Hepatitis: Newell ML

Hawkins D, Blott M, Clayden P, de Ruiter A, Foster G, Gilling-Smith C, Gosrani B, Lyall H, Mercey D, Newell ML, O'Shea S, Smith R, Sunderland J, Wood C, Taylor G, Anonymous00122. · Chelsea and Westimnster Hospital, London, UK. · HIV Med. · Pubmed #16033339 No free full text.

This publication has no abstract.

England K, Thorne C, Newell ML. · Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, University College London, London, UK. · Lancet Infect Dis. · Pubmed #16439328 No free full text.

Abstract: Both HIV and hepatitis C virus (HCV) can be transmitted from mother to child during pregnancy and delivery. Vertical transmission of HIV and HCV separately is most likely from HIV/HCV-coinfected mothers; however, transmission of both infections is less frequent. The effect of HCV coinfection on HIV-related disease remains unclear; whereas most studies indicate no effect, recent results suggest HCV in adults accelerates HIV progression. Little is known about how HIV coinfection affects HCV progression in children and the information available is based on small numbers of patients. Paediatric HIV treatment is extremely successful and it is vital to determine if HCV coinfection alters the effectiveness of this treatment. The hepatotoxicity of many HIV therapies and the possible negative impact of HCV on this treatment, alongside the interactions and contraindications of many HIV and HCV therapies, further limits the choice of paediatric treatments for coinfected children. Future research must therefore focus on vertically acquired HIV/HCV coinfection to inform treatment trials addressing coinfection management.

Pembrey L, Newell ML, Peckham C. · Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, 30 Guilford Street, London WC1N 1EH. · J Med Screen. · Pubmed #14738651 No free full text.

Abstract: Based on research evidence the UK National Screening Committee recently recommended that routine antenatal screening for hepatitis C virus (HCV) infection should not be introduced into the UK antenatal screening programme. In this paper we review the evidence on which this decision was based, addressing the criteria that need to be considered before the introduction of a new screening programme.

Newell ML, Pembrey L. · Centre for Paediatric Epidemiology, Institute of Child Health, London, UK. · Drugs Today (Barc). · Pubmed #12532168 No free full text.

Abstract: The prevalence of hepatitis C virus (HCV) infection among pregnant women in Europe is generally below 2%. Although women with a history of parenteral exposures or injecting drug use are at an increased risk of infection, a substantial proportion of infected women do not report any risk factors. Targeted screening is thus not recommended. The risk of mother-to-child, or vertical, transmission of HCV is about 5% overall but can be as high as 15%, depending on maternal HIV infection status and HCV RNA viral load. Larger studies are needed to confirm or refute the potential protective effect of elective cesarean section delivery. However, for HCV-positive women who are co-infected with HIV, elective cesarean section delivery is associated with a reduced risk of vertical transmission of HIV as well as HCV. The risk of postnatal transmission through breastfeeding cannot be excluded but is likely to be low for most HCV-infected women. The long-term natural history of vertically acquired HCV needs further elucidation and the efficacy of potential therapies for infected children need to be evaluated in randomized controlled trials.

Zanetti AR, Tanzi E, Newell ML. · Institute of Virology, University of Milan, Italy. · J Hepatol. · Pubmed #10622569 No free full text.

Abstract: The rate of mother-to-infant transmission of hepatitis C virus (HCV) is approximately 5%, but is higher when the mother is co-infected with HIV Vertical transmission is restricted to infants whose mothers are viraemic. The risk of transmission increases with increasing maternal viral load but a specific cut-off value predicting infection cannot be defined. There is no specific HCV genotype which is preferentially transmitted. The mode of delivery (caesarean versus vaginal) does not appear to influence the rate of transmission, but firm evidence is lacking. There is no evidence to suggest an increased risk of HCV transmission through breast feeding. Pregnancy is not contra-indicated in HCV-infected women. Without drugs to treat established infections in mothers and infants and interventions to prevent vertical transmission, routine HCV screening is not recommended in pregnant women.

