Depth effect on point shear wave velocity elastography: Evidence in a chronic hepatitis C patient cohort.

Background and Aims: This study investigated the depth-related bias and the influence of scan plane angle on performance of point-shear-wave elastometry in a chronic hepatitis C patient cohort. Materials and Methods: We included 104 patients affected by chronic liver disease related to the hepatitis C virus. Liver surface nodularity was the reference to diagnose cirrhosis. The ultrasound platform was the Siemens S2000, equipped with point-shear-wave elastometry software. Measurements were obtained in left lateral decubitus from the liver surface to the maximum depth of 8 cm in two orthogonal scan planes according to a standard sampling plane. Scatterplot and box plots explored the depth-related bias graphically. The area under the receiver operating characteristic was used to determine the point-shear-wave elastometry diagnostic performance at progressive depths according to liver surface nodularity. Results: Of the 104 patients, 68 were cirrhotics. Depth-related bias equally modified point-shear-wave elastometry in the two orthogonal scan planes. A better point-shear-wave elastometry diagnostic performance was observed between depths of 4 and 5 cm. The frontal scan plane assured better discrimination between cirrhotic patients and non-cirrhotic patients. Conclusion: Depth is crucial for point-shear-wave elastometry performance. Excellent diagnostic performance at a depth between 4 and 5 cm can also be obtained with a smaller number of measurements than previously recommended.

Molecular Typing and Resistance Profile of Acinetobacter baumannii Isolates during the COVID-19 Pandemic: Findings from the "EPIRADIOCLINF" Project.

Due to the COVID-19 pandemic, there has been a shift in focus towards controlling the spread of SARS-CoV-2, which has resulted in the neglect of traditional programs aimed at preventing healthcare-associated infections and combating antimicrobial resistance. The present work aims to characterize the colonization or infection with Acinetobacter baumannii of COVID-19 patients and to identify any clonality between different isolates. Specifically, data and resistance profiles of A. baumannii isolates were prospectively collected from patients recruited by the EPIRADIOCLINF project. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were used for molecular typing. Overall, we analyzed 64 isolates of A. baumannii from 48 COVID-19 patients. According to our analysis, we have identified the spread of a clonally related isolate, referred to as B. The PFGE pattern B includes four subtypes: B1 (consisting of 37 strains), B2 (11), B3 (5), and B4 (2). Furthermore, in the isolates that were examined using MLST, the most observed sequence type was ST/281. In terms of resistance profiles, 59 out of the total isolates (92.2%) were found to be resistant to gentamicin, carbapenems, ciprofloxacin, and tobramycin. The isolation and identification of A. baumannii from COVID-19 patients, along with the high levels of transmission observed within the hospital setting, highlight the urgent need for the implementation of effective prevention and containment strategies.

In-vitro NET-osis induced by COVID-19 sera is associated to severe clinical course in not vaccinated patients and immune-dysregulation in breakthrough infection.

Since neutrophil extracellular traps formation (NET-osis) can be assessed indirectly by treating healthy neutrophils with blood-derived fluids from patients and then measuring the NETs response, we designed a pilot study to convey high-dimensional cytometry of peripheral blood immune cells and cytokines, combined with clinical features, to understand if NET-osis assessment could be included in the immune risk profiling to early prediction of clinical patterns, disease severity, and viral clearance at 28 days in COVID-19 patients. Immune cells composition of peripheral blood, cytokines concentration and in-vitro NETosis were detected in peripheral blood of 41 consecutive COVID-19 inpatients, including 21 mild breakthrough infections compared to 20 healthy donors, matched for sex and age. Major immune dysregulation in peripheral blood in not-vaccinated COVID-19 patients compared to healthy subjects included: a significant reduction of percentage of unswitched memory B-cells and transitional B-cells; loss of naïve CD3+CD4+CD45RA+ and CD3+CD8+CD45RA+ cells, increase of IL-1ß, IL-17A and IFN-γ. Myeloid compartment was affected as well, due to the increase of classical (CD14++CD16-) and intermediate (CD14++CD16+) monocytes, overexpressing the activation marker CD64, negatively associated to the absolute counts of CD8+ CD45R0+ cells, IFN-γ and IL-6, and expansion of monocytic-like myeloid derived suppressor cells. In not-vaccinated patients who achieved viral clearance by 28 days we found at hospital admission lower absolute counts of effector cells, namely CD8+T cells, CD4+ T-cells and CD4+CD45RO+ T cells. Percentage of in-vitro NET-osis induced by patients' sera and NET-osis density were progressively higher in moderate and severe COVID-19 patients than in mild disease and controls. The percentage of in-vitro induced NET-osis was positively associated to circulating cytokines IL-1ß, IFN-γ and IL-6. In breakthrough COVID-19 infections, characterized by mild clinical course, we observed increased percentage of in-vitro NET-osis, higher CD4+ CD45RO+ and CD8+ CD45RO+ T cells healthy or mild-COVID-19 not-vaccinated patients, reduced by 24 h of treatment with ACE inhibitor ramipril. Taken together our data highlight the role of NETs in orchestrating the complex immune response to SARS-COV-2, that should be considered in a multi-target approach for COVID-19 treatment.

