Factors predisposing to the occurrence of cryoglobulinemia in two cohorts of Egyptian and Japanese patients with chronic hepatitis C infection: ethnic and genotypic influence.

The association between cryoglobulinemia and hepatitis C virus (HCV) infection has been reported. However, the factors underlying its wide variation of occurrence have not yet been well identified. To investigate this, cryoglobulinemia was studied in four cohorts of Egyptian and Japanese patients. Fifty Egyptian patients with chronic hepatitis C, infected with genotype 4 (the predominant HCV genotype in Egypt), were compared with 50 age- and sex-matched Japanese patients, infected with HCV genotype 1b (the predominant HCV genotype in Japan). Thirty-two Egyptian and 30 age- and sex-matched Japanese patients with chronic hepatitis B were included as controls. All patients were noncirrhotic. Antinuclear antibody (ANA), immunoglobulins (Ig), and cryoglubulins were assessed. Results showed a significantly higher prevalence of cryoglobulinemia in chronic hepatitis C Japanese genotype 1b (40%) as compared with Egyptian genotype 4 (14%), P = 0.003, while no difference was found between Japanese (17%) and Egyptian chronic hepatitis B controls (13%). Symptomatic cryoglobulinemia was more prevalent in the Japanese than in the Egyptian chronic hepatitis C group (10% vs. 4%), but the difference was not statistically significant. Univariate analysis showed no association between cryoglobulinemia and either age, sex, alanine aminotransferase level, or HCV viral load in Japanese or Egyptian patients, while the mean IgM level was significantly higher in the cryoglobulin-positive than in the cryoglobulin-negative chronic hepatitis C patients in each group (P = 0.003 and 0.017, respectively). Cryoglobulinemia was found to be significantly associated with both high IgG level (P = 0.020), and positive ANA (P < 0.001) in Japanese patients with chronic hepatitis C, genotype 1b but not in Egyptians with genotype 4. Multivariate analysis showed that the only factors predisposing to cryoglobulinemia were Japanese ethnicity with HCV genotype1b (P = 0.002, OR = 2.56), high IgM level of >245 mg/dl (P = 0.018, OR = 2.05) and female gender (P = 0.040, OR = 1/0.66). In conclusion, cryoglobulinemia is prevalent in Japanese patients with chronic hepatitis C infected with genotype 1b, but cryoglobulinemia is not common in Egyptians with HCV genotype 4. Although it was not possible to evaluate ethnicity and HCV genotype separately in this study, HCV genotype 1b appears to predispose more to cryoglobulinemia than does genotype 4. Female gender and high serum IgM level were also related.