The impact of azathioprine on chronic viral hepatitis in renal transplantation: a long-term, single-center, prospective study on azathioprine withdrawal.
BACKGROUND
In transplanted patients, viral hepatitis progresses to chronic liver disease and patient's death after many years of transplantation. Also, it is well known that azathioprine (AZA) is harmful to the liver of these patients. However, it is unclear whether a low dose of AZA still represents a threat to the viral liver disease.


METHODS
A total of 79 patients with hepatitis C, B, or both, transplanted between 1973 and 1990, were grouped according to whether they had AZA either withdrawn from the immunosuppressive regimen [group (G) I, n=45] or a dosage reduction only (group II, n=34). The decision to remove or to keep AZA was restricted to the patient's doctor. Patients records were reviewed by April 1997.


RESULTS
After an equal time of follow-up, after the AZA changing (64+/-26 vs. 58+/-29 months), patients in GI showed a significant decrease in the serum liver parameters when compared to baseline [alanine aminotransferase (ALT): P=0.001; gamma-glutamyl transferase (gamma-GT): P=0.001 and total bilirubin: P=0.002], whereas in GII only ALT decreased (P=0.04) although gamma-GT and total bilirubin did not. Compared to baseline, serum creatinine (SCr) increased only in GI (P=0.001) but, at last follow-up, did not differ from GII. The intention-to-perform liver biopsies was equal in GI and GII (16 vs. 14) but the hystological findings of severe chronic liver disease (either chronic active hepatitis or cirrhosis) were more frequent in GII (P=0.004). Death with a functioning graft was much more frequent in GII than in GI (P=0.001). Infection and cirrhosis were more common as a cause of death in GII than in GI.


CONCLUSIONS
The use AZA is harmful to renal transplantation patients with both chronic hepatitis C and B and, therefore, should be avoided. AZA withdrawal, but not dose adjustments, diminishes the serum liver enzymes and the progression rate of the chronic viral liver disease as well as the rate of death secondary to infection and cirrhosis.
David-Neto
E
E
Renal Transplantation Unit, Hospital das Clinicas of the University of São Paulo School of Medicine, Brazil.
Americo da Fonseca
J
J
Jota de Paula
F
F
Nahas
W C
WC
Sabbaga
E
E
Ianhez
L E
LE
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001379:Azathioprine / Q000009:adverse effects* / Q000627:therapeutic use*; D001663:Bilirubin / Q000097:blood; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control; D019694:Hepatitis B, Chronic / Q000209:etiology* / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000209:etiology* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013375:Substance Withdrawal Syndrome / Q000209:etiology*; D005723:gamma-Glutamyltransferase / Q000097:blood
D007166:Immunosuppressive Agents; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D001379:Azathioprine; D001663:Bilirubin