Elizabeth H. Boxall

Effect of hepatitis B immunisation in newborn infants of mothers positive for hepatitis B surface antigen: systematic review and meta-analysis

Abstract Objective To evaluate the effects of hepatitis B vaccine and immunoglobulin in newborn infants of mothers positive for hepatitis B surface antigen. Design Systematic review and meta-analysis of randomised clinical trials. Data sources Electronic databases and hand searches. Review methods Randomised clinical trials were assessed for methodological quality. Meta-analysis was undertaken on three outcomes: the relative risks of hepatitis B occurrence, antibody levels to hepatitis B surface antigen, and adverse events. Results 29 randomised clinical trials were identified, five of which were considered high quality. Only three trials reported inclusion of mothers negative for hepatitis B e antigen. Compared with placebo or no intervention, vaccination reduced the occurrence of hepatitis B (relative risk 0.28, 95% confidence interval 0.20 to 0.40; four trials). No significant difference in hepatitis B occurrence was found between recombinant vaccine and plasma derived vaccine (1.00, 0.71 to 1.42; four trials) and between high dose versus low dose vaccine (plasma derived vaccine 0.97, 0.55 to 1.68, three trials; recombinant vaccine 0.78, 0.31 to 1.94, one trial). Compared with placebo or no intervention, hepatitis B immunoglobulin or the combination of plasma derived vaccine and hepatitis B immunoglobulin reduced hepatitis B occurrence (immunoglobulin 0.50, 0.41 to 0.60, one trial; vaccine and immunoglobulin 0.08, 0.03 to 0.17, three trials). Compared with vaccine alone, vaccine plus hepatitis B immunoglobulin reduced hepatitis B occurrence (0.54, 0.41 to 0.73; 10 trials). Hepatitis B vaccine and hepatitis B immunoglobulin seem safe, but few trials reported adverse events. Conclusion Hepatitis B vaccine, hepatitis B immunoglobulin, and vaccine plus immunoglobulin prevent hepatitis B occurrence in newborn infants of mothers positive for hepatitis B surface antigen.

High pre-treatment serum hepatitis B virus titre predicts failure of lamivudine prophylaxis and graft re-infection after liver transplantation

BACKGROUND/AIMS Orthotopic liver transplantation has an established role for the treatment of patients with chronic liver failure secondary to hepatitis B virus (HBV) infection. Unfortunately, recurrent infection of the graft can be associated with aggressive disease, and with diminished graft and patient survival. Currently, the role of nucleoside analogues for prevention of graft re-infection is being evaluated. Preliminary results are encouraging, but treatment failure has been associated with emergence of drug-resistant virus. METHODS We have studied ten consecutive patients who received lamivudine prophylaxis for prevention of HBV graft reinfection. Sequential sera, collected prelamivudine then during treatment before and after liver transplantation, were examined. Conventional serological markers were measured, as were serum viral DNA levels with a sensitive quantitative polymerase chain reaction assay. RESULTS Lamivudine treatment effected a reduction in serum HBV levels, but six patients still had measurable viral DNA at the time of transplantation. Five patients developed graft re-infection with lamivudine-resistant virus. Resistant virus emerged 8 to 15 months post-transplant. The likelihood of emergence of resistant virus was related to the pre-treatment serum HBV titre. Persistent serum viral DNA positivity and evidence of graft re-infection during the early post-transplant period did not predict the subsequent emergence of resistant virus. CONCLUSIONS Our observations suggest that the resistant species may be present in the viral quasispecies in the serum and liver of patients with high-level replication prior to lamivudine exposure. The resistant species can persist during lamivudine treatment prior to transplantation, and emerge following transplantation. These observations suggest strategies which might prevent the emergence of drug-resistant species, and imply that graft re-infection may be a preventable phenomenon.

Transmission of HBsAg from mother to infant in four ethnic groups.

