Thyroid Dysfunction in Primary Biliary Cholangitis: A Comparative Study at Two European Centers

Floreani, Annarosa; Mangini, Chiara; Reig, A.; Franceschet, I.; Cazzagon, Nora; Perini, L.; Caballería, Llorenç; Cocchio, Silvia; Baldo, Vincenzo; Parés, Albert

doi:10.1038/ajg.2016.479

Cited by 39 publications

(28 citation statements)

References 34 publications

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“…These results are in line with findings from other European groups, which demonstrated that presence of extrahepatic autoimmune conditions does not significantly affect the survival of patients with PBC [7,8]. Furthermore, Muratori et al [47] showed no differences between subgroups of PBC patients with and without concomitant autoimmune disorder in terms of age at diagnosis, serum level of antibodies and long-term complications of liver disease.…”

Section: Discussionsupporting

confidence: 87%

“…Autoimmune thyroid disease (AITD) is one of the disorders with the highest evidence for association with PBC. Indeed, a recent study [8] demonstrates that 14% of patients with PBC might suffer from AITD. Prevalence of thyroid disorder is confirmed by the presence of positive thyroid antibodies, and is clinically manifested mainly as Hashimoto thyroiditis (HT) or Graves' disease (GD).…”

Section: Introductionmentioning

confidence: 99%

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Genetic Risk Factors for Autoimmune Thyroid Disease might Affect the Susceptibility to and Modulate the Progression of Primary Biliary Cholangitis

Kuś

Arłukowicz-Grabowska

Szymański

et al. 2017

JGLD

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Background & Aims: Patients with primary biliary cholangitis (PBC) frequently suffer from extrahepatic autoimmune conditions, of which autoimmune thyroid disease (AITD) is one of the most common. Previous studies identified several genetic variants increasing the odds of developing AITD. Here we investigate whether AITD-associated polymorphisms might also play a role in the development and clinical course of PBC and PBC associated with AITD (PBC-AITD).Methods: To this end, we prospectively recruited 230 patients with PBC and 421 healthy controls. Among recruited patients, 64 (30.9%) had PBC-AITD as diagnosed by elevated serum TPO-antibodies. In all subjects we genotyped 10 variants previously associated with AITD.Results: We detected significant associations between the PTPN22 polymorphism and risk of developing PBC (rs2476601, OR=1.43, P=0.035) as well as PBC-AITD (OR=1.74, P=0.028). The IL2RA polymorphism was associated with liver cirrhosis (rs41295061, OR=1.76, P=0.033) whereas the MMEL1 polymorphism increased the risk of requiring liver transplantation (rs2843403, OR=1.70, P=0.023). Although no significant differences in clinical or biochemical characteristics between patients with PBC and PBC-AITD were seen (all P>0.05), liver function tests and metabolic traits in PBC patients were significantly (all P<0.05) affected by the CTLA4 (rs3087243), MMEL1 (rs2843403), PTPN22 (rs2476601) and RNASET2 (rs9355610) variants.Conclusion: Our study demonstrates the existence of a genetic overlap between PBC and AITD. Apparently, genetic variants known to increase the AITD risk might affect the clinical course of PBC. On the other hand, AITD per se does not seem to significantly influence the natural history of PBC.Abbreviations: AITD: autoimmune thyroid disease; ALP: alkaline phosphatase; ALT: alanine transaminase; AMA: anti-mitochondrial autoantibodies; AST: aspartate aminotransferase; DM1: diabetes mellitus type 1; ELISA: enzyme-linked immunosorbent assay method; GGT: gamma-glutamyl transpeptidase; GD: Graves’ disease; GWAS: genome-wide association studies; HT: Hashimoto thyroiditis; HWE: Hardy-Weinberg equilibrium; Lyp: lymphoid-specific protein tyrosine phosphatase non-receptor type 22; OR: odds ratio; PBC: primary biliary cholangitis; RA: rheumatoid arthritis; SLE: systemic lupus erythematosus; TPOAb: thyroid peroxidase antibody; UDCA: ursodeoxycholic acid.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Genetic Risk Factors for Autoimmune Thyroid Disease might Affect the Susceptibility to and Modulate the Progression of Primary Biliary Cholangitis

Kuś

Arłukowicz-Grabowska

Szymański

et al. 2017

JGLD

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“…8,9 A recent study on 921 patients focused on thyroid diseases in PBC. 8 Another study compared the prevalence of EHAIDs in 1032 patients with PBC and in healthy controls. 9 These earlier reports 5,8,9 did not find associations between the presence of EHAIDs and clinical presentation or development of major hepatic events, but their findings warrant further studies.…”

Section: Introductionmentioning

confidence: 99%

Extrahepatic autoimmune diseases in primary biliary cholangitis: Prevalence and significance for clinical presentation and disease outcome

