Treatment of refractory, symptomatic, hepatitis C virus related mixed cryoglobulinemia with ribavirin and interferon-alpha.
OBJECTIVE
To assess the benefit of interferon-alpha/ribavirin combination therapy in hepatitis C virus (HCV) infected patients with symptomatic mixed cryoglobulinemia (MC) who failed to respond to treatment with interferon-alpha (IFN-alpha).


METHODS
Nine patients (mean age 57 +/- 14 yrs) with type II symptomatic MC who failed to respond to IFN-alpha monotherapy were re-treated with combination treatment of IFN-alpha 3 times weekly and ribavirin 15 mg/kg daily for 6 months. Five of 9 patients had previously received additional treatment during IFN-alpha monotherapy. Clinical and laboratory evaluations (including cryocrit level) were performed weekly for the first month and monthly thereafter.


RESULTS
Baseline mean alanine aminotransferase (ALT) and cryocrit levels were 119 +/- 97 IU/l and 7.9% +/- 10%, respectively. All patients were HCV-RNA positive and 5 had cirrhosis. At the end of therapy, mean ALT level was 84 +/- 79 IU/l (p = 0.02), while normal ALT levels were observed in 4 of 9 patients (44%). However, complete virological response was achieved in only 2 patients (22%). Cryoglobulin became undetectable within 6 weeks of therapy in 7 patients (78%) and decreased significantly in 2 others (p = 0.008). A substantial improvement in MC related symptoms (arthralgia/arthritis, proteinuria, skin vasculitis) was achieved in all patients within 10 weeks of combination therapy, although polyneuropathy related symptoms were relatively resistant to treatment.


CONCLUSIONS
Symptomatic, refractory HCV related MC should be considered as an indication for combination therapy with IFN-alpha and ribavirin. Improvement in MC related symptoms can be achieved even without complete biochemical or virological response.
Zuckerman
E
E
Liver Clinic, Department of Internal Medicine A, B'nai Zion Medical Center, Bruce Rappaport Faculty of Medicine, Technion, Israel.
Keren
D
D
Slobodin
G
G
Rosner
I
I
Rozenbaum
M
M
Toubi
E
E
Sabo
E
E
Tsykounov
I
I
Naschitz
J E
JE
Yeshurun
D
D
D000328:Adult; D000368:Aged; D003449:Cryoglobulinemia / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000008:administration & dosage*
D016898:Interferon-alpha; D012254:Ribavirin