Margarita Ramonet

Follow-up of children with autoimmune hepatitis treated with cyclosporine.

Objectives: To evaluate the effectiveness of cyclosporine in inducing and maintaining remission of the inflammatory process in autoimmune hepatitis, when used in combination with low doses of prednisone and azathioprine and to identify the prognostic factors associated with sustained remission. Methods: Eighty-four patients with autoimmune hepatitis were consecutively recruited from 5 centers between January 1994 and March 2001. Cyclosporine was administered during the first 6 months. Thereafter, in patients with aminotransferase levels of lower than twice the normal values, prednisone and azathioprine were initiated. Results: Normal aminotransferase levels were observed in 94.05% (79/84) of the patients, 72% of them within the first 6 months of treatment. Total serum bilirubin level of greater than 1.2 mg/dL and portal hypertension at diagnosis jointly predicted a significant delay in remission. Adverse effects related to cyclosporine remained mild and transient. Low doses of prednisone and standard doses of azathioprine were not implicated in relapse of the disease during the follow-up of any patient. Conclusions: This protocol allowed control of the liver inflammatory process and was well tolerated. The response to this immunosuppressive therapy can be predicted with accuracy. Factors delaying remission can be identified early at diagnosis and may contribute to the development of more effective treatment policies for this condition.

Prognostic factors in paediatric acute liver failure

Objectives: To study the aetiology, outcome and prognostic indicators in children with acute liver failure (ALF). Study design: Retrospective chart review of 210 patients (107 males/103 females; median age: 5.33 years, range: 1–17.4). Patients were followed until discharge (group 1), death (group 2) or liver transplantation (LT; group 3). Data from group 1 were compared to data from the other two groups and King’s College criteria were also assessed. Results: Final diagnoses were: 128 (61%) hepatitis A, 68 (32%) indeterminate and 14 (7%) others. The characteristics of patients who survived (n = 59), died (n = 61) and underwent LT (n = 90) were analysed. In multivariate analysis, prothrombin time and encephalopathy III/IV were the most significant parameters suggesting a high likelihood of death. When King’s College criteria were applied on admission in patients with and without transplantation, the positive predictive values were 96% and 95%, and the negative predictive values were 82% and 82%, respectively. Conclusions: Hepatitis A is the main cause of ALF in children in Argentina. Advanced encephalopathy and prolonged prothrombin time were significantly associated with death or need for LT. King’s College criteria for predicting the outcome of ALF are applicable in children, including those with ALF due to hepatitis A infection.

Single-Dose Universal Hepatitis A Immunization in Argentina: Low Viral Circulation and High Persistence of Protective Antibodies Up to 4 Years

BACKGROUND Single-dose hepatitis A virus (HAV) vaccination was implemented in all Argentinean children aged 12 months in 2005. Between 2005 and 2011, a dramatic decline was observed in HAV infection rates, fulminant hepatitis, and liver transplantation. This study assessed current viral circulation and estimated protective antibody persistence 4 years after vaccination. METHODS Prevalence of prevaccination anti-HAV antibodies in 12-month-old children was evaluated as an indirect estimation of viral circulation (Group A). Seroprevalence was also measured in 5-year-old children who received 1 dose of HAV vaccine at 1 year of age (Group B). Blood samples were tested for immunoglobulin (Ig)G anti-HAV antibodies (seroprotection = ≥10 mIU/mL). All Group A-positive samples were tested for IgM anti-HAV antibodies to identify recent infections. Logistic regression analysis was done to evaluate associations between demographic and socioeconomic variables and seroprotection. RESULTS Of 433 children from Group A, 29.5% (95% confidence interval [CI], 25.2-33.8) were positive for IgG anti-HAV antibodies with a geometric mean concentration (GMC) of 6.17 mIU/mL (95% CI, 5.33-7.15 mIU/mL); all IgM anti-HAV were negative. From 1139 in Group B, 93% (95% CI, 91.7-94.6) maintained seroprotection with a GMC of 97.96 mIU/mL (95% CI, 89.21-107.57 mIU/mL). Kindergarten attendance was associated with seroprotection in Group B (odds ratio [OR], 2.0; 95% CI, 1.26-3.3). In contrast, high maternal educational level was associated with a lack of seroprotection in this group (OR, .26; 95% CI, .09-.8). CONCLUSIONS Single-dose, universal hepatitis A immunization in infants resulted in low HAV circulation and persistent immunologic protection up to 4 years in Argentina. Variables associated with presence or absence of seroprotection in vaccinated children could be related to differences in hygiene habits in settings with residual viral circulation.

Single-dose Universal Hepatitis A Immunization in One-year-old Children in Argentina: High Prevalence of Protective Antibodies up to 9 Years After Vaccination.

Background: Single-dose hepatitis A virus (HAV) vaccination was implemented in all Argentinean children 12 months of age in 2005. Previous studies demonstrated high prevalence of protective antibody response 4 years after single-dose vaccination. This study assessed long-term seroprotection against HAV after vaccination. Methods: Children who received 1 dose of HAV vaccine at 1 year of age at least 6 years before enrollment were included at 5 centers in Argentina between 2013 and 2014. Demographic and socioeconomic characteristics were collected through a questionnaire. Blood samples were tested for anti-HAV antibodies. Antibody values ≥10 mIU/mL were considered seroprotective. Logistic regression analysis was performed to evaluate the association between demographic and socioeconomic variables and seroprotection. Results: A total of 1088 children were included, with a median postvaccination interval of 7.7 years (range 6.3–9.2 years). Of these children, 97.4% (95% confidence interval: 96.3%–98.3%) had protective antibodies against HAV. No association between demographic or socioeconomic variables and seroprotection was found. Geometric mean concentration of antibody levels against HAV was 170.5 mUI/mL (95% confidence interval: 163.2–178.2 mUI/mL). Conclusions: Single-dose universal hepatitis A immunization in 1-year-old children resulted in sustained immunologic protection for up to 9 years in Argentina. These findings, along with the low current disease burden, confirm the success of the intervention.