Bevilacqua E, Fabris A, Floreano P, Pembrey L, Newell ML, Tovo PA, Amoroso A, Anonymous00127. · Servizio di Genetica Medica, I.R.C.C.S. Burlo Garofolo, Via dell'Istria 65/1, 34137 Trieste, Italy. · Virology. · Pubmed #19481774 No free full text.

Abstract: HCV infection transmission rate in infants born to HCV-positive mothers is about 5%. HIV co-infection and high maternal RNA viral load are associated with increased transmission. The only genetic factor previously evaluated is HLA. We investigated the role of genetic factors already associated in adults with HCV infection evolution (HLA-DRB1, MBL2, TNF-alpha, IFN-gamma and IL-10), or liver disease progression (HFE and TGF-beta1). 384 Italian subjects were recruited, including 38 HCV-positive mother/child pairs; 104 infected, non-transmitting mothers with their 114 children; 21 vertically infected children and 69 HCV-exposed, uninfected children. Samples were analysed for previously described gene polymorphisms. Maternal HLA-DRB104 correlated with protection from vertical transmission (p=0.023), while HLA-DRB110 in children was a risk factor (p=0.036). Investigation of concordance degree in HLA-DRB1 locus revealed that a HLA mismatch between mother and child was a protective factor (p=0.017) indicating that alloreactive immune responses are involved in preventing HCV vertical transmission.

England K, Thorne C, Castelli-Gattinara G, Vigano A, El Mehabresh MI, Newell ML. · MRC Centre of Epidemiology for Child Health, UCL Institute of Child Health, University College London, London, UK. · Curr HIV Res. · Pubmed #19442133 No free full text.

Abstract: Shared transmission routes of HCV and HIV mean parenteral HIV/HCV coinfection still occurs, often in resource-limited settings. The extent to which coinfection and treatment impact on morbidity and mortality in HIV/HCV coinfected children remains unknown thus optimal management and treatment is difficult to achieve. Using data from a unique, large, prospective cohort of parenterally HIV/HCV coinfected children in Libya we determine the immunological, virological and clinical profiles of HIV/HCV coinfected children documenting the natural and treated history of parenterally acquired coinfection for the first time in such a large group. 160 parenterally HIV/HCV coinfected children were analysed. Thirty-three (21%) received antiretroviral treatment (ART) for HIV disease during follow-up. In children receiving ART, HIV RNA viral load decreased in two-thirds 6-12 months after initiation. 85% (17/20) experienced a positive immunological response to ART with a median increase in CD4 cell count z-score of 131%. Half had progressed to moderate or severe immunosuppression and/or moderate or severe clinical symptoms three years after infection. In those who progressed during follow-up, 85% had done so within three years of infection. Children progressing to moderate or severe immunosuppression and/or clinical symptoms were significantly more likely to be receiving ART. This novel investigation of the natural and treated history of parenterally HIV/HCV coinfected children in a large prospectively followed group demonstrates minimal clinical symptoms and immunosuppression to date, despite low prevalence of treatment, and a response to ART similar to vertically HIV-only infected children.

Pembrey L, Newell ML, Tovo PA, Anonymous00299. · Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health and Great Ormond Hospital for Children NHS Trust, University College London, London, UK. · Pediatr Infect Dis J. · Pubmed #18664931 No free full text.

Abstract: BACKGROUND: Investigation of immunologic values in children vertically exposed to hepatitis C virus (HCV) infection could help explain the higher risk of infection in girls and indicate mechanisms of spontaneous viral clearance and possible long-term immunologic effects. METHODS: Prospective study of children born to HCV-infected women. Lymphocyte and neutrophil measurements were age-standardized using the LMS method (this summarizes the changing age distribution of a variable). Associations between maternal and infant characteristics and lymphocyte and neutrophil z-scores were quantified using linear regression allowing for repeated measures. RESULTS: HCV-infected children, girls, and those born to HCV/human immunodeficiency virus (HIV)-coinfected women had significantly higher lymphocyte z-scores than HCV-uninfected children, boys, and children born to HCV-only-infected women, respectively. Peak absolute lymphocytes were significantly lower for infected children with evidence of viral clearance than for persistently infected children. Girls also had significantly higher neutrophil z-scores than boys but HCV-infected children had significantly lower neutrophil z-scores than uninfected children. CONCLUSIONS: The gender associations are in line with those observed among children born to HIV-infected women, suggesting general gender-based differences in response to infection. Age-related standards for uninfected children could be used to assess immune function in other pediatric diseases and these results suggest that gender-specific reference values should be used at least for the first 2 years of life.

