Hepatitis C virus increases the risk of kidney disease among HIV‐positive patients: Systematic review and meta‐analysis

Abstract

Kidney disease has become an important co-morbidity among human immunodeficiency virus-infected patients as they live longer in the era of highly effective antiretroviral therapy. It remains unclear how co-infection with hepatitis C virus impacts on the trajectory of kidney disease among HIV-infected patients. To evaluate the effect of co-infection with HCV on the risk of kidney disease in HIV-infected populations. We conducted a systematic review of the published medical literature to determine if hepatitis C co-infection is associated with increased likelihood of chronic kidney disease in HIV-positive adults. We used the random effects model of DerSimonian and Laird to generate a summary estimate of the relative risk for chronic kidney disease (defined by reduced glomerular filtration rate and/or detectable proteinuria) with hepatitis C virus across the published studies. Meta-regression and stratified analysis were also conducted. We identified 19 studies (146,151 unique patients with HIV) and separate meta-analyses were performed according to the outcome. Aggregation of longitudinal studies (n = 8, 105,462 unique patients) showed a relationship between HCV infection and increased risk of reduced glomerular filtration rate among HIV-infected individuals, the summary estimate for adjusted hazard ratio was 1.64 (95%CI, 1.28; 2.0, P < 0.001) in HIV-HCV co-infected individuals compared with those having HIV mono-infection. No between-studies heterogeneity was noted (P-value by Q test = 0.08). HCV positive serology was an independent risk factor for proteinuria; adjusted effect estimate, 1.23 (95% confidence interval, 1.18; 1.28, P = 0.001) (n = 6 studies; 26,835 unique patients). In meta-regression, we noted the impact of ageing (P = 0.0001) upon the adjusted hazard ratio of incidence of reduced glomerular filtration rate among HCV-HIV co-infected patients; a negative association between frequency of males (P = 0.001) and the adjusted hazard ratio of prevalence of low glomerular filtration rate was found. Hepatitis C co-infection is associated with a significant increase in the risk of reduced glomerular filtration rate and/or detectable proteinuria among HIV-infected individuals.

The association of hepatitis C infection with the onset of CKD and progression into ESRD

“…Studies performed in other subpopulations, including HCV/HIV‐coinfected patients and kidney transplant recipients, have provided further support for an impact of HCV infection on incident CKD. The presence of HCV coinfection in patients with HIV infection has been identified as a risk factor for CKD in several studies of different cohorts . A recent meta‐analysis incorporating studies that adjusted for potential confounders such as age, race, and history of injection drug use found a pooled aHR of 1.64 (95% CI, 1.28‐2.00) for the risk of incident CKD conferred by HCV coinfection .…”

Association between hepatitis C virus and chronic kidney disease: heterogeneity begets heterogeneity

“…Recent meta-analyses of general-population [3] and HIV-positive [4] cohorts reported 45% and 64% increased risks of developing CKD (stage 3 or higher), respectively, in HCV seropositive versus seronegative individuals.…”

KDIGO 2018 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease

“…In particular, emergency department visits related to kidney disease were much more common among coinfected patients (37%) than among those with HIV infection alone (10%). 62 Another meta-analysis of observational studies 63 reported a relationship between positive anti-HCV serologic status and an increased risk of reduced GFR among HIV-infected individuals, with an adjusted HR of 1.64 (95% CI: 1.28-2.0), compared with those having HIV infection alone.…”

“…281 A large meta-analysis of 107,356 patients 7 reported that anti-HCV-positive serology was an independent risk factor for proteinuria in the adult general population (adjusted OR: 1.51 [95% CI: 1.19-1.89)]. 65,66,[282][283][284][285] Another pooled analysis 63 demonstrated that anti-HCVpositive serology was an independent risk factor for proteinuria among HIV-infected patients with an adjusted effect estimate of 1.23 (95% CI: 1.18-1.28). [286][287][288][289][290][291] 5.1: We recommend that a kidney biopsy be performed in HCV-infected patients with clinical evidence of glomerular disease (Not Graded).…”