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The predictive factors of long-term clinical benefits in patients with hepatitis C virus (HCV)—related liver cirrhosis after Direct Antiviral Agents (DAA) treatment are still undefined. The aim of this study was to identify any predictors of liver failure, hepatocellular carcinoma (HCC) and/or death in patients with compensated liver cirrhosis who achieved the sustained virological response (SVR). To this purpose, 324 consecutive cirrhotic patients who started DAA treatment from 1 April 2015 to 31 December 2016 were retrospectively analyzed. All patients were followed up for a median time of 63 months (range 19−77) through clinical/biochemical/instrumental examinations performed at baseline and after stopping the DAA treatment. At the end of the evaluation, 230 (71%) individuals showed stable clinical liver disease over time, 43 (13.3%) developed HCC, and 24 (7.4%) developed hepatic decompensation without HCC. Overall, 49 (15,1%) patients died. Multivariate regression analysis showed that hepatic decompensation was significantly associated with at baseline older age, higher liver stiffness, higher spleen longitudinal size values and hypergammaglobulinemia (p = 0.003, p = 0.005, p = 0.001, p = 0.029, respectively). HCC development was significantly associated with hypergammaglobulinemia (p < 0.001). Death was associated with older age and hypergammaglobulinemia (p < 0.001 and p = 0.007, respectively). Finally, survival analysis confirmed that patients with gamma globulin levels ≥ 1.8 gr/dl had a significantly higher risk of death compared to those with gamma globulin levels < 1.8 gr/dl (p < 0.001). In conclusion, hypergammaglobulinemia before starting DAA therapy represents a strong predictor of hepatic decompensation, HCC and death in cirrhotic patients even after HCV clearance.

Insufficient information is available about co-factors favoring the progression of non-alcoholic fatty liver disease (NAFLD) toward cirrhosis. We aimed to evaluate the impact of a limited alcohol intake and of occult hepatitis B virus (HBV) infection (OBI) on the severity of NAFLD. Three-hundred-seventy-four alcohol non-abusers and HBV surface antigen negative NAFLD patients (223 males; mean age 55.4 years), consecutively admitted to the outpatients clinic of a referral liver unit from January 1st, 2018 to December 31st, 2019, were studied. Anti-HBV core antigen antibody [(anti-HBc), a surrogate marker of OBI] was assessed in all patients. Patients were distinguished between teetotal and moderate alcohol consumers (intake of less than 30 g and 20 g if males or females, respectively). Liver fibrosis was non-invasively assessed by FIB-4 and transient elastography. Uni- and multivariate analyses were performed to identify predictors of advanced fibrosis. Patients had a mean BMI of 28.5 kg/m 2 , and the majority presented metabolic and cardio-vascular comorbidities [258 patients (69%) had insulin resistance/diabetes, 249 (66.6%) dyslipidemia, 200 (53.5%) arterial hypertension]. Multivariate analysis showed that anti-HBc positivity (p = 0.046, OR 2.153) was a factor associated with advanced fibrosis at FIB-4 score testing, whereas moderate alcohol intake was not associated with severe NAFLD both at FIB-4 and transient elastography evaluations. The study showed that a moderate alcohol intake has no impact on NAFLD severity and suggested that OBI might negatively affect the NAFLD outcome., (© 2022. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Background: The negative clinical impact of bacterial infections (BI) in patients with cirrhosis is well documented. In cirrhotic patients, failure to isolate the pathogen is a frequent event, occurring in 30-40% of cases., Aim: The aim of this study was to compare the clinical characteristics, early (30-day) and short-term (90-day) mortality rates, in a cohort of cirrhotic patients with BI, between those with positive (C-pos) and those with negative (C-neg) microbiological cultures., Methods: We retrospectively enrolled 279 consecutive hospitalized cirrhotic patients with BI. Survival and predictors of 30-day and 90-day mortality were assessed by Kaplan-Meier curves and logistic regression analysis, respectively., Results: Cultures tested negative in 108/279 (38.7%) patients. C-neg patients were more frequently males (p = 0.035), had higher Child-Pugh-Turcotte (CPT; p = 0.007) and model for end-stage liver disease-sodium (MELD-Na; p = 0.043) scores, and had more frequently decompensated liver disease (p = 0.04). Mortality rate was higher in C-neg than in C-pos patients, both at 30 days (22.2% versus 11.7%, p = 0.024) and 90 days (46.3% versus 33.3%, p = 0.030). MELD-Na score and non-selective beta-blockers (NSBBs) were independent risk factors for 30-day and 90-day mortality. In particular, the use of NSBBs was independently associated with a lower 30-day and 90-day mortality risk (OR 0.41, CI95% 0.17-0.94, p = 0.040; and OR 0.43, CI95% 0.25-0.75, p = 0.003, respectively)., Conclusions: Cirrhotic patients with BI and negative microbiological cultures have significantly higher mortality compared to those with positive cultures. Early mortality and short-term mortality are mainly influenced by the underlying severity of liver disease. In this contest, therapy with NSBBs has a positive impact on short-term survival., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To evaluate the predictive factors for surgical success in sleep apnea surgical techniques addressing the lateral pharyngeal wall., Materials and Methods: This is a retrospective review of consecutive cases treated by functional expansion pharyngoplasty for OSA. Collected data included patients demographics, ENT physical examination and somnographic data. Furthermore inter pterygoid distance was assessed by CT scans. To determine predictors of surgical success, physical examination, CT findings, polysomnographic and demographic data were compared between the success and failure group., Results: Fifty two patients were enrolled. The mean AHI decreased significantly from 44.3 to 17 (p = 0.001). A total of 33 patients (63.5%) met the surgical success criteria. An inter pterygoid distance longer than 34 mm was the only significant predictor of success., Conclusions: Inter pterygoid distance seems to be a promising parameter associated with the surgical outcomes that should be further studied to be validated as predictor of success., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Data concerning the impact of hepatitis C virus (HCV) cure on type 2 diabetes mellitus (T2DM) are controversial. The aim of the study was to evaluate the effects of anti-HCV direct-acting antiviral (DAA) treatments on long-term glucose control in HCV/T2DM patients with chronic hepatitis C (CHC) or with cirrhosis., Methods: One hundred and eighty-two consecutive HCV/T2DM patients who achieved a viral clearance by DAA treatment were enrolled. Seventy or 182 of them had CHC, and 112 had cirrhosis. Clinical, biochemical and instrumental parameters were recorded at baseline and at 48, 96 and 120 weeks (48w, 96w and 120w, respectively) after stopping DAA therapy., Results: At baseline, the overall study population had a mean of glycated haemoglobin (HbA1c) value of 7.2% (ranging from 5 to 11.2), without any significant differences between CHC and cirrhosis [7.1 and 7.2, respectively]. Evaluation over time of HbA1c variations showed a significant improvement of glucose control at all post-treatment time points compared with baseline in CHC patients (P = .001). In cirrhotic patients, a significant decrease of HbA1c levels was only found when comparing HbA1c values between baseline and 48w time-point (P = .001), whereas this improvement disappeared at both 98w and 120w (P = .8 and P = .3, respectively). Multivariate logistic regression analysis showed that patients with chronic hepatitis have a 2.5 (CI 1.066-5.945) times greater chance of achieving an improvement of glycaemic values than patients with liver cirrhosis (P = .035)., Conclusion: DAA-based HCV cure induces a significant and persistent amelioration of glycaemic control in HCV/diabetic patients with chronic hepatitis, whereas cirrhotic HCV/diabetic subjects have only a transient benefit from the virus elimination., (© 2021 The Authors. Liver International published by John Wiley & Sons Ltd.)

