Gad Amal, Tanaka Eiji, Matsumoto Akihiro, el-Hamid Serwah Abd, Ali Khalil, Makledy Fathy, el-Gohary Ahmed, Orii Koji, Ijima Akihiro, Rokuhara Akinori, Yoshizawa Kaname, Nooman Zohair, Kiyosawa Kendo
Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
J Med Virol. 2003 Aug;70(4):594-9. doi: 10.1002/jmv.10435.
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.
冷球蛋白血症与丙型肝炎病毒（HCV）感染之间的关联已有报道。然而，其发生率广泛变异背后的因素尚未得到很好的确定。为了对此进行研究，在埃及和日本患者的四个队列中对冷球蛋白血症进行了研究。50例感染4型基因型（埃及主要的HCV基因型）的埃及慢性丙型肝炎患者与50例年龄和性别匹配、感染1b型基因型（日本主要的HCV基因型）的日本患者进行了比较。32例埃及慢性乙型肝炎患者和30例年龄及性别匹配的日本慢性乙型肝炎患者作为对照。所有患者均无肝硬化。对抗核抗体（ANA）、免疫球蛋白（Ig）和冷球蛋白进行了评估。结果显示，与埃及4型基因型（14%）相比，日本1b型基因型慢性丙型肝炎患者冷球蛋白血症的患病率显著更高（40%），P = 0.003，而日本（17%）和埃及慢性乙型肝炎对照组（13%）之间未发现差异。有症状的冷球蛋白血症在日本慢性丙型肝炎组中比埃及组更常见（10%对4%），但差异无统计学意义。单因素分析显示，在日本或埃及患者中，冷球蛋白血症与年龄、性别、丙氨酸转氨酶水平或HCV病毒载量均无关联，而每组中冷球蛋白阳性的慢性丙型肝炎患者的平均IgM水平显著高于冷球蛋白阴性患者（分别为P = 0.003和0.017）。在1b型基因型的日本慢性丙型肝炎患者中，冷球蛋白血症与高IgG水平（P = 0.020）和ANA阳性（P < 0.001）均显著相关，但在4型基因型的埃及患者中并非如此。多因素分析显示，易患冷球蛋白血症的唯一因素是感染1b型HCV基因型的日本种族（P = 0.002，OR = 2.56）、IgM水平>245 mg/dl（P = 0.018，OR = 2.05）和女性性别（P = 0.040，OR = 1/0.66）。总之，感染1b型基因型的日本慢性丙型肝炎患者中冷球蛋白血症很常见，但感染HCV 4型基因型的埃及患者中冷球蛋白血症并不常见。尽管在本研究中无法分别评估种族和HCV基因型，但1b型HCV基因型似乎比4型基因型更容易引发冷球蛋白血症。女性性别和高血清IgM水平也与之相关。
