Best Practice & Research Clinical Gastroenterology RSS feed: Current Issue. In practical paperback format, each 200 page topic-based issue of Best Practice & Research Clinical Gastroenterology will provide a comprehensive review of current clinical practice and thinking within the specialty of gastroenterology. All chapters are commissioned and written by an international team of practising clinicians with the Guest Editors for each issue drawn from a pool of renowned experts and opinion leaders. Reference is made to: • the latest original research • Cochrane Reviews • audits and confidential enquiries • national and international conferences • national and international guidelines • personal communications All chapters take the form of practical, evidence-based reviews that seek to address key clinical issues of diagnosis, treatment and patient management. Each issue follows a problem-orientated approach that focuses on the key questions to be addressed, clearly defining what is known and not known. Management will be described in practical terms so that it can be applied to the individual patient. Boxed and bulleted Learning Objectives and Practice Points are features within each chapter and will highlight the core and essential knowledge that will help the physician to provide the best care to their patients. The series' objective is to provide a continuous update for the busy clinician and researcher. 2012 topics 26.1 February - Aspirine and nNaids Angel Lanas 26.2 April - Small Bowel Endoscopy Peter Mensink and Q Mackay 26.3 June - Chronic Hepatitis C: Diagnoses and Treatment Harry Janssen and Antonio Craxi 2011 topics 25:1 February - Chronic constipation Mark Benninga and Marc Scott 25:2 April - Liver fibrosis Massimo Pinzani 25:3 June - Chemoprevention in Gastroenterology Richard Logan 25:4 August - Auto-immune and cholestatic liver disease Ulrich Beuer 25:5 October - Quality assurance in Gastroenterology Peter Cotton and Michael Bretthauer 25:6 December - liver failure and liver transplantation Herold J Metselaar 2010 topics Vol 24:1 February - Gastrointestinal lymphomas W. Fischbach and H. Boot Vol 24:2 April - Adverse events of GI Pharmacology C. Beglinger Vol 24:3 June - Chronic Pancreatitis M. Bruno Volume 24:4 August - New developments in colorectal cancer Screening G. Hoff and N. Segnan Vol 24:5 October - Hereditary liver disease F. Lammert Vol 24:6 December - Not yet confirmed 2009 topics Vol 23:1 February - Emerging Diseases of the Gastrointestinal Tract Ernst J. Kuipers (The Netherlands) Vol 23:2 April - Genetic Testing in Gastroenterology Hans Vasen Vol 23:3 June - Mandatory and Optional Functions Tests in Gastroenterology and Hepatology Jutta Keller, Ansgar Lohse and Peter Layer Vol 23:4 August - special issue devoted to common proctology scenarios Vol 23:5 October - Endosonography in Gastroenterology G.N.J. Tytgat Vol 23:6 December - Management of GI Diseases in the Elderly A. Pilotto 2008 topics Vol 22:3 June - Eosinophils in Healthy Gut and Gastrointestinal Diseases S. C. Bischoff (Germany) and A. Straumann (Switzerland) Vol 22:4 April - Advances in diagnostic assessment of the oesophageal mucosa J Dent (Australia), P Sharma (USA), G N Tytgat (The Netherlands) Vol 22: 5 October - Gastrointestinal Endoscopy G N Tytgat (The Netherlands) Vol 22: 6 December - Recent Developments in Hepatitis B & C S. W. Schalm and H. L. A. Janssen (The Netherlands) 2007 topics, volume 21, issues 1-6 Vol 21:1 February - Complications of cirrhosis D Lebrec (France) Vol 21:2 April - Helicobacter Pylori A Axon (UK) Vol 21:3 June - The difficult patient in gastroenterology J Tack (Belgium) and J Scholmerich (Germany) Vol 21:4 August - Severe gastrointestinal motor disorders G E Boeckxstaens (The Netherlands) Vol 21:5 October - Pregnancy-related gastroenterological and hepatological diseases and complications F Shanahan (Ireland) Vol 21:6 December - The multidisciplinary management of gastrointestinal cancer E. van Gutsem (Belgium) 2006 topics, volume 20, issues 1-6 Vol 20:1 February - Advances in imaging of the GI tract G Bianchi Porro (Italy) Vol 20:2 April - Pancreatic cancer J Neoptolemos UK) Vol 20:3 June - Novel developments in GI nutrition L Mathus-Vliegen (The Netherlands)and A Thomson (UK) Vol 20:4 August - Gastric cancer K McColl (UK) Vol 20:5 October - Oesophageal cancer J van Lanschot and G Tytgat (The Netherlands) Vol 20:6 December - Gallstone disease K van Erpecum and P Portincasa (The Netherlands) http://www.bpgastro.com/?rss=yesElsevier Inc.en © 2011 Published by Elsevier Inc. All rights reserved. Best Practice & Research Clinical Gastroenterology1521-6918256December 2011 © 2011 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.bpgastro.com/article/PIIS1521691811001090/abstract?rss=yesAims & Scope/ Editorial Board10.1016/S1521-6918(11)00109-0Best Practice & Research Clinical Gastroenterology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Gastroenterology2011-12-01256S1521-6918(11)X0006-9iiiiiihttp://www.bpgastro.com/article/PIIS1521691811000965/abstract?rss=yesAutoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are the three major autoimmune liver diseases. So-called overlap syndromes are diseases exhibiting clinical, laboratory and or histological features of at least two of these genuine autoimmune liver diseases. In autoimmune hepatitis and primary biliary cirrhosis there is a high predominance of females, around 80%, while in primary sclerosing cholangitis males are in the majority. In autoimmune hepatitis the primary target of the disease process is the hepatocyte, the main parenchymal liver cell, while the primary target of the disease process in primary biliary cirrhosis and primary sclerosing cholangitis is the biliary tract. Primary biliary cirrhosis is better termed chronic non suppurative cholangitis, the inflammatory disease process is targeting the small intrahepatic bile ducts finally leading to a progressive destruction of bile ducts and thus finally to biliary cirrhosis. In primary sclerosing cholangitis large intra- and extra-hepatic bile ducts are affected exhibiting multiple stenoses and dilatations of the intra- and extra-hepatic biliary tree. While in autoimmune hepatitis as well as primary biliary cirrhosis characteristic autoantibodies are present in serum no specific serologic markers like autoantibodies are found in primary sclerosing cholangitis – apart from anti-neutrophilic cytoplasmic antibodies (ANCA). Like most autoimmune diseases autoimmune liver diseases are frequently associated with other mainly extra-hepatic autoimmune disorders. Autoimmune liver diseases are characterized by a rather complex genetic background. Genome Wide Association Studies (GWAS) have been applied to demonstrate and unravel the genetic background in particular for PBC and PSC. It became clear that the strongest genetic association is with genes of the MHC locus. However, the genetic background related to the MHC locus is responsible only for around 50% of the genetic risk. Recently, several non-MHC genes have been identified for PSC that are either important for bile formation or are relevant for inflammatory reactions.Autoimmune liver diseaseMichael P. Manns10.1016/j.bpg.2011.10.008Best Practice & Research Clinical Gastroenterology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Gastroenterology2011-12-01256S1521-6918(11)X0006-9641642http://www.bpgastro.com/article/PIIS1521691811000941/abstract?rss=yesAutoimmune hepatitis (AIH) is a chronic liver disease which is normally recognized during late stage of the disease. Due to limited knowledge about the onset and course of disease and need for chronic immunosuppression with significant side-effects there is a requirement for a good preclinical animal model, mirroring main characteristics of AIH. In addition to the exclusion of other liver diseases, AIH is characterized by elevated serum transaminases, specific autoantibodies and elevated gammaglobulins as well as a specific liver histopathology. A good preclinical model should mirror most of these criteria. In the last decades several models have been published using different approaches to break hepatic tolerance and induce liver damage. The induction of a chronic hepatitis similar to the human disease remained a difficult challenge. Nevertheless, these models helped to get more information about the aspects of AIH induction and liver immunology.The benefit of animal models for autoimmune hepatitisElmar Jaeckel, Matthias Hardtke-Wolenski, Katja Fischer10.1016/j.bpg.2011.10.006Best Practice & Research Clinical Gastroenterology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Gastroenterology2011-12-01256S1521-6918(11)X0006-9643651http://www.bpgastro.com/article/PIIS1521691811000862/abstract?rss=yesThe mechanisms underlying the pathogenesis of autoimmune hepatitis are not fully understood, though there is growing evidence that genetic predisposition, molecular mimicry and/or impairment of regulatory T-cells are involved in the initiation and perpetuation of the autoimmune liver attack. The histological picture of interface hepatitis, characterized by a dense portal mononuclear cell infiltrate, was the first to suggest an autoaggressive cellular immune attack in the pathogenesis of this condition. Liver damage is likely to be orchestrated by CD4pos T-cells recognizing an autoantigenic liver peptide. For autoimmunity to arise, the peptide must be presented by antigen-presenting cells to naïve CD4pos T-helper (Th0) cells. Once