{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:55:52Z","timestamp":1790780152385,"version":"4.1.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Liver diseases in dogs are often diagnosed at advanced stages due to the organ\u2019s high functional reserve. Early supportive therapy with hepatoprotective nutraceuticals may help slow disease progression in dogs with asymptomatic elevation of liver parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>The aim of this pilot study was to evaluate the hepatoprotective effect of a multi-component preparation containing phospholipids, selected amino acids, betaine, and milk thistle extract in client-owned dogs with asymptomatic elevation of liver parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Seventeen dogs were included in the open-label study. The animals received Hepatiale Forte Advanced (Vet Expert) for 8\u202fweeks at the manufacturer\u2019s recommended dose. Liver enzyme activities (ALT, AST, ALP, GGT), total bilirubin, serum bile acids, hematological parameters, and abdominal ultrasonography were assessed at baseline and after 8\u202fweeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Supplementation resulted in statistically significant reductions in ALT (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.004), AST (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.004), ALP (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.001), total bilirubin (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.001) and serum bile acids (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.007). A trend toward a decrease was observed for GGT (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.052). Hematological parameters remained stable, and the preparation was well tolerated with no adverse effects reported. Ultrasonographic findings were mostly stable or improved (resolution of biliary sludge in some cases).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Eight-week supplementation with the multi-component hepatoprotective preparation was associated with significant improvement in liver biochemical parameters in dogs with asymptomatic elevation of liver parameters. The results support further research in a randomized, placebo-controlled trial.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2026.1938591","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:05:16Z","timestamp":1790777116000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of the hepatoprotective effect of a multi-component preparation containing phospholipids, selected amino acids, betaine, and milk thistle extract in dogs with asymptomatic elevation of liver parameters: a pilot study"],"prefix":"10.3389","volume":"13","author":[{"given":"Renata","family":"Nieradka","sequence":"first","affiliation":[{"name":"Department of Clinical Diagnostics, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn","place":["Olsztyn, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Jank","sequence":"additional","affiliation":[{"name":"Department of Pre-clinical Sciences and Infectious Diseases, Faculty of Veterinary Medicine and Animal Sciences, Poznan University of Life Sciences","place":["Pozna\u0144, Poland"]},{"name":"Vet Planet LLC","place":["\u0141omianki, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Otto","sequence":"additional","affiliation":[{"name":"Vet Planet LLC","place":["\u0141omianki, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Kurosad","sequence":"additional","affiliation":[{"name":"Vet Planet LLC","place":["\u0141omianki, 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Nutr"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"S62","DOI":"10.1093\/jn\/121.suppl_11.S62","article-title":"Effect of portosystemic shunting on nitrogen retention of dogs","volume":"121","author":"Laflamme","year":"1991","journal-title":"J Nutr"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.3390\/ijms18051051","article-title":"The roles of glutamine in the intestine and its implications in intestinal diseases","volume":"18","author":"Min-Hyun","year":"2017","journal-title":"Int J Mol Sci"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1186\/s12917-021-02929-3","article-title":"Effects of silybin supplementation on nutrient digestibility, hematological parameters, liver function indices, and liver-specific mi-RNA concentration in dogs","volume":"17","author":"Gogulski","year":"2021","journal-title":"BMC Vet 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