Lipoprotein(a) levels are associated with liver fibrosis grade in patients with NAFLD

14 Dec 2021

One of the most important characteristics of Non alcoholic fatty liver disease (NAFLD) is certainly its association with many mechanisms related also to an increased cardiovascular risk, such as insulin resistance, obesity, type 2 diabetes mellitus and atherogenic dyslipidemia [Ref 1]. Considering the latter, in particular, it has been demonstrated that a high level of low-density lipoprotein (LDL) cholesterol increases the risk of developing cardiovascular diseases in patients with NAFLD. Moreover, the risk seems to increase proportionally to the degree of liver fibrosis [Ref 2].

Among the various fatty acid transport proteins, lipoprotein(a) is a type of lipoprotein responsible for the transport of cholesterol in the bloodstream and is, in fact, a LDL associated with an apolipoprotein (Apolipoprotein(a)). Lipoprotein(a) promotes the accumulation of cholesterol on the blood vessel promoting the formation of atherosclerotic plaques, while the Apolipoprotein(a) is able to inhibit the enzymes responsible for the dissolution of clots. Therefore, Lipoprotein(a), containing Apolipoprotein(a), helps to promote the accumulation of blood clots in the arterial level. Unlike other classes of lipoproteins, Lipoprotein(a) concentrations are scarcely influenced by dietary factors, while over 90% are determined by genetic factors that regulate hepatic synthesis [Ref 3].

Although lipoprotein abnormalities have been related to cardiovascular risk in patients with NAFLD, the impact of quality and quantity of Lipoprotein(a) in the development of NAFLD is still relatively unknown. A recent study from Meroni M et al. tried to evaluate the association between Lipoprotein(a) levels and advanced liver damage in patients with NAFLD [Ref 4].

They enrolled 600 adult patients with biopsy-proven NAFLD and collected clinical and laboratory data, including also Lipoprotein(a) serum concentration.

Levels of Lipoprotein(a) lower than the 25th percentile (i.e. <13.9 nmol/L) were associated with higher transaminases values, higher HOMA index, higher grade of fibrosis or cirrhosis. Fitting data by logistic regression models, at multivariable analysis (adjusted for sex, age, BMI, type 2 diabetes, ALT, total cholesterol, triglycerides and statins), an inverse correlation between Lipoprotein(a) levels and fibrosis (OR, 0.76; 95% CI, 0.59-0.96; P= 0.02), fibrosis >F2 (OR, 0.48; 95% CI, 0.30-0.76; P= 0.002), and between Lipoprotein(a) levels and cirrhosis (OR, 0.31; 95% CI, 0.14-0.65; P=0.002) were observed.  Diagnostic accuracy of circulating Lipoprotein(a) in predicting liver fibrosis (grade F4) performing a ROC curve showed an AUC of 0.79, P<0.0001. The AUC of this ROC curve was even higher when at multivariate analysis the levels of Lipoprotein(a) were adjusted for transaminases (alanine-aminotransferase and aspartate-aminotransferase) levels (AUC 0.87, P<0.0001).

Moreover, the study showed that Lipoprotein(a) concentration was positively correlated with its hepatic expression, confirming the concept that circulating Lipoprotein(a) reflects its hepatic synthesis. In conclusion, this study proves the association between serum Lipoprotein(a) levels and advanced liver fibrosis in patients with NAFLD. Moreover, it supports the hypothesis that Lipoprotein(a) in combination with transaminases concentration may be considered as an early biomarker to predict hepatic fibrosis in patients with NAFLD [Ref 4].


  1. Bril F, Sninsky JJ, Baca AM, Superko HR, Portillo Sanchez P, Biernacki D, et al. Hepatic steatosis and insulin resistance, but not steatohepatitis, promote atherogenic dyslipidemia in NAFLD. J Clin Endocrinol Metab 2016;101:644- 652.
  2. Dongiovanni P, Paolini E, Corsini A, Sirtori CR, Ruscica M. Nonalcoholic fatty liver disease or metabolic dysfunction-associated fatty liver disease diagnoses and cardiovascular diseases: from epidemiology to drug approaches. Eur J Clin Invest 2021;51:e13519.
  3. McCormick SP. Lipoprotein(a): biology and clinical importance. Clin Biochem Rev. 2004;25(1):69-80.
  4. Meroni M, Longo M, Lombardi R, Paolini E, Macchi C, Corsini A, Sirtori CR, Fracanzani AL, Ruscica M, Dongiovanni P. Low Lipoprotein(a) Levels Predict Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Hepatol Commun. 2021 Oct 22. Epub ahead of print.