Contrasting Pattern of Chronic Inflammatory Bowel Disease in Primary and Autoimmune Sclerosing Cholangitis.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pagePrimary sclerosing cholangitis (PSC) and autoimmune sclerosing cholangitis (AISC) are related, but distinct chronic liver diseases. PSC is associated with a high prevalence of ulcerative colitis while the intestinal inflammation associated with AISC is less well characterised.To assess and contrast aspects of intestinal inflammation in patients with AISC and PSC and compare the clinical features with those of patients with ulcerative colitis and Crohn's disease.23 and 22 patients with AISC and PSC, respectively, underwent review of colonoscopy and biopsy findings, capsule enteroscopy and assessment of clinical and inflammatory (faecal calprotectin) disease activity, which was compared with that of patients with ulcerative colitis and Crohn's disease (n = 55 each).Five and 6 patients with AISC and PSC, respectively, had normal colonoscopy and faecal calprotectin levels of 34.4 ± 8.3 and 39.7 ± 8.4 μg/g, respectively (normal 0.05) between patients with intestinal inflammation in AISC (588 ± 549 μg/g), PSC (421 ± 351 μg/g), ulcerative colitis (501 ± 656 μg/g) or Crohn's disease (476 ± 571 μg/g). Capsule enteroscopy showed that 7 of 18 (39%) (p < 0.03) of those with AISC had small bowel mucosal breaks whereas no patient with PSC had these findings.Collectively these findings lend support to the suggestion that the chronic inflammatory bowel disease associated with PSC and in particular AISC may represent a distinct nosologic entity different from classic ulcerative colitis and Crohn's disease

Mericitabine and Either Boceprevir or Telaprevir in Combination with Peginterferon Alfa-2a plus Ribavirin for Patients with chronic Hepatitis C Genotype 1 Infection and Prior Null Response: The Randomized DYNAMO 1 and DYNAMO 2 Studies.

Most patients with chronic hepatitis C virus (HCV) genotype 1 infection who have had a pre- vious null response ( < 2-log 10 reduction in HCV RNA by treatment week 12) to peginter- feron/ribavirin (PegIFN/RBV) do not achieve a sustained virological response (SVR) when re-treated with a first-generation HCV protease inhibitor (PI) administered in combination with PegIFN/RBV. We studied the incremental benefits associated with adding mericitabine (nucleoside analog inhibitor of HCV polymerase) to PI plus PegIFN alfa-2a/RBV-based therapy in two double-blind randomized multicenter phase 2 trials (with boceprevir in DYNAMO 1, and with telaprevir in DYNAMO 2). The primary endpoint in both trials was SVR, defined as HCV RNA < 25 IU/mL 12 weeks after the end of treatment (SVR12). Over- all, the addition of mericitabine to PI plus PegIFN alfa-2a/RBV therapy resulted in SVR12 rates of 60 - 70% in DYNAMO 1 and of 71 - 96% in DYNAMO 2. SVR12 rates were similar in patients infected with HCV genotype 1a and 1b in both trials. The placebo control arms in both studies were stopped because of high rates of virological failure. Numerically lower relapse rates were associated with longer treatment with mericitabine (24 versus 12 weeks), telaprevir-containing regimens, and regimens that included 48 weeks of PegIFN alfa-2a/RBV therapy. No mericitabine resistance mutations were identified in any patient in either trial. The addition of mericitabine did not add to the safety burden associated with either telaprevir or boceprevir-based regimens. These studies demonstrate increased SVR rates and reduced relapse rates in difficult-to-treat patients when a nucleoside polymerase inhibitor with intermediate antiviral potency is added to regimens containing a first-genera- tion PI

Oral contraceptives and the risk of focal nodular hyperplasia of the liver: A case-control study

OBJECTIVE: A role of female hormones, including oral contraceptives, has been suggested in the etiology of focal nodular hyperplasia of the liver. There is, however, no epidemiologic quantification of this relationship. STUDY DESIGN: A hospital-based case-control study was conducted in Italy of 23 women with histologically confirmed focal nodular hyperplasia of the liver and 94 controls in the hospital for acute diseases. Odds ratios (ORs) were computed by use of multiple logistic regression models. RESULTS: Focal nodular hyperplasia was not associated with menstrual and reproductive factors. Ever oral contraceptive use was reported by 83% of cases and 59% of controls. The multivariate OR was 2.8 (95% confidence interval [CI], 0.8-9.4) for ever use, and 4.5 (95% CI, 1.2-16.9) for use 653 years. The trend in risk with duration was statistically significant. CONCLUSIONS: This study confirms previous clinical observations, and provides a quantitative estimate of the association between use of oral contraceptives and focal nodular hyperplasia of the liver

Hepatocellular adenoma in glycogen storage disorder type I: A clinicopathological and molecular study

Aims: Glycogen storage disease type I is a metabolic disorder resulting from deficiency of the glucose-6-phosphate complex. Long-term complications include the development of hepatocellular adenoma (HCA). In this retrospective study, our aim was to reclassify according to geno-phenotypic characteristics nodular lesions identified in hepatectomy specimens of such patients transplanted between 1998 and 2008 at our institution. Methods and results: Clinicopathological data of seven consecutive transplanted patients with glycogen storage disease type I were reviewed. Liver nodules were re-examined histologically and by immunohistochemistry. Molecular analysis was performed additionally in a case with specific features. Four patients had multiple tumours. We concluded that 26 of 38 nodules available for study had features of inflammatory hepatocellular adenomas, seven comprised adenomas not otherwise specified and five were found to be focal nodular hyperplasia. Conclusions: Further studies are needed to clarify the pathogenesis of hepatocellular adenomas in glycogen storage disease; in particular to determine whether they share abnormal metabolic pathways with inflammatory adenomas in the general population. Testing for acute phase proteins may be a helpful tool in the early detection of HCA in such patients. Finally, there is a need to further define their risk of malignant transformation, in relation to age and possible cofactors. © 2012 Blackwell Publishing Ltd