mercaptopurine and Liver-Cirrhosis

Topics: Azathioprine; B-Lymphocytes; Chronic Disease; Denmark; Drug Evaluation; Female; Glucocorticoids; Hepatitis; Humans; Immunity, Cellular; Immunosuppressive Agents; Liver Cirrhosis; Liver Diseases; Male; Mercaptopurine; Placebos; T-Lymphocytes

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Chlorambucil; Cyclophosphamide; Granulomatosis with Polyangiitis; Hepatitis; Humans; Immunosuppressive Agents; Liver Cirrhosis; Lupus Erythematosus, Systemic; Mercaptopurine; Methotrexate; Mice; Mice, Inbred NZB; Multiple Sclerosis; Nephritis; Nephrosis; Nitrogen Mustard Compounds; Penicillins; Psoriasis; Uveitis, Anterior

Topics: Adrenal Cortex Hormones; Aspartate Aminotransferases; Azathioprine; Blood Proteins; Chronic Disease; Female; Hepatitis; Humans; Liver Cirrhosis; Liver Function Tests; Mercaptopurine; Prednisone; Rest; Serum Albumin; Serum Globulins; Time Factors

Topics: Adrenal Cortex Hormones; Azathioprine; Chronic Disease; Diagnosis, Differential; False Positive Reactions; Hepatitis; Hepatitis A; Humans; Liver; Liver Cirrhosis; Liver Diseases; Liver Function Tests; Mercaptopurine

Topics: Acute Disease; Glucocorticoids; Hepatitis; Humans; Immunosuppressive Agents; Liver; Liver Cirrhosis; Liver Diseases; Mercaptopurine; Prednisolone; Prednisone

Liver biopsies were done on 20 patients with histiocytosis X (HX) as part of pretreatment evaluation prior to entry on two Childrens Cancer Study Group protocols. Seventeen patients had hepatomegaly, and seven had one or more abnormal laboratory parameters using Lahey's criteria for liver dysfunction. Nineteen of 20 specimens showed various abnormalities of the portal triads. A single biopsy revealed normal liver. Among the changes were triaditis, bile duct proliferation, variable fibrosis with histiocytic infiltrates, and cirrhosis. One patient had typical granulomas of HX within the liver parenchyma in addition to portal triaditis. Patients with larger livers and dysfunction tended to show more marked histologic abnormalities in the portal triads. However, correlations among liver size, function, and pathology showed considerable overlap. Early death among these patients was more likely to be associated with progressive HX in other sites and/or infection. Death from cirrhosis and liver failure per se occurred in one patient 4 years after initial biopsy, but five other children had evidence of cirrhosis on biopsy or at autopsy. The majority of patients with triaditis initially did not have clinical evidence of progressive liver disease although four expired with other manifestations of HX or infection. Conversely, patients showing fibrohistiocytic changes or cirrhosis initially were likely to have continuing or progressive liver disease. Although the liver histology was not diagnostic of HX, the types of portal changes usually predicted the subsequent course of liver disease.

Topics: Biopsy, Needle; Child; Child, Preschool; Cyclophosphamide; Follow-Up Studies; Hepatitis; Hepatomegaly; Histiocytosis, Langerhans-Cell; Humans; Infant; Liver; Liver Cirrhosis; Liver Function Tests; Mercaptopurine; Methotrexate; Multicenter Studies as Topic; Prednisone; Vinblastine

The possibility of developing idiopathic portal hypertension has been described with thiopurine treatment despite compromises the prognosis of these patients, the fact its true prevalence is unknown.. A cross-sectional study was conducted in a cohort of inflammatory bowel disease (IBD) patients followed at our unit, to determine the prevalence of diagnosis of idiopathic portal hypertension (IPH) and its relationship with thiopurine treatment.. At the time of the analysis, 927/1,419 patients were under treatment with thiopurine drugs (65%). A total of 4 patients with IBD type Crohn's disease with idiopathic portal hypertension probably related to the thiopurine treatment were identified (incidence of 4.3 cases per 1,000). Seventy-five percent of patients started with signs or symptoms of portal hypertension. Only one patient was asymptomatic but the diagnosis of IPH because of isolated thrombocytopenia is suspected. However, note that all patients had thrombocytopenia previously. Abdominal ultrasound with fibroscan, hepatic vein catheterization and liver biopsy were performed on all of them as part of the etiology of portal hypertension. In the abdominal ultrasound, indirect portal hypertension data were observed in all patients (as splenomegaly) cirrhosis was also ruled out. The fibroscan data showed significant liver fibrosis (F2-F3).. Idiopathic portal hypertension following thiopurine treatment in IBD patients is a rare occurrence, but it must be borne in mind in the differential diagnosis for early diagnosis, especially in patients undergoing thiopurine treatment over a long period. The presence of thrombocytopenia is often the only predictor of its development in the preclinical stage.

