Systematic Reviews
Copyright ©The Author(s) 2020.
World J Clin Cases. Sep 26, 2020; 8(18): 4075-4093
Published online Sep 26, 2020. doi: 10.12998/wjcc.v8.i18.4075
Table 1 Baseline features in 109 patients with overlap syndrome (primary sclerosing cholangitis/autoimmune hepatitis)
VariablePatients (n = 109)
Mean age (yr)25.52
Sex (male)46 (42.59%)
Race10 (6.78%)
White7 (70%)
Black3 (30%)
IBD48 (44.44%)
CD13 (27.65%)
UC32 (68.08%)
Non-specific3 (6.38%)
PSC
Small Ducts4 (3.70%)
AIH (median)
SAH pre-treatment (pts)17 (13-22)
SAH post-treatment (pts)19 (13-25)
Clinical presentation
Fever7 (6.48%)
Dyspnea1 (0.93%)
Headache1 (0.93%)
Jaundice31 (28.70%)
Pruritus11 (10.19%)
Urine alteration6 (5.55%)
Choluria5 (83.33%)
Hematuria1 (16.66%)
Nausea4 (3.70%)
Emesis8 (7.40%)
Without blood4 (50%)
Hematemesis4 (50%)
Diarrhea11 (10.19%)
Stools18 (16.66%)
Hematochezia1 (5.55%)
Melena1 (5.55%)
Incontinence1 (5.55%)
Acholia3 (16.66%)
Watery stools11 (61.11%)
Steatorrhea1 (5.55%)
Abdominal pain21 (19.44%)
Joint pain2 (1.85%)
Weight loss9 (8.33%)
Fatigue22 (20.37%)
Family history4 (3.70%)
Hepatomegaly15 (13.89%)
Splenomegaly12 (11.11%)
Ascites7 (6.48%)
Fecal occult blood3 (2.78%)
Cirrhosis17 (15.74%)
Encephalopathy2 (1.85%)
Comorbidities
Esophageal varices13 (12.03%)
Hypothyroidism1 (0.93%)
Anemia1 (0.93%)
Alcohol-induced pancreatitis1 (0.93%)
Hepatic insufficiency1 (0.93%)
Rheumatoid arthritis1 (0.93%)
Smoker1 (0.93%)
Membranous glomerulonephritis1 (0.93%)
Hepatocarcinoma1 (0.93%)
Pyoderma gangrenosum1 (0.93%)
Reflux nephropathy1 (0.93%)
Post-infantile giant cell hepatitis4 (3.70%)
Renal cell carcinoma1 (0.93%)
Autoimmune thyroiditis1 (0.93%)
Biopsy109 (100%)
Grade (Batts-Ludwig)29 (26.85%)
None2 (6.89%)
Minimal1 (3.44%)
Mild10 (34.48%)
Moderate11 (37.93%)
Severe5 (17.24%)
Stage (Batts-Ludwig)37 (34.25%)
None1 (2.70%)
Portal fibrosis14 (37.83%)
Periportal fibrosis10 (27.02%)
Septal fibrosis9 (24.32%)
Cirrhosis3 (8.10%)
Laboratory tests (mean)
Hb (g/dL)10.20
Ht (%)32.8
Leucocytes (mm3) (median)7600
Platelets (mm3) (median)185000
Prothrombin time (s)15.35
INR1.41
ALT (U/L)378.2
AST (U/L)378.2
GGT (U/L)316.6
ALP (U/L)693.4
Total bilirubin (mg/dL)5.14
Direct bilirubin (mg/dL)4.43
Total protein (g/dL)17.82
Albumin (g/dL) (median)3.09
Total globulins (mg/L)51410
IgG total (mg/dL)2762
IgA total (mg/dL)230.3
IgM total (mg/dL)729.7
Antibodies
LKM13 (2.78%)
AMA3 (2.78%)
ANA59 (54.63%)
SMA33 (30.56%)
pANCA36 (33.33%)
HLA18 (16.66%)
Medications63 (58.33%)
Steroids62 (98.41%)
Azathioprine48 (76.19%)
6-mercaptopurine1 (1.58%)
Ursodeoxycholic acid47 (74.60%)
Mesalazine7 (11.11%)
Antibiotics3 (4.76%)
D-penicillamine1 (1.58%)
Cyclosporine A1 (1.58%)
Mycophenolate mofetil2 (3.17%)
Clinical improvement61 (56.48%)
Relapse41 (37.96%)
Transplantation13 (12.87%)
Mean time from diagnosis-transplant (mo), n = 10 (76.92%)74.90
