Hepatitis A and B virus infections in children in Kuwait

In a 1-year prospective study of 1788 cases of acute viral hepatitis, 26 (1.5%) presented with evidence of simultaneous hepatitis A (HAV) and hepatitis B (HBV) virus infection. Twenty-three of 26 (88.5%) of these cases had serological evidence of a recent HAV infection in a chronic HBV carrier. The remaining 3 (11.5%) showed serological evidence of a recent concomitant HAV/HBV infection. Twenty-four of the 26 (92.3%) patients with simultaneous infection were children with a mean age of 4.6 years. Clinical and laboratory data indicated that the disease in patients with a recent concomitant HAV/HBV infection was not different from that in patients who had HAV infection superimposed on a chronic HBV carrier or that in age and sex matched patients presenting with an acute viral hepatitis A infection alone. Furthermore, the outcome of the disease was not affected by the HBeAg/anti-HBe status of the hepatitis B positive patient. All patients recovered completely and on follow-up none showed any signs of chronic liver disease. Simultaneous HAV/HBV infection, therefore, does not result in a more severe disease.     

THROMBOCYTOPENIA AND EMPERIPOLESIS IN A PATIENT WITH HEPATITIS A INFECTION

Immune thrombocytopenia is a benign, self-limiting disease in children, responding well to treatment and generally associated with viral infections. A 13-year-old girl was admitted to a hospital with the epistaxis and purpura after an attack of jaundice 6 weeks before. The diagnosis of hepatitis A virus (HAV)-induced thrombocytopenia was made. Furthermore, erythrophagocytosis by megakaryocytes was demonstrated in the bone marrow of the patient. Although hematologic complications following hepatitis B and C viruses are commonly reported, the association of hepatitis A virus and thrombocytopenia has rarely been described.     

Concurrent reactivation of latent EBV with hepatitis A can affect clinical feature of childhood hepatitis

Aims: Some children with acute hepatitis A virus (HAV) infection have concurrent Epstein–Barr virus (EBV) reactivation serologically. We studied the frequency of EBV reactivation during HAV infection and determined whether simultaneous occurrence of EBV reactivation and HAV infection affected the clinical features of HAV infection. Methods: The medical records of patients under 19 years of age diagnosed with acute hepatitis A between January 1996 and June 2009 were reviewed. Results: Among 72 patients with acute hepatitis A, 22 patients (30.6%) had EBV reactivation. A markedly prolonged duration of full recovery from hepatitis was observed in reactivated group. The peak levels of AST and ALT in reactivated group were higher than non‐reactivated group (p = 0.012 and p < 0.001, respectively). Higher peak levels of AST and ALT in reactivated subgroups over 10 years old were observed compared to non‐reactivated subgroup (p = 0.027 and p = 0.001, respectively). Duration of recovery showed significant differences between two subgroups. Conclusions: Concurrent reactivation of latent EBV and HAV infections is common. EBV reactivation with HAV infection adversely affects the clinical feature of hepatitis. Therefore, we should keep in mind that the concurrence especially in older children may cause worse injury to the liver.     

Unusual cause of abdominal pain in pediatric emergency medicine

Atypical manifestations of acute hepatitis A virus (HAV) infection include ascites, pleural effusion, acute renal failure, aplastic anemia, and neurological manifestations. Although association of HAV and acute cholecystitis is known, presentation of hepatitis A infection with acute cholecystitis has not been reported in pediatric emergency medicine literature. Primary acute acalculous cholecystitis in children is rare and commonly attributed to systemic infections. We report a case of a child developing acute viral cholecystitis as a presenting feature of sporadic HAV infection and review HAV-associated cholecystitis in children. The article provides a brief illustration of evaluating acute abdominal pain in older children in the emergency department in a developing country.     