Ultrasound (US) detection of liver nodules in cirrhotic patients requires further radiological examinations and often a follow-up with repeated short-term evaluations to verify the presence of hepatocellular carcinoma (HCC). Aims of the study were to assess the rate of HCC diagnosis and to identify HCC predictors in a cohort of cirrhotics followed-up after US detection of the liver nodule(s). One-hundred-eighty-eight consecutive cirrhotic patients (124 males, mean age 64.2 years) with liver nodule(s) detected by US were enrolled. All patients underwent second-level imaging [computed tomography (TC) or magnetic resonance (MR)], and those without a definite diagnosis of HCC were followed-up with TC and/or RM repeated every 3-6 months up to 18 months if HCC was not diagnosed. After 18 months, non-HCC patients came back to routine US surveillance. HCC was diagnosed in 73/188 cases (38.8%). In 66/73 patients (90.4%) HCC was identified at first radiological evaluation after US, while in the remaining seven subjects it was diagnosed at the subsequent imaging examination. Age (p = 0.001) and nodule dimension (p = 0.0001) were independent predictors of HCC at multivariate analysis. Fourty-nine/188 patients were lost at follow up after 18 months. Twenty/139 remaining patients developed HCC and 3/139 cholangiocarcinoma; 77 died between 3 and 110 months from the beginning of the study (61 for end-stage liver disease, 8 for extrahepatic causes, eight for unknown causes). Patients who developed liver cancer earlier during the follow up had the shortest overall survival. US-detected liver nodules are not neoplastic in more than half of cirrhotic patients. A definite diagnosis may be obtained at the time of the first radiologic evaluation after US in the vast majority of the cases. Patients in whom nodules are found not to be tumoral may return to the US surveillance program routinely applied to all cirrhotics.

Iron deficiency (ID) is recognized as an important comorbidity in patients undergoing cardiac surgery; however, it still remains under-diagnosed and under-treated in clinical practice. This study aims at comparing efficacy and the effects on exercise capacity of intravenous ferric carboxymaltose (FCM) versus ferric gluconate (FG) in patients with ID anemia (IDA) resulting from cardiac surgery. We retrospectively analyzed data from our records of in-hospital patients with IDA after cardiac surgery undergoing cardiac rehabilitation. Group I was treated with FG, group II with FCM. Efficacy measures included changes (baseline vs discharge) in hemoglobin (Hb) and in distance traveled at six-minutes walking test (6MWT). Data from 74 in-patients (mean age 67.5±10.4 years, 43% women) were analyzed. At discharge, patients treated with FCM showed higher levels of Hb (11.1±1.2g/dl vs 10.2±1.1 g/dl; p=0.001), greater distance traveled at 6MWT (279.2±108.8 meters vs 236.3±72.7 meters; p=0.048), and lower in-hospital rehabilitation length of stay (20.3±7 vs 25.3±11.7 days; p=0.043) as compared to FG group. At multivariate analysis, the most powerful predictors of Hb increase >1 g/dl at discharge were transferrin levels (p=0.019) and treatment with FCM (p<0.001). FCM replacement therapy and iron serum levels were the most powerful predictors of 6MWT distance improvement (>100 meters) at discharge (p=0.13 and p=0.003, respectively). In patients with IDA following cardiac surgery, intravenous FCM is effective in restoring Hb levels and in improving exercise capacity after cardiac surgery.

Background: Sacubitril/valsartan has been shown to be superior to enalapril in reducing the risks of death and hospitalization for heart failure (HF). However, knowledge of the impact on cardiac performance remains limited. We sought to evaluate the effects of sacubitril/valsartan on clinical, biochemical and echocardiographic parameters in patients with heart failure and reduced ejection fraction (HFrEF)., Methods: Sacubitril/valsartan was administered to 205 HFrEF patients., Results: Among 230 patients (mean age 59 ± 10 years, 46% with ischemic heart disease) 205 (89%) completed the study. After a follow-up of 10.49 (2.93 ± 18.44) months, the percentage of patients in New York Heart Association (NYHA) class III changed from 40% to 17% ( p < 0.001). Median N-Type natriuretic peptide (Nt-proBNP) decreased from 1865 ± 2318 to 1514 ± 2205 pg/mL, ( p = 0.01). Furosemide dose reduced from 131.3 ± 154.5 to 120 ± 142.5 ( p = 0.047). Ejection fraction (from 27± 5.9% to 30 ± 7.7% ( p < 0.001) and E/A ratio (from 1.67 ± 1.21 to 1.42 ± 1.12 ( p = 0.002)) improved. Moderate to severe mitral regurgitation (from 30.1% to 17.4%; p = 0.002) and tricuspid velocity decreased from 2.8 ± 0.55 m/sec to 2.64 ± 0.59 m/sec ( p < 0.014)., Conclusions: Sacubitril/valsartan induce "hemodynamic recovery" and, consistently with reduction in Nt-proBNP concentrations, improve NYHA class despite diuretic dose reduction., Competing Interests: The authors declare no conflict of interest.

