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677 Association of fibrosis with inflammatory activity in autoimmune hepatitis: Reversal during corticosteroid therapy
HEPATOLOGY, Vol. 34, No. 4, Suppl. 1, 2003
AASLD ABSTRACTS
676 DIAGNOSING AUTOIMMUNE HEPATITIS IN CHILDREN: IS THE INTERNATIONAL AUTOIMMUNE HEPATITIS GROUP SCORING SYSTEM USEFUL? Regan L ~ bbeson, Richard
A Schreiber, University of British Columbia, BC Children's Hospital, Vancouver, BC, Canada Objective: In 1999, the International Autoimmune Hepatitis Group (IAIHG) revised a scoring system to differentiate adult patients with "definite" or "probable" autoimmune hepatitis (AIH) from those with "other" forms of chronic hepatitis. The present study assessed the utility of the scoring system in pediatric patients. We considered the exdusion of a score for alcohol intake and analyzed the variations in dassification when GGT was substituted for ALP as the enzymatic indicator of biliary disease. Methods: 28 pediatric patients with AIH and/or sclerosing cholangitis were reviewed. Clinical, laboratory, and histological data were collected in order to score patients both before and after standard treatment. All cholangiographic studies were reviewed. Results: There were 8 males and 20 females. The median age at diagnosis was 11 years (range 2-16). 21/28 were diagnosed as AIH, 3 as overlap syndrome, and 4 as primary sclerosing cholangitis (PSC). At presentation, 18121 (86%) with AIH scored as "definite" AIH; 3/21 (14%) scored as "probable". No patient clinically diagnosed as AIH scored as "other". Post-treatment, 4/21 (19%) scored as "probable": 2 have no evidence of biliary disease, 1 had an inconclusive ERCP, and I is awaiting ERCP. 7/28 patients had proven sclerosing cholangitis (SC): 4 had been considered to have PSC and all scored "other"; and 3 had been considered to have overlap syndrome and all scored as "definite" AIH. After removing points credited for <25 g alcohol intake and recalculating the scores, none of the patients were reclassified. W h e n GGT was substituted for ALP, 5 patients were reclassified from "definite" to "probable" pre-treatment. 4 of these 5 (80%) had an incomplete response to therapy: 2/4 have overlap syndrome, 1/4 had an inconclusive ERCP, and 1/4 has ultrasound evidence of extrahepatic biliary tree thickening and is awaiting ERCP. Conclusion: The revised IAIHG scoring system has utility in children. Patients who fall into the "other" category pre-treatment should have an ERCP study. The use of GGT instead of ALP in the scoring system may improve the specificity for pediatric patients, thus identifying those unlikely to respond to treatment and likely to have an overlapping syndrome. When GGT is used, patients dassified as "probable" pretreatment should also be considered for ERCP. Disclosures: Regan L Ebbeson - No relationships to disclose Richard A Schreiber - No relationships to disclose 677 ASSOCIATION OF FIBROSIS WITH INFLAMMATORY ACTIVITY IN AUTOIMMUNE HEPATITIS: REVERSAL DURING CORTICOSTEROID THERAPY. Albert J Czaja,
Herschel A Carpenter, Mayo Clinic, Rochester, MN Inflammatory activity stimulates fibrogenesis, and it is the key feature of autoimmune hepatitis and main target of corticosteroid therapy. Aims: Our goals were to assess the association of inflammatory activity with fibrosis and to evaluate the effect of corticosteroid therapy on the development of fibrosis. Methods: Three hundred twenty-five liver biopsy samples from 87 treated patients who had undergone successive tissue examinations were reviewed in batch under code by one pathologist and scored by the Ishak method for inflammatory activity (HAI) and fibrosis. Results: Fibrosis scores decreased (3.4+0.2 vs 2.6+02, p =0.0002) during 63+6 months of treatment and follow-up (range, 6-225 months), and the HAI also diminished (6.8+0.5 vs 2.1+02, p<0.0001). Fibrosis scores improved in 46 patients (53%) during 57+7 months and did not progress in 23 patients during 62+12 months. Only 18 patients (21%) had worsening fibrosis scores, and only 12 (14%) had fibrosis scores that increased by at least two points during 79+13 months. Liver tissue specimens obtained at presentation had higher fibrosis scores (3.5+0.2 vs 2.4+02, p=0.005) and HAI (10.5+0.5 vs 1.5+0.1, p<0.0001) than tissue samples obtained at remission. Similarly, liver specimens obtained at treatment failure had higher fibrosis scores (4+0.4 vs 1.7+0.5, p=0.03) and HAI (8.6+1.6 vs 12+0,3, p<0.0001) than those obtained during sustained remission after treatment. The fibrosis score improved more commonly in patients who had improvement in the histological activity indices than in
