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Simple Summary: Few data are available on HCC outcomes in people living with HIV (PLWH), especially regarding HCC treatment and recurrence. We focused our study on survival and recurCitation: Bertoni, C.; Galli, L.; Lolatto, R.; Hasson, H.; Siribelli, A.; Messina, E.; Castagna, A.; Uberti-Foppa, C.; Morsica, G. rence in HCC/PLWH under invasive therapy by considering also associated factors. To the best of our knowledge, this is the first study investigating survival and recurrence in HCC/HIV people who received invasive therapy, showing that HCC/PLWH under invasive therapy can achieve a good 2- and 5-year survival regardless of HCC recurrence or not. We also showed that the best outcome in terms of survival was obtained in transplanted participants. Our findings, although obtained in a small sample size, suggest that HCC/PLWH should have the same treatment opportunities as HIV-negative participants also in terms of re-treatment. As for the counterpart of HIV-uninfected participants, a more aggressive treatment than what was recommended by the BCLC system could be offered after careful selection to HCC/PLWH. Background and Aims: To address the overall survival (OS) and recurrence (RE) in people living with HIV (PLWH) treated with invasive therapy (IT) for hepatocellular carcinoma (HCC). Methods: This is a retrospective cohort study on 41 PLWH with HCC receiving IT, defined as liver resection (LR), orthotopic liver transplantation (OLT), radiofrequency thermo-ablation (RFTA) trans arterial chemo, or radioembolization (CRE). OS and RE were investigated by Kaplan–Meier curves. The Cox proportional hazard regression model was used for multivariate analyses. Results: Recurrence occurred in 46.3% PLWH; in 36.7% of participants at 2 years and in 52% at 5 years from HCC diagnosis; it was less frequent in males, p = 0.036. Overall, 2- and 5-year survival after HCC diagnosis was 72% and 48%, respectively. Two-and five-year survival was 100% and 90.9%, respectively, in PLWH receiving OLT, compared to other IT (60.9% and 30.6%, respectively) log-rank p = 0.0006. Two- and five-year survival in participants with no-RE was 70.5% and 54.6%, respectively, and 73.7% and 42.1% among RE, respectively, log-rank p = 0.7772. By multivariate analysis, AFP at values < 28.8 ng/mL, at HCC diagnosis, was the only factor predicting survival. Conclusions: Fifty percent of PLWH survived five years after HCC diagnosis; 90.9% among OLT patients. Recurrence after IT was observed in 46% of HCC/PLWH. AFP cut-off levels of 28.8 ng/mL were the only independent variable associated with survival. [ABSTRACT FROM AUTHOR]

Resistance-associated substitutions (RASs) may exist prior to treatment and contribute to the failure of treatment with direct-acting antivirals (DAAs). As the major site of HCV replication, naturally occurring variants with RASs may segregate into the liver. In the present study, we performed viral population sequencing to retrospectively investigate the NS3 and NS5A RAS profiles in 34 HIV/HCV coinfected patients naïve to anti-HCV treatment who underwent diagnostic liver biopsy between 2000 and 2006 and had liver and plasma samples available. Sixteen were infected by HCV genotype (GT) 1a, 11 by GT3a, and 7 by GT4d. The analysis of the NS3 domain in GT1a showed a difference in strain between the liver and plasma in three cases, with a preponderance of specific RASs in the liver compartment. In GT4d samples, 6/7 coupled liver and plasma samples were concordant with no RASs. Sequence analysis of the NS5A domain showed the presence of RASs in the livers of 2/16 patients harboring GT1a but not in the corresponding plasma. In GT4d, NS5A RASs were detected in 7/7 liver tissues and 5/7 plasma samples. NS3 domain and NS5A domain were found to be conserved in plasma and livers of patients infected with GT3a. Thus, RASs within GT1a and GT4d more likely segregate into the liver and may explain the emergence of resistant strains during DAA treatment. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 first emerged in China during late 2019 and rapidly spread all over the world. Alterations in the inflammatory cytokines pathway represent a strong signature during SARS-COV-2 infection and correlate with poor prognosis and severity of the illness. The hyper-activation of the immune system results in an acute severe systemic inflammatory response named cytokine release syndrome (CRS). No effective prophylactic or post-exposure treatments are available, although some anti-inflammatory compounds are currently in clinical trials. Studies of plant extracts and natural compounds show that polyphenols can play a beneficial role in the prevention and the progress of chronic diseases related to inflammation. The aim of this manuscript is to review the published background on the possible effectiveness of polyphenols to fight SARS-COV-2 infection, contributing to the reduction of inflammation. Here, some of the anti-inflammatory therapies are discussed and although great progress has been made though this year, there is no proven cytokine blocking agents for COVID currently used in clinical practice. In this regard, bioactive phytochemicals such as polyphenols may become promising tools to be used as adjuvants in the treatment of SARS-CoV-2 infection. Such nutrients, with anti-inflammatory and antioxidant properties, associated to classical anti-inflammatory drugs, could help in reducing the inflammation in patients with COVID-19. [ABSTRACT FROM AUTHOR]

