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Direct acting antiviral agents (DAAs) have revolutionized the landscape of chronic hepatitis C (CHC) enabling treatment of all those infected. It remains to be determined how the characteristics of those receiving treatment are changing. We retrospectively analysed all the patients with CHC who received treatment with DAAs in a large referral centre since 01/01/2015. We stratified their demographic, clinical and virological characteristics at baseline and the sustained virological response (SVR) rates according to the year of treatment. In the study were included 2565 patients. During the study period, the yearly proportion of men and cirrhotic patients decreased (p <0.001) whereas mean age increased from 59.8 to 62.2 years old (p =0.04). An increasing trend was observed in the foreign-born patients from 4.3% to 7.9%, without reaching statistical significance. The prevalence of comorbidities had also increased during the study period (p <0.001). Instead, the yearly number of experienced patients decreased significantly (p <0.001) as well as the mean MELD score of cirrhotic patients from 9 to 7.6 (p <0.001). SVR rates increased significantly, from 93.4% in 2015 to 97.1% in 2018 (P <0.05). The population of patients with CHC receiving DAAs is becoming older and with more comorbidities. Nevertheless, this did not impact SVR rates. [ABSTRACT FROM AUTHOR]

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Abstract: Purpose: Because the use of IgM and IgA enriched polyclonal intravenous immunoglobulins (eIg) is a standard of care in critically ill patients admitted to our intensive care unit (ICU) with the diagnosis of severe sepsis or septic shock, we investigated if the delay from the onset of severe sepsis and septic shock and their administration could influence the outcome. Materials and Methods: The medical records of all patients with severe sepsis or septic shock admitted to our ICU from July 2004 through October 2009 and treated with eIg (Pentaglobin®; Biotest, Dreieich, Germany) were retrospectively examined. Results: A total of 129 adult patients with severe sepsis or septic shock were considered eligible. Thirty-two percent of patients died during the ICU stay. Survivors were given eIg significantly earlier than nonsurvivors (23 vs 63 hours, P < .05). The delay in the administration of eIg and the Simplified Acute Physiology Score II were the only variables that entered stepwise a propensity score-adjusted logistic model. The delay in the administration of eIg was a significant predictor of the odds of dying during the ICU stay (odds ratio for 1 hour of delay, 1.007; P < .01; 99% confidence interval from 1.001 to 1.010) and proved to be independent from the Simplified Acute Physiology Score II and other variables. Conclusions: The efficacy of eIg, being maximal in early phases of severe sepsis and/or septic shock, is probably time dependent. [Copyright &y& Elsevier]

Background & Aims: The phenotypic and functional characteristics of natural killer (NK) cells in chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are incompletely defined and largely controversial. Methods: We studied NK cell receptor expression, cytotoxic activity, and cytokine production in peripheral blood mononuclear cells from 35 patients with chronic hepatitis C, 22 with chronic hepatitis B, and 30 healthy controls. Results: Patients with chronic HBV infection had an increased proportion of NKG2C+ NK cells with normal inhibitory receptor expression and a lower proportion of activated NK cells compared with HCV+ patients, which was associated with normal or reduced cytolytic activity and markedly dysfunctional tumor necrosis factor-α and interferon-γ production. Patients with chronic HCV infection showed a predominantly activating phenotype, featuring a decreased percentage of cells expressing the inhibitory receptor KIR3DL1 and a concomitant increase in the proportion of NKG2D+ NK cells. Expression of the CD69 early activation antigen on NK cells positively correlated with serum alanine aminotransferase and HCV RNA values, suggesting participation of virus-induced effector NK cells in liver necroinflammation. Phenotypic changes in HCV+ patients were associated with enhanced cytokine-induced cytolytic activity and increased usage of natural cytotoxicity and NKG2D receptor pathways, accompanied by defective cytokine production, although to a lesser extent than patients with chronic HBV infection. Conclusions: These findings provide evidence for a functional dichotomy in patients with chronic HBV and HCV infections, featuring conserved or enhanced cytolytic activity and dysfunctional cytokine production, which may contribute to virus persistence. [Copyright &y& Elsevier]

Background/aims: Cyclosporine A based immunosuppression protocols have improved the results of liver transplantation. However, there is no general agreement concerning the most appropriate initial dose of cyclosporine or the precise moment we should start its administration., Materials and Methods: Two cyclosporine A administration procedures in liver transplantation were analyzed by means of a prospective study using 91 consecutive patients and dividing them into two groups: Group A: 50 consecutive transplants in which cyclosporine was started since the surgery at 4 mg/kg/day, and Group B: the following 41 consecutive transplants in which cyclosporine was started 24 hours after transplantation at 2 mg/kg/day., Results: Cyclosporine levels were higher in Group A in the first month (without significant differences). There were differences in the need for hemodialysis (14% vs 0%, p < 0.01), in the length of time (h) on mechanical ventilation (147.5 +/- 36 vs 48.7 +/- 15.7, p < 0.05) and in the time (d) spent in intensive care (10.5 +/- 1.6 vs 6.5 +/- 0.8, p < 0.05). There were no differences in the incidence of acute rejection, arterial blood pressure, septic and neurological complications, or in the actuarial survival rate for patients and grafts at 36 months., Conclusions: Delayed administration of cyclosporine simplifies the treatment of patients in the first 24 hours, it has several beneficial features and does not appear to be associated with a high acute rejection rate. On the basis of these results, our group has adopted delayed and low-dosage cyclosporine procedure.