miravirsen and Dyslipidemias

miR-122 is the predominant liver miRNA that regulates hepatic lipid metabolism and inflammation. Hepatitis C virus (HCV) modulates host intracellular lipid metabolism. HCV stability and propagation also depend on an interaction between virus and miR-122. Our aims were to examine the associations between miR-122, apolipoproteins, and serum makers of fibrosis in chronic hepatitis C (CHC) patients. We evaluated baseline sera from 36 CHC genotype 1 patients who completed the Phase IIa study of miravirsen (LNA oligonucleotide targeting miR-122). Samples were assessed for liver transaminases, IL 28B genotype, IP-10, and lipid profiles. The noninvasive markers of liver fibrosis, APRI, and FIB-4, were calculated using standard formulae. miR-122 levels were measured using RT-PCR and expressed as fold-change compared to normal healthy controls. CHC patients were mostly male (61%) with mean age 47.5 ± 11.6 years. Patients with higher ApoB (ApoB/ULN ≥ 0.5) has significantly lower miR-122 levels in compared to patients with lower ApoB (ApoB/ULN < 0.5). (8.28 ± 6.23 vs. 16.28 ± 13.71; P = 0.02). There were no similar associations between miR-122 and ApoA-1 or between HCV RNA and lipoproteins. There were no differences in miR-122 levels between patients with different stages of fibrosis determined by APRI or FIB-4. Patients with lower ApoB had higher serum miR-122 levels. However, we cannot identify significant association between miR-122, ApoA-1, or fibrosis markers in this small cohort of CHC genotype 1 patients. The mechanism of HCV dyslipidemia is complex and could partly relate to the effect of miR-122 on lipid metabolism which requires further evaluation in a larger study.

Topics: Adolescent; Adult; Aged; Alanine Transaminase; Apolipoprotein A-I; Apolipoproteins B; Aspartate Aminotransferases; Biomarkers; Chemokine CXCL10; Dyslipidemias; Female; Genotype; Hepatitis C, Chronic; Humans; Liver; Liver Cirrhosis; Male; MicroRNAs; Middle Aged; Oligonucleotides; Real-Time Polymerase Chain Reaction; Severity of Illness Index; Young Adult