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Clinical Reviews in Allergy & Immunology
Published in: Clinical Reviews in Allergy & Immunology 2-3/2015

01-06-2015

Extrahepatic Malignancies in Primary Biliary Cirrhosis: A Comparative Study at Two European Centers

Authors: Annarosa Floreani, Alice Spinazzè, Llorenc Caballeria, Ana Reig, Nora Cazzagon, Irene Franceschet, Alessandra Buja, Patrizia Furlan, Kenichi Harada, Patrick SC Leung, M. Eric Gershwin, Albert Pares

Published in: Clinical Reviews in Allergy & Immunology | Issue 2-3/2015

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Abstract

Limited information and divergent results are available on the prevalence/incidence, survival, and risk factors for developing extrahepatic malignancies (EMs) in primary biliary cirrhosis (PBC). The aim of the study was to analyze the epidemiology and survival rates for EM in PBC patients. The study was conducted on two series of patients followed up at two European centers (361 in Padova, Italy, and 397 in Barcelona, Spain) for a mean 7.7 ± 7 and 12.2 ± 7 years, respectively. The cancer incidence was compared with the standardized incidence ratios (SIRs) calculated using the Cancer Registry of the Veneto Region (Italy) and the Cancer Registry of Tarragona (Spain). Seventy-two patients developed EM. The prevalence of cases was similar in Padova (9.7 %) and Barcelona (9.4 %). The overall cancer incidence was similar to the expected incidence for the general population in the same geographical area (SIR = 1.2), and so was the crude EM rate (855.01 vs 652.86 per 100,000 patient-years, respectively, RR = 1.3). Logistic regression analysis showed that advanced histological stage and extrahepatic autoimmune diseases were significantly associated with the onset of EM. Survival was similar for PBC patients with and without EM (p = n.s.), and actual survival was similar to the one predicted by the Mayo model. The incidence of EM in PBC patients was found similar in Italy and Spain and no different from that of the general population. Advanced histological stage and extrahepatic autoimmune disease were risk factors significantly associated with EM developing in PBC. The onset of cancer in PBC patients does not influence the natural history of their liver disease.
Literature
1.
Bernatsky S, Ramsey-Goldman R, Clarke A (2006) Malignancy and autoimmunity. Curr Opin Rheumatol 18:129–134CrossRefPubMed
2.
Szekanecz E, Andras C, Sandor Z, Antal-Szalmas P, Szanto J, Tamasi L, Kiss E et al (2006) Malignancies and soluble tumor antigens in rheumatic diseases. Autoimmun Rev 6:42–47CrossRefPubMed
3.
Ngu JH, Gearry RB, Frampton CM, Stedman CA (2012) Mortality and the risk of malignancy in autoimmune liver diseases: a population-based study in Canterbury, New Zealand. Hepatology 55:522–529CrossRefPubMed
4.
Wong RJ, Gish R, Frederick T, Bzowej N, Frenette C (2011) Development of hepatocellular carcinoma in autoimmune hepatitis patients: a case series. Dig Dis Sci 56:578–585CrossRefPubMed
5.
Werner M, Almer S, Prytz H, Lindgren S, Wallerstedt S, Bjornsson E, Bergquist A et al (2009) Hepatic and extrahepatic malignancies in autoimmune hepatitis. A long-term follow-up in 473 Swedish patients. J Hepatol 50:388–393CrossRefPubMed
6.
Bergquist A, Ekbom A, Olsson R, Kornfeldt D, Loof L, Danielsson A, Hultcrantz R et al (2002) Hepatic and extrahepatic malignancies in primary sclerosing cholangitis. J Hepatol 36:321–327CrossRefPubMed
7.
Ananthakrishnan AN, Cagan A, Gainer VS, Cheng SC, Cai T, Szolovits P, Shaw SY et al (2014) Mortality and extraintestinal cancers in patients with primary sclerosing cholangitis and inflammatory bowel disease. J Crohns Colitis
8.
