Published online Oct 14, 2019. doi: 10.3748/wjg.v25.i38.5826
Peer-review started: June 20, 2019
First decision: August 28, 2019
Revised: September 9, 2019
Accepted: September 27, 2019
Article in press: September 27, 2019
Published online: October 14, 2019
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.
To investigate the role of APOE -ε2, -ε3, and -ε4 alleles and the metabolic profile in the outcome of HCV infection.
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.
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).
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.
Core tip: Cholesterol is a metabolic regulator of the hepatitis C virus (HCV) life cycle. Genetic polymorphisms in the APOE gene can regulate cholesterol and modify the outcome of the HCV infection. Our findings suggest that APOE ε4 allele and low-density lipoprotein cholesterol (LDL-c) confer a protective effect in the course of the HCV infection in the context of high body mass index (BMI). Levels of LDL-c, BMI, and ALT may estimate the risk of chronicity in HCV-infected patients. An individualized therapy accounting the host´s genetic, environmental, and metabolic factors could aid in the clinical management of HCV infection, especially in populations with a high prevalence of overweight and obesity.