Transplant medications, n = 44 (30.76%)
Steroids4 (100%)
Basiliximab1 (25%)
Cyclosporine2 (50%)
Azathioprine1 (25%)
Tacrolimus2 (50%)
Mycophenolate mofetil2 (50%)
Mean time follow-up (mo)59.18
Death4 (3.70%)
IBD: Inflammatory bowel disease; CD: Crohn’s disease; UC: Ulcerative colitis; PSC: Primary sclerosing cholangitis; AIH: Autoimmune hepatitis; SAH: Score for autoimmune hepatitis; INR: International normalized ratio; ALT: Alanine transaminase; AST: Aspartate transaminase; GGT: Gamma-glutamyl transferase; ALP: Alkaline phosphatase; LKM1: Liver kidney microsome type 1 antibody; AMA: Anti-mitochondrial antibodies; ANA: Antinuclear antibody; SMA: Smooth muscle antibodies; pANCA: Perinuclear anti-neutrophil cytoplasmic antibodies.
Table 2 Summary of systematically reviewed clinical cases (primary sclerosing cholangitis/autoimmune hepatitis overlap syndrome)
Ref.CountrySexAgeClinical presentationIBDCo-morbiditiesAntibodiesHLATreatmentRelapseOutcomeMiscellaneous
Wurbs et al[3], 1995GermanyF28Fever, Choluria, Weight Loss, FatigueNNonepANCA, SMADRSteroids, AZANRecovery
Lawrence et al[4], 1994United StatesM39Nausea, Emesis, Fatigue, Hepatomegaly, Occult stool bloodUCCirrhosisSMANASteroids, AZA, Cyclosporine ANRecovery
Nalepa et al[5], 2017PolandM10Jaundice, Diarrhea, Abdominal Pain, Hepatomegaly, Splenomegaly, Ascites, HematemesisUCCirrhosis, Esophageal VaricesANA, SMANASteroids, AZA, UDCA, MSMYRecoveryLiver transplantation
Luketic et al[6], 1997United StatesF38Jaundice, Nausea, Fatigue, Ascites, HematemesisNNoneANANASteroids, AZAYRecoveryLiver transplantation
Mueller et al[7], 2018GermanyF15Vomiting, FatigueNNoneANA, pANCA, SMA, AMANASteroids, UDCANRecovery
Guerrero-Hernández et al[8], 2007MexicoF22Jaundice, Choluria, FatigueNNoneANA, pANCANASteroids, AZA, UDCANRecovery
Takiguchi et al[9], 2002JapanF36FeverNNoneANA, pANCAA24, A31, B35, B61, Cw4, DR4Steroids, AZA, UDCAYRecovery
McNair et al[10], 1998United KingdomM38Jaundice, Watery Stools, Abdominal Pain, Weight LossUCEncephalopathyANA, LKM1, pANCA, SMAB8, DR3Steroids, AZAYDeath
McNair et al[10], 1998United KingdomF20Jaundice, ItchingNNoneANA, pANCA, SMANDSteroids, AZA, UDCAYRecovery
McNair et al[10], 1998United KingdomM26Dyspnea, JaundiceNNoneANA, pANCAA1, B8, DR3Steroids, AZAYRecovery
McNair et al[10], 1998United KingdomM14Jaundice, Diarrhea, Abdominal PainUCNoneANA, pANCA, SMAA1, B8, DR3Steroids, AZAYRecovery
McNair et al[10], 1998United KingdomM18Jaundice, Diarrhea, Abdominal Pain, Weight LossNNonepANCA, SMANDSteroids, AZA, UDCANRecovery
Man et al[11], 2017RomaniaM13Jaundice, Hepatomegaly, SplenomegalyNEsophageal VaricesSMANASteroids, AZA, UDCA, Mycophenolate MofetilYRecovery
Malik et al[12], 2010United StatesF22Diarrhea, Abdominal PainCDNoneNANASteroids, AZA, UDCA, Mycophenolate MofetilYRecovery
