Long-term evolution and predictive factors of mild inflammatory bowel disease.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are potentially progressive diseases. Few data are available on the prevalence and the factors associated with mild inflammatory bowel diseases (IBD). AIM: Our aim was to assess the natural history of mild CD and mild UC and to identify predictive factors of mild evolution over the long term. METHODS: Retrospective study of IBD patients registered in the database of the university hospital CHU of Liège, Belgium. Mild CD was defined as an inflammatory luminal disease (no stricture, abdominal or perianal fistulae) requiring no immunomodulator (IM), anti-TNF and no surgery. Mild UC was defined as no requirement for IM, anti-TNF and no colectomy. RESULTS: Four hundred and seventy-three CD and 189 UC were included (median follow-up: 13 and 11 years respectively). At 1 year, 147 patients had mild CD. At 5 years and the maximum follow-up, 56% and 13% patients still had mild CD, respectively. At 1 year, 142 patients had mild UC. At 5 years and the maximum follow-up, 72% and 44% still had a mild UC, respectively. Factors associated with long-term mild CD and UC were older age at diagnosis and absence of corticosteroids in the first year. In UC proctitis location was associated with mild UC. CONCLUSIONS: In this cohort, 90% of CD patients and 3/4 of UC with mild disease at 1 year lost their mild disease status over time. An old age at diagnosis was predictive of the persistence of a mild CD and UC.

[FROM EVIDENCE-BASED MEDICINE TO PERSONALIZED MEDICINE IN CROHN'S DISEASE]. / DE L'"EVIDENCE-BASED MEDICINE" À LA MÉDECINE PERSONNALISÉE DANS LA MALADIE DE CROHN.

The therapeutic armamentarium in Crohn's disease includes mesalazine, steroids (including topical drugs), anti-metabolites (purines, methotrexate), anti-TNFα antibodies and, more recently, selective inhibitors of lymphocytes homing (vedolizumab). The efficacy of these drugs has been shown in pivotal phase 3 placebo-controlled trials and meta-analyses. However, the use of these drugs in routine practice still remains ill-defined. Those are rather the cohort studies, natural history data and therapeutic strategy trials that help the clinician to determine, for each individual patient, the treatment leading to an optimal benefit/risk profile, aiming at moving from evidence-based medicine towards personalized medicine.

[Genetics and environment in chronic inflammatory bowel diseases]. / Génétique et environnement dans les maladies inflammatoires chroniques de l'intestin.

Inflammatory bowel diseases are both environmental and genetic illnesses. More than one hundred genes or loci involved in the regulation of innate or acquired immune response as well as intestinal mucosa homeostasis have been identified. Environmental studies have been less numerous up to now and only smoking and appendectomy have been validated, as protector for ulcerative colitis, while smoking is clearly associated with an increased risk and more severe forms of Crohn's disease. An important role is also currently suspected for the intestinal flora and the dysbiosis described in inflammatory bowel disease could contribute to the triggering or the persistence of the inflammation. New therapeutic strategies are currently studied, particularly aiming at targeting immune, inflammatory or homeostatic pathways corresponding to the predisposing gene variants.

[Fifteen years of use of anti-TNF antibodies in moderate to severe Crohn's disease: how to make the best of this experience]. / Quinze ans d'anti-TNF dans la maladie de Crohn: comment tirer le meilleur de cette révolution thérapeutique?

After fifteen years of use, the anti-TNF antibodies have become the corner stone of the treatment of moderate and severe Crohn's disease. The skill acquired over the years through experimental trials and clinical experience leads to increased therapeutic efficacy and minimized risks. These antibodies are introduced increasingly earlier in Crohn's disease as well as in a broader range of patients, aiming at changing the natural history of the diseases by avoiding the development of intestinal tissue damage and complications.

[Challenges to reduce mortality due to hepatitis C: improving accessibility to therapy and compliance]. / Défis pour réduire la mortalité liée a l'hepatite C: améliorer l'accessibilité au traitement et l'observance thérapeutique.