Background: Previous studies showed that troponin blood levels may increase after exercise. In this study we assessed whether, among patients admitted with suspected unstable angina, the increase in high-sensitive troponin T (hs-TnT) levels after exercise stress test (EST) might help identify those with obstructive coronary artery disease (CAD) and predict symptom recurrence during short term follow-up., Methods: Maximal treadmill EST was performed in 69 consecutive patients admitted to the emergency room with a suspicion of unstable angina (acute chest pain but confirmed normal serum levels of cardiac troponins) was measured before and 4 hours after EST. Coronary angiography was performed in 22 patients (32.8%)., Results: hs-TnT increased after EST compared to baseline in the whole population (from 0.84±0.65 to 1.17±0.87 ng/dL, p<0.001). The increase was similar in patients with positive (n = 14) and negative (n = 55) EST (p = 0.72), and was also similar in patients with (n = 12) and without (n = 10) obstructive CAD at angiography (p = 0.91). The achievement of a heart rate at peak EST ≥85% of that predicted for age was the variable mainly associated with the post-EST hs-TnT increase at multivariable linear regression analysis (p = 0.005). The change after EST of hs-TnT did not predict the recurrence of symptoms or readmission for chest pain at 6-month follow-up., Conclusions: Our data show that hs-TnT increased after EST in patients with suspected unstable angina, which seemed largely independent of most clinical and laboratory variables. Thus, hs-TnT assessed after EST does not seem to be helpful to identify patients with obstructive CAD in this kind of patients., Competing Interests: The authors declare that no competing interests exist.

Background: Data on erectile dysfunction (ED) in cirrhotic patients are limited as yet. Aim of this study was to investigate the prevalence of ED and the factors potentially involved in its development in compensated cirrhosis., Methods: We prospectively enrolled 102 male (mean age 63 ± 10 years) affected by cirrhosis in Child-Pugh Class A. The following questionnaires were used: simplified International Index of Erectile Function (IIEF-5) Questionnaire, Centre of Epidemiologic Studies Depression Scale and ANDROTEST., Results: ED was found in 57/102(55.9%) patients, and was mild, moderate and severe in 21(36.8%), 6(10.5%) and 30(52.6%) subjects, respectively. ED patients were significantly older than those without (66 ± 10 vs 60 ± 10,p = 0.006); ED prevalence gradually increased with age. There was no statistically significant difference between patients with and without ED concerning the coexistence of diabetes, hypertension, and cardiovascular disease. Age(p = 0.040) and serum haemoglobin(p = 0.027) were identified as predictors of ED on multivariate analysis. Liver-related factors and pharmacological treatment, including β-blockers, were not associated with the presence of ED., Conclusions: In patients with compensated liver cirrhosis, even in concomitance with other chronic comorbidities, the prevalence of ED is not markedly different from the general population. Compensated cirrhosis per se is not a risk factor for ED occurrence. Older age and low haemoglobin values are significantly associated with ED in cirrhotics., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Sacubitril/valsartan in heart failure (HF) with reduced ejection fraction (HFrEF) was shown to be superior to enalapril in reducing the risk of death and hospitalization for HF. Our aim was to evaluate the cardiopulmonary effects of sacubitril/valsartan in patients with HFrEF., Methods: We conducted an observational study. Ninety-nine ambulatory patients with HFrEF underwent serial cardiopulmonary exercise tests (CPET) after initiation of sacubitril/valsartan in addition to recommended therapy., Results: At baseline, 37% of patients had New York Heart Association (NYHA) class III. After a median follow-up of 6.2 months (range 3⁻14.9 months) systolic blood pressure decreased from 117 ± 14 to 101 ± 12 mmHg ( p < 0.0001), left ventricular ejection fraction (LVEF) increased from 27 ± 6 to 29.7 ± 7% ( p < 0.0001), peak oxygen consumption (VO₂) improved from 14.6 ± 3.3 (% of predicted = 53.8 ± 14.1) to 17.2 ± 4.7 mL/kg/min (% of predicted = 64.7 ± 17.8) ( p < 0.0001), minute ventilation/carbon dioxide production relationship (VE/VCO₂ Slope) decreased from 34.1 ± 6.3 to 31.7 ± 6.1 ( p = 0.006), VO₂ at anaerobic threshold increased from 11.3 ± 2.6 to 12.6 ± 3.5 mL/kg/min ( p = 0.007), oxygen pulse increased from 11.5 ± 3.0 to 13.4 ± 4.3 mL/kg/min ( p < 0.0001), and ∆VO₂/∆Work increased from 9.2 ± 1.5 to 10.1 ± 1.8 mL/min/watt ( p = 0.0002)., Conclusion: Sacubitril/valsartan improved exercise tolerance, LVEF, peak VO₂, and ventilatory efficiency at 6.2 months follow-up. Further studies are necessary to better clarify underlying mechanisms of this functional improvement.

Heart failure (HF) with reduced ejection fraction (HFrEF) has a well-known epidemic relevance in western countries. It affects up to 1-2% of patients > 60 years and reaches a prevalence of 12% in octogenarian patients. The role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitive troponin I (hsTnI) in risk stratifying HFrEF patients has been established; at present, evidence is exclusively based on one-time assessments, and the prognostic usefulness of serial biochemical assessments in this population still remains to be determined. We prospectively recruited 226 patients with chronic HFrEF, who were all referred to the Outpatient Clinic of our institution from November 2011 through September 2014. Recruited patients underwent full clinical evaluation with complete history taking and physical examination as well as ECG, biochemical assessment, and standard 2D and Doppler flow echocardiography at the first visit, and then again at each visit during the follow-up, repeated every 6 months. During the follow-up period, cardiovascular (CV) death, which occurred in 16 patients, was not statistically correlated with gender (p = 0.088) or age (p = 0.1636); however, baseline serum levels of NT-proBNP, which were 3 times higher in deceased patients, were significantly related to this clinical event (p = 0.001). We found that NT-proBNP represents a strong and independent predictor of CV outcome; serum levels of hsTnI, which are significantly related to an increased risk of hospitalization, cannot properly predict the relative risk of CV mortality. Our study validates, eventually, the multimarker strategy, which reflects the complexity of the HF pathophysiology., (© 2019 S. Karger AG, Basel.)

