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Updated: Jun 4, 2025
Generation of Two-color Antigen Microarrays for the Simultaneous Detection of IgG and IgM Autoantibodies
Published on: September 15, 2016
Rheumatoid factor levels indicate cryoglobulinemia severity in hepatitis B e antigen-negative hepatitis B virus
Jen-Wei Wu1,2, Wei-Ting Chen1,2, Chung-Guei Huang3,4
1Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, No 5, Fu Hsing Street, Kuei Shan, Taoyuan, Taiwan.
Background:
The phenotype of cryoglobulinemia in hepatitis B virus (HBV) carriers remains elusive.
Methods:
A 7-year prospective cohort of 648 hepatitis B e antigen (HBeAg)-negative Taiwanese HBV carriers [males: 344 (53%)] was conducted.
Results:
Among 648, 189 (29.2%) had cryoglobulinemia, and 26 (4.0%) had cryoglobulinemic syndrome (CS). More females; higher levels of rheumatoid factor (RF), immunoglobulin M (IgM) and fibrosis-4 indices; higher proportions of proteinuria, hematuria and hepatocellular carcinoma; and lower levels of quantitative HBsAg, C3, C4 and eGFR were noted in patients with than in those without cryoglobulinemia. The associations were RF levels with cryoglobulinemia (cutoff > 12.55 IU/mL), and RF levels and baseline autoimmune diseases with CS. CS patients, symptomless cryoglobulinemia patients and patients without cryoglobulinemia had the highest, moderate, and lowest RF levels, respectively. A greater percentage of mixed cryoglobulins [IgG (2 +), IgM (2 +) and IgA (1 +)] was noted in cryoglobulinemia patients with than in those without CS (11.5% vs. 0.81%, p = 0.002). Among the 7 CS patients treated with nucleos(t)ide analogues (Nucs), cryoglobulinemia disappeared in 3 and symptoms improved in 5 during therapy. The CS prevalence was highest (6%) in patients with a baseline age of 31-40 years. Among the 26 CS patients, 23 (88.5%), 20 (76.9%), and 16 (61.5%) had peripheral neuropathy, articular and skin involvement, respectively. The cumulative incidences of major outcomes and mortality did not differ between patients with and without cryoglobulinemia.
Conclusions:
The prevalence rates of cryoglobulinemia and CS in HBeAg-negative HBV carriers were 29.2% and 4.0%, respectively. RF levels correlate with cryoglobulinemia severity. Mixed cryoglobulins of IgG (2 +), IgM (2 +) and IgA (1 +) are likely linked to CS, which might be alleviated by Nucs in some patients. The impact of cryoglobulinemia on long-term outcomes might be negligible.
