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De novo hepatitis C in children after liver transplantation
S V McDiarmid1, A Conrad, M E Ament
1Division of Pediatrics, Gastroenterology and Nutrition, UCLA Medical Center, Los Angeles, California 90095-1752, USA.
Insights
De novo hepatitis C virus (HCV) infection after pediatric liver transplant has a 23% mortality rate. Interferon therapy showed limited success, with only 15% achieving sustained improvement.
Area of Science:
- Hepatology
- Transplantation Immunology
- Virology
Background:
- Hepatitis C virus (HCV) infection can occur de novo after pediatric liver transplantation.
- Understanding the incidence and outcomes of de novo HCV is crucial for managing pediatric transplant recipients.
Purpose of the Study:
- To describe the incidence of de novo hepatitis C virus (HCV) hepatitis after pediatric liver transplantation (OLT).
- To evaluate the results of interferon therapy and the overall outcome for these patients.
Main Methods:
- Retrospective analysis of pediatric OLT recipients from 1984 to September 1996.
- Diagnosis of HCV confirmed by antibody testing, PCR, and liver biopsy.
- Interferon-2alpha therapy administered based on patient weight.
Main Results:
- 13 out of 321 (4.0%) pediatric OLT survivors developed de novo HCV disease.
- Children transplanted before HCV screening had a 10.2% incidence.
- Interferon therapy led to sustained ALT improvement in only 15% of patients; 23% overall mortality.
Conclusions:
- De novo HCV hepatitis carries a significant mortality risk (23%) in pediatric liver transplant recipients.
- Re-transplantation for HCV hepatitis often results in early recurrence and poor outcomes.
- Interferon therapy demonstrates limited efficacy in treating de novo HCV post-OLT.
Background:
We describe the incidence, results of interferon therapy, and outcome of hepatitis C virus (HCV) hepatitis occurring de novo after pediatric orthotopic liver transplantation (OLT).
Methods And Results:
Of children undergoing OLT between 1984 and September 1996, 321 children survived for more than 1 year. Of these, 13 (4.0%) developed previously undiagnosed HCV disease, as suggested by HCV antibody testing and HCV polymerase chain reaction and confirmed by liver biopsy. Of the 117 children who received transplants before HCV screening of blood products or donors, 10.2% developed de novo HCV disease. The mean age at diagnosis of HCV hepatitis was 13.2+/-5.0 years, and the mean time to diagnosis after OLT was 8.1 years (range, 4-11 years). The mean alanine aminotransferase (ALT) level at diagnosis was 108 IU/ml, and the liver biopsy specimen showed chronic active or chronic persistent hepatitis in 11 children, cirrhosis in 1 child, and nonspecific changes in 1 child. Twelve children were treated with interferon-2alpha; children who weighed > or =20 kg received 3 x 10(6) units every other day, and those who weighed <20 kg received 1.5 x 10(6) units every other day. Four patients developed rapidly progressive liver failure while receiving interferon therapy and required urgent re-transplantation. Three of the four children again developed histologic evidence of recurrent HCV 4-6 months after the second OLT, and all three subsequently died of HCV-induced liver failure. One patient remains alive and well with no evidence of HCV recurrence and a negative HCV RNA. Of the remaining eight children treated with interferon, only two have had a sustained response (normal ALT) and one is now HCV RNA negative. HCV RNA levels did not correlate with outcome or disease severity. HCV antibody levels were unreliable, with two patients having negative HCV antibody but a positive HCV RNA at diagnosis. Six patients were able to be genotyped: four were la and two were 1b.
Conclusion:
Overall mortality for de novo HCV hepatitis was 23%. Seventy-five percent of children who received a second transplant for HCV hepatitis had early histologic recurrence that led to liver failure and death. Interferon therapy resulted in a sustained improvement in ALT in only 15% of children. The time to onset and progression of clinical disease both in the original graft and the retransplant graft were accelerated compared with nonimmunosuppressed individuals.