Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 7/2022

28-06-2021 | Liver Transplantation | Original Article

Anti-mitochondrial Antibody-Negative Primary Biliary Cholangitis Is Part of the Same Spectrum of Classical Primary Biliary Cholangitis

Authors: Guilherme Grossi Lopes Cançado, Michelle Harriz Braga, Maria Lucia Gomes Ferraz, Cristiane Alves Villela-Nogueira, Debora Raquel Benedita Terrabuio, Eduardo Luiz Rachid Cançado, Mateus Jorge Nardelli, Luciana Costa Faria, Nathalia Mota de Faria Gomes, Elze Maria Gomes Oliveira, Vivian Rotman, Maria Beatriz Oliveira, Simone Muniz Carvalho Fernandes da Cunha, Marlone Cunha-Silva, Liliana Sampaio Costa Mendes, Claudia Alexandra Pontes Ivantes, Liana Codes, Valéria Ferreira de Almeida e Borges, Fabio Heleno de Lima Pace, Mario Guimarães Pessoa, Izabelle Venturini Signorelli, Gabriela Perdomo Coral, Paulo Lisboa Bittencourt, Cynthia Levy, Cláudia Alves Couto, Members of the Brazilian Cholestasis Study Group Consortium

Published in: Digestive Diseases and Sciences | Issue 7/2022

Login to get access

Abstract

Background

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease in which anti-mitochondrial antibodies (AMA) are the diagnostic hallmark. Whether AMA-negative PBC patients represent a different phenotype of disease is highly debated.

Aims

The purpose of our study was to compare AMA-positive and AMA-negative PBC patients in a large non-white admixed Brazilian cohort.

Methods

The Brazilian Cholestasis Study Group multicentre database was reviewed to assess demographics, clinical features and treatment outcomes of Brazilian PBC patients, stratifying data according to AMA status.

Results

A total of 464 subjects (95.4% females, mean age 56 ± 5 years) with PBC were included. Three hundred and eighty-four (83%) subjects were AMA-positive, whereas 80 (17%) had AMA-negative PBC. Subjects with AMA-negative PBC were significantly younger (52.2 ± 14 vs. 59.6 ± 11 years, p = 0.001) and had their first symptom at an earlier age (43.2 ± 13 vs. 49.5 ± 12 years, p = 0.005). Frequency of type 2 diabetes was significantly increased in subjects with AMA-negative PBC (22.5% vs. 12.2%, p = 0.03). Lower IgM (272.2 ± 183 vs. 383.2 ± 378 mg/dL, p = 0.01) and triglycerides (107.6 ± 59.8 vs.129.3 ± 75.7 mg/dL, p = 0.025) and higher bilirubin (3.8 ± 13.5 vs. 1.8 ± 3.4 mg/dL, p = 0.02) levels were also observed in this subgroup. Response to ursodeoxycholic acid varied from 40.5 to 63.3% in AMA-positive and 34 to 62.3% in AMA-negative individuals, according to different response criteria. Outcomes such as development of liver-related complications, death and requirement for liver transplantation were similar in both groups.

