Relationship Between Cryoglobulinemia-associated Nephritis and HCV Infection

Dario Roccatello; Osvaldo Giachino; Elisa Menegatti; Simone Baldovino


Expert Rev Clin Immunol. 2008;4(4):515-524. 

In This Article

Standard Immunosuppression

Despite the unquestionable evidence of a viral etiology, immunosuppression is still regarded as the first-line intervention if renal involvement is severe. Immunosuppression may be taken into consideration for patients failing to respond to interferon treatment in combination with ribavirin or during acute immunological flare-ups. In these cases, antiviral treatment, albeit able to reduce viremia, is usually either insufficient to control renal disease or even detrimental. In many centers, high-dose corticosteroids, plasmapheresis and, in more severe cases, cytotoxic therapy are commonly administered,[3] but no trials have prospectively evaluated these treatments. These therapeutic approaches may cause an increase in the levels of viremia, thus exacerbating chronic hepatitis C disease. Nevertheless, renal disease is often a compelling indication for these treatments. Purpura is the most frequent indication for corticosteroids, which remain the most amenable therapy. Another indication is peripheral neuropathy, even though its general refractoriness to any treatment is widely recognized. Patients who need such therapies generally require multiple courses. Symptoms often recur after periods of quiescence or may flare-up after periods of stability.

By comparing data regarding a robust sample of patients with MC-associated GN[3] with the only comparable cohort described 10 years earlier,[33] it was clear that, besides a better survival rate (80 vs 50% at 10 years), cardiovascular death had become predominant as compared with the previous study in which the number of deaths due to infections and hepatic failure were dominant. There could be several reasons for this changing picture: the better survival profiles that have been obtained over the last decade could be the consequence of an aggressive, time-limited intervention for acute renal involvement, together with the long-term antiviral therapy that was used to control moderate manifestations of renal and extrarenal involvement.

Among the current immunosuppressive protocols, cyclophosphamide (1.5-2 mg/kg/day administered orally or 0.5-1 g administered intravenously, every 2-4 weeks) in association with oral steroids (0.5-1 mg/kg/day for 1 month with subsequently reducing the dose by 2.5-5 mg/week) often preceded by three pulses of 10-15 mg/kg methylprednisolone represents the most popular combination therapy in severe manifestations of or in patients with uncontrolled symptoms. Mycophenolate mofetil and cyclosporin (claimed to interfere with the polymerase-binding affinity to HCV RNA[34]) have become feasible alternatives.

Plasma exchange, especially double-filtration plasmapheresis (which selectively removes molecules greater than 600 kDa) continues to be successfully used in escalation protocols to treat rapidly progressing GN, skin ulcers, sensory motor neuropathy, widespread vasculitis and hyperviscosity syndrome.

A standard course of combined antiviral therapy is often indicated following immunosuppression in order to attenuate the viral replication that is induced.


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