Acute Hepatitis B in a patient previously positive for antibody to surface antigen (anti-HBs) determined by radioimmunoassay: case report and review of the literature

The determination of anti-HBs as a screening test before vaccination has been advisable in order to encounter immune individuals that don't need to receive vaccine protection. A case-report is presented and three other cases are reviewed from the literature. Anti-HBs was positive in these health-care personnels that developped typical acute B hepatitis. Different subtyping involving the d/y determinants were found in the first case, but false-positive anti-HBs even with high titres, determined by RIA, were found in the other cases. Concomitant determination of anti-HBc or absence of screening tests seem to be more reasonable policies until a low-cost and risk-free vaccine is produced.

Confluent peripheral multiple mononeuropathy associated to acute hepatitis B: a case report

A thirty three year-old, male patient was admitted at the Hospital of the São Paulo University School of Medicine, at the city of São Paulo, Brazil, with complaint of pains, tingling and decreased sensibility in the right hand for the last four months. This had progressed to the left hand, left foot and right foot, in addition to a difficulty of flexing and stretching in the left foot. Tests were positive for HBeAg, IgM anti-HBc and HBsAg, thus characterizing the condition of acute hepatitis B. The ALT serum level was 15 times above the upper normal limit. Blood glucose, cerebral spinal fluid, antinuclear antibodies (ANA) and anti-HIV and anti-HCV serum tests were either normal or negative. Electroneuromyography disclosed severe peripheral neuropathy with an axon prevalence and signs of denervation; nerve biopsy disclosed intense vasculitis. The diagnosis of multiple confluent mononeuropathy associated to acute hepatitis B was done. This association is not often reported in international literature and its probable cause is the direct action of the hepatitis B virus on the nerves or a vasculitis of the vasa nervorum brought about by deposits of immune complexes.

Inhibitory effect of liposomal quercetin on acute hepatitis and hepatic fibrosis induced by concanavalin A

Immune response plays an important role in the development of hepatic fibrosis. In the present study, we investigated the effects of quercetin on hepatitis and hepatic fibrosis induced by immunological mechanism. In the acute hepatitis model, quercetin (2.5 mg/kg) was injected iv into mice 30 min after concanavalin A (Con A) challenge. Mice were sacrificed 4 or 24 h after Con A injection, and aminotransferase tests and histopathological sections were performed. Treatment with quercetin significantly decreased the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Consistent with this observation, treatment with quercetin markedly attenuated the pathologic changes in the liver. A hepatic fibrosis model was also generated in mice by Con A challenge once a week for 6 consecutive weeks. Mice in the experimental group were treated with daily iv injections of quercetin (0.5 mg/kg). Histopathological analyses revealed that treatment with quercetin markedly decreased collagen deposition, pseudolobuli development, and hepatic stellate cells activation. We also examined the effects of quercetin on the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transforming growth factor beta (TGF-β) pathways by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR). NF-κB and TGF-β production was decreased after treatment with quercetin, indicating that the antifibrotic effect of quercetin is associated with its ability to modulate NF-κB and TGF-β production. These results suggest that quercetin may be an effective therapeutic strategy in the treatment of patients with liver damage and fibrosis.

Acute pancreatitis associated with acute viral hepatitis: case report and review of literature

This case report, along with the review presented, describes a patient diagnosed with acute viral hepatitis, who developed a framework of intense abdominal pain and laboratorial alterations compatible with acute pancreatitis. The association of acute pancreatitis complicating fulminant and non-fulminant acute hepatitis virus (AHV) has been reported and several mechanisms have been proposed for this complication, but so far none is clearly involved. As acute hepatitis is a common disease, it is important to stimulate the development of other studies in order to determine local incidence and profile of patients presenting this association in our environment.

Acute exacerbation in chronic hepatitis B virus infection

A case of an acute exacerbation of liver injury in a chronic HBV infected young male is reported. The correlation between the severe symptomatic hepatitis is done with the histopathologic findings of extense areas of bridging necrosis on the Iwer biopsy. The serological pattern for markers of HBV (HBsAg +, anti HBs g -, HBeAg -, anti HBe +, anti HBcIgG + and IgM -) confirm a chronic infection, ana the authors propose that the episode of severe hepatitis relates to the recent spontaneous seroconvertion of HBe Ag to anti HBe. Other causes of hepatitis were excluded, and the control liver biopsy (6 months later) showed normalization of hepatic architecture and absence of markers of viral replication in tissue and serum. A review of literature is done in an attempt to elucidate the diagnostic possibilities in this case, with emphasis on new immunoassays useful in differentiating between acute hepatitis B and acute exacerbation of a chronic hepatitis by the same virus.

