{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:14:41Z","timestamp":1787015681866,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2013,5,19]],"date-time":"2013-05-19T00:00:00Z","timestamp":1368921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Viral hepatitis E clinically ranges between acute self\u2010limiting hepatitis (\n                      <jats:styled-content style=\"fixed-case\">AVH<\/jats:styled-content>\n                      ) and acute liver failure (\n                      <jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content>\n                      ). The varied clinical course of the disease possibly thought to be immune\u2010mediated. High\u2010mobility group box 1 (\n                      <jats:styled-content style=\"fixed-case\">HMGB<\/jats:styled-content>\n                      1) is a non\u2010histone chromosomal nuclear protein with recently discovered pro\u2010inflammatory and immunomodulatory action. Its presence in abundance within hepatocytes is thought provoking in patients with hepatitis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      The present study was designed to elucidate the role of circulating\n                      <jats:styled-content style=\"fixed-case\">HMGB<\/jats:styled-content>\n                      1 and its gene expression in patients with viral hepatitis E.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Blood samples were obtained from\n                      <jats:styled-content style=\"fixed-case\">AVH<\/jats:styled-content>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a038),\n                      <jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a034) and healthy controls (\n                      <jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content>\n                      ,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a030). The\n                      <jats:styled-content style=\"fixed-case\">HMGB<\/jats:styled-content>\n                      1 levels were estimated in serum by quantitative\u2010micro\u2010\n                      <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content>\n                      . Gene expression levels were studied in the patient's\n                      <jats:styled-content style=\"fixed-case\">PBMC<\/jats:styled-content>\n                      s by real\u2010time\n                      <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>\n                      . Lymphocyte proliferation was estimated by colorimetric\u2010\n                      <jats:styled-content style=\"fixed-case\">MTT<\/jats:styled-content>\n                      assay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mean circulating\n                      <jats:styled-content style=\"fixed-case\">HMGB<\/jats:styled-content>\n                      1 levels in\n                      <jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content>\n                      ,\n                      <jats:styled-content style=\"fixed-case\">AVH<\/jats:styled-content>\n                      and\n                      <jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content>\n                      patients were found to be 12.04\u00a0\u00b1\u00a02.23, 112.6\u00a0\u00b1\u00a013.33 and 225.3\u00a0\u00b1\u00a015.04\u00a0ng\/ml respectively. The levels were significantly higher in\n                      <jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content>\n                      than\n                      <jats:styled-content style=\"fixed-case\">AVH<\/jats:styled-content>\n                      and\n                      <jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content>\n                      (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001). Moreover, 88.2% of\n                      <jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content>\n                      patients with\n                      <jats:styled-content>&gt;<\/jats:styled-content>\n                      250\u00a0ng\/ml of circulating\n                      <jats:styled-content style=\"fixed-case\">HMGB<\/jats:styled-content>\n                      1 had a fatal outcome. The gene expression of\n                      <jats:styled-content style=\"fixed-case\">HMGB<\/jats:styled-content>\n                      1 in the\n                      <jats:styled-content style=\"fixed-case\">PBMC<\/jats:styled-content>\n                      s of\n                      <jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content>\n                      and\n                      <jats:styled-content style=\"fixed-case\">AVH<\/jats:styled-content>\n                      patients were comparable. A positive correlation was observed between\n                      <jats:styled-content style=\"fixed-case\">HMGB<\/jats:styled-content>\n                      1 level and\n                      <jats:styled-content style=\"fixed-case\">INR<\/jats:styled-content>\n                      . A significantly low lymphocyte proliferation was observed in\n                      <jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content>\n                      patients (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.008).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Massive necrosis of hepatocytes in\n                      <jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content>\n                      patients might predispose to excessive accumulation of extracellular\n                      <jats:styled-content style=\"fixed-case\">HMGB<\/jats:styled-content>\n                      1 leading to suppression of T\u2010cell proliferation. Therefore, it is proposed that excessive circulating\n                      <jats:styled-content style=\"fixed-case\">HMGB<\/jats:styled-content>\n                      1 might play an important role in immunosuppression and fulminant course of the disease following\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      infection.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.12197","type":"journal-article","created":{"date-parts":[[2013,4,19]],"date-time":"2013-04-19T05:41:11Z","timestamp":1366350071000},"page":"1341-1348","source":"Crossref","is-referenced-by-count":28,"title":["High levels of circulating\n                    <scp>HMGB<\/scp>\n                    1 as a biomarker of acute liver failure in patients with viral hepatitis E"],"prefix":"10.1111","volume":"33","author":[{"given":"Manasi","family":"Majumdar","sequence":"first","affiliation":[{"name":"Department of Virology 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