Review
Copyright ©The Author(s) 2017.
World J Gastroenterol. Feb 7, 2017; 23(5): 776-791
Published online Feb 7, 2017. doi: 10.3748/wjg.v23.i5.776
Table 1 Studies regarding the association of primary sclerosing cholangitis and celiac disease
Type of articleNo. of patientsSymptomsCeliac antibodiesDuodenal biopsyResponse to gluten-free dietLiver biopsyERCPComorbiditiesCountry, yearRef.
Case report3Weight loss, steatorrhoeaNoTypical1YesYesYes2 Chronic ulcerative colitisUnited States, 1988Hay et al[35]
Abstract69Screening55% AGA (+)0/26 altered----Ireland, 1992MacMathuna et al[46]
Case report1Diarrhea, weight loss, growth retardationNoTypical1YesYesYesChronic colitisFrance, 1995Lacaille et al[37]
Turner’s syndrome
Case report2AnemiaAGA IgA (+)Villous atrophyYesYesYes-Italy, 1996Fracassetti et al[36]
Case report1DiarrheaNoVillous atrophyYesYesYesUlcerative colitisSweden, 1994Tysk[41]
Case report1Folic acid deficiencyAGA (-)Typical1YesYesUlcerative colitisFrance, 1994Brazier et al[44]
EmA (+)Hashimoto’s thyroiditis
Case report2Weight lossEmA (+)Typical1YesYesYes-Italy, 1998Venturini et al[49]
Case report1AnemiaNoNot mentionedNot mentionedYesYesRheumatoid arthritisUnited Kingdom, 2001Gow et al[50]
Case series1DiarrheatTG (+)Villous atrophyNo adherenceYesNot mentionedNot mentionedFinland, 2002Kaukinen et al[51]
ProtrudingEmA (-)
abdomen
Failure to thrive
Case report2Active screening for CDEmA (+)Typical1YesYesYesUlcerative colitisPoland, 2002Habior et al[43]
tTG (+)
Prospective cohort61Active screening for CD1.6% EmA (+)100% (1/1) Typical1YesYesYes-Italy/Spain 2002Volta et al[52]
3.3% tTG (+)
Case report2Weight loss, steatorrhoeaEmA (+)Villous atrophyYesNoYesUlcerative colitisUnited Kingdom, 2003Wurm et al[42]
Case report1Routine UDEAGA (+)Typical1YesYesYes-United States, 2004Al-Osaimi et al[53]
EmA (+)
Case report1DiarrheaEmA (+)Typical1YesYesYes-Spain, 2005Cadahía et al[54]
Prospective cohort155Screening3% EmA (+)-----United States, 2008Rubio-Tapia et al[48]
9% tTG (+)
Case report1Short stature and anemiatTG (+)Typical1YesYesNo, MRC-Saudi Arabia, 2013Al-Hussaini et al[55]
Table 2 Case reports2 regarding the association of primary biliar cholangitis and celiac disease
Number of patientsSymptomsCeliac antibodiesDuodenal biopsyResponse to gluten-free dietLiver biopsyAMAComorbiditiesCountry, yearRef.
4Weight loss, steatorrhea, anemiaNoTypical1YesYes(+)serum-IgA deficiencyScotland, 1978Logan et al[58]
1Weight loss, diarrhea, anorexiaNoTypical1YesYesNo-United Kingdom, 1978Lee et al[59]
1MalabsorptionNoTypical1Poor adherenceYes(+)-Canada, 1979Iliffe et al[60]
1Diarrhea, anemia, short statureSubtotal villous atrophyYes, but PBC was diagnosed afterwardsYes(+)-Ireland, 1983Shanahan et al[62]
1Dermatitis herpetiformisNoTypical1YesYes(+)Dermatitis herpetiformisNorway, 1985Gabrielsen et al[64]
1AnemiaAGA (-)Typical1YesYes(+)Renal tubular acidosis, Sjögren SyndromeIreland, 1987Whitehead et al[68]
1Weight loss, diarrheaNoTypical1YesYes(+)-United States, 1992Ginn et al[69]
1Weight loss, anemiaNoTypical1YesYes(+)-Canada, 1994Freeman[70]
1DiarrheaNoTypical1Yes, but PBC was diagnosed afterwardsYes(+)-Germany, 1994Löhr et al[196]
1Diarrhea, weight lossAGA (+)Typical1NoYes(+)-Spain, 1994Gálvez et al[97]
1Weight loss, steatorrheaAGA (+)Typical1YesYes(+)Bacterial overgrowthUnited States, 1998DiBaise et al[71]
EmA (+)
1AnemiaEmA (+)TypicalYesYesNo-United States, 2002Sedlack et al[84]
1Diarrhea, weight lossEmA (+)Typical1YesYes(+)Renal tubular acidosis, Sjögren Syndrome,Italy, 2004Fracchia et al[98]
Graves’ disease
1Inability to walk, anemiaAGA (-)Typical1YesYes(+)Osteomalacic MyopathyTurkey, 2008Demirag et al[99]
EmA (-)
1Bone painAGA (+)Typical1YesYes(+)Fanconi syndromeParis, 2008Terrier et al[100]
EmA (+)
tTG (+)
1DispepsiatTG (+)Typical1YesYes(+)Helicobacter pyloriItaly, 2010Abenavoli et al[83]
1Diarrhea, bloatingEmA (+)Typical1YesYes(+)India, 2013Lodh et al[101]
tTG (+)
Table 3 Research on screening celiac disease in patients with primary biliar cholangitis
StudyScreening methodNumber of positive patientsTypical duodenal biopsy12Response to gluten-free dietCountry, yearRef.
