Hepatitis: United Kingdom

Webster DP, Klenerman P, Collier J, Jeffery KJ. · Department of Microbiology, John Radcliffe Hospital, Oxford, UK. · Lancet Infect Dis. · Pubmed #19179226 No free full text.

Abstract: Hepatitis C virus (HCV) infection is a major and growing global health problem, affecting about 170 million people worldwide, and is a leading cause of liver cirrhosis and hepatocellular carcinoma. Currently, treatment is restricted to interferon alfa and ribavirin, which leads to a successful outcome in only about 50% of individuals. New effective treatments with tolerable side-effect profiles are needed urgently, but development has been hindered by an inability to culture HCV and a scarcity of animal models. Herein, we review progress in HCV biology, including cell culture and new animal models, and the contribution of this work to our understanding of the virus' life-cycle and pathogenesis and development of specifically targeted antiviral treatment. We also discuss changes in our understanding of HCV epidemiology, clinical manifestations, and diagnostics.

Heydtmann M, Adams DH. · NIHR Biomedical Research Unit for Liver Disease, MRC Centre for Immune Regulation, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom. · Hepatology. · Pubmed #19177577 No free full text.

Abstract: Chronic infection with the hepatitis C virus, a noncytopathic hepatotropic RNA virus, affects over 170 million people worldwide. In the majority of cases, neither the early innate immune response nor the later adaptive immune response succeeds in clearing the virus, and the infection becomes chronic. Furthermore, in many patients, the ineffective inflammatory response drives fibrogenesis and the development of cirrhosis. It is critical to understand this immune pathology if preventative and curative therapies are to be developed. Chemokines are a superfamily of small proteins that promote leukocyte migration and orchestrate the immune response to viruses, including hepatitis C virus. Chemokines are crucial for viral elimination, but inappropriate persistence of expression in chronic hepatitis C infection can drive tissue damage and inflammation. Here we review the role of chemokines and their receptors in hepatitis C virus infection.

Gurusamy KS, Osmani B, Xirouchakis E, Burroughs AK, Davidson BR. · University Department of Surgery, Royal Free Hospital and University College School of Medicine, 9th Floor, Royal Free Hospital, Pond Street, London, UK, NW3 2QG. · Cochrane Database Syst Rev. · Pubmed #19160303 No free full text.

Abstract: BACKGROUND: Antiviral therapy to treat recurrent hepatitis C infection after liver transplantation is controversial. OBJECTIVES: To compare the therapeutic efficacy and side effects of different antiviral regimens in patients with hepatitis C re-infected grafts after liver transplantation. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until September 2007. SELECTION CRITERIA: Only randomised clinical trials (irrespective of language, blinding, or publication status) comparing various antiviral therapies (alone or in combination) in the treatment of hepatitis C virus recurrence in liver transplantation were considered for the review. DATA COLLECTION AND ANALYSIS: Two authors collected the data independently. We calculated the relative risk (RR) or weighted mean difference (WMD) with 95% confidence intervals (CI) using the fixed-effect and the random-effects models based on available case-analysis. MAIN RESULTS: A total of 389 liver transplant recipients with proven hepatitis C recurrence were randomised in eleven trials to various interventions and controls. The mean proportion of genotype I was 77.8% in the seven trials that reported the genotype. Only one or two trials were included under each comparison. All the trials were of high risk of bias. There was no difference in the mortality, graft rejection, or in re-transplantation between intervention and control in any of the comparisons that reported these outcomes. None of the trials reported liver decompensation or quality of life. Life-threatening adverse effects were not reported in either group in any of the comparisons. Up to 87.5% of patients required reduction in dose and up to 42.9% of patients required cessation of treatment in the various comparisons because of adverse effects or because of patient's choice to stop treatment. AUTHORS' CONCLUSIONS: 1. Considering the lack of clinical benefit and the frequent adverse effects, there is currently no evidence to recommend antiviral treatment for recurrent liver graft infection with HCV. 2. Further randomised clinical trials with adequate trial methodology and adequate duration of follow-up are necessary.

Hartwell D, Shepherd J. · University of Southampton, Southampton, UK. · Int J Technol Assess Health Care. · Pubmed #19126252 No free full text.

