Hepatitis C virus eradication in people living with human immunodeficiency virus: Where are we now?

Hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV, according to World Health Organization. People living with HIV (PLWH) are six times greater affected by HCV, compared to HIV negative ones; the greater prevalence is encountered among people who inject drugs and men who have sex with men: the risk of HCV transmission through sexual contact in this setting can be increased by HIV infection. These patients experience a high rate of chronic hepatitis, which if left untreated progresses to end-stage liver disease and hepatocellular carcinoma (HCC) HIV infection increases the risk of mother to child vertical transmission of HCV. No vaccination against both infections is still available. There is an interplay between HIV and HCV infections. Treatment of HCV is nowadays based on direct acting antivirals (DAAs), HCV treatment plays a key role in limiting the progression of liver disease and reducing the risk of HCC development in mono- and coinfected individuals, especially when used at an early stage of fibrosis, reducing liver disease mortality and morbidity. Since the sustained virological response at week 12 rates were observed in PLWH after HCV eradication, the AASLD has revised its simplified HCV treatment algorithm to also include individuals living with HIV. HCV eradication can determine dyslipidemia, since HCV promotes changes in serum lipid profiles and may influence lipid metabolism. In addition to these apparent detrimental effects on the lipid profile, the efficacy of DAA in HCV/HIV patients needs to be considered in light of its effects on glucose metabolism mediated by improvements in liver function. The aim of the present editorial is to describe the advancement in HCV treatment among PLWH.

Hepatitis B virus infection reactivation in patients under immunosuppressive therapies: Pathogenesis, screening, prevention and treatment.

With a 5.3% of the global population involved, hepatitis B virus (HBV) is a major public health challenge requiring an urgent response. After a possible acute phase, the natural history of HBV infection can progress in chronicity. Patients with overt or occult HBV infection can undergo HBV reactivation (HBVr) in course of immunosuppressive treatments that, apart from oncological and hem-atological diseases, are also used in rheumatologic, gastrointestinal, neurological and dermatological settings, as well as to treat severe acute respiratory syndrome coronavirus 2 infection. The risk of HBV reactivation is related to the immune status of the patient and the baseline HBV infection condition. The aim of the present paper is to investigate the risk of HBVr in those not oncological settings in order to suggest strategies for preventing and treating this occurrence. The main studies about HBVr for patients with occult hepatitis B infection and chronic HBV infection affected by non-oncologic diseases eligible for immunosuppressive treatment have been analyzed. The occurrence of this challenging event can be reduced screening the population eligible for immunosuppressant to assess the best strategies according to any virological status. Further prospective studies are needed to increase data on the risk of HBVr related to newer immunomodulant agents employed in non-oncological setting.

Safety of direct acting antiviral treatment for hepatitis C in oncologic setting: A clinical experience and a literature review.

With a globally estimated 58 million people affected by, chronic hepatitis C virus (HCV) infection still represents a hard challenge for scientific community. A chronic course can occur among patients with a weak innate ad adaptive response with cirrhosis and malignancies as main consequences. Oncologic patients undergoing chemotherapy represent a special immunocompromised population predisposed to HCV reactivation (HCVr) with undesirable changes in cancer treatment and outcome. Aim of the study highlight the possibility of HCVr in oncologic population eligible to chemotherapy and its threatening consequences on cancer treatment; underline the importance of HCV screening before oncologic therapy and the utility of direct aging antivirals (DAAs). A comprehensive overview of scientific literature has been made. Terms searched in PubMed were: "HCV reactivation in oncologic setting" "HCV screening", "second generation DAAs". Pharmacokinetic and Pharmacodynamics characteristics of DAAs are reported, along with drug - drug interactions among chemotherapeutic drug classes regimens and DAAs. Clinical trials conducted among oncologic adults with HCV infection eligible to both chemotherapy and DAAs were analyzed. Viral eradication with DAAs in oncologic patients affected by HCV infection is safe and helps liver recovery, allowing the initiation of cancer treatment no compromising its course and success.

Are nucleotide inhibitors, already used for treating hepatitis C virus infection, a potential option for the treatment of COVID-19 compared with standard of care? A literature review.

