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Hepatitis: HELP
Articles from Cambridgeshire
Based on 118 articles published since 2008

These are the 118 published articles about Hepatitis that originated from Cambridgeshire during 2008-2019.
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Editorial Liver transplantation for alcoholic hepatitis: Being consistent about where to set the bar. 2018

Thursz, Mark / Allison, Michael. ·Department of Surgery and Cancer, Imperial College, London, United Kingdom. · Cambridge Liver Unit Cambridge Biomedical Campus, Cambridge University Hospitals, Cambridge, United Kingdom. ·Liver Transpl · Pubmed #29694706.

ABSTRACT: -- No abstract --

2 Review Individualizing Care: Management Beyond Medical Therapy. 2018

Cristoferi, Laura / Nardi, Alessandra / Invernizzi, Pietro / Mells, George / Carbone, Marco. ·Division of Gastroenterology and Hepatology, Department of Medicine and Surgery, University of Milan Bicocca, Piazza dell'Ateneo Nuovo, 1, 20126 Milan, Italy. · Department of Mathematics, Tor Vergata University of Rome, Via della Ricerca Scientifica 1, Rome, Italy. · Academic Department of Medical Genetics, University of Cambridge, Hills Road 1, Cambridge, UK. · Division of Gastroenterology and Hepatology, Department of Medicine and Surgery, University of Milan Bicocca, Piazza dell'Ateneo Nuovo, 1, 20126 Milan, Italy; Academic Department of Medical Genetics, University of Cambridge, Cambridge, UK. Electronic address: marco.carbone@unimib.it. ·Clin Liver Dis · Pubmed #30259852.

ABSTRACT: The evolving research landscape, with advances in the omics technologies, availability of large-scale patient cohorts, and forthcoming availability of novel drugs in primary biliary cholangitis (PBC), is creating a unique opportunity for developing a precision medicine (PM) program. PM has potential to change the paradigm of management. Diagnostic work-up of PBC patients may include information on genetic variants and molecular signature to define a particular subtype of disease and provide an estimate of treatment response and survival. To reach this point, specific interventions, such as sequencing more genomes, creating bigger biobanks, and linking biological information to health data, are needed.

3 Review Tumour virus vaccines: hepatitis B virus and human papillomavirus. 2017

Stanley, Margaret. ·Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK mas1001@cam.ac.uk. ·Philos Trans R Soc Lond B Biol Sci · Pubmed #28893935.

ABSTRACT: Two of the most important human oncogenic viruses are hepatitis B virus (HBV) and human papillomavirus (HPV). HBV infection has been preventable by vaccination since 1982; vaccination of neonates and infants is highly effective, resulting already in decreased rates of new infections, chronic liver disease and hepato-cellular carcinoma. Nonetheless, HBV remains a global public health problem with high rates of vertical transmission from mother to child in some regions. Prophylactic HPV vaccines composed of virus-like particles (VLPs) of the L1 capsid protein have been licensed since 2006/2007. These target infection by the oncogenic HPVs 16 and 18 (the cause of 70% of cervical cancers); a new vaccine licensed in 2014/2015 additionally targets HPVs 31, 33, 45, 52, 58. HPV vaccines are now included in the national immunization programmes in many countries, with young adolescent peri-pubertal girls the usual cohort for immunization. Population effectiveness in women is now being demonstrated in countries with high vaccine coverage with significant reductions in high-grade cervical intra-epithelial neoplasia (a surrogate for cervical cancer), genital warts and vaccine HPV type genoprevalence. Herd effects in young heterosexual men and older women are evident. Cancers caused by HBV and HPV should, in theory, be amenable to immunotherapies and various therapeutic vaccines for HPV in particular are in development and/or in clinical trial.This article is part of the themed issue 'Human oncogenic viruses'.

4 Review Screening and diagnosis of HBV in low-income and middle-income countries. 2016

Allain, Jean-Pierre / Opare-Sem, Ohene. ·Department of Haematology, University of Cambridge, Science Village, Chesterford Research Park, Little Chesterford CB10 1XL, UK. · Department of Medicine, Kwame Nkrumah University of Science and Technology, University Post Office, Kumasi, Ghana. ·Nat Rev Gastroenterol Hepatol · Pubmed #27625189.

ABSTRACT: HBV testing and diagnosis of HBV-related liver disease in low-income and middle-income countries differs substantially from that in developed countries in terms of access to resources and expensive technologies requiring highly specialized staff. For identification and classification of HBV infection, genomic amplification methods to detect and quantify HBV DNA are often nonexistent or available only in central laboratories of major cities. When samples from peripheral locations do arrive, delays in receiving results generate loss to follow-up. Testing is often limited to measurement of hepatitis B surface antigen (HBsAg), alanine aminotransferase levels, aspartate aminotransferase to platelet ratio index and hepatitis B e antigen (HBeAg) to determine indications for antiviral therapy (AVT). Utilization of AVT is limited by cost and availability, particularly when patients are not covered by health insurance. The natural history of HBV infection is influenced by genotypes B and C in East Asia, where decades of immune tolerance have led to mostly vertical transmission; in sub-Saharan Africa, where genotypes A1 and E predominate, infection is transmitted horizontally between young children, followed by a nonreplicative phase. In both regions, cirrhosis and hepatocellular carcinoma are common and would be considerably ameliorated by AVT. Implementation of the HBV vaccine since the 1990s in Asia and 2000s in Africa has decreased the incidence of HBV, but vaccine failure and insufficiently effective prevention remain concerning issues.