Landes M, Newell ML, Barlow P, Fiore S, Malyuta R, Martinelli P, Posokhova S, Savasi V, Semenenko I, Stelmah A, Tibaldi C, Thorne C. · Department of Family and Community Medicine, University of Toronto, Toronto, Canada. · HIV Med. · Pubmed #18554310 No free full text.

Abstract: OBJECTIVES: The aim of the study was to investigate the prevalence of and risk factors for hepatitis C or B virus (HCV or HBV) coinfection among HIV-infected pregnant women, and to investigate their immunological and virological characteristics and antiretroviral therapy use. METHODS: Information on HBV surface antigen (HBsAg) positivity and HCV antibody (anti-HCV) was collected retrospectively from the antenatal records of HIV-infected women enrolled in the European Collaborative Study and linked to prospectively collected data. RESULTS: Of 1050 women, 4.9% [95% confidence interval (CI) 3.6-6.3] were HBsAg positive and 12.3% (95% CI 10.4-14.4) had anti-HCV antibody. Women with an injecting drug use(r) (IDU) history had the highest HCV-seropositivity prevalence (28%; 95% CI 22.8-35.7). Risk factors for HCV seropositivity included IDU history [adjusted odds ratio (AOR) 2.92; 95% CI 1.86-4.58], age (for > or =35 years vs. <25 years, AOR 3.45; 95% CI 1.66-7.20) and HBsAg carriage (AOR 5.80; 95% CI 2.78-12.1). HBsAg positivity was associated with African origin (AOR 2.74; 95% CI 1.20-6.26) and HCV seropositivity (AOR 6.44; 95% CI 3.08-13.5). Highly active antiretroviral therapy (HAART) use was less likely in HIV/HCV-seropositive than in HIV-monoinfected women (AOR 0.34; 95% CI 0.20-0.58). HCV seropositivity was associated with a higher adjusted HIV RNA level (+0.28 log(10) HIV-1 RNA copies/mL vs. HIV-monoinfected women; P=0.03). HIV/HCV-seropositive women were twice as likely to have detectable HIV in the third trimester/delivery as HIV-monoinfected women (AOR 1.95; P=0.049). CONCLUSIONS: Although HCV serostatus impacted on HAART use, the association between HCV seropositivity and uncontrolled HIV viraemia in late pregnancy was independent of HAART.

Tovo PA, Newell ML. · Department of Pediatrics, University of Turin, Turin, Italy. · Curr Opin Infect Dis. · Pubmed #17035787 No free full text.

Abstract: Mother-to-child, or vertical transmission, of hepatitis C virus is now the dominant mode of acquisition of infection for children. The rate of transmission is low in women who are not also HIV-positive. Whether the mode of delivery is associated with transmission remains questionable; breast-feeding does not appear to be a source of infection. The detection of hepatitis C virus RNA using the polymerase chain reaction is a sensitive method for the early diagnosis of infection in perinatally exposed infants, but false positive results can occur. The natural history of hepatitis C virus infection in children is not well defined, but chronic infection is common in most cases. The disease progression is slower than in adults. Therapeutic trials (not placebo controlled) in a small number of children suggested a sustained response to interferon treatment in only a minority of cases. The option of combination therapy with ribavirin looks promising and needs evaluation.

Polywka S, Pembrey L, Tovo PA, Newell ML. · Institute for Infectious Diseases, University Hospital Eppendorf, Martinistrasse, Hamburg, Germany. · J Med Virol. · Pubmed #16372293 No free full text.

