Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Sep;36(9):1378-82.
doi: 10.1111/liv.13143. Epub 2016 Apr 28.

Low incidence of primary biliary cirrhosis (PBC) in the first-degree relatives of PBC probands after 8 years of follow-up

Aliya F Gulamhusein  1 , Brian D Juran  2 , Elizabeth J Atkinson  3 , Bryan McCauley  3 , Erik Schlicht  2 , Konstantinos N Lazaridis  2
Affiliations

Low incidence of primary biliary cirrhosis (PBC) in the first-degree relatives of PBC probands after 8 years of follow-up

Aliya F Gulamhusein et al. Liver Int. 2016 Sep.

Abstract

Background & aims: Primary biliary cirrhosis (PBC) is characterized by chronic cholestasis and disease-specific antimitochondrial antibodies (AMA). A high prevalence of AMAs in first-degree relatives (FDRs) of PBC probands has been reported, although the natural history of such patients has not been described. We aimed to assess the risk of developing PBC in AMA+ FDRs of patients with PBC.

Methods: First-degree relatives recruited to the Mayo Clinic PBC Genetic Epidemiology Registry and Biorepository were followed for disease onset after recruitment. Development of PBC was ascertained via self-report during a telephone interview and/or via proband report on a questionnaire. Chi-squared test and t-test were used to assess the differences between categorical and continuous variables respectively. A mixed-effects model was used to assess the change in biochemical profiles over time.

Results: Forty AMA+ and 423 AMA- subjects were included and followed for a median of 8.9 and 8.4 years respectively. Overall, 3% (n = 15) of FDRs were diagnosed with PBC, and AMA+ FDRs had a higher risk than AMA- FDRs (24% vs. 0.7%, P < 0.01). However, among undiagnosed FDRs, only 4% of AMA+ (n = 1) and 0.4% of AMA- (n = 1) FDRs were diagnosed with PBC (P = 0.17) during the follow-up period. None of the AMA+ FDRs with normal alkaline phosphatase at baseline developed PBC in follow-up.

Conclusions: Our results suggest a low risk of developing PBC over time in FDRs of patients with PBC, particularly those without biochemical evidence of cholestasis at baseline. These data are useful in counselling and reassuring relatives of their overall favourable prognosis.

Keywords: antimitochondrial antibody; familial primary biliary cirrhosis; first-degree relative.

PubMed Disclaimer

Conflict of interest statement

The author’s declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flow diagram outlining AMA+ and AMA− FDRs included and followed up over time. The left side of the diagram outlines eligible and included AMA+ FDRs with the associated relevant data available at baseline and in follow-up and the right side provides identical information for AMA− relatives. A low proportion of contacted AMA+ FDRs (4%, 1/22) reported an interval diagnosis of PBC and this was in a subject with an elevated AP at baseline. Only 0.4% (1/240) contacted AMA− FDRs reported an interval diagnosis of PBC in follow-up and this subject had a normal AP at baseline assessment. AMA, anti-mitochondrial antibody; AP, alkaline phosphatase; FDR, first-degree relative; PBC, primary biliary cirrhosis; QN, questionnaire; ULN, upper limit normal
See this image and copyright information in PMC

References

    1. Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ. Primary biliary cirrhosis. Hepatology. 2009;50(1):291–308. - PubMed
    1. Leung PS, Van De Water J, Coppel RL, Gershwin ME. Molecular characterization of the mitochondrial autoantigens in primary biliary cirrhosis. Immunol Res. 1991;10(3–4):518–527. - PubMed
    1. Podda M, Selmi C, Lleo A, Moroni L, Invernizzi P. The limitations and hidden gems of the epidemiology of primary biliary cirrhosis. J Autoimmun. 2013;46:81–87. - PubMed
    1. Lazaridis KN, Juran BD, Boe GM, Slusser JP, de Andrade M, Homburger HA, et al. Increased prevalence of antimitochondrial antibodies in first-degree relatives of patients with primary biliary cirrhosis. Hepatology. 2007;46(3):785–792. - PubMed
    1. Metcalf JV, Mitchison HC, Palmer JM, Jones DE, Bassendine MF, James OF. Natural history of early primary biliary cirrhosis. Lancet. 1996;348(9039):1399–1402. - PubMed

Publication types

LinkOut - more resources