Chapter 11.5
Overlap Syndromes
Ulrich Beuers,
Ulrich Beuers
Search for more papers by this authorUlrich Beuers,
Ulrich Beuers
Search for more papers by this authorBook Editor(s):Juan Rodés MD,
Jean-Pierre Benhamou MD,
Andres T. Blei MD,
Jürg Reichen MD,
Mario Rizzetto MD,
Juan Rodés MD
Director General, Hospital Clinic; Professor of Medicine, University of Barcelona, Barcelona, Spain
Search for more papers by this authorJean-Pierre Benhamou MD
Professor of Hepatology, Université Denis Diderot Paris 7, Assistance Publique — Hôpitaux de Paris and Inserm U773, Service d'Hépatologie, Hôpital Beaujon, Clichy, France
Search for more papers by this authorAndres T. Blei MD
Professor of Medicine and Surgery, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
Search for more papers by this authorJürg Reichen MD
Professor of Medicine, University of Bern; Chief of Hepatology, University Hospital, Bern, Switzerland
Search for more papers by this authorMario Rizzetto MD
Professor of Gastroenterology, University of Turin, Turin, Italy
Search for more papers by this authorFirst published: 18 June 2007

References
- Czaja AJ (1996) The variant forms of autoimmune hepatitis. Ann Intern Med 125, 588–598.
- Heathcote EJ (1999) Overlap syndromes. In: JBJ Bircher, N McIntyre, M Rizzetto et al.(eds) Oxford Textbook of Clinical Hepatology,Vol. 2. Oxford: Oxford University Press, pp. 1135–1140.
- Woodward J, Neuberger J (2001) Autoimmune overlap syndromes. Hepatology 33, 994–1002.
- Poupon R (2003) Autoimmune overlapping syndromes. Clin Liver Dis 7, 865–878.
- Beuers U (2005) Hepatic overlap syndromes. J Hepatol 42, S93–S99.
- Colombato LA, Alvarez F, Cote J et al. (1994) Autoimmune cholan-giopathy: the result of consecutive primary biliary cirrhosis and autoimmune hepatitis' Gastroenterology 107, 1839–1843.
- Chazouilleres O, Wendum D, Serfaty L et al. (1998) Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: clinical features and response to therapy. Hepatology 28, 296–301.
- Gregorio GV, Portmann B, Karani J et al. (2001) Autoimmune hepati-tis/sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study. Hepatology 33, 544–553.
- Abdo AA, Bain VG, Kichian K et al. (2002) Evolution of autoimmune hepatitis to primary sclerosing cholangitis: a sequential syndrome. Hepatology 36, 1393–1399.
- Alvarez F, Berg PA, Bianchi FB et al. (1999) International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 31, 929–938.
- Kanzler S, Weidemann C, Gerken G et al. (1999) Clinical significance of autoantibodies to soluble liver antigen in autoimmune hepatitis. J Hepatol 31, 635–640.
- Terjung B, Bogsch F, Klein R et al. (2004) Diagnostic accuracy of atypical p-ANCA in autoimmune hepatitis using ROC- and multivariate regression analysis. Eur J Med. Res 9, 439–448.
- Prince MI, Chetwynd A, Craig WL et al. (2004) Asymptomatic primary biliary cirrhosis: clinical features, prognosis, and symptom progression in a large population based cohort. Gut 53, 865–870.
- Vierling JM (2004) Primary biliary cirrhosis and autoimmune cholan-giopathy. Clin Liver Dis 8, 177–194.
- Heathcote EJ (2000) Management of primary biliary cirrhosis. The American Association for the Study of Liver Diseases practice guidelines. Hepatology 31, 1005–1013.
- Wiesner RH, LaRusso NF, Ludwig J et al. (1985) Comparison of the clinicopathologic features of primary sclerosing cholangitis and primary biliary cirrhosis. Gastroenterology 88, 108–114.