5 Review Magnetic resonance elastography for staging liver fibrosis in non-alcoholic fatty liver disease: a diagnostic accuracy systematic review and individual participant data pooled analysis. 2016

Singh, Siddharth / Venkatesh, Sudhakar K / Loomba, Rohit / Wang, Zhen / Sirlin, Claude / Chen, Jun / Yin, Meng / Miller, Frank H / Low, Russell N / Hassanein, Tarek / Godfrey, Edmund M / Asbach, Patrick / Murad, Mohammad Hassan / Lomas, David J / Talwalkar, Jayant A / Ehman, Richard L. ·Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. · Department of Radiology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, 55905, USA. Venkatesh.Sudhakar@mayo.edu. · NAFLD Translational Research Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Diego, CA, USA. · Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA. · Liver Imaging Group, Department of Radiology, University of California, San Diego, CA, USA. · Department of Radiology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, 55905, USA. · Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. · Sharp and Children's MRI Center, San Diego, CA, USA. · Liver Centers of Southern California, Coronado, CA, USA. · Department of Radiology, Addenbrooke's Hospital, Cambridge, UK. · Department of Radiology, Charité-Universitätsmedizin Berlin, Charité Campus Mitte, Berlin, Germany. ·Eur Radiol · Pubmed #26314479.

ABSTRACT: OBJECTIVES: We conducted an individual participant data (IPD) pooled analysis on diagnostic accuracy of MRE to detect fibrosis stage in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: Through a systematic literature search, we identified studies of MRE (at 60-62.5 Hz) for staging fibrosis in patients with NAFLD, using liver biopsy as gold standard, and contacted study authors for IPD. Through pooled analysis, we calculated the cluster-adjusted AUROC, sensitivity and specificity of MRE for any (≥stage 1), significant (≥stage 2) and advanced (≥stage 3) fibrosis and cirrhosis (stage 4). RESULTS: We included nine studies with 232 patients with NAFLD (mean age, 51 ± 13 years; 37.5% males; mean BMI, 33.5 ± 6.7 kg/m(2); interval between MRE and biopsy <1 year, 98.3%). Fibrosis stage distribution (stage 0/1/2/3/4) was 33.6, 32.3, 10.8, 12.9 and 10.4%, respectively. Mean AUROC (and 95% CIs) for diagnosis of any, significant or advanced fibrosis and cirrhosis was 0.86 (0.82-0.90), 0.87 (0.82-0.93), 0.90 (0.84-0.94) and 0.91 (0.76-0.95), respectively. Similar diagnostic performance was observed in stratified analysis based on sex, obesity and degree of inflammation. CONCLUSIONS: MRE has high diagnostic accuracy for detection of fibrosis in NAFLD, independent of BMI and degree of inflammation. KEY POINTS: • MRE has high diagnostic accuracy for detection of fibrosis in NAFLD. • BMI does not significantly affect accuracy of MRE in NAFLD. • Inflammation had no significant influence on MRE performance in NAFLD for fibrosis.

6 Review Hepatitis C virus treatment as prevention in people who inject drugs: testing the evidence. 2015

Hickman, Matthew / De Angelis, Daniela / Vickerman, Peter / Hutchinson, Sharon / Martin, Natasha Kaleta. ·aSchool of Social and Community Medicine, University of Bristol bMRC Biostatistics Unit, University of Cambridge and Public Health England cGlasgow Caledonian University and Health Protection Scotland, UK dDivision of Global Public Health, University of California San Diego, California, USA. ·Curr Opin Infect Dis · Pubmed #26524330.

ABSTRACT: PURPOSE OF REVIEW: The majority of hepatitis C virus (HCV) infections in the United Kingdom and many developing countries were acquired through injecting. New clinical guidance suggests that HCV treatment should be offered to people with a transmission risk - such as people who inject drugs (PWID) - irrespective of severity of liver disease. We consider the strength of the evidence base and potential problems in evaluating HCV treatment as prevention among PWID. RECENT FINDINGS: There is good theoretical evidence from dynamic models that HCV treatment for PWID could reduce HCV chronic prevalence and incidence among PWID. Economic evaluations from high-income settings have suggested HCV treatment for PWID is cost-effective, and that in many settings HCV treatment of PWID could be more cost-effective than treating those at an equivalent stage with no ongoing transmission risk. Epidemiological studies of older interferon treatments have suggested that PWID can achieve similar treatment outcomes to other patient groups treated for chronic HCV. Impact and cost-effectiveness of HCV treatment is driven by the potential 'prevention benefit' of treating PWID. Model projections suggest that more future infections, end stage liver disease, and HCV-related deaths will be averted than lost through reinfection of PWID treated successfully for HCV. However, there is to date no empirical evidence from trials or observational studies that test the model projections and 'prevention benefit' hypothesis. In part this is because of uncertainty in the evidence base but also there is unlikely to have been a change in HCV prevalence due to HCV treatment because PWID HCV treatment rates historically in most sites have been low, and any scale-up and switch to the new direct acting antiviral has not yet occurred. There are a number of key uncertainties in the data available on PWID that need to be improved and addressed to evaluate treatment as prevention. These include estimates of the prevalence of PWID, measurements of HCV chronic prevalence and incidence among PWID, and how to interpret reinfection rates as potential outcome measures. SUMMARY: Eliminating HCV through scaling up treatment is a theoretical possibility. But empirical data are required to demonstrate that HCV treatment can reduce HCV transmission, which will require an improved evidence base and analytic framework for measuring PWID and HCV prevalence.