Vascular Dysfunction of COVID-19 Is Partially Reverted in the Long-Term.

BACKGROUND: COVID-19 is characterized by severe inflammation during the acute phase and increased aortic stiffness in the early postacute phase. In other models, aortic stiffness is improved after the reduction of inflammation. We aimed to evaluate the mid- and long-term effects of COVID-19 on vascular and cardiac autonomic function. The primary outcome was aortic pulse wave velocity (aPWV). METHODS: The cross-sectional Study-1 included 90 individuals with a history of COVID-19 and 180 matched controls. The longitudinal Study-2 included 41 patients with COVID-19 randomly selected from Study-1 who were followed-up for 27 weeks. RESULTS: Study-1: Compared with controls, patients with COVID-19 had higher aPWV and brachial PWV 12 to 24 (but not 25-48) weeks after COVID-19 onset, and they had higher carotid Young's elastic modulus and lower distensibility 12 to 48 weeks after COVID-19 onset. In partial least squares structural equation modeling, the higher the hs-CRP (high-sensitivity C-reactive protein) at hospitalization was, the higher the aPWV 12 to 48 weeks from COVID-19 onset (path coefficient: 0.184; P=0.04). Moreover, aPWV (path coefficient: -0.186; P=0.003) decreased with time. Study-2: mean blood pressure and carotid intima-media thickness were comparable at the end of follow-up, whereas aPWV (-9%; P=0.01), incremental Young's elastic modulus (-17%; P=0.03), baroreflex sensitivity (+28%; P=0.049), heart rate variability triangular index (+15%; P=0.01), and subendocardial viability ratio (+12%; P=0.01×10-4) were significantly improved. There was a trend toward improvement in brachial PWV (-6%; P=0.14) and carotid distensibility (+18%; P=0.05). Finally, at the end of follow-up (48 weeks after the onset of COVID-19) aPWV (+6%; P=0.04) remained significantly higher in patients with COVID-19 than in control subjects. CONCLUSIONS: COVID-19-related arterial stiffening involves several arterial tree portions and is partially resolved in the long-term.

Natalizumab administration in multiple sclerosis patients during active SARS-CoV-2 infection: a case series.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) caused by the new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become a pandemic, affecting the therapeutic management for Multiple Sclerosis (MS). Any decision regarding the discontinuation of high-potency agents for moderate and highly active MS should be carefully evaluated, taking into account the potential risk of rebound of the disease. In particular, no data about clinical outcome of patients with MS receiving Natalizumab (NTZ) during active COVID-19 infection have been reported yet. CASES PRESENTATION: We reported on 6 patients treated with NTZ for relapsing MS during active COVID-19 infection, who recovered without reporting any worsening or new symptoms. Most of the patients were asymptomatic, with the exception of one patient who had a slight worst COVID-19 clinical course. No patients received O2-therapy or required intensive care. No neurological complications were observed. CONCLUSIONS: This paper reported the clinical outcome of patients with MS receiving NTZ during active COVID-19 infection. This case series suggests that treatment with NTZ during pandemic is relatively safe and might be continued in selected patients who are infected by COVID-19, thereby reducing the risk of MS disease rebound.

Reply to Ialongo et al. Vitamin D, SARS-CoV-2 and Causal Associations in Transversal Studies: The Time-Series Analysis to Reveal Potential Confounders. Comment on "Gaudio et al. Vitamin D Levels Are Reduced at the Time of Hospital Admission in Sicilian SARS-CoV-2-Positive Patients. Int. J. Environ. Res. Public Health 2021, 18, 3491".

We read the comment by Ialongo et al. [...].

Vitamin D Levels Are Reduced at the Time of Hospital Admission in Sicilian SARS-CoV-2-Positive Patients.

