#1050 Diabetes mellitus mediates the association between chronic hepatitis C virus infection and incidence of end-stage kidney disease
Authors: Lai Tai-Shuan , Huang Yi-Ting , Huang Yen-Tsung , Yang Hwai-I 
Published: May 2024

Abstract

Background and Aims
Chronic infection with the hepatitis C virus (HCV) is known to lead to extra-hepatic complications, notably affecting the kidneys. While prior research has established a link between chronic HCV infection and chronic kidney disease (CKD), there remains ongoing debate regarding whether this association is influenced by the presence of diabetes mellitus.

Method
This study, part of the REVEAL-HCV project in Taiwan, investigated the relationship between chronic HCV infection and end-stage kidney disease (ESKD). Initially, 23,820 individuals aged 30-65 from Taiwan were enrolled since 1991-1992. Data included physical exams, blood tests, and questionnaires covering sociodemographics, lifestyle, and comorbidities. The cohort was linked to Taiwan's National Health Insurance Research Database, providing extensive patient data. Hepatitis C status was determined by HCV RNA testing. ESKD was identified using ICD-9-CM codes from the health database. Covariates like age, sex, lifestyle factors, comorbidities, and lab results were considered. The study emphasized accurate diagnosis of diabetes based on insurance claims with well validation.
The mediation analysis was done by constructing 2 logistic regression models, with one regressing the risk of ESKD on chronic HCV infection status and the other regressing the risk of ESKD on diabetes status. The direct and indirect (mediated through the risk of diabetes) effects of chronic HCV infection on the risk of ESKD were estimated using odds ratios. Confidence intervals for direct and indirect effects were estimated using 5000 bootstrapping replicates.

Results
The study examined 22,800 participants, with a mean age of 46.9 years. Among them, 738 were chronically infected with HCV. These HCV-infected participants were generally older, more likely to be female, had lower education levels, and higher prevalence of diabetes, hypertension, and CKD. During the 16.8-year median follow-up, covering 319,474 person-years, 378 end-stage kidney disease (ESKD) events occurred. The incidence of ESKD was higher in HCV-infected subjects (2.6%) compared to non-HCV-infected (1.6%). The univariate and multivariate-adjusted odds ratios (ORs) and 95% confidence interval for ESKD in HCV-infected participants were 2.06 (0.90-2.08) and 1.57 (1.01-2.44), respectively.
HCV infection also showed a significant association with diabetes mellitus. The multivariable-adjusted OR for diabetes in HCV-infected individuals was 1.53 (1.31-1.78). Further, the study identified a diabetes-mediated pathway linking HCV infection to ESKD. In this pathway, HCV infection increased the odds of ESKD by 0.8%. This indirect pathway mediated by diabetes accounted for 16% of the overall association between HCV infection and ESKD with statistically significant. The direct pathway, though not statistically significant, indicated a 57% increased odds of ESKD in HCV-infected individuals compared to those without HCV.

Conclusion
Chronic HCV infection is linked to higher incidences of diabetes and ESKD. The mechanisms are intricate, with diabetes serving as a significant mediator in the pathway from HCV infection to ESKD.