Liver failure attributable to hepatitis A virus infection in a developing country

In young children hepatitis A virus (HAV) infections are usually subclinical events. However, HAV is also associated with progressive hepatic failure and even death in some patients. This study was undertaken to characterize the course of hepatitis A-related acute liver failure in children from a developing country where hepatitis A is endemic and produces significant morbidity. Patients <15 years of age with confirmed hepatitis A, seen at the Aga Khan University Hospital between January 1991 and August 1998 were identified using the patient registry. Of the 2735 patients seen with hepatitis A, 232 were admitted to the hospital. Of these 30 patients developed progressive hepatic dysfunction and liver failure. During this period, 45 children were admitted with liver failure attributable to other causes. Of the patients admitted with hepatitis A-related liver failure, 25 (83.3%) were encephalopathic at presentation and 36.7% of the patients died. The prothrombin time was the most significant predictor of survival. There was a significant difference between those who survived and those who died on discriminant analysis with respect to age, grade of hepatic encephalopathy, duration of hospitalization, prothrombin time, and duration of jaundice when taken as a group. There is a striking prevalence of liver dysfunction progressing to hepatic failure among children seen at a hospital in Karachi, Pakistan. This study demonstrates the significant morbidity and mortality that can attend HAV infections in children in a developing country despite tertiary medical facilities. The risk of HAV and its sequelae could probably be effectively reduced in these settings with improved sanitation and universal immunization.     

Acute cholecystitis disclosing A virus hepatitis

Three children presenting with HAV hepatitis had an initial clinical onset suggestive of acute cholecystitis (pain and guarding in the right hypochondrium, fever and delayed jaundice) associated with important ultrasonographic abnormalities, also very suggestive of acute cholecystitis: bladder wall thickness greater than 10 mm (3 cases), the presence of 2 or 3 layers of different echogenicities (3 cases), presence of an ultrasonographic Murphy's sign (one case), contents of the gallbladder echogenic (one case). The authors discuss the hypothesis of an actual initial acute cholecystitis.     

Hepatitis A as an etiologic agent of acute liver failure in Latin America

BACKGROUND: This prospective, multicenter study examined the importance of hepatitis viruses as etiological agents of acute liver failure (ALF) and the outcome of ALF cases in Latin American children and adolescents. METHODS: The study was conducted for minimum 12 months in 9 centers in Argentina, Brazil, Chile, Colombia, Costa Rica, and Mexico during 2001-2002. Hospitalized patients aged 1-20 years with a suspected diagnosis of ALF were included in the study and tested for serologic markers for hepatitis A, B, and C viruses. RESULTS: Of the 106 patients enrolled, 88 were included in the analysis. Median age was 5 years, and 55% with ALF were aged 1-5 years. A total of 37 individuals (43%) tested positive for anti-hepatitis A virus (HAV) immunoglobulin M (IgM) as marker of acute HAV infection; one was positive for anti-hepatitis B core antigen IgM and negative for hepatitis B surface antigen. None had markers of hepatitis C virus infection. Mortality rates in the overall study cohort (45%) and for those who tested anti-HAV IgM positive (41%) were similar. Forty-one percent of all patients and 46% of those positive for anti-HAV IgM underwent transplantation. The mortality rate in those with liver transplantation was half of that in patients who were not transplanted (28% versus 57%). CONCLUSIONS: HAV was the main etiologic agent of ALF in the population studied.     

Severe neonatal toxoplasmosis after third trimester maternal infection

We report an unusual case of neonatal toxoplasmosis. After a late third trimester maternal infection, the infant developed severe disseminated intravascular coagulopathy with thrombocytopenia, hepatitis, jaundice and severe pneumonitis. Clinicians that manage infants with severe unexplained systemic disease should consider the possibility of congenital toxoplasmosis.     

Septo-optic dysplasia and hemophagocytic lymphohistiocytosis in an infant

Macrophage activation in hemophagocytic lymphohistiocytosis (HLH) leads to severe inflammation resulting in cytopenias and multi-organ dysfunction. Septo-optic dysplasia (SOD) is an as-yet unaffiliated disorder that manifests with optic, hepatic, endocrine and/or constitutional defects. We detail the first reported occurrence of both HLH and SOD in one patient. This two-month old patient presented with acute hepatitis, direct hyperbilirubinemia, anemia and thrombocytopenia. Treatment followed standard of care practices for SOD and HLH. The patient subsequently underwent an allogeneic bone marrow transplant within eight months of diagnosis and remained in full remission at day +90. We suggest considering a diagnosis of HLH in patients with SOD who present with severe liver failure refractory to standard therapy.     

