The immunogenicity of a single dose of hepatitis A virus vaccines (Havrix® and Epaxal®) in Korean young adults.

PURPOSE: Assessing the immunogenicity of a single dose of hepatitis A virus (HAV) vaccines is important because some people receive only a single dose. However, previous studies have shown variable results and have not examined the effects of demographic characteristics other than gender. This study was performed to examine the immunogenicity of a single dose of HAV vaccine according to the vaccine type and demographic characteristics in young adults. MATERIALS AND METHODS: Seronegative medical school students were randomly allocated to receive either Havrix or Epaxal. RESULTS: After approximately 11 months, the seroconversion rate in 451 participants was 80.7%. In men, the Havrix group showed a significantly higher seroconversion rate (81.9%) than the Epaxal group (69.2%), whereas both vaccine groups showed similarly high immunogenicity in women (Havrix: 90.1%, Epaxal: 92.9%; P for interaction=0.062). According to the results of a multivariate analysis, Epaxal showed significantly lower immunogenicity than Havrix only in men. Age, obesity, drinking, smoking, and follow-up time did not significantly affect seroconversion in either gender. CONCLUSION: The seroconversion rate of single-dose HAV vaccines was low in men, particularly in those who received Epaxal. Our results suggest that gender effects should be considered when comparing the immunogenicity of different HAV vaccines.

Clinical features and outcomes of acute kidney injury among patients with acute hepatitis A.

BACKGROUND: Although acute hepatitis A is usually self-limited, the clinical manifestations can vary from mild to severe liver dysfunction. However, little is known about risk factors for and outcomes of acute kidney injury (AKI) in acute hepatitis A. OBJECTIVES: To identify the risk factors for and outcomes of AKI in acute hepatitis A. STUDY DESIGN: We identified 396 patients with acute hepatitis A, which registered between January 2006 and June 2009 at a tertiary care university hospital. Retrospective case-control studies were conducted in order to identify risk factors for AKI. RESULTS: Thirty patients (7.6%) developed AKI. On multivariate analysis, fulminant hepatitis, leukocytosis, and elevated CRP were independent risk factors for AKI associated with hepatitis A, and higher total bilirubin, leukocytosis, and elevated CRP were independent risk factor for AKI within nonfulminant hepatitis A. Of the 30 patients with AKI, 23 (76.7%) patients fully recovered, 2 patients maintained hemodialysis after hospital discharge and 5 patients died due to hepatic failure without recovery from AKI. Among 20 patients with AKI in nonfulminant subgroup, 19 patients (95%) recovered without hemodialysis. CONCLUSIONS: AKI is not a rare complication of acute hepatitis A and severity of hepatitis and hepatic injury influence the development of AKI in acute hepatitis A.

Comparative analysis of disease severity between genotypes IA and IIIA of hepatitis A virus.

Although hepatitis A is a major health problem worldwide, it has not yet been clarified whether or not viral factors affect the clinical characteristics. This study aimed to investigate if a genotype of hepatitis A virus (HAV) affects disease severity among adolescent and adult populations. Clinical data and specimens were collected from patients ≥16-years-of-age with acute hepatitis A at two university hospitals in Korea during the two study periods: 1998 and 1999 (n = 45), and 2009 (n = 66). Nucleotide sequencing of the complete VP1 region of the HAV isolates was performed for phylogenetic analysis and genotyping. Clinical parameters related to disease severity were compared by HAV genotype to determine its clinical relevance. Of the 87 patients, 47 were male and the mean age was 29.8 ± 8.1 years. The genotype IIIA (93.0%, 53/57) was predominant in the year 2009, whereas IA (93.3%, 28/30) was the major genotype in 1998 and 1999. When comparing disease severity between the two HAV genotypes, the patients with genotype IIIA were older and had higher alanine aminotransferase (ALT) levels, prolonged prothrombin times and lower serum albumin levels. In a multivariate logistic regression model, higher ALT levels ≥ 1,000 IU/L (odds ratio [OR] 11.7, 95% confidence interval [CI] 2.5-54.0) and longer hospitalization (OR 22.49, 95%CI 4.6-132.5) were associated independently with genotype IIIA. In conclusion, this study indicates that HAV genotype might be one of the viral factors responsible for the disease severity of hepatitis A.

An outbreak of hepatitis A in Roma populations living in three prefectures in Greece.

