Cutting edge issues in autoimmune hepatitis

Autoimmune hepatitis (AIH) is a severe liver disease affecting all age groups worldwide. Novel basic and clinical aspects of AIH, addressed at a Monothematic Conference in London in September 2015, are highlighted in this review. The diagnosis of AIH relies upon detection of characteristic autoantibodies, hypergammaglobulinemia, and interface hepatitis on liver histology. The International Autoimmune Hepatitis Group (IAIHG) has devised diagnostic scoring systems to help in comparative studies and clinical practice. AIH arises in a genetically predisposed host, when yet unknown triggers – such an encounter with a pathogen – lead to a T cell-mediated immune response targeting liver autoantigens. This immune response is inadequately controlled because regulatory mechanisms are impaired. The mainstay of treatment for AIH is immunosuppression, which should be instituted as soon as the diagnosis is made. Standard treatment regimens include relatively high doses of predniso(lo)ne, which are tapered gradually as azathioprine is introduced. Recent guidelines have described newer treatment regimens and have tightened the goal of therapy to complete normalization of biochemical, serological and histological parameters. Mycophenolate mofetil, calcineurin inhibitors, mTOR inhibitors and biological agents are potential salvage therapies, but should be reserved for selected non-responsive patients and administered only in experienced centers. Liver transplantation is a life-saving option for those patients who progress to end-stage liver disease. Further dissection of cellular and molecular pathways involved in AIH pathogenesis is likely to lead to the discovery of novel, tailored and better tolerated therapies.     

HCV Therapy: Treat now or wait?

The combination of first generation protease inhibitors, telaprevir or boceprevir with pegylated interferon and ribavirin has significantly improved response rates when compared to pegylated interferon and ribavirin alone. While safe and effective for many patients, the potential of current DAA based therapy has been limited by tolerability, especially in those with extensive co-morbidities. Newer therapies, likely with improved efficacy and safety profiles are under development, however the timing of availability of these agents remains speculative. The choice to treat with currently available therapy or to wait for newer therapy is complex. These decisions require understanding of unique patient characteristics as well as safety and efficacy of both available therapy and new therapies undergoing investigation.     

Effectiveness of contrast-enhanced ultrasound for characterisation of intestinal inflammation in Crohn's disease: A comparison with surgical histopathology analysis

BackgroundDifferentiation between predominantly inflammatory versus fibrous-predominant lesions is particularly important in order to decide the optimal therapy in patients with refractory symptoms in Crohn's disease (CD).ObjectiveThe purpose of this investigation was to evaluate the accuracy of several US parameters, especially of contrast-enhanced US, for evaluation of mural inflammation in CD, with histopathology as the reference.Materials and methodsPreoperative ultrasound examination, including contrast-enhanced ultrasound (CEUS) was performed in 25 consecutive patients with Crohn's disease undergoing elective bowel resection. Ultrasound variables, such as wall thickness, transmural complications, colour Doppler grade, quantitative analysis of the enhancement and the presence and severity of strictures, were prospectively evaluated and compared with the histopathology results. Histopathology grading of acute inflammation using the acute inflammatory score and the degree of fibrostenosis was performed in each segment and the results were compared with all the US variables as well as with a previously defined ultrasound score system for inflammatory and fibrostenotic changes.Results28 segments were analysed. In pathology analysis there were 12 predominantly inflammatory segments, 9 predominantly fibrostenotic and 7 compound lesions. When the pathology score was dichotomised into two groups (inflammatory and fibrostenotic) the number of stenoses correctly classified by US was 23 out 28, with a substantial agreement (kappa = 0.632). There was a good correlation between the sonographic and pathology scores, both inflammation (Spearman's, r = 0.53) and fibrostenosis (Spearman's, r = 0.50). Transmural complications, colour Doppler grade and percentage of increase in contrast enhancement were significantly associated with the pathology inflammatory score (p = 0.018, p = 0.036 and p = 0.005, respectively). There was a significantly negative association between the colour Doppler grade and the pathologic fibrostenotic score.ConclusionsUltrasound, including CEUS, can be a useful tool for distinguishing inflammatory from fibrostenotic lesions in CD. This information can be useful in the management of CD.