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Low Lipoprotein(a) Levels Predict Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

Meroni, Marica, Longo, Miriam, Lombardi, Rosa, Paolini, Erika, Macchi, Chiara, Corsini, Alberto, Sirtori, Cesare R., Fracanzani, Anna Ludovica, Ruscica, Massimiliano, Dongiovanni, Paola·2022·Hepatology Communications
DOI 10.1002/hep4.1830
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Abstract

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‐proven 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 ( LPA ) 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 = 183). In patients with NAFLD, elevated Lp(a) levels were modestly associated with circulating lipids, carotid plaques, and hypertension ( P < 0.05). Conversely, patients with low serum Lp(a) displayed insulin resistance ( P < 0.05), transaminase elevation ( P < 0.05), and increased risk of developing severe fibrosis ( P = 0.007) and cirrhosis ( P = 0.002). 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; P < 0.0001). Hepatic LPA expression reflected serum Lp(a) levels ( P = 0.018), and both were reduced with the progression of NAFLD ( P < 0.05). Hepatic LPA messenger RNA levels correlated with those of genes involved in lipoprotein release, lipid synthesis, and fibrogenesis ( P < 0.05). Finally, transmembrane 6 superfamily member 2 ( TM6SF2 ) rs58542926, apolipoprotein E ( ApoE ) rs445925, and proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) rs7552841, known variants that modulate circulating lipids, may influence serum Lp(a) levels ( P < 0.05). Conclusion: Circulating Lp(a) combined with transaminases may represent a novel noninvasive biomarker to predict advanced fibrosis in patients with NAFLD.

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  • EHBP1 mRNA levels are reduced in human liver biopsies from patients carrying the rs10496099 C allele.

    “we evaluated EHBP1 expression in human liver biopsies from which RNA-seq data were available36 (Table S4) and observed reduced mRNA levels in patients carrying the C allele (Figure 1H)”

    From EHBP1 suppresses liver fibrosis in metabolic dysfunction-associated steatohepatitis (2025) · cites this paper as [36]

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Metadata

Authors
Meroni, M., Longo, M., Lombardi, R., Paolini, E., Macchi, C., Corsini, A., Sirtori, C. R., Fracanzani, A. L., Ruscica, M., & Dongiovanni, P.
Affiliations
  • General Medicine and Metabolic Diseases,Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Cà Granda Ospedale Maggiore Policlinico,Milan,Italy
  • Department of Pharmacological and Biomolecular Sciences,Università degli Studi di Milano,Milan,Italy
ORCID
Dongiovanni, Paola
Venue
Hepatology Communications
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2021-10-22
Volume
6
Issue
3
Pages
535-549
ISSN
2471-254X
DOI
10.1002/hep4.1830
Cited by
47
References
5
Language
en
Licence
creativecommons.org/licenses/by-nc-nd/4.0/ (unspecified)

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