Original Article
Azathioprine for Long-Term Maintenance of Remission in Autoimmune Hepatitis
N Engl J Med 1995; 333:958-963October 12, 1995
- Abstract
Background
In most patients with autoimmune hepatitis, remission can be maintained with prednisolone, usually in combination with azathioprine, but the majority of patients have a relapse when treatment is stopped and therefore require long-term therapy. Because prolonged corticosteroid therapy may have serious toxic effects, in 1984 we undertook a controlled trial of maintenance therapy with azathioprine alone. None of the 25 patients in that trial had relapses during the follow-up period of one year. We have now followed these 25 patients for 10 years and have treated an additional 47 patients in a similar manner.
Methods
The 72 patients (median age, 47 years; range, 14 to 71) had been in complete remission for at least one year with 5 to 15 mg of prednisolone per day and 1 mg of azathioprine per kilogram of body weight per day. The dose of azathioprine was increased to 2 mg per kilogram per day, and the prednisolone was gradually withdrawn. Remission was defined as the absence of symptoms suggestive of a relapse and serum globulin and aspartate aminotransferase concentrations within the normal range, with or without a liver biopsy showing only minimal inflammation.
Results
Sixty patients (83 percent) remained in remission while receiving azathioprine alone for a median of 67 months (range, 12 to 128). Of 48 follow-up liver biopsies in 42 patients, 45 showed inactive or minimal disease, and 3 showed moderate disease (2 after one year of therapy and 1 after eight years). After the prednisolone had been withdrawn, 26 patients lost their cushingoid facies, and 32 patients lost weight (median loss, 6.4 kg; range, 1.5 to 22.3). The most common adverse effect was arthralgia (in 38 patients). With the higher dose of azathioprine, four patients had myelosuppression, defined as a decrease in the leukocyte and platelet counts to less than 4000 and 150,000 per cubic millimeter, respectively. Two of these patients (both with pancytopenia) relapsed when the azathioprine was withdrawn; in the other two, remission was maintained with the resumption of prednisolone. Lymphopenia developed in 32 of 56 patients treated with 2 mg of azathioprine per kilogram per day for more than two years. During follow-up, nine patients died: one of liver failure and eight of causes not directly related to their liver disease.
Conclusions
Many patients with autoimmune hepatitis who have been in complete remission for at least one year with prednisolone and azathioprine can remain in remission with a higher dose of azathioprine alone.
Media in This Article
Figure 1
Kaplan–Meier Analysis of the Cumulative Probability of Sustained Remission during Treatment with 2 mg of Azathioprine per Kilogram per Day in Patients with Autoimmune Hepatitis.Table 1
Base-Line Characteristics of 72 Patients with Autoimmune Hepatitis Treated with Azathioprine.Article Activity
- Article
Since the early 1970s corticosteroids, often in combination with azathioprine, have been standard therapy for autoimmune hepatitis.1-4 Most patients can be maintained in remission for long periods, but a true cure is rare. Since the majority of patients have a relapse when treatment is withdrawn,5,6 prolonged immunosuppressive therapy is usually required. In addition to the well-recognized cosmetic effects of corticosteroids, there is a risk of more severe complications, such as cataracts, diabetes mellitus, hypertension, osteoporosis, and psychosis. Azathioprine can induce myelosuppression and has possible teratogenic and oncogenic effects.7
We have conducted three controlled trials of the withdrawal of one or both medications in patients with autoimmune hepatitis who remained in remission for long periods with 5 to 15 mg of prednisolone per day and 1 mg of azathioprine per kilogram of body weight per day. In the first trial,5 conducted in 1980, we withdrew both medications in a group of 30 patients. Only 5 of the 30 (17 percent) were still in remission by the end of the 1-year trial period; 3 of these patients subsequently had relapses 1.5, 2, and 11 years after stopping treatment. In the second trial, azathioprine was stopped and prednisolone was continued at maintenance doses (5 to 12.5 mg per day) in 27 patients. The calculated cumulative probability of a relapse within three years was 32 percent in this group of patients, as compared with 6 percent in 23 patients who continued to take both medications.8 In 1984, we began a third trial, in which patients received a higher dose of azathioprine (2 mg per kilogram per day) after the withdrawal of prednisolone.9 In contrast to the results of the previous trials, no patients had relapses during the one-year follow-up period. Because the side effects of prolonged use of azathioprine at this dose were uncertain, we continued to monitor the patients. We report data from the 10-year prospective follow-up of the first 25 patients undergoing this regimen, as well as data on an additional 47 patients treated in a similar manner.
Methods
The 72 patients were selected from a total cohort of 101 patients born in the United Kingdom (24 males and 77 females) who met the enrollment criteria, had had regular follow-up examinations at our clinic for at least 3 years (median, 12; range, 3 to 25), and had complete records available. Twenty-nine patients continued to receive prednisolone (21 with azathioprine and 8 without it) for the following reasons: they had not had a complete remission continuously for at least one year with maintenance therapy (11 patients); they had adverse reactions (myelosuppression, rashes, or nausea and malaise) when azathioprine was first introduced, necessitating the discontinuation of the drug (8 patients); they had relapses whenever the dose of corticosteroid was reduced to less than 5 mg per day (3 patients); or they declined to stop taking the corticosteroid (5 patients). In addition, two patients had not received any treatment since 1980.5
At presentation, the 72 patients ranged in age from 14 to 71 years (median, 47). All 72 had had hyperglobulinemia, elevated serum aspartate aminotransferase concentrations (normal value, <50 U per liter), and liver biopsies showing moderate periportal inflammation with piecemeal necrosis or severe inflammation (with bridging necrosis) (Table 1Table 1
Base-Line Characteristics of 72 Patients with Autoimmune Hepatitis Treated with Azathioprine.). All the patients met the provisional criteria for the diagnosis of definite or probable autoimmune hepatitis.10 Sixty-three patients had circulating antinuclear or smooth-muscle autoantibodies (or both) at titers of 1:40 or higher (median, 1:160; range, 1:40 to 1:5120), and two had elevated titers of liver–kidney microsomal antibodies (1:320 and 1:640, respectively). The seven patients who did not have any of these autoantibodies were seropositive for antibodies against the hepatic asialoglycoprotein receptor.11 None of the patients had a history of parenteral exposure to blood or blood products. All were seronegative for hepatitis B surface antigen and for antibodies against the hepatitis C virus. Other possible causes of liver disease were excluded by appropriate investigations. HLA phenotypes were determined in 64 patients, as previously described.12,13 The study was approved by the ethics committee of King's College Hospital. All patients provided written informed consent.The first 25 patients9 and the additional 47 patients had had complete clinical, biochemical, and histologic remission with 5 to 15 mg of prednisolone per day and 1 mg of azathioprine (Imuran) per kilogram per day for at least 1 year (median, 22 months; range, 12 to 74) before the prednisolone was withdrawn. The dose of azathioprine was increased to the nearest approximation of 2 mg per kilogram per day obtainable with 25-mg tablets (100 to 200 mg per day). Prednisolone was withdrawn in decrements of 2.5 mg per day every two weeks. Twenty-six of the 72 patients consented to a reduction of the dose of azathioprine to 1.5 mg per kilogram per day for 1 month, then to 1 mg per kilogram per day, after they had been in remission with a dose of 2 mg per kilogram per day for at least 1 year (median, 40 months; range, 12 to 70).
