{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T01:42:57Z","timestamp":1785894177214,"version":"3.56.0"},"reference-count":25,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T00:00:00Z","timestamp":1599177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Guidelines recommend liver biopsy to rule out significant inflammatory activity in chronic hepatitis B (CHB) patients with elevated hepatitis B virus (HBV) DNA but without other indications for treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To study rates and determinants of clinically significant liver inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We selected patients with HBV DNA\u00a0&gt;\u00a02000\u00a0IU\/mL from the SONIC\u2010B database. The presence of significant inflammation (METAVIR\u00a0\u2265\u00a0A2 or HAI\u00a0\u2265\u00a09) was assessed by liver biopsy and correlated with alanine aminotransferase (ALT) levels (according to AASLD upper limits of normal [ULN]) and stratified by the presence of significant liver fibrosis (Ishak\u00a0\u2265\u00a03 or METAVIR\u00a0\u2265\u00a0F2).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The cohort included 2991 patients; 1672 were HBeAg\u2010positive. ALT was\u00a0&lt;\u00a0ULN in 270 (9%), 1\u20102 times ULN in 852 (29%) and\u00a0&gt;\u00a02 times ULN in 1869 (63%). Significant fibrosis was found in 1419 (47%) and significant inflammatory activity in 630 (21%). Significant inflammatory activity was found in 34% of patients with liver fibrosis, compared to 9.5% of those without (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). Among patients without fibrosis, significant inflammatory activity was detected in 3.6% of those with normal ALT, 5.0% of those with ALT 1\u20102 times ULN and in 13% of those with ALT\u00a0&gt;\u00a02 times ULN (<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.001). ALT\u00a0&lt;\u00a02 times ULN had a negative predictive value of 95% for ruling out significant inflammatory activity among patients without liver fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Among patients without significant fibrosis, an ALT level\u00a0&lt;\u00a02 times ULN is associated with\u00a0&lt;\u00a05% probability of significant inflammatory activity. If fibrosis can be ruled out using non\u2010invasive methods, liver biopsy solely to assess inflammatory activity should be discouraged.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.16067","type":"journal-article","created":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T17:17:11Z","timestamp":1693934231000},"page":"1399-1406","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Very low probability of significant liver inflammation in chronic hepatitis B patients with low ALT levels in the absence of liver fibrosis"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9253-563X","authenticated-orcid":false,"given":"Milan J.","family":"Sonneveld","sequence":"first","affiliation":[{"name":"Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8713-1481","authenticated-orcid":false,"given":"Willem P.","family":"Brouwer","sequence":"additional","affiliation":[{"name":"Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina E.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7790-1611","authenticated-orcid":false,"given":"Henry L.\u2010Y.","family":"Chan","sequence":"additional","affiliation":[{"name":"Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teerha","family":"Piratvisuth","sequence":"additional","affiliation":[{"name":"Hat Yai Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4673-8890","authenticated-orcid":false,"given":"Ji\u2010Dong","family":"Jia","sequence":"additional","affiliation":[{"name":"Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Zeuzem","sequence":"additional","affiliation":[{"name":"Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong\u2010Nan","family":"Chien","sequence":"additional","affiliation":[{"name":"Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Choi","sequence":"additional","affiliation":[{"name":"Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0934-6975","authenticated-orcid":false,"given":"Robert J.","family":"de Knegt","sequence":"additional","affiliation":[{"name":"Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Wat","sequence":"additional","affiliation":[{"name":"Welwyn Garden City UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vedran","family":"Pavlovic","sequence":"additional","affiliation":[{"name":"Welwyn Garden City UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuj","family":"Gaggar","sequence":"additional","affiliation":[{"name":"Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Xie","sequence":"additional","affiliation":[{"name":"Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0732-3078","authenticated-orcid":false,"given":"Maria","family":"Buti","sequence":"additional","affiliation":[{"name":"Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"de Man","sequence":"additional","affiliation":[{"name":"Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry L.A.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Rotterdam The Netherlands"},{"name":"Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the SONIC\u2010B Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,4]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"370","article-title":"Clinical Practice Guidelines on the management of hepatitis B virus infection","volume":"2017","author":"European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL","year":"2017","journal-title":"J Hepatol"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29800"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2009.248"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-33412-z"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.13163"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0000000000000544"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2010.01270.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15311"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)17701-0"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2010.186"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.12468"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043470"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040431"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24555"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0802878"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(02)00357-4"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.02.075"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2011.11.030"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2007.07.022"},{"key":"e_1_2_9_21_1","first-page":":237\u2013264","article-title":"EASL\u2010ALEH Clinical Practice Guidelines: Non\u2010invasive tests for evaluation of liver disease severity and prognosis","volume":"63","author":"European Association for Study of L, Asociacion Latinoamericana para el Estudio del H","year":"2015","journal-title":"J Hepatol"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(19)30087-1"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa192"},{"issue":"1","key":"e_1_2_9_24_1","article-title":"Tenofovir for preventing progression of chronic hepatitis B in patients with minimally raised aminotransferase \u2010 final results of a multicenter double\u2010blind placebo\u2010controlled trial","volume":"70","author":"Hsu YC","year":"2019","journal-title":"Hepatology"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.07.018"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20535"}],"container-title":["Alimentary Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apt.16067","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T17:17:31Z","timestamp":1693934251000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apt.16067"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,4]]},"references-count":25,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,10]]}},"alternative-id":["10.1111\/apt.16067"],"URL":"https:\/\/doi.org\/10.1111\/apt.16067","archive":["Portico"],"relation":{},"ISSN":["0269-2813","1365-2036"],"issn-type":[{"value":"0269-2813","type":"print"},{"value":"1365-2036","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,4]]},"assertion":[{"value":"2020-05-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}