487A
others (61% versus 32%, p-0.02), and the frequency of histological cirrhosis decreased from 16% (14 patients) to 11% (10 patients), induding 8 patients in whom cirrhosis disappeared and 4 patients in whom cirrhosis developed. Conclusions:Fibrosis scores commonly improve or do not progress during corticosteroid therapy of autoimmune hepatitis. Improvement in fibrosis is associated with reduction in inflammation, and corticosteroid therapy may prevent or reverse fibrosis by reducing inflammatory activity. Histological cirrhosis may disappear. Disclosures: Herschel A Carpenter - No relationships to disclose Albert J Czaja - No relationships to disclose 678 AUTOIMMUNE HEPATITIS IN THE AFRICAN AMERICAN POPULATION. ~ nrique A Valdivia, Henry Ford Hospital, Detroit,
MI; Julia Greet, Wayne State University School of Medicine, Detroit, MI; Ivan P Cubas, Henry Ford Hospital, Detroit, MI; Milt Mutchnick, Wayne State University School of Medicine, Detroit, MI; Kimberly Brown, Dilip Moonka, Henry Ford Hospital, Detroit, MI Autoimmune hepatitis (AIH) is a persistent inflammation of the fiver of unknown etiology that predominately affects women. Several studies have suggested that gender and genetics can affect prognosis as well as susceptibility. However, few studies have looked at the effect of race and ethnicity on AIH. The current study specifically addresses the hypothesis that AIH has a more severe presentation and behaves more aggressively in the African American (AA) population. Methods: Using the database and the medical records of the Henry Ford Health System and the Wayne State University School of Medicine, we were able to identify 95 patients with a diagnosis of AIH. Of these, 42 patients were AA, 47 were white and 6 were other. The diagnosis was based on the International Autoimmune Hepatitis group scoring system. The AA patients were compared to the non-AA across a wide array of parameters evaluating severity of presentation, response to therapy and clinical outcome. Results: AA patients did not differ from non-AA in age (42.5 _+ 2.5 vs 45.9 _+ 23) or the percent of female patients (86% vs 81%).The baseline characteristics were similar in AA and non-AA patients. In both groups, over 70% of patients were symptomatic at presentation and jaundice was present in over half of patients (52% vs 58%) regardless of ethnidty. 17% of AA patients and 21% of non-AA presented with signs of hepatic decompensation and 10% and 6% presented with fulminant hepatic failure. 29% of AA patients and 43% of non-AA patients had other autoimmune phenomena and the rate of thyroid dysfunction was significantly less in AA patients (5%) than non-AA patients (34%: p<0.01). More AA patients (73%) had either cirrhosis or bridging fibrosis on biopsy than non-AA (58%) but this difference was not significant (p =0.182). There was no difference between AA and non-AA patients in bilirubin (8.1 -+ 1.5 vs 8.0 -+ 1.8 mg/dl), protime (17.9 _4_ _ 2,3 vs 15.1 -+ 1.2 sec) and ALT (556 _+ 93 vs 775 _+ 191 IU/L) at presentation. No significant differences were found between AA and non-AA with regards to response to therapy. In 52% and 68% (p =0.123) of patients respectively, fiver fi~-nctiontests returned to normal. A complete response was seen in 50% and 63% (p=0~238); partial response in 38% and 23% (p =0.135); no response in 13% and 15% (p=0.777); and relapse in 49% and 45% (p=0.709) respectively. There was no difference in prednisone doses at 3 and 12 months. Compliance with therapy was similar in both groups, with 60% of patients being hilly compliant. Mortality rates were also similar in both groups (10% vs 4%, p =0-239). Liver transplant was performed in 12% of AA and 15% of non-AA (p =0.653) patients. Conclusions: AA patients with AIH did not differ substantively compared to the non-AA population in the severity of presentation, prognosis, mortality or response to therapy. While more AA patients had either bridging fibrosis or cirrhosis on biopsy than non-AA patients, this difference was not significant (p=0.182). The only significant difference between groups was a more frequent association with thyroid dysfi~ncfion in the non-AA group. Similar numbers of patients ended up requiring fiver transplantation in both groups. Disclosures: Kimberly Brown - No relationships to disclose Ivan P Cubas - No relationships to disclose Julia Greer - No relationships to disclose Dilip Moonka - No relationships to disclose Mflt Mutchnick - No relationships to disclose Enrique A Valdivia - No relationships to disclose