Background & Aims: The outcome of compensated cirrhosis may vary considerably and cannot be predicted by routinely performed tests at present. The aim of this study was to evaluate possible predictors of clinical evolution in patients with Child-Pugh (C-P) class A cirrhosis because of untreatable causes by analysing clinical/biochemical/instrumental parameters evaluated at the time of diagnosis and during the subsequent long-lasting follow-up., Methods: Two hundred and seventy-two consecutive C-P class A cirrhotic patients (155 males; median age 63 years, range 34-81) were analysed. All patients were followed up for a median time of 96 months (range 21-144) through periodically performed clinical/biochemical/ultrasonographic and esophagogastroduodenoscopic examinations., Results: During the follow-up, 97 individuals (36%) were clinically stable, 104 (38%) developed hepatocellular carcinoma (HCC) and 71 (26%) progressed towards C-P class B/C without developing cancer. One hundred and thirty-one patients (48%) died or underwent liver transplantation. Multivariate regression analysis showed that clinical stability was significantly associated with older age (P < .001), the absence of diabetes (P = .04) and of oesophageal varices (P < .001), serum albumin >3.5 gr/dL (P = .01) and gamma globulin <1.8 gr/dL (P = .01). HCC development was significantly associated with younger age (P = .01) and serum gamma globulin values ≥1.8 gr/dL (P < .001). C-P score progression was associated with oesophageal varices (P < .001), lower serum albumin (P = .03) and cholesterol (P = .01) values, and hypergammaglobulinemia (P = .02). Death was associated with younger age (P < .001) and hypergammaglobulinemia (P = .01). Multivariate Cox regression analysis and Kaplan-Meier's survival test confirmed that gammaglobulinemia ≥1.8 g/dL was a significant predictor of death (P < .02, and P < .01 respectively)., Conclusions: Hypergammaglobulinemia identifies C-P class A cirrhotic patients at higher risk of disease progression, HCC development and death., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Patients with cirrhosis are at high risk of bacterial infections. Invasive procedures are generally believed to increase this susceptibility., Aims: We investigated the incidence of bacterial infections in cirrhotic patients undergoing elective endoscopic variceal ligation (EVL)., Methods: We enrolled 60 consecutive cirrhotic patients who underwent a total number of 112 elective EVL procedures. One to seven bands were applied at each session until variceal eradication. Markers of inflammation/infection and blood cultures were obtained before and 24 h after EVL., Results: Aetiology of liver disease was metabolic in 27 (45%), viral in 21 (35%), alcoholic in 12 (20%) patients. Child-Pugh class A/B/C distribution was 29/26/5, respectively, 23 (38%) patients had ascites and 15 (25%) had hepatocellular carcinoma. Blood cultures were negative in all samples before EVL, whereas 3/112 (2.7%) cultures tested positive after endoscopy. Streptococcus mitis and Staphylococcus epidermidis were isolated in 1 and 2 cases, respectively. None of these three patients developed any features of clinically relevant infection, suggesting that the positive cultures were an expression of a transient bacteraemia with no clinical sequelae., Conclusions: Bacterial infection is an uncommon occurrence after elective EVL in cirrhotic patients, and antibiotic prophylaxis is not necessary in this clinical setting., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Species distribution models have great potential to efficiently guide management for threatened species, especially for those that are rare or cryptic. We used MaxEnt to develop a regional-scale model for the koala Phascolarctos cinereus at a resolution (250 m) that could be used to guide management. To ensure the model was fit for purpose, we placed emphasis on validating the model using independently-collected field data. We reduced substantial spatial clustering of records in coastal urban areas using a 2-km spatial filter and by modeling separately two subregions separated by the 500-m elevational contour. A bias file was prepared that accounted for variable survey effort. Frequency of wildfire, soil type, floristics and elevation had the highest relative contribution to the model, while a number of other variables made minor contributions. The model was effective in discriminating different habitat suitability classes when compared with koala records not used in modeling. We validated the MaxEnt model at 65 ground-truth sites using independent data on koala occupancy (acoustic sampling) and habitat quality (browse tree availability). Koala bellows ( n  = 276) were analyzed in an occupancy modeling framework, while site habitat quality was indexed based on browse trees. Field validation demonstrated a linear increase in koala occupancy with higher modeled habitat suitability at ground-truth sites. Similarly, a site habitat quality index at ground-truth sites was correlated positively with modeled habitat suitability. The MaxEnt model provided a better fit to estimated koala occupancy than the site-based habitat quality index, probably because many variables were considered simultaneously by the model rather than just browse species. The positive relationship of the model with both site occupancy and habitat quality indicates that the model is fit for application at relevant management scales. Field-validated models of similar resolution would assist in guiding management of conservation-dependent species.

