{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:37:10Z","timestamp":1792103830026,"version":"4.4.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T00:00:00Z","timestamp":1642377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012659","name":"Foundation for Innovative Research Groups of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570535, 81770587"],"award-info":[{"award-number":["81570535, 81770587"]}],"id":[{"id":"10.13039\/501100012659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013098","name":"Scientific and Innovative Action Plan of Shanghai","doi-asserted-by":"publisher","award":["16CR1002A"],"award-info":[{"award-number":["16CR1002A"]}],"id":[{"id":"10.13039\/501100013098","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012303","name":"Key Disciplines Construction Project of Shanghai Municipal","doi-asserted-by":"publisher","award":["shslczdzk01103"],"award-info":[{"award-number":["shslczdzk01103"]}],"id":[{"id":"10.13039\/501100012303","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012157","name":"Shanghai Key Discipline Construction Project","doi-asserted-by":"publisher","award":["15GWZK0102"],"award-info":[{"award-number":["15GWZK0102"]}],"id":[{"id":"10.13039\/501100012157","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Backgrounds and Purpose<\/jats:title><jats:p>Concurrent non-alcoholic fatty liver disease (NAFLD) in chronic hepatitis B (CHB) patients is a frequent and increasingly concerning problem because of the NAFLD pandemic. Admittedly, NAFLD can progress to non-alcoholic steatohepatitis (NASH) and severe fibrosis. Direct evidence of the fibrotic effect of NAFLD or NASH in chronic hepatitis B virus (HBV) infection remains lacking. We aimed to reveal the influence of concurrent histologically proven fatty liver diseases in fibrogenesis with chronic HBV infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a retrospective cross-sectional study on a liver biopsy population of CHB patients without excessive alcohol intake to evaluate the prevalence of concurrent histologically proven NAFLD or NASH according to the fatty liver inhibition of progression (FLIP) algorithm and its association with the liver fibrosis stage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 1,081 CHB patients, concurrent NAFLD was found in 404 patients (37.4%), among whom 24.0% (97\/404) have NASH. The presence of NASH was an independent predictor of significant fibrosis (odds ratio (OR), 2.53; 95% CI, 1.52\u20134.21; <jats:italic>p<\/jats:italic> &amp;lt; 0.001) and severe fibrosis (OR, 1.83; 95% CI, 1.09\u20133.09; <jats:italic>p<\/jats:italic> = 0.023) in all patients, as well as in patients with normal alanine aminotransferase (ALT) (predicting significant fibrosis, OR, 2.86, 95% CI, 1.34\u20136.10; <jats:italic>p<\/jats:italic> = 0.007). The presence of lobular inflammation (<jats:italic>p<\/jats:italic> &amp;lt; 0.001) or presence of cytological ballooning (<jats:italic>p<\/jats:italic> &amp;lt; 0.001), rather than presence of steatosis (<jats:italic>p<\/jats:italic> = 0.419), was related with severity of fibrosis in Spearman\u2019s correlation analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Concurrent NAFLD is common in CHB patients, and NASH is an independent risk factor potentiating significant fibrosis by 2.53-fold and severe fibrosis by 1.83-fold. While coping with chronic HBV infection, routine assessment of co-existing NAFLD or NASH is also important.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2021.733348","type":"journal-article","created":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T05:57:10Z","timestamp":1642399030000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Application of Fatty Liver Inhibition of Progression Algorithm and Steatosis, Activity, and Fibrosis Score to Assess the Impact of Non-Alcoholic Fatty Liver on Untreated Chronic Hepatitis B Patients"],"prefix":"10.3389","volume":"11","author":[{"given":"Yan","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinyi","family":"Gan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongtao","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simin","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zike","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gangde","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhujun","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1136\/gutjnl-2017-313884","article-title":"Non-Alcoholic