Direct Oral Anticoagulants in Patients with Liver Disease in the Era of Non-Alcoholic Fatty Liver Disease Global Epidemic: A Narrative Review.

Atrial fibrillation (AF) and venous thromboembolism (VTE) are highly prevalent and relevant healthcare issues. Direct oral anticoagulants (DOACs) are now the first-choice for anticoagulant treatment of these conditions displaying a better efficacy/safety profile than vitamin-K antagonists, mainly due to significantly reduced risk of major bleeding, especially of intracranial haemorrhage. Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in developed countries showing a continuously growing prevalence. Nonalcoholic steatohepatitis (NASH), its evolutive form, will be the leading cause for liver transplantation by 2020. NAFLD is independently associated with an increased risk of abnormalities of cardiac structure and function, including cardiac rhythm disorders (mainly AF). Moreover, data suggest an increased risk of unprovoked VTE associated with NAFLD/NASH. Therefore, a growing number of patients with chronic liver disease (CLD) will be candidate for anticoagulant therapy in the near future. Cirrhosis of any etiology is characterized by an unstable thrombosis/bleeding haemostatic balance, making anticoagulant therapy particularly challenging in this condition. Given that patients with significant active liver disease and cirrhosis were excluded from all pivotal randomized controlled trials on DOACs, this comprehensive review aims at critically discussing real-world evidence, including the latest population studies, regarding the use of DOACs in patients with CLD/cirrhosis.

Semi-Quantitative Ultrasonographic Evaluation of NAFLD.

Nonalcoholic fatty liver disease (NAFLD) embraces histopathological entities ranging from the relatively benign simple steatosis to the progressive form nonalcoholic steatohepatitis (NASH), which is associated with fibrosis and an increased risk of progression to cirrhosis and hepatocellular carcinoma. NAFLD is the most common liver disease and is associated with extrahepatic comorbidities including a major cardiovascular disease burden. The non-invasive diagnosis of NAFLD and the identification of subjects at risk of progressive liver disease and cardio-metabolic complications are key in implementing personalized treatment schedules and follow-up strategies. In this review, we highlight the potential role of ultrasound semiquantitative scores for detecting and assessing steatosis severity, progression of NAFLD, and cardio-metabolic risk. Ultrasonographic scores of fatty liver severity act as sensors of cardio-metabolic health and may assist in selecting patients to submit to second-line non-invasive imaging techniques and/or liver biopsy.

Epidemiology and outcome of Clostridium difficile infections in patients hospitalized in Internal Medicine: findings from the nationwide FADOI-PRACTICE study.

BACKGROUND: Clostridium difficile (CD) is a leading cause of diarrhoea among hospitalized patients. The objective of this study was to evaluate the rate, the optimal diagnostic work-up, and outcome of CD infections (CDI) in Internal Medicine (IM) wards in Italy. METHODS: PRACTICE is an observational prospective study, involving 40 IM Units and evaluating all consecutive patients hospitalized during a 4-month period. CDI were defined in case of diarrhoea when both enzyme immunoassay for GDH, and test for A/B toxin were positive. Patients with CDI were followed-up for recurrences for 4 weeks after the end of therapy. RESULTS: Among the 10,780 patients observed, 103 (0.96 %) showed CDI, at admission or during hospitalization. A positive history for CD, antibiotics in the previous 4 weeks, recent hospitalization, female gender and age were significantly associated with CDI (multivariable analysis). In-hospital mortality was 16.5 % in CD group vs 6.7 % in No-CD group (p < 0.001), whereas median length of hospital stay was 16 (IQR = 13) vs 8 (IQR = 8) days (p < 0.001) among patients with or without CDI, respectively. Rate of CD recurrences was 14.6 %. As a post-hoc evaluation, 23 out of 34 GDH+/Tox- samples were toxin positive, when analysed by molecular method (a real-time PCR assay). The overall CD incidence rate was 5.3/10,000 patient-days. CONCLUSIONS: Our results confirm the severity of CDI in medical wards, showing high in-hospital mortality, prolonged hospitalization and frequent short-term recurrences. Further, our survey supports a 2-3 step algorithm for CD diagnosis: EIA for detecting GDH, A and B toxin, followed by a molecular method in case of toxin-negative samples.