- Ludwig J, Colina F, Poterucha JJ (1995) Granulomas in primary sclerosing cholangitis. Liver 15, 307–312.
- Lee YM, Kaplan MM (1995) Primary sclerosing cholangitis. N Engl J Med 332, 924–933.
- Heathcote J (1997) Autoimmune cholangitis. Gut 40, 440–442.
- Brunner G, Klinge O (1987) [A chronic destructive nonsuppurative cholangitis-like disease picture with antinuclear antibodies (immuno-cholangitis)]. Dtsch Med Wochenschr 112, 1454–1458.
- Ben-Ari Ari, Dhillon AP, Sherlock S (1993) Autoimmune cholangio-pathy: part of the spectrum of autoimmune chronic active hepatitis. Hepatology 18, 10–15.
- Sherlock S (1998) Ludwig Symposium on biliary disorders. Autoimmune cholangitis: a unique entity? Mayo Clin Proc 73, 184–190.
- Czaja AJ, Carpenter HA, Santrach PJ et al. (2000) Autoimmune cholangitis within the spectrum of autoimmune liver disease. Hepatology 31, 1231–1238.
- Michieletti P, Wanless IR, Katz A et al. (1994) Antimitochondrial antibody negative primary biliary cirrhosis: a distinct syndrome of autoimmune cholangitis. Gut 35, 260–265.
- Taylor SL, Dean PJ, Riely CA (1994) Primary autoimmune cholangitis. An alternative to antimitochondrial antibody-negative primary biliary cirrhosis. Am J Surg Pathol 18, 91–99.
- Goodman ZD, McNally PR, Davis DR et al. (1995) Autoimmune cholangitis: a variant of primary biliary cirrhosis. Clinicopathologic and serologic correlations in 200 cases. Dig Dis Sci 40, 1232–1242.
- Omagari K, Ikuno N, Matsuo I et al. (1996) Autoimmune cholangitis syndrome with a bias towards primary biliary cirrhosis. Pathology 28, 255–258.
- Invernizzi P, Crosignani A, Battezzati PM et al. (1997) Comparison of the clinical features and clinical course of antimitochondrial antibody-positive and -negative primary biliary cirrhosis. Hepatology 25, 1090–1095.
- Kinoshita H, Omagari K, Whittingham S et al. (1999) Autoimmune cholangitis and primary biliary cirrhosis — an autoimmune enigma. Liver 19, 122–128.
- Neuberger J, Thomson R (1999) PBC and AMA — what is the connection? Hepatology 29, 271–276.
- Miyakawa H, Tanaka A, Kikuchi K et al. (2001) Detection of antimitochondrial autoantibodies in immunofluorescent AMA-negative patients with primary biliary cirrhosis using recombinant autoanti-gens. Hepatology 34, 243–248.
- Tsuneyama K, Van De Water J, Van Thiel D et al. (1995) Abnormal expression of PDC-E2 on the apical surface of biliary epithelial cells in patients with antimitochondrial antibody-negative primary biliary cirrhosis. Hepatology 22, 1440–1446.
- Ikuno N, Scealy M, Davies JM et al. (2001) A comparative study of antibody expressions in primary biliary cirrhosis and autoimmune cholangitis using phage display. Hepatology 34, 478–486.
- Gordon SC, Quattrociocchi-Longe TM, Khan BA et al. (1995) Antibodies to carbonic anhydrase in patients with immune cholan-giopathies. Gastroenterology 108, 1802–1809.
- Ohana M, Okazaki K, Hajiro K et al. (1998) Antilactoferrin antibodies in autoimmune liver diseases. Am J Gastroenterol 93, 1334–1339.
- Comay D, Cauch-Dudek K, Hemphill D et al. (2000) Are antibodies to carbonic anhydrase II specific for antimitochondrial antibody-negative primary biliary cirrhosis' Dig Dis Sci 45, 2018–2021.
- Muratori L, Muratori P, Zauli D et al. (2001) Antilactoferrin antibodies in autoimmune liver disease. Clin Exp Immunol 124, 470–473.
