Natural history and clinical impact of cryoglobulins in chronic hepatitis C: 10-year prospective study of 343 patients.
OBJECTIVE
Serum cryoglobulins (CGs) are present in patients with chronic hepatitis C virus (HCV) infection, but their long-term clinical importance has not been established. We assessed the development rates, morbidity, and influence on the evolutionary course of hepatitis C of CG.


METHODS
A cohort of 343 HCV-RNA seropositive outpatients (173 men; age, 58 y; 82 with cirrhosis; 61 treated with interferon) with persistently increased aminotransferase levels and histologically defined liver disease was investigated. Patients initially were investigated for the presence, amount, and type of CG and prospectively followed up with clinical and laboratory examinations every 6 months.


RESULTS
At enrollment, CGs were found in 163 (47%) patients at a mean level of 173 +/- 142 mg/L; 80% were type III, and associated to female sex (61% vs 40%, P = .0002) and cirrhosis (29% vs 19%, P = .04). Over the course of 17-130 months (median, 116 mo), de novo CG developed in 25 patients (2.3% per year), including 5 with cryoglobulinemic syndrome (.3% per year). The 10-year rates of progression to cirrhosis and of liver and extrahepatic complications were similar in CG (+) and CG (-) patients (32% vs 34%; 23% vs 16%; 5% vs 3%). The 10-year survival rates were lower for cirrhotic than for noncirrhotic patients (57% vs 91%, P < .00001), independently of CGs.


CONCLUSIONS
CGs are common in patients with chronic HCV infection, mainly are type III, and do not influence the clinical course of hepatitis C during the first decades, except for the few rare cases of cryoglobulinemic syndrome.
Division of Gastroenterology, Istituto di Ricovero e Cura a Carattere Scientifico Maggiore Hospital Fondazione Policlinico, Mangiagalli e Regina Elena, Centro A. M. & A. Migliavacca, University of Milan, Milan, Italy.
Mauro
M
Viganò
Pietro
P
Lampertico
Maria Grazia
MG
Rumi
Christian
C
Folli
Lorena
L
Maggioni
Alberto
A
Morabito
Ersilio
E
Del Ninno
Marco
M
Cicardi
Massimo
M
Colombo
D000328:Adult; D000368:Aged; D001706:Biopsy; D015331:Cohort Studies; D003450:Cryoglobulins / Q000032:analysis*; D018450:Disease Progression; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016019:Survival Analysis
D003450:Cryoglobulins