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Birmingham, United Kingdom

Many HBsAg-positive/HBeAg-negative patients show normal alanine aminotransferase levels. However, in this group of patients two different virological and clinical subsets do exist: inactive HBV carriers and patients with chronic hepatitis B with transient virological and biochemical remission. Natural history and outcome, severity of liver damage and need for liver biopsy and antiviral treatment differ significantly between these groups of patients. It is not always easy to distinguish between inactive HBV carriers and patients suffering from HBeAg-negative chronic hepatitis with transient disease remission, as they share similar biochemical (normal serum ALT values) and virological (HBeAg negativity and low HBV DNA levels) features. In clinical practice, it is very important to differentiate inactive carriers from patients with chronic hepatitis B with spontaneous transient remission, as the former have a good prognosis with a very low risk of complications, while the latter have active liver disease with a high risk of progression to advanced hepatic fibrosis, cirrhosis and hepatocellular carcinoma. Thus, a careful assessment and adequate follow-up periods are needed. The aim of this review, written in the form of a dialog between a hepatologist and a newly diagnosed patient with HBV infection and normal alanine aminotransferase levels, is to give evidence-based suggestions for the management in clinical practice of HBsAg patients, on the basis of more recent international guidelines, covering many aspects of the condition, including advice on lifestyle and vaccination, indications for liver biopsy and treatment, the types and side effects of treatment and treatment endpoints. © 2012 European Federation of Internal Medicine. Source

Dyson J.,Liver Unit | Day C.,Northumbria University
Digestive Diseases

Non-alcoholic fatty liver disease (NAFLD) is now the commonest cause of chronic liver disease in developed countries. Treatment depends on the stage of disease, and non-invasive methods for risk stratification are urgently needed. Lifestyle modification (aimed at weight loss and increasing physical activity) and management of the features of metabolic syndrome are vital for all patients with NAFLD. Metformin is the first-line therapy for diabetic patients with NAFLD and also reduces the risk of hepatocellular carcinoma. Clinicians should have a low threshold for introducing a statin for the management of dyslipidaemia. Antihypertensive agents that target the renin-angiotensin system should be first-line in NAFLD for the management of hypertension. For patients with progressive disease, liver-directed pharmacotherapy with vitamin E should be considered. Non-alcoholic steatohepatitis cirrhosis is an increasingly common indication for liver transplantation. © 2014 S. Karger AG, Basel. Source

Carbone M.,Addenbrookes Hospital | Carbone M.,DoNation | Neuberger J.M.,Liver Unit | Neuberger J.M.,DoNation
Journal of Hepatology

Summary 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 5 years. 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. © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Source

The drugs currently licensed for the treatment of hepatitis C are Peg-Interferon (PEG-IFN) and ribavirin. In recent years, the recommendation to treat hepatitis C virus genotype 2- and 3-infected patients with a fixed 800 mg/day dose of ribavirin in combination with PEG-IFN and for just 24 weeks has been challenged by the concept of tailoring the length of therapy according to on-treatment viral response. Therefore, the objective of the present review was to highlight the different designs of the studies on short treatment duration and the role of wk4-R as a predictor of sustained virological response after an abbreviated course of treatment. The secondary aim was to verify whether we had enough evidence to support the implementation of a short treatment course in subsets of patients with genotype 2 and 3 infection. We will also focus on how drug dosing may have influenced the outcome of treatment. To clarify reasons for discrepant results in the studies so far published, the recently discovered genetic variant near the interleukin 28B gene will be presented and its predictive role will be discussed. Finally, we will face the debated issue of whether the subset of patients with genotype 2 or 3 requires an extended treatment duration. © 2010 John Wiley & Sons A/S. Source

PURPOSE OF REVIEW: Follow-up data from donors following cardiac death (DCD) liver transplants suggest an increased risk of graft failure and morbid complications, and the risk increased with grafts from marginal donors. Donor warm ischaemia (dWIT) stands out as the common aetiological factor. Aim of this review is to examine if super-rapid technique had developed sufficiently enough to improve the effects of dWIT that had been started since treatment withdrawal in category III DCD marginal donors. RECENT FINDINGS: The recent findings suggest limited evolvement, but these have not been contributed to reduce dWIT significantly. Evidence suggests hypoperfusion and circulatory stop occurring well before electrophysical inactivity; hence, dWIT is probably underestimated. Time spent since cardiac death to aortic cross clamp is directly linked to ischaemic complications; limited modifications to surgical technique alone have failed to make an impact on these complications. Marginal grafts generally perform worse, increasing the overall financial cost of patient management. SUMMARY: Irrespective of the speed at which aortic perfusion is instituted, the technical developments have not been able to improve outcomes/utility of marginal DCD grafts. The future of the DCD programmes should explore the means of reviving organ damage incurred during dWIT that are incorporated to the super-rapid technique of organ harvest. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

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