Incidence of mixed cryoglobulinemia and its significance in the development of extrahepatic manifestations in chronic hepatitis C and co-infection chronic hepatitis C/HIV infection


Cryoglobilinemia (CG) is pathological state that can be developed in patients with chronic infection caused by the hepatitis C virus (HCV) and also in patients co-infected with human immunodeficiency virus (HIV).

Aim of the study was to investigate incidence of mixed CG and its clinical relationship to extrahepatic manifestations (EHM) like arthralgia, cutaneous vasculitis and polyneuropathy in patients with chronic hepatitis C and chronic hepatitis C/HIV co-infection.

Material and methods. 331 patients (254 with HCV infection and 77 with HCV/HIV co-infection) were included in a selective non-randomized outpatient study. Patients were examined for the presence of CG and rheumatoid factor. In 74 CG patients monoclonal immunoglobulin was also investigated.

Results. CG was detected in 51% [95% confidence interval (CI) 43–55] cases, n=167. Among patients with HCV infection and HCV/HIV co-infection, there were no statistically significant differences in the frequency of CG: 49% (95% CI 43–55) vs 55% (95% CI 44–65), χ2=0.672, p=0.412. The presence of cryoglobulins correlated with the detection of rheumatoid factor at both 37C° (φ=0.435, p<0.001) and 4C° (φ=0.377, p<0.001). Low (1–4%) and medium (5–9%) levels of cryocrit predominated among tested patients. In most cases type III CG was detected – 81% (95% CI 71–88), n=60/74. Detection of II type CG was less frequent – 19% (95% CI 12–29), n=14/74. Type I CG was not recorded. Among patients with type II CGM, IgM-κ was detected in 86% (95% CI 60–96) of cases (n=12/14). The incidence of arthralgia (63 vs 21%, p<0.001), cutaneous vasculitis (38 vs 2%, p<0.001), Meltzer triad (30 vs 2%, p<0.001) and polyneuropathy (25 vs 2%, p<0.001) was statistically significantly higher in HCV infected with CG than in patients without CG. The incidence of arthralgia (62 vs 26%, p=0.001), Meltzer triad (19 vs 3%, p=0.028) and polyneuropathy (29 vs 3%, p=0.003) was also significantly higher in HCV/HIV infected with CG than in patients without CG, and the frequency of cutaneous vasculitis did not differ statistically (29 vs 20%, p=0.385). Analysis of the data of patients with CG did not reveal a statistically significant difference between the HCV and HCV/HIV-infected groups in the incidence of arthralgia (p=0.881), cutaneous vasculitis (p=0.290), Meltzer triad (p=0.154), polyneuropathy (p=0.629).

Conclusion. CG associated with HCV and HCV/HIV co-infection can be found in half of disease cases, and is mostly polyclonal. Type II CG in 86% is caused by monoclonal IgM-κ. Development of CG related EHM (arthralgia, cutaneous vasculitis and polyneuropathy is not related to HIV co-infection.

Keywords:cryoglobulins; cryoglobulinemia; extrahepatic manifestations; virus hepatitis C; HIV

Funding. The study had no sponsor support.

Conflict of interest. The authors declare no conflicts of interest.

Contribution. Concept and design – Dunaeva N.V., Gusev D.A.; data collection – Dunaeva N.V., Mazing A.V.; statistical processing – Dunaeva N.V.; text writing, design – Dunaeva N.V.; editing – Lapin S.V., Gusev D.A.

For citation: Dunaeva N.V., Mazing A.V., Lapin S.V., Gusev D.A. Incidence of mixed cryoglobulinemia and its significance in the development of extrahepatic manifestations in chronic hepatitis C and co-infection chronic hepatitis C/HIV infection. Infektsionnye bolezni: novosti, mneniya, obuchenie [Infectious Diseases: News, Opinions, Training]. 2022; 11 (2): 69–76. DOI:


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Yushchuk Nikolay Dmitrievich
Academician of the Russian Academy of Sciences, Professor, head of the Infectious Diseases and Epidemiology Department, President of the Moscow State University of Medicine and Dentistry named after A.I. Evdokimov, Board member of the National Scientific Infectiologists? Society.
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