Coronavirus disease 2019 (COVID-19) is global pandemic with various clinical presentations, ranging from cold to sometimes unrecoverable acute respiratory distress syndrome. Although urgently needed, currently there are no specific treatments for COVID-19. Repurposing existing pharmaceuticals to treat COVID-19 is crucial to control the pandemic. In silico and in vitro studies suggest that a nucleotide inhibitor called Sofosbuvir, has also antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), apart from suppressing other positive-strand ribonucleic Acid viruses with conserved polymerase (hepatitis C virus). The aim of this study was to assess if Sofosbuvir improves clinical outcomes in patients with moderate or severe COVID-19. A compre-hensive overview of scientific literature has been made. Terms searched in PubMed were: COVID-19, SARS-CoV-2, nucleotide inhibitors, pandemic, Sofosbuvir. Results clinical trials conducted among adults with moderate or severe COVID-19 were analyzed. Patients were divided in treatment and control arms, receiving Sofosbuvir plus standard care and standard care alone respectively. The addition of Sofosbuvir to standard care significantly reduced the duration of hospital stay compared with standard care alone in clinical trials examined. If efficacy of these repurposed, cheap and easily available drug against SARS-CoV-2 is further demonstrated, it could be essential to refine the treatment of COVID-19.

Experimental Pharmacotherapy for COVID-19: The Latest Advances.

The coronavirus infectious disease-2019 (COVID-19) has overwhelmed like a shock wave in a completely unprepared world. Despite coronavirus infections were involved in previous epidemic outbreaks, no antiviral agent was developed for specific treatment. As a consequence, since the beginning of this pandemic, both repositioned and experimental drugs were used to treat the infected patients without evidence of clinical efficacy. Just based on experience coming from the use of antiviral agents to treat other viruses (eg, lopinavir/ritonavir, remdesivir) and supposed antiviral or immunomodulatory activities of drugs with no approved antiviral indications (eg hydroxychloroquine, tocilizumab), clinicians have faced the ongoing pandemic. Currently, after about 9 months from the COVID-19 spread, there is still no antiviral agent capable of ensuring the cure of this syndrome. Clinical trials are beginning to confirm the benefits of some drugs, while for other compounds, efficacy and safety have not yet been confirmed. Randomized clinical trials (RCT) have denied or downsized the beneficial effects attributed to certain molecules, such as aminoquinolines, largely used in clinical practice at the beginning of COVID-19 spread. Conversely, at the same time, they have provided evidence for unexpected effectiveness of other agents that have been underutilized, such as steroids, which were not used in SARS treatment because of the threatened effect on viral replication. Evidence deriving from pathologic studies have demonstrated that the prothrombotic effects of SARS-CoV-2 can be prevented by heparin prophylaxis, underlining the need for personalized treatment for patients with severe disease. The main aim of this review is to synthesize the available information and evidence on both repositioned and experimental drugs for the treatment of COVID-19, focusing on the need to exercise caution on the use of unproven medical therapies.

Emerging antibiotic resistance: carbapenemase-producing enterobacteria. Bad new bugs, still no new drugs.

Antimicrobial resistance (AMR) is a global health security threat requiring actions across government sectors and society. Many factors are involved in this phenomenon, being overuse of antibiotics, incorrect antibiotic prophylaxis, and use of antibiotics for zootechnic reasons the main causes of the increasing rate of multi-drug resistant (MDR) bacteria. The impact of resistance to antimicrobials is an important threat due also to the emergence of MDR Gram-negative bacteria resistant to carbapenems, and the lack of the research for new active molecules. The production of extended spectrum beta-lactamase enzymes has been the first threatening mechanism for Gram-negative resistance to antibiotics, which prompted the development of new classes of antibiotics such as carbapenems. Unfortunately, resistance to carbapenems developed because of multiple mechanisms including efflux pumps, porin mutations and enzyme production, being the latter particularly relevant in terms of diffusion due to the genes located within plasmids that drive their horizontal diffusion. In this scenario, antimicrobial stewardship programs (ASP) are a mandatory resource in fighting the resistance spread. The reduction of total amount of antibiotics administration in the hospital setting and guiding prescribers in the correct administration of antibiotics for the smallest period possible, at the correct dosage, can be defined as the first goals of an ASP. Anyway, in an efficacious ASP, apart from antibiotic administration, efforts must been made in ensuring the lowest probability of spreading of MDR by efficacious measures of isolation of carriers, and by offering tools for a rapid diagnosis of viral infections avoiding the administration of unnecessary antibiotics. A continuous audit of the ASP programs and a correct assessment of the allergy to drugs such as penicillin have to complete the program. Currently, only a few options are available for patients with an infection sustained by Gram-negative MDR bacteria. All the options actually available are based on the administration of colystin, an old drug whose real efficacy is reduced due to its relevant toxicity, or on the administration of recently proposed drugs such as ceftolozane-tazobactam, ceftazidime-avibactam and meropenem-vaborbactam. All these new drugs do not have a novel mechanism of action and have limited spectrum in term of activity against MDR bacteria. In conclusion, antimicrobial resistance is a global emergence and AMP is the most powerful tool actually available. Few limited options are available to treat infections due to Carbapenem Resistant Enterobacteria. Antimicrobial molecules with true novel mechanism of action are needed to win the fight against antimicrobial resistance.

