Czaja AJ. Difficult treatment decisions in autoimmune hepatitis. World J Gastroenterol 2010; 16(8): 934-947 [PMID: 20180231 DOI: 10.3748/wjg.v16.i8.934]
Corresponding Author of This Article
Albert J Czaja, MD, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street S.W., Rochester, MN 55905, United States. czaja.albert@mayo.edu
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
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]