7 Review How do economic crises affect migrants' risk of infectious disease? A systematic-narrative review. 2015

Kentikelenis, Alexander / Karanikolos, Marina / Williams, Gemma / Mladovsky, Philipa / King, Lawrence / Pharris, Anastasia / Suk, Jonathan E / Hatzakis, Angelos / McKee, Martin / Noori, Teymur / Stuckler, David. ·1 Department of Sociology, University of Cambridge, Cambridge, UK aek37@cam.ac.uk. · 2 European Observatory on Health Systems and Policies, London School of Hygiene and Tropical Medicine, London, UK. · 3 LSE Health, London School of Economics and Political Science, London, UK. · 4 Department of International Development, London School of Economics and Political Science, London, UK. · 1 Department of Sociology, University of Cambridge, Cambridge, UK. · 5 European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden. · 6 Medical School, University of Athens, Athens, Greece. · 7 Department of Sociology, University of Oxford, Oxford, UK. ·Eur J Public Health · Pubmed #26318852.

ABSTRACT: BACKGROUND: It is not well understood how economic crises affect infectious disease incidence and prevalence, particularly among vulnerable groups. Using a susceptible-infected-recovered framework, we systematically reviewed literature on the impact of the economic crises on infectious disease risks in migrants in Europe, focusing principally on HIV, TB, hepatitis and other STIs. METHODS: We conducted two searches in PubMed/Medline, Web of Science, Cochrane Library, Google Scholar, websites of key organizations and grey literature to identify how economic changes affect migrant populations and infectious disease. We perform a narrative synthesis in order to map critical pathways and identify hypotheses for subsequent research. RESULTS: The systematic review on links between economic crises and migrant health identified 653 studies through database searching; only seven met the inclusion criteria. Fourteen items were identified through further searches. The systematic review on links between economic crises and infectious disease identified 480 studies through database searching; 19 met the inclusion criteria. Eight items were identified through further searches. The reviews show that migrant populations in Europe appear disproportionately at risk of specific infectious diseases, and that economic crises and subsequent responses have tended to exacerbate such risks. Recessions lead to unemployment, impoverishment and other risk factors that can be linked to the transmissibility of disease among migrants. Austerity measures that lead to cuts in prevention and treatment programmes further exacerbate infectious disease risks among migrants. Non-governmental health service providers occasionally stepped in to cater to specific populations that include migrants. CONCLUSIONS: There is evidence that migrants are especially vulnerable to infectious disease during economic crises. Ring-fenced funding of prevention programs, including screening and treatment, is important for addressing this vulnerability.

8 Review Ultra-deep sequencing provides insights into the virology of hepatitis C super-infections in a case of three sequential infections with different genotypes. 2015

Chung, Emily / Ferns, R Bridget / He, Miao / Rigatti, Roberto / Grant, Paul / McCormick, Adele / Bhagani, Sanjay / Webster, Daniel Peter / Nastouli, Eleni / Waters, Laura Jane. ·Mortimer Market Centre, Central and North West London NHS Foundation Trust, London WC1E 6JB, England, UK. · Clinical Microbiology and Virology, University College London NHS Foundation Trust, London W1T 4EU, England, UK. · Illumina Cambridge Ltd, Chesterford Research Park, Little Chesterford, Cambridge CB10 1XL, England, UK. · Royal Free London NHS Foundation Trust, London NW3 2QG, England, UK. · Clinical Microbiology and Virology, University College London NHS Foundation Trust, London W1T 4EU, England, UK. Electronic address: e.nastouli@ucl.ac.uk. ·J Clin Virol · Pubmed #26305822.

ABSTRACT: The current epidemic of Hepatitis C infection in HIV-positive men who have sex with men is associated with increasing use of recreational drugs. Multiple HCV infections have been reported in haemophiliacs and intravenous drug users. Using ultra-deep sequencing analysis, we present the case of an HIV-positive MSM with evidence of three sequential HCV infections, each occurring during the acute phase of the preceding infection, following risk exposures. We observed rapid replacement of the original strain by the incoming genotype at subsequent time points. The impact of HCV super-infection remains unclear and UDS may provide new insights.

9 Review Autoimmune liver disease, autoimmunity and liver transplantation. 2014

Carbone, Marco / Neuberger, James M. ·Division of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom; Organ Donation and Transplantation, National Health Service Blood and Transplant (NHSBT), Bristol, United Kingdom. · Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom; Organ Donation and Transplantation, National Health Service Blood and Transplant (NHSBT), Bristol, United Kingdom. Electronic address: James.Neuberger@nhsbt.nhs.uk. ·J Hepatol · Pubmed #24084655.

ABSTRACT: Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) represent the three major autoimmune liver diseases (AILD). PBC, PSC, and AIH are all complex disorders in that they result from the effects of multiple genes in combination with as yet unidentified environmental factors. Recent genome-wide association studies have identified numerous risk loci for PBC and PSC that host genes involved in innate or acquired immune responses. These loci may provide a clue as to the immune-based pathogenesis of AILD. Moreover, many significant risk loci for PBC and PSC are also risk loci for other autoimmune disorders, such type I diabetes, multiple sclerosis and rheumatoid arthritis, suggesting a shared genetic basis and possibly similar molecular pathways for diverse autoimmune conditions. There is no curative treatment for all three disorders, and a significant number of patients eventually progress to end-stage liver disease requiring liver transplantation (LT). LT in this context has a favourable overall outcome with current patient and graft survival exceeding 80% at 5years. Indications are as for other chronic liver disease although recent data suggest that while lethargy improves after transplantation, the effect is modest and variable so lethargy alone is not an indication. In contrast, pruritus rapidly responds. Cholangiocarcinoma, except under rigorous selection criteria, excludes LT because of the high risk of recurrence. All three conditions may recur after transplantation and are associated with a greater risk of both acute cellular and chronic ductopenic rejection. It is possible that a crosstalk between alloimmune and autoimmune response perpetuate each other. An immunological response toward self- or allo-antigens is well recognised after LT in patients transplanted for non-autoimmune indications and sometimes termed "de novo autoimmune hepatitis". Whether this is part of the spectrum of rejection or an autoimmune process is not clear. In this manuscript, we review novel findings about disease processes and mechanisms that lead to autoimmunity in the liver and their possible involvement in the immune response vs. the graft after LT.

