Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis
Open accessAbstract
The predictive role of antinuclear antibodies (ANAs) remains elusive in the long-term outcome of primary biliary cirrhosis (PBC). The progression of PBC was evaluated in association with ANAs using stepwise Cox proportional hazard regression and an unconditional stepwise logistic regression model based on the data of 276 biopsy-proven, definite PBC patients who have been registered to the National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ). When death of hepatic failure/liver transplantation (LT) was defined as an end-point, positive anti-gp210 antibodies (Hazard ratio (HR) = 6.742, 95% confidence interval (CI): 2.408, 18.877), the late stage (Scheuer's stage 3, 4) (HR = 4.285, 95% CI:1.682,10.913) and male sex (HR = 3.266, 95% CI: 1.321,8.075) were significant risk factors at the time of initial liver biopsy. When clinical progression to death of hepatic failure/LT (i.e., hepatic failure type progression) or to the development of esophageal varices or hepatocellular carcinoma without developing jaundice (Total bilirubin < 1.5 mg/dL) (i.e., portal hypertension type progression) was defined as an end-point in the early stage (Scheuer's stage 1, 2) PBC patients, positive anti-gp210 antibodies was a significant risk factor for hepatic failure type progression [odds ratio (OR) = 33.777, 95% CI: 5.930, 636.745], whereas positive anti-centromere antibodies was a significant risk factor for portal hypertension type progression (OR = 4.202, 95% CI: 1.307, 14.763). Histologically, positive anti-gp210 antibodies was most significantly associated with more severe interface hepatitis and lobular inflammation, whereas positive anticentromere antibodies was most significantly associated with more severe ductular reaction. Conclusion: These results indicate 2 different progression types in PBC, hepatic failure type and portal hypertension type progression, which may be represented by positive-anti-gp210 and positive-anticentromere antibodies, respectively. (Hepatology 2007;45:118–127.)
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There is evidence to suggest that PBC-linked ANA (in particular anti-gp210/anti-nuclear rim antibody) may be associated with more rapidly progressive disease and disease which is less responsive to UDCA therapy.
“There is evidence to suggest that PBC-linked ANA (in particular anti-gp210/anti-nuclear rim antibody) may be associated with more rapidly progressive disease and disease which is less responsive to UDCA therapy.76 79–82”
From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [76]
The Discussion (page unavailable) identifies persistent anti-gp210 antibodies as a strong risk factor for progression to end-stage hepatic failure. It also links antibody disappearance after UDCA initiation with a favorable clinical course, but does not establish that anti-gp210-positive disease is less responsive to UDCA therapy. (LLM, conf=0.83)
Experimental — accuracy not yet measuredThere are data to suggest that ANA +ve patients progress more rapidly.
“There are data to suggest that ANA +ve patients progress more rapidly.76”
From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [76]
The Univariate Analysis of Transplantation-Free Survival reports greater progression to liver-associated death or transplantation among anti-gp210-positive PBC patients, but no significant difference for patients positive for several other ANAs. The Discussion also links anti-centromere positivity to a different progression pattern. These findings support an association for specific ANA subtypes, not ANA positivity in general. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAnti-centromere antibodies have been reported to have potential prognostic impact, with a portal hypertensive phenotype.
“Anti-centromere antibodies have also been reported to have potential prognostic impact (portal hypertensive phenotype) [79,80,78].”
From EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. (2017) · cites this paper as [80]
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- Authors
- Nakamura, M., Kondo, H., Mori, T., Komori, A., Matsuyama, M., Ito, M., Takii, Y., Koyabu, M., Yokoyama, T., Migita, K., Daikoku, M., Abiru, S., Yatsuhashi, H., Takezaki, E., Masaki, N., Sugi, K., Honda, K., Adachi, H., Nishi, H., Watanabe, Y., Nakamura, Y., Shimada, M., Komatsu, T., Saito, A., Saoshiro, T., Harada, H., Sodeyama, T., Hayashi, S., Masumoto, A., Sando, T., Yamamoto, T., Sakai, H., Kobayashi, M., Muro, T., Koga, M., Shums, Z., Norman, G. L., & Ishibashi, H.
- Affiliations
- Nagasaki Medical Center (JP)
- Nagasaki University (JP)
- National Hospital Organization (JP)
- Corresponding author
- Nakamura, Minoru
- ORCID
- Venue
- Hepatology
- Published
- 2007-01
- Volume
- 45
- Issue
- 1
- Pages
- 118-127
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W1967089359
- Semantic Scholar
- c4e437b3b0a4f53b651fd63bd091d5504a587ccd
- Cited by
- 365
- References
- 49
- Citations by year
- 2026: 17 · 2025: 14 · 2024: 12 · 2023: 24 · 2022: 15 · 2021: 17 · 2020: 15 · 2019: 22 · 2018: 23 · 2017: 18 · 2016: 11 · 2015: 15 · 2014: 22 · 2013: 21 · 2012: 27
- FWCI
- 10.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Health, Labour and Welfare
- Japan Society for the Promotion of Science
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Health Sciences › Medicine › Rheumatology › IgG4-Related and Inflammatory Diseases
- Keywords
- anti-gp210 antibodies, anti-centromere antibodies, antinuclear antibodies, disease progression, liver failure, liver transplantation, portal hypertension, esophageal varices, hepatocellular carcinoma, interface hepatitis, ductular reaction, lobular inflammation, risk factors, prognostic factors, sex differences
- MeSH terms
- Adult, Aged, Aged, 80 and over, Antibodies, Antinuclear, Autoantigens, Centromere, Chromatin, Esophageal and Gastric Varices, Female, Humans, Hypertension, Portal, Liver Cirrhosis, Biliary, Male, Middle Aged, Nuclear Proteins, Prospective Studies, Retrospective Studies, Risk Factors, Multivariate Analysis, Liver Failure, Disease Progression, Nuclear Pore Complex Proteins, Antigens, Nuclear
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