et al. / Digestive and Liver Disease xxx (2019) xxx-xxxpaid particular attention to practical issues with the aim to support gastroenterologists in their clinical practice when dealing with patients with anaemia.

The diet of industrialized nations may contribute to the pathogenesis of both ulcerative colitis (UC) and Crohn disease (CD). Malnutrition is relatively unusual in UC, but in CD, which often affects the small intestine, it is frequent and may be severe. Nutrition support is therefore frequently indicated. First principles of artificial nutrition can be applied effectively using the gut whenever possible. Parenteral nutrition is generally required only in those with short bowel syndrome. An increasing literature (especially in pediatrics) favors the use of defined exclusive enteral nutrition (EN) in the primary treatment of active CD. Controlled trials are, however, lacking, and recommendations are accordingly not of the highest rank. It appears that in this context, simple polymeric regimens are usually sufficient, and there is currently insufficient evidence to make a strong recommendation for disease-specific feeds. In the maintenance of remission in CD, controlled data demonstrate that defined EN reduces the risk of relapse requiring steroid treatment. There are no data in support of primary nutrition therapy in UC either in management of the acute flare or in maintenance. In conclusion, nutrition therapy in adults with inflammatory bowel disease is probably both undervalued and underused, but the evidence base needs to be strengthened to confirm its efficacy, determine better those patients most likely to benefit, and optimize the regimens to be employed.

The genetic diversity of hepatitis B virus (HBV) strains has evolved through mutations such as point mutations, deletions or insertions, and recombination. We identified and characterized a novel type of mutation which is a complex of external insertion, deletion, and internal duplication in sequences from one of six patients with chronic hepatitis B virus genotype E (HBV/E). We provisionally named this mutation a "replacement mutation"; the core promoter upstream regulatory sequence/basic core promoter was replaced with a part of the S1 promoter covering the hepatocyte nuclear factor 1 (HNF1) binding site, followed by a tandem repeat of the HNF1 site. A longitudinal analysis of the HBV population over 6 years showed the clonal change from wild-type HBV/E to replacement-mutant type, resulting in a lower hepatitis B (HB) e antigen titer, a high HBV DNA level in serum, and progression of liver fibrosis. In an in vitro study using a replication model, the replacement-mutant HBV showed higher replication levels than the wild-type HBV/E replicon, probably mediated by altered transcription factor binding. Additionally, this HNF1 site replacement mutation was associated with excessive HB nucleocapsid protein expression in hepatocytes, in both in vivo and in vitro studies. This novel mutation may be specific to HBV genotype E, and its prevalence requires further investigation.

Genetic variability of HCV-1a NS5A does not predict responsiveness to IFN- alpha . Differences in early kinetics during combination therapy are not due to selection of IFN-resistant HCV strains.