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EUR-8 Liver

Discipline Report on (Bio)Medical and Health Sciences Research in the Netherlands 1998

EUR - Faculty of Medicine and Health Sciences, Erasmus University Rotterdam

EUR-8 Liver & Gastrointestinal research

Objectives

The general objective of this predominantly clinical research program is to alleviate the suffering of chronic conditions in hepatology and gastroenterology. The program, which constitutes the core of the research on liver and gastrointestinal disease in the Erasmus medical complex, is characterised by a multidisciplinary approach with participation of several departments: hepatogastroenterology and internal medicine, surgery, radiology and virology. The research in hepatology focuses on identification of etiologic factors, the mechanisms of disease progression, and elimination of causative factors at the one hand, and organ replacement on the other hand. The research in gastroenterology focuses on delineation of subgroups of the population that could benefit from screening for highly prevalent gastrointestinal carcinoma, on identification of the role of mediators on inflammation in intestinal disease, and on diagnostic methods in slow intestinal transit syndromes. The research in nutrition and metabolic diseases is centred around mechanisms of malnutrition in liver disease and cancer in general; and on studying the interaction between heme, alcohol and iron in porphyrianext hit. Radiology imaging techniques are used for diagnosis and as guidance techniques for minimally invasive therapy.

Results

Research in liver disease has focused on determinants of disease progression in chronic viral hepatitis and chronic cholestatic liver disease. An important finding is emerging that suppression of hepatic inflammation itself is key to prevention of liver insufficiency and hepatocellular carcinoma. Clearance of viral infection is one important, but incomplete route in chronic viral hepatitis; complete suppression of hepatic inflammation by non-specific routes appears also highly effective. This finding opens up therapeutic interventions in disease of unknown aetiology such as chronic cholestatic liver disease. Prevention of complications of cirrhosis (variceal bleeding, encephalopathy) may affect the quality of life, but not survival; this finding gradually modifies the indication for liver transplantation.

Research in gastroenterology regarding the detection of premalignant conditions in the oesophagus and colon has led to the finding that general screening appears of limited benefit in relation to costs; identification of sub-groups with high cancer risk is now tested as the approach to screening for the major gastrointestinal carcinomas. Research in inflammatory bowel disease has yielded information on the role of mediators of inflammation with respect to disease activity, and the effect of standard and new drugs (nicotine, somatostatin and IL10) on these interactions. New diagnostic tools such as barostat measurements, laser doppler flowmetry, endorectal ultrasound and magnetic resonance imaging has been evaluated in colorectal slow transit disorders; new mechanisms of disease were discovered, allowed the application of appropriate surgical procedures (rectocele repair, anterior anal repair).

Research in nutrition provided evidence that glycogen depletion overnight is facilitated in liver cirrhosis, causing increased protein catabolism. Hepatic gluconeogenesis is also increased in cancer cachexia, which negatively affects life expectancy. In previous hitporphyria many different gene defects have been identified. In radiology, a new endoanal Magnetic Resonance Imaging (MRI) coil was developed. A new type of stent for the palliative treatment of patients with malignant bile duct obstruction was evaluated.

Future plans

The studies in hepatology will continue to focus on chronic viral hepatitis, chronic cholestatic liver disease, whereas research in liver transplantation will concentrate on immunological interactions in the liver. Antiviral research will concentrate on virus suppression, and prevention of resistance on the one hand, and immunological clearance of virus infected hepatocytes on the other hand. The latter approach will be done in close collaboration with the hepatitis group at the department of virology with its focus on virus immune interactions. The testing of hypothesis on the effect of interventions on the natural history of the disease will be done within the existing networks of Eurohep, the Benelux Study Group on hepatitis C, the Euro PBC group and the Benelux PSC Study Group, all co-ordinated in Rotterdam. Both in chronic viral hepatitis and in cholestatic liver disease therapeutic approaches that markedly suppress hepatic inflammation will pursued and tested for prevention of liver disease progression and hepatocellular carcinoma. In gastroenterology the pursuit of developing a simple mean to identify subgroups with high risk for oesophageal and colon cancer will continue; endoscopic methods to treat premalignant colonic lesions are better developed than those for oesophageal disease, the latter being a focus of an intensive research project (photodynamic therapy). Joint basic and clinical research on the role of nicotine, its mechanism of action and the clinical efficacy will dominate studies in inflammatory bowel disease. In slow transit disorders studies on the compliance, elasticity and contractibility of the rectal wall will continue; the pathogenetic-based surgical techniques will be tested in clinical trials.

In nutrition, studies as energy and protein requirements in cirrhosis will continue, with emphasis on the clinical application of stable isotope measurements of intermediary metabolism and magnetic resonance spectroscopy. The same techniques will be applied to studies on cancer cachexia and in adult patients with inborn errors of metabolism (phenylketonuria). New strategies for cancer cachexia will be tested in clinical trials.

In radiology, new application for MRI endocoils will be developed, as well as temperature sensitive MRI techniques for monitoring interstitial laser therapy.

This main research theme is assessed in cluster VIII

Discipline Report on (Bio)Medical and Health Sciences Research in the Netherlands 1998
Medical Committee KNAW

 

 

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