HEV, TTV and GBV-C/HGV markers in patients with acute viral hepatitis

The aim of the present study was to evaluate the prevalence of HEV, TTV and GBV-C/GBV-C/HGV in patients with acute viral hepatitis A, B and non-A-C. We evaluated sera of 94 patients from a sentinel program who had acute hepatitis A (N = 40), B (N = 42) and non-A-C (N = 12); 71 blood donors served as controls. IgM and anti-HEV IgG antibodies were detected by enzyme immunoassay using commercial kits. TTV and GBV-C/HGV were detected by nested PCR; genotyping was done by sequencing and phylogenetic analysis. Anti-HEV IgG was present in 38, 10 and 17% of patients with hepatitis A, B and non-A-C. Four patients with hepatitis A and 1 with non-A-C hepatitis also had anti-HEV IgM detected in serum. TTV was detected in 21% of patients with acute hepatitis and in 31% of donors. GBV-C/HGV was detected in 9% of patients with hepatitis, and in 10% of donors. We found TTV isolates of genotypes 1, 2, 3, and 4 and GBV-C/HGV isolates of genotypes 1 and 2. Mean aminotransferase levels were lower in patients who were TTV or GBV-C/HGV positive. In conclusion, the detection of anti-HEV IgM in some acute hepatitis A cases suggests co-infection with HEV and hepatitis E could be the etiology of a few cases of sporadic non-A-C hepatitis in Salvador, Brazil. TTV genotype 1, 2, 3 and 4 isolates and GBV-C/HGV genotype 1 and 2 strains are frequent in the studied population. TTV and GBV-C/HGV infection does not appear to have a role in the etiology of acute hepatitis.

Detection of hepatitis A antibodies by ELISA using saliva as clinical samples

The possibility of detecting acute infection and immunity using body fluids that are easier to collect than blood, mainly in children, would facilitate the investigation and follow-up of outbreaks of hepatitis A (HAV). Our study was carried out to evaluate the detection of anti-HAV IgM, IgA and total antibodies in saliva using serum samples as reference. Forty three paired serum and saliva samples were analyzed. From this total, 24 samples were obtained from children and 1 from one adult during the course of acute hepatitis A; an additional 18 samples were obtained from health professionals from Adolfo Lutz Institute. The sensitivity to detect anti-HAV IgM was 100% (95%CI: 79.1 to 100.0%), employing saliva as clinical samples. In detecting anti-HAV IgA, the sensitivity was 80.8% (95%CI: 60.0 to 92.7%) and for the total antibodies was 82.1% (95%CI: 62.4 to 93.2%). The specificity was 100% for each. The rate of agreement was high comparing the results of serum and saliva samples for detecting HAV antibodies. We conclude that saliva is an acceptable alternative specimen for diagnosing acute hepatitis A infection, and for screening individuals to receive hepatitis A vaccine or immunoglobulin.

Labrea-like hepatitis in Vitoria, Espirito Santo state, Brazil: report of a case

A case of fulminat hepatitis with microvesicular steatosis resembling Labrea 's fever, diagnosed in Vitoria (ES) is reported. The 16 year old bcy presented with severe epistaxis, agitation, jaundice and hemorrhagic vomiting and died two days after admission to the emergency unit of the Vnivesity Hospital. The disease started five days before with fever, myalgias, dark urine and jaundice andprogressed withpsychic agitation, torpor and coma. The liver andspleen were notpalpable. HBsAg was negative in the serum. The autopsy showed acute hepatitis with tylic necrosis confluent in the midizonal and periportal areas with massive microvesicular steatosis in the remaining hepatocytes. Mononuclear cellspredominated in the exudate. The reticulum showed condensation in the necrotic areas without typical bands of collapse. The portal tracts were edematous with mononuclear infiltration and mild bile duct proliferation. Absence of cholestasis. Exceptfor the confluent midzonalandperiportal necrosis this case showed several clinical and morphological aspects of the Labreafever describedfrom the East Amazon, demonstrating that the anatomical picture of this disease probabty is not in related to afactor peculiar to the Amazon region.