10 Review Is sustained virological response a marker of treatment efficacy in patients with chronic hepatitis C viral infection with no response or relapse to previous antiviral intervention? 2013

Gurusamy, Kurinchi S / Wilson, Edward / Koretz, Ronald L / Allen, Victoria B / Davidson, Brian R / Burroughs, Andrew K / Gluud, Christian. ·Department of Surgery, University College London, London, United Kingdom. · Health Economics Group, University of East Anglia, Norwich, United Kingdom ; Cambridge Centre for Health Services Research, University of Cambridge, Cambridge, United Kingdom. · Cochrane Hepato Biliary Group, Granada Hills, California, United States of America. · Sheila Sherlock Liver Centre and Institute of Liver and Digestive Health, Royal Free Hospital, and UCL, London, United Kingdom. · Cochrane Hepato-Biliary Group, The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet,Copenhagen University Hospital, Copenhagen, Denmark. ·PLoS One · Pubmed #24349487.

ABSTRACT: BACKGROUND: Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs. METHODS: We created a decision tree model based on a Cochrane systematic review on interferon retreatment for patients who did not respond to initial therapy or who relapsed following SVR. Extrapolating data to 20 years, we modelled the outcome from three scenarios: (1) observed medium-term (5 year) annual mortality rates continue to the long term (20 years); (2) long-term annual mortality in retreatment responders falls to that of the general population while retreatment non-responders continue at the medium-term mortality; (3) long-term annual mortality in retreatment non-responders is the same as control group non-responders (i.e., the increased treatment-related medium mortality "wears off"). RESULTS: The mean differences in life expectancy over 20 years with interferon versus control in the first, second, and third scenarios were -0.34 years (95% confidence interval (CI) -0.71 to 0.03), -0.23 years (95% CI -0.69 to 0.24), and -0.01 (95% CI -0.3 to 0.27), respectively. The life expectancy was always lower in the interferon group than in the control group in scenario 1. In scenario 3, the interferon group had a longer life expectancy than the control group only when more than 7% in the interferon group achieved SVR. CONCLUSIONS: SVR may be a good prognostic marker but does not seem to be a valid surrogate marker for assessing HCV treatment efficacy of interferon retreatment. The SVR threshold at which retreatment increases life expectancy may be different for different drugs depending upon the adverse event profile and treatment efficacy. This has to be determined for each drug by RCTs and appropriate modelling before SVR can be accepted as a surrogate marker.

11 Review Novel insights into autoimmune liver diseases provided by genome-wide association studies. 2013

Mells, George F / Kaser, Arthur / Karlsen, Tom H. ·Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge, UK; Academic Department of Medical Genetics, University of Cambridge, Cambridge, UK. ·J Autoimmun · Pubmed #23931959.

ABSTRACT: Autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are complex disorders, resulting from the interaction of genetic and environmental factors. For many years, investigators have attempted to delineate the genetic architecture of these conditions, aiming to elucidate disease pathogenesis and identify molecular targets for pharmacotherapy. Early genetic studies consisted of HLA association studies and non-HLA candidate gene association studies, designed to identify association with selected HLA or non-HLA loci. HLA association studies identified HLA risk loci that are now well-established. Non-HLA candidate gene studies were less fruitful because they were mostly underpowered to detect modest effects and were frequently designed to investigate one or two functional polymorphisms, meaning that gene coverage was poor. Furthermore, weak associations detected in one small cohort were often never validated. If replication studies were undertaken, the results were often conflicting. More recently, a series of genome-wide association studies (GWAS) and related study designs have evaluated the impact of common genetic variants (frequency >5% in the general population) across the entire genome. These studies have identified several non-HLA risk loci for autoimmune liver disease. The majority of risk loci detected are similar to those of non-hepatic immune-mediated diseases, suggesting that outcomes from GWAS and related genetic studies reflect broad phenotypic themes rather than traditional clinical conditions. The specific genetic basis of these PBC and PSC associated inflammatory themes as determined by GWAS is described and discussed in the context of interacting genetic and non-genetic (including environmental) factors.

12 Review Hepatitis C virus and nonliver solid organ transplantation. 2013

Carbone, Marco / Mutimer, David / Neuberger, James. ·Liver Unit, Addenbrooke's Hospital, Cambridge, United Kingdom. Marco.carbone@nhs.net ·Transplantation · Pubmed #23172130.

ABSTRACT: : Hepatitis C virus (HCV) infection is common in solid organ allograft recipients and is a significant cause of morbidity and mortality after transplantation, so effective management will improve outcomes. In this review, we discuss the extent of the problem associated with HCV infection in donors and kidney, heart, and lung transplant candidates and recipients and recommend follow-up and treatment.Patients with end-stage kidney disease without cirrhosis and selected patients with early-stage cirrhosis can be considered for kidney transplant alone. In HCV-infected kidney allograft recipients, the progression of fibrosis should be evaluated serially by Fibroscan or serologic measures of fibrosis. Transplantation of kidneys from HCV-positive donors should be restricted to HCV-positive recipients as it is associated with a reduced time waiting for a graft and does not affect posttransplant outcomes. Hepatitis C virus antiviral therapy should be considered for all HCV-RNA-positive kidney transplant candidates, irrespective of the baseline liver histopathology. Protease inhibitors have yet to be fully evaluated in patients with renal dysfunction and in the transplant population. As these agents may cause anemia in patients with normal renal function, tolerability may be a problem in patients with end-stage kidney disease.The impact of HCV infection on survival in heart and lung transplantation is unclear. Because of the shortage of organs, few HCV-infected patients are accepted for transplantation.Universal use of nucleic acid amplification testing (NAT) for the screening of potential organ donors should be reserved to high-risk donors. Assays that quantify HCV core antigen may become more cost-effective than NAT for the screening of potential organ donors.