Conclusions

AMA-negative PBC patients are similar to their AMA-positive counterparts with subtle differences observed in clinical and laboratory features.
Literature
1.
Lleo A, Wang G-Q, Gershwin ME, Hirschfield GM. Primary biliary cholangitis. Lancet (London, England) 2020; 396:1915–1926.
2.
Leung KK, Deeb M, Hirschfield GM. Review article: pathophysiology and management of primary biliary cholangitis. Aliment Pharmacol. Ther. 2020; 52:1150–1164.
3.
Lindor KD, Bowlus CL, Boyer J et al. Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019; 69:394–419.
4.
5.
Hurlburt KJ, McMahon BJ, Deubner H et al. Prevalence of autoimmune liver disease in Alaska Natives. Am J Gastroenterol. 2002; 97:2402–7.
6.
Arbour L, Rupps R, Field L et al. Characteristics of primary biliary cirrhosis in British Columbia’s First Nations population. Can. J. Gastroenterol. 2005; 19:305–10.
7.
Muratori P, Muratori L, Gershwin ME et al. “True” antimitochondrial antibody-negative primary biliary cirrhosis, low sensitivity of the routine assays, or both? Clin Exp Immunol. 2004; 135:154–8.
8.
Selmi C, Zuin M, Bowlus CL, Gershwin ME. Anti-mitochondrial antibody-negative primary biliary cirrhosis. Clin Liver Dis. 2008; 12:173–85, ix.
9.
Mattalia A, Quaranta S, Leung PS et al. Characterization of antimitochondrial antibodies in health adults. Hepatology. 1998; 27:656–61.
10.
Cunha LM, Bittencourt PL, Abrantes-Lemos CP et al. Prevalence of non-organ-specific autoantibodies in a rural community from northeastern Brazil: a population-based study. Hum Immunol. 2012; 73:70–4.
11.
Shibata M, Onozuka Y, Morizane T et al. Prevalence of antimitochondrial antibody in Japanese corporate workers in Kanagawa prefecture. J Gastroenterol. 2004; 39:255–9.
12.
Farias AQ, Goncalves LL, Bittencourt PL et al. Applicability of the IAIHG scoring system to the diagnosis of antimitochondrial/anti-M2 seropositive variant form of autoimmune hepatitis. J Gastroenterol Hepatol. 2006; 21:887–893.
13.
Sun C, Xiao X, Yan L et al. Histologically proven AMA positive primary biliary cholangitis but normal serum alkaline phosphatase: Is alkaline phosphatase truly a surrogate marker? J Autoimmun. 2019; 99:33–38.
14.
Metcalf J V., Mitchison HC, Palmer JM et al. Natural history of early primary biliary cirrhosis. Lancet (London, England) 1996; 348:1399–402.
15.
16.
Dahlqvist G, Gaouar F, Carrat F et al. Large-scale characterization study of patients with antimitochondrial antibodies but non established primary biliary cholangitis. Hepatology. 2017; 65:152–163.
17.
Zandanell S, Strasser M, Feldman A, Tevini J, Strebinger G, Niederseer D, Pohla-Gubo G, Huber-Schönauer U, Ruhaltinger S, Paulweber B, Datz C, Felder TK, Aigner E. Low rate of new-onset primary biliary cholangitis in a cohort of anti-mitochondrial antibody-positive subjects over six years of follow-up. J Intern Med. 2020 Apr;287:395-404.
18.
Oertelt S, Rieger R, Selmi C et al. A sensitive bead assay for antimitochondrial antibodies: Chipping away at AMA-negative primary biliary cirrhosis. Hepatology. 2007; 45:659–65.
19.
Liu B, Shi XH, Zhang FC et al. Antimitochondrial antibody-negative primary biliary cirrhosis: a subset of primary biliary cirrhosis. Liver Int. 2008; 28:233–9.
20.
Mendes F, Lindor KD. Antimitochondrial antibody-negative primary biliary cirrhosis. Gastroenterol Clin North Am. 2008; 37:479–84, viii.
21.
22.
Sakauchi F, Mori M, Zeniya M, Toda G. Antimitochondrial antibody negative primary biliary cirrhosis in Japan: utilization of clinical data when patients applied to receive public financial aid. J Epidemiol. 2006; 16:30–4.
23.
Zhang F-K, Jia J-D, Wang B-E. Clinical evaluation of serum antimitochondrial antibody-negative primary biliary cirrhosis. Hepatobiliary Pancreat Dis Int. 2004; 3:288–291.
24.
Kim WR, Poterucha JJ, Jorgensen RA et al. Does antimitochondrial antibody status affect response to treatment in patients with primary biliary cirrhosis? Outcomes of ursodeoxycholic acid therapy and liver transplantation. Hepatology. 1997; 26:22–6.
