Eradicating chronic Hepatitis C Viraemia : lessons learnt during the last decade

Over the last decade a better understanding of the mechanism for immune disposal of hepatocytes infected with the Hepatitis C virus enabled the design of antiviral regimens with increasing efficacy. The poor rates of sustained viral clearance initially obtained with recombinant interferon (12%) have now improved to over 70 % with the use of a combination of pegylated interferon and the guanosine analogue ribavarine. The relatively poor response of genotype 1 strains to this regimen continues to challenge scientists and clinicians. This article reviews the theoretical and practical aspects of selection of patients for viral eradication, their management during treatment and subsequent follow-up.peer-reviewedpeer-reviewe

Difficulties encountered when treating coeliac disease : from molecule to miracle cure?

Dietary treatment of coeliac disease should be based on a sound theoretical knowledge of the different immunogenicities of various cereal grains, an appreciation of the limitations of the current Codex Alimentarius recommendations and an understanding of the factors that limit dietary compliance in many patients. The expertise of dieticians, nutritional chemists, gastroenterologists and clinical pharmacists should be made readily available to coeliac patients, to coeliac societies and to coeliac self-help groups. Various enzymatic and pharmacological modalities that may be used to treat coeliac disease in the future are highlighted as potential ways to improve quality of life in these patients in whom the coeliac diet often promotes poor compliance or may lead to significant social alienation.peer-reviewe

Recurrent chemical pancreatitis complicating choledochal cystic disease

A seventeen year old lady presented with a twelve year history of self-limiting attacks of severe epigastric pain, associated with occasional fever, normal total white cell count (WCC), normal or mildly elevated serum alanine transaminase (ALT) (13-200iu/l) and variable hyperamylasaemia (127-460iu/l). At age 5 years, abdominal ultrasonography had shown non-cystic dilatation of the intrahepatic and extrahepatic biliary system without choledocholithiasis. Despite endoscopic sphincterotomy of a normal ampulla with extraction of bile duct stones at age eleven years, followed by laparoscopic resection of a dilated gall bladder, the attacks increased in frequency. Subsequent endoscopic retrograde cholangio pancreatography (ERCP) confirmed biliary dilatation in the absence of stones but the pancreatic duct was poorly outlined. At age 15 years a magnetic resonance cholangiopancreatogram (MRCP) showed generalised dilatation of the extrahepatic biliary tree involving the common hepatic duct and the porta hepatis with a large elongated choledochal cyst arising out of the lateral wall of the common bile duct (CBD). These findings are best seen in a coronal view (Figure 1) which also shows a normal pancreatic duct joining the CBD about 15mm proximal to the level of the ampulla. This suggests a long common pancreatobiliary channel running through the pancreatic head before entering the duodenal wall (Figure 2). The patient underwent excision of the dilated biliary tract above the anomalous pancreaticobiliary junction with Roux en Y hepatico-jejunostomy. A small cystic lesion in the jejunal wall was also excised. Histology of the resected specimens showed mildly inflamed choledochal malformations with no dysplasia. Postoperative recovery was uneventful. Follow up MRCP surveillance for neoplasia at six month intervals showed a patent hepatico-jejunostomy and an unchanging filling defect in the intapancreatic bile duct stump remnant with anterior meniscal indentation typical of a trapped air bubble (Figure 3).peer-reviewe

The Hepatitis C virus : your part in its downfall : getting to know the virus and its host

The cloning of the genome of the Hepatitis C virus (HCV) in 1989 provided sensitive screening tools and specific diagnostic assays which helped health workers to limit viral spread and scientists to design effective anti-viral agents. The uncorrected intrinsic error rate of HCV's key replicating enzyme (RNAdependent RNA polymerase) leads to antigenically different'"quasispecies" which allow the virus to escape immune recognition by the host and leads to an ill-sustained clearance of virus by T lymphocytes. This article discusses the factors which may lead to progressive liver fibrosis and provides a theoretical framework for the selection of patients for viral eradication using pegylated preparations of recombinant interferon in conjunction with the oral antiviral ribavarine.peer-reviewe

Parenteral glutamine in critical illness : just what the gut needs

The role of glutamine as a metabolic fuel for the starving intestines, its capacity to limit bacterial translocation, lung sepsis and a pro-inflammatory cytokine response are reviewed in the context of uncertainities regarding current recommendations for glutamine supplementation in parenterally-fed critically ill patients. Weaknesses in the evidence-base showing benefit of intravenous glutamine supplementation are discussed together with aspects of glutamine supplementation via the enteral route.peer-reviewe

Pathogenetic sequences in coeliac disease : closing the jigsaw puzzle

Coeliac disease is one of the best understood models of adaptive immunity in which a known dietary component triggers over-presentation of a known autoantigen in genetically predisposed individuals. The dynamics of this gene-nutrient interaction and the mechanism responsible for accelerated programmed death of the enterocytes lining the upper small intestine are explored in order to generate insight into the large number of candidate pharmacological agents that may well aid or replace cumbersome dietary treatment in years to come.peer-reviewe

Eradication of gastric Helicobacter Pylori : are we getting there?

In 1984 a curved bacillus living in the stomach of patients with gastritis and peptic ulceration was discovered and isolated. This organism named as Helicobacter Pylori (HP), has been shown to play a major role in the causation of duodenal ulcers. Persistence of helicobacter pylori has been partly attributed to re-infection of the stomach, especially where sanitary conditions are poor. Recent developments in the field of duodenal ulcer therapy have raised the hopes that this therapeutic hurdle can now be overcome by an alternative approach.peer-reviewe

Medical management of inflammatory bowel disease

Patients who have recently been diagnosed as suffering from inflammatory bowel disease face two disturbing realities: firstly the true cause of the disease has not yet been defined and secondly the long term prognosis is unpredictable. In this article the author attempts to put in perspective the therapeutic regimens that have established themselves so far in this field, and to provide practical guidelines for their use in commonly encountered scenarios.peer-reviewe

Neurogenic disturbances of cardiac rhythm

Arrhythmias are disturbances of electrical activation of the heart and are commonly encountered clinical conditions. Although typically associated with cardiac pathology, they have also been described in stroke and epilepsy. Two closely related structures, the insula and the temporal lobe, particularly the mesial region, have been implicated. Derangement of central autonomic control appears to be a key driver in neurogenic arrhythmogenesis and both these structures appear to play some role in influencing autonomic activity. Our understanding of this phenomenon is only in its infancy, and more research will be necessary to further it.peer-reviewe