Risk of professional accidental exposure to biological agents in health care workers: a retrospective analysis carried out in a southern Italian tertiary hospital.

Worldwide the needlestick injuries of health care workers (HCWs) still represent a major health problem. The authors aimed to evaluate the risk of HCW needlestick injuries in a tertiary university hospital in southern Italy in relation to some HCW characteristics (age, sex, professional profile, work department) and the source of infection. All HCWs of the University Hospital "Federico II" in Naples, Italy, attending the Infectious Diseases Unit after potential accidental contact to blood-borne viruses through needlestick injuries were enrolled during a 22-year period. HCWs underwent clinical analysis and were administered a specific questionnaire to collect (in anonymous fashion) data about age, sex, professional profile and work department. From 1995 to 2016 1,477 needlestick injuries in the same number of people (one accident per person) were recorded by our service. The HCWs were predominately males (n = 806, 55%) and the mean age was 39.4 years (±10.1 SD). The job categories most involved were: physicians (41%), followed by nurses (33%) and healthcare assistants (HCAs, 10%). The incidence proportion was calculated for these highest-risk categories in three defined time points (at the beginning, in the middle and at the end of the study period): 104/2149 (4.86%) in 1995, 41/2498 (1.64%) in 2005 and 25/2057 (1.22%) in 2015. Most injuries occurred in General Surgery (14.21%), Gynecology and Obstetrics (9%) and Pediatrics (6.49%). In about 34% the HCWs had been exposed to HCV infected fluids. Over time, a significant decrease in accidental exposure was recorded for physicians (p= 0.019), nurses (p< 0.0001) and HCAs (p< 0.0001). Our results confirm that some profiles, namely physicians, nurses and healthcare assistants, are still at risk of needlestick injuries, especially in surgical areas, including obstetric wards. Further primary and secondary prevention strategies are needed to decrease the incidence of new cases of needlestick injuries.

Alexithymia in HIV, HCV and coinfections.

Recent studies show that alexithymia, an impairment of emotional processing, plays a role in HIV and HCV infections, although little is known about about alexithymia in HIV/HCV coinfection. This study aimed to assess alexithymia in patients suffering from HIV, HCV or HIV/HCV coinfection and observe major differences. We selected 153 subjects, excluding those with psychiatric diagnosis, cognitive impairment or opportunistic diseases, of whom 70 (46%) had HIV infection, 57 (37%) HCV infection and 26 (17%) HIV/HCV coinfection. For the evaluation of alexithymia, we used the Toronto Alexithymia Scale (TAS-20), a self-report questionnaire which allows the results to be assessed both on a dimensional level and on defined cutoff scores. Data analysis showed significant differences between monoinfected and coinfected subjects. The coinfected group had a mean score of 54.00 ±13.43, higher than HIV (48.11 ± 12.38) and HCV (48.28 ± 10.71) (p <0.05). Furthermore, we found clinically relevant scores (≥51) in 65.38% of coinfected subjects, in 42.85% of HIV and in 40.35% of HCV (p <0.05). Given the medical and behavioral correlates of alexithymia highlighted in the literature, we suggest that further investigations are needed to clarify the relationship between alexithymia and HIV/HCV coinfection.

