Mixed cryoglobulinemia decelerates hepatocellular carcinoma development in hepatitis C patients with SVR by downregulating regulatory B cells: a 12-year prospective cohort study

How mixed cryoglobulinemia (MC) affects cancer risk in chronic hepatitis C patients with sustained virologic response (SVR) remains unclear. In a 12-year prospective study, post-SVR MC was assessed every 3‒6 months. Among the 891 SVR patients, 265 (29.7%) had baseline (24 weeks after completing anti...

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Main Authors: Ming-Ling Chang, Jur-Shan Cheng, Wei-Ting Chen, Yi-Jyun Shen, Chia-Jung Kuo, Rong-Nan Chien
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:OncoImmunology
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Online Access:https://www.tandfonline.com/doi/10.1080/2162402X.2025.2470128
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author Ming-Ling Chang
Jur-Shan Cheng
Wei-Ting Chen
Yi-Jyun Shen
Chia-Jung Kuo
Rong-Nan Chien
author_facet Ming-Ling Chang
Jur-Shan Cheng
Wei-Ting Chen
Yi-Jyun Shen
Chia-Jung Kuo
Rong-Nan Chien
author_sort Ming-Ling Chang
collection DOAJ
description How mixed cryoglobulinemia (MC) affects cancer risk in chronic hepatitis C patients with sustained virologic response (SVR) remains unclear. In a 12-year prospective study, post-SVR MC was assessed every 3‒6 months. Among the 891 SVR patients, 265 (29.7%) had baseline (24 weeks after completing anti-HCV therapy) MC, and the 12-year cancer cumulative incidence was 19.7%. Among the 73 patients who developed cancer, 37 (50.7%) had hepatocellular carcinoma (HCC), with the following associated baseline variables: for cancer, male sex, age and alanine aminotransferase (ALT) levels; for HCC, male sex, age, and cirrhosis; and for non-HCC cancer, rheumatoid factor levels. Among patients with post-SVR HCC, the mean time to HCC was longer in those with than in those without baseline MC (1545.4 ± 276.5 vs. 856.9 ± 115.2 days, p = 0.014). Patients with baseline MC had decreased circulating interleukin-10 (IL-10)-positive B cell (CD19+IL-10+cells/CD19+cells) (31.24 ± 16.14 vs. 40.08 ± 15.42%, p = 0.031), regulatory B cell (Breg) (CD19+CD24hi CD27+cells/CD19+cells) (10.45 ± 7.10 vs. 15.76 ± 9.14%, p = 0.035), IL-10-positive Breg (CD19+CD24hiCD27+IL-10+cells/CD19+cells) (5.06 ± 4.68 vs. 8.83 ± 5.46%, p = 0.015) and HCC-infiltrating Breg (18.6 ± 10 vs. 33.51 ± 6.8%, p = 0.022) ratios but comparable circulating and HCC-infiltrating regulatory T cell ratios relative to patients without baseline MC. In conclusion, old male SVR patients with elevated ALT levels or cirrhosis require intensive monitoring for cancer development, especially HCC. Tailored HCC follow-up is needed for SVR patients according to their baseline MC, which might downregulate Bregs to decelerate HCC development for almost 2 years.