Abstract: OBJECTIVES: Traditionally, patients with chronic hepatitis C virus (HCV) infection have not received treatment until their infection reaches the moderate to severe stage. The aim of this systematic review was to assess the clinical effectiveness of pegylated (PEG) and non-pegylated interferon (IFN) alfa and ribavirin (RBV) for the treatment of adults with histologically mild HCV. METHODS: We performed a sensitive search of fourteen electronic bibliographic databases for literature that met criteria defined in a research protocol. Two reviewers independently selected studies, extracted data and assessed methodological quality. RESULTS: Ten randomized, controlled trials (RCTs) were included. Treatment with PEG + RBV combination therapy resulted in significantly higher sustained virological response (SVR) rates than treatment with IFN + RBV combination therapy. Treatment for 48 weeks with PEG + RBV was significantly more effective than the same treatment for 24 weeks. Significantly higher SVR rates were seen with IFN + RBV compared with either IFN monotherapy or no treatment. In the meta-analysis (four IFN trials), the relative risk of not experiencing an SVR was 0.59 (95 percent CI, 0.51 - 0.69) and was statistically significant (p < .00001). SVRs were higher for patients with genotype non-1 compared with genotype 1 for both PEG + RBV and IFN + RBV treatments. CONCLUSIONS: Patients with histologically mild HCV can be successfully treated with both PEG and IFN combination therapy, and response rates are broadly comparable with those achieved in patients with advanced disease. Treating patients in the early milder stages of HCV is, therefore, a clinically effective option.

Sheldon J, Sarmento E Castro R, Soriano V. · Servicio de Enfermedades Infecciosas, Hospital Carlos III, Madrid, España. · Enferm Infecc Microbiol Clin. · Pubmed #19100231 links to  free full text

Abstract: The development hepatitis B virus (HBV) polymerase inhibitors has revolutionised the treatment of chronic HBV infection. However, the emergence of resistance mutations can compromise their clinical efficacy and it is mandatory to know the mechanisms of these resistances, its clinical implications, strategies for prevention and how to deal with the rescue. Since HBV has a high degree of replication and a high error rate, during their life cycle it will produce a large number of punctual mutations in individuals with active replication. Due to the large size of the HBV genome, all the possible changes may occur daily and should be screened before starting any antiviral therapy. Therefore, in individuals infected with HBV there is a mixture of similar viruses that evolves over time (quasispecies), some of which are carriers of resistance mutations to antivirals, which explains why they can be selected quickly after exposure to drug. Of the five drugs approved in Europe for the treatment of hepatitis B, three of them (lamivudine, adefovir and entecavir) are likely to be affected directly by these mutations, as well as other active drugs, such as telbivudine, tenofovir and the emtricitabine. The characterization of the resistance mutations is helpful for the prevention and the optimization of antiviral therapies.

Low E, Vogel M, Rockstroh J, Nelson M. · Department of Sexual Health and HIV, Chelsea and Westminster Hospital, London, UK. · AIDS Rev. · Pubmed #19092980 No free full text.

Abstract: Due to the asymptomatic nature of acute hepatitis C it can be difficult to diagnose in the early stage of infection, but with the higher treatment success rates and reduced treatment duration at this stage, it is imperative that diagnoses are made. Therefore, physicians should routinely screen at-risk individuals and investigate abnormal liver function tests. Serum HCV RNA should be considered in any HCV-antibody-negative individual in whom acute HCV is clinically suspected, or annually in those high-risk individuals with previous infection. Acute hepatitis C transmission may be facilitated by the presence of an erosive genital lesion, such as syphilis or lymphogranuloma venereum, and thus testing at this time should be encouraged. Reinfection with HCV does occur and patients need to be informed of the sexual and other high-risk behaviors that put them at risk of reinfection. Public awareness of the possibility of HCV infection, and subsequent reinfection, in high-risk groups should be increased. The question of the optimal treatment regimen is still disputed. However, ongoing trials and the proposed randomized controlled trial from the European AIDS Treatment Network should answer many of our questions. In the meantime, units faced with HIV/acute hepatitis C coinfection should follow recommendations from the HCV-HIV International Panel.

Farquhar MJ, McKeating JA. · Division of Immunity and Infection, University of Birmingham, UK. · J Viral Hepat. · Pubmed #19087224 No free full text.

