Significance of HLA DR4 in type 1 autoimmune hepatitis

Czaja, Albert J.; Carpenter, Herschel A.; Santrach, Paula J.; Moore, S. Breanndan

doi:10.1016/0016-5085(93)90157-8

Cited by 198 publications

(114 citation statements)

References 33 publications

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“…These findings extend earlier observations relating clinical features and treatment results to HLA status [17][18] by demonstrating that the differences in clinical phenotype and outcome emerge gradually with age progression and that these transitions occur mainly at age 40 years and higher. The age-related differences in the nature of the immune diseases associated with autoimmune hepatitis also support the hypothesis that a transition occurs during adult life in immune response and targets.…”

Section: Discussionsupporting

confidence: 88%

“…Treatment failure is uncommon in patients with HLA DR4, 17,18 and the antigenic triggers of the immune response and the cytokine milieu propagated by immunocytes activated by the DR4-antigen complex may favor corticosteroid responsiveness. The pathogenic mechanisms in patients with HLA DR4 may be more dependent on cytokines modified by corticosteroid therapy than patients with HLA DR3.…”

Section: Discussionmentioning

confidence: 99%

“…27 Concurrent immune diseases were sought systematically in each patient according to protocol, 23 and HLA DR3 and DR4 were determined in each individual by restriction fragment length polymorphism (84 patients) or polymerase chain reaction with sequence specific primers (121 patients) according to methods reported previously. 17,18 Our study had been approved by the Institutional Review Board of the Mayo Clinic.…”

Section: Methodsmentioning

confidence: 99%

“…HLA DR3 has been associated with an earlier age of disease onset than HLA DR4 and a poorer response to corticosteroid therapy. 17,18 In Japan where HLA DR3 is uncommon, patients with autoimmune hepatitis typically have HLA DR4, and they tend to be elderly with mild disease and excellent treatment outcomes. 19,20 The HLA pheno-types of different age groups with autoimmune hepatitis in North America have not been fully defined.…”

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confidence: 99%

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Distinctive clinical phenotype and treatment outcome of type 1 autoimmune hepatitis in the elderly

2006

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Autoimmune hepatitis is classically a disease of young women. Our aims were to determine its occurrence, clinical phenotype, and outcome in elderly patients and contrast findings to young adults. Two-hundred-and-five white North American adults with definite type 1 autoimmune hepatitis were grouped according to age at presentation and the groups compared. Forty-seven patients (23%) were aged >60 years (median age, 68 years), and 31 patients (15%) were aged <30 years (median age, 25 years). The patients >60 years had a higher frequency of cirrhosis at presentation than the patients <30 years (33% versus 10%, P ‫؍‬ .03). They also had thyroid or rheumatic diseases more commonly (42% vs. 13%, P ‫؍‬ .006). HLA DR3 occurred more frequently in the patients <30 years than in those >60 years (58% vs. 23%, P ‫؍‬ .004), and HLA DR4 occurred more often in the patients >60 years (47% vs. 13%, P ‫؍‬ .003). Patients aged >60 years failed corticosteroid treatment less commonly than those aged <30 years (5% vs. 24%, P ‫؍‬ .03). Autoimmune hepatitis occurred in patients aged 18-30 years (15%), 31-39 years (15%), 40-49 years (21%), 50-59 years (25%), and >60 years (23%). Differences in age distribution, HLA frequencies, and treatment outcome occurred after age >40 years. In conclusion, elderly patients have a greater frequency of cirrhosis at presentation and HLA DR4 than patients <30 years, and they have a lower occurrence of treatment failure. Transitions in clinical and genetic phenotypes occur after age >40 years. Genetic susceptibilities may favor etiologic factors that are age-related. (HEPATOLOGY 2006;43:532-538.)

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Distinctive clinical phenotype and treatment outcome of type 1 autoimmune hepatitis in the elderly

2006

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“…Furthermore, HLA-DR3 was significantly more frequent in our patients with recurrence than in ethnically similar healthy subjects (71% v 19%; P ϭ .005). Because HLA DR3 is associated with a greater frequency of treatment failure than HLA-DR4, 27,44 its common occurrence in patients with type 1 autoimmune hepatitis who undergo liver transplantation is not surprising. 1,7 Our findings indicate that transplant recipients with HLA-DR3 and/or HLA-DR4 should be monitored closely for recurrent disease after transplantation.…”

