Decline in HAV-associated fulminant hepatic failure and liver transplant in children in Argentina after the introduction of a universal hepatitis A vaccination program

Abstract

Guillermo Cervio1, Julio Trentadue2, Daniel D'Agostino3, Carlos Luque4, Mariano Giorgi5, Judith Armoni6, Roberto Debbag6 1Unidad de Transplante Hepatico, Hospital Prof Dr Juan P Garrahan, 2Unidad de Terapia Intensiva, Hospital Universitario Fundación Favaloro, 3Unidad de Gastroenterología, Hospital Italiano De Buenos Aires, 4Unidad de Transplante Hepatico, Hospital Universitario Austral, 5Departamento de Farmacologia, Escuela de Medicina de la Universidad Austral, 6Sanofi Pasteur, Buenos Aires, Argentina Introduction: Hepatitis A virus (HAV) infection is a vaccine-preventable disease. The most severe complication in children is fulminant hepatic failure (FHF), estimated to occur in 0.4% of cases; patients with FHF often require a liver transplant (LT). Following another outbreak of HAV infection in Argentina during 2003–2004, a one-dose HAV universal immunization (UI) program was started in 2005, resulting in a reduction in the incidence of HAV infection. We have investigated the impact of HAV UI on the trends in the occurrence of FHF and LT in children. Methods: All pediatric cases of FHF admitted to four pediatric centers in Buenos Aires during March 1993–July 2005 were retrospectively reviewed, and data of cases during August 2005–December 2008 were collected. Information about demography, HAV infections and vaccination status, diagnostic data for FHF using the Pediatric Acute Liver Failure criteria, clinical laboratory results, encephalopathy, the severity of liver disease using the Pediatric End Stage Liver Disease score, assessment of patients on the LT waiting list using King's College Criteria for LT, treatment given for FHF (pre- and post-transplant), and clinical outcome were collected using a case report form. The frequency and outcomes of HAV-associated FHF and LT cases before and after UI were analyzed. Results: During the pre-immunization period, March 1993–July 2005, 54.6% (N = 165) of FHF cases were caused by HAV; HAV-associated FHF cases peaked during 2003–2004. During the post-immunization period, August 2005–December 2008, only 27.7% (N = 18) of FHF cases were caused by HAV infection; only one of these patients had received the HAV vaccine (one dose only). The number of HAV-associated FHF cases decreased from 2005, and no cases were reported from November 2006–December 2008. Multivariate analyses showed that the association of FHF with HAV infection rather than other etiologies decreased with increasing age (P = 0.03), UI against HAV (P = 0.002), and anti-actin antibodies (P = 0.002), and increased with increasing weight (P = 0.0004). Conclusions: The number of children with HAV-associated FHF in Argentina has strongly decreased since the initiation of the UI program. Further monitoring is required to confirm the long-term health and economic benefits of UI against HAV infection. Keywords: hepatitis A vaccine, fulminant hepatic failure, immunization