Abstract: Much of our current understanding of hepatitis C virus (HCV) replication has hailed from the use of a small number of cloned viral genomes and transformed hepatoma cell lines. Recent evidence suggests that lipoproteins play a key role in the HCV life cycle and virus particles derived from the sera of infected patients exist in association with host lipoproteins. This report will review the literature on HCV replication in primary hepatocytes and transformed cell lines, focusing largely on host factors defining particle entry.

McAvoy NC, Hayes PC. · Royal Infirmary of Edinburgh, Department of Hepatology, Edinburgh EH164SA, UK. norma.mcavoy.ed.ac.uk · Expert Rev Gastroenterol Hepatol. · Pubmed #19072432 No free full text.

Abstract: 'Epidemic' is defined as the occurrence of many cases of a disease within an area, whereas 'pandemic' is used to emphasize its occurrence over a wide geographical area. This article reviews the epidemiology of cirrhosis in Europe and particularly within Britain, illustrating the different mortality trends in different countries. The rapid rise in mortality rate in Scotland is discussed and potential explanations explored. The major causes of cirrhosis that are increasing, namely alcohol abuse, hepatitis C and nonalcoholic fatty liver disease, are reviewed. Hepatitis B, of course, remains a major cause of cirrhosis worldwide but is not responsible for the recent increased deaths from cirrhosis discussed in this article. The burden of this disease, which largely consists of variceal hemorrhage, hepatocellular carcinoma and orthotopic liver transplantation, are also discussed.

Sharlala H, Adebajo A. · Rheumatology Department, Barnsley Foundation Hospital NHS Trust, Barnsley, S75 2EP and Academic Rheumatology Group, University of Sheffield Medical School, Sheffield, S10 2RX, South Yorkshire, United Kingdom. · Curr Rheumatol Rep. · Pubmed #19007534 No free full text.

Abstract: There is a growing understanding of the different syndromes that have a definite, and in some cases a possible, association with viral infections. Hepatitis C virus-associated mixed cryoglobulinemias and hepatitis B virus-associated polyarteritis nodosa are examples of a vasculitis with a definite viral association. However, various types of cutaneous vasculitis are examples of a vasculitis with only a possible association with a viral infection.

Davison SM, Kelly DA. · Children's Liver and GI Unit, St James's University Teaching Hospital, Leeds, UK. · Paediatr Drugs. · Pubmed #18998746 No free full text.

Abstract: Chronic hepatitis C virus (HCV) infection is a major cause of morbidity and mortality worldwide. Progression to cirrhosis and hepatocellular carcinoma occurs in 20% of infected adults. The natural history following childhood infection is less well defined, although cirrhosis in children is described. Since blood product screening for HCV infection was introduced in 1990, most children who acquire HCV do so by vertical transmission from an infected mother. Transmission to offspring occurs in approximately 5%. Most children with HCV infection are asymptomatic. Diagnosis is made by testing those at risk for HCV RNA by polymerase chain reaction (PCR) and HCV antibody (anti-HCV) by enzyme immunoassay (EIA). The clinical impact of HCV infection is assessed by monitoring symptoms and signs, blood testing of liver enzymes, ultrasound imaging, and by liver biopsy. Improved efficacy and tolerability of treatment strategies in adults have had a significant impact on the management of children with HCV infection. The emphasis is now on promoting awareness, early diagnosis, and treatment. Treatment strategies have evolved from monotherapy with interferon alfa (IFNalpha), to combination therapy with ribavirin. Pegylated IFNalpha is superior to conventional IFNalpha, and forms the basis of current recommendations. The genotype of HCV influences treatment efficacy. Treatment is generally well tolerated in children, although adverse effects are common. Preparation and support throughout treatment for the whole family is needed. A proportion of children with HCV infection have co-morbidity, including viral co-infection or hematologic disease. Although treatment may be contraindicated, risks and benefits must be considered before denying treatment. Anemia is more common in those with HIV co-infection, renal insufficiency, thalassemia, or cirrhosis, and may be aggravated by treatment. Children with thalassemia may have iron overload, and transfusion requirements may increase during treatment. Further refinements of combination therapy and development of new drugs are in progress. Vaccine candidates are undergoing phase I and II treatment trials.

