Progressive histological damage in liver allografts following pediatric liver transplantation

A new study on the long-term outcome of children undergoing liver transplants found that chronic hepatitis (CH) was common and that it was not detectible using standard blood tests.

The presence of autoantibodies (antibodies that attack the body's own tissues) in these patients indicates that although not fully understood, CH may be related to the immune response.

The results of this study appear in the May 2006 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). Published by John Wiley & Sons, Inc., Hepatology is available online via Wiley InterScience.

Children normally undergo liver transplants for diseases that do not recur and are potentially curable by the procedure. Although their long-term survival rates are over 80 percent, little is known about tissue changes that occur over time in these young patients. "An important question within the field of paediatriac liver transplantation is whether children who have undergone successful transplantation can expect a normal life expectancy or whether there will be a gradual decline in liver function and eventual graft loss," the authors write.

Led by Helen M. Evans of the Birmingham Children's Hospital in Birmingham, United Kingdom, the study involved children who received liver transplants at the hospital's Liver Unit between 1983 and 1996. Patients underwent standard liver function tests, sonograms and liver biopsies at approximately 1, 5 and 10 years following transplant, and autoantibodies were measured at 5 and 10 years. A total of 113 children had liver biopsies at the one year mark, 135 had biopsies after 5 years, and 64 underwent biopsies at 10 years.

The results showed that there was a decrease over time in the proportion of biopsies considered to be normal, with chronic hepatitis being the most common abnormality (22 percent at 1 year, 43 percent at 5 years, 64 percent at 10 years). While liver function tests at 5 years were not significantly different in children who had CH, the presence of autoantibodies was significantly higher at 5 and 10 years in children with CH (72 percent and 80 percent respectively). In addition, there was a strong association between the presence of CH and the development of progressive fibrosis (the formation of scar-like tissue). The authors note that "the finding of increasing fibrosis in children with chronic hepatitis has not been reported before and has potentially important implications for long term graft function."

The authors note that transient autoantibody production following transplant sometimes occurs during episodes of rejection. In addition, late rejection may be associated with tissue changes that are different to those normally seen in acute rejection but more closely resemble those seen in chronic viral or autoimmune hepatitis. "It is therefore possible that some cases of otherwise unexplained chronic hepatitis in the liver allograft may represent a form of late cellular rejection," the authors suggest.

The results of the present study indicate that important tissue abnormalities can be detected in biopsies obtained from children who are clinically well and have normal liver function tests, the authors state. "Screening for chronic allograft hepatitis using liver biochemistry is therefore not possible and may instead require regular measurement of autoantibodies," they conclude.