Early development of chronic active hepatitis in recurrent hepatitis C virus infection after liver transplantation: association with treatment of rejection.
OBJECTIVE
We retrospectively studied 63 consecutive patients (mean age 54+/-8) with hepatitis C virus genotype 1b recurrence after liver transplantation and with a minimum histological follow-up of 1 year, in order to determine whether an early severe recurrence, defined as the development of chronic active hepatitis within the first 2 years post-liver transplantation, was associated with increased immunosuppression.


METHODS
The 1st year immunosuppression data (rejection episodes, boluses of methyl-prednisolone, cumulative doses of prednisone and azathioprine, OKT3 use) were recorded, and evaluated as predictive of severe recurrence at 1 and 2 years post-liver transplantation. Chronic active hepatitis and rejection were defined by histological criteria. Immunosuppression consisted of cyclosporine, azathioprine and prednisone. The treatment of rejection was based on a "bolus" of 1 g methyl-prednisolone/3 days.


RESULTS
At 1 year, 64% (40/63) of the patients had chronic active hepatitis, whereas of the 40 patients who had a 2nd year biopsy available, 75% had chronic active hepatitis at 2 years. At 1 year post-liver transplantation, no significant association was observed between immunosuppression and the development of chronic active hepatitis. In contrast, at 2 years, rejection (p=0.006), treatment of rejection (p=0.05), methyl-prednisolone boluses (p=0.013) and the number of rejection episodes (p=0.0034) occurring during the 1st year post-liver transplantation were significantly more common in patients with chronic active hepatitis. There was also a trend towards higher cumulative steroids (9447+/-3176.5 vs 7891.5+/-2111 mg) and higher cumulative azathioprine doses (13472+/-11154 vs 6233.5+/-5937 mg) in patients with chronic active hepatitis as compared to those who did not develop chronic active hepatitis.


CONCLUSIONS
Rejection and/or its treatment may accelerate the natural history of hepatitis C virus genotype 1b infection post-liver transplantation.
Berenguer
M
M
Hepatogastroenterology Service, Hospital Universitario LA FE, Valencia, Spain. jb101v@nacom.es
Prieto
M
M
Córdoba
J
J
Rayón
J M
JM
Carrasco
D
D
Olaso
V
V
San-Juan
F
F
Gobernado
M
M
Mir
J
J
Berenguer
J
J
D000410:Alanine Transaminase / Q000097:blood; D001379:Azathioprine / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D016679:Genome, Viral; D006084:Graft Rejection / Q000188:drug therapy*; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D006526:Hepatitis C / Q000601:surgery*; D019698:Hepatitis C, Chronic / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors
D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D016572:Cyclosporine; D000410:Alanine Transaminase; D001379:Azathioprine; D011241:Prednisone; D008775:Methylprednisolone