Current therapies with pegylated interferon and ribavirin are effective to eradicate the virus C. Improvements are foreseen in the near future with combination of the current treatment with antiviral therapies (antiproteases, antipolymerases). Eradication of the virus, when obtained, has a favorable impact on an individual basis. However, to reduce the mortality related to the virus C at a population level, an important point is the accessibility to therapy. It has been calculated that the impact of current management to reduce mortality is minimal, as compared to the absence of treatment, due to a poor accessibility to therapy. To obtain a significant additional reduction of mortality, a better screening, a better access to the threatment are crucial.

[Clinical case of the month. Cystic lymphangioma of the mesentery]. / Le cas clinique du mois. Le lymphangiome kystique du mésentère.

Cystic lymphangioma of the mesentery is a benign condition, probably of malformative origin, and frequently appearing in infancy. Its symptomatology can be very polymorphic. Its diagnosis is suspected by ultrasonography and computed tomography, and definitely confirmed by pathology. About a recent case of cystic lymphangioma of the mesentery diagnosed and operated on at the university hospital of Liège in an adult patient, the authors review its classification and its therapeutic strategy. Surgical resection is indicated in symptomatic cystic lymphangioma.

Anti-tumor necrosis factor nonresponders in Crohn's disease: therapeutic strategies.

Anti-TNF antibodies have revolutionized the treatment of Crohn's disease. In pivotal trials, however, the frequencies of primary and secondary nonresponders appeared rather high with, by the end of 1 year of scheduled treatment, only one fifth of the patients initially treated still in sustained remission. Other studies and monocentric experiences have indicated that these seemingly disappointing results were partly due to suboptimal selection of the patients and absence of treatment optimization. Optimal selection of the patient includes proving active intestinal lesions and systemic inflammation as well as excluding stricturing or infectious complications. Treatment optimization includes potential immunosuppressive co-treatment and dose or administration interval adjustment of the anti-TNF. When a failure is confirmed with an anti-TNF despite such optimization, second- or third-line anti-TNFs have proved useful. Beyond that, a transient steroid course and surgical procedures still represent rescue option, waiting for new promising biologics in development.

[Biologic therapies in chronic inflammatory bowel diseases]. / Thérapies biologiques et maladies inflammatoires chroniques intestinales.

Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases which can be difficult to control with conventional therapies. Thanks to a better knowledge of their physiopathology, new therapies aimed at specific targets of the inflammatory cascade were developed. Three monoclonal anti-TNF antibodies were produced. Infliximab and adalimumab, currently widely used, can induce sustained remission in Crohn's disease. Infliximab is also efficacious in UC. Certolizumab pegol provides good short term results; its long term efficacy, however, remains to be assessed by further clinical trials. Therapies targeting leucocyte trafficking (anti-integrine) have also been provided and are associated with good clinical responses in Crohn's disease. Natalizumab (anti-alpha4) is responsible for significant side effects and is no longer in use in gasrtoenterology in Europe whereas MLN02 (anti-alpha417) has a good profile in terms of efficacy and safety. Monoclonal anti bodies targeting other cytokines are under development, mainly ustekinumab which inhibits IL12 and IL23. Ustekinumab generates favourable clinical responses in Crohn's disease. The development of biologic therapies in inflammatory bowel disease has dramatically altered the course and management of these disorders.

[Adenocarcinoma of the small intestines complicating coeliac disease in an adult: case report]. / Adénocarcinome de l'intestin grêle compliquant une maladie coeliaque de l'adulte: à propos d'un cas.

Coeliac disease is an auto-immune disease due to gluten intolerance. One per cent of the European population is concerned. This small bowel adenocarcinoma is rare and concerns less than 5% of the digestive neoplasias. However the frequency of this rare cancer is higher in presence of coeliac disease. We are reporting the case of a 67-years-old woman whose coeliac disease has been complicated 5 years thereafter by a jejunal adenocarcinoma. The latter was found during an etiology search for iron deficiency anemia.

[Genomics of inflammatory bowel diseases: basis for a new molecular classification and new therapeutic strategies of these diseases]. / Génomique des maladies inflammatoires intestinales. Base pour une nouvelle classification moléculaire de ces maladies et source de nouvelles stratégies thérapeutiques.