AASLD ABSTRACTS
676 DIAGNOSING AUTOIMMUNE HEPATITIS IN CHILDREN: IS THE INTERNATIONAL AUTOIMMUNE HEPATITIS GROUP SCORING SYSTEM USEFUL? Regan L ~ bbeson, Richard
A Schreiber, University of British Columbia, BC Children's Hospital, Vancouver, BC, Canada Objective: In 1999, the International Autoimmune Hepatitis Group (IAIHG) revised a scoring system to differentiate adult patients with "definite" or "probable" autoimmune hepatitis (AIH) from those with "other" forms of chronic hepatitis. The present study assessed the utility of the scoring system in pediatric patients. We considered the exdusion of a score for alcohol intake and analyzed the variations in dassification when GGT was substituted for ALP as the enzymatic indicator of biliary disease. Methods: 28 pediatric patients with AIH and/or sclerosing cholangitis were reviewed. Clinical, laboratory, and histological data were collected in order to score patients both before and after standard treatment. All cholangiographic studies were reviewed. Results: There were 8 males and 20 females. The median age at diagnosis was 11 years (range 2-16). 21/28 were diagnosed as AIH, 3 as overlap syndrome, and 4 as primary sclerosing cholangitis (PSC). At presentation, 18121 (86%) with AIH scored as "definite" AIH; 3/21 (14%) scored as "probable". No patient clinically diagnosed as AIH scored as "other". Post-treatment, 4/21 (19%) scored as "probable": 2 have no evidence of biliary disease, 1 had an inconclusive ERCP, and I is awaiting ERCP. 7/28 patients had proven sclerosing cholangitis (SC): 4 had been considered to have PSC and all scored "other"; and 3 had been considered to have overlap syndrome and all scored as "definite" AIH. After removing points credited for <25 g alcohol intake and recalculating the scores, none of the patients were reclassified. W h e n GGT was substituted for ALP, 5 patients were reclassified from "definite" to "probable" pre-treatment. 4 of these 5 (80%) had an incomplete response to therapy: 2/4 have overlap syndrome, 1/4 had an inconclusive ERCP, and 1/4 has ultrasound evidence of extrahepatic biliary tree thickening and is awaiting ERCP. Conclusion: The revised IAIHG scoring system has utility in children. Patients who fall into the "other" category pre-treatment should have an ERCP study. The use of GGT instead of ALP in the scoring system may improve the specificity for pediatric patients, thus identifying those unlikely to respond to treatment and likely to have an overlapping syndrome. When GGT is used, patients dassified as "probable" pretreatment should also be considered for ERCP. Disclosures: Regan L Ebbeson - No relationships to disclose Richard A Schreiber - No relationships to disclose 677 ASSOCIATION OF FIBROSIS WITH INFLAMMATORY ACTIVITY IN AUTOIMMUNE HEPATITIS: REVERSAL DURING CORTICOSTEROID THERAPY. Albert J Czaja,
Herschel A Carpenter, Mayo Clinic, Rochester, MN Inflammatory activity stimulates fibrogenesis, and it is the key feature of autoimmune hepatitis and main target of corticosteroid therapy. Aims: Our goals were to assess the association of inflammatory activity with fibrosis and to evaluate the effect of corticosteroid therapy on the development of fibrosis. Methods: Three hundred twenty-five liver biopsy samples from 87 treated patients who had undergone successive tissue examinations were reviewed in batch under code by one pathologist and scored by the Ishak method for inflammatory activity (HAI) and fibrosis. Results: Fibrosis scores decreased (3.4+0.2 vs 2.6+02, p =0.0002) during 63+6 months of treatment and follow-up (range, 6-225 months), and the HAI also diminished (6.8+0.5 vs 2.1+02, p<0.0001). Fibrosis scores improved in 46 patients (53%) during 57+7 months and did not progress in 23 patients during 62+12 months. Only 18 patients (21%) had worsening fibrosis scores, and only 12 (14%) had fibrosis scores that increased by at least two points during 79+13 months. Liver tissue specimens obtained at presentation had higher fibrosis scores (3.5+0.2 vs 2.4+02, p=0.005) and HAI (10.5+0.5 vs 1.5+0.1, p<0.0001) than tissue samples obtained at remission. Similarly, liver specimens obtained at treatment failure had higher fibrosis scores (4+0.4 vs 1.7+0.5, p=0.03) and HAI (8.6+1.6 vs 12+0,3, p<0.0001) than those obtained during sustained remission after treatment. The fibrosis score improved more commonly in patients who had improvement in the histological activity indices than in