For the purposes of this study, a relapse of hepatitis was defined as a threefold increase in the serum aspartate aminotransferase concentration above the normal value (<50 U per liter) or, in four cases, a smaller increase (71 to 109 U per liter) with an elevated serum globulin concentration (4.1 to 5.2 g per deciliter; normal value, <3.5) and the reemergence of symptoms (increasing lethargy, anorexia, malaise, nausea, abdominal pain, arthralgia or myalgia, or jaundice). Remission was defined as the absence of symptoms suggestive of a relapse and serum globulin and aspartate aminotransferase concentrations within the normal range, with or without a liver biopsy showing only minimal inflammation and no necrosis.
Three main time points were used for the analysis: the date of presentation, the date on which the prednisolone was stopped, and the date of the patient's most recent clinic visit before June 1, 1995, or the date on which treatment with azathioprine alone (2 mg per kilogram per day) was changed, for whatever reason. Statistical analyses were performed with the paired t-test, the Mann–Whitney U test, or Fisher's exact test, as appropriate.14 All tests were two-tailed.
Results
Of the 72 patients whose treatment was changed to azathioprine alone at a dose of 2 mg per kilogram per day, 12 had relapses. Seven of the 12 patients with relapses (1 each at 7, 9, 12, 14, 23, 40, and 59 months) had no obvious precipitating factors. Pancytopenia developed in two patients (at six months in one, and at eight months in the other); in both, the dose of azathioprine was reduced to 1 mg per kilogram per day, and both had relapses within a month after the dose reduction. Three patients had relapses with precipitating factors: chickenpox in one patient at 14 months, pregnancy in another patient, and the discontinuation of therapy at 23 months in the third. The other 60 patients (83 percent) remained in remission with azathioprine alone at a dose of 2 mg per kilogram per day for a median of 67 months (range, 12 to 128) (Figure 1Figure 1
Kaplan–Meier Analysis of the Cumulative Probability of Sustained Remission during Treatment with 2 mg of Azathioprine per Kilogram per Day in Patients with Autoimmune Hepatitis.).Forty-two patients consented to undergo liver biopsies on at least one occasion after one to eight years of treatment with the higher dose of azathioprine (Table 2Table 2
Histologic Findings in 48 Liver-Biopsy Specimens from 42 Patients with Autoimmune Hepatitis Treated with Azathioprine Alone (2 mg per Kilogram per Day).). One patient had a biopsy at one year that showed moderate disease activity, but clinical and biochemical remission continued for four more years before relapse. A second patient with a biopsy showing moderate activity at one year was still in complete clinical and biochemical remission five years later. A third patient had histologically inactive disease at two years, but another biopsy six years later showed moderate disease activity. She was still asymptomatic, with normal biochemical liver tests, three years after the second biopsy. The biopsies in the other 39 patients showed inactive disease or only minimal inflammation without necrosis. Two patients with minimal activity at 1 year had relapses 2 and 6 years later, within 8 and 24 months, respectively, after the reduction of the dose of azathioprine to 1 mg per kilogram per day.Changes in Hematologic and Biochemical Variables
Four patients had overt myelosuppression, defined for purposes of this study as a progressive decrease in both leukocyte and platelet counts to values below the lower limits of normal (4000 and 150,000 per cubic millimeter, respectively). In addition to the two patients who had pancytopenia and relapses when the dose of azathioprine was reduced, two patients had myelosuppression after 19 and 22 months, respectively. In both patients, remission was maintained by readministering prednisolone before discontinuing azathioprine; the myelosuppression resolved in both cases. A fifth patient had transient leukopenia that was corrected within three months (without the reintroduction of prednisolone) by reducing the dose of azathioprine to 1 mg per kilogram per day. The leukopenia did not recur when the dose of azathioprine was subsequently increased to 2 mg per kilogram per day. Two other patients had leukocyte counts between 3000 and 4000 per cubic millimeter throughout the study, but no adjustment in the dose of azathioprine was considered necessary. Apart from these seven patients, all the patients had leukocyte counts within the normal range. There was, however, a significant overall decrease in the white-cell count between the start and the end of the study in the patients receiving 2 mg of azathioprine per kilogram per day (Table 3Table 3
Hematologic and Serum Biochemical Indexes of Cholestasis in 58 of the 60 Patients with Autoimmune Hepatitis Who Did Not Have Relapses with Azathioprine Alone (2 mg per Kilogram per Day).). Ten patients had platelet counts of less than 150,000 per cubic millimeter at the start of the period when the dose of prednisolone was tapered. The thrombocytopenia did not worsen (and improved in five of the patients) with the higher dose of azathioprine given alone.Lymphopenia was a frequent finding. The mean (±SD) lymphocyte count in the 56 patients receiving 2 mg of azathioprine per kilogram per day for at least two years was 1300±500 per cubic millimeter, with 32 patients having counts below the lower normal limit of 1500 per cubic millimeter. These counts were not significantly affected by reducing the dose of azathioprine to 1 mg per kilogram per day (mean lymphocyte counts before and after the dose reduction in 26 patients, 1300±400 and 1400±500 per cubic millimeter, respectively; P = 0.19), nor were the counts significantly different from those in the 27 patients who continued to receive either prednisolone alone (1000±500 per cubic millimeter) or combination therapy (1200±500 per cubic millimeter; P = 0.47).
There was no evidence that the higher dose of azathioprine induced cholestasis. Between the start and the end of the study, there was a significant reduction in serum γ-glutamyltransferase activity (Table 3).
Effects of Corticosteroid Withdrawal
Forty patients (56 percent) had symptoms associated with the withdrawal of prednisolone; in 38 of the 40, the main symptom was arthralgia affecting the knees, elbows, and fingers. In 30 patients, the arthralgia lasted less than six months and was relieved with mild analgesic treatment (acetaminophen). In eight patients, the arthralgia was more prolonged and severe, requiring the administration of nonsteroidal antiinflammatory drugs. In 10 patients, the arthralgia was accompanied by myalgias (lasting 2 to 10 months; median, 4) affecting the legs and arms. Other symptoms included increased lethargy (in seven patients), nausea for no more than 2 months (in five), diarrhea for no more than 10 days (in three), bilateral Achilles tendinitis for 2 months (in one), a petechial rash lasting 3 weeks (in one), and pruritus for 1 week (in one).
Cushingoid facies (in 26 patients initially) disappeared after the prednisolone had been withdrawn. Thirty-two patients lost 1.5 to 22.3 kg of body weight (median, 6.4).
After one year of therapy with azathioprine alone, the patients were asked, “How do you feel since stopping steroids?” Thirty-six patients, including 15 who had arthralgia, responded that they were “better” or “much better,” and 32 said they were “about the same.” Four patients said they felt “worse” but did not wish to resume treatment with prednisolone.
