Autoimmune hepatitis

Azathioprine induced severe bone marrow suppression

천안 충무병원 소화기내과 류기현

206810 이O희 48/F

• C.C.: OT/PT elevation

• P.I.: 외부병원 급성 간염 소견으로 추가 검

사 위해 의뢰 됨.

Initial Blood Examination

• CBC: 4300-11.3-35.2-163K

• PT/PTT: 11.7/27.2

• OT/PT: 586/822, TB/DB: 1.3/1.0, GGT:676

• HBsAg/Anti-HBsAb (-/+), Anti-HCV(-)

Blood Examination

• ANA(+,1:1280), ASMA(+), Anti LKM Ab(-)

• AMA(-)

• IGG: 3415mg/dl(700~1600)

• SPEP: polyclonal gammopathy

• Bridging necrosis with early cirrhotic changes

Biopsy

Impression

• Autoimmune hepatitis

Progress

• 2013-7-2

– Pd(15)+Azt(50) combination therapy start

• 2013-7-9

– Hair loss, sore throat

– ANC: 71.4

Progress

Progress

• G-CSF 약 2주간의 투여 후 백혈구 수치의

호전.

• 혈색소 수치는 약 2개월 후 회복.

Autoimmune hepatitis

• 자가면역질환

– 면역 이상으로 특정 자가세포를 외부세포로 인지하고 공격하여 파괴하는 질환

• Autoimmune hepatitis.

– Unresolving, predominantly periportal hepatitis of unknown etiology.

– Usually with hypergammaglobulinemia and tissue autoantibodies.

– Which is responsive to immunosuppressive therapy.

Dignostic Scoring System

Indications for Treatment

Absolute Relative None

Serum AST≥10 fold ULN Symptoms (fatigue, arthralgia,

jaundice)

Asymptomatic with normal or

near normal serum AST and γ

globulin levels

Serum AST≥5 fold ULN and γ

globulin level≥2 fold ULN

Serum AST and/or c globulin

less than absolute criteria

Inactive cirrhosis or mild portal

inflammation

(portal hepatitis)

Bridging necrosis or multiacinar

necrosis on histological

examination

Interface hepatitis Severe cytopenia (white blood

cell counts <2.5X109/L or

platelet counts <50X109/L)

or known complete deficiency of

TPMT activity precludes

treatment with azathioprine

Incapacitating symptoms Osteopenia, emotional instability,

hypertension, diabetes, or

cytopenia (white blood cell

counts 2.5 109/L

or platelet counts 50 109/L)

Vertebral compression,

psychosis, brittle diabetes,

uncontrolled hypertension,

known intolerances to

prednisone or azathioprine

Immunosuppressive Treatment

Azathioprine-Related Side Effects

hypoxanthine guanine

phosphoribosyl transferase

Interfere with purine nucleotide synthesis within the cell cycle and

impair proliferation of rapidly dividing T and B lymphocytes

Thiopurine

methyltransferase

6-mercaptopurine

6-methyl mercaptopurine

6-thioguanines

Myelosuppression is an important and potentially lethal complication of azathioprine treatment. The

blood count has been reviewed in all patients treated with azathioprine for inflammatory bowel disease

over 27 years in one hospital. Altogether 739 patients (422 with Crohn's disease, 284 with ulcerative

colitis, and 33 with indeterminate colitis) were treated with 2 mg/kg/day azathioprine for a median of

12.5 months (range 0.5-132) between 1964 and 1991. Full blood counts were performed monthly for

the duration of treatment. In 37 patients (5%) who developed bone marrow toxicity, the drug was

withdrawn or the dose reduced. Thirty two of these patients were asymptomatic and five developed

symptoms. Leucopenia (white blood count less than 3.0 x 10g/l) occurred in 28 (3.8%) patients, in nine

of whom it was severe (white blood count < 2.0 x 10(9)/l). Of these nine patients, three were

pancytopenic: two died from sepsis and the other had pneumonia but recovered. A further two patients

with severe leucopenia developed a mild upper respiratory infection only. Thrombocytopenia (platelet

count < 100,000 x 10(6)/l) in 15 patients was associated with leucopenia in six and developed in

isolation in a further nine (total 2%). Isolated thrombocytopenia was never clinically severe.

Myelotoxicity from azathioprine developed at any time during drug treatment (range 2 weeks-11 years

after starting the drug) and occurred either suddenly or over several months. Bone marrow

suppression as a result of azathioprine treatment is uncommon when a moderate dose is used, but is

potentially severe. Leucopenia is the commonest and most important haematological complication.

Regular monitoring of the full blood count is recommended during treatment.

Result

Result(1)

Result(2)

감사합니다.