Abstract: The aim of the study was to estimate the sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and likelihood ratios for HCV-RNA PCR tests for the early diagnosis or exclusion of HCV infection in vertically exposed children. Data were included for children with confirmed HCV infection status from a European multi-center study. Confirmation was dependent on antibody status at or beyond 18 months, the 'gold standard' measure of infection status against which the use of qualitative HCV-RNA PCR tests was assessed. Of the 547 children included in this analysis, 193 were HCV-infected and 354 were not. Sensitivity of the HCV-RNA PCR test was low at birth (22%), but increased to 85% by 6 months. Specificity of RNA PCR was constant over age at 98%. The PPV of the PCR test rose from 33% at birth to 78% at 9 months of age, while NPV ranged from 96% to 99%. The high positive likelihood ratios from 1 month of age indicate strong evidence to diagnose infection but the negative likelihood ratios were consistent with weak evidence to exclude infection. The results suggest that the first qualitative HCV-RNA PCR test should be delayed until after the first month of life given the low sensitivity in the first few weeks. Although a negative test result after this time indicates probable absence of infection, this should be confirmed with a negative anti-HCV antibody test between 9 and 15 months of age as negative PCR results can be observed in infected children with fluctuations in viremia.

Pembrey L, Newell ML, Tovo PA, Anonymous00283. · Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, London, UK. · J Hepatol. · Pubmed #16144064 No free full text.

Abstract: BACKGROUND/AIMS: As evidence accumulates relating to mother-to-child (vertical) transmission of hepatitis C virus (HCV), it is timely to draw up guidelines for the clinical management of HCV infected pregnant women and their children. METHODS: A review of evidence from the European Paediatric HCV Network (EPHN) prospective study of HCV infected women and their children and other published studies. Meeting of EPHN clinical experts to reach a consensus on recommendations for management. Each recommendation was graded according to the level of evidence. RESULTS/CONCLUSIONS: Although several risk factors for mother-to-child transmission have been identified, none are modifiable and there are currently no interventions available to prevent vertical transmission of HCV. Data on timing of loss of maternal antibodies and reliability of diagnostic tests inform the optimum follow-up schedule for confirmation or exclusion of infection in children born to HCV infected women. Based on the current evidence, routine antenatal screening for HCV should not be introduced and neither elective caesarean section nor avoidance of breastfeeding should be recommended to HCV infected women to prevent mother-to-child transmission of HCV. HCV/HIV co-infected women should follow existing HIV guidelines.

England K, Pembrey L, Tovo PA, Newell ML, Anonymous00180. · Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, University College London, London, United Kingdom. · J Pediatr. · Pubmed #16126055 No free full text.

Abstract: OBJECTIVES: To identify the effect of vertical hepatitis C virus (HCV) infection or exposure on growth in childhood. STUDY DESIGN: Children (n=1203) born to HCV-infected mothers were followed up from birth prospectively in centers of the European Paediatric Hepatitis C virus Network. Z-scores compared height- and weight-for-age in HCV-infected and -uninfected children, adjusting for other factors using linear regression. We also quantified the effect of maternal chronic infection with HCV on childhood growth. RESULTS: There was no significant effect of vertical HCV infection on growth (height P=.223, weight P=.095) nor a significant effect of maternal chronic infection with HCV (height P=.733, weight P=.274). Prematurity and maternal injecting drug use were associated with a significant reduction in height (P < .001) and weight (P < .001) in all HCV-exposed children. CONCLUSIONS: This population of HCV exposed infants has higher rates of maternal injecting drug use and prematurity than standard populations and so there are implications for growth of these children, but this is not a direct result of HCV infection or exposure to chronic maternal HCV infection.

England K, Pembrey L, Tovo PA, Newell ML, Anonymous00181. · Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, University College London, London, UK. · Acta Paediatr. · Pubmed #16092459 No free full text.

Abstract: AIM: To identify the age at which HCV infection can be accurately excluded by serology in young children born to HCV-infected mothers and to determine an appropriate schedule of antibody testing, most informative to clinical practice. METHODS: Children born to HCV-infected mothers were followed in centres of the European Paediatric HCV Network. Turnbull survival analysis techniques were used to estimate the age at which HCV-uninfected children will lose maternally acquired HCV antibodies. Factors associated with age at antibody loss were assessed in logistic regression. RESULTS: In 1104 children followed from birth and later confirmed to be HCV uninfected, an estimated 57% will have lost passively acquired HCV antibodies before 6 mo of age and an estimated 95% by 12 mo. Maternal HCV viraemia antenatally was associated with later, and maternal HIV-HCV co-infection with earlier loss of antibody. Actual antibody testing of uninfected children at 12 mo identified 82% of those tested to be anti-HCV negative. CONCLUSIONS: Serological confirmation of HCV uninfection remains necessary given the uncertainty in the specificity of virological tests. These results suggest that, in most children, HCV infection can be ruled out with serological testing at an earlier age than previously thought, and that nearly all children born to HCV-infected mothers will have lost passively acquired maternal antibodies by 1 y of age. Antibody loss was significantly later among children born to HCV viraemic mothers. The earlier loss of HCV antibodies in children born to HIV co-infected mothers may be due to HIV treatment.