Dalton HR, Bendall R, Ijaz S, Banks M. · Peninsula College of Medicine and Dentistry, Royal Cornwall Hospital Trust, Truro, UK. · Lancet Infect Dis. · Pubmed #18992406 No free full text.

Abstract: Hepatitis E is endemic in many developing countries where it causes substantial morbidity. In industrialised countries, it is considered rare, and largely confined to travellers returning from endemic areas. However, there is now a growing body of evidence that challenges this notion. Autochthonous hepatitis E in developed countries is far more common than previously recognised, and might be more common than hepatitis A. Hepatitis E has a predilection for older men in whom it causes substantial morbidity and mortality. The disease has a poor prognosis in the context of pre-existing chronic liver disease, and is frequently misdiagnosed as drug-induced liver injury. The source and route of infection remain uncertain, but it might be a porcine zoonosis. Patients with unexplained hepatitis should be tested for hepatitis E, whatever their age or travel history.

Holt AP, Salmon M, Buckley CD, Adams DH. · Liver Research Group, MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK. · Clin Liver Dis. · Pubmed #18984471 No free full text.

Abstract: Liver cirrhosis is caused by iterative cycles of tissue injury, inflammation, and repair. Although most causes of acute hepatitis resolve without scarring, chronic hepatitis is associated with persistent inflammation and matrix remodeling, which leads to fibrosis and, eventually, cirrhosis. The mechanisms that govern wound healing involve interactions between the innate and adaptive immune systems and stromal cells within a microenvironment composed of cytokines, growth factors, and modified matricellular proteins. The immune system plays a central role in the regulation of fibrosis, tissue repair, and recovery that is vital for the maintenance of tissue homeostasis. Chronic inflammation and fibrosis are inextricably linked and the cellular interactions between immune effector cells, local fibroblasts, and tissue macrophages at sites of scar formation determine the outcome of liver injury and the development of scarring.

Antoine DJ, Williams DP, Park BK. · University of Liverpool, MRC Centre for Drug Safety Science, Department of Pharmacology & Therapeutics, L69 3GE, UK. · Expert Opin Drug Metab Toxicol. · Pubmed #18950283 No free full text.

Abstract: Drug-induced liver injury (DILI) represents a major impediment to the development of new drugs and is a leading cause of drug withdrawal. The occurrence of hepatotoxicity has been closely associated with the formation of chemically reactive metabolites. Huge investment has focused on the screening of chemically reactive metabolites to offer a pragmatic approach to produce safer drugs and also reduce drug attrition and prevent market place withdrawal. However, questions surrounding the importance of chemically reactive metabolites still remain. Increasing evidence now exists for the multi-factorial nature of DILI, in particular the role played by the host immune system or disease state in the pathogenesis of DILI. This review aims to evaluate the current measures for the prediction and diagnosis of DILI and to highlight investigations being made to understand the multidimensional nature. Some of the steps being made to generate improved physiological systems to identify more sensitive, reflective mechanism-based biomarkers to aid the earlier identification of DILI and develop safer medicines are also discussed.

Robson D, Welch E, Beeching NJ, Gill GV. · Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. · QJM. · Pubmed #18854350 No free full text.

Abstract: Though medical consequences of war attract attention, the health consequences of the prisoner-of-war (POW) experience are poorly researched and appreciated. The imprisonment of Allied military personnel by the Japanese during the World War II provides an especially dramatic POW scenario in terms of deprivation, malnutrition and exposure to tropical diseases. Though predominantly British, these POWs also included troops from Australia, Holland and North America. Imprisonment took place in various locations in Southeast Asia and the Far East for a 3.5-year period between 1942 and 1945. Nutritional deficiency syndromes, dysentery, malaria, tropical ulcers and cholera were major health problems; and supplies of drugs and medical equipment were scarce. There have been limited mortality studies on ex-Far East prisoners (FEPOWs) since repatriation, but these suggest an early (up to 10 years post-release) excess mortality due to tuberculosis, suicides and cirrhosis (probably related to hepatitis B exposure during imprisonment). In terms of morbidity, the commonest has been a psychiatric syndrome which would now be recognized as post-traumatic stress disorder--present in at least one-third of FEPOWs and frequently presenting decades later. Peptic ulceration, osteoarthritis and hearing impairment also appear to occur more frequently. In addition, certain tropical diseases have persisted in these survivors--notably infections with the nematode worm Strongyloides stercoralis. Studies 30 years or more after release have shown overall infection rates of 15%. Chronic strongyloidiasis of this type frequently causes a linear urticarial 'larva currens' rash, but can potentially lead to fatal hyperinfection if immunity is suppressed. Finally, about 5% of FEPOW survivors have chronic nutritional neuropathic syndromes--usually optic atrophy or sensory peripheral neuropathy (often painful). The World War II FEPOW experience was a unique, though often tragic, accidental experiment into the longer term effects of under nutrition and untreated exotic disease. Investigation of the survivors has provided unique insights into the medical outcome of deprivation in tropical environments.