activated, Th0-cells can differentiate into Th1-, Th2-, or Th17-cells, initiating a cascade of immune reactions that are determined by the cytokines they produce. Autoantigen recognition and the above effector mechanisms are opposed by regulatory T-cells, a cell subset numerically and functionally impaired in autoimmune hepatitis.Pathogenesis of autoimmune hepatitisRodrigo Liberal, Maria Serena Longhi, Giorgina Mieli-Vergani, Diego Vergani10.1016/j.bpg.2011.09.009Best Practice & Research Clinical Gastroenterology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Gastroenterology2011-12-01256S1521-6918(11)X0006-9653664http://www.bpgastro.com/article/PIIS1521691811000928/abstract?rss=yesThe clinical spectrum of autoimmune hepatitis is very wide. In addition, autoimmune hepatitis can present in any age group. Diagnosis is usually made by a combination of clinical, laboratory and histological features. Diagnostic scores can help both in the daily diagnostic work-up of patients, and in allowing comparability of clinical scientific studies. However, all diagnostic scores have limitations in individual cases, which are discussed in this review.Diagnostic criteria for autoimmune hepatitisAnsgar W. Lohse, Christiane Wiegard10.1016/j.bpg.2011.10.004Best Practice & Research Clinical Gastroenterology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Gastroenterology2011-12-01256S1521-6918(11)X0006-9665671http://www.bpgastro.com/article/PIIS1521691811000849/abstract?rss=yesAutoimmune hepatitis was the first chronic liver disease with a favourable response to drug therapy and a dismal prognosis when left untreated. Since its original description in 1950 and first treatment studies the basic therapeutic strategy of inducing remission with steroids and azathioprine has not been modified in principle. A timely diagnosis before cirrhosis develops, the avoidance of immunosuppressant side effect, non-responders to standard induction therapy, and adherence to therapy are the greatest challenges. Alternative immunosuppressive drugs have been tested in small series and include transplant immunosuppressants. A recent large multicenter prospective treatment trial suggests that budesonide may offer an alternative in non-cirrhotic AIH patients capable of minimizing unwanted steroid effects. The ultimate treatment approach upon drug treatment failure is liver transplantation. Only four precent of transplant candidates are transplanted for AIH but the risk for graft loss because of recurrence has to be considered and recurrent AIH treated after transplantation.Therapy of autoimmune hepatitisChristian P. Strassburg, Michael P. Manns10.1016/j.bpg.2011.08.003Best Practice & Research Clinical Gastroenterology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Gastroenterology2011-12-01256S1521-6918(11)X0006-9673687http://www.bpgastro.com/article/PIIS1521691811000886/abstract?rss=yesAutoimmune hepatitis has diverse clinical phenotypes that challenge conventional diagnostic criteria and treatment strategies. The goals of this review are to characterize these special populations and provide guidelines for their management. Patients with acute or acute severe (fulminant) presentations may have centrilobular zone 3 hepatic necrosis, but they can respond to conventional corticosteroid therapy. Asymptomatic mild disease warrants corticosteroid treatment because spontaneous resolution is uncertain and 10-year survival is less than expected. Male gender or the absence of conventional autoantibodies does not preclude the diagnosis or need for treatment, and patients with cholestatic changes warrant cholangiography and possible combination therapy with ursodeoxycholic acid. Different ethnic groups commonly have advanced hepatic fibrosis, rapidly progressive disease, or cholestatic features, and elderly patients typically respond well to corticosteroid therapy. Pregnancy is usually well-tolerated by mother and foetus but requires protection against postpartum exacerbation. Special populations must be recognized and treated with tailored regimens.Autoimmune hepatitis in special patient populationsAlbert J. Czaja10.1016/j.bpg.2011.09.011Best Practice & Research Clinical Gastroenterology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Gastroenterology2011-12-01256S1521-6918(11)X0006-9689700http://www.bpgastro.com/article/PIIS152169181100093X/abstract?rss=yesPrimary biliary cirrhosis is the archetypal autoimmune liver disease, with the disease label describing a chronic granulomatous lymphocytic small bile duct cholangitis, which now most commonly presents asymptomatically and at an early pre-cirrhotic stage. Disease is more common than thought, with 1 in 1000 women over the age of 40 affected. Characteristic