13 Review Hepatitis B virus in transfusion medicine: still a problem? 2012

Allain, Jean-Pierre / Candotti, Daniel / Anonymous2590717. ·Dept. of Haematology, University of Cambridge, UK. jpa1000@cam.ac.uk ·Biologicals · Pubmed #22305086.

ABSTRACT: Hepatitis B virus (HBV) has probably evolved with humans for nearly 35,000 years. HBV diversified into 9 genotypes (A-I) presenting specific features directing epidemiology, clinical expression and testing. Genotypes E and C are more infectious and carry higher risk of chronicity and cancer. HBsAg blood screening implemented 40 years ago enormously decreased the risk of transfusion transmission but the remaining risk requires extremely sensitive nucleic acid testing (NAT) to be removed. Limitations of the host immune system, the impact of immunodeficiency and the mechanisms utilised for viral persistence were recently identified. HBV replication produces excess HBsAg and infectious and defective viral particles but screening assays for HBsAg or viral particles alone do not allow fully efficient detection, making necessary screening for both. The host immune system fails to completely control the virus that escapes and persists unrecognized at very low levels or as immuno-selected variants. Variants may not be identified by assays, explaining false negative results. Specific mutations may affect post-transcriptional mechanisms including HBV RNA splicing. Asymptomatic HBV infected blood donors are at risk of long-term complications through mechanisms to be understood for appropriate counselling. Infectivity of occult HBV infection (OBI) by transfusion appears low, anti-HBc (anti-core antigen) only being more infectious than anti-HBs (anti-S protein) positive units.

14 Review Challenges in hepatitis B detection among blood donors. 2011

Allain, Jean-Pierre / Cox, Laura. ·Department of Haematology, University of Cambridge, Cambridge, UK. jpa1000@cam.ac.uk ·Curr Opin Hematol · Pubmed #21912252.

ABSTRACT: PURPOSE OF REVIEW: The availability of hepatitis B virus (HBV) nucleic acid testing (NAT) for donor blood screening led to its implementation in low prevalence and high prevalence countries. Genomic detection was a substantial addition to HBV surface protein (HBsAg) screening by detecting window period infections and 'occult' HBV infections (OBIs), characterized by undetectable HBsAg, low viral load and presence of serological markers (anti-HBc and/or anti-HBs). OBIs are the result of multiple, poorly understood mechanisms including incomplete immune control mutations of the HBsAg antigenic determinants; abnormal expression of S gene; and inhibition of genome transcription. Infectivity for the recipient is high for window period blood and relatively low for OBIs. RECENT FINDINGS: The number of cases identified by NAT ranges between 1 : 1000 and 1 : 50 000, depending on epidemiology and assay sensitivity whether NAT is implemented in individual donations or pools of samples. OBI donors are generally older than 45 years except in Africa, carry very low viral load (median 11-25  IU/ml) and have normal alanine transaminase levels. Cases carrying anti-HBc alone are more infectious than those with low level of anti-HBs. Evidence of HBsAg escape mutants that are undetected by commercial assays has been published. Inhibition of HBsAg mRNA production and export are potential mechanisms of OBI occurrence. SUMMARY: HBV blood safety is improved by NAT for HBV DNA when applied to individual donations. Until the sensitivity of NAT is improved, both this method and HBsAg screening are needed to eliminate potentially infectious blood donations. Occult HBV characterization clarifies new facets of HBV natural history.

15 Review Diagnostic algorithm for HBV safe transfusion. 2009

Allain, Jean-Pierre / Candotti, Daniel. ·Division of Transfusion Medicine, Dept of Haematology, University of Cambridge, Cambridge, United Kingdom. jpa1000@cam.ac.uk ·Blood Transfus · Pubmed #19657480.

ABSTRACT: -- No abstract --

16 Review Transfusion-transmitted hepatitis B virus infection. 2009

Candotti, Daniel / Allain, Jean-Pierre. ·National Health Service Blood & Transplant, Cambridge Blood Centre, Long Road, Cambridge CB2 2PT, UK. dc241@cam.ac.uk ·J Hepatol · Pubmed #19615780.

ABSTRACT: Hepatitis B virus (HBV) remains a major risk of transfusion-transmitted infection due to the pre-seroconversion window period (WP), infection with immunovariant viruses, and with occult carriage of HBV infection (OBI). Reduction of HBV residual risk depends upon developing more sensitive HBV surface antigen (HBsAg) tests, adopting anti-HBc screening when appropriate, and implementing HBV nucleic acid testing (NAT), either in minipools or more efficiently in individual samples. HBV NAT combines the ability to significantly reduce the window period and to detect occult HBV carriage substantiating decades of clinical observation that HBsAg-negative/anti-HBc-positive blood could transmit HBV. Clinical observations suggest limited transmission rate of occult HBV compared to WP. Low transmission rate might be related to low viral load observed in OBIs or to the presence of mutants associated with occult carriage. OBIs carrying detectable anti-HBs ( approximately 50%) are essentially not infectious by transfusion. However, recent data suggest that the neutralizing capacity of low anti-HBs may be inefficient when overcome by exposure to high viral load. Anti-HBc blood units without detectable anti-HBs appear moderately infectious except in immunocompromised recipients. Immunodeficient elderly and patients receiving immunosuppressive treatments may be susceptible to infection with lower infectious dose even in the presence of anti-HBs. The immune status of blood recipients should be taken into consideration when investigating "post-transfusion" HBV infection. Pre-transfusion testing and post-transfusion long-term follow-up of recipients, and molecular analysis of the virus infecting both donor and recipient are critical to definitively incriminate transfusion in the transmission of HBV.