Heydtmann M. · Liver Research Laboratories, Institute for Biomedical Research, Birmingham University, Birmingham B15 2TT, United Kingdom. · J Virol. · Pubmed #18842723 No free full text.

This publication has no abstract.

O'Grady JG. · King's College Hospital, Denmark Hill, London, United Kingdom. john.o' · Liver Transpl. · Pubmed #18825687 No free full text.

Abstract: 1. Establishing the cause of fulminant hepatitis is an important determinant in outcomes after liver transplantation. 2. Liver transplantation is an integral part of the management of ALF. 3. In addition to generic posttransplant care, neurologic, septic, and hematologic issues need to be addressed. 4. Outcomes after liver transplantation are poorer than those for elective transplantation but superior to those found for comparably ill patients being transplanted for chronic liver disease. 5. Multiple factors have an influence on outcome, and risk stratification is beginning to emerge.

Dhawan A. · Paediatric Liver Centre, King's College London School of Medicine, King's College Hospital, London, United Kingdom. · Liver Transpl. · Pubmed #18825678 No free full text.

Abstract: 1. The etiology of acute liver failure in children differs from that in adults, with metabolic conditions being commoner in Europe and North America and hepatitis A being the commonest cause in Asia and South America. 2. Encephalopathy usually is a late feature and is not essential for the diagnosis. 3. Unlike adults, there are no good prognostic criteria that can predict survival without liver transplantation. 4. It is important to exclude genetic multisystem disorders before liver transplantation is considered.

Rhodes T, Treloar C. · Centre for Research on Drugs and Health Behaviour, London School of Hygiene and Tropical Medicine, University of London, London, UK. · Addiction. · Pubmed #18821870 No free full text.

Abstract: BACKGROUND: Intervention impact on reductions in hepatitis C virus (HCV) incidence among injecting drug users (IDUs) are modest. There is a need to explore how drug injectors' interpret HCV risk. AIMS: To review English-language qualitative empirical studies of HCV risk among IDUs. METHODS: Qualitative synthesis using a meta-ethnographic approach. Searching of eight electronic databases and reference lists identified manually papers in peer-reviewed journals since 2000. Only studies investigating IDU perspectives on HCV risk were included. Themes across studies were identified systematically and compared, leading to a synthesis of second- and third-order constructs. FINDINGS: We included 31 papers, representing 24 studies among over 1000 IDUs. Seven themes were generated: risk ubiquity; relative viral risk; knowledge uncertainty; hygiene and the body; trust and intimacy; risk environment; and the individualization of risk responsibility. Evidence supports a perception of HCV as a risk accepted rather than avoided. HCV was perceived largely as socially accommodated and expected, and in relative terms to human immunodeficiency virus (HIV) as the 'master status' of viral dangers. Symbolic knowledge systems, rather than biomedical risk calculus, and especially narratives of hygiene and trust, played a primary role in shaping interpretations of HCV risk. Critical factors in the risk environment included policing, homelessness and gendered risk. CONCLUSIONS: Appealing to risk calculus alone is insufficient. Interventions should build upon the salience of hygiene and trust narratives in HCV risk rationality, and foster community changes towards the perceived preventability of HCV. Structural interventions in harm reduction should target policing, homelessness and gendered risk.

Turner J, Green J. · Department of Gastroenterology, University Hospital Llandough, Cardiff CF64 2XX. · Br J Hosp Med (Lond). · Pubmed #18819303 No free full text.