immunologic features of the disease assist clinicians in ready non-invasive diagnosis of patients, even if asymptomatic with only anicteric/cholestatic liver biochemical profiles. Over 90% of patients are anti-mitochondrial antibody positive, and for those negative, a significant proportion have highly specific anti-nuclear antibody profiles. Liver biopsy remains useful in certain settings where clarity is needed to confirm diagnosis, exclude alternative disease, and assess the relative contribution of PBC to other co-existent liver injury, and seeks to demonstrate in particular the classic bile duct lesions, as well as the degree of interface activity.Diagnosis of primary biliary cirrhosisGideon M. Hirschfield10.1016/j.bpg.2011.10.005Best Practice & Research Clinical Gastroenterology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Gastroenterology2011-12-01256S1521-6918(11)X0006-9701712http://www.bpgastro.com/article/PIIS1521691811000874/abstract?rss=yesPrimary sclerosing cholangitis (PSC) is a chronic and severe inflammatory disease leading to fibrotic bile duct destruction and in most cases liver cirrhosis. As in other complex genetic diseases, the sibling risk of PSC is more than ten times that of the general population. Recent genome-wide association studies have consistently identified several genetic susceptibility loci. The overlap of these loci with susceptibility loci in other chronic inflammatory diseases is considerable, and offers intriguing opportunities for transfer of pathogenetic knowledge and potentially treatment options. In the present article we summarise the present knowledge on PSC genetics with a particular emphasis on the major histocompatibility complex (MHC). We discuss the clinical relevance of the risk loci and elaborate on the insight that may be obtained from associated inflammatory conditions and existing murine knock-out models.Genetics in primary sclerosing cholangitisTrine Folseraas, Espen Melum, Andre Franke, Tom H. Karlsen10.1016/j.bpg.2011.09.010Best Practice & Research Clinical Gastroenterology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Gastroenterology2011-12-01256S1521-6918(11)X0006-9713726http://www.bpgastro.com/article/PIIS1521691811000977/abstract?rss=yesPrimary sclerosing cholangitis (PSC) represents a chronic cholestatic liver disease with fibroobliterative sclerosis of intra- and/or extrahepatic bile ducts, eventually leading to biliary cirrhosis.The association with human leukocyte antigen (HLA) and non-HLA haplotypes and the presence of autoantibodies in sera of PSC patients support a crucial role for immune-mediated mechanisms in the initiation and progression of PSC. The strong clinical association between PSC and inflammatory bowel diseases led to intriguing pathogenetic concepts, in which the inflamed gut with translocation of bacterial products and homing of gut-primed memory T lymphocytes via aberrantly expressed adhesion molecules plays a fundamental role. Genetically or chemically modified bile composition was shown to induce sclerosing cholangitis and liver fibrosis in a number of animal models ("toxic bile concept"). The potential role of vascular injury with ischemia of bile duct epithelium cells in the development of sclerosing cholangitis is supported by animal models of endothelial cell injury showing close morphological similarities with human PSC.Pathogenesis of primary sclerosing cholangitisMarion J. Pollheimer, Emina Halilbasic, Peter Fickert, Michael Trauner10.1016/j.bpg.2011.10.009Best Practice & Research Clinical Gastroenterology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Gastroenterology2011-12-01256S1521-6918(11)X0006-9727739http://www.bpgastro.com/article/PIIS1521691811000916/abstract?rss=yesPrimary sclerosing cholangitis (PSC) is a rare cholestatic liver disease mainly affecting young male patients. PSC is characterised by chronic inflammation and fibrotic strictures of the intra- and extrahepatic biliary system, which eventually lead to cholestasis and biliary cirrhosis. However, the clinical course remains very variable. As the aetiology remains unknown, the development of a causative treatment is challenging and today no specific medical therapy is available. Ursodeoxycholic acid has been widely used for the treatment of PSC, but improved only biochemistry and/or symptoms in low- or medium dosages and is probably harmful in higher dosages. Other drugs such as immunosuppressive, antifibrotic or antibiotic agents have not been proven to be effective in large clinical trials. The endoscopic therapy encompasses balloon-dilatation and/or stenting of strictures, relieves clinical symptoms and improves a cholestatic enzyme profile. However, endoscopic therapy is limited to patients in advanced