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Commentary

Department of Pathology, University of Washington Medical Center, Seattle, WA.

Address correspondence to the author at: University of Washington Medical Center, Department of Pathology, 1959 NE Pacific St., Box 356100, Seattle, WA 98195. E-mail calp{at}u.washington.edu.

Schnable et al. describe a patient with a nearly 20-year history of hepatitis C virus (HCV) infection who developed acute manifestations of glomerulonephritis associated with concurrent cryoglobulinemia. A renal biopsy demonstrated "proliferative glomerulonephritis" that we are meant to infer was membranoproliferative glomerulonephritis of the type typically associated with cryoglobulinemia and HCV infection.

HCV has been associated with multiple extrahepatic manifestations, including cryoglobulinemia, glomerulonephritis, skin disorders (porphyria cutanea tarda, lichen planus), arthritis, a siccalike syndrome, and lymphoproliferative disorders. The strongest associations are with cryoglobulinemia and membranoproliferative glomerulonephritis. Renal manifestations are usually associated with long-standing (i.e., >10 years) HCV infection, as in the reported case. Most often, there are concurrent clinical and laboratory features of chronic hepatitis and/or cirrhosis. Renal manifestations may occur in the absence of other signs of cryoglobulinemia or liver disease, however, and the diagnosis of HCV infection may be made during evaluation of a renal disorder. Pathologic findings in a renal biopsy (including glomerular intracapillary globular accumulations of eosinophilic material containing precipitated cryoglobulins, and glomerular immune complex deposits with a finely fibrillar or tactoid pattern of organization visualized by electron microscopy) can sometimes be the first clue to a diagnosis of cryoglobulinemia and corresponding HCV infection. Circulating cryoglobulins, either at the time of presentation or at some point in the patient’s history, are generally detected in only approximately 50%–70% of patients with HCV-associated glomerulonephritis.

This case report is timely in view of several recent studies that point to the potential magnitude of the problem of HCV infection and kidney disease. A recent analysis of the current National Health and Nutrition Examination Survey that involved >15 000 patients indicates stable prevalences in the US of HCV seropositivity (1.6%, estimated 4.1 x 10⁶ infected persons) and HCV viremia (1.3%, 3.2 x 10⁶ actively infected persons) (1). Because the incidence of acute HCV infection has declined to its lowest rate ever (2), the sustained high prevalence is due to a reservoir of infections acquired decades previously. Because kidney disease and cryoglobulinemia are late manifestations of HCV infection, as was the case for the described patient, an increase in HCV-associated renal disease and cryoglobulinemia can be anticipated in the near term. A heightened awareness of this growing problem should lead to more timely diagnoses and improve management strategies for infected patients.

Acknowledgments

Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.

Authors’ Disclosures of Potential Conflicts of Interest: Upon manuscript submission, all authors completed the Disclosures of Potential Conflict of Interest form. Potential conflicts of interest:

Employment or Leadership: None declared.

Consultant or Advisory Role: None declared.

Stock Ownership: None declared.

Honoraria: None declared.

Research Funding: C.E. Alpers, NIH grant DK66802.

Expert Testimony: None declared.

Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.

References

1. Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med 2006;144:705-714.[Abstract/Free Full Text]
2. Wasley A, Grytdal S, Gallagher K, . Centers for Disease Control and Prevention (CDC). Surveillance for acute viral hepatitis – United States, 2006. MMWR Surveill Summ 2008;57:1-24.[Medline] [Order article via Infotrieve]

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