Overall Outcome
During the follow-up period, nine patients (all women) died: one of liver failure and eight of causes not directly related to the liver disease (Table 4Table 4
Data on the Nine Women with Autoimmune Hepatitis Who Died during Follow-up.). Four of the patients died of primary cancers. Another patient, a man with autoimmune hepatitis for seven years, had a lymphoma on his forehead after six years of treatment with azathioprine alone at a dose of 2 mg per kilogram per day. The tumor was excised, and he was given local radiotherapy. No evidence of lymphoma at other sites was found, and he was well two years later. The cumulative dose of azathioprine in the 5 patients with cancer (median, 282 g; range, 198 to 499) was not significantly different from the cumulative dose in the 67 patients without malignant disease (median, 354 g; range, 87 to 734; P = 0.33).Three unplanned pregnancies occurred in two patients receiving azathioprine alone at a dose of 2 mg per kilogram per day. One patient had a relapse at 29 weeks' gestation (after 26 months of treatment with the higher dose of azathioprine), and prednisolone was restarted. She had no other problems with her pregnancy and subsequently delivered a healthy baby. The other patient, who had been receiving 2 mg of azathioprine per kilogram per day for 75 months, died of severe pulmonary hypertension at 25 weeks' gestation (Table 4). Four years earlier, while taking the higher dose of azathioprine, she had delivered a healthy baby after an uncomplicated pregnancy.
Of the 26 patients who agreed to have the dose of azathioprine reduced to 1 mg per kilogram per day, 5 had relapses (1 each at 8, 13, 24, 25, and 26 months after the dose reduction), 1 died of a myocardial infarction 1 year after the dose reduction (Table 4), and 14 continued to be in remission for a median of 57 months (range, 24 to 77). The other six patients requested that all treatment be stopped (one each at 6, 18, 20, 24, 25, and 32 months after the dose reduction); two had relapses (one 10 months and one 26 months after stopping treatment), and four continued to be in remission for 6, 8, 46, and 55 months.
Overall, treatment with azathioprine alone (2 mg per kilogram per day) was changed or stopped in 49 of the 72 patients: the dose was electively reduced in 26 patients, and the treatment was altered or discontinued in 23 because of relapses, complications, or death. The other 23 patients remained in remission with the higher dose of azathioprine alone for a median of 109 months (range, 39 to 128). No variables were identified at presentation or subsequently that predicted which patients would remain in remission with either dose of azathioprine alone or in which patients the drug could be withdrawn altogether.
Discussion
In a previous study of 30 patients with autoimmune hepatitis, we found that 25 (83 percent) of those who had a remission with immunosuppressive therapy had relapses within one year after all treatment had been stopped.5 Three additional patients had relapses after a longer period of follow-up, for a total relapse rate of 93 percent. The current study indicates that the higher dose of azathioprine alone is a therapeutic option for about 80 percent of patients with autoimmune hepatitis who have had a complete remission for at least one year with maintenance doses of prednisolone and azathioprine. For an individual patient, the most appropriate maintenance regimen depends on the frequency and severity of the side effects associated with these two drugs when taken for both short and long periods. Treatment with azathioprine alone at a dose of 2 mg per kilogram per day reversed the cushingoid facies and weight gain that had been associated with prednisolone therapy in 44 percent of our patients (other complications were rare), and most of the patients reported that they felt better (or at least did not feel worse), despite the development of arthralgias after the prednisolone had been withdrawn. The psychological benefit of discontinuing corticosteroid therapy is substantial. We believe that this approach is likely to improve compliance with therapy, particularly among young women.
Most of our patients did not have serious myelosuppression or other toxic effects. Azathioprine has been implicated in the development of nodular regenerative hyperplasia in the recipients of liver, kidney, and bone marrow transplants and in isolated cases of other conditions (multiple sclerosis, myasthenia gravis, and psoriasis).15,16 Liver biopsies showed no evidence of such abnormalities in our patients, nor were there the clinical indications of portal hypertension or the biochemical evidence of cholestasis usually associated with nodular regenerative hyperplasia.15 Since many patients declined a liver biopsy when they were asymptomatic and had normal liver-function tests, we cannot be certain that all the patients had histologic remission. Nonetheless, the data reported here and in our previous study9 suggest that the majority of the patients had histologic remission. It is noteworthy, however, that periodic abnormal findings on liver biopsy did not predict relapses (possibly because of a sampling bias). Nevertheless, liver biopsies at two-to-three-year intervals should probably be part of the routine follow-up of patients receiving the treatment used in this study.
Among the patients who had relapses or myelosuppression, the failure to remain in remission with azathioprine alone may have been related to genetic differences in the metabolism of the drug.17-21 We found no evidence of two other potential side effects of high doses of azathioprine or long-term treatment with the drug: teratogenesis and carcinogenesis. The incidence of azathioprine-related congenital abnormalities is reportedly very low,22 but experience is limited, and the drug's safety during pregnancy has not yet been fully established.22 The risk to the fetus associated with a relapse of autoimmune hepatitis during pregnancy is much higher than that associated with azathioprine therapy.23 Nevertheless, our current policy with women who plan to become pregnant while taking azathioprine is to reintroduce, or increase the dose of, corticosteroids and withdraw azathioprine.
There is concern that immunosuppressive therapy, particularly with higher doses of azathioprine, may increase the risk of malignant disease. An increased risk of extrahepatic cancer (odds ratio, 1.4; 95 percent confidence interval, 0.6 to 2.9) was reported in 103 patients with autoimmune hepatitis receiving 50 mg of azathioprine per day, as compared with 103 age- and sex-matched normal persons.24 An increased incidence of both lymphomatous and nonlymphomatous cancers was noted in 202 patients with rheumatoid arthritis receiving very high doses of azathioprine (median dose, 300 mg per day).25 This incidence did not differ significantly from that in patients with rheumatoid arthritis who did not receive the drug, suggesting that there was some risk associated with rheumatoid arthritis itself.25 Viteri et al.26 have suggested that, like some other diseases in which immune responsiveness is disturbed, autoimmune hepatitis may be associated with an inherently increased risk of malignant disease that is further increased by immunosuppressive therapy. Our data suggest that this additional risk is small. Most cancers associated with immunosuppressive therapy are lymphomas or squamous carcinomas of the skin.27 In our series, there was one lymphoma; the other cancers that developed were those that are common in people in the age range of our patients.
The use of corticosteroids and azathioprine for the treatment of autoimmune hepatitis was developed empirically, but the rationale is now understood. Liver injury in autoimmune hepatitis is probably mediated by antibody-dependent cellular cytotoxic reactions, in which liver-specific autoantibodies cooperate with a subpopulation of non–T lymphocytes (K cells) in damaging hepatocytes, rather than by direct cytotoxic effects mediated by T cells or natural killer cells.28 Prednisolone rapidly suppresses the production of immunoglobulins (including autoantibodies), whereas azathioprine is thought to act on K cells (and natural killer cells), but its effects are manifested more slowly.29-32 Indeed, it seems to take up to six months for K cells to disappear from the circulation,33 which probably explains why remission cannot usually be induced by azathioprine alone and why the drug needs to be administered for several months before its corticosteroid-sparing effect allows the reduction of the dose of prednisolone to low maintenance levels.
In summary, our findings indicate that once complete remission has been induced and sustained with combination therapy for at least one year, prednisolone can be withdrawn, and the majority of patients will remain in remission with azathioprine given alone. After a further period of remission with the higher dose of azathioprine, it is possible in many instances to maintain the remission at the more conventional dose of 1 mg of azathioprine per kilogram per day.