The coronavirus disease 2019 (COVID-19) pandemic poses a worldwide healthcare challenge that needs an efficient response. Unfortunately, to date there is no highly effective treatment, so a deep understanding of COVID-19 risk factors could be an important step in treating the disease. Vitamin D affects the immune system in many different ways, and other authors already found that COVID-19 patients have low levels of vitamin D. In our retrospective study, we evaluated the vitamin D status at the time of hospital admission in 50 COVID-19 patients in Sicily, which is the southernmost region of Italy, and compared them with 100 control subjects matched for age and sex. Our data showed markedly low levels of vitamin D in patients with a positive polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but no association was found with inflammation markers or clinical severity. Vitamin D levels were reduced at the time of hospital admission in Sicilian SARS-CoV-2-positive patients, but it is not clear whether this condition has an impact on the clinical course of COVID-19.

Liver and cardiovascular mortality after hepatitis C virus eradication by DAA: Data from RESIST-HCV cohort.

Real-world evidence on the course of Hepatitis C Virus (HCV) chronic liver disease after Sustained Virologic Response (SVR) obtained with direct-acting antiviral drugs (DAAs) are still limited, and the effects on mortality remain unclear. We evaluated the post-treatment survival of 4307 patients in the RESIST-HCV cohort (mean age 66.3 ± 11.6 years, 56.9% males, 24.7% chronic hepatitis, 66.9% Child-Pugh A cirrhosis and 8.4% Child-Pugh B cirrhosis) treated with DAAs between March 2015 and December 2016 and followed for a median of 73 weeks (range 16-152). Proportional cause-specific hazard regression for competing risks was used to evaluate the survival and to assess the predictors of liver and cardiovascular death. Overall, 94.7% of patients achieved SVR while 5.3% were HCV RNA-positive at last follow-up. Sixty-three patients (1.4%) died during the observation period. SVR was associated with a decreased risk of liver mortality (hazard ratio,HR0.09, beta -2.37, p < .001). Also, platelet count (HR 0.99, beta-0.01, p = .007) and albumin value (HR 0.26, beta -1.36 p = .001) were associated with liver mortality by competing risk analysis. SVR was associated with a reduced risk of cardiovascular mortality regardless of presence of cirrhosis (HR 0.07, beta-2.67, p < .001). Presence of diabetes (HR 3.45, beta 1.24, p = .014) and chronic kidney disease class ≥3 (HR 3.60, beta 1.28, p = 0.016) were two factors independently associated with higher risk of cardiovascular mortality. Patients with SVR to a DAA therapy have a better liver and cardiovascular survival, and the effects of HCV eradication are most evident in patients with compensated liver disease.

Is Transient Elastography Needed for Noninvasive Assessment of High-Risk Varices? The REAL Experience.

INTRODUCTION: The Baveno VI consensus guidelines and an expanded algorithm suggest that transient elastography (TE) and platelet (PLT) count can be used to identify patients with cirrhosis who can avoid esophagogastroduodenoscopy (EGD). The primary aims of this study were to assess the ability of a simple algorithm, which uses only laboratory parameters, to predict medium/large esophageal varices (EV) in patients with hepatitis C virus (HCV) and cirrhosis from the Rete Sicilia Selezione Terapia-HCV (RESIST-HCV) cohort and to compare the performance of the algorithm with Baveno VI and Expanded Baveno VI criteria. The secondary aim was to assess the role of TE in ruling out large EV. METHODS: In total, 1,381 patients with HCV-associated cirrhosis who had EGD and TE within 1 year of starting treatment with direct-acting antivirals were evaluated. Using multivariate logistic analysis, laboratory variables were selected to determine which were independently associated with medium/large EV to create the RESIST-HCV criteria. These criteria were tested in a training cohort with patients from a single center (Palermo) and validated with patients from the 21 other centers of the RESIST-HCV program (validation cohort). RESULTS: In the entire cohort, medium/large EV were identified in 5 of 216 patients (2.3%) using the Baveno VI criteria and 13 of 497 patients (2.6%) using the Expanded Baveno VI criteria. PLT count and albumin level were independently associated with medium/large EV. The best cut-off values were a PLT count greater than 120 × 10 cells/µL and serum albumin level greater than 3.6 g/dL; negative predictive values (NPVs) were 97.2% and 94.7%, respectively. In the training cohort of 326 patients, 119 (36.5%) met the RESIST-HCV criteria and the NPV was 99.2%. Among 1,055 patients in the validation cohort, 315 (30%) met the RESIST-HCV criteria and the NPV was 98.1%. Adding TE to the RESIST-HCV criteria reduced the avoided EGDs for approximately 25% of patients and the NPV was 98.2%. DISCUSSION: The "easy-to-use" RESIST-HCV algorithm avoids EGD for high-risk EV screening for more than 30% of patients and has the same performance criteria as TE. Using these criteria simplifies the diagnosis of portal hypertension.