17 Review Transfusion-transmitted infectious diseases. 2009

Allain, Jean-Pierre / Stramer, Susan L / Carneiro-Proietti, A B F / Martins, M L / Lopes da Silva, S N / Ribeiro, M / Proietti, F A / Reesink, Henk W. ·Dept. of Haematology, University of Cambridge, Cambridge, UK. jpa1000@cam.ac.uk ·Biologicals · Pubmed #19231236.

ABSTRACT: A spectrum of blood-borne infectious agents is transmitted through transfusion of infected blood donated by apparently healthy and asymptomatic blood donors. The diversity of infectious agents includes hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency viruses (HIV-1/2), human T-cell lymphotropic viruses (HTLV-I/II), Cytomegalovirus (CMV), Parvovirus B19, West Nile Virus (WNV), Dengue virus, trypanosomiasis, malaria, and variant CJD. Several strategies are implemented to reduce the risk of transmitting these infectious agents by donor exclusion for clinical history of risk factors, screening for the serological markers of infections, and nucleic acid testing (NAT) by viral gene amplification for direct and sensitive detection of the known infectious agents. Consequently, transfusions are safer now than ever before and we have learnt how to mitigate risks of emerging infectious diseases such as West Nile, Chikungunya, and Dengue viruses.

18 Review Liver transplantation for liver disease caused by hepatitis C virus infection. 2009

Shankar, Arun / Alexander, Graeme. ·Department of Hepatology, Addenbrooke's Hospital, Cambridge. ·Br J Hosp Med (Lond) · Pubmed #19229150.

ABSTRACT: Hepatitis C is an important problem that often requires liver transplantation. However, outcomes have not improved in line with liver transplants for other indications. This article explores the issues surrounding this difficult area of transplant hepatology.

19 Review The case for combination antiviral therapy for chronic hepatitis B virus infection. 2008

Nash, Kathryn L / Alexander, Graeme J M. ·Department of Hepatology, University Department of Medicine, Addenbrooke's Hospital, Cambridge, UK. klnash11@yahoo.co.uk ·Lancet Infect Dis · Pubmed #18485825.

ABSTRACT: The treatment of hepatitis B virus (HBV) infection has been revolutionised in the past decade by the increased availability of effective antiviral agents. Many studies have shown the benefits of single agent therapy, but there is an alarming and rising rate of viral resistance, and clear evidence that viruses that harbour resistant mutations can cause liver disease and death. Current national guidelines for the treatment of HBV recommend a programme that starts with monotherapy, followed by sequential monotherapy or add-on therapy for those infections in which mutations have arisen. Very few studies starting with combination therapy have been undertaken, so there is little evidence of the clinical benefit of this approach to treatment. The studies that have been done have been short term and have concentrated on clinical parameters rather than virological resistance, which is likely to be the key determinant in the longer term. We argue that we should not wait for the evidence to use combination therapy for the treatment of HBV, since such trials may never be done and it would take several years for a benefit to become apparent. In the meantime, multidrug-resistant strains continue to hinder HBV control.

20 Clinical Trial Chronic Hepatitis B Virus Infection: The Relation between Hepatitis B Antigen Expression, Telomere Length, Senescence, Inflammation and Fibrosis. 2015

Tachtatzis, Phaedra M / Marshall, Aileen / Arvinthan, Aloysious / Verma, Suman / Penrhyn-Lowe, Sue / Mela, Marianna / Scarpini, Cinzia / Davies, Susan E / Coleman, Nicholas / Alexander, Graeme J M. ·Department of Hepatology, St James's University Hospital, Leeds, United Kingdom. · Department of Hepatology, Royal Free Hospital, London, United Kingdom. · Institute of Liver Studies, King's College Hospital, London, United Kingdom. · Hutchison/MRC Research Centre, University of Cambridge, Cambridge, United Kingdom. · Division of Gastroenterology and Hepatology, University of Cambridge, Cambridge, United Kingdom. · Department of Pathology, University of Cambridge, Cambridge, United Kingdom. · Pancreatic Cancer Centre, University of Cambridge, Cambridge, United Kingdom. ·PLoS One · Pubmed #26024529.

