New guidelines for screening,evaluation and management of hepatobiliary disease in cystic fibrosis

The recently published guidelines on screening,monitoring and treatment update previous guidelines published 25 years ago(1,2).This update is timely as much has happened in the interim.Cystic fibrosis(CF)modulator therapy has dramatically improved prognosis for patients with CF,although it is not yet clear whether liver disease is improved.Our understanding of the pathophysiology of CF liver disease has also changed with the recognition of the importance of non-cirrhotic portal hypertension(3,4).Non-invasive tests for fibrosis and elastography have changed the practice of hepatology and reduced the need for liver biopsy.The guideline committee was made up of experts from North America and Europe and included adult and paediatric hepatologists and pulmonologists together with allied health practitioners and representatives of the CF community.A systematic literature search was performed and a vote of 80%was required to adopt a recommendation.The guidelines contain 7 recommendations for screening,13 for disease monitoring and 14 for treatment.

Oral mixture of autologous colon-extracted proteins for the Crohn's disease: A double-blind trial

AIM: To evaluate the safety and efficacy of oral administration of AlequelTM, an autologous proteincontaining colon extract.a randomized,placebo-controlled,double-blind trial.Patients were orally administered with autologous protein-containing colon extract three doses of autologous study drug per week for 15 wk,for a total of45 doses.Patients were followed for safety parameters.Remission was defined as a Crohn’s disease activity index(CDAI)score of less than or equal to 150.All patients were followed for changes in subsets of T cells by fluorescence-activated cell sorting analysis.RESULTS:Analysis was performed on a total number of evaluable patients of 14 in the study drug group and15 in the placebo group.Treatment was well tolerated by all patients.No major treatment-related adverse events were reported or observed in any of the treated patients during the feeding or follow-up periods.Between weeks 6 and 9 of the study,six of the 14(43%)evaluable subjects who received the study drug achieved a CDAI of 150 or lower.In contrast,five of the 15(33%)evaluable subjects in the placebo group achieved remission.Between weeks 9 and 12,the remission rates were 50%and 33%for the drug group and placebo group,respectively.Among the drug-treated subjects who achieved remission,the effect of the drug was judged as stable in eight of the 14 subjects as measured by at least two CDAI scores indicating remission in the 15-wk treatment period.A decreased percentage of peripheral natural killer T regulatory cells(a decrease of 28%vs an increase of 16%)and an increased ratio of CD4+/CD8+T lymphocytes(an increase of 11%vs a decrease of9%)were noted in subjects with a significant clinical response.CONCLUSION:Oral administration of the autologous colonic extract could be a safe and effective for the treatment of patients with moderate to severe Crohn’s disease.

Oral immune regulation using colitis extracted proteins for treatment of Crohn's disease: Results of a phase Ⅰ clinical trial

AIM: To evaluate safety and possible efficacy of induction of oral immune regulation using colitis extracted proteins (CEP) in Crohn's disease (CD) subjects. METHODS: Ten CDs were treated orally with autologous CEP thrice weekly for 16 wk. Subjects were monitored for CDAI and IBDQ. Immune modulatory effect was assessed by T-lymphocyte FACS analysis, CEP-specific IFNγ ELISPOT assay and cytokine levels. RESULTS: Induction of oral immune regulation significantly ameliorated disease activity. All (10/10) subjects had clinical response (CDAI≤70) and 7/10 achieved clinical remission (CDAI≤150). Significant increase in mean IBDQ score was noted (134±9 vs 164±12). No treatment-related adverse events were noted. High levels of CEP-specific IFNγ spot forming colonies were detected in five subjects prior to treatment and in all five, a marked decrease was observed. The CD4+/CD8+ lymphocyte ratio and peripheral NKT cell numbers increased significantly, in 7/10 and in 5/10 subjects, respectively. Significant increase in serum IL-10 and IL-4 levels was observed in 7/10 subjects during treatment period. CONCLUSION: Immune regulation via oral administration of CEP is a safe and possibly effective treatment for subjects with moderate CD and may provide means of antigen-specific immune modulation.