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Background and aims. Hepatitis C virus (HCV) elimination for Italy is an ambitious,but achievable goal. In Italy, there is political will, which aims to achieve the World HealthOrganization (WHO) elimination goals recognizing the need to identify undiagnosed individuals in key high-risk groups and in the general population, however there is concernregarding HCV treatment implementation in Italian Regions.Methods. A modelling analysis was conducted, using the "Italy Polaris" model, to forecastthe impact of different HCV treatment rates in achieving the HCV elimination goals inItaly. The model assessed two treatment scenarios: 2018 Scenario and 2019 Scenario, usingthe annually HCV treatment rate in Italy.Results. Considering a high treatment rate, as assumed by the 2018 Scenario, all HCVelimination targets would be achieved. Considering the 2019 Scenario, in which a decreasingnumber of newly diagnosed individuals and as consequence, a decline in thenumber of treated patients, were assumed, only the 65% HCV mortality reduction wouldbe an achievable goal in Italy. The other elimination targets could be achievable over 7years later than the year 2030.Conclusions. Establishing an ad hoc fund for DAAs for each Italian Region, binding resourcesboth for case finding, through active screening and activities for rapid linkage tocare and treatment, is of paramount importance, in order to keep Italy on track to achievethe WHO elimination targets by 2030.

Metabolic associated fatty liver disease (MAFLD) is the most prevalent liver disease in Western nations, with high heritability. A recent study of Japanese patients with the disease suggested that TLL1 rs17047200 is associated with fibrosis; whether a similar association is observed in Caucasian patients with MAFLD is unknown. We investigated the association of the TLL1 rs17047200 polymorphism with liver fibrosis in a cohort of Caucasian patients with MAFLD (n = 728). We also investigated whether TLL1 expression is altered during liver injury in humans, in murine models of fibrosis, and in in-vitro. While TLL1 expression is upregulated in the liver of humans with MAFLD and in mice, the rs17047200 variant was not associated with fibrosis or any other histological features, or with hepatic TLL1 expression. In conclusion, the TLL1 rs17047200 variant is not a risk variant for fibrosis in Caucasian patients with MAFLD. However, TLL1 could be involved in the pathogenesis of liver fibrosis. ; ME and JG are supported by the Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney; National Health and Medical Research Council of Australia (NHMRC) Program Grants (1053206 and 1149976) and Project grants (1107178 and 1108422). EB is supported by Horizon 2020 under grant 634413 for the project EPoS. AB is supported by an Australian Government Research Training Program (RTP) scholarship.

This article also appears in: Health, Medical, and Life Sciences Virtual Issue for Advanced Science. ; Fibroblast growth factor 21 (FGF21) is a liver-derived hormone with pleiotropic beneficial effects on metabolism. Paradoxically, FGF21 levels are elevated in metabolic diseases. Interventions that restore metabolic homeostasis reduce FGF21. Whether abnormalities in FGF21 secretion or resistance in peripheral tissues is the initiating factor in altering FGF21 levels and function in humans is unknown. A genetic approach is used to help resolve this paradox. The authors demonstrate that the primary event in dysmetabolic phenotypes is the elevation of FGF21 secretion. The latter is regulated by translational reprogramming in a genotype- and context-dependent manner. To relate the findings to tissues outcomes, the minor (A) allele of rs838133 is shown to be associated with increased hepatic inflammation in patients with metabolic associated fatty liver disease. The results here highlight a dominant role for translation of the FGF21 protein to explain variations in blood levels that is at least partially inherited. These results provide a framework for translational reprogramming of FGF21 to treat metabolic diseases. ; M.E. and J.G. were supported by the Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney; a National Health and Medical Research Council of Australia (NHMRC) Program Grant (APP1053206) and Project and ideas grants (APP2001692, APP1107178 and APP1108422). A.B. was supported by an Australian Government Research Training Program (RTP) scholarship. E.B. was supported by Horizon 2020 under grant 634413 for the project EPoS.