Background & Aims: Serial evaluation of hepatitis B virus (HBV) DNA and aminotransferase values is required for identification of inactive HBV carriers (ICs). Recently, HBV surface antigen quantification (qHBsAg) and liver stiffness measurement (LSM) have been proposed as diagnostic tools in chronic HBV infection. The aim of this study was to evaluate the efficacy of HBV DNA quantification, qHBsAg and LSM in diagnosing ICs at a single time point., Methods: Fifty-seven previously characterized ICs and 90 untreated HBsAg-/anti-HBe-positive patients [49 chronic hepatitis (CH), 41 cirrhosis] were enrolled. HBV DNA ≤2000 IU/mL, LSM ≤6.2 kPa and qHBsAg ≤1000 IU/mL were used as cut-offs to evaluate sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy (DA)., Results: Combined HBV DNA quantification and qHBsAg correctly identified 30/57 (52.6%) ICs showing 94% sensitivity, 96% specificity, 98% PPV, 87% NPV and 95% DA. HBV DNA coupled with LSM identified 40/57 (70.2%) ICs showing 97% sensitivity, 97% specificity, 98% PPV, 95% NPV and 97% DA. Combined LSM and qHBsAg identified 33/57 (57.9%) ICs showing 95% sensitivity, 78% specificity, 89% PPV, 89% NPV and 89% DA. The evaluation of the three parameters altogether allowed the identification of 23/57 (40.3%) ICs showing 100% specificity, 96% sensitivity, 100% PPV, 92% NPV and 97% DA. Similar results were obtained when either CH or cirrhotic patients were excluded from the analysis., Conclusions: Combined evaluation of HBV DNA amount with LSM and/or qHBsAg is a highly reliable tool allowing the identification of a considerable number of HBV ICs at a single time point evaluation., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Contrast medium administration is one of the leading causes of acute kidney injury (AKI) in different clinical settings. The aim of the study was to investigate occurrence and predisposing factors of AKI in cirrhotic patients undergoing contrast-enhanced computed tomography (CECT).Datasets of 1279 consecutively hospitalized cirrhotic patients were retrospectively analyzed. Two hundred forty-nine of 1279 patients (mean age 64 ± 11 years, 165 male) who had undergone CECT were selected on the basis of the availability of serum creatinine (sCr) values evaluated before and after CECT (CECT group). In analogy, 203/1279 cases (mean age 66 ± 10 years, 132 male) who had not undergone CECT and had been tested twice for sCr in 7 days were also included as controls (Control group). AKI network criteria were employed to assess contrast-induced AKI (CI-AKI) development. Apart from lack of narrowed double sCr measurements, additional exclusion criteria were active bacterial infections, nephrotoxic drugs intake, and estimated glomerular filtration rate <30 mL/min.AKI developed in 22/249 (8.8%) and in 6/203 (3%) of the CECT and the Control groups, respectively (P = 0.01). The multivariate logistic regression analysis showed that AKI was significantly associated with contrast medium administration (odds ratio [OR]: 3.242, 95% confidence interval [CI]: 1.255-8.375; P = 0.015), female sex (OR: 0.339, 95% CI: 0.139-0.827; P = 0.017), and sCr values (OR: 0.124, 95% CI: 0.016-0.975; P = 0.047). In the CECT group, presence of ascites (OR: 2.796, 95% CI: 1.109-7.052; P = 0.029), female sex (OR: 0.192, 95% CI: 0.073-0.510; P = 0.001), and hyperazotemia (OR: 1.018, 95% CI: 1.001-1.037; P = 0.043) correlated with CI-AKI development at multivariate analysis.CI-AKI is a quite frequent occurrence in cirrhotic patients with female sex, presence of ascites, and hyperazotemia being the predisposing factors., Competing Interests: The authors have no conflicts of interest to disclose.

Aortic valve disease is a prevalent disorder that affects approximately 2% of the general adult population. Surgical aortic valve replacement is the gold standard treatment for symptomatic patients. This treatment has demonstrably proven to be both safe and effective. Over the last few decades, in an attempt to reduce surgical trauma, different minimally invasive approaches for aortic valve replacement have been developed and are now being increasingly utilized. A narrative review of the literature was carried out to describe the surgical techniques for minimally invasive aortic valve surgery and report the results from different experienced centers. Minimally invasive aortic valve replacement is associated with low perioperative morbidity, mortality and a low conversion rate to full sternotomy. Long-term survival appears to be at least comparable to that reported for conventional full sternotomy. Minimally invasive aortic valve surgery, either with a partial upper sternotomy or a right anterior minithoracotomy provides early- and long-term benefits. Given these benefits, it may be considered the standard of care for isolated aortic valve disease.

Aortic stenosis (AS) is a common valvular heart disease in the Western populations, with an estimated overall prevalence of 3% in adults over 75 years. To understand its patho-biological processes represents a priority. In elderly patients, AS usually involves trileaflet valves and is referred to as degenerative calcific processes. Scientific evidence suggests the involvement of an active "atherosclerosis-like" pathogenesis in the initiation phase of degenerative AS. To the contrary, the progression could be driven by different forces (such as mechanical stress, genetic factors and interaction between inflammation and calcification). The improved understanding presents potentially new therapeutic targets for preventing and inhibiting the development and progression of the disease. Furthermore, in clinical practice the management of AS patients implies the evaluation of generalized atherosclerotic manifestations (i.e., in the coronary and carotid arteries) even for prognostic reasons. In counselling elderly patients, the risk stratification should address individual frailty beyond the generic risk scores. In these regard, the co-morbidities, and in particular those linked to the global atherosclerotic burden, should be carefully investigated in order to define the risk/benefit ratio for invasive treatment strategies. We present a detailed overview of insights in pathogenesis of AS with possible practical implications.