Antiviral therapy for hepatitis C: Has anything changed for pregnant/lactating women?

Hepatitis C virus (HCV) affects about 3% of the world's population, with the highest prevalence in individuals under 40. The prevalence in pregnant women varies with geographical distribution (highest in developing countries). Prevalence also increases in sub-populations of women at high risk for blood-transmitted infections. HCV infection in pregnancy represents a non-negligible problem. However, most of the past antiviral regimens cannot be routinely offered to pregnant or breastfeeding women because of their side effects. We briefly reviewed the issue of treatment of HCV infection in pregnant/breastfeeding women focusing on the effects of the new direct-acting antivirals on fertility, pregnancy and lactation in animal studies and on the potential risk for humans based on the pharmacokinetic properties of each drug. Currently, all new therapy regimens are contraindicated in this setting because of lack of sufficient safety information and adequate measures of contraception are still routinely recommended for female patients of childbearing potential.

Efficacy and Safety of Sofosbuvir in the Treatment of Chronic Hepatitis C: The Dawn of a New Era.

Hepatitis C virus (HCV) infection affects about 160 million people worldwide. Currently, it is treated with pegylated interferon (PEG-IFN) plus ribavirin, associated with a protease inhibitor in case of genotype 1 infection. However, this combination is often contraindicated and associated with severe adverse events that limit its use in clinical practice. Several drugs active against HCV are in an advanced phase of clinical development. Among these, sofosbuvir appears one of the most promising candidates for use in association with both interferon and interferon-free combinations. This review focuses on the results of several sofosbuvir-based phase III trials that have very recently become available. These studies show that the co-administration of sofosbuvir, PEG-IFN and ribavirin for 12 weeks is associated with a very high rate of sustained virological responses (SVR) (about 90%) in naïve patients with genotypes 1, 4, 5 or 6. In patients infected by genotypes 2 or 3, the interferon-free combination of sofosbuvir and ribavirin administered for 12 weeks is associated with a SVR of 97% and 56% in naïve patients, and of 86% and 30% in experienced genotype 2 or 3 patients, respectively. The safety and tolerability profile is optimal and consistent with that of the other drugs administered in the combination (ribavirin and/or interferon). In conclusion, the recent phase III trials of sofosbuvir confirm the excellent results of phase II studies in terms of efficacy and safety and will probably open a new era in the fight against HCV.

Amino acid-based formula as a rescue strategy in feeding very-low-birth-weight infants with intrauterine growth restriction.

BACKGROUND AND AIM: Very-low-birth-weight (VLBW) neonates may develop severe intolerance to standard preterm formula especially if they are associated with intrauterine growth restriction (IUGR). We tested the hypothesis that these infants may tolerate an elemental, amino acid-based formula as a rescue feeding strategy. METHODS: In a prospective, case-control pilot study, we enrolled VLBW IUGR infants enterally fed with standard preterm formula (SPF) at daily increments of 16 mL/kg. If gastric residuals accounted for >70% of milk feed in the previous 24 hours, then feedings were temporarily withheld and then resumed with amino acid formula (AAF) increased at the same speed. Cases on AAF were compared to controls on SPF and with cases themselves while on SPF. Primary outcome was the time to reach full enteral feedings. Secondary outcomes were time on parenteral nutrition, time on central venous catheter, and formula tolerability based on the amount of gastric residual volume. RESULTS: Sixty-four infants (22 cases) were enrolled. Although during the total duration of nutrition, cases had worse primary and secondary outcomes, when on AAF, cases were comparable to controls in time to full enteral feeding (14.4 vs 14 days), time on parenteral nutrition, and time on central venous catheter. Cases on AAF and controls had similar gastric residual volumes. At day 3 after AAF introduction, cases had a significantly reduced number (%) of gastric residual volume >5 mL/kg over total number of feedings (5.6 vs 1.5%; P < 0.05) and the mean gastric residual volume (2.7 vs 0.6 mL; P < 0.05) compared to themselves while on SPF. No difference was detected in weight at 21 and 28 days, in main serum parameters and outcome at discharge. Growth at 12 months of corrected age was also comparable. CONCLUSIONS: In our population of VLBW IUGR newborns with severe feeding intolerance, a short course on AAF was a safe and effective means of nutritional rescue.