title: BMI, male sex and IL28B genotype associated with persistently high hepatitis C virus RNA levels among chronically infected drug users up to 23 years following seroconversion.
abstract: The natural course of serum HCV RNA levels during chronic infection remains unclear. We investigated HCV RNA levels and factors associated with HCV RNA levels for the entire course from HCV seroconversion. We measured HCV RNA levels of 54 HCV seroconverters from the Amsterdam Cohort Studies among drug users at yearly intervals up to 23 years using bDNA (VERSANT 3.0, lower limit of detection 615 IU/mL). Samples below the cut-off of the assay were tested by TMA (Siemens VERSANT, detection limit 5 IU/mL). We used a latent class linear mixed model to examine the HCV RNA patterns and factors associated with HCV RNA levels. The median follow-up time was 10.8 years (IQR 6.5-14.9). We found two distinct HCV RNA patterns characterized by 45/54 cases and 9/54 cases. In multivariable analyses, HCV RNA levels were 0.41 log(10) IU/mL (95% confidence interval (CI) 0.06-0.75) higher for males as compared to females. Individuals with the IL28B CC genotype had 0.40 log(10) IU/mL (95% 0.08-0.73) higher HCV RNA levels than individuals with IL28B CT/TT genotypes. Body mass index (BMI) was associated with higher HCV RNA levels, 0.055 log(10) IU/mL per BMI point (95% CI 0.027-0.083). In this unique study, which examines the HCV RNA patterns over an extended period and following seroconversion, male sex, IL28B CC genotype and BMI were independently associated with higher average HCV RNA levels. These results contribute to defining the natural history of HCV infection and could play an important part in clinical decision-making.
authors.affiliation: Cluster of Infectious Diseases, Department of Research, Amsterdam Public Health Service, Amsterdam, The Netherlands; Center of Infectious Diseases and Immunology Amsterdam (CINIMA), Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: B P X
authors.initials: BP
authors.lastname: Grady
authors.forename: M
authors.initials: M
authors.lastname: Prins
authors.forename: S
authors.initials: S
authors.lastname: Rebers
authors.forename: R
authors.initials: R
authors.lastname: Molenkamp
authors.forename: R B
authors.initials: RB
authors.lastname: Geskus
authors.forename: J
authors.initials: J
authors.lastname: Schinkel
mesh_terms: D000328:Adult; D015992:Body Mass Index; D015331:Cohort Studies; D055030:Drug Users; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D018937:Hepatitis C Antibodies / Q000097:blood / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D012737:Sex Factors; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D018937:Hepatitis C Antibodies; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: drug users; interferon lambda 3; latent class analysis; longitudinal; viral load; viremia