Rapid decline of fasting glucose in HCV diabetic patients treated with direct-acting antiviral agents

Association between HCV infection and diabetes has been widely postulated. Little is known about the impact of direct acting antiviral agents (DAAs) on glycemic control. Aim of our study was to evaluate the glycemic control modifications in a case series of HCV+ diabetic population receiving DAAs. We retrospectively evaluated 149 HCV+ patients in two different institutions affiliated to the Sapienza University: Policlinico Umberto I of Rome and Ospedale Santa Maria Goretti of Latina. We were able to identify 29 patients with T2DM (19% of total population) who were receiving different IFN-free regimens. During-treatment fasting glucose values were available for 21 patients and analysis showed a statistically significant reduction (p=0,007), the reduction mean value was -52,86 mg/dl. An A1C value during treatment (week 4 or week 8 or week 12) was available for 10 patients and the analysis showed a statistically significant reduction (p=0,021) with a reduction mean value of -1,95%. 6 patients (23%) needed to reduce hypoglycemic drugs, 8 of 10 patients showed reduction of A1C, 14 of 21 patients (67%) showed reduced FG during treatment. FG and A1C reductions values were independent from which DAA was present in the regimen, HCV genotype, BMI and HIV status. In order to avoid hypoglycemic events, diabetic patients undergoing DAAs should be closely monitorized for reduction of hypoglycemic drugs. Furthermore, diabetes could be considered, in our opinion, as an element to prioritize treatment in those patients with no apparent liver disease

Systemic adipokines, hepatokines and interleukin-6 in HCV-monoinfected and HCV/HIV coinfected patients treated with direct antiviral agents (DAAs)

In this study, we demonstrated that that altered levels ofadipokines/hepatokines in HCV-infected patients, including HIV coinfected, can be restored by treatment with direct antiviral agents (DAAs), thus indicating the important metabolic changes occurring during the eradication of this viral infection

Persistent high plasma levels of sCD163 and sCD14 in adult patients with measles virus infection

Background and aims: Measles is an infectious disease that represents a serious public health problem worldwide, being associated with increased susceptibility to secondary infections, especially in the respiratory and gastrointestinal tracts. The aim of this study was to evaluate sCD163 and sCD14 levels in measles virus (MV) infected patients, as markers of immune activation, in order to better understand their role in the pathogenesis of the disease. TNF-α plasma levels were also evaluated. Methods: sCD163, sCD14 and TNF-α were measured by ELISA in plasma samples of 27 MV infected patients and 27 healthy donors (HD) included as controls. Results: At the time of hospital admission, sCD163 and sCD14 levels were significantly higher in MV infected patients than in HD, while a decrease in TNF-α levels were found even if without statistical significance. sCD163 and sCD14 levels were significantly decreased after two months from acute infection compared to hospital admission although they remained significantly higher compared to HD. TNF-α levels increased significantly during the follow-up period. Considering clinical parameters, sCD163 levels positively correlated with aspartate aminotransferase, white blood cell count and neutrophils rate, while negatively correlated with the lymphocyte percentage. sCD14 levels positively correlated with the neutrophil and lymphocyte percentages. Conclusions. These results indicate that, despite the resolution of symptoms, an important macrophage/ monocyte activation persists in measles patients, even after two months from infection

Changes in inflammatory biomarkers in HCV-infected patients undergoing direct acting antiviral-containing regimens with or without interferon

Background and aims Increased levels of chemokine interferon-gamma (IFN-γ)-inducible protein-10 (CXCL10), soluble CD163 (sCD163) and soluble CD14 (sCD14) have been reported in HCV infection. The aim of this study was to compare, sCD163 and sCD14 levels in HCV-infected patients undergoing direct acting antiviral (DAA)-containing regimens with or without interferon (IFN). Methods sCD163, sCD14 and CXCL10 were longitudinally measured by ELISA in 159 plasma samples from 25 HCV-infected patients undergoing IFN-based treatment plus telaprevir or boceprevir and 28 HCV infected subjects treated with DAA IFN-free regimens. Twenty-five healthy donors (HD) were included as controls. Results At baseline CXCL10, sCD163 and sCD14 levels were higher in HCV-infected patients than in HD. CXCL10 and sCD163 levels were significantly decreased in responder (R) patients who achieved sustained virological response (SVR), with both IFN-based and IFN-free regimens, while they were persistently elevated in non-responders (NR) patients who stopped IFN-based treatments because of failure or adverse events. Conversely, sCD14 levels were apparently unchanged during therapy, but at the end of treatment the levels reached normal ranges. Comparing the two regimens, the extent of CXCL10 reduction was more pronounced in patients undergoing DAA IFN-free therapies, whereas sCD163 and sCD14 reduction was similar in the two groups. Interestingly, only in IFN-based regimens baseline sCD163 levels were significantly higher in NR than in R patients, while in the IFN-free treatment group also patients with highsCD163 plasma levels obtained SVR. At the end of therapy, even if the biomarkers were largely decreased, their levels remained significantly higher compared to HD. Only in the early fibrosis stages, sCD163 values tended to normalize. Conclusions These results indicate that IFN-free regimens including newer DAA induce an early and marked decrease in circulating inflammatory biomarkers. However, the full normalization of biomarkers was not obtained, especially in patients with advanced fibrosis, thus underlying the need for a treatment in the early stages of HCV infection