Efe

Torğutalp

Henriksson

et al. 2020

J of Gastro and Hepatol

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Background and Aim: The prevalence and clinical significance of extrahepatic autoimmune diseases (EHAIDs) have not been evaluated in a large cohort of primary biliary cholangitis (PBC). Methods: The medical records of 1554 patients with PBC from 20 international centers were retrospectively reviewed. Development of decompensated cirrhosis (ascites, variceal bleeding, and/or hepatic encephalopathy) and hepatocellular carcinoma were considered clinical endpoints. Results: A total of 35 different EHAIDs were diagnosed in 440 (28.3%) patients with PBC. Patients with EHAIDs were more often female (92.5% vs 86.1%, P < 0.001) and seropositive for anti-mitochondrial antibodies (88% vs 84%, P = 0.05) and antinuclear antibodies and/or smooth muscle antibodies (53.8% vs 43.6%, P = 0.005). At presentation, patients with EHAIDs had significantly lower levels of alkaline phosphatase (1.76 vs 1.98 × upper limit of normal [ULN], P = 0.006), aspartate aminotransferase (1.29 vs 1.50 × ULN, P < 0.001), and total bilirubin (0.53 vs 0.58 × ULN, P = 0.002). Patients with EHAIDs and without EHAIDs had similar rates of GLOBE high-risk status (12.3% vs 16.1%, P = 0.07) and Paris II response (71.4% vs 69.4%, P = 0.59). Overall, event-free survival was not different in patients with and without EHAIDs (90.8% vs 90.7%, P = 0.53, log rank). Coexistence of each autoimmune thyroid diseases (10.6%), Sjögren disease (8.3%), systemic sclerosis (2.9%), rheumatoid arthritis (2.7%), systemic lupus erythematosus (1.7%), celiac disease (1.7%), psoriasis (1.5%), and inflammatory bowel diseases (1.3%) did not influence the outcome. Conclusions: Our study confirms that EHAIDs are frequently diagnosed in patients with PBC. The presence of EHAIDs may influence the clinical phenotype of PBC at presentation but has no impact on PBC outcome.

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“…Common extrahepatic autoimmune conditions include Sjögren syndrome (SS), autoimmune thyroid diseases, and systemic lupus erythematosus (SLE) 8 . Although extrahepatic autoimmune diseases might be associated with EM development in PBC 7 , whether extrahepatic autoimmune diseases affect the prognosis of PBC patients remains conflicting 15,16 . In addition, PBC patients are prone to hypercholesteremia 2 .…”

Section: Introductionmentioning

confidence: 99%

The extrahepatic events of Asian patients with primary biliary cholangitis: A 30-year cohort study

Lin

Cheng

Chang

et al. 2019

Sci Rep

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The extrahepatic complications of primary biliary cholangitis (PBC) in Asian patients remain elusive. A 30-year cohort study of 150 Taiwanese PBC patients treated with ursodeoxycholic acid (UDCA) was conducted. Patients with alkaline phosphatase levels >1.67 × ULN after 1-year treatment were considered suboptimal responders. At baseline, of 150 patients (mean age: 53.75 years), 128 (85.3%) were females, and 34 (22.8%) had cirrhosis. The cumulative incidences of various incident events were all-cause mortality or liver transplantation: 46.7%; extrahepatic mortality: 24.5%; extrahepatic malignancies: 8.1%; hypertension: 46.2%; dyslipidemia: 44.1%; diabetes: 30.6%; hyperuricemia: 11.2%; acute coronary syndrome: 3.1%; cerebral vascular accident (CVA): 8.9%; autoimmune diseases: 16%; and osteoporosis: 20.9%. The 5- to 20-year cumulative incidences for all-cause mortality or liver transplantation and extrahepatic mortality were 16.2–41.3% and 3.1–11.9%, respectively. Baseline associations were age and alpha-fetoprotein levels with extrahepatic mortality, 80% due to sepsis; age with extrahepatic malignancies and hypertension; gender and hyperuricemia with CVA; and UDCA response with autoimmune disease. Conclusions: Sepsis accounted for most extrahepatic mortality in PBC patients, and the longer the follow-up was, the higher the extrahepatic/all-cause mortality ratio. Baseline age is crucial for incident extrahepatic events and only CVA shows gender-dimorphism; the association between UDCA response and autoimmune disease requires further investigation.

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Thyroid Dysfunction in Primary Biliary Cholangitis: A Comparative Study at Two European Centers

Abstract: TDs, and autoimmune TD like Hashimoto's thyroiditis in particular, are often associated with PBC, but the presence of TD does not influence the rate of hepatic complications or the natural history of PBC.

Cited by 39 publications

References 34 publications

Genetic Risk Factors for Autoimmune Thyroid Disease might Affect the Susceptibility to and Modulate the Progression of Primary Biliary Cholangitis

Genetic Risk Factors for Autoimmune Thyroid Disease might Affect the Susceptibility to and Modulate the Progression of Primary Biliary Cholangitis

Extrahepatic autoimmune diseases in primary biliary cholangitis: Prevalence and significance for clinical presentation and disease outcome

The extrahepatic events of Asian patients with primary biliary cholangitis: A 30-year cohort study

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