An outbreak of hepatitis A virus (HAV) infection affected Roma populations living in three prefectures of northeastern Greece. Between July and November 2007, 124 cases were reported. We carried out investigations to characterize the pathogen, to identify the source of infection and the route of transmission. Using the RT-PCR technique, HAV strains of the same genotype were detected in all sera from a subset of patients with acute disease. These showed more than 99.8% identity, suggesting a common source. A questionnaire was also completed to collect clinical and epidemiological information. The outbreak affected mainly Roma children aged <10 years. An inspection of Roma settlements showed that poor sanitary conditions were associated with the HAV outbreak.

Acute viral infections in patients with systemic lupus erythematosus: description of 23 cases and review of the literature.

Few studies have evaluated the impact of viral infections on the daily management of patients with systemic lupus erythematosus (SLE). We analyzed the etiology and clinical features of acute viral infections arising in patients with SLE and their influence on the diagnosis, prognosis, and treatment of SLE. Cases occurring within the last 5 years were selected from the databases of 3 large teaching hospitals. Acute viral infections were confirmed by the identification of specific antiviral IgM antibodies and subsequent seroconversion with detection of specific IgG antibodies. In autopsy studies, macroscopic findings suggestive of viral infection were confirmed by direct identification of the virus or viruses in tissue samples. We performed a MEDLINE search for additional cases reported between January 1985 and March 2008. We included 88 cases (23 from our clinics and 65 from the literature review) of acute viral infections in patients with SLE. Twenty-five patients were diagnosed with new-onset SLE (fulfillment of the 1997 SLE criteria) associated with infection by human parvovirus B19 (n = 15), cytomegalovirus (CMV; n = 6), Epstein-Barr virus (EBV; n = 3), and hepatitis A virus (n = 1). The remaining 63 cases of acute viral infections arose in patients already diagnosed with SLE: in 18 patients, symptoms related to infection mimicked a lupus flare, 36 patients, including 1 patient from the former group who presented with both conditions, presented organ-specific viral infections (mainly pneumonitis, colitis, retinitis, and hepatitis), and 10 patients presented a severe, multiorgan process similar to that described in catastrophic antiphospholipid syndrome-the final diagnosis was hemophagocytic syndrome in 5 cases and disseminated viral infection in 5. Twelve patients died due to infection caused by CMV (n = 5), herpes simplex virus (n = 4), EBV (n = 2), and varicella zoster virus (n = 1). Autopsies were performed in 9 patients and disclosed disseminated herpetic infection in 6 patients (caused by herpes simplex in 4 cases, varicella in 1, and CMV in 1) and hemophagocytic syndrome in 3. A higher frequency of renal failure (54% vs. 19%, p = 0.024), antiphospholipid syndrome (33% vs. 6%, p = 0.023), treatment with cyclophosphamide (82% vs. 37%, p = 0.008), and multisystemic involvement at presentation (58% vs. 8%, p < 0.001); and a lower frequency of antiviral therapy (18% vs. 76%, p < 0.001) were found in patients who died, compared with survivors. The most common viral infections in patients with SLE are parvovirus B19 (predominantly mimicking SLE presentation) and CMV (predominantly presenting in severely immunosuppressed patients). CMV infection may mimic a lupus flare or present with specific organ involvement such as gastrointestinal bleeding or pulmonary infiltrates. Other herpesviruses are common in immunosuppressed SLE patients and may produce a wide range of manifestations. Physicians should examine the pharynx, eyes, skin, and genitalia and should conduct serologic and molecular studies to improve early detection of viral infection in patients with SLE.

Genetic analysis of hepatitis A virus protein 2C in sera from patients with fulminant and self-limited hepatitis A.

BACKGROUND/AIMS: To examine whether genetic differences in hepatitis A virus (HAV) are responsible for the range of clinical severities, we analyzed the HAV 2C genome, whose mutations have previously been shown to be important for enhanced replication in cell culture systems and to be related to virulence in simians. METHODOLOGY: Serum samples from 45 Japanese patients with sporadic hepatitis A, comprising 9 patients with fulminant hepatitis (FH), 10 with severe acute hepatitis (AHs), and 26 with self-limited acute hepatitis (AH), were examined for HAV RNA. RESULTS: Compared with the sequence of wild-type HAV strain HM-175, the nucleotide sequences of 2C had homology of 89.0 +/- 0.6% in FH, 88.6 +/- 0.9% in AHs, and 89.0 +/- 1.6% in AH. Differences were not statistically significant among the three groups. Deduced amino acid sequences had homology of 97.6 +/- 0.4% in FH, 96.5 +/- 1.9% in AHs, and 96.8 +/- 1.7% in AH. The difference between FH and AH was statistically significant (p < 0.05), although there were no specific nucleotide or amino acid substitutions. CONCLUSIONS: Fulminant hepatitis patients had fewer amino acid substitutions in 2C, indicating the association between severity of hepatitis A and amino acid variations in 2C of HAV.

