Serum MFAP4, a novel potential biomarker for liver cirrhosis screening, correlates with transient elastography in NAFLD patients.

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in different countries. Liver fibrosis is considered as the most appropriate predictor of NAFLD-associated outcome. Microfibrillar-associated protein 4 (MFAP4) is a glycoprotein located in the extracellular matrix. Circulatory MFAP4 has been suggested as a noninvasive biomarker for the assessment of hepatitis C virus and alcoholic liver disease associated liver fibrosis. In this study, we aimed to investigate the association between serum MFAP4 and liver fibrosis severity in NAFLD patients. Methods: A case-control study was conducted in which NAFLD patients (n = 25) and healthy participants (n = 12) were recruited. Liver fibrosis/cirrhosis was assessed by transient elastography (TE) and biochemical parameters were collected. Serum MFAP4 was measured by sandwich ELISA based on two monoclonal anti-MFAP4 antibodies and calibrated with a standard of recombinant MFAP4. Results: Serum MFAP4 levels increased with fibrosis severity and were highly upregulated in patients with cirrhosis (F4 fibrosis stage). In addition, serum MFAP4 levels positively correlated with TE measurement and showed significant association with the severely advanced fibrotic stage in NAFLD patients, in multiple linear regression analysis following adjustment for age, gender, and body mass index. Conclusion: This study suggests the use of MFAP4 as a potential diagnostic noninvasive biomarker for cirrhosis screening in NAFLD patients.

Identification of a Variant in APOB Gene as a Major Cause of Hypobetalipoproteinemia in Lebanese Families.

Familial hypobetalipoproteinemia (FHBL) is a codominant genetic disorder characterized by reduced plasma levels of low-density lipoprotein cholesterol and apolipoprotein B. To our knowledge, no study on FHBL in Lebanon and the Middle East region has been reported. Therefore, we conducted genetic studies in unrelated families and probands of Lebanese origin presenting with FHBL, in order to identify the causes of this disease. We found that 71% of the recruited probands and their affected relatives were heterozygous for the p.(Arg490Trp) variant in the APOB gene. Haplotype analysis showed that these patients presented the same mutant haplotype. Moreover, there was a decrease in plasma levels of PCSK9 in affected individuals compared to the non-affected and a significant positive correlation between circulating PCSK9 and ApoB levels in all studied probands and their family members. Some of the p.(Arg490Trp) carriers suffered from diabetes, hepatic steatosis or neurological problems. In conclusion, the p.(Arg490Trp) pathogenic variant seems a cause of FHBL in patients from Lebanese origin, accounting for approximately 70% of the probands with FHBL presumably as a result of a founder mutation in Lebanon. This study is crucial to guide the early diagnosis, management and prevention of the associated complications of this disease.