Mok J, Pembrey L, Tovo PA, Newell ML, Anonymous00030. · Paediatric HIV Service, Royal Hospital for Sick Children, Edinburgh, Scotland, UK. · Arch Dis Child Fetal Neonatal Ed. · Pubmed #15724041 links to  free full text

Abstract: OBJECTIVE: To investigate when hepatitis C virus (HCV) infection from mother to child occurs, and evaluate possible associated factors. DESIGN: Prospective cohort study. PATIENTS: Fifty four HCV infected children tested within three days of birth and their mothers. MAIN OUTCOME MEASURES: HCV RNA polymerase chain reaction (PCR) results. RESULTS: Seventeen of the children (31%, 95% confidence interval 19% to 46%) were positive in the first 3 days of life and could be assumed to have acquired infection in utero. Testing PCR positive was not associated with sex (53% v 49% boys; p=0.77) or mode of delivery (29% elective caesarean section in both groups; p=0.98). Children with evidence of intrauterine infection were significantly more likely to be of lower birth weight and infected with genotype 1 (58% v 12%, p=0.01). Although a higher proportion of infants born to HCV/HIV co-infected women were PCR positive in the first 3 days of life, this difference did not reach statistical significance; excluding infants born to co-infected women did not affect the results. Thirty seven of the children (68%) were negative in the first 3 days of life, 27 of whom were positive when tested again at 3 months, and nine were first PCR positive after 3 months (one child had no further tests). CONCLUSIONS: These results suggest that at least one third and up to a half of infected children acquired infection in utero. Although postpartum transmission cannot be excluded, these data suggest that it is rare. The role of HCV genotypes in the timing and mechanism of infection should be explored further.

Pembrey L, Newell ML, Tovo PA, van Drimmelen H, Quinti I, Furlini G, Galli S, Meliconi MG, Burns S, Hallam N, Sönnerborg A, Cilla G, Serrano E, Laccetti P, Portella G, Polywka S, Icardi G, Bruzzone B, Balbo L, Alfarano A, Anonymous00307. · Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, London, United Kingdom. · J Med Virol. · Pubmed #12683407 No free full text.

Abstract: To investigate whether it is appropriate to assume comparability of hepatitis virus C (HCV)-RNA results across laboratories in multi-centre studies, nine laboratories of the European Paediatric HCV Network participated in an international proficiency study of HCV-RNA assays. A panel of 12 samples of different dilutions and genotypes was sent to each laboratory and tested with qualitative and/or quantitative HCV-RNA assays according to local procedures. Commercial assays were used in seven laboratories and in-house assays in two. All six laboratories in which a commercial qualitative assay was used were proficient, as were four of six runs (in five laboratories) in which a commercial quantitative assay was used. The proficiency of the laboratories where in-house assays were used could not be assessed according to the VQC definition because of differences in the methods used. Overall, there were several false-negative results, but only one false-positive result with a quantitative assay and none with a qualitative assay. The false-negative results may have implications for the diagnosis of infection, and highlight the need for an antibody test to be performed at 18 months to confirm the absence of infection. The results of qualitative assays were generally consistent across laboratories but it was difficult to evaluate and compare the results of quantitative assays. Multivariate analysis of data collected in multi-centre studies should therefore allow for centre and/or assay used.

Tovo PA, Pembrey LJ, Newell ML. · Department of Pediatrics, University of Turin, Piazza Polonia 94, 10126 Turin, Italy. · J Infect Dis. · Pubmed #10669321 No free full text.