Preliminary results on blood carnitine levels in children with hepatic pathology

A deficiency of exogenous and endogenous carnitine is present in those pathologies in which the most important clinical sign is represented by weakness and steatosis. We have studied the serum levels of carnitine in 14 children with hepatic disease (8 with acute HAV hepatitis, 2 with acute HBV hepatitis, 2 with toxic hepatitis, 2 with chronic hepatitis). In patients with acute, infective and toxic hepatitis we have found levels of carnitine (25.71 +/- 2.14 nM/ml) below normal (50.87 +/- 1.46 nM/ml). In 5 cases we have performed two blood tests, at admittance to the hospital and at the end of the illness. The variability in carnitine levels in these two blood exams shows a clear correlation with clinical improvement, decrease in aminotransferase and increase in serum carnitine. In chronic hepatitis we have found normal levels of carnitine. Probably it is correlated with the absence of steatosis seen at hepatic biopsy.     

Disappearance of IgM antibodies to hepatitis A virus after an acute infection in children and adolescents

The kinetics of IgM antibodies to hepatitis A virus (HAV) following an acute infection, were studied in 17 children. Antibodies disappeared in two patterns, one group at 113 +/- 18 days after the acute infection in the children, and the second group at 283 +/- 90 days. The same two patterns of kinetics were seen in adults. We conclude that IgM anti-HAV antibodies can be found in the sera of children for over 6 months after the acute infection, as was observed in adults.     

Hepatitis viruses of man: transmission, epidemiology and immunology (author's transl)

The isolation and characterization of the hepatitis A virus (HAV) and the hepatitis B virus (HBV) resulted in great advances in the serological diagnosis and the prophylaxis. About 20% of the viral hepatitis cases are caused by the HAV. The hepatitis A never becomes chronic and can be diagnosed by the detection of HAV antibodies of the IgM type. The HBV is the etiologic agent in 60% of the hepatitis cases and 10% of these become chronic. It is possible to immunize against the HBV and to reduce the number of neonatal infections.     

Negative serology for hepatitis A and B viruses in 18 cases of neonatal cholestasis

Serologic evidence of hepatitis A virus (HAV) or hepatitis B virus (HBV) infection was sought in 14 patients with biliary atresia and in four patients with neonatal hepatitis; maternal serum was also analyzed. Specific sensitive radioimmunoassays were used to detect HBV surface antigen (HBsAg) and antibody (anti-HBs); complement fixation was used to detect antibody to HBV core antigen (anti-HBc). Antibody to HAV (anti-HAV) was assayed by radioimmunoassay, as well as by immune adherence hemagglutination. There was no evidence of active or past HBV infection in any infant or mother studied. All three infants with detectable anti-HAV were born to mothers similarly anti-HAV positive; serial testing of sera from two of these infants documented disappearance of detectable anti-HAV by 9 months of age. It is unlikely, therefore, that either HAV or HBV had an etiologic role in neonatal cholestasis in these patients. The role of other (non-A, non-B) hepatitis viruses or nonviral etiologies must be investigated.     

Thrombocytopenia and Plasmodium falciparum malaria in children with different exposures.