Inflammatory Bowel Disease, Crohn's disease and ulcerative colitis, are complex, multifactorial, polygenic diseases. Huge progresses in the knowledge of human genome and genotyping techniques have allowed the identifications of dozens of genes and loci associated with these diseases. These discoveries set the path for a new molecular classification of these diseases and let us see new therapeutic possibilities. The present paper highlights, in the setting of the Synthèse CHU 2009 meeting, the contributions of the team of the CHU and university of Liège in this field.

[Monoclonal antibodies therapies for colorectal cancer: cétuximab, panitumumab and bevacizumab]. / Apports des anticorps monoclonaux dans le traitement du cancer colorectal: cétuximab, panitumumab et bévacizumab.

Colorectal cancer is the third most common form of cancer in Europe, Its prognosis is poor, since median survival time for metastatic patients is about 20 months. Progresses in molecular biology have lead to significant improvement in the management of metastatic colorectal cancer with targeted therapies. The monoclonal antibodies anti-EGFR and anti-VEGFR improve the overall and the progression-free survival. The anti-EGFR antibodies (cétuximab and panitumumab) have been marketed in Belgium, as monotherapy or in association with chemotherapy (FOLFIRI) for third line use in patients with wild type K-ras. The anti-VEGFR bevacizumab is the standard first line treatment in metastatic colorectal cancer with irinotecan based chemotherapy. For the future, the place of monoclonal antibodies therapies in adjuvant or in first line settings and the value of combining targeted therapies have to be further defined.

[Colorectal cancer screening: an absolute necessity and a concrete reality in the French community]. / Le dépistage généralisé du cancer colorectal: une absolue nécessité et une réalité imminente en Communauté française.

Colorectal cancer is a real problem of public health. Screening is an absolute necessity. An ambitious program of screening is launched in the French Community. Faecal occult blood test will be proposed to average risk patients in the general population. A total colonoscopy will be performed if FOBT is positive. First step colonoscopy will be proposed to high or very high risk patients. General practitioners are in the core of the multi-disciplinary program.

[Treatment of (unresectable) hepatocellular carcinoma at an intermediate or advanced stage]. / Straitement des carcinomes hépatocellulaires à un stade intermédiaire ou avancé.

Hepatocellular carcinoma is the main primitive tumor of the liver. It occurs in the setting of liver cirrhosis in more than 90% of the cases in developing countries. The prognosis depends on the size, number and extension of the tumor as well as on the severity of the underlying liver disease. The Barcelona Clinic Classification takes into account these different parameters and helps the clinician in the therapeutic decision. Some patients (around 25%) are amenable to therapy with a curative intent (liver transplantation, resection, destruction by radiofrequency). In patients with hepatocellular carcinoma at an intermediate stage, lipiodolized chemoembolization gives a survival advantage in comparison with placebo. No conventional regimen of chemotherapy has a proven survival benefit. In patients with a hepatocellular carcinoma at an advanced stage, sorafenib, an oral multi-targeted kinase inhibitor, is the first compound to demonstrate a significant effect on survival free of disease progression in a selected group of patients. Its toxicity profile is particularly favourable. Combination of surgical and medical therapies should be properly evaluated in clinical trials in the near future.

Are we giving biologics too much time? When should we stop treatment?

The optimal duration of biological treatment, particularly anti-TNF, in inflammatory bowel disease (IBD) is a very important question both for patients and physicians. There is no published evidence to clearly and definitely answer this question. However data on natural history of IBD, long term safety of biologics, immunosuppressors (IS) cessation and some preliminary studies on biologics cessation may help us to discuss this topic. The decision to stop a biological treatment is currently based on a compromise between the benefits and risks associated with the prolongation of this treatment. IBD, more particularly CD, are characterized by the development of complications and the need for recurrent hospitalizations and surgeries in approximately 2/3 of cases. In these patients potentially in need of biological treatments, it is probable that, as it has been demonstrated for IS, the longer a stable remission has be achieved under treatment, the lower the risk of relapse is after treatment cessation. Further prospective studies should now aim at disclosing patient characteristics associated with a low risk of relapse to implement this strategy.