Acute liver failure in children: observations in Vitória, Espírito Santo State, Brazil

In this communication we report 46 cases of acute liver failure in children diagnosed at the Hospital Infantil Nossa Senhora da Glória in Vitória, E Santo. Serology for IgM anti-HAV, IgM anti-HBc, HbsAg, anti-HCV and biochemical tests were performed in all cases in a routine laboratory. The M/F ratio was 1.1:1 and the mean age was 4.7±3.2 years, without gender difference. Anti-HAV IgM+ in 38 (82.6%) cases, anti-HbcIgM+ in two (4.3 %) cases and 6 (13.1%) cases were negative for all viral markers investigated. Anti- HCV+ in one anti-HAV IgM+ case. HbsAg+ in two anti-HbcIgM+ and in two HAVIgM+ cases. Among the six A, B and C negative cases, four (8.6%) did not have the suspected exogenous intoxication. Mortality was 50%, without gender or age differences. These results demonstrate that HAV infection is the main etiology of acute liver failure in children in Brazil, confirming that, although it is a self limited, relatively mild illness, it can cause serious and even fatal disease. The observation of four cases without A, B and C viral markers and no history of exogenous intoxication, agree with the observation of non A-E acute sporadic hepatitis in Northeastern Brazil.

Evaluation of an enzyme immunoassay for hepatitis C virus antibody detection using a recombinant protein derived from the core region of hepatitis C virus genome

This study was undertaken to evaluate an enzyme immunoassay (EIA) for hepatitis C virus antibody detection (anti-HCV), using just one antigen. Anti-HCV EIA was designed to detect anti-HCV IgG using on the solid-phase a recombinant C22 antigen localized at the N-terminal end of the core region of HCV genome, produced by BioMérieux. The serum samples diluted in phosphate buffer saline were added to wells coated with the C22, and incubated. After washings, the wells were loaded with conjugated anti-IgG, and read in a microtiter plate reader (492 nm). Serum samples of 145 patients were divided in two groups: a control group of 39 patients with non-C hepatitis (10 acute hepatitis A, 10 acute hepatitis B, 9 chronic hepatitis B, and 10 autoimmune hepatitis) and a study group consisting of 106 patients with chronic HCV hepatitis. In the study group all patients had anti-HCV detected by a commercially available EIA (Abbott®), specific for HCV structural and nonstructural polypeptides, alanine aminotransferase elevation or positive serum HCV-RNA detected by nested-PCR. They also had a liver biopsy compatible with chronic hepatitis. The test was positive in 101 of the 106 (95%) sera from patients in the study group and negative in 38 of the 39 (97%) sera from those in the control group, showing an accuracy of 96%. According to these results, our EIA could be used to detect anti-HCV in the serum of patients infected with hepatitis C virus.

Detection of hepatitis A, B, and C virus-specific antibodies using oral fluid for epidemiological studies

In this report, we examine the adaptability of commercially available serological kits to detect antibodies markers for viral hepatitis in oral fluid samples. We also assessed the prevalence of hepatitis A, B, and C virus-specific antibodies, and related risk factors for these infectious diseases through sensitivity of the tests in saliva samples to evaluate if oral fluid can be an alternative tool to substitute serum in diagnosis of acute viral hepatitis and in epidemiological studies. One hundred and ten paired serum and saliva specimens from suspect patients of having acute hepatitis were collected to detect antibodies to hepatitis A (total and IgM), hepatitis B (anti-HBs, total anti-HBc and IgM anti-HBc), and hepatitis C (anti-HCV) using commercially available enzyme-linked immunossorbent assay (EIA). In relation to serum samples, oral fluid assay sensitivity and specificity were as follows: 87 and 100% for total anti-HAV, 79 and 100% for anti-HAV IgM, 6 and 95% for anti-HBs, 13 and 100% for total anti-HBc, 100 and 100% for anti-HBc IgM, and 75 and 100% for anti-HCV. The consistency observed between antibodies tests in saliva and expected risk factors for hepatitis A and C suggests that the saliva method could replace serum in epidemiological studies for hepatitis A and C.

Molecular characterization of hepatitis A virus isolates from Goiânia, Goiás, Brazil

Hepatitis A virus (HAV) infection is a public health problem worldwide and the virus has been classified into six genotypes. In Brazil, the only genotype that has been found is genotype I, predominately from subgenotype IA. Here, the HAV genotypes were analyzed of 18 isolates circulating between 1996-2001 in Goiânia, state of Goiás, Brazil. Viral RNA was extracted from 18 serum samples and amplified (RT-PCR/nested-PCR), followed by the genomic sequencing of the VP1/2A junction region of the HAV genome. Sequences of 168 nucleotides were compared and analyzed using the BLAST N, Clustal X and PAUP v. 4.10b programs. All samples were classified as genotype I, with 10 belonging to subgenotype IA and eight to subgenotype IB. The subgenotype IA isolates showed greater diversity than the subgenotype IB isolates at the nucleotide level. Elevated identity values were found between isolates obtained in this study and those from other regions of the world, including Brazil, highlighting the high conservation among different isolates of this virus. However, changes in the HAV subgenotype circulation could also be observed during the evaluated period.