We studied thrombocytopenia during acute Plasmodium falciparum malaria in 64 traveller children from Paris (France), 85 children from Dakar (Senegal) with an intermittent exposure (69 with severe attack or cerebral malaria), and 81 children from Libreville (Gabon) with a perennial exposure (43 with severe attack or cerebral malaria). Initial thrombocytopenia was present in 43-58% of children with P falciparum malaria but was not more frequent in severe outcome or cerebral malaria. Low parasitaemia may lead to the misdiagnosis of malaria and delayed treatment when there is associated thrombocytopenia     

Thrombocytopenia and Plasmodium falciparum malaria in children with different exposures

We studied thrombocytopenia during acute Plasmodium falciparum malaria in 64 traveller children from Paris (France), 85 children from Dakar (Senegal) with an intermittent exposure (69 with severe attack or cerebral malaria), and 81 children from Libreville (Gabon) with a perennial exposure (43 with severe attack or cerebral malaria). Initial thrombocytopenia was present in 43-58% of children with P falciparum malaria but was not more frequent in severe outcome or cerebral malaria. Low parasitaemia may lead to the misdiagnosis of malaria and delayed treatment when there is associated thrombocytopenia     

Virological and serological study in children hospitalized for acute hepatitis (detection of HBsAg, HAAg, anti-HAV and specific IgM-anti-HAV)

Serological methods were used to detect different markers of hepatitis A and B infection in a series of 36 children aged 3.5-13 years with acute viral hepatitis, hospitalized from August 1978 to October 1978. Hepatitis A was verified serologically in 30 patients (83.3%) with the demonstration of specific IgM-anti-HAV. Hepatitis B infection was serologically confirmed in only 2 patients (5.5%). After exclusion of hepatitis A and B as well as of hepatitis due to cytomegalovirus, leptospira and Epstein-Barr virus, 3 patients (8.3) were classified to have post-transfusion non-A non-B hepatitis, and 1 patient (2.5%) showed a sporadic non-A non-B hepatitis. The finding of HBsAg in 5 of 30 patients with hepatitis A suggests that the presence of HBsAg during the acute icteric phase of viral hepatitis is not sufficient for a diagnosis of HB. The presence of HAAg in one of 30 patients with HA confirms previous studies that faecal shedding of HAV stops with the appearance of jaundice. Finally, the above results establish the value of the new radioimmunoassay technique for detection of specific IgM-anti-HAV, which appears to be the best diagnostic test for hepatitis A.     

Asymptomatic viral hepatitis types A and B in an adolescent population.

Sera from 95 adolescents were examined for markers of hepatitis B virus (HBV) infection and hepatitis A virus (HAV) infection. HBV markers were found in eight adolescents (8%) and evidence of previous HAV infection was found in 18 adolescents (19%); none had a history of clinically recognizable hepatitis. These findings support the growing evidence that HBV and HAV infections are diseases of the pediatric age group, and that testing of HBV vaccines when they become available for patient use will have to include a pediatric population.     

甲肝减毒活疫苗及加服牛磺酸在接种乙肝疫苗免疫失败儿童中的致免疫性

目的为了估价甲肝减毒活疫苗在接种乙肝疫苗免疫失败儿童中的致免疫性和牛磺酸对该疫苗免疫性的影响。方法应用随机对照临床试验。选择９０名健康儿童随机分成二组：４３名接种甲肝减毒活疫苗和口服牛磺酸（Ⅰ组）；４７名接种疫苗加口服安慰剂（Ⅱ组）。另选择６２名由携带ＨＢＶ的无症状母亲所生接种过乙肝疫苗但是免疫失败者（Ⅲ组）和４４名同龄由ＨＢｓＡｇ阴性母亲所生接种乙肝疫苗正常免疫反应的健康儿童（Ⅳ组），均接种甲肝减毒活疫苗作比较。所有对象均除外甲肝感染，接种后观察反应，２个月后检测血清－ＨＡＶＩｇＧ抗体。结果Ⅰ组抗ＨＡＶＩｇＧ平均值显著高于Ⅱ组（ｔ＝７．１０９，Ｐ＜０．０１）；Ⅳ组接种甲肝疫苗后抗－ＨＡＶＩｇＧ平均值与Ⅲ组比较，差异有显著性，（ｔ＝１．９９８，Ｐ＜０．０５）。结论接种乙肝疫苗免疫失败儿童接种甲肝减毒活疫苗的免疫效果比健康儿童差。甲肝减毒活疫苗接种后随访未发现明显副反应。牛磺酸对疫苗接种效果的辅助作用值得推广应用。