Epidemiology and outcome of candidemia in internal medicine wards: A regional study in Italy.

BACKGROUND: More than one-third of candidemia episodes occur in Internal Medicine Wards (IMWs) but only few studies have focused on this setting and specific data about epidemiology, clinical characteristics and risk factors for mortality are scant. OBJECTIVE: To describe epidemiology and to assess risk factors for in-hospital mortality among patients with candidemia in IMWs. METHODS: Multicenter retrospective cohort study on patients with candidemia cared for in IMWs of an Italian region (Emilia Romagna) from January 2012 to December 2013. Non survivors were compared with survivors; variables with p≤0.1 at univariate analysis were entered into a multivariate Cox regression model. RESULTS: 232 patients were included. Overall candidemia incidence was 2.2 cases/1000 admissions. Candida albicans accounted for 59% of cases. Antifungal treatment was started <24h, 24-72h, and >72h from blood cultures in 47%, 27% and 12% of patients, respectively; 13.8% of patients received no antifungal treatment. In-hospital mortality was 40%. At multivariate analysis, chronic-obstructive-pulmonary-disease (HR 2.72, 95%CI 1.66-4.45, p<0.001) and isolation of C. tropicalis (HR 2.18, 95%CI 1.19-3.99, p=0.01) were the independent risk factors for in-hospital mortality; central-venous-catheter removal (HR 0.59, 95%CI 0.36-0.96, p=0.03) and adequate and timely (within 72h from blood drawing) empirical therapy (HR 0.42, 95%CI 0.25-0.69, p=0.001) were protective factors. CONCLUSIONS: The present study conducted in a relatively large geographic area confirms high incidence and mortality of candidemia in IMWs, with a worrisome rate of inappropriateness in patient management. Specific interventions aimed to increase awareness of IMWs about candidemia are needed.

[Locoregional treatment of hepatocellular carcinoma: comparison between percutaneous alcohol administration and intraarterial chemoembolization]. / Trattamento locoregionale del carcinoma epatocellulare: confronto tra alcolizzazione percutanea e chemioembolizzazione intrarteriosa.

Between 1991 and 1998, 45 cirrhotic patients with hepatocellular carcinoma (1 or 2 lesions smaller than 5 cm) were treated either with percutaneous ethanol injection (26 patients) or with trans arterial chemoembolization (19 patients) in our Department. Percutaneous ethanol injection was performed on 37 nodules: mean diameter of 3.1 +/- 0.8 cm. Transarterial chemoembolization was performed on 27 nodules: mean diameter of 2.8 +/- 0.7 cm. Therapeutic success at first treatment was obtained in 81.5% of percutaneous ethanol injection treated lesions and in 60.0% of trans arterial chemoembolization treated lesions. Local recurrence after first treatment occurred in 7 of 22 percutaneous ethanol injection patients (31.8%) and 8 of 15 transarterial chemoembolization patients (53.3%). Distant hepatic recurrence after first treatment occurred in 16 of 26 (61.5%) alcolization treated patients and in 14 of 25 (56.0%) chemoembolization treated. Multivariate analysis selected therapeutic success and modality of treatment as the best predictor of better survival probability in all treated patients. Survival probability at 12/24/36/48 months was 96.1/80.8/61.6/42.3% in percutaneous ethanol injection group and 89.5/68.4/36.8/15.8% in transarterial chemoembolization group (p < 0.05 Log rank). Few data are available comparing the efficacy of percutaneous ethanol injection and transarterial chemoembolization in patients with hepatocellular carcinoma. Our data confirm that percutaneous ethanol injection is better than trans arterial chemoembolization in the treatment of patients with one or two lesions of hepatocellular carcinoma.