Lamia et al[13], 2012TunisiaM4Hematuria, Diarrhea, Hepatomegaly, SplenomegalyNSICNoneANA, pANCA, SMANASteroids, AZA, UDCA, 6-MPYRecovery
Lee et al[14], 2005MalaysiaF5Jaundice, Itching, SteatorrheaNNoneANA, SMANASteroids, UDCANRecovery
Santos et al[15], 2012ColombiaM36Jaundice, Hematemesis, Abdominal Pain, Hepatomegaly, AscitesNCirrhosis, Encephalopathy, Esophageal VaricesANANASteroids, AZA, UDCAYRecoveryLiver transplantation
Santos et al[15], 2012ColombiaF35Headache, Jaundice, FatigueUCEsophageal VaricesANA, pANCA, SMANASteroids, UDCA, MSMYRecovery
Santos et al[15], 2012ColombiaF45Jaundice, Choluria, Acholia, HepatomegalyNSICHypothyroidismANA, SMANASteroids, AZA, UDCANRecovery
Saltik-Temizel et al[16], 2004TurkeyM11Jaundice, Itching, Abdominal Pain, Hepatomegaly, Splenomegaly, Fecal Occult BloodUCNonepANCA, SMANASteroids, AZA, UDCA, MSMYRecovery
Gopal et al[17], 1999; Nagral et al[18], 1999IndiaF14Jaundice, Hepatomegaly, Splenomegaly, AscitesNCirrhosis, Esophageal VaricesANANASteroids, D-penicillamineYRecoveryLiver transplantation
Lüth et al[19], 2009GermanyNANANANANANANANANANA
Farid et al[20], 2015BahrainF11Jaundice, Nausea, Vomit, Abdominal PainUCCirrhosisNANASteroids, AZAYDeathLiver transplantation
Floreani et al[21], 2005ItalyF26NANANANANANANANA
Floreani et al[21], 2005ItalyM19NANANANANANANANA
Floreani et al[21], 2005ItalyM32NANANANANANANANA
Floreani et al[21], 2005ItalyM27NANANANANANANANA
Floreani et al[21], 2005ItalyF15NANANANANANANANALiver transplantation
Floreani et al[21], 2005ItalyF15NANANANANANANANA
Floreani et al[21], 2005ItalyF16NANANANANANANANA
Gohlke et al[22], 1996; Zenouzi et al[23], 2014GermanyM19NANEsophageal VaricesANA, pANCA, SMAA1, A32, B8, Cw3, Cw7, DR3, DR4Steroids, AZA, UDCAYRecovery
Gohlke et al[22], 1996; Zenouzi et al[23], 2014GermanyM28NAUCEsophageal VaricesANA, pANCAA1, A32, B7, B8, Cw7, DR3, DR4, DR52, DR53, DQ2, DQ3Steroids, AZA, UDCAYRecovery
Gohlke et al[22], 1996; Zenouzi et al[23], 2014GermanyM18NANCirrhosis, Esophageal VaricesANA, pANCA, SMAA1, A25, B8, DR3Steroids, AZA, UDCAYRecoveryLiver transplantation
Abdo et al[24], 2002CanadaM15Jaundice, FatigueUCNoneANA, SMANASteroids, AZAYRecovery
Abdo et al[24], 2002CanadaM51Abdominal Pain, Weight Loss, FatigueNNoneANA, SMANASteroids, AZA, UDCAYRecovery
Abdo et al[24], 2002CanadaM54Abdominal Pain, Fatigue, SplenomegalyUCCirrhosis, Alcohol-induced PancreatitisNANASteroids, AZA, UDCA, MSMYRecovery
Abdo et al[24], 2002CanadaF25Jaundice, Itching, Abdominal Pain, Fatigue, HepatomegalyNNoneANA, SMANASteroids, AZA, UDCAYRecovery
Abdo et al[24], 2002CanadaF23FatigueUCNoneANA, SMANASteroids, AZA, UDCA, MSMYRecovery
Abdo et al[24], 2002CanadaM20Jaundice, Abdominal Pain, Weight Loss, Hepatomegaly, SplenomegalyNCirrhosisANA, SMANASteroids, AZA, UDCAYRecoveryLiver transplantation
van Buuren et al[25], 2000NetherlandsM7NAUCNoneANA, SMANASteroids, AZANARecovery
