Intrahepatic immune response in chronic viral hepatitis : an immunohistochemical study

The hepatitis B virus (HBV) is a 42 nm viral particle and belongs to a family of closely related DNA viruses called the hepadnaviruses. All the hepadnaviruses have similar hepatotropism and life cycles in their hosts. It is an enveloped small circular, partially double stranded DNA virus. The viral genome has a length of approximately 3200 base pairs that encodes four open reading frames (ORF). These are the pre-Surface (pre-S) and Surface (S) gene, the pre-Core (pre-C) and Core (C) gene, the X-gene and the Polymerase (P)-gene. The pre-S and pre-C genes are upstream regions of the S and C genes. The viral envelope encoded by the S gene contains three distinct configurations synthesized in all infected persons, termed the large, middle and major envelope proteins, which are produced by beginning transcription at, respectively, the pre-S1, pre-S2 or the S gene. The pre-S1 and pre-S2 represent two of the more immunogenic portions of hepatitis B surface antigen (HBsAg). The development of cellular and humoral immunity to HBsAg is protective, and recombinant HBsAg provides the basis for the HBV vaccines currently available. The hepatitis B core antigen (HBcAg) is the nucleocapsid that encloses the viral DNA. When HBcAg-derived peptides are presented by MHC-molecules present on the surface of hepatocytes, they can initiate a cellular immune response that is important for viral clearance

Phenotype of inflammatory bowel disease at diagnosis in the Netherlands: A population-based inception cohort study (the Delta Cohort)

Background: To describe the clinical characteristics of inflammatory bowel disease (IBD) at diagnosis in Netherlands at the population level in the era of biologics. Methods: All patients with newly diagnosed IBD (diagnosis made between January 1, 2006 and January 1, 2007) followed in 9 general hospitals in the southwest of the Netherlands were included in this population-based inception cohort study. Results: A total of 413 patients were enrolled, of which 201 Crohn's disease (CD) (48.7%), 188 ulcerative colitis (UC) (45.5%), and 24 IBD unclassified (5.8%), with a median age of 38 years (range, 14-95). Seventy-eight patients with CD (38.8%) had ileocolonic disease and 73 patients (36.3%) had pure colonic disease. In 8 patients (4.0%), the upper gastrointestinal tract was involved. Nineteen patients with CD (9.5%) had perianal disease. Thirty-nine patients with CD (19.4%) had stricturing phenotype. Of the patients with UC and IBDU, 39 (18.4%) suffered from pancolitis and 61 (29%) from proctitis. Severe endoscopic lesions at diagnosis were seen in 119 patients (28.8%, 68 CD, 49 UC, and 2 IBDU), whereas 98 patients (23.7%) had severe histological disease activity. Thirteen patients (3.1%, 10 CD and 3 UC) had extraintestinal manifestations at diagnosis. Twenty-three patients (5.6%, 20 CD and 3 UC) had fistula at diagnosis. Conclusions: In this cohort, 31% of the patients with CD had complicated disease at diagnosis, 39% had ileocolonic disease, 9.5% had perianal disease, and in 4% the upper gastrointestinal tract was involved. Most patients with UC suffered from left-sided colitis (51%). Severe endoscopic lesions were reported in 34% of the patients with CD and 26% of the patients with UC. Three percent of the patients with IBD had extraintestinal manifestations. Copyrigh

Benefit of earlier anti-TNF treatment on IBD disease complications?

Background: Anti-tumour necrosis factor [anti-TNF] treatment was demonstrated to have disease-modifying abilities in inflammatory bowel disease [IBD]. In this study, we aimed to determine the effect of anti-TNF treatment timing on IBD disease complications and mucosal healing [MH]. Methods: The following IBD-related complications were tested in relation to timing of anti-TNF therapy start in newly diagnosed IBD patients [n = 413]: Fistula formation, abscess formation, extra-intestinal manifestations [EIM], surgery, referral to academic centre, and MH. Results: A total of 85 patients [21%] received anti-TNF (66 Crohn's disease [CD], 16 ulcerative colitis [UC], 3 inflammatory bowel disease unclassified [IBDU]) of whom 57% [48 patients] were treated 16 months] regarding gender, age, smoking status, and familial IBD. More importantly, patients receiving anti-TNF early did not suffer less IBD-related complications during follow-up as compared with patients started on anti-TNF late, nor was more MH observed. Similar results were obtained when anti-TNF treated patient were stratified more stringently, ie 2 4 months [24 patients]. Cox regression analysis showed no beneficial correlations between anti-TNF timing and IBD-related complications. Anti-TNF treated patients achieving MH were 11 times less likely to develop EIMs compared with patients who did not achieved MH while on anti-TNF. Conclusions: This study was unable to confirm a benefit of earlier anti-TNF treatment on IBD disease complications. This could be explained by more aggressive treatment earlier in disease, resulting in fewer IBD complications. However, it seems more likely that inappropriate selection of patients for therapy leads to suboptimal treatment and subsequently suboptimal outcome