stages of PSC with biliary obstruction.Medical and endoscopic therapy of primary sclerosing cholangitisTobias J. Weismüller, Tim O. Lankisch10.1016/j.bpg.2011.10.003Best Practice & Research Clinical Gastroenterology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Gastroenterology2011-12-01256S1521-6918(11)X0006-9741752http://www.bpgastro.com/article/PIIS1521691811000904/abstract?rss=yesCholangiocarcinoma complicates primary sclerosing cholangitis (PSC) in approximately 10% of cases, but no risk factor that can identify this subgroup of patients is known. No imaging modalities or serum tumour markers that can diagnose early cholangiocarcinoma are available, but endoscopic retrograde cholangiography with brush cytology is recommended when clinically indicated. Liver transplantation with neoadjuvant therapy is carried out in specialist centres in cases of limited stage cancer. Transplantation should also be considered in patients with biliary dysplasia without evident tumour. Gallbladder polyps in PSC are often malignant, and liberal indication for cholecystectomy is recommended. Hepatocellular carcinoma develops in 2%–4% of patients with end-stage liver disease. Patients with inflammatory bowel disease are at risk of colorectal neoplasia. Surveillance colonoscopies are recommended, also after liver transplantation. Epigenetic markers represent one among several classes of potential biomarkers for early diagnosis of malignancies in PSC that should be further explored.Primary sclerosing cholangitis and malignancyKirsten Muri Boberg, Guro E. Lind10.1016/j.bpg.2011.10.002Best Practice & Research Clinical Gastroenterology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Gastroenterology2011-12-01256S1521-6918(11)X0006-9753764http://www.bpgastro.com/article/PIIS1521691811000850/abstract?rss=yesLiver transplantation is indicated for terminal phases of autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis. Indications for transplantation in autoimmune liver diseases are similar to those used in other acute or chronic liver diseases. Therapeutic advances have reduced the need for transplantation for autoimmune hepatitis and primary biliary cirrhosis but not for primary sclerosing cholangitis. Overall, outcomes of transplantation for autoimmune liver diseases are excellent. However, recurrence of autoimmune liver diseases in the allograft has variable impacts on graft and patient survivals. Treatment of recurrent diseases requires changes in immunosuppression or addition of ursodeoxycholic acid. Among autoimmune liver diseases, only autoimmune hepatitis occurs de novo in recipients transplanted for other diseases. Patients transplanted for autoimmune hepatitis or primary sclerosing cholangitis are at risk for reactivation or de novo onset of ulcerative colitis. Better understanding of the pathogenesis of recurrent autoimmune liver diseases is needed to devise effective means of prevention and treatment.Liver transplantation in autoimmune liver diseasesJawad A. Ilyas, Christine A. O’Mahony, John M. Vierling10.1016/j.bpg.2011.09.008Best Practice & Research Clinical Gastroenterology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Gastroenterology2011-12-01256S1521-6918(11)X0006-9765782http://www.bpgastro.com/article/PIIS1521691811000953/abstract?rss=yesAutoimmune liver disorders in childhood include autoimmune hepatitis, autoimmune sclerosing cholangitis and de novo autoimmune hepatitis after liver transplant. These inflammatory liver disorders are characterised histologically by interface hepatitis, biochemically by elevated transaminase levels and serologically by autoantibodies and increased levels of immunoglobulin G. Autoimmune hepatitis is particularly aggressive in children and progresses rapidly unless immunosuppressive treatment is started promptly. With appropriate treatment 80% of patients achieve remission and long-term survival. Autoimmune sclerosing cholangitis responds to the same treatment used for autoimmune hepatitis in regards to parenchymal inflammation, but bile duct disease progresses in about 50% of cases, leading to a worse prognosis and higher transplantation requirement; it has a high recurrence rate post-liver transplant. De novo autoimmune hepatitis after liver transplant affects children transplanted for non-autoimmune conditions and responds well to the same treatment schedule used for autoimmune hepatitis, but not to the schedule used for acute rejection.Autoimmune liver diseases in children – What is different from adulthood?Giorgina Mieli-Vergani, Diego Vergani10.1016/j.bpg.2011.10.007Best Practice & Research Clinical Gastroenterology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Gastroenterology2011-12-01256S1521-6918(11)X0006-9783795