Genetic polymorphisms of NAT2, CYP2E1 and GST enzymes and the occurrence of antituberculosis drug-induced hepatitis in Brazilian TB patients

Isoniazid (INH), one of the most important drugs used in antituberculosis (anti-TB) treatment, is also the major drug involved in hepatotoxicity. Differences in INH-induced toxicity have been attributed to genetic variability at several loci, such as NAT2, CYP2E1, GSTM1 and GSTT1, that code for drug-metabolising enzymes. Our goal was to examine the polymorphisms in these enzymes as susceptibility factors to anti-TB drug-induced hepatitis in Brazilian individuals. In a case-control design, 167 unrelated active tuberculosis patients from the University Hospital of the Federal University of Rio de Janeiro, Brazil, were enrolled in this study. Patients with a history of anti-TB drug-induced acute hepatitis (cases with an increase to 3 times the upper limit of normal serum transaminases and symptoms of hepatitis) and patients with no evidence of anti-TB hepatic side effects (controls) were genotyped for NAT2, CYP2E1, GSTM1 and GSTT1 polymorphisms. Slow acetylators had a higher incidence of hepatitis than intermediate/rapid acetylators [22% (18/82) vs. 9.8% (6/61), odds ratio (OR), 2.86, 95% confidence interval (CI), 1.06-7.68, p = 0.04). Logistic regression showed that slow acetylation status was the only independent risk factor (OR 3.59, 95% CI, 2.53-4.64, p = 0.02) for the occurrence of anti-TB drug-induced hepatitis during anti-TB treatment with INH-containing schemes in Brazilian individuals.

Risk of hepatitis B virus transmission by diagnostic hysteroscopy

Few data are available in the literature concerning the efficacy of standard hysteroscope disinfection procedures to prevent hepatitis B transmission. The aim of the present study was to determine the risk of hepatitis B virus (HBV) transmission during hysteroscopy among anti-HBc-seropositive women. Serum and hysteroscopic samples were collected from 62 women after diagnostic hysteroscopy. All samples were tested for serologic HBV markers. Polymerase chain reactions (PCR) were carried out to amplify regions C and S of the viral genome and only samples amplified by both pairs of primers were considered to be positive. Anti-HBc was repeatedly reactive in 48 (77%) of 62 serum samples, and HBsAg was detected in 8 (13%). At least one HBV serologic marker was found in 49 (79%) samples. Only one sample was HBsAg positive and anti-HBc negative. HBV-DNA was detected by PCR in 7 serum samples but in only 3 hysteroscopic samples obtained just after hysteroscopy. It is noteworthy that high levels of anti-HBc IgM were detected in one HBsAg-negative patient who showed an HBV-DNA-positive hysteroscopic sample. An elevated sample/cut-off ratio for anti-HBc IgM suggests recent infection and reinforces the need for testing for HBsAg and anti-HBc before hysteroscopy, since acute hepatitis B can be clinically asymptomatic. Viral DNA was not detected in any hysteroscopic samples collected after washing and disinfecting procedures with glutaraldehyde. We conclude that HBV-DNA can be found in the hysteroscope soon after hysteroscopy, but standard disinfecting procedures are effective in viral removal.

Co-circulation of genotypes IA and IB of hepatitis A virus in Northeast Brazil

The Northeast region is the location of most cases of acute hepatitis A virus (HAV) in Brazil. In the present study, the genotypes of HAV strains from Pernambuco State, one of most populous states in the Northeast region, were characterized. Blood samples positive for anti-HAV IgM from 145 individuals (mean age = 29.1 years), collected during 2002 and 2003, were submitted to nested RT-PCR for amplification of the 5'non-translated region (5'NTR) and VP1/2A regions of the HAV genome. The VP1/2A and 5'NTR regions were amplified in 39 and 21% of the samples, respectively. Nucleotide sequencing was carried out in 46% of VP1/2A and in 53% of 5'NTR isolates. The identity in nucleotide sequence of the VP1/2A region ranged from 93.6 to 100.0%. Phylogenetic analysis of the VP1/2A sequences showed that 65% belong to sub-genotype IA and 35% to sub-genotype IB. Co-circulation of both sub-genotypes was observed in the two years studied. Distinct clusters of highly related sequences were observed in both sub-genotypes, suggesting endemic circulation of HAV strains in this area. In the 5'NTR isolates, 92.7-99.2% identity was observed and two isolates presented one deletion at position 413. Phylogenetic analysis showed that genotype IA strains cluster in the tree in the same way as genotype IB strains, but one IIIA isolate from Spain clusters with genotype IB strains. These results do not allow us to state that 5'NTR could be used to genotype HAV sequences. This is the first report of co-circulation of sub-genotypes IA and IB in this region, providing additional information about the molecular epidemiology of HAV strains in Brazil.