van Buuren et al[25], 2000NetherlandsM14NACDNoneANA, SMANASteroids, AZANARecovery
van Buuren et al[25], 2000NetherlandsF21NAUCNoneANA, pANCANASteroids, AZANARecovery
van Buuren et al[25], 2000NetherlandsF22NACDNoneANA, SMANASteroids, AZAYRecoveryLiver transplantation
van Buuren et al[25], 2000NetherlandsM20NAUCNoneSMANASteroids, AZA, UDCANARecovery
van Buuren et al[25], 2000NetherlandsM23NAUCCirrhosis, Esophageal VaricesANA, pANCANASteroids, AZA, UDCANARecovery
van Buuren et al[25], 2000NetherlandsM37NANNoneANANASteroids, AZA, UDCANARecovery
van Buuren et al[25], 2000NetherlandsM54NACDNoneANA, SMANASteroids, AZA, UDCAYRecoveryLiver transplantation
van Buuren et al[25], 2000NetherlandsF44JaundiceUCHepatic InsufficiencypANCANASteroids, AZA, UDCAYRecoveryLiver transplantation
Li et al[26], 2017ChinaM52Jaundice, ItchingNRheumatoid ArthritisNANASteroidsNRecovery
Gharibpoor et al[27], 2017IranM26Jaundice, Itching, Choluria, Acholia, Abdominal Pain, Weight Loss, HepatomegalyNNoneANA, SMANASteroids, AZA, UDCANRecovery
Sander et al[28], 2007GermanyM24CDNoneANA, SMAB8, DR4Steroids, AZA, UDCAYRecovery
Smolka et al[29], 2016Czech RepublicM16JaundiceNNoneANA, pANCANANANANA
Smolka et al[29], 2016Czech RepublicM17Diarrhea, Abdominal PainUCNonepANCANANANANA
Smolka et al[29], 2016Czech RepublicF15FatigueNNonepANCANANANANA
Smolka et al[29], 2016Czech RepublicM14UCNoneNA, pANCA, SMANANANANA
Smolka et al[29], 2016Czech RepublicF16CDNonepANCANANANANA
Smolka et al[29], 2016Czech RepublicF10Fever, Weight Loss, FatigueNSICNoneLKM1, pANCANANANANA
Smolka et al[29], 2016Czech RepublicM12Abdominal PainUCNonepANCANANANANA
Smolka et al[29], 2016Czech RepublicF9Melena, FatigueUCNoneANA, pANCANANANANA
Smolka et al[29], 2016Czech RepublicM3Diarrhea, Abdominal PainUCNoneANA, pANCANANANANA
Smolka et al[29], 2016Czech RepublicF9NNoneANA, pANCA, SMANANANANA
Smolka et al[29], 2016Czech RepublicF15Itching, Diarrhea, Abdominal PainCDNoneANA, pANCANANANANA
Griga et al[30], 2000United KingdomF24DiarrheaCDNoneANA, pANCANASteroids, MSM, UDCANRecovery
Griga et al[30], 2000United KingdomM28Jaundice, ItchingNNoneANA, pANCAB8, DR4Steroids, UDCANRecovery
Warling et al[31], 2014BelgiumM29Jaundice, FatigueUCMembranous GlomerulonephritispANCADR3Steroids, AZA, UDCA, MSM, 6-MPYRecovery
Hyslop et al[32], 2010United StatesNA40NAUCNoneANANANANANA
Hyslop et al[32], 2010United StatesNA24NAUCNoneANANANANANA
Hyslop et al[32], 2010United StatesNA53NACDCirrhosisANANANANANA
Hyslop et al[32], 2010United StatesNA37NAUCNoneANANANANANA
Hyslop et al[32], 2010United StatesNA32NAUCCirrhosisANANANANANA
Hyslop et al[32], 2010United StatesNA61NACDCirrhosisANANANANANA
Hyslop et al[32], 2010United StatesNA52NACDNoneANANANANANA
Hyslop et al[32], 2010United StatesNA26NACDCirrhosisANANANANANA
Hyslop et al[32], 2010United StatesNA33NAUCNoneANANANANANA
Hyslop et al[32], 2010United StatesNA44NAUCCirrhosisANANANANANA