Topics: Adult; Aged; Azathioprine; Cross-Sectional Studies; Female; Humans; Hypertension, Portal; Idiopathic Noncirrhotic Portal Hypertension; Immunosuppressive Agents; Inflammatory Bowel Diseases; Liver Cirrhosis; Male; Mercaptopurine; Middle Aged; Pancytopenia; Splenomegaly; Treatment Outcome

Topics: Child; Endoscopy, Digestive System; Female; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Liver Cirrhosis; Mercaptopurine; Prednisone; Remission Induction; Ultrasonography

During therapy consisting of 6MP and MTX, metabolites accumulate in the erythrocytes. The erythrocyte levels of metabolites reflect the intensity of therapy. Whether they are associated with hepatotoxicity manifested as histological liver changes is not known. We studied the association of the metabolites and cumulative doses of 6MP and MTX with histological liver disease.. Serial measurements of E-TGN, E-MTX, and ALT during maintenance therapy were performed and cumulative doses of 6MP and MTX were calculated as g/m2 in 16 children with ALL. Each subject underwent a percutaneous liver biopsy at the end of therapy to screen for histological liver disease.. No differences in E-TGN, E-MTX, or cumulative doses of 6MP or MTX were detected in the children with ALL with liver fibrosis compared to those without fibrosis, or in the children with less liver fatty change compared to those with more fatty change. Serum median ALT levels correlated significantly positively with cumulative doses of 6MP during therapy (rS = 0.527, P = 0.036), but not with cumulative doses of MTX, or E-TGN, or E-MTX.. Erythrocyte levels of the metabolites or the cumulative doses of 6MP and MTX do not predict histological liver disease in children treated for ALL.

Topics: Adolescent; Antimetabolites, Antineoplastic; Biomarkers; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Monitoring; Erythrocytes; Female; Humans; Liver Cirrhosis; Male; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Statistics, Nonparametric

Azathioprine is a key drug in the management of autoimmune hepatitis (AIH), with effects mediated via conversion to 6-thioguanine (6-TG) and 6-methylmercaptopurine (6-MMP), the latter controlled by thiopurine methyltransferase (TPMT). Our aims were to evaluate the role of TPMT genotyping and phenotyping and to examine 6-TG and 6-MMP metabolite levels in patients with AIH.. TPMT genotyping and phenotyping was performed on 86 patients with AIH, and metabolites evaluated in assessable patients.. Eighty-six patients with AIH received azathioprine; 22 developed toxicity and 4/22 were heterozygous for TPMT alleles. Cirrhosis was more common amongst patients who developed toxicity (12/22 (54.5%) versus 19/64 (29.6%), P=0.043). Patients who required persistent prednisone at equivalent azathioprine doses had a higher mean fibrosis stage (P=0.044). TPMT activity, but not metabolites, was lower in patients with stage III/IV fibrosis versus stage I/II fibrosis (30+/-1.92 versus 35.2+/-1.93, P=0.044). Azathioprine dose significantly correlated with measured 6-TG levels (r=0.409, P<0.0001) and 6-MMP levels (r=0.387, P<0.001).. Advanced fibrosis but not TPMT genotype or activity predicts azathioprine toxicity in AIH. Overlap in 6-TG and 6-MMP metabolite levels is noted whether or not steroid therapy is used to maintain remission.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Azathioprine; Drug Monitoring; Female; Genotype; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Liver; Liver Cirrhosis; Male; Mercaptopurine; Methyltransferases; Middle Aged; Phenotype; Prednisone; Thioguanine

Hepatocellular carcinoma (HCC) occurred in a 28-year-old woman treated for acute lymphocytic leukemia (ALL) with methotrexate (MTX) and 6-mercaptopurine (6-MP), off all therapy for 15 years, who was also heterozygous for alpha-1 antitrypsin (alpha-1 AT) deficiency. MTXD is responsible for the development of HCC in this patient. The literature concerning the incidence of HCC in patients treated with MTX and 6-MP and in alpha-1 antitrypsin deficiencies is reviewed.