Abstract: Data were collected from 104 infected children who were followed up from birth for a mean of 49 (range, 6-153) months in 22 European centers, to outline the natural history of perinatal hepatitis C virus (HCV) infection. Fifty-four children were persistently HCV RNA positive, 44 were occasionally positive, and 6 never had detectable viremia. At least 90% of the children had evidence of ongoing infection at the latest analysis. Eighteen children became HCV RNA negative at their last assessments, but 40% of these had high alanine aminotransferase (ALT) concentrations. Infection was asymptomatic in all but 2 children, who developed hepatomegaly. Mean ALT concentrations decreased substantially after the first 2 years of life; 14 children had persistently normal ALT values. Signs of minimal to moderate inflammation were noted in all 20 patients who underwent liver biopsy. Perinatal HCV infection is usually asymptomatic in the first years of life, but the virus persists in most children, even in the absence of elevated ALT activity.

Pembrey L, Newell ML, Tovo PA. · University of Turin, Department of Pediatrics, Division of Immunology and Infectious Diseases, Regina Margherita Children's Hospital, Piazza Polonia 94, I-10126 Turin, Italy. · Eur J Pediatr. · Pubmed #10486090 No free full text.

Abstract: A postal survey of 31 European centres was conducted to document current practices regarding screening and management of hepatitis C virus (HCV)-infected pregnant women and their children. Antenatal HCV prevalence was low. Universal antenatal screening programmes were in place in ten centres, selective screening occurred in ten other centres, two did not specify the type of policy, and there was no screening programme in nine centres. Numbers of HCV-infected children were low. Breastfeeding was recommended for infants of infected mothers in ten centres, discouraged in ten centres, in three centres women were merely informed of the risks, and there were no guidelines in eight centres. Polymerase chain reaction was available in all centres. In 17 centres children born to HCV-infected women were seen every 3 months for at least the 1st year. CONCLUSION: The optimum antenatal hepatitis C virus screening approach and the appropriateness of breastfeeding recommendations are unclear and this survey highlights the lack of uniformity in current practice.

Newell ML, Thorne C, Pembrey L, Nicoll A, Goldberg D, Peckham C. · Department of Epidemiology and Public Health, Institute of Child Health, London, UK. · Br J Obstet Gynaecol. · Pubmed #10426262 No free full text.

Abstract: OBJECTIVES: To assess antenatal hepatitis B and syphilis screening policies in the UK. DESIGN: Postal questionnaire survey. SETTING: One hundred and ninety-two obstetric units and 116 Public Health directorates. MAIN OUTCOME MEASURES: Antenatal screening policy and line of responsibility for ensuring vaccine uptake in hepatitis B virus exposed children. RESULTS: Replies were received from 140 (73%) obstetric centres and 99 (85%) Public Health directors. Forty per cent of obstetric centres now offer hepatitis B virus tests to all pregnant women, and nearly one-quarter (24.1%) of all births in the UK in 1996 occurred in centres with a universal testing policy. The prevalence of chronic hepatitis B virus ranged from 0.3 to 17.5 per 1000 deliveries. Universal antenatal screening for serological evidence of syphilis was the norm, but five obstetric centres respondents and three Public Health directors were considering its discontinuation. In the nine London centres, syphilis prevalence was 2.06 per 1000 pregnant women, compared with 0.24 per 1000 elsewhere. Responses from Public Health directors indicated the nonspecific nature of the antenatal care contract. Responsibility for hepatitis B virus vaccination of the newly born infant rests with the hospital paediatrician, with transfer of responsibility to the community usually occurring through a discharge letter. Only two areas had a monitoring system to ensure full hepatitis B virus vaccination coverage of exposed infants. CONCLUSIONS: If antenatal screening policies are to be equitable there is a need for a clear national policy, and systems need to be established to monitor local policy and practice.

Pembrey L, Newell ML, Tovo PA. · No affiliation provided · J Infect Dis. · Pubmed #16544263 No free full text.

This publication has no abstract.

Fiore S, Newell ML, Pembrey L, Zanetti A, Coll O. · No affiliation provided · Lancet. · Pubmed #11197417 No free full text.

This publication has no abstract.