mercaptopurine and Cholangitis--Sclerosing

Hepatic involvement is often encountered in gastrointestinal (GI) diseases, in part because of the close anatomic and physiologic relations between the liver and GI tract. Drainage of the mesenteric blood supply to the portal vein permits absorbed and/or translocated nutrients, toxins, bacterial elements, cytokines, and immunocytes to gain hepatic access. Liver problems in digestive disorders may range from nonspecific hepatocellular enzyme elevations to significant pathologic processes that may progress to end-stage liver disease. Hepatobiliary manifestations of primary GI diseases in childhood and adolescence are not uncommon and include several well-described associations, such as sclerosing cholangitis with inflammatory bowel disease. Liver damage may also result from the effects of drugs used to treat GI diseases, for example, the hepatotoxicity of immunomodulatory therapies. This review highlights the important features of the hepatic and biliary abnormalities associated with 3 common pediatric GI conditions: inflammatory bowel disease, celiac disease, and cystic fibrosis.

Topics: Adolescent; Antibodies, Monoclonal; Azathioprine; Celiac Disease; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Cholagogues and Choleretics; Cholangitis, Sclerosing; Cystic Fibrosis; Humans; Infant; Inflammatory Bowel Diseases; Infliximab; Liver Diseases; Liver Function Tests; Mercaptopurine; Methotrexate; Tumor Necrosis Factor-alpha; Ursodeoxycholic Acid

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Antipruritics; Azathioprine; Cholangitis, Sclerosing; Cholestasis; Cholestyramine Resin; Humans; Mercaptopurine; Methotrexate; Penicillamine; Ursodeoxycholic Acid; Vitamins

BACKGROUND Systemic IgG4-related disease is a rare disease that can affect the hepatobiliary system and may lead to tissue fibrosis and organ failure. Diagnostic criteria for IgG4-related disease are well established, and systemic glucocorticoids are recommended for initiation of treatment. Besides the beneficial properties of glucocorticoids, the long-term treatment with systemic steroids carries the risk of toxicity, especially in elderly patients, in whom IgG4-related disease is more common. Furthermore, disease relapses may occur during the tapering of steroids. Overall, the optimal treatment approach for maintenance therapy has not been clarified yet and is an area of current clinical research. CASE REPORT We present a patient with IgG4-related sclerosing cholangitis and histologically confirmed systemic (multi-organ) IgG4-related disease who was at increased risk of disease recurrence. The effects of immunosuppressants (prednisolone, 6-mercaptopurine, budesonide) on clinical symptoms, laboratory parameters (AST, ALT, AP, γGT, bilirubin), and imaging examinations (magnetic resonance cholangiography) were documented over 56 months. Control of IgG4-related sclerosing cholangitis was achieved - without systemic prednisolone - with the locally acting glucocorticoid budesonide in combination with low-dose 6-mercaptopurine. During treatment with 6-mercaptopurine, transient hepatotoxicity occurred, which was reversed by intermittent pausing and subsequent dose reduction. In addition, gangrenous cholecystitis occurred as a complication of immunosuppression and was treated by emergency cholecystectomy. CONCLUSIONS Budesonide could be a new treatment modality for IgG4-related sclerosing cholangitis. Systemic manifestations of immunoglobulin G4-related disease can be controlled with low-dose 6-mercaptopurine. Gangrenous cholecystitis may occur as a complication of immunosuppressive treatment.

Topics: Aged; Budesonide; Cholangitis, Sclerosing; Humans; Immunoglobulin G; Immunoglobulin G4-Related Disease; Mercaptopurine

Autoimmune hepatitis (AIH) is an immune-mediated liver disease, which requires long-term immunosuppression. Ten to fifteen percent of patients experience insufficient/intolerance response to standard therapy. Although alternate immunosuppression has been applied, there is little long-term data reported on safety, efficacy, steroid-dose reduction and disease evolution in patients with difficult AIH who were on Tacrolimus therapy.. Clinical, biochemical, immunological profiles, treatment response and side effects of 17 AIH patients treated with Tacrolimus between 2003 and 2014 were analyzed from two tertiary referral liver centers.. Tacrolimus was started on 16/17 (94%) patients due to insufficient response to standard therapy. The median duration of treatment was 24 months and patients were followed up for median of 60 months. Tacrolimus dosage was 2 mg/day (median). During first year of therapy, there was a significant improvement in immunoglobulin G and Aspartate transaminase level. 9/17 (52%) compliant and definite AIH patients remained on Tacrolimus at end of follow-up and prednisolone dose reduction was achieved from 10 to 5 mg. All patients are alive and one patient underwent liver transplantation. 4/17 (24%) patients developed overlap with primary sclerosing cholangitis over follow-up period. No significant side effects were observed with Tacrolimus therapy.. Tacrolimus could be used in compliant patients with difficult to treat AIH in experienced centers. Its use is safe and can improve liver biochemistry, IgG and reduce steroid requirement. However, due to the lack of immunomodulatory effect, unmet need for effective immune-regulatory therapies still remain for AIH patients.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Aspartate Aminotransferases; Azathioprine; Cholangitis, Sclerosing; Cyclosporine; Female; Follow-Up Studies; Hepatitis, Autoimmune; Humans; Immunoglobulin G; Immunosuppressive Agents; Male; Mercaptopurine; Middle Aged; Mycophenolic Acid; Prednisolone; Retreatment; Tacrolimus; Time Factors; Treatment Outcome; Young Adult

Crohn's disease is rare in South African black people and primary sclerosing cholangitis (PSC) is also rare in black patients with IBD, from South Africa. The presence of HLA-B27 is generally associated with seronegative spondylo-arthropathies and correlates with the occurrence of ankylosing spondylitis, recurrent mouth ulcers and uveitis, in patients with IBD. We describe two women with the combination of Crohn's disease, PSC and HLA-B27 from our cohort of the last 5 years of three black patients with Crohn's disease. Crohn's disease, PSC and HLA-B27 respectively, occur rarely in black South Africans and their concurrent presence in two black women suggests a pathogenetic link of HLA-B27 between Crohn's disease and PSC in this population. Female gender might be an additional determinant in this setting.

Topics: Adult; Alkaline Phosphatase; Azathioprine; Back Pain; Black People; Cholagogues and Choleretics; Cholangiopancreatography, Magnetic Resonance; Cholangitis, Sclerosing; Colonoscopy; Crohn Disease; Diarrhea; Female; gamma-Glutamyltransferase; Genetic Predisposition to Disease; HLA-B27 Antigen; Humans; Immunosuppressive Agents; Mercaptopurine; Methotrexate; Severity of Illness Index; South Africa; Treatment Outcome; Ursodeoxycholic Acid

Topics: Allopurinol; Antimetabolites; Child; Cholangitis, Sclerosing; Female; Follow-Up Studies; Hepatitis, Autoimmune; Humans; Male; Mercaptopurine; Salvage Therapy; Transaminases