Elsevier

Journal of Hepatology

Volume 49, Issue 5, November 2008, Pages 831-844
Journal of Hepatology

Special article
Hepatitis C infection and risk of diabetes: A systematic review and meta-analysis

https://doi.org/10.1016/j.jhep.2008.08.006Get rights and content

Background/Aims

Several studies found hepatitis C (HCV) increases risk of Type II diabetes mellitus (DM). However, others found no or only sub-group specific excess risk. We performed meta-analyses to examine whether HCV infection does increase DM risk in comparison to the general population and in other sub-groups with increased liver disease rates including with hepatitis B (HBV).

Methods

We followed standard guidelines for performance of meta-analyses. Two independent investigators identified eligible studies through structured keyword searches in relevant databases including PubMed.

Results

We identified 34 eligible studies. Pooled estimators indicated significant DM risk in HCV-infected cases in comparison to non-infected controls in both retrospective (ORadjusted = 1.68, 95% CI 1.15–2.20) and prospective studies (HRadjusted = 1.67, 95% CI 1.28–2.06). Excess risk was also observed in comparison to HBV-infected controls (ORadjusted = 1.80, 95% CI 1.20–1.40) with suggestive excess observed in HCV+/HIV+ cases in comparison to HIV+ controls (ORunadjusted = 1.82, 95% CI 1.27–2.38).

Conclusions

Our finding of excess DM risk with HCV infection in comparison to non-infected controls is strengthened by consistency of results from both prospective and retrospective studies. The excess risk observed in comparison to HBV-infected controls suggests a potential direct viral role in promoting DM risk, but this needs to be further examined.

Introduction

An estimated 3% of the world’s population (170+ million persons) are infected with the hepatitis C virus (HCV), 55–80% with chronic infection [1]. HCV is a significant cause of global morbidity and mortality, responsible for approximately 25% of both chronic liver disease (CLD) and hepatocellular carcinoma (HCC).

HCV infection has also been convincingly linked to several extra-hepatic manifestations including essential mixed cryoglobulinemia, glomeronephritis, and porphyria cutanea tarda [2]. Based on early clinical observation, type II diabetes mellitus (DM) was suggested to be another potential extrahepatic manifestation of HCV infection, with excess risk postulated to be due to either direct viral involvement or secondary to HCV-induced liver damage. However, even a small increase in DM risk in HCV-infected patients may be clinically important, as available pharamcotherapies for HCV are less effective with concomitant DM [3] and progression of liver disease has been shown to be worsened [4].

A number of epidemiologic studies have demonstrated significant excess DM risk with HCV infection [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18]. However, others found no significant excess risk [19], [20], [21], [22], [23], [24], [25], [26] or excess risk limited to specific segments of the population [27], [28], [29], [30], [31]. Differences in source of controls, case definition, sample size and underlying target population may explain much of this observed variability among studies. Several general narrative reviews have examined the association between HCV infection and DM. However, they have typically been limited in scope or non-systematic [32], [33]. The only published meta-analysis examined the association between HCV and DM in a highly limited sub-population of kidney transplant recipients [34].

Our primary goal was, therefore, to conduct meta-analyses to assess whether HCV infection conveys excess DM risk compared to that observed in the general population. We aimed to quantify and appropriately qualify any observed excess risk, to identify any high-risk sub-groups, and to explore potential sources of between-study heterogeneity. A secondary goal was examining DM risk with HCV infection in comparison to that observed in other sub-groups at risk of CLD, including those mono-infected with HBV or HIV. In addition to providing a greater understanding about the association between HCV and DM risk, the findings of these meta-analyses may also help inform clinical practice guidelines and suggest gaps in current understanding that may be important to address in future research.

Section snippets

Eligibility criteria

We followed published guidelines for the conduct and reporting of meta-analyses [35]. All published epidemiologic studies providing, or with data to calculate, an estimate of risk of type II or adult-onset diabetes mellitus (DM) among adults infected with hepatitis C (HCV+) compared to adults without infection (HCV−) or an estimate of risk of HCV among adults with DM compared to adults without DM were considered for possible inclusion in the current meta-analysis. To be eligible, both case and

Searches

We identified 223 potentially eligible reports. Review of abstracts and manuscripts resulted in exclusion of 190 reports (85%). The most frequent reasons for exclusion were: publication in an ineligible format including letters/abstracts or the results provided were not from original research including reviews/editorials (n = 66); there was no comparator group or else an ineligible case or comparator group (n = 45); it contained data on post-transplant patients (n = 37); it had a total sample size of

Discussion

This is the first meta-analysis to specifically examine the association between HCV infection and risk of diabetes (DM) in the general population as well as in sub-groups at particularly increased risk of chronic liver disease (CLD) including those with hepatitis B (HBV) or HIV infection, or with other causes of liver disease (OLD) like alcohol-related liver disease. Among 34 eligible studies identified for this review, eighteen (15 retrospective and 3 prospective) evaluated DM risk in

Acknowledgments

This research was supported in part by the Houston Center for Quality of Care & Utilization Studies, Health Services Research and Development Service, Office of Research and Development, Department of Veterans Affairs and a Department of Veterans Affairs Merit Review Award.

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    The authors declare that they do not have anything to disclose regarding funding from industries or conflict of interest with respect to this manuscript. H.B. El-Serag received funding from NIH NIDDK K-24-04-107.

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