9.
Hirschfield GM, Invernizzi P (2011) Progress in the genetics of primary biliary cirrhosis. Semin Liver Dis 31:147–156CrossRefPubMed
10.
Liu X, Invernizzi P, Lu Y, Kosoy R, Bianchi I, Podda M, Xu C et al (2010) Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis. Nat Genet 42:658–660CrossRefPubMedCentralPubMed
11.
12.
Cavazza A, Caballeria L, Floreani A, Farinati F, Bruguera M, Caroli D, Pares A (2009) Incidence, risk factors, and survival of hepatocellular carcinoma in primary biliary cirrhosis: comparative analysis from two centers. Hepatology 50:1162–1168CrossRefPubMed
13.
Harada K, Hirohara J, Ueno Y, Nakano T, Kakuda Y, Tsubouchi H, Ichida T et al (2013) Incidence of and risk factors for hepatocellular carcinoma in primary biliary cirrhosis: national data from Japan. Hepatology 57:1942–1949CrossRefPubMed
14.
Jones DE, Metcalf JV, Collier JD, Bassendine MF, James OF (1997) Hepatocellular carcinoma in primary biliary cirrhosis and its impact on outcomes. Hepatology 26:1138–1142CrossRefPubMed
15.
Floreani A, Farinati F (2013) Risk factors associated with hepatocellular carcinoma in primary biliary cirrhosis. Hepatology 58:1520–1521CrossRefPubMed
16.
Liang Y, Yang Z, Zhong R (2012) Primary biliary cirrhosis and cancer risk: a systematic review and meta-analysis. Hepatology 56:1409–1417CrossRefPubMed
17.
Goudie BM, Burt AD, Boyle P, Macfarlane G, Birnie GG, Mills PR, Gillis CR et al (1985) Breast cancer in women with primary biliary cirrhosis. Br Med J (Clin Res Ed) 291:1597–1598CrossRef
18.
Witt-Sullivan H, Heathcote J, Cauch K, Blendis L, Ghent C, Katz A, Milner R et al (1990) The demography of primary biliary cirrhosis in Ontario, Canada. Hepatology 12:98–105CrossRefPubMed
19.
Wolke AM, Schaffner F, Kapelman B, Sacks HS (1984) Malignancy in primary biliary cirrhosis. High incidence of breast cancer in affected women. Am J Med 76:1075–1078CrossRefPubMed
20.
Deutsch M, Papatheodoridis GV, Tzakou A, Hadziyannis SJ (2008) Risk of hepatocellular carcinoma and extrahepatic malignancies in primary biliary cirrhosis. Eur J Gastroenterol Hepatol 20:5–9CrossRefPubMed
21.
Floreani A, Baragiotta A, Baldo V, Menegon T, Farinati F, Naccarato R (1999) Hepatic and extrahepatic malignancies in primary biliary cirrhosis. Hepatology 29:1425–1428CrossRefPubMed
22.
Howel D, Metcalf JV, Gray J, Newman WL, Jones DE, James OF (1999) Cancer risk in primary biliary cirrhosis: a study in northern England. Gut 45:756–760CrossRefPubMedCentralPubMed
23.
Piscaglia F, Sagrini E (2008) Malignancies in primary biliary cirrhosis. Eur J Gastroenterol Hepatol 20:1–4CrossRefPubMed
24.
Mells GF, Kaser A, Karlsen TH (2013) Novel insights into autoimmune liver diseases provided by genome-wide association studies. J Autoimmun 46:41–54CrossRefPubMed
25.
Henao-Mejia J, Elinav E, Thaiss CA, Licona-Limon P, Flavell RA (2013) Role of the intestinal microbiome in liver disease. J Autoimmun 46:66–73CrossRefPubMed
26.
Liu Y, Li H, Xiao T, Lu Q (2013) Epigenetics in immune-mediated pulmonary diseases. Clin Rev Allergy Immunol 45:314–330CrossRefPubMed
27.