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spelling doaj-art-a2c1f74bc7274b389d1e10b19d3db5142025-08-20T01:56:56ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2025.2470128Mixed cryoglobulinemia decelerates hepatocellular carcinoma development in hepatitis C patients with SVR by downregulating regulatory B cells: a 12-year prospective cohort studyMing-Ling Chang0Jur-Shan Cheng1Wei-Ting Chen2Yi-Jyun Shen3Chia-Jung Kuo4Rong-Nan Chien5Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, Taoyuan, TaiwanDepartment of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, Taoyuan, TaiwanDepartment of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, Taoyuan, TaiwanDepartment of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, Taoyuan, TaiwanDepartment of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, Taoyuan, TaiwanDepartment of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, Taoyuan, TaiwanHow mixed cryoglobulinemia (MC) affects cancer risk in chronic hepatitis C patients with sustained virologic response (SVR) remains unclear. In a 12-year prospective study, post-SVR MC was assessed every 3‒6 months. Among the 891 SVR patients, 265 (29.7%) had baseline (24 weeks after completing anti-HCV therapy) MC, and the 12-year cancer cumulative incidence was 19.7%. Among the 73 patients who developed cancer, 37 (50.7%) had hepatocellular carcinoma (HCC), with the following associated baseline variables: for cancer, male sex, age and alanine aminotransferase (ALT) levels; for HCC, male sex, age, and cirrhosis; and for non-HCC cancer, rheumatoid factor levels. Among patients with post-SVR HCC, the mean time to HCC was longer in those with than in those without baseline MC (1545.4 ± 276.5 vs. 856.9 ± 115.2 days, p = 0.014). Patients with baseline MC had decreased circulating interleukin-10 (IL-10)-positive B cell (CD19+IL-10+cells/CD19+cells) (31.24 ± 16.14 vs. 40.08 ± 15.42%, p = 0.031), regulatory B cell (Breg) (CD19+CD24hi CD27+cells/CD19+cells) (10.45 ± 7.10 vs. 15.76 ± 9.14%, p = 0.035), IL-10-positive Breg (CD19+CD24hiCD27+IL-10+cells/CD19+cells) (5.06 ± 4.68 vs. 8.83 ± 5.46%, p = 0.015) and HCC-infiltrating Breg (18.6 ± 10 vs. 33.51 ± 6.8%, p = 0.022) ratios but comparable circulating and HCC-infiltrating regulatory T cell ratios relative to patients without baseline MC. In conclusion, old male SVR patients with elevated ALT levels or cirrhosis require intensive monitoring for cancer development, especially HCC. Tailored HCC follow-up is needed for SVR patients according to their baseline MC, which might downregulate Bregs to decelerate HCC development for almost 2 years.https://www.tandfonline.com/doi/10.1080/2162402X.2025.2470128CancerHCCHCVmixed cryoglobulinemiasustained virologic response
spellingShingle Ming-Ling Chang
Jur-Shan Cheng
Wei-Ting Chen
Yi-Jyun Shen
Chia-Jung Kuo
Rong-Nan Chien
Mixed cryoglobulinemia decelerates hepatocellular carcinoma development in hepatitis C patients with SVR by downregulating regulatory B cells: a 12-year prospective cohort study
OncoImmunology
Cancer
HCC
HCV
mixed cryoglobulinemia
sustained virologic response
title Mixed cryoglobulinemia decelerates hepatocellular carcinoma development in hepatitis C patients with SVR by downregulating regulatory B cells: a 12-year prospective cohort study
title_full Mixed cryoglobulinemia decelerates hepatocellular carcinoma development in hepatitis C patients with SVR by downregulating regulatory B cells: a 12-year prospective cohort study
title_fullStr Mixed cryoglobulinemia decelerates hepatocellular carcinoma development in hepatitis C patients with SVR by downregulating regulatory B cells: a 12-year prospective cohort study
title_full_unstemmed Mixed cryoglobulinemia decelerates hepatocellular carcinoma development in hepatitis C patients with SVR by downregulating regulatory B cells: a 12-year prospective cohort study
title_short Mixed cryoglobulinemia decelerates hepatocellular carcinoma development in hepatitis C patients with SVR by downregulating regulatory B cells: a 12-year prospective cohort study
title_sort mixed cryoglobulinemia decelerates hepatocellular carcinoma development in hepatitis c patients with svr by downregulating regulatory b cells a 12 year prospective cohort study
topic Cancer
HCC
HCV
mixed cryoglobulinemia
sustained virologic response
url https://www.tandfonline.com/doi/10.1080/2162402X.2025.2470128
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