C型肝炎病毒感染與慢性腎臟病的風險：從斷面研究到長期追蹤世代研究

Abstract

Background Chronic kidney disease (CKD) has become a major public health problem worldwide. The traditional risk factors cannot fully explain the occurrence of the disease, especially in some high prevalent countries like Taiwan. Hepatitis C virus (HCV) infection has been linked to glomerulonephritis, but the association between HCV infection and CKD remain controversial. The role of viral load and genotype on renal outcomes has not yet investigated. The dissertation aims to compare the prevalence of chronic kidney diseases, renal disease related mortality and incidence of end-stage renal disease (ESRD) between participants with and without chronic hepatitis C virus (HCV) infection and to examine the impact of HCV viral load and genotype on incidence of end-stage renal disease (ESRD). Methods In a community based prospective study, a total of 20,175 participants aged 30 to 65 years with informed consent was enrolled in 1991 to 1992. Structured questionnaires were interviewed and blood samples for serological and biochemical tests were provided at study entry. Serum HCV RNA level and genotype were tested for participants with anti-HCV seropositive. CKD was defined by proteinuria or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Deaths from renal disease were ascertained through computerized linkage with national death certification profiles. Participants were followed up until December 31, 2008. Logistic regression models and Cox proportional hazard models were used to estimate prevalence odds ratio (PORadj) and mortality hazard ratio (MHRadj) of CKD for chronic HCV infection after adjusting other risk factors. The dose-response relationship of HCV RNA level and renal-related death was tested for trend. The ESRD, defined as the onset of chronic dialysis or renal transplantation, were ascertained by linkage with National Health Insurance Research Database. Competing risk analyses were used to determine the true hazard for incidence of ESRD associated with HCV after taking into account with death prior to ESRD. Results The prevalence of anti-HCV seropositive was 0.5% and the prevalence of CKD was 28.6%. Comparing seropositive to seronegative anti-HCV participants, the PORadj (95% confidence interval [CI], p-value) for CKD was 1.44 (1.26–1.65, P<0.001) after adjustment for demographic factors. The PORadj (95% confidence interval [CI]) of CKD was 1.30 (1.01–1.68), 1.33 (1.08–1.61), and 2.05 (1.47–2.87) (P for trend<0.001) for anti-HCV-seropositive participants with undetectable, low and high HCV viral load compared with anti-HCV-seronegative participants. During the 323,412 person-years of follow-up, CKD mortality rate was 26.0 and 103.6 per 10,000 person-years, respectively, for participants seronegative and seropositive for anti-HCV. Comparing with anti-HCV-seronegative participants, the MHRadj from CKD was 0.87 (0.12-6.26), 4.80 (2.40-9.59) and 8.12 (3.28-20.12) (P for trend<0.001), respectively, for anti-HCV-seropositives with undetectable, low and high HCV viral load. There was no significant association with CKD prevalence and mortality for HCV genotype among anti-HCV-seropositive participants with detectable HCV RNA. After adjusting pre-ESRD death as the competing risk, participants with HCV infection had higher risk of developing ESRD compared with participants without HCV infection. (HR: 2.03 (1.31-3.15); subhazard ratio: 1.98 (1.27-3.10)) in cause-specific hazard model and Fine and Gray model. Comparing with anti-HCV-seronegative participants, the subhazard ratio from developing ESRD was 1.51 (0.62-3.68), 2.18 (1.16-4.10) and 2.83 (1.12-7.14) (P for trend<0.001), respectively, for anti-HCV-seropositives with undetectable, low and high HCV viral load. Conclusion Chronic HCV infection is associated with an increased CKD morbidity and mortality and increased incidence of ESRD. HCV viral load rather than genotype is a strong CKD and ESRD predictor.