Fukuda et al[33], 2012JapanM72AscitesNCirrhosis, Hepatocellular CarcinomaANA, AMADRB1*0405, DRB1*0901Steroids, UDCAYDeath
Hatzis et al[34], 2001GreeceF46Fever, Arthralgia, Fatigue, SplenomegalyNNephrectomy for Reflux NephropathyANA, pANCA, SMAA3, A11, B16, B35, Cw4, DR13, DR14, DR52, DQ6Steroids, AZA, UDCA, AntibioticsNRecovery
Thakker et al[35], 2010IndiaF9Fever, Jaundice, Itching, Arthralgia, Fatigue, Hepatomegaly, SplenomegalyNNoneANANASteroids, UDCANRecovery
Koskinas et al[36], 1999GreeceM18Fever, Jaundice, Hematochezia, Fatigue, Hepatomegaly, Splenomegaly, AscitesUCPyoderma GangrenosumNAA2, A32, B7, B21, B49, Bw4, Bw6, DR6, DR10, DR13Steroids, AZA, UDCA, MSM, AntibioticsYRecovery
Lucas et al[37], 2007United StatesM18Fecal incontinence, Abdominal PainUCNANANANANANA
Protzer et al[38], 1996SwitzerlandM22Jaundice, Nausea, Diarrhea, Abdominal Pain, FatigueUCPIGCHSMAA1, A2, B8, B44, Cw5, Cw7, DR3, DR52, DQ2Steroids, UDCAYRecovery
Protzer et al[38], 1996SwitzerlandF32NPIGCHpANCAA2, A28, B55, B67, Cw3, DR4, DR11, DQ2, DQ3Steroids, AZAYRecovery
Protzer et al[38], 1996SwitzerlandM28NCirrhosis, PIGCHANAA1, B8, DR3Steroids, AZAYDeath
Protzer et al[38], 1996SwitzerlandM26NPIGCHANAA1, B8, DR3Steroids, UDCAYRecovery
Hong-Curtis et al[39], 2004United StatesF34Jaundice, Itching, FatigueUCAnemiaANANASteroids, UDCA, AntibioticsYRecovery
Simão et al[40], 2012PortugalM15ItchingNNoneANA, AMANASteroids, AZA, UDCAYRecovery
Larsen et al[41], 2012DenmarkM10Vomiting, Diarrhea, Abdominal Pain, Weight LossCDNonepANCA, SMANASteroids, AZA, UDCANRecovery
Guerra et al[42], 2016PeruF22Jaundice, Choluria, Fatigue, Splenomegaly, AscitesNCirrhosis, Esophageal VaricesANAA2, A11, B35, B60, DR9, DR13Steroids, UDCAYRecoveryLiver transplantation
Ng et al[43], 2011AustraliaF33NANANANANAUDCANANA
Igarashi et al[44], 2017JapanF19NNoneANANASteroids, UDCAYRecovery
Igarashi et al[44], 2017JapanM61NRenal Cell CarcinomaNANASteroids, UDCAYRecovery
Gargouri et al[45], 2013TunisiaM10Jaundice, Abdominal Pain, Fatigue, Hepatomegaly, SplenomegalyNEsophageal VaricespANCANASteroids, AZA, UDCANRecovery
Patrico et al[46], 2013ItalyF7Fever, Acholia, HepatomegalyNNoneLKM1NASteroids, AZYRecovery
M: Male; F: Female; NA: Not available; ND: Not determined, IBD: Inflammatory bowel disease; CD: Crohn’s Disease, UC: Ulcerative Colitis, NSIC: Non Specific Inflammatory Colitis, OS: Overlap syndrome, PSC: Primary sclerosing cholangitis, AIH: Autoimmune hepatitis, PIGCH: Post-infantile Giant Cell Hepatitis, MSM: Mesalamine, SFZ: Sulfasalazine, UDCA: Ursodeoxycholic Acid, AZA: Azathioprine, 6-MP: 6-Mercaptopurine, IFX: Infliximab, ADM: Adalimumab, LKM1: Liver kidney microsome type 1 antibody, AMA: Anti-mitochondrial antibodies, ANA: Antinuclear antibody, SMA: Smooth muscle antibodies, pANCA: Perinuclear anti-neutrophil cytoplasmic antibodies.