MBOAT7 rs641738 POLYMORPHISM IS LINKED TO ALTERED PORTAL BLOOD FLOW ASSESSED USING 13C METHACETIN TEST

Background MBOAT7 rs641738 is a common genetic variant associated with non-alcoholic fatty liver disease (NAFLD), inflammation and liver fibrosis, which increases the progression from simple liver steatosis to hepatocellular carcinoma. Liver biopsy is still considered the “gold standard” method in quantifying the degree of liver injury in patients with NAFLD, despite potential complications due to its invasive nature. Consequently, non-invasive tools are seen as alternatives to liver biopsy. Here, we aimed to study the dynamic function of the liver by oral administration of 13C methacetin in individuals carrying the MBOAT7 rs641738 variant.

Patients and Methods In 92 subjects (age: 43.9 ± 1.5 years, body mass index: 28.8 ± 0.7 kg/m2, females: 42 %, NAFLD: 63 %, obese: 40 %), portal blood flow (delta over baseline value after 15 min: DOB15) and microsomal function (cumulative per cent dose recovery after 30 min: cPDR30) were assessed by oral administration of 13C methacetin. Subjects were stratified according to allele types (wild-type, heterozygous, mutant). Liver steatosis and fibrosis were assessed non-invasively by ultrasonography (degree: 0-3) and acoustic radiation force impulse (ARFI) technique (degree: 0-4), respectively.

Results Mean degree of liver steatosis and liver fibrosis in NAFLD patients was 1.6 ± 0.1 and 1.1 ± 0.2 (mean±SEM), respectively. MBOAT7 genotypes were neither associated with liver fibrosis nor steatosis. Portal blood flow was significantly lower in homozygous carriers of the MBOAT7 risk variant as compared to heterozygous subjects (DOB15: 11.1±1.5 vs. 16.4±1.0 ‰, P=0.047), even falling below the cut-off value (DOB15 < 14.5 ‰). Microsomal function tended to be lower in subjects who are homozygous for the MBOAT7 risk allele for in comparison to heterozygous subjects (9.9±0.9 vs.12.4±0.6 ‰, P=0.065), but remained well above the cut-off value (cPDR30 < 8.1 %).

Conclusions The MBOAT7 rs641738 variant might be associated with impaired portal blood flow. Microsomal function was preserved but tended to decrease in carriers of the gene variant, too. In the future, more studies should link the MBOAT7 rs641738 variant with NAFLD severity using non-invasive liver function tests.

Publication History

Article published online:
04 January 2021