We are indebted to Dr. B.C. Portmann for histologic assessment of the liver-biopsy specimens, to Dr. P.T. Donaldson for providing the HLA data, and to Dr. Barbara M. McFarlane for providing the data on anti–asialoglycoprotein-receptor antibodies.
Source Information
From the Institute of Liver Studies, King's College Hospital and School of Medicine and Dentistry, London.
Address reprint requests to Dr. McFarlane at the Institute of Liver Studies, King's College Hospital, Denmark Hill, London SE5 9RS, United Kingdom.
- References
References
1
The Copenhagen Study Group for Liver Diseases
Web of Science | Medline2
Cook GC ,Mulligan R ,Sherlock S . Controlled prospective trial of corticosteroid therapy in active chronic hepatitis. Q J Med 1971;40:159-185
Web of Science | Medline3
Soloway RD ,Summerskill WHJ ,Baggenstoss AH , et al. Clinical, biochemical, and histological remission of severe chronic active liver disease: a controlled study of treatments and early prognosis. Gastroenterology 1972;63:820-833
Web of Science | Medline4
Murray-Lyon IM ,Stern RB ,Williams R . Controlled trial of prednisone and azathioprine in active chronic hepatitis. Lancet 1973;1:735-737
CrossRef | Web of Science | Medline5
Hegarty JE ,Nouri Aria KT ,Portmann B ,Eddleston ALWF ,Williams R . Relapse following treatment withdrawal in patients with autoimmune chronic active hepatitis. Hepatology 1983;3:685-689
CrossRef | Web of Science | Medline6
Czaja AJ ,Beaver SJ ,Shiels MT . Sustained remission after corticosteroid therapy of severe hepatitis B surface antigen-negative chronic active hepatitis. Gastroenterology 1987;92:215-219
Medline7
Czaja AJ. Treatment of autoimmune hepatitis. In: Nishioka M, Toda G, Zeniya M, eds. Autoimmune hepatitis. Amsterdam: Elsevier, 1994:283-304.
8
Stellon AJ ,Hegarty JE ,Portmann B ,Williams R . Randomised controlled trial of azathioprine withdrawal in autoimmune chronic active hepatitis. Lancet 1985;1:668-670
CrossRef | Web of Science | Medline9
Stellon AJ ,Keating JJ ,Johnson PJ ,McFarlane IG ,Williams R . Maintenance of remission in autoimmune chronic active hepatitis with azathioprine after corticosteroid withdrawal. Hepatology 1988;8:781-784
CrossRef | Web of Science | Medline10
Johnson PJ ,McFarlane IG . Meeting report: International Autoimmune Hepatitis Group. Hepatology 1993;18:998-1005
CrossRef | Web of Science | Medline11
McFarlane BM ,McSorley CG ,Vergani D ,McFarlane IG ,Williams R . Serum autoantibodies reacting with the hepatic asialoglycoprotein receptor protein (hepatic lectin) in acute and chronic liver disorders. J Hepatol 1986;3:196-205
CrossRef | Web of Science | Medline12
Donaldson PT ,Doherty DG ,Hayllar KM ,McFarlane IG ,Johnson PJ ,Williams R . Susceptibility to autoimmune chronic active hepatitis: human leukocyte antigens DR4 and A1-B8-DR3 are independent risk factors. Hepatology 1991;13:701-706
CrossRef | Web of Science | Medline13
Doherty DG ,Vaughan RW ,Donaldson PT ,Mowat AP . HLA DQA, DQB, and DRB genotyping by oligonucleotide analysis: distribution of alleles and haplotypes in British caucasoids. Hum Immunol 1992;34:53-63
CrossRef | Web of Science | Medline14
Diem K, Seldrup J. Introduction to statistics, statistical tables, mathematical formulae. In: Lentner C, ed. Geigy scientific tables. Vol. 2. Basel, Switzerland: Ciba–Geigy, 1982.
15
Naber AH ,Van Haelst U ,Yap SH . Nodular regenerative hyperplasia of the liver: an important cause of portal hypertension in non-cirrhotic patients. J Hepatol 1991;12:94-99
CrossRef | Web of Science | Medline16
Gane E ,Portmann B ,Saxena R ,Wong P ,Ramage J ,Williams R . Nodular regenerative hyperplasia of the liver graft after liver transplantation. Hepatology 1994;20:88-94
CrossRef | Web of Science | Medline17
Van Scoik KG ,Johnson CA ,Porter WR . The pharmacology and metabolism of the thiopurine drugs 6-mercaptopurine and azathioprine. Drug Metab Rev 1985;16:157-174
CrossRef | Web of Science | Medline18
Schmiegelow K ,Kriegbaum NJ . 6-Thioguanine nucleotide accumulation in erythrocytes during azathioprine treatment for systemic connective tissue diseases: a possible index for monitoring treatment. Ann Rheum Dis 1993;52:152-154
CrossRef | Web of Science | Medline19
Weinshilboum RM ,Sladek SL . Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet 1980;32:651-662
Web of Science | Medline20
Lennard L ,Van Loon JA ,Weinshilboum RM . Pharmacogenetics of acute azathioprine toxicity: relationship to thiopurine methyltransferase genetic polymorphism. Clin Pharmacol Ther 1989;46:149-154
CrossRef | Web of Science | Medline21
Lennard L ,Lilleyman JS ,Van Loon J ,Weinshilboum RM . Genetic variation in response to 6-mercaptopurine for childhood acute lymphoblastic leukaemia. Lancet 1990;336:225-229
CrossRef | Web of Science | Medline22
Golbus MS . Teratology for the obstetrician: current status. Obstet Gynecol 1980;55:269-277
Web of Science | Medline23
Witter FR, King TM. Drugs and the management of chronic diseases in the pregnant patient. In: Stern L, ed. Drug use in pregnancy. Balgowlah, Australia: ADIS Health Science Press, 1984:190-211.
24
Wang KK ,Czaja AJ ,Beaver SJ ,Go VL . Extrahepatic malignancy following long-term immunosuppressive therapy of severe hepatitis B surface antigen-negative chronic active hepatitis. Hepatology 1989;10:39-43
CrossRef | Web of Science | Medline25
Silman AJ ,Petrie J ,Hazleman B ,Evans SJ . Lymphoproliferative cancer and other malignancy in patients with rheumatoid arthritis treated with azathioprine: a 20 year follow up study. Ann Rheum Dis 1988;47:988-992
CrossRef | Web of Science | Medline26
Viteri A ,Vernace SJ ,Schaffner F . Extrahepatic malignancy in chronic liver disease: report of six cases. Gastroenterology 1976;71:1075-1078
Web of Science | Medline27
Kinlen LJ . Incidence of cancer in rheumatoid arthritis and other disorders after immunosuppressive treatment. Am J Med 1985;78:44-49
CrossRef | Web of Science | Medline28
McFarlane IG, Eddleston ALWF. Chronic active hepatitis. In: Targan SR, Shanahan F, eds. Immunology and immunopathology of the liver and gastrointestinal tract. New York: Igaku-Shoin, 1990:281-304.