Background & Aims: Few information is available regarding atrial fibrillation in cirrhotic patients. The aim of this study was to investigate the occurrence and clinical impact of atrial fibrillation in these patients., Methods: Three hundred and thirty-five cirrhotic patients (219 males; mean age 65 ± 10.85 years; 196 Child-Pugh class A, 104 class B and 35 class C) were consecutively analysed and followed up for 24 months. Electrocardiograms were available for all patients before starting the study, at basaltime and during the follow-up. Echocardiography was performed in individuals with atrial fibrillation and in 100 randomly chosen patients without it., Results: Atrial fibrillation was observed in 21/335 cirrhotics (mean age 75 ± 7 years, 13 male), six of whom had permanent and 15 had paroxysmal atrial fibrillation. At univariate analysis, atrial fibrillation significantly correlated with older age, history of coronary heart disease, Child-Pugh score, serum albumin, hepatic encephalopathy, treatment with furosemide, QTc prolongation, atrial section areas, increased PAPs and thickness of interventricular septum. Age [odd ratio 1.12, 95% CI (1.05-1.2), P = 0.001], history of coronary heart disease [odd ratio 4.93, 95% CI (1.04-23.54), P = 0.04] and PAPs [odd ratio 1.12, 95% CI (1.02-1.2), P = 0.01] maintained statistical significance at multivariate analysis. Fifty-one of the 335 patients died during the follow-up. At Cox regression analysis, advanced Child-Pugh score [hazard ratio 1.546, 95% CI (1.357-1.762), P = 0.037] and increased heart rate [hazard ratio 1.117, 95% CI (1.021-1.223), P = 0.016] were significantly associated with mortality which was independent of atrial fibrillation occurrence., Conclusions: Cirrhosis is not a predisposing factor of atrial fibrillation, which in turn has no impact on mortality in cirrhotic patients., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Aim of this study was to investigate the role of aetiology, diabetes, tobacco smoking and hypertension in the survival of patients with hepatocellular carcinoma., Methods: A prospective cohort of 552 patients (81.5% males, mean age 64.4 years) first diagnosed with hepatocellular carcinoma in 1995-2001 in Brescia, Italy, was retrospectively analyzed. Data on the presence of diabetes mellitus, hypertension, heavy alcohol intake and tobacco smoking were obtained from patients' clinical charts or interviews. Survival analysis was performed using univariate and multivariate methods (Cox proportional hazards model)., Results: 33% had a history of heavy alcohol intake, 24.3% had viral hepatitis and 33.5% had both aetiologies. Diabetes, hypertension and tobacco smoking were found in 29.9%, 37.9% and 35.9%, respectively. During follow-up (median 19.9 months), the median survival was 19.9 (95% confidence interval [CI] 16.7-22.8) months. Using multivariate Cox regression models, alcohol-related liver disease and diabetes were found to be associated with mortality, with hazard ratios of 1.32 (95% CI 0.99-1.75) and 1.25 (95% CI 1.02-1.54), respectively. Hypertension and smoking habit did not influence survival., Conclusions: Alcohol aetiology and the presence of diabetes were positively associated with patient mortality with hepatocellular carcinoma, whereas tobacco smoking and hypertension were not., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Hepatitis B virus (HBV) and hepatitis C virus (HCV) share common mode of transmission and both are able to induce a chronic infection. Dual HBV/HCV chronic coinfection is a fairly frequent occurrence, especially in high endemic areas and among individuals at high risk of parenterally transmitted infections. The intracellular interplay between HBV and HCV has not yet been sufficiently clarified, also due to the lack of a proper in vitro cellular model. Longitudinal evaluation of serum HBV DNA and HCV RNA amounts has revealed that complex virological profiles may be present in coinfected patients. Dual HBV/HCV infection has been associated to a severe course of the liver disease and to a high risk of developing hepatocellular carcinoma. Despite the clinical importance, solid evidence and clear guidelines for treatment of this special population are still lacking. This review summarizes the available data on the virological and clinical features as well as the therapeutic options of the dual HBV/HCV infection, and highlights the aspects that need to be better clarified.

The long-lasting persistence of hepatitis B virus (HBV) genomes in the liver (with detectable or undetectable HBV DNA in the serum) of individuals testing negative for the HBV surface antigen (HBsAg) is termed occult HBV infection (OBI). Although in a minority of cases the lack of HBsAg detection is due to infection with variant viruses unrecognized by available assays (S-escape mutants), the typical OBI is related to replication-competent HBVs strongly suppressed in their replication activity. The causes of HBV suppression are not yet well clarified, although the host's immune surveillance and epigenetic mechanisms are likely involved. OBI is a worldwide diffused entity, but the available data of prevalence in various categories of individuals are often contrasting because of the different sensitivity and specificity of the methods used for its detection in many studies. OBI may have an impact in several different clinical contexts. In fact, it can be transmitted (i.e., through blood transfusion and liver transplantation) causing classic forms of hepatitis B in newly infected individuals. The development of an immunosuppressive status (mainly by immunotherapy or chemotherapy) may induce OBI reactivation and development of acute and often severe hepatitis. Finally, evidence suggests that OBI can favor the progression of liver fibrosis, in particular in HCV-infected patients. The possible contribution of OBI to the establishment of cirrhosis also implies its possible indirect role in the development of hepatocellular carcinoma. On the other hand, OBI may maintain most of the direct transforming properties of the overt HBV infection, such as the capacity to integrate in the host's genome and to synthesize pro-oncogenic proteins.

Aim: The metabolic syndrome (MS) is associated with increased cardiovascular and cerebrovascular risk. This study aimed to compare the difference of the three established diagnostic criteria of MS, developed by Adult Treatment Panel III (ATP III), American Heart Association (AHA) and National Heart Lung and Blood Institute (NHLBI), and International Diabetes Federation (IDF), with regard to the prevalence of the syndrome and the ability to correctly identify individuals with cardiovascular or cerebrovascular disease or subclinical atherosclerosis., Methods: We studied 947 consecutive patients underwent clinical evaluation between the 1997-2002. The project design included a medical assessment, biochemical analyses and the ecocolordoppler examination of carotid arteries., Results: The MS prevalence was 37% in ATPIII subjects, 36% in AHA/NHLBI subjects and 43% in IDF subjects. Excluding patients with diabetes (N.=259), the MS prevalence ranged from 32% (ATPIII and AHA/NHLBI subjects) and 40% (IDF subjects). By most criteria, MS-positive subjects had significant incidence of carotid atherosclerosis (P<0.05) and cardiovascular events (P<0.05) than MS-negative subjects, but not cerebrovascular events. Finally, patients with MS had higher serum levels of fibrinogen (P<0.04)., Conclusion: Subclinical atherosclerosis and cardiovascular events were increased in presence of the MS, irrespective of the several definitions.

Aim: The presence of the metabolic syndrome (MS) increases cardiovascular morbidity and mortality and we aimed to assess the outcome in subjects with the MS and subclinical atherosclerosis., Methods: We followed-up for five years 339 Mediterranean subjects with asymptomatic carotid intima-media thickness >0.9 mm (men: 60%; age: 66±5 years), of whom 130 had the MS (men: 59%; age: 66±5 years), evaluating at baseline traditional cardiovascular risk factors (including male gender, older age, obesity, hypertension, diabetes, smoking, family history of cardiovascular diseases, dyslipidemia) and plasma levels of C-reactive protein and fibrinogen., Results: Cardio- and cerebrovascular events were registered in the 29% of subjects with the MS and in the 20% of those without it and the presence of more criteria for the diagnosis of the MS was significantly associated with vascular morbidity and mortality. By multivariate analysis, including all baseline variables, independent predictive roles for the events were found for elevated markers of inflammation (OR 3.8), elevated fasting glucose (OR 2.1) and elevated triglycerides (OR 1.4)., Conclusion: These findings confirm a worst vascular outcome in subjects with more criteria for the diagnosis of the MS and further suggest the need of future research to understand the combined role of inflammation and the MS in the progression from subclinical to clinical atherosclerosis.