Liver fibrosis in HCV monoinfected and HIV/HCV coinfected patients: dysregulation of matrix metalloproteinases (MMPs) and their tissue inhibitors TIMPs and effect of HCV protease inhibitors

An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may contribute to liver fibrosis in patients with hepatitis C (HCV) infection. We measured the circulating levels of different MMPs and TIMPs in HCV monoinfected and HIV/HCV coinfected patients and evaluated the potential for anti-HCV therapy to modulate MMP and TIMP levels in HCV subjects. We analyzed 83 plasma samples from 16 HCV monoinfected patients undergoing dual or triple anti-HCV therapy, 15 HIV/HCV coinfected patients with undetectable HIV load, and 10 healthy donors (HD). Levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, TIMP-1, and TIMP-2 were measured by a SearchLight Multiplex Immunoassay Kit. MMP-2 and MMP-9 were the highest expressed MMPs among all the analyzed samples and their levels significantly increased in HCV monoinfected and HIV/HCV coinfected subjects compared to HD. TIMP-1 levels were significantly higher in HCV and HIV/HCV subjects compared to HD and were correlated with liver stiffness. These findings raise the possibility of using circulating TIMP-1 as a non-invasive marker of liver fibrosis in HCV infection. A longitudinal study demonstrated that MMP-9 levels significantly decreased (40% reduction from baseline) in patients receiving dual as well as triple direct-acting antivirals (DAA) anti-HCV therapy, which had no effect on MMP-2, TIMP-1, and TIMP-2. As the dysregulation of MMP-2 and MMP-9 may reflect inflammatory processes in the liver, the decrease of MMP-9 following HCV protease inhibitor treatment suggests a positive effect on the reduction of liver inflammation

Longitudinal virological and immunological profile in a case of human monkeypox infection

In a male with severe proctitis, monkeypox virus DNA was detected in skin lesions, blood, nasopharynx, and rectum, underlying the generalized viral spreading. Rectal involvement was still found when skin lesions disappeared. At the early-stage, increase of cytotoxic and activated T-cells, while reduction of CD56dimCD57+NK cells compared to recovery time-point was observed

Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing Enterobacterales Infections: A Multicenter Nationwide Clinical Experience (CEFTABUSE II Study)

Background. Few data are reported in the literature about the outcome of patients with severe extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) infections treated with ceftolozane/tazobactam (C/T), in empiric or definitive therapy.Methods. A multicenter retrospective study was performed in Italy (June 2016-June 2019). Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to ESBL-E infection and lack of microbiological evidence of infection. The primary end point was to identify predictors of clinical failure of C/T therapy.Results. C/T treatment was documented in 153 patients: pneumonia was the most common diagnosis (n = 46, 30%), followed by 34 cases of complicated urinary tract infections (22.2%). Septic shock was observed in 42 (27.5%) patients. C/T was used as empiric therapy in 46 (30%) patients and as monotherapy in 127 (83%) patients. Favorable clinical outcome was observed in 128 (83.7%) patients; 25 patients were considered to have failed C/T therapy. Overall, 30-day mortality was reported for 15 (9.8%) patients. At multivariate analysis, Charlson comorbidity index >4 (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9-3.5; P = .02), septic shock (OR, 6.2; 95% CI, 3.8-7.9; P < .001), and continuous renal replacement therapy (OR, 3.1; 95% CI, 1.9-5.3; P = .001) were independently associated with clinical failure, whereas empiric therapy displaying in vitro activity (OR, 0.12; 95% CI, 0.01-0.34; P < .001) and adequate source control of infection (OR, 0.42; 95% CI, 0.14-0.55; P < .001) were associated with clinical success.Conclusions. Data show that C/T could be a valid option in empiric and/or targeted therapy in patients with severe infections caused by ESBL-producing Enterobacterales. Clinicians should be aware of the risk of clinical failure with standard-dose C/T therapy in septic patients receiving CRRT

Atypical presentation of crusted (Norwegian) scabies

Atypical presentation of Norwegian scabies

Herpes virus reactivation after initiation of interferon-free antiviral agents in HIV-HCV-coinfected subjects: a new immune restoration disease?

We report four HCV-HIV-coinfected patients who developed herpes zoster or muco-cutaneous herpes virus disease shortly after starting interferon-free antiviral treatment for HCV. We suggest that in our patients the prompt clearance of HCV following direct-acting antivirals leads to a paradoxical effect on the innate and adaptive immune system mediating the reactivation of herpetic infection