ProspectiveDuodenal biopsy5/26 (19.2%)19, 2%No improvement in liver biochemestrySweden, 1982Olsson et al[61]
RetrospectivePrevious diagnose2/18 (11.1%)Not mentionedNo improvement in liver biochemestry or liver histologySweden, 1985Löfgren et al[65]
ProspectiveEmA IFI > 1:56/57 (11%) EmA (+)7%No improvement in liver biochemestryIreland, 1997Dickey et al[73]
Prospective cohortAGA IgG IgA > 1 AU0/62 (0%) EmA (+)0/0-United States/ItalyVolta et al[76]
IgA EmA IFI11/62 (16%) AGA (+)
Prospectivemalabsorption, haematinic4/67 (6%)4/67 (6%)No improvement in liver biochemestryUnited Kingdom, 1998Kingham et al[72]
deficiency, positive antigliadin antibody,
or CD family history
ProspectiveAGA IgA > 25 AU/mL4/11 (36, 4%) AGA IgA (+)18%-Argentina, 1998Niveloni et al[102]
IgG > 28 AU/mL1/11 (9%) AGA IgG (+)
EmA IFI > 1:51/11 (9%) EmA (+)
Retrospective (stored sera)EmA IFI > 1:510/378 (2.6%) EmA (+) + tTG (+)1.30%-United Kingdom, 2000Gillett et al[103]
tTG IgA ELISA > 140 AU/mL44/378 (11.6%) EmA (-) + tTG (+)
ProspectiveEmA IFI3/87 (3.4%) EmA (+)0/17-Italy, 2002Floreani et al[80]
tTG IgA > 10 IU24/87 (27.5%) tTG (+)
ProspectiveAGA IgA > 50 U/mL13/62 (21%) AGA (+)0/10-Greece, 2002Chatzicostas et al[78]
AGA IgG > 50 U/mL0/62 EmA (+)
EmA IgA IFI ≥ 1:56/62 (10%) tTG (+)
IgA tTG > 30 U/mL
Prospective cohortEmA IFI > 1:57/173 (4%) EmA (+)7/7No improvement in liver biochemestryItaly/Spain 2002.Volta et al[52]
tTG IgA > 7 AU5/173 (2.9%) tTG (+)
AGA IFI
Prospective cohortIgA tTG > 7 AU5/48 (10.4%) tTG (+)--Italy, 2003Bizzaro et al[104]
IgG anti-Ttg > 30 AU
EmA IFI
tTG < 1:1007/115 (6.1%) tTG (+)1/8Duodenal histological improvementPoland, 2003Habior et al[105]
EmA IFI1/115 (0.9%) EmA (+)
AGA Elisa8/115 (7.0%) AGA (+)
Prospective cohortSix different ELISA tTG28/105 (26.7%) tTG IgA (+)100% EmA (+)-Italy, 2006Bizzaro et al[25]
6/105 (5.7%) tTG IgG (+)0% tTG (+)
Table 4 Case reports regarding the association of autoimmune hepatitis and celiac disease
Number of patientsSymptomsAIH antibodiesCeliac antibodiesDuodenal biopsyResponse to gluten-free dietLiver biopsyComorbiditiesCountry, yearAuthors
1Anemia, infectionASM 1:500AGA IgA and IgG (+)Typical1Yes2Active chronic hepatitisErythroblastopeniaFrance, 2001Bridoux-Henno et al[124]
anti-vimentin 1:500EmA (+)
1Weight loss,ANA 1:1280, p-ANCA 1:2560, SMA 1:1200, LKM1 1:50Reticulin antibodiesTypical1No, developed AIH despite of a gluten-free dietChronic inflammationThyrotoxicosisFinland, 2002Arvola et al[34]
fatigue, abdominal pain, and diarrheato 1:2000In the portal area and proliferation of the small hepatic
AGA IgA (+)Ductules. Patchy degeneration of the liver cells.
2Diarrhea, abdominal enlargement andANA (+)??case 1: poor response to aAcute hepatitis-Italy, 2003Leonardi et al[125]
failure to thrive.SMA (+)gluten-free diet for the treatment of hepatitis;With portal bridging necrosis and fibrosis and a
antiactine (+)case 2: developed AIH despite the dietPeri-portal inflammatory infiltrate of lymphocytes,
Plasma cells and neutrophils
1Elevated liver enzymes detected, hypesthesia of the leftANA (+)AGA (+)Typical1Poor adherence to dietModerately active, chronic hepatitis withCryoglobulinaemiaSwitzerland, 2003Biecker et al[126]
foot, purpura and skin ulcers of both legs.EmA (+)Interface lesions and fibrosis of the portal tract,
Bile duct lesions and ductular
Proliferations.