Scombroid syndrome is a fish poisoning characterised by the onset of symptoms compatible with a pseudoallergic reaction; it is rarely also responsible of signs and symptoms of acute coronary syndromes, as demonstrated in this case report.

Objective: The study of the mitral valve apparatus and its modifications during functional mitral regurgitation (FMR) is better revealed by 3-dimensional (3D) transesophageal echocardiography (TOE). To plan mitral valve repair by annuloplasty and papillary muscle (PPM) relocation, we proposed a valve repair procedure oriented by the new main features obtained by real-time 3D TOE reconstruction of the mitral valve apparatus., Methods: Since January 2008, 25 patients with severe FMR before mitral valve repair were examined. Mean coaptation depth and mean tenting area were 1.3 ± 0.2 cm and 3.2 ± 0.5 cm(2), respectively. Intraoperative 2D and 3D TOE were performed, followed by a 3D offline reconstruction of the mitral valve apparatus. A schematic mitral valve apparatus model was obtained. A geometric model like a truncated cone was traced in according to the preoperative measurements. The size of the prosthetic ring was selected preoperatively according to the anterior leaflet surface. The expected truncated cone after annuloplasty was retraced. A conventional normal coaptation depth about 0.6 cm was used to detect the new position of the PPM tips., Results: Offline reconstruction of the mitral valve apparatus and respective truncated cone were feasible in all patients. The expected position of the PPM tips desirable to reach a normal tenting area with a coaptation depth 0.6 cm or less was obtained in all patients. After surgery, all parameters were calculated and no statistically significant difference was found compared with the expected data., Conclusions: PPM relocation plus ring annuloplasty reduce mitral valve tenting and may improve mitral valve repair results for patients with severe FMR. This technique may be easily and precisely guided by preoperative offline 3D echocardiographic mitral valve reconstruction., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objectives: Intraoperative three-dimensional (3D) transesophageal echocardiography (TEE) has been suggested to be a valuable technique for the evaluation of the mechanisms of ischemic mitral regurgitation (IMR). Studies comparing multiplane two-dimensional (2D) with 3D TEE reconstruction of the mitral valve using the new mitral valve quantification (MVQ) software are lacking. We undertook a prospective comparison between multiplane 2D and 3D TEE for the assessment of IMR., Methods: We evaluated echocardiographically 45 patients with IMR who underwent mitral valve surgery in our institution. 2D and 3D TEE examinations followed by a 3D offline assessment of the mitral valve apparatus were performed in all patients. Offline analysis of mitral valve apparatus was conducted with QLAB-MVQ., Results: 3D TEE image acquisitions were performed in a short period of time and were feasible in all patients. Real time 3D TEE imaging was superior to 2D in identifying specific mitral scallops (A1, A3, P1, P3) and commissures. When compared with 2D TEE, 3D offline reconstruction of the mitral valve allows an accurate quantification of the shape and diameters of the mitral annulus. Both approaches provide almost similar values for the tenting area and the coaptation depth. The 3D approach gave the advantage of direct calculation of the leaflets angles, tenting volume, and surface of the leaflets. The interpapillary muscles distance at the level of the papillary muscle head was greater in 2D than in 3D., Conclusions: 3D TEE imaging provides valuable and complementary information to multiplane 2D TEE for the assessment of patients with IMR., (© 2011, Wiley Periodicals, Inc.)

Objective: Considering that celiac disease (CD) is an autoimmune-based entity and the hepatitis C virus is suspected of being able to trigging autoimmune reactions, it has been hypothesized that hepatitis C virus infection might predispose to CD. The aim of this study was to investigate CD-related antibodies in a large series of hepatitis C virus-infected subjects that were also tested for non-organ-specific autoantibodies (NOSA) as indirect marker of autoimmune disorders., Methods: Two hundred and forty-four patients with chronic hepatitis C virus infection (HCV-patients) and 121 patients with HCV-negative liver disease (non-HCV-patients) underwent NOSA determination and celiac serology (firstly, anti-tissue transglutaminase antibodies, then the cases which tested positive were subsequently evaluated for the presence of antiendomysial antibodies). Serum samples from 42 of the HCV-patients who underwent interferon-alpha therapy after enrollment were tested for celiac antibodies and NOSA even after stopping treatment. Additionally, sera from 1,230 blood donors were assayed for celiac serology as healthy control population., Results: Positive anti-endomysial antibodies (AEA) were found in 5/244 (2%) HCV-patients, 1/121 (0.8%) non-HCV-patients and 2/1,230 (0.16%) blood donors, with a significant difference between HCV-patients and blood donors (P = 0.02; Odds ratio 12.8; 95% Confidence Interval 2.4-66). NOSA were found in 51 HCV-patients but only one of them had positive AEA. Eight out of 42 HCV-patients treated with interferon-alpha developed NOSA under therapy and none of them had CD antibodies., Conclusions: AEA occur in 2% of HCV-patients and their presence is independent of other patterns of autoimmunity.

