{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T02:53:17Z","timestamp":1794019997661,"version":"4.8.0"},"reference-count":56,"publisher":"Wiley","issue":"11-12","license":[{"start":{"date-parts":[[2020,10,18]],"date-time":"2020-10-18T00:00:00Z","timestamp":1602979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Children with intrahepatic cholestasis and genetic variants which result in the disruption of the formation and maintenance of bile (\n                      <jats:italic>ABCB11<\/jats:italic>\n                      ,\n                      <jats:italic>ABCB4<\/jats:italic>\n                      and\n                      <jats:italic>ATP8B1<\/jats:italic>\n                      ) generally have a rapidly progressive clinical course. Adults with different phenotypes of cholestasis are increasingly being evaluated for variants in these genes associated with childhood diseases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To review the literature with respect to the presence of variants in cholestasis\u2010related genes in adults with various liver phenotypes, and provide clinical implications of the findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A search of the literature on variants in specific cholestasis\u2010related genes in adults was conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The common variant p.Val444Ala in\n                      <jats:italic>ABCB11<\/jats:italic>\n                      confers increased risk of drug\u2010induced liver injury and intrahepatic cholestasis of pregnancy (ICP). Individuals with variants in\n                      <jats:italic>ABCB4<\/jats:italic>\n                      are at risk of ICP and low phospholipid\u2010associated cholelithiasis. Variants in\n                      <jats:italic>ABCB4<\/jats:italic>\n                      , and possibly\n                      <jats:italic>ABCB11<\/jats:italic>\n                      and\n                      <jats:italic>ATP8B1<\/jats:italic>\n                      , can be identified in up to a third of patients with cryptogenic chronic cholestasis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Individuals with variants in\n                      <jats:italic>ABCB11<\/jats:italic>\n                      rarely develop cholestasis until BSEP function dips below a threshold, which is also affected by other factors (e.g., drugs, hormones). However, variants in\n                      <jats:italic>ABCB4<\/jats:italic>\n                      and consequent reduction in MDR3 protein, have a more linear dose\u2010response curve. In individuals with an\n                      <jats:italic>ABCB11<\/jats:italic>\n                      variant, medications known to reduce BSEP activity should be used cautiously; they should be monitored during pregnancy for ICP; and first\u2010degree relatives should be counselled and screened. No proven management strategy exists, although ursodeoxycholic acid may be beneficial. Further work is needed to define the genotype\u2010phenotype correlation and natural history, and to evaluate the penetrance.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apt.16118","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T02:37:57Z","timestamp":1693795077000},"page":"1628-1639","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Review article: liver disease in adults with variants in the cholestasis\u2010related genes\n                    <i>ABCB11<\/i>\n                    ,\n                    <i>ABCB4<\/i>\n                    and\n                    <i>ATP8B1<\/i>"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0344-0218","authenticated-orcid":false,"given":"Jeremy S.","family":"Nayagam","sequence":"first","affiliation":[{"name":"Institute of Liver Studies King's College Hospital London 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