{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T16:13:41Z","timestamp":1792253621232,"version":"4.4.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:00:00Z","timestamp":1634860800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:p>\n                    Dyslipidemia and cardiovascular complications are comorbidities of nonalcoholic fatty liver disease (NAFLD), which ranges from simple steatosis to nonalcoholic steatohepatitis, fibrosis, and cirrhosis up to hepatocellular carcinoma. Lipoprotein(a) (Lp(a)) has been associated with cardiovascular risk and metabolic abnormalities, but its impact on the severity of liver damage in patients with NAFLD remains to be clarified. Circulating Lp(a) levels were assessed in 600 patients with biopsy\u2010proven NAFLD. The association of Lp(a) with liver damage was explored by categorizing serum Lp(a) into quartiles. The receiver operating characteristic curve was used to analyze the accuracy of serum Lp(a) in hepatic fibrosis prediction. Hepatic expression of lipoprotein A (\n                    <jats:italic toggle=\"yes\">LPA<\/jats:italic>\n                    ) and of genes involved in lipid metabolism and fibrogenic processes were evaluated by RNA sequencing in a subset of patients with NAFLD for whom Lp(a) dosage was available (n\u00a0=\u00a0183). In patients with NAFLD, elevated Lp(a) levels were modestly associated with circulating lipids, carotid plaques, and hypertension (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0&lt;\u00a00.05). Conversely, patients with low serum Lp(a) displayed insulin resistance (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0&lt;\u00a00.05), transaminase elevation (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0&lt;\u00a00.05), and increased risk of developing severe fibrosis (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0=\u00a00.007) and cirrhosis (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0=\u00a00.002). In addition, the diagnostic accuracy of Lp(a) in predicting fibrosis increased by combining it with transaminases (area under the curve fibrosis stage 4, 0.87;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0&lt;\u00a00.0001). Hepatic\n                    <jats:italic toggle=\"yes\">LPA<\/jats:italic>\n                    expression reflected serum Lp(a) levels (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0=\u00a00.018), and both were reduced with the progression of NAFLD (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0&lt;\u00a00.05). Hepatic\n                    <jats:italic toggle=\"yes\">LPA<\/jats:italic>\n                    messenger RNA levels correlated with those of genes involved in lipoprotein release, lipid synthesis, and fibrogenesis (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0&lt;\u00a00.05). Finally, transmembrane 6 superfamily member 2 (\n                    <jats:italic toggle=\"yes\">TM6SF2<\/jats:italic>\n                    ) rs58542926, apolipoprotein E (\n                    <jats:italic toggle=\"yes\">ApoE<\/jats:italic>\n                    ) rs445925, and proprotein convertase subtilisin\/kexin type 9 (\n                    <jats:italic toggle=\"yes\">PCSK9<\/jats:italic>\n                    ) rs7552841, known variants that modulate circulating lipids, may influence serum Lp(a) levels (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0&lt;\u00a00.05).\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    Circulating Lp(a) combined with transaminases may represent a novel noninvasive biomarker to predict advanced fibrosis in patients with NAFLD.\n                  <\/jats:p>","DOI":"10.1002\/hep4.1830","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T06:47:58Z","timestamp":1634885278000},"page":"535-549","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":47,"title":["Low Lipoprotein(a) Levels Predict Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease"],"prefix":"10.1097","volume":"6","author":[{"given":"Marica","family":"Meroni","sequence":"first","affiliation":[{"name":"General Medicine and Metabolic Diseases,Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) C\u00e0 Granda Ospedale Maggiore Policlinico,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Longo","sequence":"additional","affiliation":[{"name":"General Medicine and Metabolic Diseases,Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) C\u00e0 Granda Ospedale Maggiore Policlinico,Milan,Italy"},{"name":"Department of Clinical Sciences and Community Health,Universit\u00e0 degli Studi di Milano,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Lombardi","sequence":"additional","affiliation":[{"name":"General Medicine and Metabolic Diseases,Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) C\u00e0 Granda Ospedale Maggiore Policlinico,Milan,Italy"},{"name":"Department of Pathophysiology and Transplantation,Universit\u00e0 degli Studi di Milano,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Paolini","sequence":"additional","affiliation":[{"name":"General Medicine and Metabolic Diseases,Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) C\u00e0 Granda Ospedale Maggiore Policlinico,Milan,Italy"},{"name":"Department of Pharmacological and Biomolecular Sciences,Universit\u00e0 degli Studi di Milano,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Macchi","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences,Universit\u00e0 degli Studi di Milano,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Corsini","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences,Universit\u00e0 degli Studi di Milano,Milan,Italy"},{"name":"Multimedica IRCCS,Sesto San Giovanni,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesare R.","family":"Sirtori","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences,Universit\u00e0 degli Studi di Milano,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Ludovica","family":"Fracanzani","sequence":"additional","affiliation":[{"name":"General Medicine and Metabolic Diseases,Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) C\u00e0 Granda Ospedale Maggiore Policlinico,Milan,Italy"},{"name":"Department of Pathophysiology and Transplantation,Universit\u00e0 degli Studi di Milano,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Ruscica","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences,Universit\u00e0 degli Studi di Milano,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4343-7213","authenticated-orcid":false,"given":"Paola","family":"Dongiovanni","sequence":"additional","affiliation":[{"name":"General Medicine and Metabolic Diseases,Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) C\u00e0 Granda Ospedale Maggiore 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