29
Nouri-Aria KT ,Hegarty JE ,Alexander GJM ,Eddleston ALWF ,Williams R . Effect of corticosteroids on suppressor-cell activity in “autoimmune“ and viral chronic active hepatitis. N Engl J Med 1982;307:1301-1304
Full Text | Web of Science | Medline30
Pedersen BK ,Beyer JM ,Rasmussen A , et al. Azathioprine as single drug in the treatment of rheumatoid arthritis induces complete suppression of natural killer cell activity. Acta Pathol Microbiol Immunol Scand [C] 1984;92:221-225
Medline31
Prince HE ,Ettenger RB ,Dorey FJ ,Fine RN ,Fahey JL . Azathioprine suppression of natural killer activity and antibody-dependent cellular cytotoxicity in renal transplant recipients. J Clin Immunol 1984;4:312-318
CrossRef | Web of Science | Medline32
Nouri-Aria KT ,Hegarty JE ,Alexander GJM ,Eddleston ALWF ,Williams R . IgG production in “autoimmune“ chronic active hepatitis: effect of prednisolone on T and B lymphocyte function. Clin Exp Immunol 1985;61:290-296
Web of Science | Medline33
Pedersen BK ,Beyer JM . A longitudinal study of the influence of azathioprine on natural killer cell activity. Allergy 1986;41:286-289
CrossRef | Web of Science | Medline
- Citing Articles (101)
Citing Articles
1
Christian P. Strassburg, Michael P. Manns. 2012. Autoimmune Hepatitis. , 721-737.
CrossRef2
Christian P. Strassburg, Michael P. Manns. (2011) Therapy of autoimmune hepatitis. Best Practice & Research Clinical Gastroenterology 25:6, 673-687
CrossRef3
Stephen Kriese, Michael A. Heneghan. (2011) Autoimmune hepatitis. Medicine 39:10, 580-584
CrossRef4
Kalliopi Zachou, Nikolaos Gatselis, Georgia Papadamou, Eirini I. Rigopoulou, George N. Dalekos. (2011) Mycophenolate for the treatment of autoimmune hepatitis: Prospective assessment of its efficacy and safety for induction and maintenance of remission in a large cohort of treatment-naïve patients. Journal of Hepatology 55:3, 636-646
CrossRef5
Ansgar W. Lohse, Giorgina Mieli-Vergani. (2011) Autoimmune hepatitis. Journal of Hepatology 55:1, 171-182
CrossRef6
Junko Yokokawa, Yukiko Kanno, Hironobu Saito, Kazumichi Abe, Atsushi Takahashi, Hirohide Yokokawa, Hiromasa Ohira. (2011) Risk factors associated with relapse of type 1 autoimmune hepatitis in Japan. Hepatology Research 41:7, 641-646
CrossRef7
Giorgina Mieli-Vergani, Diego Vergani. (2011) Autoimmune hepatitis. Nature Reviews Gastroenterology & Hepatology 8:6, 320-329
CrossRef8
G P Aithal, P B Watkins, R J Andrade, D Larrey, M Molokhia, H Takikawa, C M Hunt, R A Wilke, M Avigan, N Kaplowitz, E Bjornsson, A K Daly. (2011) Case Definition and Phenotype Standardization in Drug-Induced Liver Injury. Clinical Pharmacology & Therapeutics 89:6, 806-815
CrossRef9
Gideon M. Hirschfield, E. Jenny Heathcote. 2011. Autoimmune Hepatitis and Overlap Syndromes. , 452-477.
CrossRef10
Mutaz I Sultan, Vincent F Biank, Grzegorz W Telega. (2011) Successful Treatment of Autoimmune Hepatitis With Methotrexate. Journal of Pediatric Gastroenterology and Nutrition 52:4, 492-494
CrossRef11
Diego Vergani, Giorgina Mieli-Vergani. (2011) Pharmacological management of autoimmune hepatitis. Expert Opinion on Pharmacotherapy 12:4, 607-613
CrossRef12
Andrew D. Yeoman, Rachel H. Westbrook, Yoh Zen, Paola Maninchedda, Bernard C. Portmann, John Devlin, John G. O'Grady, Phillip M. Harrison, Michael A. Heneghan. (2011) Early predictors of corticosteroid treatment failure in icteric presentations of autoimmune hepatitis. Hepatology 53:3, 926-934
CrossRef13
E. Kalaitzakis, G. J. M. Webster. (2011) Review article: autoimmune pancreatitis - management of an emerging disease. Alimentary Pharmacology & Therapeutics 33:3, 291-303
CrossRef14
Maha Guindi. (2010) Histology of Autoimmune Hepatitis and its Variants. Clinics in Liver Disease 14:4, 577-590
CrossRef15
Albert J. Czaja, Michael P. Manns. (2010) Advances in the Diagnosis, Pathogenesis, and Management of Autoimmune Hepatitis. Gastroenterology 139:1, 58-72.e4
CrossRef16
Mieke M.H. Lamers, Martijn G.H. van Oijen, Martine Pronk, Joost P.H. Drenth. (2010) Treatment options for autoimmune hepatitis: A systematic review of randomized controlled trials. Journal of Hepatology 53:1, 191-198
CrossRef17
Ulf Hindorf, Khatoon Jahed, Annika Bergquist, Hans Verbaan, Hanne Prytz, Sven Wallerstedt, Mårten Werner, Rolf Olsson, Einar Björnsson, Curt Peterson, Sven H.C. Almer. (2010) Characterisation and utility of thiopurine methyltransferase and thiopurine metabolite measurements in autoimmune hepatitis. Journal of Hepatology 52:1, 106-111
CrossRef18
Jérôme Dumortier, Carlos Torres Arita, Christine Rivet, Catherine LeGall, Raymonde Bouvier, Nicole Fabien, Olivier Guillaud, Sophie Collardeau-Frachon, Jean-Yves Scoazec, Alain Lachaux. (2009) Long-term treatment reduction and steroids withdrawal in children with autoimmune hepatitis: a single centre experience on 55 children. European Journal of Gastroenterology & Hepatology 21:12, 1413-1418
CrossRef19
David C. Wolf, Lizza Bojito, Marcelo Facciuto, Edward Lebovics. (2009) Mycophenolate Mofetil for Autoimmune Hepatitis: A Single Practice Experience. Digestive Diseases and Sciences 54:11, 2519-2522
CrossRef20
Neomal S. Sandanayake, Nicholas I. Church, Michael H. Chapman, Gavin J. Johnson, Dipok K. Dhar, Zahir Amin, Maesha G. Deheragoda, Marco Novelli, Alison Winstanley, Manuel Rodriguez–Justo, Adrian R.W. Hatfield, Stephen P. Pereira, George J.M. Webster. (2009) Presentation and Management of Post-treatment Relapse in Autoimmune Pancreatitis/Immunoglobulin G4-Associated Cholangitis. Clinical Gastroenterology and Hepatology 7:10, 1089-1096
CrossRef21
Diego Vergani, Maria Serena Longhi, Dimitrios P. Bogdanos, Yun Ma, Giorgina Mieli-Vergani. (2009) Autoimmune hepatitis. Seminars in Immunopathology 31:3, 421-435
CrossRef22
Albert J Czaja. (2009) Current and future treatments of autoimmune hepatitis. Expert Review of Gastroenterology & Hepatology 3:3, 269-291
CrossRef23
Lise Lotte Gluud, Eva Efsen Dahl, Ahmed Al-Rifai, Martin Prince, Lise Lotte Gluud. 2009. Medical treatments for autoimmune hepatitis. .
