This study examined the association between dynamic angiopoietin-2 assessment and COVID-19 short- and long-term clinical course. We included consecutive hospitalized patients from 1 February to 31 May 2020 with laboratory-confirmed COVID-19 from 2 Italian tertiary referral centers (derivation cohort, n = 187 patients; validation cohort, n = 62 patients). Serum biomarker levels were measured by sandwich enzyme-linked immunosorbent assay. Lung tissue from 9 patients was stained for angiopoietin-2, Tie2, CD68, and CD34. Cox model was used to identify risk factors for mortality and nonresolving pulmonary condition. Area under the receiver operating characteristic curve (AUROC) was used to assess the accuracy of 3- and 10-day angiopoietin-2 for in-hospital mortality and nonresolving pulmonary condition, respectively. Three-day angiopoietin-2 increase of at least twofold from baseline was significantly associated with in-hospital mortality by multivariate analysis (hazard ratio [HR], 6.69; 95% confidence interval [CI], 1.85-24.19; P = .004) with AUROC = 0.845 (95% CI, 0.725-0.940). Ten-day angiopoietin-2 of at least twofold from baseline was instead significantly associated with nonresolving pulmonary condition by multivariate analysis (HR, 5.33; 95% CI, 1.34-11.77; P ≤ .0001) with AUROC = 0.969 (95% CI, 0.919-1.000). Patients with persistent elevation of 10-day angiopoietin-2 levels showed severe reticular interstitial thickening and fibrous changes on follow-up computed tomography scans. Angiopoietin-2 and Tie2 were diffusely colocalized in small-vessel endothelia and alveolar new vessels and macrophages. Angiopoietin-2 course is strongly associated with COVID-19 in-hospital mortality and nonresolving pulmonary condition. Angiopoietin-2 may be an early and useful predictor of COVID-19 clinical course, and it could be a relevant part of disease pathogenesis. Angiopoietin-2 blockade may be a COVID-19 treatment option.

Vitamin D is a crucial nutrient with many pleiotropic effects on health and various chronic diseases. The purpose of this review is to provide a detailed report on the pathophysiological mechanisms underlying vitamin D deficiency in patients with chronic liver disease, addressing the different liver etiologies and the condition of advanced chronic liver disease (cirrhosis) with related complications. To date, patients with liver disease, regardless of underlying etiology, have been shown to have reduced levels of vitamin D. There is also evidence of the predictive role of vitamin D values in complications and progression of advanced disease. However, specific indications of vitamin D supplementation are not conclusive concerning what is already recommended in the general population. Future studies should make an effort to unify and validate the role of vitamin D supplementation in chronic liver disease.

Hepatitis C virus infection has a substantial effect on morbidity and mortality worldwide because it is a cause of cirrhosis, hepatocellular carcinoma, liver transplantation, and liver-related death. Direct acting antiviral drugs available today have high efficacy and excellent safety and can be used in all patients with clinically evident chronic liver disease and in groups that demonstrate risk behaviors to reduce the spread of infection. The Global Health Strategy of WHO to eliminate hepatitis infection by 2030 assumes “a 90% reduction in new cases of chronic hepatitis C, a 65% reduction in hepatitis C deaths, and treatment of 80% of eligible people with HCV infections”. In this review effective models and strategies for achieving the global elimination of HCV infection are analyzed. The screening strategies must be simple and equally effective in high-risk groups and in the general population; fast and effective models for appropriate diagnosis of liver disease are needed; strategies for direct acting antiviral drug selection must be cost-effective; linkage to care models in populations at risk and in marginalized social classes must be specifically designed and applied; strategies for obtaining an effective vaccine against HCV infection have yet to be developed.

The treatment landscape for hepatitis C virus (HCV) infection has transformed over the past few decades, evolving from the limited efficacy of interferon (IFN) monotherapy to the highly successful pan-genotypic direct-acting antivirals (DAAs) used today. Initially, alpha-interferon monotherapy, introduced in the 1990s, was the standard treatment, yet it provided low sustained virological response (SVR) rates and caused significant adverse effects, limiting its utility. The development of pegylated interferon (peg-IFN) improved the pharmacokinetic profile of IFN, allowing for less frequent dosing and modestly improved response rates. When combined with ribavirin, peg-IFN achieved higher SVR rates, especially in non-genotype 1 HCV infections, but the combination also brought additional side effects, such as anemia and depression. The advent of the first-generation DAAs, such as telaprevir and boceprevir, marked a significant milestone. Combined with peg-IFN and ribavirin, these protease inhibitors boosted response rates in patients with genotype 1 HCV. However, high rates of adverse effects and drug resistance remained challenges. Second-generation DAAs, like sofosbuvir and ledipasvir, introduced IFN-free regimens with improved safety profiles and efficacy. The most recent advances are pan-genotypic DAAs, including glecaprevir-pibrentasvir and sofosbuvir-velpatasvir, which offer high SVR rates across all genotypes, shorter treatment durations, and fewer side effects. Current pan-genotypic regimens represent a cornerstone in HCV therapy, providing an accessible and effective solution globally.

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Background: Vertical transmission of HIV infection may occur during pregnancy, at childbirth or through breastfeeding. Recommendations on the safety of breastfeeding of HIV-infected women on effective antiretroviral treatment are not univocal among international guidelines (WHO 2010, EACS 2017, DHHS 2017), leaving space for variability at the patient’s level. Methods: We collected clinical, laboratory and outcome data from 13 HIV-infected pregnant women who, between March 2017 and June 2021, elected to breastfeed their children against specific medical advice. All mothers were on antiretroviral therapy with darunavir or raltegravir plus emtricitabine/tenofovir disoproxil and remained HIV-RNA undetectable and >400 cells/mmc CD4+ lymphocytes during pregnancy and breastfeeding. Prophylactic antiretroviral therapy (zidovudine for 4 weeks) was started immediately after birth in all newborns. The mean duration of breastfeeding was 5.4 months. Newborns were tested for HIV-RNA multiple times: at birth, 1, 3, and 6 months after birth, and 1, 3 and 6 months after the end of breastfeeding. Results: None of the infants were infected by HIV. Conclusions: Our experience, gathered in the setting of freedom of choice on the patient’s side, while insufficient to address the eventual safety of breastfeeding in HIV-infected mothers since the represented cohort is numerically irrelevant, supports the extension of the U=U (Undetectable Equals Untransmittable) paradigm to this setting. Since breastfeeding is often requested by women with HIV planning pregnancy, more extensive comparative studies should be performed.