The current epidemic of non-alcoholic fatty liver disease (NAFLD) is reshaping the field of hepatology all around the world. The widespread diffusion of metabolic risk factors such as obesity, type2-diabetes mellitus, and dyslipidemia has led to a worldwide diffusion of NAFLD. In parallel to the increased availability of effective anti-viral agents, NAFLD is rapidly becoming the most common cause of chronic liver disease in Western Countries, and a similar trend is expected in Eastern Countries in the next years. This epidemic and its consequences have prompted experts from all over the word in identifying effective strategies for the diagnosis, management, and treatment of NAFLD. Different scientific societies from Europe, America, and Asia-Pacific regions have proposed guidelines based on the most recent evidence about NAFLD. These guidelines are consistent with the key elements in the management of NAFLD, but still, show significant difference about some critical points. We reviewed the current literature in English language to identify the most recent scientific guidelines about NAFLD with the aim to find and critically analyse the main differences. We distinguished guidelines from 5 different scientific societies whose reputation is worldwide recognised and who are representative of the clinical practice in different geographical regions. Differences were noted in: the definition of NAFLD, the opportunity of NAFLD screening in high-risk patients, the non-invasive test proposed for the diagnosis of NAFLD and the identification of NAFLD patients with advanced fibrosis, in the follow-up protocols and, finally, in the treatment strategy (especially in the proposed pharmacological management). These difference have been discussed in the light of the possible evolution of the scenario of NAFLD in the next years.

Immunotolerance is maintained by regulatory T cells (Tregs), including CD4 1 CD25 hi , CD8 1 CD28 2 , cd, and CD3 1 CD56 1 [natural killer T (NKT)] cells. CD4 1 CD25 hi cells are impaired in children with autoimmune hepatitis (AIH). Little is known about Tregs in adults with AIH. The aim of this study was to investigate the frequency and function of Treg subsets in adult patients with AIH during periods of active disease and remission. Forty-seven AIH patients (16 with active disease and 31 in remission) and 28 healthy controls were studied. Flow cytometry was used to evaluate surface markers and functionrelated intracellular molecules in cd, CD8 1 CD28 2 , NKT, and CD4 1 CD25 hi cells. CD4 1 CD25 hi T cell function was determined by the ability to suppress proliferation and interferon gamma (IFN-c) production by CD4 1 CD25 2 target cells. Liver forkhead box P3-positive (FOXP3 1 ) cells were sought by immunohistochemistry. In AIH patients, particularly during active disease, CD4 1 CD25 hi T cells were fewer, expressed lower levels of FOXP3, and were less effective at inhibiting target cell proliferation versus healthy controls. Moreover, although the numbers of CD8 1 CD28 2 T cells were similar in AIH patients and healthy controls, NKT cells were numerically reduced, especially during active disease, and produced lower quantities of the immunoregulatory cytokine interleukin-4 versus controls. In contrast, cd T cells in AIH patients were more numerous versus healthy controls and had an inverted Vd1/Vd2 ratio and higher IFN-c and granzyme B production; the latter was correlated to biochemical indices of liver damage. There were few FOXP3 1 cells within the portal tract inflammatory infiltrate. Conclusion: Our data show that the defect in immunoregulation in adult AIH is complex, and cd T cells are likely to be effectors of liver damage. (HEPATOLOGY 2010;52:999-1007) A utoimmune hepatitis (AIH) is an immunemediated liver disease characterized by high levels of aminotransferases and gamma-globulins, circulating autoantibodies, and histological evidence of interface hepatitis. 1-3 Two AIH subsets are conventionally recognized according to their autoantibody profile 4 : type 1 AIH (AIH-1), which is characterized by positivity for anti-nuclear antibody (ANA) and/or

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