Increased recurrence rates of hepatocellular carcinoma after DAA therapy in a hepatitis C-infected Egyptian cohort: A comparative analysis.

In Egypt, hepatocellular carcinoma (HCC) is the most common form of cancer and direct-acting antivirals (DAA) are administered on a large scale to patients with chronic HCV infection to reduce the risk. In this unique setting, we aimed to determine the association of DAA exposure with early-phase HCC recurrence in patients with a history of HCV-related liver cancer. This was a prospective cohort study of an HCV-infected population from one Egyptian specialized HCC management centre starting from the time of successful HCC intervention. The incidence rates of HCC recurrence between DAA-exposed and nonexposed patients were compared, starting from date of HCC complete radiological response and censoring after 2 years. DAA exposure was treated as time varying. Two Poisson regressions models were used to control for potential differences in the exposed and nonexposed group; multivariable adjustment and balancing using inverse probability of treatment weighting (IPTW). We included 116 patients: 53 treated with DAAs and 63 not treated with DAAs. There was 37.7% and 25.4% recurrence in each group after a median of 16.0 and 23.0 months of follow-up, respectively. Poisson regression using IPTW demonstrated an association between DAAs and HCC recurrence with an incidence rate ratio of 3.83 (95% CI: 2.02-7.25), which was similar in the multivariable-adjusted model and various sensitivity analyses. These results add important evidence towards the possible role of DAAs in HCC recurrence and stress the need for further mechanistic studies and clinical trials to accurately confirm this role and to identify patient characteristics that may be associated with this event.

Effect of grain size and microporosity on the in vivo behaviour of ß-tricalcium phosphate scaffolds.

Defining the most adequate architecture of a bone substitute scaffold is a topic that has received much attention over the last 40 years. However, contradictory results exist on the effect of grain size and microporosity. Therefore, the aim of this study was to determine the effect of these two factors on the in vivo behaviour of ß-tricalcium phosphate (ß-TCP) scaffolds. For that purpose, ß-TCP scaffolds were produced with roughly the same macropore size (≈ 150 µm), and porosity (≈ 80 %), but two levels of microporosity (low: 10 % / high: ≈ 25 %) and grain size (small: 1.3 µm /large: ≈ 3.3 µm). The sample architecture was characterised extensively using materialography, Hg porosimetry, micro-computed tomography (µCT), and nitrogen adsorption. The scaffolds were implanted for 2, 4 and 8 weeks in a cylindrical 5-wall cancellous bone defect in sheep. The histological, histomorphometrical and µCT analysis of the samples revealed that all four scaffold types were almost completely resorbed within 8 weeks and replaced by new bone. Despite the three-fold difference in microporosity and grain size, very few biological differences were observed. The only significant effect at p < 0.01 was a slightly faster resorption rate and soft tissue formation between 4 and 8 weeks of implantation when microporosity was increased. Past and present results suggest that the biological response of this particular defect is not very sensitive towards physico-chemical differences of resorbable bone graft substitutes. As bone formed not only in the macropores but also in the micropores, a closer study at the microscopic and localised effects is necessary.