kao Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.

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Lin TC, Liu WC, Hsu YH, Lin JJ, Chiu YC, Chiu HC, Cheng PN, Chen CY, Chang TT, Wu IC. Insulin Resistance Associated Disorders Pivoting Long-Term Hepatitis B Surface Antigen Decline During Entecavir Therapy. J Clin Med 2019;8:jcm8111892. [PMID: 31698809 PMCID: PMC6912775 DOI: 10.3390/jcm8111892] [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: 09/23/2019] [Revised: 10/22/2019] [Accepted: 11/04/2019] [Indexed: 11/29/2022] Open

Affiliation(s)

Tien-Ching Lin Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan; (T.-C.L.); (J.-J.L.); (Y.-C.C.); (H.-C.C.); (P.-N.C.); (C.-Y.C.); (T.-T.C.) Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan;
Wen-Chun Liu Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan 701, Taiwan;
Yu-Hsiang Hsu Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan; Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan
Jia-Jhen Lin Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan; (T.-C.L.); (J.-J.L.); (Y.-C.C.); (H.-C.C.); (P.-N.C.); (C.-Y.C.); (T.-T.C.)
Yen-Cheng Chiu Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan; (T.-C.L.); (J.-J.L.); (Y.-C.C.); (H.-C.C.); (P.-N.C.); (C.-Y.C.); (T.-T.C.)
Hung-Chih Chiu Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan; (T.-C.L.); (J.-J.L.); (Y.-C.C.); (H.-C.C.); (P.-N.C.); (C.-Y.C.); (T.-T.C.)
Pin-Nan Cheng Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan; (T.-C.L.); (J.-J.L.); (Y.-C.C.); (H.-C.C.); (P.-N.C.); (C.-Y.C.); (T.-T.C.)
Chiung-Yu Chen Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan; (T.-C.L.); (J.-J.L.); (Y.-C.C.); (H.-C.C.); (P.-N.C.); (C.-Y.C.); (T.-T.C.)
Ting-Tsung Chang Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan; (T.-C.L.); (J.-J.L.); (Y.-C.C.); (H.-C.C.); (P.-N.C.); (C.-Y.C.); (T.-T.C.) Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan; Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan 701, Taiwan; Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan
I-Chin Wu Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan; (T.-C.L.); (J.-J.L.); (Y.-C.C.); (H.-C.C.); (P.-N.C.); (C.-Y.C.); (T.-T.C.) Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan 701, Taiwan; Correspondence: ; Tel.: +886-6-2353535 (ext. 3588); Fax: +886-6-2743166

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Thi Vo T, Poovorawan K, Charoen P, Soonthornworasiri N, Nontprasert A, Kittitrakul C, Phumratanaprapin W, Tangkijvanich P. Association between Hepatitis B Surface Antigen Levels and the Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Infection: Systematic Review and Meta-Analysis. Asian Pac J Cancer Prev 2019;20:2239-2246. [PMID: 31450890 PMCID: PMC6852811 DOI: 10.31557/apjcp.2019.20.8.2239] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Indexed: 01/14/2023] Open

Tseng TC, Shih YF, Liu CJ. A simple non-invasive test for ruling out cirrhosis in chronic hepatitis B. Lancet Gastroenterol Hepatol 2019;4:495-496. [PMID: 30975476 DOI: 10.1016/s2468-1253(19)30118-9] [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: 03/21/2019] [Accepted: 03/21/2019] [Indexed: 11/25/2022]

Zhang L, Zhang FK. Recent advances in assessment and treatment of chronic hepatitis B. Shijie Huaren Xiaohua Zazhi 2019;27:209-219. [DOI: 10.11569/wcjd.v27.i4.209] [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: 02/06/2023] Open

Wang HW, Lai HC, Hu TH, Su WP, Lu SN, Lin CH, Hung CH, Chuang PH, Wang JH, Lee MH, Chen CH, Peng CY. Stratification of hepatocellular carcinoma risk through modified FIB-4 index in chronic hepatitis B patients on entecavir therapy. J Gastroenterol Hepatol 2019;34:442-449. [PMID: 29968933 DOI: 10.1111/jgh.14372] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Revised: 06/14/2018] [Accepted: 06/26/2018] [Indexed: 12/13/2022]

Affiliation(s)

Hung-Wei Wang Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
Hsueh-Chou Lai Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.,School of Chinese Medicine, China Medical University, Taichung, Taiwan
Tsung-Hui Hu Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Wen-Pang Su Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
Sheng-Nan Lu Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Chia-Hsin Lin Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
Chao-Hung Hung Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Po-Heng Chuang Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
Jing-Houng Wang Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Mei-Hsuan Lee Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
Chien-Hung Chen Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Cheng-Yuan Peng Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.,School of Medicine, China Medical University, Taichung, Taiwan

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Liu CJ, Tseng TC, Yang WT, Su TH, Yang HC, Liu CH, Chen PJ, Chen DS, Kao JH. Profile and value of FIB-4 in patients with dual chronic hepatitis C and B. J Gastroenterol Hepatol 2019;34:410-417. [PMID: 30151861 DOI: 10.1111/jgh.14455] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 07/28/2018] [Accepted: 08/03/2018] [Indexed: 12/14/2022]

Affiliation(s)

Chun-Jen Liu Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Tai-Chung Tseng Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Wan-Ting Yang Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Tung-Hung Su Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Hung-Chih Yang Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan
Chen-Hua Liu Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Pei-Jer Chen Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Ding-Shinn Chen Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Jia-Horng Kao Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan

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Liao SH, Su TH, Jeng YM, Liang PC, Chen DS, Chen CH, Kao JH. Clinical Manifestations and Outcomes of Patients with Sarcomatoid Hepatocellular Carcinoma. Hepatology 2019;69:209-221. [PMID: 30014620 DOI: 10.1002/hep.30162] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Accepted: 05/20/2018] [Indexed: 12/15/2022]

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide. Sarcomatoid HCC is a rare histological subtype of HCC with largely unclear clinical manifestations and outcomes. We evaluated the clinical manifestations and outcomes of patients with sarcomatoid HCC. We identified 5,047 patients with histologically proven HCC from the Cancer Registry Database (1996-2016) of National Taiwan University Hospital. Among them, 40 patients with sarcomatoid HCC were identified from the pathology database of National Taiwan University Hospital. We included 160 patients with nonsarcomatoid HCC through propensity score matching according to sex, age, and Barcelona Clinic Liver Cancer stage. The majority of these patients with sarcomatoid HCC were men (75%); their median age was 58 years. Only 47.5% of the patients with sarcomatoid HCC presented with typical image patterns of HCC. The pathological grading of sarcomatoid HCC was more advanced compared with that of nonsarcomatoid HCC (42.5% vs. 23.8% in grade III and IV, P < 0.0001). The sarcomatoid group had significantly shorter median recurrence-free (13.3 vs. 84.2 months, log-rank P < 0.0001) and overall (8.3 vs. 69.3 months, log-rank P < 0.0001) survival than did the nonsarcomatoid group. The results of the multivariable Cox proportional hazard model revealed histological sarcomatoid subtype as an independent factor for all-cause mortality (hazard ratio [HR], 6.47; 95% confidence interval [CI], 3.12-13.43; P < 0.0001) and tumor recurrence (HR, 4.08; 95% CI, 1.72-9.66; P = 0.001). Conclusion: Compared with nonsarcomatoid HCC, sarcomatoid HCC was associated with more advanced histological grades and atypical image patterns. Histological sarcomatoid subtype is an independent predictor of tumor recurrence after curative treatment and all-cause mortality in patients with HCC.

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Lin CC, Bair MJ, Liu CY, Lin ZY, Chen CJ, Chen MJ, Chu CH, Wang HY, Shih SC, Wang TE. High percentage atypical hepatocellular carcinoma in chronic hepatitis B patients treated with nucleos(t)ide analogs. Medicine (Baltimore) 2019;98:e13818. [PMID: 30608393 PMCID: PMC6344209 DOI: 10.1097/md.0000000000013818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open

Chien RN, Kao JH, Peng CY, Chen CH, Liu CJ, Huang YH, Hu TH, Yang HI, Lu SN, Ni YH, Chuang WL, Lee CM, Wu JC, Chen PJ, Liaw YF. Taiwan consensus statement on the management of chronic hepatitis B. J Formos Med Assoc 2018;118:7-38. [PMID: 30527436 DOI: 10.1016/j.jfma.2018.11.008] [Citation(s) in RCA: 71] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2018] [Revised: 11/06/2018] [Accepted: 11/15/2018] [Indexed: 01/10/2023] Open

Affiliation(s)

Rong-Nan Chien Liver Research Unit, Linkou Chang Gung Memorial Hospital and University College of Medicine, Taoyuan, Taiwan.
Jia-Horng Kao Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
Cheng-Yuan Peng Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
Chien-Hung Chen Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Chun-Jen Liu Graduate Institute of Clinical Medicine, Department of Internal Medicine and Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
Yi-Hsiang Huang Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
Tsung-Hui Hu Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Hwa-I Yang Department of Genomic Research Center, Sinica Academia, Taipei, Taiwan
Sheng-Nan Lu Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
Yen-Hsuan Ni Department of Pediatrics, National Taiwan University College of Medicine and Children's Hospital, Taipei, Taiwan
Won-Long Chuang Division of Hepatobiliary and Pancreas, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
Chuan-Mo Lee Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Jaw-Chin Wu Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
Pei-Jer Chen Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
Yun-Fan Liaw Liver Research Unit, Linkou Chang Gung Memorial Hospital and University College of Medicine, Taoyuan, Taiwan

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Tseng TC, Liu CJ, Su TH, Yang WT, Chen CL, Yang HC, Kuo SFT, Liu CH, Chen PJ, Chen DS, Kao JH. Fibrosis-4 index predicts cirrhosis risk and liver-related mortality in 2075 patients with chronic HBV infection. Aliment Pharmacol Ther 2018;47:1480-1489. [PMID: 29601647 DOI: 10.1111/apt.14619] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2018] [Revised: 01/26/2018] [Accepted: 02/28/2018] [Indexed: 12/14/2022]

Affiliation(s)

T-C Tseng Department of Internal Medicine, National Taiwan University Hospital, New Taipei City, Taiwan.,Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
C-J Liu Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
T-H Su Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
W-T Yang Hepatitis Research Center, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
C-L Chen Graduate Institute of Clinical Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
H-C Yang Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Microbiology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
S F-T Kuo Royal Hobart Hospital, Hobart, Australia
C-H Liu Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
P-J Chen Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
D-S Chen Genomics Research Center Academia Sinica, Taipei, Taiwan
J-H Kao Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan

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