Hepatitis C virus clearance and less liver damage in patients with high cholesterol, low-density lipoprotein cholesterol and APOE ε 4 allele

World J Gastroenterol. 2019 Oct 14;25(38):5826-5837. doi: 10.3748/wjg.v25.i38.5826.

Abstract

Background: Cholesterol is related to improvements in the rate of sustained virological response and a robust immune response against the hepatitis C virus (HCV). APOE gene polymorphisms regulate cholesterol levels modifying the course of the HCV infection. The relationship between cholesterol, APOE alleles, and the outcome of HCV infection has not been evaluated in the admixed population of Mexico.

Aim: To investigate the role of APOE -ε2, -ε3, and -ε4 alleles and the metabolic profile in the outcome of HCV infection.

Methods: A total of 299 treatment-naïve HCV patients were included in this retrospective study. Patients were stratified in chronic hepatitis C (CHC) (n = 206) and spontaneous clearance (SC) (n = 93). A clinical record was registered. Biochemical tests were assessed by dry chemistry assay. APOE genotypes were determined using a Real-Time polymerase chain reaction assay.

Results: Total cholesterol, low-density lipoprotein cholesterol (LDL-c), triglycerides, and hypercholesterolemia were higher in SC than CHC patients as well as the frequency of the APOE ε4 allele (12.4% vs 7.3%). SC patients were overweight (54.8%). The ε4 allele was associated with SC (OR = 0.55, 95%CI: 0.31-0.98, P = 0.042) and mild fibrosis (F1-F2) in CHC patients (OR 0.091, 95%CI 0.01-0.75, P = 0.020). LDL-c ≥ 101.5 mg/dL (OR = 0.20, 95%CI: 0.10-0.41, P < 0.001) and BMI ≥ 26.6 kg/m2 (OR= 0.37, 95%CI: 0.18-0.76, P < 0.001) were associated with SC status; while ALT ≥ 50.5 IU/L was negatively associated (OR = 5.67, 95%CI: 2.69-11.97, P < 0.001).

Conclusion: In SC patients, the APOE ε4 allele and LDL-c conferred a protective effect in the course of the HCV infection in the context of excess body weight.

Keywords: Body mass index; Cholesterol; Liver damage; Low-density lipoprotein; Spontaneous hepatitis C virus clearance.

MeSH terms

  • Adult
  • Alleles
  • Apolipoproteins E / genetics*
  • Apolipoproteins E / metabolism
  • Body Weight
  • Cholesterol, LDL / blood*
  • Cholesterol, LDL / metabolism
  • Female
  • Hepacivirus / isolation & purification
  • Hepacivirus / metabolism
  • Hepacivirus / pathogenicity
  • Hepatitis C / blood
  • Hepatitis C / genetics*
  • Hepatitis C / virology
  • Host-Pathogen Interactions / genetics
  • Humans
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / genetics
  • Hypercholesterolemia / metabolism*
  • Male
  • Mexico
  • Middle Aged
  • Overweight / blood
  • Overweight / genetics
  • Overweight / metabolism*
  • Polymorphism, Genetic
  • Protective Factors
  • Remission, Spontaneous
  • Retrospective Studies
  • Viral Load / genetics

Substances

  • ApoE protein, human
  • Apolipoproteins E
  • Cholesterol, LDL