Antenatal screening in the West Midlands during a three-year period identified 297 mothers who were chronic carriers of hepatitis B surface antigen (HBsAg)--a prevalence of about 1 in 850. About half of their infants had HBsAg in the cord blood, but of 122 infants followed up for over three months (mean 8.5 months) only 17 (14%) were still positive for HBsAg. Cord-blood HBsAg-positivity was evenly distributed among different ethnic groups, but the transmission rate was highest among the Chinese, and no carriers were discovered among 39 European infants. Raised serum transaminase concentrations were found in some of the carrier infants who were otherwise healthy. The results suggest that adequate follow-up of HBsAg-positive infants may be achieved by tests at 4 months and 1 year of age, and that the role of breast-feeding in mother-to-infant transmission of HBsAg is unimportant. The Chinese community may be a suitable population in which to test the effectiveness of specific immunoglobulin administration at birth in preventing the development of the HBsAg carrier state.

Hepatitis E in England and Wales.

In 2005, 329 cases of hepatitis E virus infection were confirmed in England and Wales; 33 were confirmed indigenous infections, and a further 67 were estimated to be indigenous infections. Hepatitis E should be considered in the investigation of patients with hepatitis even if they have no history of travel.

HBV DNA levels and transmission of hepatitis B by health care workers

BACKGROUND Laboratory-based study funded by the Research and Development Division of the Department of Health to inform the decision making on guidelines for the conduct of exposure prone procedures (EPPs) by health care workers who are hepatitis B carriers. OBJECTIVES Define the quantity and nature of hepatitis B virus (HBV) DNA in hepatitis carriers whose serum does not contain hepatitis B e antigen (HBeAg) and in surgeons previously cleared to conduct EPPs who have transmitted HBV to their patients. STUDY DESIGN Cross-sectional survey using HBV DNA quantification, genotyping and sequencing comparing transmitting surgeons and asymptomatic carriers. RESULTS HBV DNA could be detected and quantified in 64.5% (136 of 211) of carriers whose serum did not contain HBeAg with a median level 3.6 log(10) copies/ml (range of 5.7 log(10) copies). Pre-core mutation appeared not to affect the HBV DNA level, however, all surgeons carried codon 28 variants and transmitted these variants to their patients. The lowest HBV DNA level in a transmitting surgeon was 4 x 10(4) copies/ml. CONCLUSIONS Pre-core mutations are common in carriers whose serum does not contain HBeAg and do not specifically identify carriers whose HBV DNA levels are high. It was possible to define a level of virus above which transmission of hepatitis B during conduct of EPPs could not be excluded.

Comparison of commercial assays for the quantification of HBV DNA load in health care workers: calibration differences.

Until recently, carriers of hepatitis B virus (HBV) were allowed to undertake exposure prone procedures providing their serum did not contain HBeAg. However, the recent description of hepatitis B transmission events occurring from HBV-infected health care workers who conduct exposure prone procedures demonstrated that the then current Department of Health guidelines needed to be revised. As part of a series of studies carried out to determine if viral load measurements are a more secure means of assessing the conduct of exposure prone procedures, the suitability of commercially available assays for HBV DNA detection and quantification were investigated. This study describes a comparative analysis on the performances of three assays each based on a different methodology. The assays included the QUANTIPLEX HBV DNA Assay (bDNA), (Chiron Diagnostics Ltd.), the AMPLICOR HBV Monitor Test, (Roche Diagnostics Systems) and the Digene Hybrid Capture System HBV DNA Assay (Digene Corporation). Calibration curves from experiments using the Eurohep ad and ay HBV DNA standard controls indicated a close correlation between the three assays over the dynamic ranges claimed by the manufacturers, although the Quantiplex assay did appear to be over-reporting. This became more apparent when testing patients undergoing anti-viral therapy where the Quantiplex assay consistently over-reported by 0.5 log(10) when compared with the Amplicor assay. The results of this study indicate that based on its dynamic range, the Amplicor HBV Monitor test is the most appropriate assay for the routine investigation of anti-HBe carriers, which will have lower levels of HBV DNA. The investigation also highlights the need for using accepted standard HBV DNA control sera. This will be essential when using an assay to establish whether health care workers who are hepatitis B carriers can be allowed to perform exposure prone procedures under the new guidelines of the UK Department of Health.

