Rheumatoid factor levels indicate cryoglobulinemia severity in hepatitis B e antigen-negative hepatitis B virus carriers: a 7-year prospective cohort study

Jen-Wei Wu; Wei-Ting Chen; Chung-Guei Huang; Yung-Chang Chen; Chao-Wei Hsu; Rong-Nan Chien; Ming-Ling Chang

doi:10.1007/s12072-024-10761-8

Rheumatoid factor levels indicate cryoglobulinemia severity in hepatitis B e antigen-negative hepatitis B virus carriers: a 7-year prospective cohort study

Hepatol Int. 2024 Dec 19. doi: 10.1007/s12072-024-10761-8. Online ahead of print.

Authors

Jen-Wei Wu^{1

2}, Wei-Ting Chen^{1

2}, Chung-Guei Huang^{3

4}, Yung-Chang Chen⁵, Chao-Wei Hsu^{1

2}, Rong-Nan Chien^{1

2}, Ming-Ling Chang^{6

7}

Affiliations

¹ Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, No 5, Fu Hsing Street, Kuei Shan, Taoyuan, Taiwan.
² Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
³ Department of Laboratory Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.
⁴ Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan.
⁵ Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
⁶ Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, No 5, Fu Hsing Street, Kuei Shan, Taoyuan, Taiwan. [email protected].
⁷ Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan. [email protected].

PMID: 39699792
DOI: 10.1007/s12072-024-10761-8

Abstract

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.

Keywords: Cryoglobulinemia; HBV; HBeAg; Rheumatoid factor.