Abstract: Hepatitis E is increasingly recognized as a cause of viral hepatitis within the UK and should be considered in any patient presenting with acute hepatitis. Mortality rates of around 4% have been described, but are even higher during pregnancy.

Gould EA, Higgs S. · Unité des Virus Emergents, Faculté de Médecine Timone, 13385 Marseille, Cedex 05, France. · Trans R Soc Trop Med Hyg. · Pubmed #18799177 No free full text.

Abstract: While some skeptics remain unconvinced that global climate change is a reality, there is no doubt that during the past 50 years or so, patterns of emerging arbovirus diseases have changed significantly. Can this be attributed to climate change? Climate is a major factor in determining: (1) the geographic and temporal distribution of arthropods; (2) characteristics of arthropod life cycles; (3) dispersal patterns of associated arboviruses; (4) the evolution of arboviruses; and (5) the efficiency with which they are transmitted from arthropods to vertebrate hosts. Thus, under the influence of increasing temperatures and rainfall through warming of the oceans, and alteration of the natural cycles that stabilise climate, one is inevitably drawn to the conclusion that arboviruses will continue to emerge in new regions. For example, we cannot ignore the unexpected but successful establishment of chikungunya fever in northern Italy, the sudden appearance of West Nile virus in North America, the increasing frequency of Rift Valley fever epidemics in the Arabian Peninsula, and very recently, the emergence of Bluetongue virus in northern Europe. In this brief review we ask the question, are these diseases emerging because of climate change or do other factors play an equal or even more important role in their emergence?

Bogdanos DP, Dalekos GN. · Liver Immunopathology, Institute of Liver Studies, Division of Gene and Cell Based Therapy, King's College London School of Medicine at King's College Hospital, UK. · Curr Med Chem. · Pubmed #18781950 No free full text.

Abstract: Characterization of liver-specific autoantigens has given a fresh impetus to research in the pathogenesis of autoimmune liver diseases, viral-triggered and drug-induced autoimmunity affecting the liver. Intriguing is the fact that most of the liver-specific autoantigens are enzymes of key importance for cell's homeostasis. Detection of autoantibodies against the respective antigens is carried out for diagnostic and research purposes using indirect immunofluorescence, immunoblotting, enzyme-linked immunosorbent assays, radioimmunoassay, immunoprecipitation or assays determining inhibition of enzyme activity. In patients with autoimmune hepatitis, a liver disorder of unknown etiology and pathogenesis, disease-specific autoantibodies are frequently directed against drug metabolizing enzymes of phase 1, namely cytochrome P450 2D6 (CYP2D6). The same and other members of these families of enzymes (CYPs) have also been described as targets of liver-specific autoimmunity in chronic hepatitis C virus (HCV)-infected patients, patients with autoimmune hepatitis as part of the autoimmune polyglandular syndrome type-1 (APS-1) and drug-induced autoimmunity. How these enzymes become 'self targets' is not yet established. An antigen release following hepatocyte injury could provide the stimulus for an immune response towards epitopes on these enzymes but the highly-specific, antigen-restricted initiation of the observed autoimmune response is against such an explanation. Accordingly, in this review we will focus on the pathogenic role -if any- of autoimmune responses against liver-related CYPs in autoimmune hepatitis, HCV infection, APS-1 and drug-induced autoimmunity. Learning more about the specificity of antibody responses against these enzymes may help us better understand the mechanisms underlying liver autoimmunity and may facilitate the development of therapeutic and preventive interventions.

Shetty S, Lalor PF, Adams DH. · Liver Research Group, MRC centre for immune regulation, 5th Floor, Institute of Biomedical Research, University of Birmingham, Birmingham B15 2TT, UK. · Toxicology. · Pubmed #18775762 No free full text.

Abstract: Recirculation of blood lymphocytes through the liver occurs under normal conditions as part of the process of immune surveillance. In response to injury or infection recruitment from blood increases and the nature and distribution of the infiltrate will determine the type and outcome of the resulting hepatitis. Recruitment from blood occurs via the hepatic sinusoids and is controlled by interactions between circulating lymphocytes and the highly specialised sinusoidal endothelial cells. This is a low flow vascular bed and the molecular basis of recruitment differs from other tissues. In this review we outline the molecular basis of lymphocyte recruitment to the liver and the effect on it of the local tissue microenvironment and how dysregulation of these processes can lead to uncontrolled inflammation and liver damage.