Hepatitis C virus eradication by direct antiviral agents improves glucose tolerance and reduces post-load insulin resistance in nondiabetic patients with genotype 1.

BACKGROUND AND AIMS: Genotype 1 chronic hepatitis C is associated with an impairment of glucose homoeostasis, especially in the advanced stages of the disease. Glucose tolerance is an independent predictor of liver-related mortality in patients with cirrhosis because of chronic hepatitis C. However, no study has demonstrated so far weather hepatitis C virus clearance affects glucose tolerance. METHODS: To this aim, we performed a prospective study assessing the effects of direct antiviral agents treatment in nondiabetic cirrhotic patients with genotypes 1a/1b and impaired glucose tolerance based on a 75-g oral glucose tolerance test. Impaired glucose tolerance was diagnosed by a 2-hour plasma glucose between 140 and 199 mg/dL. Insulin resistance was estimated by the oral glucose insulin sensitivity index, an oral glucose tolerance test-derived measure. RESULTS: After meeting the inclusion criteria, the study population included 32 outpatients (26/6 genotypes 1b/1a; age 62 ± 7.4 years; 18 males) with compensated Child-A cirrhosis. All patients achieved a sustained virological response following direct antiviral agents treatment. After viral eradication, we did not observe change in fasting plasma glucose (103.5 ± 7.1 vs 102.8 ± 7.2 mg/dL, P = .15) but 2-hour plasma glucose was reduced (165.2 ± 22.7 vs 138.5 ± 21.3 mg/dL, P < .001). Hepatitis C virus eradication led also to a significant reduction in HbA1c (6.1 ± 0.2% vs 5.7 ± 0.3%, P < .001) and post-load insulin resistance as assessed by the oral glucose insulin sensitivity index (6.92 ± 1.56 vs 9.52 ± 1.39 mg/kg/min, P < .001). These effects were observed despite no change in body mass index from baseline to follow-up (25.6 ± 4.3 vs 25.8 ± 4.4, P > .5). CONCLUSIONS: Our results indicate that hepatitis C virus eradication may early improve glucose tolerance in patients with hepatitis C virus-related cirrhosis.

Is BCLC algorithm useful in clinical practice? Study on 164 HCC patients.

BACKGROUND/AIMS: The Barcelona Clinic Liver Cancer (BCLC) classification has been recently validated as the best system for treatment guidance for hepatocellular carcinoma (HCC). The aim of this retrospective study is to evaluate the usefulness of BCLC in the treatment of HCC comparing our treatment decision and the BCLC algorithm indications. METHODOLOGY: In 102 patients affected by HCC observed from 1991 to 2002 a retrospective analysis was performed. The choice of treatment was compared with the treatment schedule proposed by BCLC. Whereas the second group of 62 patients observed from 2008 to 2010 was analysed both retrospectively in comparison with the BCLC classification. RESULTS: We found a disagreement in between our decision making and the choices suggested by BCLC. We only found a statistical significance for age and performance status test. In surgical patients the median age and the PST class were lower with a statistically significant p value (0.04 and 0.03, respectively). CONCLUSIONS: The BCLC system would not have changed our decision either in the past, or in present days, especially in surgical indications. Even if the decision making is affected by BCLC, actually that process still needs the support of the experience of each clinical centre involved.

Does transient elastography (FibroScan®) have a role in decision making in hepatocellular carcinoma?

