Low Lipoprotein(a) Levels Predict Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease
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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Health/LWW
2022-03-01
|
| Series: | Hepatology Communications |
| Online Access: | https://doi.org/10.1002/hep4.1830 |
| _version_ | 1827843732425146368 |
|---|---|
| author | Marica Meroni Miriam Longo Rosa Lombardi Erika Paolini Chiara Macchi Alberto Corsini Cesare R. Sirtori Anna Ludovica Fracanzani Massimiliano Ruscica Paola Dongiovanni |
| author_facet | Marica Meroni Miriam Longo Rosa Lombardi Erika Paolini Chiara Macchi Alberto Corsini Cesare R. Sirtori Anna Ludovica Fracanzani Massimiliano Ruscica Paola Dongiovanni |
| author_sort | Marica Meroni |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T08:30:45Z |
| format | Article |
| id | doaj.art-6940123c6db24737b71d62951ada2727 |
| institution | Directory Open Access Journal |
| issn | 2471-254X |
| language | English |
| last_indexed | 2024-03-12T08:30:45Z |
| publishDate | 2022-03-01 |
| publisher | Wolters Kluwer Health/LWW |
| record_format | Article |
| series | Hepatology Communications |
| spelling | doaj.art-6940123c6db24737b71d62951ada27272023-09-02T17:41:33ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2022-03-016353554910.1002/hep4.1830Low Lipoprotein(a) Levels Predict Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver DiseaseMarica Meroni0Miriam Longo1Rosa Lombardi2Erika Paolini3Chiara Macchi4Alberto Corsini5Cesare R. Sirtori6Anna Ludovica Fracanzani7Massimiliano Ruscica8Paola Dongiovanni9General Medicine and Metabolic Diseases Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Cà Granda Ospedale Maggiore Policlinico Milan ItalyGeneral Medicine and Metabolic Diseases Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Cà Granda Ospedale Maggiore Policlinico Milan ItalyGeneral Medicine and Metabolic Diseases Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Cà Granda Ospedale Maggiore Policlinico Milan ItalyGeneral Medicine and Metabolic Diseases Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Cà Granda Ospedale Maggiore Policlinico Milan ItalyDepartment of Pharmacological and Biomolecular Sciences Università degli Studi di Milano Milan ItalyDepartment of Pharmacological and Biomolecular Sciences Università degli Studi di Milano Milan ItalyDepartment of Pharmacological and Biomolecular Sciences Università degli Studi di Milano Milan ItalyGeneral Medicine and Metabolic Diseases Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Cà Granda Ospedale Maggiore Policlinico Milan ItalyDepartment of Pharmacological and Biomolecular Sciences Università degli Studi di Milano Milan ItalyGeneral Medicine and Metabolic Diseases Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Cà Granda Ospedale Maggiore Policlinico Milan ItalyDyslipidemia 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.https://doi.org/10.1002/hep4.1830 |
| spellingShingle | Marica Meroni Miriam Longo Rosa Lombardi Erika Paolini Chiara Macchi Alberto Corsini Cesare R. Sirtori Anna Ludovica Fracanzani Massimiliano Ruscica Paola Dongiovanni Low Lipoprotein(a) Levels Predict Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease Hepatology Communications |
| title | Low Lipoprotein(a) Levels Predict Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease |
| title_full | Low Lipoprotein(a) Levels Predict Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease |
| title_fullStr | Low Lipoprotein(a) Levels Predict Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease |
| title_full_unstemmed | Low Lipoprotein(a) Levels Predict Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease |
| title_short | Low Lipoprotein(a) Levels Predict Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease |
| title_sort | low lipoprotein a levels predict hepatic fibrosis in patients with nonalcoholic fatty liver disease |
| url | https://doi.org/10.1002/hep4.1830 |
| work_keys_str_mv | AT maricameroni lowlipoproteinalevelspredicthepaticfibrosisinpatientswithnonalcoholicfattyliverdisease AT miriamlongo lowlipoproteinalevelspredicthepaticfibrosisinpatientswithnonalcoholicfattyliverdisease AT rosalombardi lowlipoproteinalevelspredicthepaticfibrosisinpatientswithnonalcoholicfattyliverdisease AT erikapaolini lowlipoproteinalevelspredicthepaticfibrosisinpatientswithnonalcoholicfattyliverdisease AT chiaramacchi lowlipoproteinalevelspredicthepaticfibrosisinpatientswithnonalcoholicfattyliverdisease AT albertocorsini lowlipoproteinalevelspredicthepaticfibrosisinpatientswithnonalcoholicfattyliverdisease AT cesarersirtori lowlipoproteinalevelspredicthepaticfibrosisinpatientswithnonalcoholicfattyliverdisease AT annaludovicafracanzani lowlipoproteinalevelspredicthepaticfibrosisinpatientswithnonalcoholicfattyliverdisease AT massimilianoruscica lowlipoproteinalevelspredicthepaticfibrosisinpatientswithnonalcoholicfattyliverdisease AT paoladongiovanni lowlipoproteinalevelspredicthepaticfibrosisinpatientswithnonalcoholicfattyliverdisease |