ABSTRACT: BACKGROUND: Chronic Hepatitis B virus (HBV) infection can lead to the development of chronic hepatitis, cirrhosis and hepatocellular carcinoma. We hypothesized that HBV might accelerate hepatocyte ageing and investigated the effect of HBV on hepatocyte cell cycle state and biological age. We also investigated the relation between inflammation, fibrosis and cell cycle phase. METHODS: Liver samples from patients with chronic HBV (n = 91), normal liver (n = 55) and regenerating liver (n = 15) were studied. Immunohistochemistry for cell cycle phase markers and HBV antigens was used to determine host cell cycle phase. Hepatocyte-specific telomere length was evaluated by quantitative fluorescent in-situ hybridization (Q-FISH) in conjunction with hepatocyte nuclear area and HBV antigen expression. The effects of induced cell cycle arrest and induced cellular senescence on HBV production were assessed in vitro. RESULTS: 13.7% hepatocytes in chronic HBV had entered cell cycle, but expression of markers for S, G2 and M phase was low compared with regenerating liver. Hepatocyte p21 expression was increased (10.9%) in chronic HBV and correlated with liver fibrosis. Mean telomere length was reduced in chronic HBV compared to normal. However, within HBV-affected livers, hepatocytes expressing HBV antigens had longer telomeres. Telomere length declined and hepatocyte nuclear size increased as HBV core antigen (HBcAg) expression shifted from the nucleus to cytoplasm. Nuclear co-expression of HBcAg and p21 was not observed. Cell cycle arrest induced in vitro was associated with increased HBV production, in contrast to in vitro induction of cellular senescence, which had no effect. CONCLUSION: Chronic HBV infection was associated with hepatocyte G1 cell cycle arrest and accelerated hepatocyte ageing, implying that HBV induced cellular senescence. However, HBV replication was confined to biologically younger hepatocytes. Changes in the cellular location of HBcAg may be related to the onset of cellular senescence.

21 Article Building a mechanistic mathematical model of hepatitis C virus entry. 2019

Kalemera, Mphatso / Mincheva, Dilyana / Grove, Joe / Illingworth, Christopher J R. ·Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, United Kingdom. · Department of Genetics, University of Cambridge, Cambridge, United Kingdom. ·PLoS Comput Biol · Pubmed #30883541.

ABSTRACT: The mechanism by which hepatitis C virus (HCV) gains entry into cells is a complex one, involving a broad range of host proteins. Entry is a critical phase of the viral lifecycle, and a potential target for therapeutic or vaccine-mediated intervention. However, the mechanics of HCV entry remain poorly understood. Here we describe a novel computational model of viral entry, encompassing the relationship between HCV and the key host receptors CD81 and SR-B1. We conduct experiments to thoroughly quantify the influence of an increase or decrease in receptor availability upon the extent of viral entry. We use these data to build and parameterise a mathematical model, which we then validate by further experiments. Our results are consistent with sequential HCV-receptor interactions, whereby initial interaction between the HCV E2 glycoprotein and SR-B1 facilitates the accumulation CD81 receptors, leading to viral entry. However, we also demonstrate that a small minority of viruses can achieve entry in the absence of SR-B1. Our model estimates the impact of the different obstacles that viruses must surmount to achieve entry; among virus particles attaching to the cell surface, around one third of viruses accumulate sufficient CD81 receptors, of which 4-8% then complete the subsequent steps to achieve productive infection. Furthermore, we make estimates of receptor stoichiometry; in excess of 10 receptors are likely to be required to achieve viral entry. Our model provides a tool to investigate the entry characteristics of HCV variants and outlines a framework for future quantitative studies of the multi-receptor dynamics of HCV entry.

22 Article Infections and associated behaviors among deceased organ donors: Informing the assessment of risk. 2019

Davison, Katy L / Ushiro-Lumb, Ines / Lawrance, Marcus / Trotter, Patrick / Powell, James J / Brailsford, Susan R. ·NHS Blood and Transplant (NHSBT)/Public Health England (PHE) Epidemiology Unit, Blood Safety, Hepatitis, Sexually Transmitted Infections (STI) and HIV Division Public Health England, London, UK. · Microbiology Services, NHS Blood and Transplant (NHSBT), London, UK. · National Infection Services, Public Health England, UK. · National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre and the NIHR Blood and Transplant Research Unit (BTRU) in Organ Donation and Transplantation at the University of Cambridge in Collaboration with Newcastle University and in Partnership with NHSBT Organ Donation and Transplantation Directorate, NHSBT, London, UK. · Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, UK. ·Transpl Infect Dis · Pubmed #30693636.

ABSTRACT: BACKGROUND: For infectious disease risk assessment among deceased organ donors, pre-donation clinical, microbiological, and behavioral information are reviewed; however, uncertainty may arise due to false negative screening results of recently acquired infections. METHOD: The burden of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV), and residual risks (RR) of undetected virus was estimated, with the impact of more sensitive screening. RESULTS: For United Kingdom potential deceased organ donors between 2010 and 2014, prevalence of HBsAg was 0.1%, HIV 0.06% and HCV 0.9%, increasing to 25.7% in people who injected drugs (PWID). Incidence, derived from new blood donors, was multiplied by duration of screening assay window periods to give RR per 100 000 donors as 0.43 (95% confidence interval [CI] 0.03-3.99) for HBV, 0.08 (95% CI 0.02-0.21) for HIV, and 5.96 (95% CI 0.82-37.89) for HCV. For PWID, HCV RR was 163.3 (95% CI 22.8-1107.8) compared to 2.76 (95% CI 0.35-17.36) for non-PWID. RR decreased significantly with nucleic acid testing (NAT), and, for HCV, antigen testing had a similar impact. CONCLUSION: While the burden of HCV risk lies within PWID, these are in small numbers therefore few HCV antigen or NAT tests would be needed to more accurately assess risk.

23 Article Multiple HBV transfusion transmissions from undetected occult infections: revising the minimal infectious dose. 2019

Candotti, Daniel / Assennato, Sonny Michael / Laperche, Syria / Allain, Jean-Pierre / Levicnik-Stezinar, Snezna. ·Department of Blood Transmitted Agents, National Institute of Blood Transfusion, Paris, France. · Department of Haematology, University of Cambridge, Cambridge, UK. · Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia. ·Gut · Pubmed #29959168.