We prospectively evaluated the frequency of natural resistance-associated substitutions (RASs) in the NS3 and NS5A regions according to different HCV genotypes and their possible effect on treatment outcome in HIV-1/HCV patients treated with direct-acting antivirals (DAAs). Baseline RASs in the NS3 and NS5A domains were investigated in 62 HIV-1/HCV patients treated with DAAs: 23 patients harbored HCV-GT1a, 26 harbored GT3a, and 13 harbored GT4d. A higher occurrence of RASs was found in the NS3 domain within GT1a (13/23) than GT3a (0/26) or GT4d (2/13). With regard to treatment outcome, NS3 RASs were detected in 14/56 patients with sustained virological response (SVR) and in 1/6 non-responder (NR) patients. Occurrence of RASs of NS5A domain was lower in SVR (4/56, had RASs) than in NR (3/6, had RASs). Evaluation of RASs at baseline instead of at virological failure, especially in the NS5A domain, could positively influence the choice of new DAA combinations for the treatment of HIV-1/HCV patients. [ABSTRACT FROM AUTHOR]

Background: Little is known about the frequency or geographic distributions of naturally occurring resistance-associated substitutions (RASs) in the nonstructural protein 5A (NS5A) domain of hepatitis-C virus (HCV) genotype-3 (GT-3) different subtypes. We investigated naturally occurring GT-3 RASs that confer resistance to NS5A inhibitors. Methods: From a publicly accessible database, we retrieved 58 complete GT-3 genomes and an additional 731 worldwide NS5A sequences from patients infected with GT-3 that were naive to direct-acting antiviral treatment. Results: We performed a phylogenetic analysis of NS5A domains in complete HCV genomes to determine more precisely HCV-GT-3 subtypes, based on commonly used target regions (e.g., 5′untranslated region and NS5B partial domain). Among 789 NS5A sequences, GT-3nonA subtypes were more prevalent in Asia than in other geographic regions (p < 0.0001). The A30K RAS was detected more frequently in HCV GT-3nonA (84.6%) than in GT-3A subtypes (0.8%), and the amino acid change was polymorphic in isolates from Asia. Conclusions: These results provided information on the accuracy of HCV-3 subtyping with a phylogenetic analysis of the NS5A domain with data from the Los Alamos HCV genome database. This information and the worldwide geographic distribution of RASs according to HCV GT-3 subtypes are crucial steps in meeting the challenges of treating HCV GT-3. [ABSTRACT FROM AUTHOR]

Different HCV subtypes may naturally harbor different resistance selection to anti-NS5a inhibitors. 2761 sequences retrieved from the Los Alamos HCV database were analyzed in the NS5a domain 1, the target of NS5a inhibitors. The NS5a resistance-associated polymorphisms (RAPs) were more frequently detected in HCV G1b compared to G1a. The prevalence of polymorphisms associated with cross-resistance to compounds in clinical use (daclatasvir, DCV, ledipasvir, LDV, ombitasvir, and OMV) or scheduled to come into clinical use in the near future (IDX719, elbasvir, and ELV) was higher in G1b compared to G1a (37/1552 (2.4%) in 1b sequences and 15/1209 (1.2%) in 1a isolates, p = 0.040). Interestingly, on the basis of the genotype-specific resistance pattern, 95 (6.1%) G1b sequences had L31M RAP to DCV/IDX719, while 6 sequences of G1a (0.5%) harbored L31M RAP, conferring resistance to DCV/LDV/IDX719/ELV (p < 0.0001). Finally, 28 (2.3%) G1a and none of G1b isolates harbored M28V RAP to OMV (p < 0.0001). In conclusion, the pattern of subtype-specific resistance selection in the naturally occurring strains may guide the treatment option in association with direct acting antivirals (DAAs) targeting different regions, particularly in patients that are difficult to cure, such as those with advanced liver disease or individuals who have failed previous DAAs.