CrossRef24
Thawab Al–Chalabi, James A. Underhill, Bernard C. Portmann, Ian G. McFarlane, Michael A. Heneghan. (2008) Effects of Serum Aspartate Aminotransferase Levels in Patients With Autoimmune Hepatitis Influence Disease Course and Outcome. Clinical Gastroenterology and Hepatology 6:12, 1389-1395
CrossRef25
Elke M. Hennes, Ye H. Oo, Christoph Schramm, Ulrike Denzer, Peter Buggisch, Christiane Wiegard, Stephan Kanzler, Marcus Schuchmann, Wulf Boecher, Peter R. Galle, David H. Adams, Ansgar W. Lohse. (2008) Mycophenolate Mofetil as Second Line Therapy in Autoimmune Hepatitis?. The American Journal of Gastroenterology 103:12, 3063-3070
CrossRef26
Jonathan T. Hlivko, Mitchell L. Shiffman, R. Todd Stravitz, Velimir A. Luketic, Arun J. Sanyal, Michael Fuchs, Richard K. Sterling. (2008) A Single Center Review of the Use of Mycophenolate Mofetil in the Treatment of Autoimmune Hepatitis. Clinical Gastroenterology and Hepatology 6:9, 1036-1040
CrossRef27
Andrew D. Yeoman, Thawab Al-Chalabi, John B. Karani, Alberto Quaglia, John Devlin, Giorgina Mieli-Vergani, Adrian Bomford, John G. O'Grady, Phillip M. Harrison, Michael A. Heneghan. (2008) Evaluation of risk factors in the development of hepatocellular carcinoma in autoimmune hepatitis: Implications for follow-up and screening. Hepatology 48:3, 863-870
CrossRef28
Karen F Murray, Uzma Shah, Neelam Mohan, Solange Heller, Regino P González-Peralta, Deirdre Kelly, Mei-Hwei Chang, Giorgina Mieli-Vergani, Paloma Jara, Tomoo Fujisawa. (2008) Chronic Hepatitis. Journal of Pediatric Gastroenterology and Nutrition 47:2, 225-233
CrossRef29
Teru Kumagi, Khalid Alswat, Gideon M. Hirschfield, Jenny Heathcote. (2008) New insights into autoimmune liver diseases. Hepatology Research 38:8, 745-761
CrossRef30
(2008) Autoimmune Pancreatitis: Optimal Therapy Has Not Been Determined. The American Journal of Gastroenterology 103:7, 1834-1835
CrossRef31
T. AL-CHALABI, B. C. PORTMANN, W. BERNAL, I. G. MCFARLANE, M. A. HENEGHAN. (2008) Autoimmune hepatitis overlap syndromes: an evaluation of treatment response, long-term outcome and survival. Alimentary Pharmacology & Therapeutics 28:2, 209-220
CrossRef32
Mamun-Al-Mahtab, Salimur Rahman, Mobin Khan, Kamal, Fazal Karim. (2008) Two Extremes of Autoimmune Hepatitis: Report of Two Cases from Bangladesh. Hungarian Medical Journal 2:2, 257-260
CrossRef33
Albert J Czaja. (2008) Safety issues in the management of autoimmune hepatitis. Expert Opinion on Drug Safety 7:3, 319-333
CrossRef34
Thawab Al-Chalabi, James A. Underhill, Bernard C. Portmann, Ian G. McFarlane, Michael A. Heneghan. (2008) Impact of gender on the long-term outcome and survival of patients with autoimmune hepatitis. Journal of Hepatology 48:1, 140-147
CrossRef35
Albert J Czaja. (2008) Clinical Features, Differential Diagnosis and Treatment of Autoimmune Hepatitis in the Elderly. Drugs & Aging 25:3, 219-239
CrossRef36
Nicholas I. Church, Stephen P. Pereira, Maesha G. Deheragoda, Neomal Sandanayake, Zahir Amin, William R. Lees, Alice Gillams, Manuel Rodriguez-Justo, Marco Novelli, Edward W. Seward, Adrian R.W. Hatfield, George J.M. Webster. (2007) Autoimmune Pancreatitis: Clinical and Radiological Features and Objective Response to Steroid Therapy in a UK Series. The American Journal of Gastroenterology 102:11, 2417-2425
CrossRef37
Hiroki Takahashi. (2007) Current topics relating to autoimmune hepatitis diagnosis and therapy. Hepatology Research 37:s3, S510-S514
CrossRef38
Philippe Ichai, Jean-Charles Duclos-Vallée, Catherine Guettier, Sonia Ben Hamida, Theresa Antonini, Valérie Delvart, Faouzi Saliba, Daniel Azoulay, Denis Castaing, Didier Samuel. (2007) Usefulness of corticosteroids for the treatment of severe and fulminant forms of autoimmune hepatitis. Liver Transplantation 13:7, 996-1003
CrossRef39
Ira Inductivo–Yu, Atoya Adams, Robert G. Gish, Adil Wakil, Natalie H. Bzowej, R. Todd Frederick, Maurizio Bonacini. (2007) Mycophenolate Mofetil in Autoimmune Hepatitis Patients Not Responsive or Intolerant to Standard Immunosuppressive Therapy. Clinical Gastroenterology and Hepatology 5:7, 799-802
CrossRef40
Thawab Al-Chalabi, Michael A. Heneghan. (2007) Remission in Autoimmune Hepatitis: What Is It, and Can It Ever Be Achieved?. The American Journal of Gastroenterology 102:5, 1013-1015
CrossRef41
Aldo J. Montano-Loza, Herschel A. Carpenter, Albert J. Czaja. (2007) Consequences of treatment withdrawal in type 1 autoimmune hepatitis. Liver International 27:4, 507-515
CrossRef42
Aldo J. Montano-Loza, Herschel A. Carpenter, Albert J. Czaja. (2007) Improving the End Point of Corticosteroid Therapy in Type 1 Autoimmune Hepatitis to Reduce the Frequency of Relapse. The American Journal of Gastroenterology 102:5, 1005-1012
CrossRef43
Aldo J Montano Loza, Albert J Czaja. (2007) Current therapy for autoimmune hepatitis. Nature Clinical Practice Gastroenterology & Hepatology 4:4, 202-214
CrossRef44
Walter EB Sipe, Philip Rosenthal. (2007) Autoimmune hepatitis in children: diagnosis, pathology and treatment. Expert Review of Clinical Immunology 3:2, 159-169
CrossRef45
Akihiro Tamori, Mayumi Shinzaki, Saori Kosaka, Takehiro Hayashi, Shuji Iwai, Masaru Enomoto, Daiki Habu, Hiroki Sakaguchi, Norifumi Kawada, Masayuki Hino, Susumu Shiomi, Shuhei Nishiguchi. (2007) Thiopurine S-methyltransferase gene polymorphism in Japanese patients with autoimmune liver diseases. Liver International 27:1,
CrossRef46
Jenny Heathcote. (2006) Treatment Strategies for Autoimmune Hepatitis. The American Journal of Gastroenterology 101:s3, S630-S632