Topics: Adult; alpha 1-Antitrypsin; alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Female; Humans; Leukemia, Lymphoid; Liver Cirrhosis; Liver Neoplasms; Mercaptopurine; Methotrexate; Neoplasm Proteins; Neoplasms, Multiple Primary

Topics: Animals; Benzimidazoles; Female; Gestational Age; Immunosuppressive Agents; Liver; Liver Cirrhosis; Mercaptopurine; Pregnancy; Rats; Thymus Gland; Transplantation, Isogeneic

A malignant hepatoma occurred in a 12-year-old girl who eight years previously had developed an acute lymphoblastic leukaemia which for eight years had been in complete haematological remission. Fourteen months after the last re-induction treatment period had been discontinued, but while on methotrexate and 6-mercaptopurine maintenance, a hepatocellular liver carcinoma developed of which the patient died after a fulminating course, still in complete haematological remission. As far as is known, no direct carcinogenic effect can be ascribed to the two antimetabolites, but it must be assumed that these two drugs, taken by the patient for over seven years, led to cirrhosis of the liver whose malignant transformation was significantly influenced by the immunosuppressive effects of methotrexate and 6-mercaptopurine, given as maintenance therapy according to protocol 02 LA 64, Paris.

Topics: Carcinoma, Hepatocellular; Child; Female; Humans; Leukemia, Lymphoid; Liver Cirrhosis; Liver Neoplasms; Mercaptopurine; Methotrexate; Remission, Spontaneous; Time Factors

The morphological criteria for diagnosing chronic hepatitis are discussed and criticised. A classification closer to clinical reality than that of De Groote et al 1968 is then proposed. Personal experience in differential laboratory diagnosis between the various forms of chronic hepatitis by means of comparative evaluation of an enzymogram and the measurement of certain proteins in the serum is then reported. Case examples are given to emphasise the possibilities of the immunological approach to the problem of active chronic hepatitis. Finally, the cardinal points of therapy are reviewed.

Topics: Adult; Anti-Inflammatory Agents; Antibodies; Azathioprine; Blood Proteins; Clinical Enzyme Tests; Drug Therapy, Combination; Female; Fluorescent Antibody Technique; Hepatitis; Hepatitis B Antigens; Humans; Immunodiffusion; Immunoglobulins; Immunosuppressive Agents; Liver Cirrhosis; Liver Function Tests; Male; Mercaptopurine; Middle Aged; Prednisone

Topics: Azathioprine; Chronic Disease; Diet Therapy; Dietary Carbohydrates; Dietary Proteins; Female; Hepatitis; Hot Temperature; Humans; Liver; Liver Cirrhosis; Mercaptopurine; Middle Aged; Penicillamine; Prednisone; Pregnancy; Pregnancy Complications; Rest; Splenectomy

Topics: Animals; Carbon Radioisotopes; Collagen; Cortisone; Hydroxyproline; In Vitro Techniques; Liver Cirrhosis; Male; Mercaptopurine; Nitriles; Peptide Biosynthesis; Proline; Rats

Topics: Animals; Azathioprine; Graft Rejection; Hepatitis A; Humans; Immune Adherence Reaction; Kinetics; Liver Cirrhosis; Liver Diseases; Liver Transplantation; Mercaptopurine; Sheep; Sulfur Isotopes

Topics: Adolescent; Adult; DNA; Hepatitis; Humans; Liver Cirrhosis; Liver Cirrhosis, Biliary; Liver Extracts; Lymphocyte Activation; Mercaptopurine; Middle Aged; Prednisolone

Topics: Chronic Disease; Hepatitis; Hepatitis B Antigens; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Liver Cirrhosis; Liver Diseases; Lymphocyte Activation; Mercaptopurine; Prednisolone

Topics: Adolescent; Adult; Aged; Azathioprine; Chronic Disease; Female; Hepatitis; Humans; Liver Cirrhosis; Male; Mercaptopurine; Middle Aged