Fatty Liver Disease and Its Relationship With Cardiovascular Disease and Other Extrahepatic Diseases","volume":"66","author":"Adams","year":"2017","journal-title":"Gut"},{"key":"B2","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1002\/hep.27173","article-title":"Utility and Appropriateness of the Fatty Liver Inhibition of Progression (FLIP) Algorithm and Steatosis, Activity, and Fibrosis (SAF) Score in the Evaluation of Biopsies of Nonalcoholic Fatty Liver Disease","volume":"60","author":"Bedossa","year":"2014","journal-title":"Hepatology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1111\/j.1478-3231.2007.01482.x","article-title":"Impact of Non-Alcoholic Fatty Liver Disease on Chronic Hepatitis B","volume":"27","author":"Bondini","year":"2007","journal-title":"Liver Int."},{"key":"B4","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1111\/jvh.12786","article-title":"Assessment of Serum Golgi Protein 73 as a Biomarker for the Diagnosis of Significant Fibrosis in Patients With Chronic HBV Infection","volume":"24","author":"Cao","year":"2017","journal-title":"J. Viral Hepat."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1612","DOI":"10.1111\/liv.13536","article-title":"Algorithm of Golgi Protein 73 and Liver Stiffness Accurately Diagnoses Significant Fibrosis in Chronic HBV Infection","volume":"37","author":"Cao","year":"2017","journal-title":"Liver Int."},{"key":"B6","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1111\/liv.13271","article-title":"The Prevalence of Steatohepatitis in Chronic Hepatitis B Patients and Its Impact on Disease Severity and Treatment Response","volume":"37","author":"Charatcharoenwitthaya","year":"2017","journal-title":"Liver Int."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1002\/hep.28778","article-title":"Metabolic Syndrome Increases Cardiovascular Events But Not Hepatic Events and Death in Patients With Chronic Hepatitis B","volume":"64","author":"Cheng","year":"2016","journal-title":"Hepatology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1002\/hep.30857","article-title":"Nonalcoholic Steatohepatitis Is Associated With Liver-Related Outcomes and All-Cause Mortality in Chronic Hepatitis B","volume":"71","author":"Choi","year":"2020","journal-title":"Hepatology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/S0140-6736(03)15268-3","article-title":"Appropriate Body-Mass Index for Asian Populations and Its Implications for Policy and Intervention Strategies","volume":"363","year":"2004","journal-title":"Lancet"},{"key":"B10","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1016\/j.jhep.2021.05.025","article-title":"EASL Clinical Practice Guidelines on Non-Invasive Tests for Evaluation of Liver Disease Severity and Prognosis - 2021 Update","volume":"75","year":"2021","journal-title":"J. Hepatol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.jhep.2017.03.021","article-title":"EASL 2017 Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection","volume":"67","year":"2017","journal-title":"J. Hepatol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1111\/jvh.12766","article-title":"Inverse Relationship Between Hepatic Steatosis and Hepatitis B Viremia: Results of a Large Case-Control Study","volume":"25","author":"Hui","year":"2018","journal-title":"J. Viral Hepat"},{"key":"B13","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1042\/BJ20081336","article-title":"Hepatitis B Virus X Protein Induces Lipogenic Transcription Factor SREBP1 and Fatty Acid Synthase Through the Activation of Nuclear Receptor LXRalpha","volume":"416","author":"Kim","year":"2008","journal-title":"Biochem. J."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1955","DOI":"10.1053\/j.gastro.2007.03.039","article-title":"Hepatitis B Virus X Protein Induces Hepatic Steatosis via Transcriptional Activation of SREBP1 and PPARgamma","volume":"132","author":"Kim","year":"2007","journal-title":"Gastroenterology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1038\/nrgastro.2013.171","article-title":"The Global NAFLD Epidemic","volume":"10","author":"Loomba","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.1053\/j.gastro.2016.02.066","article-title":"Pathogenesis of Nonalcoholic Steatohepatitis","volume":"150","author":"Machado","year":"2016","journal-title":"Gastroenterology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"S61","DOI":"10.1002\/hep.22930","article-title":"Liver Biopsy Findings in Chronic Hepatitis B","volume":"49","author":"Mani","year":"2009","journal-title":"Hepatology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2427","DOI":"10.1111\/liv.14492","article-title":"Disruption of Plin5 Degradation by CMA Causes Lipid Homeostasis Imbalance in NAFLD","volume":"40","author":"Ma","year":"2020","journal-title":"Liver Int."