Allograft Dysfunction in Liver Transplant Patients Treated with Pegylated Interferon
Plus Ribavirin for Hepatitis C
Liver
transplantation is currently the only treatment for chronic hepatitis C patients
who develop decompensated liver cirrhosis or advanced hepatocellular carcinoma.
Unfortunately, hepatitis C virus (HCV) almost always re-infects the new liver
soon after transplantation.
Post-transplant
hepatitis C therapy is undergoing intensive study, but the side effects of interferon
and ribavirin make treatment difficult or impossible for many patients. Interferon
may trigger autoimmune disorders in individuals with well-functioning immune systems,
and there is concern that it might trigger autoimmune hepatitis following a transplant.
As
described in the February 2007 issue of Gut, Italian researchers studied
44 liver transplant recipients with hepatitis C who received pegylated interferon
alpha-2b (PegIntron) plus ribavirin for at least 6 months for HCV recurrence.
They performed laboratory, microbiological, imaging, and histological assessments
to identify the origin of allograft (donor liver) dysfunction.
Results
•
9 of 44 transplanted
patients developed allograft dysfunction.
•
8 of these did so despite
HCV RNA clearance while on pegylated interferon plus ribavirin.
•
Infections (other than
HCV), anastomoses (blood vessel) complications, and organ rejection were excluded
as causes of graft dysfunction.
•
In all cases, pre-existing
(prior to transplantation) autoimmune hepatitis was also ruled out.
•
All 9 patients had
scores suggesting probable autoimmune hepatitis (+10 to +14).
•
3 individuals developed
other autoimmune disorders (cholangitis, autoimmune thyroiditis, systemic lupus
erythematosus).
•
Use of anti-lymphocyte
antibodies in immunosoppressive induction therapy was associated with the development
of graft dysfunction.
•
Use of granulocyte
colony-stimulating factor (G-CSF) to treat interferon-induced neutropenia showed
a protective role.
•
Withdrawal of anti-HCV
therapy and treatment with prednisone did not produce consistent outcomes.
•
5 patients experienced
remission of liver dysfunction, while 4 experienced graft failure (with 2 deaths).
Conclusion
In
conclusion, the authors wrote, "De novo autoimmune hepatitis should
be considered in differential diagnosis along with rejection in liver transplanted
patients developing graft dysfunction while on interferon treatment."
Reference S
Berardi, F Lodato, A Gramenzi, and others. High incidence of allograft dysfunction
in liver transplant patients treated with Peg-Interferon alfa-2b and Ribavirin
for hepatitis C recurrence: possible de novo autoimmune hepatitis? Gut
56(2): 237-242. February 2007.
