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World J Gastroenterol. Feb 28, 2010; 16(8): 934-947
Published online Feb 28, 2010. doi: 10.3748/wjg.v16.i8.934
Published online Feb 28, 2010. doi: 10.3748/wjg.v16.i8.934
Schedule | Monotherapy | Combination therapy | |
Prednisone only1 (mg/d) | Prednisone1 (mg/d) | Azathioprine (mg/d) | |
Induction period | |||
Week 1 | 60 | 30 | 50 |
Week 2 | 40 | 20 | 50 |
Week 3 | 30 | 15 | 50 |
Week 4 | 30 | 15 | 50 |
Maintenance period | |||
Fixed doses until end point | 20 | 10 | 50 |
Conditions that favor each regimen | Cytopenia (severe) Absent thiopurine methyltransferase activity Pregnancy Malignancy (active) Short trial ( ≤ 6 mo) Acute severe onset | Elderly/postmenopausal state Osteoporosis Brittle diabetes Obesity Acne Emotional instability/psychosis Hypertension Prolonged therapy (≥ 6 mo) |
Table 2 Difficult treatment decisions before starting conventional corticosteroid therapy
Problem | Response |
Acute severe (fulminant) presentation | Prompt institution of conventional corticosteroid therapy with prednisone monotherapy[44,51-53] |
Azathioprine, 50 mg/d, can be added later if treatment is to be continued for ≥ 3 mo[55] | |
Liver transplantation evaluation if laboratory indices worsen at any time during treatment, especially progressive hyperbilirubinemia, or no improvement after 2 wk[56] | |
Asymptomatic mild or mild disease | Institute conventional corticosteroid therapy with prednisone in combination with azathioprine[58,55] |
Consider empirical treatment with budesonide, 3 mg tid, in conjunction with azathioprine, 50 mg/d, if preexistent osteopenia, diabetes, hypertension, obesity, or emotional instability[25,26] | |
Autoantibody-negativity | Exclude viral, drug, toxic, metabolic causes and celiac disease[31,43] |
Apply codified scoring criteria of IAIHG for probable or definite diagnosis[31,46] | |
Institute conventional corticosteroid therapy with prednisone in combination with azathioprine or a higher dose of prednisone alone[19,47-50] | |
Overlap syndromes | Conventional corticosteroid therapy alone or in combination with azathioprine if serum alkaline phosphatase level < 2 times ULN[59-62] |
Add ursodeoxycholic acid, 13-15 mg/kg per day, to corticosteroid regimen if serum alkaline phosphatase level ≥ 2 times ULN[60,63] | |
Consider ursodeoxycholic acid alone, 13-15 mg/kg per day, if predominant features of PBC with minimal features of autoimmune hepatitis[64,65] |
Table 3 Difficult treatment decisions during conventional corticosteroid therapy
Problem | Response |
Determining treatment end point | Continue conventional therapy until normal serum AST, ALT, bilirubin and γ-globulin levels and normal liver tissue or inactive cirrhosis (ideal end point)[119-121] |
Continue conventional therapy until serum AST ≤ 2 times ULN, bilirubin and γ-globulin levels normal, and portal hepatitis or minimally active cirrhosis (satisfactory end point)[11,54,55] | |
Decrease dose of culprit drug or discontinue its use if side effects emerge (drug toxicity end point)[13,55] | |
Limit conventional corticosteroid treatment of patients aged ≥ 60 yr if an ideal or satisfactory end point has not been achieved ≤ 24 mo (incomplete response end point)[11,19,124,125] | |
Relapse after drug withdrawal | Institute original therapy until clinical and laboratory resolution, then increase azathioprine dose to 2 mg/kg per day as dose of prednisone is withdrawn[126,127] |
Continue daily azathioprine in fixed dose indefinitely[126,127] | |
Use low dose prednisone ( ≤ 10 mg/d) if severe cytopenia (leukocyte counts < 2.5 × 109/L or platelet counts < 50 × 109/L) or other azathioprine intolerances[13,55] | |
Use low dose prednisone (2.5-5 mg/d) to supplement azathioprine maintenance if abnormal serum AST level[55,128] | |
Treatment failure | Prednisone, 60 mg/d, or prednisone, 30 mg/d, in combination with azathioprine, 150 mg/d, for at least 1 mo, then dose reductions by 10 mg for prednisone and 50 mg for azathioprine each month of laboratory improvement until conventional doses reached[54,55,129] |
Evaluate for liver transplantation if minimal criteria for listing (MELD ≥ 15 points) are met[130-132] | |
Incomplete response | Azathioprine (2 mg/kg per day) indefinitely after corticosteroid withdrawal[54,55,127] |
Low-dose prednisone ( ≤ 10 mg/d) if azathioprine intolerance[54,55,128] | |
Adjustments to maintain serum AST level ≤ 3 times ULN[55,133] |
Table 4 Difficult treatment decisions after conventional corticosteroid therapy
Problem | Response |
Empirical salvage drugs | Consider cyclosporine (5-6 mg/kg per day)[144-150] or tacrolimus (4 mg bid)[21,22,151,152] if progressive disease on conventional treatment |
Consider mycophenolate mofetil (1 g bid) if corticosteroid or azathioprine intolerance[23,24,153-159] | |
Consider budesonide (3 mg tid) as frontline therapy if mild disease or if azathioprine maintenance insufficient after relapse or incomplete response[25,26] | |
Complete benefit-risk and cost analyses before use[160,161] | |
Empirical trial must not supersede liver transplantation[55,130,131] | |
Liver transplantation | Consider if acute severe (fulminant) presentation unresponsive or worse within 2 wk of conventional treatment[52,53,56,57] |
Consider if treatment dependent ≥ 3 yr and features of decompensation develop (ascites, encephalopathy or variceal bleeding)[130] | |
Consider if failure to conventional therapy and MELD score ≥ 15 points[52,131,132] | |
Elderly patients (aged ≥ 60 yr) | Restrict conventional therapy to combination regimen[124] |
Limit initial treatment to ≤ 24 mo[125] | |
Institute azathioprine maintenance therapy (2 mg/kg per day) if initial response is incomplete at 24 mo[124] | |
Consider liver transplantation if features of decompensation emerge[132] | |
Pregnant patients | Counsel regarding risks of prematurity and infant mortality[162-167] |
Institute high-risk obstetrical care[30,162] | |
Avoid azathioprine if possible[165,168] | |
Reduce doses of prednisone to lowest levels to stabilize if not resolve laboratory indices[169] | |
Reestablish conventional prednisone doses prior to delivery[169] | |
Be alert to post-partum flares[163,164,169] |
- Citation: Czaja AJ. Difficult treatment decisions in autoimmune hepatitis. World J Gastroenterol 2010; 16(8): 934-947
- URL: https://www.wjgnet.com/1007-9327/full/v16/i8/934.htm
- DOI: https://dx.doi.org/10.3748/wjg.v16.i8.934