},{"key":"B19","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1016\/j.jhep.2019.12.008","article-title":"Clinical Validation of the FLIP Algorithm and the SAF Score in Patients With Non-Alcoholic Fatty Liver Disease","volume":"72","author":"Nascimbeni","year":"2020","journal-title":"J. Hepatol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.jhep.2016.08.013","article-title":"Time Trends of Chronic HBV Infection Over Prior Decades - A Global Analysis","volume":"66","author":"Ott","year":"2017","journal-title":"J. Hepatol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1111\/j.1440-1746.2008.05478.x","article-title":"Hepatic Steatosis in Chronic Hepatitis B Patients Is Associated With Metabolic Factors More Than Viral Factors","volume":"23","author":"Peng","year":"2008","journal-title":"J. Gastroenterol. Hepatol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/S2468-1253(18)30056-6","article-title":"Global Prevalence, Treatment, and Prevention of Hepatitis B Virus Infection in 2016: A Modelling Study","volume":"3","year":"2018","journal-title":"Lancet. Gastroenterol. Hepatol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/0168-8278(91)90084-o","article-title":"Classification of Chronic Viral Hepatitis: A Need for Reassessment","volume":"13","author":"Scheuer","year":"1991","journal-title":"J. Hepatol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1111\/apt.15298","article-title":"Moderate to Severe Hepatic Steatosis Leads to Overestimation of Liver Stiffness Measurement in Chronic Hepatitis B Patients Without Significant Fibrosis","volume":"50","author":"Shen","year":"2019","journal-title":"Aliment Pharmacol. Ther."},{"key":"B25","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1097\/00042737-200603000-00002","article-title":"Prevalence of Liver Steatosis in Patients With Chronic Hepatitis B: A Study of Associated Factors and of Relationship With Fibrosis","volume":"18","author":"Thomopoulos","year":"2006","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1136\/gut.2008.157735","article-title":"Metabolic Syndrome Increases the Risk of Liver Cirrhosis in Chronic Hepatitis B","volume":"58","author":"Wong","year":"2009","journal-title":"Gut"},{"key":"B27","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/nrgastro.2017.109","article-title":"Global Burden of NAFLD and NASH: Trends, Predictions, Risk Factors and Prevention","volume":"15","author":"Younossi","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global Epidemiology of Nonalcoholic Fatty Liver Disease-Meta-Analytic Assessment of Prevalence, Incidence, and Outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"B29","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1111\/liv.14369","article-title":"Chronic Hepatitis B and Non-Alcoholic Fatty Liver Disease: Conspirators or Competitors","volume":"40","author":"Zhang","year":"2020","journal-title":"Liver Int."},{"key":"B30","doi-asserted-by":"publisher","first-page":"272","DOI":"10.7150\/ijms.7.272","article-title":"Predictors of Hepatic Steatosis in HBeAg-Negative Chronic Hepatitis B Patients and Their Diagnostic Values in Hepatic Fibrosis","volume":"7","author":"Zheng","year":"2010","journal-title":"Int. J. Med. Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1111\/jvh.12878","article-title":"Current But Not Past Hepatitis B Virus Infection Is Associated With a Decreased Risk of Nonalcoholic Fatty Liver Disease in the Chinese Population: A Case-Control Study With Propensity Score Analysis","volume":"25","author":"Zhong","year":"2018","journal-title":"J. Viral Hepats"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.733348\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T05:57:14Z","timestamp":1642399034000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.733348\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,17]]},"references-count":31,"alternative-id":["10.3389\/fcimb.2021.733348"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2021.733348","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,17]]},"article-number":"733348"}}