25.
Joshi S, Cauch-Dudek K, Heathcote EJ et al. Antimitochondrial antibody profiles: are they valid prognostic indicators in primary biliary cirrhosis? Am J Gastroenterol. 2002; 97:999–1002.
26.
Juliusson G, Imam M, Björnsson ES et al. Long-term outcomes in antimitochondrial antibody negative primary biliary cirrhosis. Scand J Gastroenterol. 2016; 51:745–52.
27.
28.
Zandanell S, Strasser M, Feldman A et al. Similar clinical outcome of AMA immunoblot-M2-negative compared to immunoblot-positive subjects over six years of follow-up. Postgrad Med. 2021:1–8.
29.
Michieletti P, Wanless IR, Katz A et al. Antimitochondrial antibody negative primary biliary cirrhosis: a distinct syndrome of autoimmune cholangitis. Gut. 1994; 35:260–265.
30.
Lacerda MA, Ludwig J, Dickson ER et al. Antimitochondrial antibody-negative primary biliary cirrhosis. Am J Gastroenterol. 1995; 90:247–249.
31.
32.
Sánchez-Pobre P, Castellano G, Colina F et al. Antimitochondrial antibody-negative chronic nonsuppurative destructive cholangitis. Atypical primary biliary cirrhosis or autoimmune cholangitis? J. Clin. Gastroenterol. 1996; 23:191–198.
33.
34.
Levy C, Bowlus CL. Role of Antinuclear Antibodies in Primary Biliary Cholangitis. Am J Gastroenterol. 2020; 115:1604–1606.
35.
Parés A, Caballería L, Rodés J. Excellent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic Acid. Gastroenterology. 2006; 130:715–20.
36.
Corpechot C, Abenavoli L, Rabahi N et al. Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis. Hepatology. 2008; 48:871–7.
37.
Kumagi T, Guindi M, Fischer SE et al. Baseline ductopenia and treatment response predict long-term histological progression in primary biliary cirrhosis. Am J Gastroenterol. 2010; 105:2186–94.
38.
39.
40.
41.
Bittencourt PL, Palácios SA, Farias AQ et al. Analysis of major histocompatibility complex and CTLA-4 alleles in Brazilian patients with primary biliary cirrhosis. J Gastroenterol Hepatol. 2003; 18:1061–1066.
42.
Metadata
Title
Anti-mitochondrial Antibody-Negative Primary Biliary Cholangitis Is Part of the Same Spectrum of Classical Primary Biliary Cholangitis
Authors
Guilherme Grossi Lopes Cançado
Michelle Harriz Braga
Maria Lucia Gomes Ferraz
Cristiane Alves Villela-Nogueira
Debora Raquel Benedita Terrabuio
Eduardo Luiz Rachid Cançado
Mateus Jorge Nardelli
Luciana Costa Faria
Nathalia Mota de Faria Gomes
Elze Maria Gomes Oliveira
Vivian Rotman
Maria Beatriz Oliveira
Simone Muniz Carvalho Fernandes da Cunha
Marlone Cunha-Silva
Liliana Sampaio Costa Mendes
Claudia Alexandra Pontes Ivantes
Liana Codes
Valéria Ferreira de Almeida e Borges
Fabio Heleno de Lima Pace
Mario Guimarães Pessoa
Izabelle Venturini Signorelli
Gabriela Perdomo Coral
Paulo Lisboa Bittencourt
Cynthia Levy
Cláudia Alves Couto
Members of the Brazilian Cholestasis Study Group Consortium
Publication date
28-06-2021
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 7/2022
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-021-07122-y

Other articles of this Issue 7/2022

Digestive Diseases and Sciences 7/2022 Go to the issue

Original Article

Adverse Events Associated with Routine Colonoscopy in Patients with End-Stage Renal Disease

Original Article

Downregulation of Programmed Death-1 Pathway Promoting CD8 + T Cell Cytotoxicity in Primary Biliary Cholangitis

Correction

Correction to: Increased Fecal Bile Acid Excretion in a Significant Subset of Patients with Other Inflammatory Diarrheal Diseases

Original Article

Clinical Characteristics and Treatment Response in Microscopic Colitis Based on Age at Diagnosis: A Multicenter Retrospective Study

Review

Heterogeneity of Randomized Controlled Trials of Fecal Microbiota Transplantation in Recurrent Clostridioides difficile Infection

Original Article

Prevalence of Adenomas on Surveillance Colonoscopies for Patients with a History of Colonic Polyps of Unknown Histology
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits