GASTROENTEROLOGY ARTICLE OF THE WEEK
April 18, 2002
Heneghan MA, McFarlane IG. Current and novel immunosuppressive therapy for autoimmune hepatitis. Hepatology 2002;35:7-13
1. Regarding standard treatment of AIH with corticosteroids + azathioprine
a. Over 80% of patients achieve a remission
b. Patients with extensive fibrosis at time of diagnosis are less likely to respond
c. If untreated, mortality is 80% among those with 5x elevations of LAE’s or 2x elevations of gamma globulins
d. HLA-DR3 positivity decreases the chances of response to therapy
2. Which of the following patients should be treated for AIH (assume other causes of liver disease have been excluded by serology)
a. Normal ALT, AST-75, normal gamma globulin, ANA positive 1:2680, negative SMA, fatty infiltration on liver biopsy
b. ALT and AST >700, gamma globulin of 4.5 grams, ANA 1:640, cirrhosis on biopsy
c. ALT of 180, ANA negative, SMA positive 1:160, gamma globulin 3.8, interface and lobular hepatitis on biopsy without fibrosis
d. ALT normal, ANA positive 1:1280, SMA positive 1:160, gamma globulin 2x elevated, liver biopsy with interface hepatitis, lobular hepatitis and bridging fibrosis
3. AIH during pregnancy
a. Azathioprine should be discontinued as soon as the patient becomes pregnant
b. Patients trying to conceive must stop azathioprine
c. Immunosuppression should be minimized during pregnancy, as flares during pregnancy are rare.
d. Post-partum flares are not unusual and may require additional immunosuppression
e. Patients who become pregnant during remission should continue same therapy and be monitored closely for relapse.
True or False
4. Discontinuation of all immunosuppressants should only be considered after biochemical and histologic remission has been maintained for at least 2 years
5. Absent TPMT activity as determined by genetic testing is a relative contraindication to the use of azathioprine.
6. High dose (40-60mg) prednisone monotherapy is superior to combination low dose prednisone (20-30mg) plus azathioprine (1mg/kg/d) in achieving an initial remission.
7. Cyclosporine is an attractive agent for long-term maintenance of remission.
8. Budesonide may be considered a therapeutic agent for patiens with AIH who have intolerable side effects to prednisone
9. Heterozygotes with low TPMT activity require a lower dose of azathioprine to achieve a clinical response
10. Mycophenolate mofetil is probably the third agent of choice when prednisone and azathioprine are unable to be tolerated or cannot achieve a remission
11. Regarding response to therapy
a. LAE’s should normalize within 6 to 12 weeks
b. Histologic improvement lags LAE’s improvement by 6 to 12 months
c. Histologic remission is achieved in 87% of patients within 6 months of therapy
d. 10-year life expectancy for patients with cirrhosis at presentation who achieve remission during therapy is >90%