Section: Discussionmentioning

confidence: 99%

Recurrent autoimmune hepatitis after orthotopic liver transplantation

González-Koch¹,

Czaja²,

Carpenter³

et al. 2001

Liver Transpl

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To determine the frequency, risk factors, and consequences of recurrent autoimmune hepatitis after liver transplantation, 41 patients with type 1 disease were monitored after surgery in accordance with a surveillance protocol. Tacrolimus or cyclosporine plus prednisone were administered to each patient, and liver biopsy examinations were performed at least annually according to protocol. Corticosteroid therapy was ultimately discontinued in only 2 patients. Recurrent disease was defined as the presence of lymphoplasmacytic infiltrates in liver tissue in the absence of other causes of allograft dysfunction. Autoimmune hepatitis recurred in 7 patients (17%), and the mean time to recurrence was 4.6 ؎ 1 years. Recurrence was asymptomatic in 4 of 7 patients and detected only by surveillance liver biopsy assessment in 2 patients. Histological changes were mild, and there was no progression to cirrhosis during 4.9 ؎ 0.9 years of observation. Five-year patient (86% v 82%; P ‫؍‬ .9) and graft (86% v 67%; P ‫؍‬ .5) survival rates were not statistically different between patients with and without recurrent disease. HLA-DR3 or HLA-DR4 occurred more commonly in patients with than without recurrence (100% v 40%; P ‫؍‬ .008) and healthy subjects (100% v 49%; P ‫؍‬ .01). Recurrent disease was unrelated to donor HLA status. In conclusion, recurrence after transplantation for type 1 autoimmune hepatitis is common. Its mild manifestations and favorable prognosis may reflect early detection by a surveillance protocol and/or continuous corticosteroid treatment. L iver transplantation is effective in the treatment of decompensated autoimmune hepatitis. Five-year patient and graft survival rates range from 83% to 92%, 1,2 and the actuarial 10-year survival rate after transplantation is 75%. 3,4 Furthermore, autoantibodies and hypergammaglobulinemia disappear in most patients within 2 years. 1,2 Despite these successes, recurrent disease is possible, 2,3,5-13 and recent reports have indicated that it may lead to cirrhosis and graft failure. 2,8,12 Furthermore, the immunoreactive propensity of the recipient may contribute to greater frequencies of acute rejection, steroid-resistant rejection, and chronic rejection, especially if corticosteroids are withdrawn in the posttransplantation period. [12][13][14][15] The reasons for recurrent disease are unclear, but associations have been made with corticosteroid withdrawal, 5,9,11,16 implantation of an HLA-DR3-negative liver into a HLA-DR3-positive recipient, 5,6,17 immunosuppressive regimens based on tacrolimus, 8,10,12 and pediatric propensities for aggressive disease. 8 However, findings in various centers have been discrepant regarding the prevalence of recurrence, its consequences, and its risk factors. The importance of HLA-DR3 mismatching between donor and recipient 3,5,6,11,12,13 and the impact of corticosteroid withdrawal on the recurrence of autoimmune hepatitis 5,9,14,18 are now disputed. Optimal results after transplantation require clarification of factors contributing to recurre...

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Increased frequency of HLA DR13 in hepatitis C virus carriers with persistently normal ALT levels

et al. 1996

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The aim of this study was to clarify the relationship between human leukocyte antigen DR allele distribution and the degree of liver cell injury of hepatitis C virus (HCV) carriers in Japan. The subjects, 68 HCV carriers, were divided into two groups according to the laboratory data and liver histology. Those in the asymptomatic carrier group (n = 19) had normal ALT levels persistently for 8-153 months (mean 25.7 months) and were diagnosed histologically as normal liver, nonspecific reactive hepatitis or chronic persistent hepatitis. Those in the chronic active hepatitis group (n = 49) had elevated ALT levels and were diagnosed histologically with chronic active hepatitis. The human leukocyte antigen DR alleles of all subjects were defined using the polymerase chain reaction restriction fragment length polymorphism method. The expression of human leukocyte antigen class I antigen and intercellular adhesion molecule 1 on the hepatocyte membrane were also examined in 14 patients from each group using an indirect immunohistochemical method. The frequency of DR13 (42.1%) in the asymptomatic carrier group was significantly higher (Pc < 0.003) than that of the chronic active hepatitis group (4.1%). There were no significant differences for the other DR alleles. The frequencies of expression of human leukocyte antigen class I antigen and intercellular adhesion molecule 1 on the hepatocyte membrane of the asymptomatic carrier group were significantly less than those of the chronic hepatitis group (64% vs. 100% P < 0.05, 29% vs. 71% P < 0.05, respectively), although there was no significant difference in the serum HCV-RNA titer between the two groups (10(6.4 +/- 1.1) vs. 10(6.5 +/- 0.7) copies/mL). These results demonstrate that the cellular immune response of the asymptomatic carrier group is less activated than the response of the chronic active hepatitis group and that HLA DR13 may be closely associated with this low activity of hepatitis among HCV carriers.

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Significance of HLA DR4 in type 1 autoimmune hepatitis

Cited by 198 publications

References 33 publications

Distinctive clinical phenotype and treatment outcome of type 1 autoimmune hepatitis in the elderly

Distinctive clinical phenotype and treatment outcome of type 1 autoimmune hepatitis in the elderly

Recurrent autoimmune hepatitis after orthotopic liver transplantation

Increased frequency of HLA DR13 in hepatitis C virus carriers with persistently normal ALT levels

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