ABSTRACT: OBJECTIVE: HBV infection by blood components is currently prevented in most developed countries by combining sensitive HBV surface antigen (HBsAg) assays, nucleic acid testing (NAT) and in a few of them antibodies against the HBV core antigen (anti-HBc) screening. HBV transmissions by blood components from three repeat donors tested negative for HBsAg and HBV DNA with a highly sensitive screening test (limit of detection (LOD): 3.4 IU/mL) were investigated. DESIGN: 30 of the 47 recipients of components produced from these three donors were examined. Transfusion transmission was confirmed by phylogenetic analysis of viral sequences obtained from recipients and donors following viral particle concentration. RESULTS: 9 of 31 (29%) recipients were infected: 7 infections were related to 200 mL of fresh frozen plasma and 2 infections to red blood cells containing 20 mL plasma. Transfusion transmission was confirmed by >99% identity of donor/recipient sequences in five cases, probable in three and possible in one. HBV active infection remained unsuspected for 24-57 months in three recipients. Five non-infected recipients carried anti-HBs when transfused. Six patients transfused with platelet concentrates treated with a pathogen reduction method were not infected. These data enabled to revise previous estimate of the minimal infectious dose from approximately 100 to 16 copies (or 3 IU) of HBV DNA. CONCLUSIONS: HBV transfusion transmission from occult HBV infection carrying extremely low viral loads is related to plasma volume transfused and possibly prevented by anti-HBs. HBV blood safety could be further improved by either anti-HBc screening, HBV DNA NAT with a LOD of 0.8 copies/mL (0.15 IU/mL) or pathogen reduction of blood components.

24 Article The art of medicine: Inflamed depression. 2018

Bullmore, Edward. ·Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge CB2 2QQ, UK; GlaxoSmithKline, Immuno-Inflammation Therapeutic Area Unit, Stevenage, UK. Electronic address: etb23@medschl.cam.ac.uk. ·Lancet · Pubmed #30712704.

ABSTRACT: -- No abstract --

25 Article Recurrence of Hepatitis B Infection in Liver Transplant Patients Receiving Long-Term Hepatitis B Immunoglobulin Prophylaxis. 2018

Beckebaum, Susanne / Herzer, Kerstin / Bauhofer, Artur / Gelson, William / De Simone, Paolo / de Man, Robert / Engelmann, Cornelius / Müllhaupt, Beat / Vionnet, Julien / Salizzoni, Mauro / Volpes, Riccardo / Ercolani, Giorgio / De Carlis, Luciano / Angeli, Paolo / Burra, Patrizia / Dufour, Jean-François / Rossi, Massimo / Cillo, Umberto / Neumann, Ulf / Fischer, Lutz / Niemann, Gabriele / Toti, Luca / Tisone, Guiseppe. ·Department of Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany. · Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany. · Corporate Medical Affairs and Corporate Clinical Research and Development, Biotest AG, Dreieich, Germany. · Cambridge Liver Unit, Addenbrooke's Hospital, Cambridge, United Kingdom. · Hepatobiliary Surgery and Liver Transplantation, Chirurgia Epatica e del Trapianto Fegato Pisa, Pisa, Italy. · Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, Netherlands. · Department of Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany. · Swiss HPB Center and Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland. · Transplantation Centre and Service of Gastroenterology and Hepatology, Lausanne, Switzerland. · Chirurgia Generale 2U, Centro Trapianto Fegato, AO Città della Salute e della Scienza di Torino, Turin, Italy. · Hepatology and Gastroenterology Unit, ISMETT-IRCCS, Palermo, Italy. · Department of General Surgery, Morgagni-Pierantoni General Hospital, University of Bologna, Bologna, Italy. · Surgery and Abdominal Transplantation Division, Niguarda Ca' Granda Hospital, Milan, Italy. · Multivisceral Transplant Unit, Padua University Hospital, Padua, Italy. · University Clinic for Visceral Surgery and Medicine, Inselspital, Bern, Switzerland. · Department of General Surgery and Organ Transplantation, Umberto I Policlinic, Sapienza University, Rome, Italy. · Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padova, Italy. · Department of Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Aachen, Germany. · Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Transplant Centre, Faculty of Medicine, Azienda Ospedaliera Policlinico Tor Vergata, Rome, Italy. ·Ann Transplant · Pubmed #30420590.

ABSTRACT: BACKGROUND Long-term real-world data are relatively sparse regarding recurrence of chronic hepatitis B virus (HBV) infection after liver transplantation using hepatitis B immunoglobulin (HBIg) and nucleos(t)ide analogue (NUC) prophylaxis. MATERIAL AND METHODS Data from 371 adults transplanted for HBV-related disease at 20 European centers and given HBIg for ³12 months ± NUC therapy were analyzed retrospectively. RESULTS HBIg comprised Hepatect® (iv HBIgB; n=299), subcutaneous Zutectra® (sc HBIg, n=236), and other HBIg preparations (n=130); 93.5% received NUC therapy. Mean follow-up was 6.8±3.5 years. The primary efficacy variable, freedom from HBV recurrence, occurred in 95.7% of patients (95% CI [93.1%, 97.5%]). The observed incidence of recurrence was 16/371 (4.3%) (annual rate 0.65%); 5/16 patients with recurrence had discontinued HBIg and 7/16 had anti-HBs <100 IU/l. Excluding these 7 patients, the HBV recurrence rate was 2.4%. The recurrence rate while on HBIg therapy was 1 per 2069 months. In patients who discontinued HBIg, risk of HBV recurrence versus sc HBIg users was increased by 5.2-fold (1 per 1 603 versus 1 per 8379 treatment months). The annual rate of HBV-related hepatocellular carcinoma (HCC) recurrence was 1.7%. CONCLUSIONS These results support the long-term use of HBIg with NUC therapy as an effective management strategy to minimize risk of HBV recurrence and virus-related complications after liver transplantation.