Background The relationship between intestinal epithelial integrity and the development of intestinal disease is of increasing interest. A reduction in mucosal integrity has been associated with ulcerative colitis, Crohn’s disease and potentially could have links with colorectal cancer development. The Ussing chamber system can be utilised as a valuable tool for measuring gut integrity. Here we describe step-by-step methodology required to measure intestinal permeability of both mouse and human colonic tissue samples ex vivo, using the latest equipment and software. This system can be modified to accommodate other tissues. Methods An Ussing chamber was constructed and adapted to support both mouse and human tissue to measure intestinal permeability, using paracellular flux and electrical measurements. Two mouse models of intestinal inflammation (dextran sodium sulphate treatment and T regulatory cell depletion using C57BL/6-FoxP3 DTR mice) were used to validate the system along with human colonic biopsy samples. Results Distinct regional differences in permeability were consistently identified within mouse and healthy human colon. In particular, mice showed increased permeability in the mid colonic region. In humans the left colon is more permeable than the right. Furthermore, inflammatory conditions induced chemically or due to autoimmunity reduced intestinal integrity, validating the use of the system. Conclusions The Ussing chamber has been used for many years to measure barrier function. However, a clear and informative methods paper describing the setup of modern equipment and step-by-step procedure to measure mouse and human intestinal permeability isn’t available. The Ussing chamber system methodology we describe provides such detail to guide investigation of gut integrity. Electronic supplementary material The online version of this article (10.1186/s12876-019-1002-4) contains supplementary material, which is available to authorized users.

Graphical abstract Highlights• Study of rituximab therapy in 22 patients with autoimmune hepatitis over a follow-up period of 24 months.• No serious adverse events were noted during followup in patients treated with rituximab.• Rituximab therapy improved liver enzymes significantly during the 2 years of follow-up.• Prednisolone dose reductions were seen in 62% of patients at 12-month follow-up.• A total of 71% of patients were free of AIH flares during the 24 months of follow-up. Lay summaryAutoimmune hepatitis is an autoimmune condition of the liver, usually treated with medications that suppress the immune system, such as steroids. However, some patients do not respond to this treatment. We analysed the safety and efficacy of rituximab in patients who were not responding to firstor second-line therapies. Rituximab was safe and improved liver blood tests in 70% of patients over a 2-year follow-up period, while enabling steroid doses to be reduced in two-thirds of patients, which is a very positive clinical outcome.Background & Aims: Treatment options remain limited for patients with autoimmune hepatitis (AIH), while there are still concerns over the consequences of long-term corticosteroid use. A few studies have suggested a role for B cell-driven autoimmune liver injury in AIH. This multicentre, international retrospective cohort study from the International Autoimmune Hepatitis Group aims to evaluate the clinical efficacy and safety of rituximab in difficult-to-manage AIH.Methods: Clinical data from 22 patients who received rituximab between 2007 and 2017 were collected from centres in the United Kingdom, Germany and Canada. Clinical response was assessed using changes in biochemical and immunological parameters up to 24 months post-rituximab infusion. In addition, we compared the doses of prednisolone used 3 months before and 12 months after treatment, and assessed freedom from AIH flares over the post-treatment period.Results: Twenty-two patients with type-1 AIH were included, with a median age of 40 years at diagnosis (range 19-79); 15/22 (68%) were female and 18/22 (82%) were Caucasian. The median period from diagnosis to the end of follow-up in these patients was 11 years (range 3-28). Values of alanine aminotransferase, aspartate aminotransferase and albumin improved significantly following rituximab therapy, and were sustained for up to 2 years (all p <0.001). Prednisolone doses were significantly reduced by 12 months post-treatment (p = 0.003), with 13/21 (62%) patients having a dose reduction. Over a median post-treatment follow-up period of 6 years (range 1-10), 5 patients developed AIH flares at a median of 22 months post-treatment, giving an estimated 71% freedom from AIH flare at 2 years. Four of these patients received a second course of treatment, of whom 2 had subsequent further flares. No serious adverse events attributable to rituximab were recorded. Conclusion:In patients with difficult-to-manage AIH, rituximab appears to be clinically effective and well tolerated. Rituximab was associated w...

Patients with two-zone devices received more shocks without any mortality benefit.

An update on the management of cholestatic liver diseases Authors: Gautham Appanna A and Yiannis Kallis B Cholestatic liver diseases are a challenging spectrum of conditions arising from damage to bile ducts, leading to build-up of bile acids and inflammatory processes that cause injury to cholangiocytes and hepatocytes. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are the two most common cholestatic disorders. In this review we detail the latest guidelines for the diagnosis and management of patients with these two conditions.

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