0021-7557/02/78-06/503 Jornal de Pediatria - Vol. 78, Nº6, 2002 503 Jornal de Pediatria Copyright © 2002 by Sociedade Brasileira de Pediatria ORIGINAL ARTICLE Prevalence of hepatitis A antibody in children and adolescents with chronic liver disease Cristina Targa Ferreira,1 Adriano N.R. Taniguchi,2 Sandra Maria Gonçalves Vieira,3 Jorge P. Lima,4 Themis Reverbel da Silveira5 Abstract Objective: to evaluate the prevalence of Hepatitis A virus (HAV) in children and adolescents with chronic liver disease in a unit of pediatric hepatology. Methods: between May 1999 and February 2001, we studied the prevalence of anti-HAV in 60 children and adolescents with chronic liver disease, aged between 1 and 16 years, from the Unit of Pediatric Hepatology of the Hospital de Clínicas de Porto Alegre. The total anti-HAV was determined by a commercially available competitive ELISA method (Abbott), and compared with age, sex, race, etiologic diagnosis and family income of each patient. Results: a one-year old child was not included in the study because she presented twice with undetermined anti-HAV results. Among the other 59 patients, 14 (24%) presented a positive result of total anti-HAV. The ages of test-positive subjects varied between 1 and 16 years old (mean = 7.7 years, median = 8.5). The differences between positive and negative groups in relation to age, sex and race were not statistically significant. Family income was lower in anti-HAV positive patients, but this difference was not significant. The differences between the etiologies of liver diseases were probably more related to the age than to the etiologies of the diseases. Conclusions: in the studied population, the majority (76%) of children and adolescents with chronic liver disease are susceptible to hepatitis A virus infection and, consequently, they could present a more severe disease or even fulminant hepatitis A. We strongly suggest that these subjects receive Hepatitis A inactivated vaccine. J Pediatr (Rio J) 2002;78(6):503-8: viral hepatitis A, prevalence, anti-HAV antibody, chronic liver disease. Introduction Acute viral hepatitis A (HAV) is a ubiquitous infection a chronic form, distinguish it from Hepatitis B and C.1 that results in significant morbidity. From an epidemiological Infection by the A virus can also cause fulminant hepatitis point of view, the rapid dissemination and the large outbreaks and be fatal, with an estimated mortality rate of 0.14 to 2%.2 of HAV, in addition to the fact that there is no evolution to There is growing evidence in medical literature that individuals with chronic liver disease exhibit an increased risk of developing more serious forms of HAV or even 1,3 1. Pediatric Gastroenterologist and Hepatologist, Hospital de Clínicas de fulminant hepatitis. Porto Alegre (HCPA). 2. Medicine student, Universidade Federal do Rio Grande do Sul. Recipients of liver transplants should avoid further 3. Pediatric Gastroenterologist and Hepatologist, HCPA. lesions to the graft, and should be immunized against HAV, 4. Associate Professor, Fundação Faculdade Federal de Ciências Médicas even when the risk of exposure is low.4 Furthermore, de Porto Alegre. 5. Associate Professor, Department of Pediatrics, School of Medicine, patients with chronic liver disease, who require liver Universidade Federal do Rio Grande do Sul. PhD. transplants, should undergo all vaccinations in advance of Manuscript received Feb 18 2002. Accepted for publication Aug 28 2002. the surgical procedure, since afterwards they will be more 503 504 Jornal de Pediatria - Vol. 78, Nº6, 2002 Prevalence of hepatitis A antibody... - Ferreira CT et alii immunocompromised than before the transplant. For this The etiologic diagnoses of the liver diseases are shown reason, this specific group of patients is indicated for in Table 1. vaccination against viral hepatitis A.4-6 Children with chronic liver disease would theoretically benefit from the HAV vaccine, since it has been shown to be Table 1 - Etiologic diagnoses of the chronic liver diseases immunogenic and safe in controlled studies with immunocompetent children.6-8 The fact that the vaccine is Diagnosis n (%) safe and effective in healthy adults and children does not guarantee similar results in populations with chronic liver EHBA 26 (43) disease.1 Studies performed with adults suggested that Autoimmune hepatitis 13 (22) while patients with chronic liver diseases are not at increased Cryptogenic cirrhosis 11 (18) risk for infection, they have a greater risk of fulminant Cystic fibrosis 2 (3) hepatitis caused by the A virus.2,9,10 American death records Hepatitis B 2 (3) indicate a greater prevalence of chronic liver disease in Hepatitis C 1 (2) people who died from fulminant HAV than in people who Histiocytosis 1 (2) died from other causes.5,6,9,10 Sclerosing cholangitis 1 (2) Congenital hepatic fibrosis 1 (2) Neither an immunization scheme nor a seroconversion