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

Five-year View: Toward a New Therapeutic Algorithm

Based on general experience, milder forms of cryoglobulinemia can be managed without immunosuppression. Combined antiviral therapy appears to be a logical choice, may target both the viral trigger and the downstream arm of autoimmunity[6] and can be usefully applied to control mild-to-moderate manifestations.[5] Some authors claim that a 1-year schedule is needed for cryoglobulinemic patients, regardless of the genotype that is involved.[28] There is some evidence that, at least for virus eradication, patients infected with genotypes 2 or 3, and who are male, white and with a normal BMI could benefit from a shorter therapy duration.

Questions do exist regarding the appropriate position of B-cell-depletion strategies in the treatment of MC. Rituximab has earned a definite role in the more severe cases ( Table 4 ). It could even be indicated as first-line therapy in life-threatening conditions or fulminant presentations, that is, peripheral necrosis of the extremities for which plasma exchange and immunosuppressive drugs were believed to be the only resource until 3 years ago.[3] Severe worsening of renal function, mononeuritis multiplex, extensive skin ulcers and distal necrosis are the main indications.[35,36,37]

Persistence of effects would appear to be time limited, with mean responses lasting 6-12 months. The '4-plus-2' protocol seems to favor a longer-lasting response.[37] Until recently, administering antiviral drugs after the critical phase was considered mandatory. However, on the basis of our own experience and on that of other authors,[35,36,39] it may actually be unnecessary in most cases. Due to the rarity of the disease, questions concerning the appropriate position and the best protocol, as well as safety and indications to retreatment, would be best addressed in multicenter trials. One such trial is currently ongoing and will involve a considerable number of Italian and French patients within the next few months.


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