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09/21/2011 - HCV, cryoglobulinemia and glomerulonephritis

posted Sep 28, 2011, 6:03 PM by Chief Resident   [ updated Sep 28, 2011, 6:58 PM by Purnema Madahar ]
In morning report, Alvin Htut presented a case of HCV-related cryoglobulinemic membranoproliferative glomerulonephritis (MPGN) to Sharon Silbiger. Historically, treatment of this disease has been attempted in two partially conflicting ways: immunosuppression to reduce the cryoglobulinemia and ensuing vasculitis at the cost of increased viral replication and/or anti-viral therapy with the goal of sustained virological response (SVR) with drugs that are relatively contra-indicated in renal failure.

Only limited data exist on the comparative benefits of either strategies. The attached review paper nicely discusses the relation of HCV, cryoglobulins and GN and summarizes the available evidence on treatment. Most trials are too small, not randomized or controlled and confounded by different HCV genotypes and non-controlled concurrent treatments to yield valid results. Nevertheless, available data suggests that anti-viral treatment improves renal function expressed as reduction in creatinine and proteinuria.

The atttached meta-analysis of the effect of interferon-alpha on renal function is affected by the same limitations as mentioned above. It showed that, not surprisingly, improvement of renal function (again creatinine levels and proteinuria) was greater in patients who achieved SVR (clearance of HCV RNA during treatment and for at least 6 months after completion of anti-virals) than those that didn't.

Finally, we wondered if cryoglobulinemia could persist of recur after successful treatment of HCV. It seems that it can: the third attached paper reports 8 patients who had a relapse of cryoglobulinemic vasculitis despite SVR; two of them were diagnosed with a B cell lymphoma.

All this might change with the arrival of new HCV anti-virals and the use of rituximab in the treatment of cryoglobulinemia. However, since it's a fairly rare disease, good RCTs will be hard to come by.
Fabrizio Fabrizi, Giovanna Lunghi, Piergiorgio Messa, Paul Martin
Journal of nephrology 21 (6) p. 813-25

Bo Feng, Garabed Eknoyan, Zhong-Sheng Guo, Michel Jadoul, Hui-Ying Rao, Wei Zhang, Lai Wei (2011)
Nephrology, dialysis, transplantation Epub 2011

Dan-Avi Landau, David Saadoun, Philippe Halfon, Michelle Martinot-Peignoux, Patrick Marcellin, Elena Fois, Patrice Cacoub (2008)
Arthritis and rheumatism 58 (2) p. 604-11