Budd-Chiari syndrome 1 (2) rate for populations with chronic hepatic diseases have been Alagille syndrome 1 (1) defined yet.1 The purpose of this study was to evaluate the prevalence EHBA = Extrahepatic biliary atresia of HAV in children and adolescents with chronic liver diseases at a pediatric hepatology service. Patients and Methods The average age of patients with extrahepatic biliary A study with 60 children and adolescents with chronic atresia (EHBA) was 3.9 years; for the patients in the liver disease was conducted between May 1999 and February autoimmune group it was 11.8 years; for those with 2001. The patients belonged to the Pediatric cryptogenic cirrhosis it was 6.2 years and for the others it Gastroenterology Unit and the Pediatric Liver Transplant was nine years. Project of the Pediatric Service of the Hospital de Clínicas The family income of these patients varied between 150 de Porto Alegre. This is a tertiary care hospital, considered and 3,000 reais (40 to 800 US dollars), with a mean average a benchmark in Pediatric Hepatology. of 595.50 reais (US$ 165). The family income of 73% of the Patients with chronic liver disease between one and 16 patients was less than or equal to 500 reais (US$ 138), that years of age, with no previous history of hepatitis A or of 63% of the patient’s families was below R$ 300 (US$ vaccination against HAV, and not carrying the human 83). The minimum salary at this time was R$ 136 (US$ 50). immunodeficiency virus (HIV) were included. They were The median of family incomes was 300 reais with all being assessed or had already been assessed for liver interquartile ranges of R$ 200 (25th percentile) and R$ transplants, some of them were already on the waiting list, 675.00 (75th percentile). others yet to be referred at the time of assessment. The The anti-HAV was obtained using a laboratory test patients suffered from chronic liver diseases confirmed which is commercially available in our setting (Abbott - histologically by liver biopsy or ultrasound scans and HAVAB MEIA - AXSYM system). Venous blood was laboratory tests. collected normally in combination with the patient’s routine blood sampling, and was centrifuged and frozen for later This was a cross-sectional study which evaluated the evaluation. The anti-HAV (total) tests were all performed in presence of the anti-HAV (total) antibody, a marker of the same clinical analysis laboratory (Laboratório hepatitis A infection. The total anti-HAV was determined Weinmann), in Porto Alegre. The results were considered and assessed according to age, sex, color, etiological positive, negative or indeterminate according to positive diagnosis of liver diseases, and patient’s family income. and negative controls. A cutoff value was calculated, below Ages varied between 12 months and 16 years, with an which the sample was positive, and above which it was average (+/- SD) of 7 years (+/- 4.9). There were 25 children negative. Tests with an absorbance within the gray scale, between one and four years old, nine between 5 and 8, 19 which corresponds to more or less 10% of the cutoff value, between 9 and 12 and seven adolescents between 13 and 16 were considered indeterminate. These tests were repeated, years old. using a fresh sample, and if they continued to yield values Thirty-three children (55%) were female and 92% were within the gray scale, i.e. indeterminate, they were eliminated white. from the study. Prevalence of hepatitis A antibody... - Ferreira CT et alii Jornal de Pediatria - Vol. 78, Nº6, 2002 505 The two groups (anti-HAV positive and negative) were Table 2 - Positivity of anti-HVA related to age compared using the chi-squared test with Yates’ correlation Age group Positive Total Percentage (for the sex variable), Fisher’s exact test (for color), the anti-HVA (n) (n) of positivity* Student’s t test (for age) and the Mann-Whitney U test (for family income). In addition, the chi-squared test for linear 1 to 4 years 5 25 20% trend was used to check the association between anti-HAV 5 to 8 years 2 9 22% and increase in the age of the patients. The significance 9 to 12 5 19 26% level was set at 0.05. 13 to16 2 7 29% The study was approved by the Ethics and Research * Chi-squared test for linear trend (p = 0.6) Committee of the Hospital de Clínicas de Porto Alegre. All of the patients’ parents or legal guardians signed consent forms after being informed of the nature of the study. The comparison between the positive and negative groups is shown in Table 3. Of the children who were anti-HAV positive, chronic Results autoimmune liver disease was detected in five, cryptogenic Of the 60 children and adolescents with chronic liver cirrhosis in four, EHBA in three, Budd-Chiari syndrome in disease, only one was excluded because, on two different one and biliary cirrhosis with associated histiocytosis in occasions, the anti-HAV antibody result was indeterminate.