Topics: Adult; Aged; Aspartate Aminotransferases; Drug Synergism; Female; Humans; Liver Cirrhosis; Long-Term Care; Mercaptopurine; Middle Aged; Prednisone; Time Factors

Topics: Autoimmune Diseases; Chronic Disease; Cortisone; Cyclophosphamide; Female; Hepatitis; Hepatitis A; Humans; Liver Cirrhosis; Long-Term Care; Lupus Erythematosus, Systemic; Mercaptopurine; Penicillamine; Tuberculosis, Hepatic

Topics: Azathioprine; Female; Humans; Liver Cirrhosis; Liver Diseases; Lupus Erythematosus, Systemic; Menopause; Mercaptopurine; Middle Aged

Topics: Animals; Autopsy; Child, Preschool; Drug Combinations; Female; Humans; Leukemia; Liver Cirrhosis; Liver Regeneration; Male; Mercaptopurine; Methotrexate; Mice; Mice, Inbred Strains; Remission, Spontaneous

Topics: Adolescent; Adult; Autoimmune Diseases; Chronic Disease; Female; Hepatitis; Humans; Liver Cirrhosis; Male; Mercaptopurine; Middle Aged; Prednisone

Topics: Adolescent; Adult; Female; Hepatitis; Humans; Leukopenia; Liver Cirrhosis; Male; Mercaptopurine; Middle Aged; Prednisolone; Thrombocytopenia

Topics: Azathioprine; Humans; Immunosuppressive Agents; Liver Cirrhosis; Mercaptopurine

Topics: Adolescent; Adult; Antimetabolites; Azaguanine; Azathioprine; Chronic Disease; Cyclophosphamide; Female; Hepatitis; Humans; Liver Cirrhosis; Male; Mercaptopurine; Middle Aged; Prednisone; Thioguanine

Topics: Adult; Angiotensin II; Animals; Bile Duct Neoplasms; Biliary Tract Diseases; Blood Pressure; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Chloramphenicol; Endopeptidases; Erythromycin; Female; Gout; Hepatitis; Humans; Hypertension; Liver; Liver Cirrhosis; Liver Diseases; Liver Function Tests; Liver Neoplasms; Male; Mercaptopurine; Middle Aged; Nephrotic Syndrome; Rats

Topics: Acute Disease; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Azathioprine; Biliary Tract Diseases; Biopsy; Child; Child, Preschool; Cholestasis; Chronic Disease; Diagnosis, Differential; Female; Hepatitis; Hepatitis A; Humans; Infant; Infant, Newborn; Liver Cirrhosis; Liver Cirrhosis, Biliary; Male; Mercaptopurine; Middle Aged; Necrosis

Topics: Adult; Alanine Transaminase; Bilirubin; Blood Glucose; Chronic Disease; Female; Hepatitis; Humans; Liver Cirrhosis; Male; Mercaptopurine; Middle Aged; Prednisolone

Topics: Cyclophosphamide; Humans; Liver Cirrhosis; Mercaptopurine

Topics: Adult; Aged; Female; Hepatitis; Humans; Liver Cirrhosis; Liver Function Tests; Male; Mercaptopurine; Middle Aged

Topics: Adult; Female; Hepatitis; Humans; Liver Cirrhosis; Male; Mercaptopurine; Middle Aged

Topics: Autoimmune Diseases; Diagnosis, Differential; Enzymes; Hepatitis; Humans; In Vitro Techniques; Liver Cirrhosis; Lupus Erythematosus, Systemic; Mercaptopurine; Transaminases

Topics: Adult; Aged; Female; Hepatitis; Humans; Hydrazines; Liver Cirrhosis; Liver Function Tests; Male; Mercaptopurine; Middle Aged

Topics: Antineoplastic Agents; Blood Protein Electrophoresis; Diagnosis, Differential; Geriatrics; Liver Cirrhosis; Mercaptopurine; Multiple Myeloma; Neoplasms, Plasma Cell; Nephrosis; Pathology; Phosphorus Isotopes; Plasmacytoma; Purpura; Urethane; Waldenstrom Macroglobulinemia

Topics: Cortisone; Diet; Diet Therapy; Drug Therapy; Hepatitis; Hepatitis A; Hepatitis, Chronic; Humans; Liver Cirrhosis; Mercaptopurine; Pathology; Prognosis; Rest