[Hepatitis E: a Third World's hepatitis found in Belgium]. / L'hépatite E: une hépatite du Tiers-Monde présente en Belgique.

Hepatitis E virus is the second cause of acute viral hepatitis of oral-fecal origin in the world. This virus has a vast distribution throughout the world and manifests itself either in epidemic or endemic-sporadic form in many developing countries. Usually, the cases of HEV infection in industrialized countries are observed after a history of travel in an endemic area. However, an increasing number of cases have been attributed to a HEV zoonotic form transmitted by swine. HEV infection can lead to deadly fulminant hepatic failure in 1-4% in the common population, but the mortality incidence reaches 20% in case of third trimester pregnant women infection. The diagnosis of HEV infection can be made using serological tests but today, RT-PCR is considered as the gold standard test. Unfortunately, this technique is not widely available in Belgium yet. There is no treatment for HEV infection, only prophylactic measures as hygiene and sewage treatment can stop epidemics. Recently, a new vaccine, still in research phase, has showed promising outcomes.

[Eosinophilic esophagitis in adults: report of a case]. / Le cas clinique du mois. L'oesophagite à éosinophiles chez l'adulte: à propos d'un cas.

Eosinophilic esophagitis is a chronic inflammatory disease. The most typical symptoms are recurrent dysphagia and episodes of food impactions. This pathology is quite frequently associated with atopy. We report the case of a 39-year-old patient, suffering from allergic asthma, admitted to hospital for an episode of food impaction. Clinical, endoscopic and histological findings lead to the diagnosis of eosinophilic esophagitis. From data of the litterature, we discuss the diagnosis, the pathogeny and the treatment of this pathology.

[The FibroScan: a new non invasive method of liver fibrosis evaluation]. / Le FibroScan: une nouvelle méthode d'évaluation non invasive de la fibrose hépatique.

The FibroScan is a device allowing a non invasive diagnosis and quantification of liver fibrosis. The procedure is based on transient elastography and allows to record liver stiffness by measuring the velocity of shear wave across liver parenchyma. The elasticity is directly correlated to velocity of the wave. In chronic hepatitis C, there is a good correlation between liver elasticity and stage of fibrosis. The FibroScan has also been studied in other chronic liver diseases, such as hepatitis B, primary biliary cirrhosis, sclerosing cholangitis, auto-immune hepatitis, alcohol, steatosis, hemachromatosis with reproductible results. In a cirrhotic patient, it also allows to assess the severity of cirrhosis and to evaluate the risk of complication. It is a painless procedure, with a good acceptability by the patients. Therefore, the FibroScan can be regularly performed, allowing the follow up of fibrosis evolution over time.

[Therapeutic update in gastroenterology]. / Actualités thérapeutiques en hépato-gastroénterologie.

During the last decade, advances in molecular biology and biotechnology allowed, the development of biological treatments aimed at more precise targets. New algorithms in inflammatory bowel diseases, chronic hepatitis C and digestive oncology are examples of the marked progress achieved by these therapies.

[Screening for colorectal cancer]. / Le dépistage du cancer colorectal.

Colorectal cancer is the second leading cause of death in Northern countries and need a national screening program to reduce mortality and improve quality of life. Screening has to be cost-effective and acceptable for patients. Many screening tools, invasive or not, are existing and often debated: FOBT, sigmoidoscopy and complete colonoscopy. New tools are in development and have to be evaluated in current practice: virtual colonoscopy, new endoscopic technologies, DNA on faeces or proteomics with markers in serum.

[Innovative therapies in inflammatory bowel disease at the CHU]. / Les thérapies innovantes au CHU dans les maladies inflammatoires chroniques de l'intestin (MICI).

Inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis are frequent illnesses in western countries. They have a dramatic impact on the health-related quality of life. The new biological treatments developed for these diseases are potentially very effective, but are also expensive and may have significant side effects. In the present paper, the authors describe new biological therapies used during the past 10 years at the CHU. More than 20 therapeutic protocols were implemented. These protocols have given the patients the opportunity to gain very rapid access to new efficient therapies, to benefit from promising techniques for the evaluation of their pathology and to be submitted to a close follow-up that frequently called their treatment into question in the light of the most innovative options.