Saito Y, Saito H, Liang G, Friedman JM (2013) Epigenetic alterations and microrna misexpression in cancer and autoimmune diseases: a critical review. Clin Rev Allergy Immunol
28.
Wichner K, Fischer A, Winter S, Tetzlaff S, Heimesaat MM, Bereswill S, Rehm A et al (2013) Transition from an autoimmune-prone state to fatal autoimmune disease in CCR7 and RORgammat double-deficient mice is dependent on gut microbiota. J Autoimmun 47:58–72CrossRefPubMed
29.
Ludwig J (2000) The pathology of primary biliary cirrhosis and autoimmune cholangitis. Bailliere Best Pract Res Clin Gastroenterol 14:601–613CrossRef
30.
31.
Panjala C, Talwalkar JA, Lindor KD (2007) Risk of lymphoma in primary biliary cirrhosis. Clin Gastroenterol Hepatol 5:761–764CrossRefPubMed
32.
Chakravarty E, Genovese MC (2003) Rheumatic syndromes associated with malignancy. Curr Opin Rheumatol 15:35–43CrossRefPubMed
33.
Zhang W, Feng S, Yan S, Zhao Y, Li M, Sun J, Zhang FC et al (2010) Incidence of malignancy in primary Sjogren’s syndrome in a Chinese cohort. Rheumatology (Oxford) 49:571–577CrossRef
34.
Schopper D, de Wolf C (2009) How effective are breast cancer screening programmes by mammography? Review of the current evidence. Eur J Cancer 45:1916–1923CrossRefPubMed
35.
Francisci S, Capocaccia R, Grande E, Santaquilani M, Simonetti A, Allemani C, Gatta G et al (2009) The cure of cancer: a European perspective. Eur J Cancer 45:1067–1079CrossRefPubMed
36.
Pardi DS, Loftus EV Jr, Kremers WK, Keach J, Lindor KD (2003) Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis. Gastroenterology 124:889–893CrossRefPubMed
37.
Serfaty L, De Leusse A, Rosmorduc O, Desaint B, Flejou JF, Chazouilleres O, Poupon RE et al (2003) Ursodeoxycholic acid therapy and the risk of colorectal adenoma in patients with primary biliary cirrhosis: an observational study. Hepatology 38:203–209CrossRefPubMed
38.
Eaton JE, Silveira MG, Pardi DS, Sinakos E, Kowdley KV, Luketic VA, Harrison ME et al (2011) High-dose ursodeoxycholic acid is associated with the development of colorectal neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis. Am J Gastroenterol 106:1638–1645CrossRefPubMedCentralPubMed
39.
Lindstrom L, Boberg KM, Wikman O, Friis-Liby I, Hultcrantz R, Prytz H, Sandberg-Gertzen H et al (2012) High dose ursodeoxycholic acid in primary sclerosing cholangitis does not prevent colorectal neoplasia. Aliment Pharmacol Ther 35:451–457CrossRefPubMed
40.
Abu-Shakra M, Buskila D, Ehrenfeld M, Conrad K, Shoenfeld Y (2001) Cancer and autoimmunity: autoimmune and rheumatic features in patients with malignancies. Ann Rheum Dis 60:433–441CrossRefPubMedCentralPubMed
41.
Goldblatt F, O’Neill SG (2013) Clinical aspects of autoimmune rheumatic diseases. Lancet 382:797–808CrossRefPubMed
42.
Invernizzi P (2013) Liver auto-immunology: the paradox of autoimmunity in a tolerogenic organ. J Autoimmun 46:1–6CrossRefPubMed
43.
Hudspeth K, Pontarini E, Tentorio P, Cimino M, Donadon M, Torzilli G, Lugli E et al (2013) The role of natural killer cells in autoimmune liver disease: a comprehensive review. J Autoimmun 46:55–65CrossRefPubMed
44.