Holiday haemodialysis and imported hepatitis C virus infection: A series of sixteen cases in two large haemodialysis units

BACKGROUND Patients in haemodialysis units are at an increased risk of blood borne virus infections. Birmingham city (West Midlands, UK) has a large number of its population from an ethnic origin other than white (30%). Recently due to the increase in number of haemodialysis centres abroad and particularly in the Indian Subcontinent, a large number of haemodialysis patients from these ethnic minorities are encouraged to take holidays in their countries of origin. OBJECTIVES To present the data on a series of cases of holiday haemodialysis acquired hepatitis C virus (HCV) infections from two large dialysis units in Birmingham. STUDY DESIGN In this retrospective study we have reviewed the case records of all patients in two large dialysis units who had holiday dialysis abroad and developed HCV infection after returning to the UK. RESULTS A total of 16 patients from two large dialysis units in Birmingham who developed HCV infection after haemodialysing abroad mainly in the Indian Subcontinent are being described. This constituted 44% of the total HCV positive patients in the two haemodialysis units (16/36). The cases occurred over a period of 9 years between 2000 and 2008. The last twelve of these fifteen cases had been diagnosed in the past 17 months. There were 10 male patients with a mean age 62.8 years (range 26-84 years) and 6 female patients with a mean age of 57 years (range 44-68 years). HCV genotypes 1, 3 and 4 were found in 9, 4 and 3 patients, respectively. CONCLUSION These cases underline the importance of enhanced surveillance and infection control procedures in haemodialysis units for patients who return after dialysing in resource poor countries. To the best of our knowledge this represents the largest series of imported HCV infection after holiday haemodialysis, and demonstrates clearly the significance of the perceived risk with increasing number of incident infections.

Epidemiology of precore mutants of hepatitis B in the United Kingdom.

A point mutation assay was used to study the codon 28 and codon 1 precore mutant status of 310 chronic hepatitis B carriers (82 HBeAg positive and 228 HBeAg negative). Fourteen of 228 (6%) of HBeAg negative carriers had high levels of serum HBV DNA. Nine of these were explained by precore variants, three by core promoter variants, and two were not explained by recognised precore changes. Nested PCR detected serum HBV DNA in 36% (82/228) of HBeAg negative carriers and 63% (52/82) of these had precore variants. Four of 82 (4%) of the HBeAg positive carriers had precore variants, all as mixed mutant/wild type populations and evidence indicated that these carriers were seroconverting. Overall 23% (52/228) of HBeAg negative carriers had both serum HBV DNA and codon 1 or 28 precore mutations. A sexual transmission event from an HBeAg negative carrier with a relatively low serum HBV DNA level (104–106 genome copies/ml) and only core promoter mutations was observed. Despite high rates of variant carriage in the antenatal sub‐group perinatal transmission was not observed. The results of direct sequencing on 45 carriers validated the point mutation assay and also showed that codon 28 mutations were only seen in carriers with the genotype CCT at codon 15. For the Caucasian population a higher prevalence of codon 28 mutations (13/25 or 52%) than expected was seen. Liver biopsy data indicated that there was no link between the presence or absence of precore mutants and the severity of liver disease. J. Med. Virol. 62:463–470, 2000.

Fifth of e antigen negative carriers of hepatitis B virus should not perform exposure prone procedures.

Martyn Halle has reported on a surgeon with hepatitis B who transmitted the infection to a patient who subsequently died.1 2 This case has put pressure on the Department of Health to review guidelines on the employment of healthcare workers with hepatitis B who carry out exposure prone procedures. The current guidelines exclude all carriers of hepatitis B virus who are also positive for hepatitis B e antigen (that is, those with high infectivity) from carrying out such procedures. It has been recognised that carriers of hepatitis B …

Prognosis of children who are carriers of hepatitis B.

Fifteen children who had become positive for hepatitis B surface antigen (HBsAg) by perinatal transmission were traced and re-examined after a mean of 8.1 years; all had been born in England to mothers from ethnic minorities who were carriers of HBsAg. Fourteen of the children remained carriers of HBsAg; of these, more girls than boys developed antibody to hepatitis B e antigen (anti-HBe). Those children whose transaminase activities had been above normal within the first three years of life were more likely to have developed anti-HBe. The earlier production of anti-HBe suggests that girls have a more effective immune response. Increased transaminase activity early in the course of asymptomatic carriage of HBsAg may be a favourable prognostic sign.