1Jaundice and pale stools.All negative. Score probableAGA IgA (+)Typical1Liver disease progressed despite the dietModerate to severe.-Italy, 2004Iorio et al[127]
AGA IgG (+)lobular inflammatory activity, mononuclear portal
Ema (+)inflammation, interface hepatitis, and portal and periportal
tTG IgA (+)fibrosis with septae; rosetting of liver cells
and some giant cells.
1Ferropenia-tTG (+)Villous atrophyElevation of aminotranferases despite the diet.severe ymphocytic inflammatory infiltratePeru, 2006Tagle et al[128]
and elevation of aminotransferases.with slight increase of collagen in
portal tracts, foci of lobular necrosis and presence
acidophilus bodies
1Anorexia, severe diarrhea, rapid loss of weight,ANA (+)EmA (+)Villous atrophyDeveloped cirrhosis despite the dietCirrhosisHolmes-Adie syndromeHungary, 2006Csak et al[129]
amenorrhea and anemia.SMA (+)tTG (+)
1JaundiceSMA (+)AGA (+)Typical1Poor adherence to dietConfirmed the diagnosis of acute AIHMultiple sclerosisItaly, 2008Ferrò et al[130]
EmA (+)
tTG IgA (+) IgG (+)
1Weight loss, anorexia, fatigue, and diarrhea.ANA+++AGA IgA (+)Typical1Liver disease was diagnosed on a gluten-free dietModerately active, chronic hepatitis with interface lesionsAutoimmune cholangitis overlap, Autoimmune thyroiditisTurkey, 2009Ozaslan et al[131]
AGA IgG (+)And fibrosis of the portal tracts, ductular injury and ductopenia.
EmA (+)
tTG (+)
1Malaise,ANA, SMA, LKM-1, mitochondrial, anti-LC1,EmA (+)Typical1No, developed AIH despite of a gluten-free dietLymphoplasmacytic hepatitis (portal interface and lobular)-United Kingdom, 2009Quail et al[132]
intermittent pyrexia and vomiting, an urticarial-vasculiticanti-SLA/LP, parietal celltTG (+)With moderate to marked activity and minimal
rash and joint pains.antibodies, all negativeChronicity (fibrosis stage 1/6).
1Two miscarriages, iron deficiency anemia, osteopenia and alternating bowel habit, elevated aminotransferasesANA +++, homogeneous; SMA ++, anti-dsDNAEmA 1:160Severe villous atrophyYes2ChronicLupusItaly, 2010Tovoli et al[133]
0.1527778Active hepatitis with piecemeal necrosis and lympho-plasmacellular periportal infiltrate
1anemia, weakness and highANA 1:640,EmA (+)Flat mucosaNo, developed acute liver failureSevere fibrosisNoneItaly, 2013Volta et al[134]
aminotransferase levelsSMA 1:320,tTG (+)
pANCA 1:160
1Miscontrol of diabetesANA 1:160IgA tTG (+)Typical1Yes2Moderate interface hepatitis and chronic inflammatory infiltrate, and foci of necrosisAutoimmune thyroiditis and type 1 diabetesSpain, 2016Dieli-crimi et al[135]
Altered liver enzymesEmA (-)
Table 5 Research screening celiac disease in patients with autoimmune hepatitis
StudyScreening methodNumber of positive patientsTypical duodenal biopsy12Response to gluten-free dietCountry, yearAuthors
Prospective cohortAGA IgG IgA > 1 AU8/181 (4.4%) EmA (+)5/5-United States/Italy, 1998Volta et al[76]
IgA EmA IFI7/181 (3.9%) AGA (+)
RetrospectiveEmA3/47 (6.4%)3/3-Italy, 2005Villalta et al[136]
tTG IgA IgG
RetrospectiveEmA19/140 (14%)?NoItaly, 2008Caprai et al[120]
tTG IgA IgG
RetrospectiveAGA IgA, IgG5/40 (13%)5/5Mild decrease of transaminases, but never a complete normalizationItaly, 2008Diamanti et al[137]
EmA IgA
tTG IgA
RetrospectiveAGA IgA, IgG7/15 (47%)7/7-Turkey, 2009Tosun et al[138]
EmA IgA
tTG IgA
Retrospective?3/278 (1.1%)?-Germany, 2010Teufel et al[139]
ProspectiveIgA EmA IFI4/26 (15%)3/4-Egypt, 2011El-Shabrawi et al[140]
tTG ELISA
RetrospectiveEmA IgA, IgG15/79 (19%)?All of the 15 patients achieved sustainedItaly, 2013Nastasio et al[122]
tTG IgA, IgGremission when treated with prednisone and azathioprine or cyclosporine
ProspectivetTG IgA ELISA3/64 (4.7%) tTG (+)3/3-Iran, 2014Najafi et al[141]
ProspectiveIgA EmA IIF6 previous diagnoses--Netherlands, 2014van Gerven et al[118]
tTG ELISA10/460 tTG + EmA + HLA
HLA DQ2 DQ8-3.50%