Ekstrom Smedly K, Vajdic CM, Palster M et al (2008) Autoimmune disorders and risk in non-Hodgkin lymphoma subtypes: a pooled analysis within the Interlymph Consortium. Blood III:4029–4038CrossRef
45.
Bernatsky S, Ramsey-Goldman R, Rajan R, Boivin JF, Joseph L, Lachance S, Cournoyer D et al (2005) Non-Hodgkin’s lymphoma in systemic lupus erythematosus. Ann Rheum Dis 64:1507–1509CrossRefPubMedCentralPubMed
46.
Zhang W, Tsuda M, Yang GX, Tsuneyama K, He XS, Ansari AA, Ridgway WM et al (2012) Lymphoma-like T cell infiltration in liver is associated with increased copy number of dominant negative form of TGFbeta receptor II. PLoS One 7:e49413CrossRefPubMedCentralPubMed
47.
Oertelt S, Lian ZX, Cheng CM, Chuang YH, Padgett KA, He XS, Ridgway WM et al (2006) Anti-mitochondrial antibodies and primary biliary cirrhosis in TGF-beta receptor II dominant-negative mice. J Immunol 177:1655–1660CrossRefPubMed
48.
Wang J, Yang GX, Tsuneyama K, Gershwin ME, Ridgway WM, Leung PS (2014) Animal models of primary biliary cirrhosis. Semin Liver Dis 34:285–296CrossRefPubMed
49.
Leung PS, Yang GX, Dhirapong A, Tsuneyama K, Ridgway WM, Gershwin ME (2012) Animal models of primary biliary cirrhosis: materials and methods. Methods Mol Biol 900:291–316CrossRefPubMed
50.
Yang CY, Leung PS, Yang GX, Kenny TP, Zhang W, Coppel R, Norman GL et al (2012) Epitope-specific anti-nuclear antibodies are expressed in a mouse model of primary biliary cirrhosis and are cytokine-dependent. Clin Exp Immunol 168:261–267CrossRefPubMedCentralPubMed
51.
Ando Y, Yang GX, Tsuda M, Kawata K, Zhang W, Nakajima T, Tsuneyama K et al (2012) The immunobiology of colitis and cholangitis in interleukin-23p19 and interleukin-17A deleted dominant negative form of transforming growth factor beta receptor type II mice. Hepatology 56:1418–1426CrossRefPubMedCentralPubMed
52.
Tsuda M, Zhang W, Yang GX, Tsuneyama K, Ando Y, Kawata K, Park O et al (2013) Deletion of interleukin (IL)-12p35 induces liver fibrosis in dominant-negative TGFbeta receptor type II mice. Hepatology 57:806–816CrossRefPubMedCentralPubMed
53.
Yoshida K, Yang GX, Zhang W, Tsuda M, Tsuneyama K, Moritoki Y, Ansari AA et al (2009) Deletion of interleukin-12p40 suppresses autoimmune cholangitis in dominant negative transforming growth factor beta receptor type II mice. Hepatology 50:1494–1500CrossRefPubMedCentralPubMed
54.
Moritoki Y, Lian ZX, Lindor K, Tuscano J, Tsuneyama K, Zhang W, Ueno Y et al (2009) B-cell depletion with anti-CD20 ameliorates autoimmune cholangitis but exacerbates colitis in transforming growth factor-beta receptor II dominant negative mice. Hepatology 50:1893–1903CrossRefPubMedCentralPubMed
55.
Yang GX, Lian ZX, Chuang YH, Moritoki Y, Lan RY, Wakabayashi K, Ansari AA et al (2008) Adoptive transfer of CD8(+) T cells from transforming growth factor beta receptor type II (dominant negative form) induces autoimmune cholangitis in mice. Hepatology 47:1974–1982CrossRefPubMedCentralPubMed
56.
Tanaka H, Zhang W, Yang GX, Ando Y, Tomiyama T, Tsuneyama K, Leung P et al (2014) Successful immunotherapy of autoimmune cholangitis by adoptive transfer of Foxp3 regulatory T cells. Clin Exp Immunol
57.