487A
others (61% versus 32%, p-0.02), and the frequency of histological cirrhosis decreased from 16% (14 patients) to 11% (10 patients), induding 8 patients in whom cirrhosis disappeared and 4 patients in whom cirrhosis developed. Conclusions:Fibrosis scores commonly improve or do not progress during corticosteroid therapy of autoimmune hepatitis. Improvement in fibrosis is associated with reduction in inflammation, and corticosteroid therapy may prevent or reverse fibrosis by reducing inflammatory activity. Histological cirrhosis may disappear. Disclosures: Herschel A Carpenter - No relationships to disclose Albert J Czaja - No relationships to disclose 678 AUTOIMMUNE HEPATITIS IN THE AFRICAN AMERICAN POPULATION. ~ nrique A Valdivia, Henry Ford Hospital, Detroit,
MI; Julia Greet, Wayne State University School of Medicine, Detroit, MI; Ivan P Cubas, Henry Ford Hospital, Detroit, MI; Milt Mutchnick, Wayne State University School of Medicine, Detroit, MI; Kimberly Brown, Dilip Moonka, Henry Ford Hospital, Detroit, MI Autoimmune hepatitis (AIH) is a persistent inflammation of the fiver of unknown etiology that predominately affects women. Several studies have suggested that gender and genetics can affect prognosis as well as susceptibility. However, few studies have looked at the effect of race and ethnicity on AIH. The current study specifically addresses the hypothesis that AIH has a more severe presentation and behaves more aggressively in the African American (AA) population. Methods: Using the database and the medical records of the Henry Ford Health System and the Wayne State University School of Medicine, we were able to identify 95 patients with a diagnosis of AIH. Of these, 42 patients were AA, 47 were white and 6 were other. The diagnosis was based on the International Autoimmune Hepatitis group scoring system. The AA patients were compared to the non-AA across a wide array of parameters evaluating severity of presentation, response to therapy and clinical outcome. Results: AA patients did not differ from non-AA in age (42.5 _+ 2.5 vs 45.9 _+ 23) or the percent of female patients (86% vs 81%).The baseline characteristics were similar in AA and non-AA patients. In both groups, over 70% of patients were symptomatic at presentation and jaundice was present in over half of patients (52% vs 58%) regardless of ethnidty. 17% of AA patients and 21% of non-AA presented with signs of hepatic decompensation and 10% and 6% presented with fulminant hepatic failure. 29% of AA patients and 43% of non-AA patients had other autoimmune phenomena and the rate of thyroid dysfunction was significantly less in AA patients (5%) than non-AA patients (34%: p<0.01). More AA patients (73%) had either cirrhosis or bridging fibrosis on biopsy than non-AA (58%) but this difference was not significant (p =0.182). There was no difference between AA and non-AA patients in bilirubin (8.1 -+ 1.5 vs 8.0 -+ 1.8 mg/dl), protime (17.9 _4_ _ 2,3 vs 15.1 -+ 1.2 sec) and ALT (556 _+ 93 vs 775 _+ 191 IU/L) at presentation. No significant differences were found between AA and non-AA with regards to response to therapy. In 52% and 68% (p =0.123) of patients respectively, fiver fi~-nctiontests returned to normal. A complete response was seen in 50% and 63% (p=0~238); partial response in 38% and 23% (p =0.135); no response in 13% and 15% (p=0.777); and relapse in 49% and 45% (p=0.709) respectively. There was no difference in prednisone doses at 3 and 12 months. Compliance with therapy was similar in both groups, with 60% of patients being hilly compliant. Mortality rates were also similar in both groups (10% vs 4%, p =0-239). Liver transplant was performed in 12% of AA and 15% of non-AA (p =0.653) patients. Conclusions: AA patients with AIH did not differ substantively compared to the non-AA population in the severity of presentation, prognosis, mortality or response to therapy. While more AA patients had either bridging fibrosis or cirrhosis on biopsy than non-AA patients, this difference was not significant (p=0.182). The only significant difference between groups was a more frequent association with thyroid dysfi~ncfion in the non-AA group. Similar numbers of patients ended up requiring fiver transplantation in both groups. Disclosures: Kimberly Brown - No relationships to disclose Ivan P Cubas - No relationships to disclose Julia Greer - No relationships to disclose Dilip Moonka - No relationships to disclose Mflt Mutchnick - No relationships to disclose Enrique A Valdivia - No relationships to disclose