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Background An unexpected increased HCC recurrence and occurrence rate among HCV patients treated with direct acting antivirals combination has been reported. Aim of the study was the evaluation of early HCC occurrence rate and its risk factors in a HCV infected population, treated with direct-acting-antivirals. Methods According to the Italian ministerial guidelines for direct-acting-antivirals treatment, 1022 consecutive HCV patients treated with direct-acting-antivirals were enrolled. Patients either with active HCC at imaging or history of previous treated HCC, HBV or HIV co-infection, or liver transplant recipients were excluded. The SVR, defined as the persistent absence of detectable serum HCV-RNA 12 weeks after the end of treatment (SVR12), was assessed for all enrolled patients. Abdominal ultrasound was performed before starting antiviral therapy, and repeated every 6 months. HCC was diagnosed according to the international guidelines. Patients showing either nodular patterns suggestive of HCC or with uncertain dynamic vascular behaviour were excluded from a further follow-up. Results Nine hundred and eighty-five patients completed the 48 weeks follow-up after the end of treatment. A Sofosbuvir-based regimen was administered in the 74.9% of patients, among whom, the 71.6% underwent a simultaneous Ribavirin administration. A sustained virological response at 12 weeks off treatment was documented in 966 patients (98.2%). During the post treatment follow-up HCC was detected in 35 patients, with a cumulative incidence rate of the 3.55%. At multivariate analysis, four variables resulted independently associated with HCC development, both in a cirrhosis based and a class B Child based model, respectively: cirrhosis/class B Child, therapeutic schedule including Sofosbuvir without Ribavirin, liver stiffness values, male gender and presence of diabetes. A multivariate analysis performed on Child A cirrhotic patients, showed that Sofosbuvir based therapeutic treatment without Ribavirin had a HCC occurrence 5.7 higher than Ribavirin-based schedules with or without Sofosbuvir (p < 0.0001, OR: 5.686, 95% CI 2.455–13.169). Conclusions Our data suggest that early HCC occurrence appears more frequently related to Sofosbuvir-based therapy without Ribavirin which, indeed, seems to play a protective role on HCC onset. Therefore, a careful follow-up should be mandatory, especially in those regimens including Sofosbuvir without Ribavirin.

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Purpose Invasive mould infections, in particular invasive aspergillosis (IA), are comparatively frequent complications of immunosuppression in patients undergoing solid organ transplantation (SOT). Guidelines provide recommendations as to the procedures to be carried out to diagnose and treat IA, but only limited advice for SOT recipients. Methods Literature review and expert consensus summarising the existing evidence related to prophylaxis, diagnosis, treatment and assessment of response to IA and infections by Mucorales in SOT patients Results Response to therapy should be assessed early and at regular intervals. No indications of improvement should lead to a prompt change of the antifungal treatment, to account for possible infections by Mucorales or other moulds such as Scedosporium. Imaging techniques, especially CT scan and possibly angiography carried out at regular intervals during early and long-term follow-up and coupled with a careful clinical diagnostic workout, should be evaluated as diagnostic tools and outcome predictors, and standardised to improve therapy monitoring. The role of biomarkers such as the galactomannan test and PCR, as well as selected inflammation parameters, has not yet been definitively assessed in the SOT population and needs to be studied further. The therapeutic workup should consider a reduction of immunosuppressive therapy. Conclusions The role of immunosuppression and immune tolerance mechanisms in the response to invasive fungal infection treatment is an important factor in the SOT population and should not be underestimated. The choice of the antifungal should consider not only their toxicity but also their effects on the immune system, two features that are intertwined.

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