Objective: Current data on the prevalence of occult hepatitis B virus (HBV) infection in HIV-positive individuals conflict. As occult HBV infection could have an impact on the outcome of liver disease in HIV-positive patients, we investigated a large number of HIV-positive/HBV-surface-antigen (HBsAg) negative subjects with hepatitis C virus (HCV) infection by using the 'gold standard' approach for occult HBV detection--analysis of liver DNA extracts., Methods: The presence or absence of HBV DNA was determined by PCR testing of four different viral genomic regions in DNA extracts of needle liver biopsy specimens of 101 HBsAg negative individuals with HIV/HCV co-infection. HBV genotyping was performed by sequencing analysis of the preS-S gene in occult HBV isolates from 18 cases., Results: Occult HBV infection was diagnosed in 42 of the 101 cases (41%). No clinically relevant difference was found between occult HBV-positive and -negative patients. HBV genotype D and A were detected, respectively, in 11 (61%) and 7 (39%) of 18 cases analysed., Conclusions: Occult HBV infection frequently occurs in HIV/HCV co-infected patients indicating the importance of performing prospective studies able to clarify its clinical impact in these patients. HBV genotype A is highly prevalent in HIV-infected subjects with occult HBV infection in a similar way to HBsAg/HIV-positive individuals.

Background and Aim: There is suspicion of a decrease in warning regarding the hepatitis B virus as a health problem both by the infected individuals and their doctors. The aim of this study was to investigate whether the clinical/virology investigation of chronic hepatitis B virus infected individuals is at present accurate., Methods: The chronic hepatitis B virus surface antigen carriers consecutively attending 13 different hospital divisions in Calabria from July to December 2005 were evaluated to investigate the available information on the grade of their liver disease, their virologic profile and the hepatitis B virus status of their family members., Results: Four-hundred-thirty hepatitis B virus surface antigen positive individuals were enrolled, 417 of whom were Calabrians. Most of them had a diagnosis of chronic liver disease, but a liver biopsy had been performed only in 13.5% of the cases, whereas more than 1/3 of them had not been tested for hepatitis Delta virus co-infection. The majority of these individuals were unaware of the hepatitis B virus status of their family members. Moreover, anti-hepatitis B virus vaccination procedures were not performed in most of the hepatitis B virus surface antigen carrier families., Conclusions: This study revealed that fundamental clinical, virological, and epidemiological aspects of chronic hepatitis B virus infection are not investigated in many hepatitis B virus surface antigen carriers, suggesting that the general knowledge as regards hepatitis B virus is mostly inadequate.

Background: Occult hepatitis B virus (HBV) infection frequently occurs in patients with HBV surface antigen (HBsAg)-negative chronic liver disease, and much evidence suggests that it is a risk factor for hepatocellular carcinoma (HCC) development. However, to the authors' knowledge, no follow-up study has been performed to date evaluating HCC occurrence over time in chronic hepatitis patients with or without occult HBV infection., Methods: A cohort of the 380 HBsAg-negative chronic hepatitis patients attending the study institution between 1991-2000 were evaluated and tested for occult HBV DNA by analysis of liver biopsy specimens., Results: There were 135 patients (35.5%) with occult HBV and 245 patients (64.5%) without occult HBV. Cirrhosis was significantly associated with occult HBV infection (P = 0.01). One hundred thirty-four of these patients were followed for a minimum of 50 months (median, 82.8 +/- 32.6 mos). Fifty-three patients (39%) were occult HBV carriers and 81 (61%) were not. Nine patients developed HCC during the follow-up; eight were positive and one was negative for occult HBV (P = 0.002)., Conclusions: The current observational cohort study showed that, among the HBsAg-negative patients with chronic hepatitis, HCC develops for the most part in carriers of occult HBV. Therefore, the evaluation of HBV genomes in chronic hepatitis patients appears to be a powerful tool for the identification of individuals at higher risk of HCC development., ((c) 2006 American Cancer Society.)

Unlabelled: STUDY SUBJECT: We longitudinally evaluated the virological behaviour and the hepatitis B virus (HBV) genomic variability in inactive HBV surface antigen (HBsAg) chronic carriers., Patients and Methods: Fourteen HBsAg-positive healthy workers (13 inactive carriers and 1 with active HBV infection) were followed up for 12 months by monthly evaluation of aminotransferase, HBV DNA, and IgM anti HBV core antigen (IgM anti-HBc) values. Moreover, HBV serum isolates from each case were amplified, cloned and sequenced to evaluate the presence of the potentially clinical relevant core-promoter and precore mutations. The same technical procedures were used to examine the S gene of isolates from 3 randomly selected inactive carriers and the patients with active HBV infections., Results: Aminotransferase values were constantly normal in all cases. Viremia levels appear to fluctuate widely over time in each individual case, although the HBV DNA remained below 2 x 10(4) copies/ml in all samples. Only four serum samples from two inactive carriers had IgM anti-HBc values higher than the specific cut-off limit of the assay. Either wild type or core-promoter/precore HBV variants or a mixture of them were detected in the inactive carriers. S gene nucleotide homology among the clones from the three inactive carriers and the subject with active infection was 98.9%, 98.3%, 98.1% and 98.2%, respectively., Conclusions: The degree of suppression of HBV replication in inactive carriers is variable over time, and the entity and quality of HBV variability is comparable between active and inactive carriers.

Background/aims: PreS2-defective hepatitis B virus (HBV) variants may emerge during chronic HBV infection. These variants carry mutation(s) at the ATG-start-codon and/or in-frame deletion into the preS2 genomic region and are commonly detected by sequencing analyses. We evaluated the prevalence of these variants in a large series of chronic HBV infected patients through non-sequencing molecular approaches., Methods: We examined HBV isolates from 110 HBV carriers: 15 were inactive carriers (IC); 50 had chronic hepatitis (CH); 25 were cirrhotics; 19 had hepatocellular carcinoma (HCC). The entire preS2 genomic region was amplified by PCR technique. The amplicons were processed: (A) through electrophoresis on acrylamide gel to reveal deleted genomes; (B) through electrophoresis on agarose gel after digestion by NlaIII enzyme that cuts the wild ATG-start-codon but not the mutated one., Results: We detected preS2 variants in 56/110 cases (51%). In particular, we found preS2-defective mutants in 2/15 IC, 25/50 CH, 13/26 cirrhotics, and 16/19 HCC. The presence of these variants was thus significantly associated with active infection and liver disease (P<0.002). Moreover, among cases with liver disease preS2-mutants were more prevalent in HCC patients (P<0.02)., Conclusions: Our non-sequencing molecular methods are sensitive and specific, and simplify the identification of all preS2 HBV variant forms. Infection by these variants is significantly associated with active infection and HCC.