CrossRef47
A. FLOREANI, G. NIRO, E. ROSA RIZZOTTO, S. ANTONIAZZI, F. FERRARA, I. CARDERI, V. BALDO, A. PREMOLI, F. OLIVERO, E. MORELLO, M. DURAZZO. (2006) Type I autoimmune hepatitis: clinical course and outcome in an Italian multicentre study. Alimentary Pharmacology and Therapeutics 24:7, 1051-1057
CrossRef48
Sanjoy Banerjee, Riad Rahhal, Warren P. Bishop. (2006) Azathioprine Monotherapy for Maintenance of Remission in Pediatric Patients With Autoimmune Hepatitis. Journal of Pediatric Gastroenterology and Nutrition 43:3, 353-356
CrossRef49
Albert J. Czaja, Herschel A. Carpenter. (2006) Thiopurine Methyltransferase Deficiency and Azathioprine Intolerance in Autoimmune Hepatitis. Digestive Diseases and Sciences 51:5, 968-975
CrossRef50
Michael A Heneghan, Thawab Al-Chalabi, Ian G McFarlane. (2006) Cost-effectiveness of pharmacotherapy for autoimmune hepatitis. Expert Opinion on Pharmacotherapy 7:2, 145-156
CrossRef51
H-F. Lu, M-C. Shih, Y-S. Chang, J-Y. Chang, Y-C. Ko, S-J. Chang, J-G. Chang. (2006) Molecular analysis of thiopurine S-methyltransferase alleles in Taiwan aborigines and Taiwanese. Journal of Clinical Pharmacy and Therapeutics 31:1, 93-98
CrossRef52
Krawitt, Edward L., . (2006) Autoimmune Hepatitis. New England Journal of Medicine 354:1, 54-66
Full Text53
Jean-Charles Duclos-Vallée, Eric Ballot, Stéphanie Huguet, Catherine Johanet. (2005) Hépatites autoimmunes. Gastroentérologie Clinique et Biologique 29:12, 1236-1243
CrossRef54
Albert J Czaja, Herschel A Carpenter. (2005) Empiric Therapy of Autoimmune Hepatitis With Mycophenolate Mofetil. Journal of Clinical Gastroenterology 39:9, 819-825
CrossRef55
H.-F. Lu, M.-C. Shih, S.-C. Hsueh, C.-M. Chen, J.-Y. Chang, J.-G. Chang. (2005) Molecular analysis of the thiopurine S-methyltransferase alleles in Bolivians and Tibetans. Journal of Clinical Pharmacy and Therapeutics 30:5, 491-496
CrossRef56
Hong Wei, Shufeng Zhou, Chengrong Li, Jianping Zhang, Jueheng Wu, Min Huang. (2005) Phenotyping and Genotyping Studies of Thiopurine S-Methyltransferase in Kazaks. Pharmaceutical Research 22:10, 1762-1766
CrossRef57
Y. H. Oo, James Neuberger. (2005) Use of mycophenolate in the treatment of autoimmune hepatitis. Liver International 25:4, 687-691
CrossRef58
Srinivas Seela, Harinath Sheela, James L. Boyer. (2005) Autoimmune hepatitis type 1: safety and efficacy of prolonged medical therapy. Liver International 25:4, 734-739
CrossRef59
Patrick Tan, Paul Marotta, Cameron Ghent, Paul Adams. (2005) Early treatment response predicts the need for liver transplantation in autoimmune hepatitis. Liver International 25:4, 728-733
CrossRef60
Jordan J. Feld, Huong Dinh, Tamara Arenovich, Victoria A. Marcus, Ian R. Wanless, E. Jenny Heathcote. (2005) Autoimmune hepatitis: Effect of symptoms and cirrhosis on natural history and outcome. Hepatology 42:1, 53-62
CrossRef61
R. D'Souza, P. Sinnott, M. J. Glynn, C. A. Sabin, G.R. Foster. (2005) An unusual form of autoimmune hepatitis in young Somalian men. Liver International 25:2, 325-330
CrossRef62
Nanne K.H. de Boer, Carin M.J. van Nieuwkerk, M. Nieves Aparicio Pages, Sybrand Y. de Boer, Luc J.J. Derijks, Chris J.J. Mulder. (2005) Promising treatment of autoimmune hepatitis with 6-thioguanine after adverse events on azathioprine. European Journal of Gastroenterology & Hepatology 17:4, 457-461
CrossRef63
C. Verslype, C. George, E. Buchel, F. Nevens, W. van Steenbergen, J. Fevery. (2005) Diagnosis and treatment of autoimmune hepatitis at age 65 and older. Alimentary Pharmacology and Therapeutics 21:6, 695-699
CrossRef64
Carolina Rumbo, Benjamin L. Shneider, Sukru H. Emre. (2004) Utility of azathioprine metabolite measurements in post-transplant recurrent autoimmune and immune-mediated hepatitis. Pediatric Transplantation 8:6, 571-575
CrossRef65
DIEGO VERGANI, GIORGINA MIELI-VERGANI. (2004) Autoimmune hepatitis: diagnostic and management challenges. Journal of Gastroenterology and Hepatology 19:s7, S388-S390
CrossRef66
Carolina Rumbo. (2004) Azathioprine metabolite measurements: Its use in current clinical practice. Pediatric Transplantation 8:6, 606-608
CrossRef67
Fernando Alvarez. (2004) Treatment of autoimmune hepatitis: Current and future therapies. Current Treatment Options in Gastroenterology 7:5, 413-420
CrossRef68
R. K. Weersma, F. T. M. Peters, L. E. Oostenbrug, A. P. Berg, M. Haastert, R. J. Ploeg, M. D. Posthumus, J. J. Homan van der Heide, P. L. M. Jansen, H. M. Dullemen. (2004) Increased incidence of azathioprine-induced pancreatitis in Crohn's disease compared with other diseases. Alimentary Pharmacology and Therapeutics 20:8, 843-850
CrossRef69
I. Kohn, V. Petri, N. Ag??ero, T. Filli. (2004) P0159 PP IS IT POSSIBLE TO MAINTAIN BIOCHEMICAL AND HISTOLOGICAL REMISSION IN PEDIATRICS PATIENTS WITH AUTOINMUNE HEPATITIS USING AZATHIOPRINE AS UN SINGLE DRUG REGIMEN?. Journal of Pediatric Gastroenterology and Nutrition 39:Supplement 1, S119
CrossRef70
Albert J. Czaja, Herschel A. Carpenter. (2004) Progressive fibrosis during corticosteroid therapy of autoimmune hepatitis. Hepatology 39:6, 1631-1638
CrossRef71
M. Sciveres, S. Caprai, G. Palla, C. Ughi, G. Maggiore. (2004) Effectiveness and safety of ciclosporin as therapy for autoimmune diseases of the liver in children and adolescents. Alimentary Pharmacology and Therapeutics 19:2, 209-217
CrossRef72
Diego Vergani, Giorgina Mieli-Vergani. (2003) Autoimmune hepatitis. Autoimmunity Reviews 2:5, 241-247
CrossRef73