Kawata K, Yang GX, Ando Y, Tanaka H, Zhang W, Kobayashi Y, Tsuneyama K et al (2013) Clonality, activated antigen-specific CD8(+) T cells, and development of autoimmune cholangitis in dnTGFbetaRII mice. Hepatology 58:1094–1104CrossRefPubMedCentralPubMed
58.
Podda M, Selmi C, Lleo A, Moroni L, Invernizzi P (2013) The limitations and hidden gems of the epidemiology of primary biliary cirrhosis. J Autoimmun 46:81–87CrossRefPubMed
59.
Imam MH, Talwalkar JA, Lindor KD (2013) Clinical management of autoimmune biliary diseases. J Autoimmun 46:88–96CrossRefPubMed
60.
Myszor M, James OF (1990) The epidemiology of primary biliary cirrhosis in north-east England: an increasingly common disease? Q J Med 75:377–385PubMed
61.
Danielsson A, Boqvist L, Uddenfeldt P (1990) Epidemiology of primary biliary cirrhosis in a defined rural population in the northern part of Sweden. Hepatology 11:458–464CrossRefPubMed
62.
Kim WR, Lindor KD, Locke GR 3rd, Therneau TM, Homburger HA, Batts KP, Yawn BP et al (2000) Epidemiology and natural history of primary biliary cirrhosis in a US community. Gastroenterology 119:1631–1636CrossRefPubMed
63.
Sood S, Gow PJ, Christie JM, Angus PW (2004) Epidemiology of primary biliary cirrhosis in Victoria, Australia: high prevalence in migrant populations. Gastroenterology 127:470–475CrossRefPubMed
64.
Pla X, Vergara M, Gil M, Dalmau B, Cistero B, Bella RM, Real J (2007) Incidence, prevalence and clinical course of primary biliary cirrhosis in a Spanish community. Eur J Gastroenterol Hepatol 19:859–864CrossRefPubMed
65.
Wong RK, Lim SG, Wee A, Chan YH, Aung MO, Wai CT (2008) Primary biliary cirrhosis in Singapore: evaluation of demography, prognostic factors and natural course in a multi-ethnic population. J Gastroenterol Hepatol 23:599–605CrossRefPubMed
66.
Kubota J, Ikeda F, Terada R, Kobashi H, Fujioka S, Okamoto R, Baba S et al (2009) Mortality rate of patients with asymptomatic primary biliary cirrhosis diagnosed at age 55 years or older is similar to that of the general population. J Gastroenterol 44:1000–1006CrossRefPubMed
67.
Floreani A, Caroli D, Variola A, Rizzotto ER, Antoniazzi S, Chiaramonte M, Cazzagon N et al (2011) A 35-year follow-up of a large cohort of patients with primary biliary cirrhosis seen at a single centre. Liver Int 31:361–368CrossRefPubMed
68.
Baldursdottir TR, Bergmann OM, Jonasson JG, Ludviksson BR, Axelsson TA, Bjornsson ES (2012) The epidemiology and natural history of primary biliary cirrhosis: a nationwide population-based study. Eur J Gastroenterol Hepatol 24:824–830CrossRefPubMed
Metadata
Title
Extrahepatic Malignancies in Primary Biliary Cirrhosis: A Comparative Study at Two European Centers
Authors
Annarosa Floreani
Alice Spinazzè
Llorenc Caballeria
Ana Reig
Nora Cazzagon
Irene Franceschet
Alessandra Buja
Patrizia Furlan
Kenichi Harada
Patrick SC Leung
M. Eric Gershwin
Albert Pares
Publication date
01-06-2015
Publisher
Springer US
Published in
Clinical Reviews in Allergy & Immunology / Issue 2-3/2015
Print ISSN: 1080-0549
Electronic ISSN: 1559-0267
DOI
https://doi.org/10.1007/s12016-014-8446-7

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