OBJECTIVES: Portal hypertension has been reported as a negative prognostic factor and a relative contraindication for liver resection. This study considers a possible role of fibrosis evaluation by transient elastography (FibroScan(®)) and its correlation with portal hypertension in patients with cirrhosis, and discusses the use of this technique in planning therapeutic options in patients with hepatocellular carcinoma (HCC). METHODS: A total of 77 patients with cirrhosis, 42 (54.5%) of whom had HCC, were enrolled in this study during 2009-2011. The group included 46 (59.7%) men. The mean age of the sample was 65.2 years. The principle aetiology of disease was hepatitis C virus (HCV)-related cirrhosis (66.2%). Liver function was assessed according to Child-Pugh classification. In all patients liver stiffness (LS) was measured using FibroScan(®). The presence of portal hypertension was indirectly defined as: (i) oesophageal varices detectable on endoscopy; (ii) splenomegaly (increased diameter of the spleen to ≥ 12 cm), or (iii) a platelet count of <100,000 platelets/mm(3). RESULTS: Median LS in all patients was 27.9 kPa. Portal hypertension was recorded as present in 37 patients (48.1%) and absent in 40 patients (51.9%). Median LS values in HCC patients with and without portal hypertension were 29.1 kPa and 19.6 kPa, respectively (r = 0.26, P < 0.04). Liver stiffness was used to implement the Barcelona Clinic Liver Cancer algorithm in decisions about treatment. CONCLUSIONS: The evaluation of liver fibrosis by transient elastography may be useful in the follow-up of patients with cirrhosis and a direct correlation with portal hypertension may aid in the evaluation of surgical risk in patients with HCC and in the choice of alternative therapies.

Treatment induced seroconversion to HBsAb following HBV reactivation in the immunosuppressed haematology and oncology patient: a clinical survey of 5 cases in Catania, Italy.

BACKGROUND: In onco-haematological patients inactive or occult HBV infection may be reactivated as a result of disease-related immuno-suppression and/or chemotherapy with rituximab. OBJECTIVES: This study reports the clinical features of five patients affected by onco-haematological disorders who experienced hepatitis B reactivation. STUDY DESIGN: From 2005 to 2010, five onco-haematological patients with hepatitis B reactivation were admitted to the department of Infectious Diseases, Ferrarotto Hospital, Catania, Italy. RESULTS: At the time of onco-haematological disease diagnosis, 3 patients were HBcAb positive; 1 HBsAb and HBcAb positive; and 1 HBsAg positive, HBV DNA negative. None of the patients received hepatitis B prophylaxis. Reactivation was observed following chemotherapy. One patient was treated with lamivudine, 2 with tenofovir and 2 with telbivudine. Following treatment all patients achieved undetectable HBV DNA and normalization of transaminases. Three patients, those treated with lamivudine and tenofovir, cleared HBsAg and developed protective titres of HBsAb. The remaining patients, who were treated with telbivudine, were HBV DNA negative and HBsAg positive one at 27 months and the other at 5 months of therapy. Treatment thus continued in these patients. CONCLUSION: HBV reactivation can be a severe complication in onco-haematological patients undergoing chemotherapy with rituximab. In our experience all nucleos(t)ide analogues were safe and effective. Three patients seroconverted to HBsAb. This may be as a result of the antivirals enhancing the immune response to HBV. A similar role may also be played by immune recovery following the withdrawal of immune-suppressive treatment. This report confirms the importance of anti-viral prophylaxis in patients with a high risk of HBV reactivation.

[Clinical, virological and epidemiological aspects of acute B hepatitis in the Catania area (Italy)]. / Valutazione epidemiologica, virologica e clinica dell'epatite acuta B nella provincia di Catania.

Starting from January 1997 we prospectively evaluated all cases of acute hepatitis B admitted to two of the main Infectious Diseases Units in Catania (eastern Sicily). The survey was extended throughout a 10-year period up to December 2007. Between 1997 and 1999 we observed 21 cases of acute hepatitis B; between 2000 and 2002 18 cases; between 2003 and 2005 22 cases and, finally, 37 cases were reported in the period 2006-2007. We found an increase in acute hepatitis B cases among people aged 26 to 44 years (from 38% in 1997-99 to 70% in 2006-07). A progressive decrease in intravenous drug abuse as a risk factor for acute hepatitis B was also observed (from 61% to 14%) together with a parallel increase in cases due to sexual transmission (from 19% to 56%) and outpatient cosmetic surgical procedures. Mean time to serum HBsAg negativization was longer in the last period (2006-07), with 6 cases out of 37 showing HBsAg persistence beyond 12 months from the clinical onset. Furthermore, in 2006-07 there were 12 cases (42%) of acute hepatitis due to HBV genotypes A and F. In our area, a progressive drop of hepatitis B cases due to intravenous drug abuse occurred, whereas heterosexual and iatrogenic cases increased. Cases due to HBV non-D genotypes may well be related to migration from endemic areas towards Sicily.