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

Hepatitis C Virus Infection and the Risk of Chronic Kidney Disease: from Cross-sectional Study to Longitudinal Cohort Study

賴台軒(Tai-Shuan Lai)

指導教授 ： 簡國龍

共同指導教授 ： 陳建仁(Chien-Jen Chen)

國立臺灣大學/公共衛生學院/流行病學與預防醫學研究所/博士(2015年)

https://doi.org/10.6342/NTU.2015.10195

摘要

無資料

關鍵字

蛋白尿 ； C型肝炎 ； 慢性腎臟病 ； 末期腎病變 ； 死亡率 ； C型肝炎核糖核酸

並列摘要

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.

並列關鍵字

proteinuria ； hepatitis C virus ； chronic kidney disease ； end-stage renal disease ； mortality ； HCV RNA

參考文獻

1. Foley RN, Collins AJ. The usrds: What you need to know about what it can and can't tell us about esrd. Clinical journal of the American Society of Nephrology : CJASN. 2013;8:845-851

2. United States Renal Data System: USRDS 2013 Annual Data Report. Available at: http://www.Usrds.Org/2013/pdf/v2_ch1_13.Pdf. Accessed by July 20, 2015

3. Hallan SI, Coresh J, Astor BC, Asberg A, Powe NR, Romundstad S, Hallan HA, Lydersen S, Holmen J. International comparison of the relationship of chronic kidney disease prevalence and esrd risk. Journal of the American Society of Nephrology : JASN. 2006;17:2275-2284

4. Hallan SI, Vikse BE. Relationship between chronic kidney disease prevalence and end-stage renal disease risk. Current opinion in nephrology and hypertension. 2008;17:286-291

5. Wen CP, Cheng TY, Tsai MK, Chang YC, Chan HT, Tsai SP, Chiang PH, Hsu CC, Sung PK, Hsu YH, Wen SF. All-cause mortality attributable to chronic kidney disease: A prospective cohort study based on 462 293 adults in taiwan. Lancet. 2008;371:2173-2182