- Lacerda MA, Ludwig J, Dickson ER et al. (1995) Antimitochondrial antibody-negative primary biliary cirrhosis. Am J Gastroenterol 90, 247–249.
- Kim WR, Poterucha JJ, Jorgensen RA et al. (1997) Does antimitochondrial antibody status affect response to treatment in patients with primary biliary cirrhosis' Outcomes of ursodeoxycholic acid therapy and liver transplantation. Hepatology 26, 22–26.
- James OF, Bhopal R, Howel D et al. (1999) Primary biliary cirrhosis once rare, now common in the United Kingdom? Hepatology 30, 390–394.
- Kim WR, Lindor KD, Locke GR 3rd, et al. (2000) Epidemiology and natural history of primary biliary cirrhosis in a US community. Gastroenterology 119, 1631–1636.
- Boberg KM, Aadland E, Jahnsen J et al. (1998) Incidence and prevalence of primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis in a Norwegian population. Scand J Gastroenterol 33, 99–103.
- Geubel AP, Baggenstoss AH, Summerskill WH (1976) Responses to treatment can differentiate chronic active liver disease with cholangitic features from the primary biliary cirrhosis syndrome. Gastroenterology 71, 444–449.
- Kloppel G, Seifert G, Lindner H et al. (1977) Histopathological features in mixed types of chronic aggressive hepatitis and primary biliary cirrhosis. Correlations of liver histology with mitochondrial antibodies of different specificity. Virchows Arch A Pathol Anat Histol 373, 143–160.
- Gheorghe L, Iacob S, Gheorghe C et al. (2004) Frequency and predictive factors for overlap syndrome between autoimmune hepatitis and primary cholestatic liver disease. Eur J Gastroenterol Hepatol 16, 585–592.
- Lohse AW, zum Buschenfelde KH, Franz B et al. (1999) Characterization of the overlap syndrome of primary biliary cirrhosis (PBC) and autoimmune hepatitis: evidence for it being a hepatitic form of PBC in genetically susceptible individuals. Hepatology 29, 1078–1084.
- Yamamoto K, Terada R, Okamoto R et al. (2003) A scoring system for primary biliary cirrhosis and its application for variant forms of autoimmune liver disease. J Gastroenterol 38, 52–59.
- Terjung B, Spengler, U (2005) Role of auto-antibodies for the diagnosis of chronic cholestatic liver diseases. Clin Rev Allerg Immunol 28, 117–132.
- Kanzler S, Bozkurt S, Herkel J et al. (2001) [Presence of SLA/LP autoantibodies in patients with primary biliary cirrhosis as a marker for secondary autoimmune hepatitis (overlap syndrome)]. Dtsch Med Wochenschr 126, 450–456.
- Leuschner U (2005) Autoimmunkrankheiten der Leber und Over-lapsyndrome, 2nd edn. Bremen: UNI-MED Verlag AG.
- Duclos-Vallee Vallee, Hadengue A, Ganne-Carrie N et al. (1995) Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. Corti-coresistance and effective treatment by cyclosporine A. Dig Dis Sci 40, 1069–1073.
- el-Shabrawi Shabrawi, Wilkinson ML, Portmann B et al. (1987) Primary sclerosing cholangitis in childhood. Gastroenterology 92, 1226–1235.
- Rabinovitz M, Demetris AJ, Bou-Abboud CF et al. (1992) Simultaneous occurrence of primary sclerosing cholangitis and autoimmune chronic active hepatitis in a patient with ulcerative colitis. Dig Dis Sci 37, 1606–1011.
- Lawrence SP, Sherman KE, Lawson JM et al. (1994) A 39 year old man with chronic hepatitis. Semin Liver Dis 14, 97–105.
- Debray D, Pariente D, Urvoas E et al. (1994) Sclerosing cholangitis in children. J Pediatr 124, 49–56.