Spontaneous renal laceration as the presenting feature of polyarteritis nodosa in a patient with familial Mediterranean fever after hepatitis A infection.

We report a life-threatening spontaneous renal laceration with no history of bleeding diathesis or any trauma in a patient with FMF after acute hepatitis A virus (HAV) infection. Right nephrectomy was inevitable and histological investigation of the removed right kidney revealed a polyarterits nodosa (PAN). This case underlines the possibility that simultaneous PAN and immunsupressive treatment besides colchicine should be considered for patients with FMF. Also, patients with FMF who are not immune may be vaccinated for HAV which could be a predisposing mechanism for vasculitic hemorrhage.

Mechanisms of inactivation of hepatitis A virus in water by chlorine dioxide.

In this study, to elucidate the mechanisms of inactivation of hepatitis A virus (HAV) by chlorine dioxide, cell culture, enzyme-linked immunosorbent assay (ELISA), and long-overlapping RT-PCR were used to detect the infectivity, antigenicity, and entire genome of HAV before and after disinfection. The results revealed the complete inactivation of infectivity after a 10-min exposure to 7.5mg of chlorine dioxide per liter; and the highest level of sensitivity in the 5'non-translated regions (5'NTR) (the sequence from bp 1 to 671), inactivation of which took as much time as the inactivation of infectivity of HAV by chlorine dioxide; the complete destruction of antigenicity after a 10-min exposure to 7.5mg of chlorine dioxide per liter. It is suggested that the inactivation mechanism of HAV by chlorine dioxide was due to the loss of the 5'NTR and/or destruction of the antigenicity, which is not similar to that of chlorine (Appl Environ Microbiol 68: 4951).

Hepatitis A virus suppresses monocyte-to-macrophage maturation in vitro.

To analyze the pathogenetic mechanism of hematopoietic dysregulation associated with hepatitis A virus (HAV) infections, we studied the influence of HAV on monocyte (MO)-to-macrophage (MAC) maturation in vitro. Exposure of peripheral blood-derived mononuclear cells (MNC) to HAV led to diminished adherence of MO to plastic. Furthermore, HAV inhibited the ability of peripheral blood MO to differentiate toward MAC. Freshly isolated and 14-day-old MO cultures demonstrated reduced differentiation and decreased phagocytic capacity after challenge with HAV. Viral replication in MO/MAC cultures was confirmed by titration of infectious virus. We also determined the influence of HAV on the MO/MAC population in human long-term bone marrow cultures (LTBMCs). Inoculation of bone marrow MNC with HAV suppressed the establishment of an adherent stromal layer containing a reduced number of MAC. Furthermore, increased MO numbers in the nonadherent fraction of HAV-challenged LTBMCs are indicative of the disturbance of MO adherence. These findings suggest that HAV infection leads to a disorder of the mononuclear phagocytic system which may contribute to functional abnormalities of the bone marrow stroma.

Serological and molecular testing in viral hepatitis: an update.

The routine serological diagnoses of the three major forms of viral hepatitis - A, B and C - as well as delta hepatitis, are important in the evaluation of acute and chronic viral hepatitis. Increasingly, molecular virology is also being used to evaluate patients with chronic hepatitis C, with genotype and viral load testing to plan therapy.

Hepatitis A: old and new.

