{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:00:29Z","timestamp":1790200829288,"version":"4.1.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":304,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Suomen Akatemia","doi-asserted-by":"publisher","award":["138566"],"award-info":[{"award-number":["138566"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Epilepsy Research Foundation, Finland, dor Dr. Johanna Hynynen"},{"name":"Foundation for Pediatric Research, Finland"},{"name":"Marie Curie IOF for Dr. Reetta Hinttala","award":["273669"],"award-info":[{"award-number":["273669"]}]},{"name":"Special State Grants for Health Research, Dept of Pediatrics and Adolescence, Oulu University Hospital"},{"name":"the National Clinical Graduate School, Finland, for Dr. Tuomas Komulainen"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Patients with mutations in the\n                      <jats:italic toggle=\"yes\">POLG1<\/jats:italic>\n                      gene encoding mitochondrial DNA polymerase gamma have an increased risk of valproate-induced liver failure.\n                      <jats:italic toggle=\"yes\">POLG1<\/jats:italic>\n                      mutations are common, and these patients often suffer from intractable seizures. The role of liver transplantation in the treatment of patients with mitochondrial diseases has been controversial. We studied valproate-induced liver failure associated with\n                      <jats:italic toggle=\"yes\">POLG1<\/jats:italic>\n                      mutations and the prognosis for these patients after liver transplantation.\n                      <jats:italic toggle=\"yes\">POLG1<\/jats:italic>\n                      was analyzed in blood DNA, mitochondrial DNA (mtDNA) was quantified in liver samples, and clinical data were collected. Five patients with valproate-induced liver failure associated with\n                      <jats:italic toggle=\"yes\">POLG1<\/jats:italic>\n                      mutations were retrospectively identified. Three patients were previously suspected to have Wilson's disease. Four patients with homozygous p.W748S and p.E1143G mutations had mtDNA depletion in the liver. One of these patients died before anticipated transplantation; the other 3 patients with liver transplantation have survived 4 to 19 years. Two patients have presented with occasional epileptic seizures, and 1 patient has been seizure-free for 11 years. One patient with a heterozygous p.Q1236H mutation (but without mtDNA depletion in the liver) died suddenly 2 years after liver transplantation. In conclusion, the\n                      <jats:italic toggle=\"yes\">POLG1<\/jats:italic>\n                      mutation status and the age at presentation of valproate-induced liver failure can affect the prognosis after liver transplantation. A heterozygous\n                      <jats:italic toggle=\"yes\">POLG1<\/jats:italic>\n                      p.Q1236H mutation was related to valproate-induced liver failure without mtDNA depletion, whereas patients homozygous for\n                      <jats:italic toggle=\"yes\">POLG1<\/jats:italic>\n                      p.W748S and p.E1143G mutations had mtDNA depletion. An analysis of the\n                      <jats:italic toggle=\"yes\">POLG1<\/jats:italic>\n                      gene should be performed for all patients with suspected mitochondrial disease before the introduction of valproate therapy, and treatment with valproic acid should be avoided in these patients.\n                      <jats:italic toggle=\"yes\">Liver Transpl 20:1402\u20131412, 2014<\/jats:italic>\n                      . \u00a9 2014 AASLD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/lt.23965","type":"journal-article","created":{"date-parts":[[2014,7,28]],"date-time":"2014-07-28T05:54:15Z","timestamp":1406526855000},"page":"1402-1412","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":68,"title":["Acute liver failure after valproate exposure in patients with POLG1 mutations and the prognosis after liver 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