Extrahepatic malignancy following long-term immunosuppressive therapy of severe hepatitis B surface antigen-negative chronic active hepatitis

Wang, Kenneth K.; Czaja, Albert J.; Beaver, Sandra J.; Go, Vay Liang W.

doi:10.1002/hep.1840100110

Cited by 72 publications

(32 citation statements)

References 27 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Chronic immune suppression in AIH has been associated with an increased risk of malignancy. The incidence of extrahepatic neoplasm in treated AIH is 1 per 194 patient-years and the probability of tumour occurrence is 3% after 10 years [123] . In a large population-based study in New Zealand, the incidence of extrahepatic malignancy was shown to be significantly increased by more than 2-fold in patients with AIH with notable increased risk for NMSC and hematological cancers, namely, acute myeloid leukaemia, chronic lymphocytic leukaemia and nonHodgkin's B cell lymphoma.…”

Section: Extrahepatic Manifestations As Complications Of Aih Treatmenmentioning

confidence: 99%

“…Extrahepatic side effects of Azathioprine therapy in AIH include pancreatitis [120] , rash [118] , bone marrow suppression [121,122] and slightly increased risk of malignancy (1.4-fold greater than normal) [123] . The frequency of cytopenia in azathioprine therapy for AIH is 46% and the occurrence of severe haematological abnormalities is 6% [124] .…”

Section: Extrahepatic Manifestations As Complications Of Aih Treatmenmentioning

confidence: 99%

See 1 more Smart Citation

Association of Extrahepatic Manifestations with Autoimmune Hepatitis

Wong

Heneghan²

2015

Dig Dis

View full text Add to dashboard Cite

For many patients with autoimmune hepatitis (AIH), the presence of extrahepatic features is well recognised both at the time of presentation and during long-term follow-up. Concomitant ‘autoimmune disorders' have been described in 20-50% of patients with AIH, both in adults and children. Indeed, the presence of these associated phenomena has been incorporated into both the original and revised International AIH group scoring systems as an aid to codifying the diagnosis. In acute index presentations, non-specific joint pains sometimes flitting in nature have been reported in 10-60% of patients, and while joint swelling is uncommon, rheumatoid arthritis and mixed connective tissue disease have been reported in 2-4% of patients with AIH. For a majority of patients, these joint symptoms resolve within days of the introduction of immunosuppressive therapy. Rarer features at index presentation include a maculopapular skin rash and unexplained fever, which are features that tend to resolve quickly with treatment. Interestingly, joint pain and stiffness are also well recognised in the context of steroid withdrawal and cessation in AIH. The occasional co-presentation of AIH with coeliac disease is clinically important (1-6%), since for some patients, there is a risk of immunosuppression malabsorption, thus delaying effective treatment. Similarly, the co-existence of selective IgA deficiency (IgAD) can occur in patients with coeliac disease or in isolation. Selective IgAD as a co-existing extraheaptic feature seems to be more common in paediatric patients with AIH. For these patients, they are at an increased risk of respiratory and sinus infections. Although, typically associated with primary sclerosing cholangitis, the presence of inflammatory bowel disease (IBD; both Crohn's disease and ulcerative colitis) has been described in 2-8% of patients with AIH. Interestingly, for patients with autoimmune sclerosing cholangitis, a distinct pattern of IBD has been recently described. Other conditions have been reported at a lower frequency, including Sjogren's syndrome 1-7%, systemic lupus erythematosus 1-3% and glomerulonephritis 1%. Rarer still and at a frequency of <1% include fibrosing alveolitis, haemolytic anaemia, uveitis, mononeuritis multiplex, polymyositis and multiple sclerosis. In contrast, the reported associations between AIH and thyroiditis 8-23%, diabetes 1-10% and psoriasis 3% are commonly seen and notable in clinical practice.

show abstract

Section: Extrahepatic Manifestations As Complications Of Aih Treatmenmentioning

confidence: 99%

Section: Extrahepatic Manifestations As Complications Of Aih Treatmenmentioning

confidence: 99%

Association of Extrahepatic Manifestations with Autoimmune Hepatitis

Wong

Heneghan²

2015

Dig Dis

View full text Add to dashboard Cite

show abstract

“…40 Lymphoma is otherwise rare in patients with type 1 autoimmune hepatitis who are treated before transplantation with prednisone alone or in combination with azathioprine. 41 Five of the 7 patients with recurrent autoimmune hepatitis were treated by adjustments in the immunosuppressive regimen. However, a uniform treatment strategy was not applied, and an optimal approach cannot be deduced.…”

Section: Discussionmentioning

confidence: 99%

Recurrent autoimmune hepatitis after orthotopic liver transplantation

González-Koch¹,

Czaja²,

Carpenter³

et al. 2001

Liver Transpl

Self Cite

182

156

View full text Add to dashboard Cite

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...

show abstract

“…On the other hand, repeated trials of treatment withdrawal can result in slightly more optimistic relapse rates of 63% in 1 year and 75% in 5 years (10) . It is possible to maintain most AIH patients in remission on maintenance doses of prednisone, or of prednisone/azathioprine (PA) or of azathioprine, but there is the added theoretical risk of malignancies associated with the immunosuppressor (19,36) . Therefore, the management of patients in remission is still a matter of debate.…”

Section: Introductionmentioning

confidence: 99%

Chloroquine for the maintenance of remission of autoimmune hepatitis: results of a pilot study

Mucenic

Mello

Cançado

2005

Arq. Gastroenterol.

View full text Add to dashboard Cite

-Background -Due to the risks related to long-term treatment with prednisone and azathioprine, most clinicians try to withdraw these drugs when patients with autoimmune hepatitis are in remission. However, there is a high probability of relapse, and most patients end up receiving maintenance treatment. Aim -To evaluate the safety and efficacy of maintenance treatment with chloroquine in the prevention of autoimmune hepatitis relapses. Methods -Classical treatment was stopped after achievement of biochemical and histological remission of autoimmune hepatitis. Chloroquine diphosphate, 250 mg daily, was given for at least 12 months or until the occurrence of relapses defined by levels of aminotransferases at least twice the upper normal values. Results -Fourteen patients were consecutively treated and compared with 18 historical controls. There was a 6.49 (1.38-30.30) greater chance of relapse in the historical controls when compared with patients treated with chloroquine (72.2% x 23.5%; 0.031). Conclusions -The group treated with chloroquine had a lower frequency of relapses. Chloroquine was safe in patients with autoimmune hepatitis and hepatic cirrhosis without decompensation, on 250 mg daily up to 2 years. These preliminary results provide a basis for upcoming controlled studies comparing chloroquine with placebo or for maintenance treatment with prednisone and/or azathioprine for the prevention of autoimmune hepatitis relapses.

show abstract

Extrahepatic malignancy following long-term immunosuppressive therapy of severe hepatitis B surface antigen-negative chronic active hepatitis

Cited by 72 publications

References 27 publications

Association of Extrahepatic Manifestations with Autoimmune Hepatitis

Association of Extrahepatic Manifestations with Autoimmune Hepatitis

Recurrent autoimmune hepatitis after orthotopic liver transplantation

Chloroquine for the maintenance of remission of autoimmune hepatitis: results of a pilot study

Contact Info

Product

Resources

About