Association of Hepatitis C Infection and Risk of Kidney Cancer

A Systematic Review and Meta-analysis of Observational Studies

Di Wu; Shiping Hu; Guozi Chen; Longjiao Chen; Jian Liu; Wenlin Chen; Youwen Lv; Xiaoni Chen; Shan Lin; Fenfang Wu

Disclosures

J Viral Hepat. 2021;28(2):226-235. 

In This Article

Abstract and Introduction

Abstract

Although some epidemiological studies have investigated the association between Hepatitis C virus (HCV) infection and the development of kidney cancer, the results are far from consistent. We conducted a systematic review and meta-analysis of observational studies to determine the association. PubMed, EMBASE and Cochrane database were searched from 1 January 1975 to 7 January 2020. Study selection, data extraction and bias assessment (using the Newcastle-Ottawa scale) were performed independently by 2 authors. Pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated using a random-effects model. In all, 16 studies (11 cohort studies and 5 case-control studies) involving a total of 391,071 HCV patients and 38,333,839 non-HCV controls were included. The overall analysis showed a 47% higher risk to develop kidney cancer among the patients with HCV infection (pooled OR 1.47; 95% CI 1.14–1.91), despite significant heterogeneity (I 2 = 87.6%). The multivariable meta-regression showed that study design, age, sample size and HIV co-infection were significant sources of variance, and totally accounted for 82% of the I 2. The risk of KC in HCV patients was further increased in studies without HCV/HBV- and HCV/HIV- co-infection (pooled OR 1.66; 95%CI 1.23–2.24). Multiple sensitivity analyses did not change the significant association. The present meta-analysis indicated that HCV-infected patients have a significantly higher risk of developing kidney cancer. Our results highlighted the rationale for improved renal surveillance in HCV patients for the early diagnosis of kidney cancer. Further investigations for the mechanisms underlying HCV-induced kidney cancer are warranted.

Introduction

Hepatitis C virus (HCV), being a single-stranded RNA virus, has infected 71 million individuals worldwide, with its seroprevalence increased to 2.8% over the last decade.[1] The clinical presentation of HCV carriers varies from minimal fibrosis to cirrhosis and its complications.[2] On the basis of strong epidemiological and clinical evidence, the International Agency for Research on Cancer classified HCV as a proven cause of hepatocellular carcinoma.[3] In addition to the oncogenic effect on liver, chronic HCV infection has been reported to be associated with increased incidence of extrahepatic malignancies, including non-Hodgkin's lymphoma,[4] lung cancer,[5] pancreatic cancer,[6] head and neck cancer,[7] and perhaps kidney cancer.[8] The oncogenic mechanism are speculated to be in both direct and indirect approach.[9] HCV antigens and/or RNA have been identified in these tissues.[10–14] Thus, the virus may promote carcinogenesis either directly, by inducing persistent inflammation in local microenvironment and alterations of the immune repertoire, or indirectly, by promoting a low-grade, proinflammatory systemic state (as shown in chronic kidney disease[15]), which eventually favour cancer development.

Kidney cancer (KC) has the highest mortality rate of urologic malignancies and accounts for approximately 2.2% of all new cancer cases worldwide.[16] Known risk factors for developing KC mainly include smoking, obesity, hypertension, chronic kidney disease, diabetes and hereditary factors.[15,17] The impact of HCV infection on the risk of KC is however debated, owing to the inconsistent results from epidemiological studies.[18–33] Given the clinical relevance, but also the controversy of this topic, we conducted a meta-analysis of all available observational studies to systematically evaluate the association between HCV infection and the risk of developing KC, overcoming the limitations of individual studies.

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