Bailey AC, Fisher M. · Department of Sexual Health and HIV, Brighton and Sussex University Hospitals NHS Trust, Royal Sussex County Hospital, Eastern Road, Brighton BN2 5BE, UK. · Br Med Bull. · Pubmed #18757468 No free full text.

Abstract: INTRODUCTION: Antiretroviral therapy for HIV infection has transformed it from a terminal illness to a chronic manageable condition. This review summarizes the history of the treatment and explains the current practice in the field, including uses in prevention strategies. SOURCES OF DATA: National and international guidelines, important publications in peer reviewed literature and recent important conference abstracts. AREAS OF AGREEMENT: There is a broad agreement on the choice of drug regimens and on the need to treat patients with symptomatic HIV infection and with CD4 cell counts less than 350 cells/mm(3). The need to adapt therapy to individual circumstances is also well accepted, e.g. hepatitis co-infection and pregnancy. AREAS OF CONTROVERSY: Treatment of acute HIV infection and the optimum time to commence therapy in asymptomatic chronic infection remain controversial. Use of antiretrovirals for prevention, e.g. pre-exposure and post-exposure prophylaxis, is still developing. GROWING POINTS: This article summarizes the current use of anti-HIV medication and the evidence behind it for the non-specialist. AREAS TIMELY FOR DEVELOPING RESEARCH: New strategies for using current drugs, the best use of newly available drugs and new uses of antiretroviral drugs, such as in prevention of HIV transmission, are key areas for research. Further research addressing the question of when to start antiretrovirals and assessing their long-term effects is also needed.

Alazawi W, Foster GR. · The Liver Unit, Barts and The London School of Medicine, London, UK. · Curr Opin Infect Dis. · Pubmed #18725801 No free full text.

Abstract: PURPOSE OF REVIEW: Hepatitis B virus is responsible for much morbidity and mortality worldwide. Although the armament of drugs licensed for its treatment grows, it is increasingly apparent that the efficacy of these drugs is dependent upon much more that their pharmacology. RECENT FINDINGS: A better understanding of the natural history of chronic hepatitis B infection together with recent advances in the molecular biology of antiviral resistance have given added dimensions to physicians' decision-making thought processes. SUMMARY: The present review outlines the recent advances in diagnostic testing that enable a better understanding of an individual patient's phase of illness and also how such information can update treatment choices better. In the second part of this review, the licensed therapies and their relative merits are discussed, as is their role in managing resistance to antiviral therapy.

Xirouchakis E, Triantos C, Manousou P, Sigalas A, Calvaruso V, Corbani A, Leandro G, Patch D, Burroughs A. · The Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital, London, UK. · J Viral Hepat. · Pubmed #18673428 No free full text.

Abstract: SUMMARY: Pegylated interferon with ribavirin (Peg/R) is the most effective therapy for chronic hepatitis C virus (HCV) but its utility and effectiveness after liver transplantation has been difficult to assess. We evaluated efficacy, tolerability, and safety of Peg/R in liver transplant candidates and recipients with HCV cirrhosis. We searched medical databases and conference proceedings between January 1999 and January 2008 selecting randomized and nonrandomized studies. Primary end points meta-analytically were: (1) sustained viral response (SVR) and (2) histological response. Secondary end points were: (1) treatment discontinuation, (2) mortality, and (3) rejection episodes. Pegylated interferons using either 1-1.5 mcg/kg of pegylated interferon alpha-2b or 180 microg (pegylated interferon alpha-2a combined with ribavirin 800-1200 mg/day were the most effective compared to any other regimen or no therapy. In three pretransplant studies the median SVR was 19.6% (19.6-50%). In six postransplant studies where a meta-analysis was done the cumulative risk difference in SVR was 0.31% (95% CI, 0.18-0.44, p < 0.001). However histological response was not significantly better compared to no therapy or other antiviral regimens. There were no significant differences in discontinuation of therapy, acute or chronic rejection or mortality between optimal Peg/R vs no treatment or other regimens. Hence pegylated interferon plus ribavirin in full doses is effective pre and post transplant but has a low SVR rate. To date no significant histological improvement has been reported.