Page 262 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

236 Clodoveo Ferri, Dilia Giuggioli and Marco Sebastiani

MC, hypocomplementemia, with frequent autoimmune-vasculitic manifestations, and a
higher risk of lymphoma [16].

Autoimmune hepatitis may be associated with HCV infection in the same geographic
areas where HCV-associated CV occurs. The differential diagnosis between CV and
autoimmune hepatitis may be difficult due to the presence of hepatic and extrahepatic
autoimmune phenomena in both entities [1, 4, 12]. The presence of the typical features of CV
including LCV, hypocomplementemia, glomerulonephritis, and mild hepatitis may
collectively be a clue in differentiating CV from classical autoimmune hepatitis [1, 4, 12].

Prognosis

The overall 10-year survival of CV is estimated to be about 50% [9]. The clinical course
and prognosis of CV relates mainly to disease manifestations, response to treatments and
comorbid disorders, as well as, complications accrued to CV and its treatment [9]. Those with
renal disease, liver failure, lymphoproliferative and other malignancies demonstrate the least
favorable outcome [1, 4, 9, 12]. Careful monitoring of patients for life-threatening
complications of CV including, nephropathy, widespread systemic vasculitis, hepatitis, and
malignancy all positively impact on its overall prognosis.

Treatment

Figure 4 summarizes the therapeutic approach to CV. Taking into account three
important aspects of disease pathogenesis, treatment can be aimed at chronic immune
stimulation by eradicating HCV infection, attenuating the resultant T- and B-cell activation,
and the production of cryoglobulins and IC, as well as the identification and treatment of B-
cell lymphoproliferation to avert the development of B-NHL. This multistep, multifactorial
etiopathogenesis-oriented approach to therapy targets HCV infection, B-cell proliferation, and
the resultant CV involvement. Combination treatment with INF? and ribavirin led to
sustained clearance of HCV in up to 60% of patients so treated, particularly those with the
2a/2c HCV genotype [4, 17]. Triple therapy with PEGylated-INF?, ribavirin, and specifically
targeted antiviral agents such as protease inhibitors in selected patients, significantly
improves the percentage of sustained virologic response [4]. However, IFN-?, which is both
antiviral and immunomodulatory, can trigger or exacerbate subclinical symptoms in
predisposed patients, with associated immune-mediated side effects such as peripheral
neuropathy, thyroiditis, and rheumatoid-like polyarthritis [1, 4, 12]. There are anecdotal
reports of improvement in autoimmune lymphoproliferative-related disorders after HCV
eradication similar to H.pylori-associated gastric lymphomas [1, 4] that suggest a favorable
biologic and genetic responsiveness to treatment of HCV in the early phase of CV.

Physicians treating CV must choose from among available symptomatic and pathogenic
therapies including a low-antigen-content (LAC) diet, plasma exchange (PE), and
immunosuppressant regimens employing corticosteroids, rituximab and cyclophosphamide
[1, 4, 17].

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