The hepatitis A virus (HAV), a picornavirus, is a common cause of hepatitis worldwide. Spread of infection is generally person to person or by oral intake after fecal contamination of skin or mucous membranes; less commonly, there is fecal contamination of food or water. Hepatitis A is endemic in developing countries, and most residents are exposed in childhood. In contrast, the adult population in developed countries demonstrates falling rates of exposure with improvements in hygiene and sanitation. The export of food that cannot be sterilized, from countries of high endemicity to areas with low rates of infection, is a potentially important source of infection. After ingestion and uptake from the gastrointestinal tract, the virus replicates in the liver and is excreted into the bile. Cellular immune responses to the virus lead to destruction of infected hepatocytes with consequent development of symptoms and signs of disease. Humoral immune responses are the basis for diagnostic serologic assays. Acute HAV infection is clinically indistinguishable from other causes of acute viral hepatitis. In young children the disease is often asymptomatic, whereas in older children and adults there may be a range of clinical manifestations from mild, anicteric infection to fulminant hepatic failure. Clinical variants include prolonged, relapsing, and cholestatic forms. Management of the acute illness is supportive, and complete recovery without sequelae is the usual outcome. Research efforts during World War II led to the development of passive immunoprophylaxis. Pooled immune serum globulin is efficacious in the prevention and attenuation of disease in exposed individuals. More recently, active immunoprophylaxis by vaccination has been accomplished. Future eradication of this disease can now be contemplated.

Hepatitis A.

Hepatitis A remains an important cause of community-acquired hepatitis in the United States and in the world. In recent years, improvements in personal hygiene and environmental sanitation have led to declines in overall hepatitis A infection rates in developed countries, although sporadic outbreaks still occur with similar rates of hospitalization and loss of work. Therapy remains supportive and prevention holds the key to elimination of widespread infection. Acute infection can be prevented or attenuated with IG or with inactivated, highly immunogenic vaccines. Elderly persons and those with advanced liver disease are at higher risk of the consequences of acute HAV, and they represent target populations for immediate vaccination. Challenges for the future include strategies for broad-based population vaccination, including cost-effective approaches.

Evaluation of occupational transmission of hepatitis A virus among wastewater workers.

To provide information concerning potential occupational transmission of hepatitis A virus (HAV) among wastewater workers in a large city in the United States, a cross-sectional survey was performed using a saliva test to detect antibodies to HAV (anti-HAV). Fifty-nine (20%) of 302 participants tested positive for anti-HAV. After controlling for the confounding effects of age and race, wastewater work was not significantly associated with an increase in the prevalence of anti-HAV (prevalence ratio = 1.3; 95% confidence interval 0.7 to 2.4). Additionally, when examining only the wastewater workers, no statistically significant occupational risk factors for anti-HAV were identified. The results of this survey are consistent with the position of the Centers for Disease Control and Prevention regarding groups at risk for HAV infection.

The hepatitis alphabet--hepatitis A-G and TTV.

During the past three decades the number of viruses known to be capable to inducing liver inflammation has been considerably expanded. This short review gives a quick overview of the virologic characteristics, clinical manifestations, diagnosis, and treatment options. Newer hepatitis viruses such as hepatitis E virus (HEV), hepatitis GB-virus C/hepatitis G virus (GBV-C/HGV), and transfusion-transmitted virus (TTV) are discussed and data concerning their disease-inducing capacity reviewed.

Utilization of chimeras between human (HM-175) and simian (AGM-27) strains of hepatitis A virus to study the molecular basis of virulence.

Chimeras between human (HM-175) and simian (AGM-27) strains of hepatitis A virus (HAV) were constructed to evaluate the effect of the 2C gene of AGM-27 on HAV replication in cell culture and virulence in tamarins (Saguinus mystax) and chimpanzees (Pan troglodytes). Kinetic studies and radioimmunofocus assays demonstrated that replacement of the 2C gene of HAV/7, a cell culture-adapted strain of HM-175, with that of AGM-27 drastically reduced the ability of the virus to replicate in cultured cells. Intragenic chimeras containing AGM-27 sequences in either the 5' or 3' half of the 2C gene replicated in cell culture at an intermediate level. Whereas HAV/7 is attenuated for tamarins, a chimera containing the simian virus 2C gene in the HAV/7 background was virulent in tamarins, demonstrating that the simian virus 2C gene alone can confer the phenotype of virulence to an otherwise attenuated virus. Clusters of AGM-27-specific residues near both ends of the 2C protein were required for virulence since a chimera containing AGM-27 sequences in the carboxy-terminal half of 2C was partially attenuated for tamarins while one containing AGM-27 sequences only in the amino-terminal half of 2C was even more attenuated. Chimeras containing either the entire or only the 3' half of the simian virus 2C gene in the HAV/7 background were attenuated for chimpanzees.