Raymond C Givens, Paul B Watkins. (2003) Pharmacogenetics and clinical gastroenterology. Gastroenterology 125:1, 240-248
CrossRef74
Thomas R Ziegler, Concepción Fernández-Estívariz, Li H Gu, Michael W Fried, Lorraine M Leader. (2003) Severe villus atrophy and chronic malabsorption induced by azathioprine. Gastroenterology 124:7, 1950-1957
CrossRef75
Christian P Strassburg, Michael P Manns. (2003) Autoimmune hepatitis. Best Practice & Research Clinical Gastroenterology 17:2, 291-306
CrossRef76
J. Medina, L. Garcia-Buey, R. Moreno-Otero. (2003) Immunopathogenetic and therapeutic aspects of autoimmune hepatitis. Alimentary Pharmacology and Therapeutics 17:1, 1-16
CrossRef77
Oya Uygur-Bayramiçli, Didem Aydin, Öznur Ak, Nimet Karadayi. (2003) Hyperprolactinemia Caused by Azathioprine. Journal of Clinical Gastroenterology 36:1, 79-80
CrossRef78
Carolina Rumbo, Karan M. Emerick, Sukru Emre, Benjamin L. Shneider. (2002) Azathioprine Metabolite Measurements in the Treatment of Autoimmune Hepatitis in Pediatric Patients: A Preliminary Report. Journal of Pediatric Gastroenterology and Nutrition 35:3, 391-398
CrossRef79
Jaakko Perheentupa. (2002) APS-I/APECED: the clinical disease and therapy. Endocrinology & Metabolism Clinics of North America 31:2, 295-320
CrossRef80
Dany Anglicheau, Sylvia Sanquer, Marie-Anne Loriot, Philippe Beaune, Eric Thervet. (2002) Thiopurine methyltransferase activity: new conditions for reversed-phase high-performance liquid chromatographic assay without extraction and genotypic–phenotypic correlation. Journal of Chromatography B 773:2, 119-127
CrossRef81
Jan-Gowth Chang, Long-Shyong Lee, Chih-Mei Chen, Mu-Chin Shih, Mei-Chen Wu, Fuu-Jen Tsai, Der-Cheng Liang. (2002) Molecular analysis of thiopurine S-methyltransferase alleles in South-east Asian populations. Pharmacogenetics 12:3, 191-195
CrossRef82
Giorgina Mieli-Vergani, Diego Vergani. (2002) Autoimmune liver disease. The Indian Journal of Pediatrics 69:1, 93-98
CrossRef83
J A Al-Khalid, A J Czaja. (2001) Current concepts in the diagnosis, pathogenesis, and treatment of autoimmune hepatitis.. Mayo Clinic Proceedings 76:12, 1237-1252
CrossRef84
Omar I Saadah, Arnold L Smith, Winita Hardikar. (2001) Long-term outcome of autoimmune hepatitis in children. Journal of Gastroenterology and Hepatology 16:11, 1297-1302
CrossRef85
Sybille Andries, Lucia Casamayou, Christine Sempoux, Muriel Burlet, Raymond Reding, Jean Bernard Otte, Jean-Paul Buts, Etienne Sokal. (2001) POSTTRANSPLANT IMMUNE HEPATITIS IN PEDIATRIC LIVER TRANSPLANT RECIPIENTS: INCIDENCE AND MAINTENANCE THERAPY WITH AZATHIOPRINE. Transplantation 72:2, 267-272
CrossRef86
Michael P. Manns, Christian P. Strassburg. (2001) Autoimmune hepatitis: Clinical challenges. Gastroenterology 120:6, 1502-1517
CrossRef87
Suradej Hongeng, Werasak Sasanakul, Ampaiwan Chuansumrit, Samart Pakakasama, Apisit Chattananon, Phongjan Hathirat. (2000) Frequency of thiopurine S-methyltransferase genetic variation in Thai children with acute leukemia. Medical and Pediatric Oncology 35:4, 410-414
CrossRef88
Albert J. Czaja. (1999) Special report: Autoimmune hepatitis. Current Treatment Options in Gastroenterology 2:5, 423-436
CrossRef89
Albert J. Czaja. (1999) The immunoreactive propensity of autoimmune hepatitis: Is it corticosteroid-dependent after liver transplantation?. Liver Transplantation and Surgery 5:5, 460-463
CrossRef90
I.G. McFarlane. (1999) Pathogenesis of autoimmune hepatitis. Biomedicine & Pharmacotherapy 53:5-6, 255-263
CrossRef91
Erwin Gerhard Rambusch, Michael Peter Manns. (1999) Therapie der Autoimmunhepatitis. Medizinische Klinik 94:3, 171-172
CrossRef92
Piotr Milkiewicz, Monzur Ahmed, Mark Hathaway, Elwyn Elias. (1999) Factors associated with progression of the disease before transplantation in patients with autoimmune hepatitis. Liver International 19:1, 50-54
CrossRef93
Elisa Prados, Valent??n Cuervas-Mons, Manuel de la Mata, Enrique Fraga, Antonio Rimola, Mart??n Prieto, Gerardo Clemente, Emilio Vicente, Teresa Casanovas, Emilio Fabrega. (1998) OUTCOME OF AUTOIMMUNE HEPATITIS AFTER LIVER TRANSPLANTATION1. Transplantation 66:12, 1645-1650
CrossRef94
KIMIHIDE NAKAMURA, MASASHI YONEDA, SHIRO YOKOHAMA, KEISUKE TAMORI, YOICHI SATO, KAZUNOBU ASO, MASARU AOSHIMA, TAKENAO HASEGAWA, ISAO MAKING. (1998) Efficacy of ursodeoxycholic acid in Japanese patients with type 1 autoimmune hepatitis. Journal of Gastroenterology and Hepatology 13:5, 490-495
CrossRef95
M. Gulati, M. Grover, M. Singh, S. Singh. (1998) Study of azathioprine encapsulation into liposomes. Journal of Microencapsulation 15:4, 485-494
CrossRef96
C. Sempoux, Y. Horsmans, J. Lerut, J. Rahier, A. Geubel. (1997) Acute lobular hepatitis as the first manifestation of recurrent autoimmune hepatitis after orthotopic liver transplantation. Liver 17:6, 311-315
CrossRef97
Robert P. Baughman, Elyse E. Lower. (1997) STEROID-SPARING ALTERNATIVE TREATMENTS FOR SARCOIDOSIS. Clinics in Chest Medicine 18:4, 853-864
CrossRef98
MICHAEL P MANNS. (1997) Recent developments in autoimmune liver diseases. Journal of Gastroenterology and Hepatology 12:9-10, S256-S271
CrossRef99
J. H. Hoofnagle, D. Lau, H. Conjeevaram, D. Kleiner, A. M. Di Bisceglie. (1996) Prolonged therapy of chronic hepatitis C with ribavirin. Journal of Viral Hepatitis 3:5, 247-252
CrossRef100
Krawitt, Edward L., . (1996) Autoimmune Hepatitis. New England Journal of Medicine 334:14, 897-903
Full Text101
Meyer zum Büschenfelde, Karl-Hermann, Lohse, Ansgar W., . (1995) Autoimmune Hepatitis. New England Journal of Medicine 333:15, 1004-1005
Full Text