- Wilschanski M, Chait P, Wade JA et al. (1995) Primary sclerosing cholangitis in 32 children: clinical, laboratory, and radiographic features, with survival analysis. Hepatology 22, 1415–1422.
- Gohlke F, Lohse AW, Dienes HP et al. (1996) Evidence for an overlap syndrome of autoimmune hepatitis and primary sclerosing cholangitis. J Hepatol 24, 699–705.
- McNair AN, Moloney M, Portmann BC et al. (1998) Autoimmune hepatitis overlapping with primary sclerosing cholangitis in five cases. Am J Gastroenterol 93, 777–784.
- van Buuren HR, van Hoogstraten HJE, Terkivatan T et al. (2000) High prevalence of autoimmune hepatitis among patients with primary sclerosing cholangitis. J Hepatol 33, 543–548.
- Kaya M, Angulo P, Lindor KD (2000) Overlap of autoimmune hepatitis and primary sclerosing cholangitis: an evaluation of a modified scoring system. J Hepatol 33, 537–542.
- Beuers U, Spengler U, Kruis W et al. (1992) Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: a placebo-controlled trial. Hepatology 16, 707–714.
- Stiehl A (1994) Ursodeoxycholic acid therapy in treatment of primary sclerosing cholangitis. Scand J Gastroenterol Suppl 204, 59–61.
- Lindor KD (1997) Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing Cholangitis-Ursodeoxycholic Acid Study Group. N Engl J Med 336, 691–695.
- Mitchell SA, Bansi DS, Hunt N et al. (2001) A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis. Gastroenterology 121, 900–907.
- Czaja AJ, Carpenter HA (2001) Autoimmune hepatitis with incidental histologic features of bile duct injury. Hepatology 34, 659–665.
- Li CP, Tong MJ, Hwang SJ et al. (2000) Autoimmune cholangitis with features of autoimmune hepatitis: successful treatment with immunosuppressive agents and ursodeoxycholic acid. J Gastroenterol Hepatol 15, 95–98.
- Rubel LR, Seeff LB, Patel V (1984) Primary biliary cirrhosis-primary sclerosing cholangitis overlap syndrome. Arch Pathol Lab Med 108, 360–361.
- Burak KW, Urbanski SJ, Swain MG (2001) A case of coexisting primary biliary cirrhosis and primary sclerosing cholangitis: a new overlap of autoimmune liver diseases. Dig Dis Sci 46, 2043–2047.
- Zanger UM, Hauri HP, Loeper J et al. (1988) Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type II. Proc Natl Acad Sci USA 85, 8256–8260.
- Manns MP, Johnson EF, Griffin KJ et al. (1989) Major antigen of liver kidney microsomal autoantibodies in idiopathic autoimmune hepatitis is cytochrome P450db1. J Clin Invest 83, 1066–1072.
- Manns MP, Griffin KJ, Sullivan KF et al. (1991) LKM-1 autoantibodies recognize a short linear sequence in P450IID6, a cytochrome P-450 monooxygenase. J Clin Invest 88, 1370–1378.
- Manns MP, Obermayer-Straub P (1997) Cytochromes P450 and uridine triphosphate-glucuronosyltransferases: model autoantigens to study drug-induced, virus-induced, and autoimmune liver disease. Hepatology 26, 1054–1066.
- Lunel F, Abuaf N, Frangeul L et al. (1992) Liver/kidney microsome antibody type 1 and hepatitis C virus infection. Hepatology 16, 630–636.
- Pawlotsky JM, Ben Yahia M, Andre C et al. (1994) Immunological disorders in C virus chronic active hepatitis: a prospective case-control study. Hepatology 19, 841–848.
- Lunel F, Cacoub P (1999) Treatment of autoimmune and extrahepatic manifestations of hepatitis C virus infection. J Hepatol 31, 210–216.
- Chazouilleres O (2000) Diagnosis of primary sclerosing cholangitis -autoimmune hepatitis overlap syndrome: to score or not to score? J Hepatol 33, 661–663.