The Italian compassionate use of sofosbuvir in HCV patients waitlisted for liver transplantation: A national real-life experience.

BACKGROUND & AIMS: This study aimed to assess the real-life clinical and virological outcomes of HCV waitlisted patients for liver transplantation (LT) who received sofosbuvir/ribavirin (SOF/R) within the Italian compassionate use program. METHODS: Clinical and virological data were collected in 224 patients with decompensated cirrhosis and/or hepatocellular carcinoma (HCC) receiving daily SOF/R until LT or up a maximum of 48 weeks. RESULTS: Of 100 transplanted patients, 51 were HCV-RNA negative for >4 weeks before LT (SVR12: 88%) and 49 negative for <4 weeks or still viraemic at transplant: 34 patients continued treatment after LT (bridging therapy) (SVR12: 88%), while 15 stopped treatment (SVR12: 53%). 98 patients completed SOF/R without LT (SVR12: 73%). In patients with advanced decompensated cirrhosis (basal MELD ≥15 and/or C-P ≥B8), a marked improvement of the scores occurred in about 50% of cases and almost 20% of decompensated patients without HCC reached a condition suitable for inactivation and delisting. CONCLUSIONS: These real-life data indicate that in waitlisted patients: (i) bridging antiviral therapy can be an option for patients still viraemic or negative <4 weeks at LT; and (ii) clinical improvement to a condition suitable for delisting can occur even in patients with advanced decompensated cirrhosis.

Prediction of Conventional Oxygen Therapy Failure in COVID-19 Patients With Acute Respiratory Failure by Assessing Serum Lactate Concentration, PaO2/FiO2 Ratio, and Body Temperature.

One of the challenges that emerged during the coronavirus disease 2019 (COVID-19) pandemic and is still relevant today is the need to identify patients with acute respiratory failure (ARF) who could benefit from conventional oxygen therapy (COT) - oxygen supplementation with nasal cannulas, Venturi masks, and non-rebreather masks - without recurring to advanced respiratory therapy, such as high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), non-invasive ventilation (NIV), or invasive mechanical ventilation. The aim of the study was to develop a clinical tool able to predict the failure of COT in COVID-19 patients presenting to the emergency department (ED) with ARF. This was a retrospective monocentric cohort study carried out in the ED of the University Hospital of Bologna Sant'Orsola-Malpighi Polyclinic, Italy. The cohort comprised 101 COVID-19 patients with ARF from the first pandemic wave who received COT. This cohort was used to develop a scale that considers serum lactate concentration, partial arterial oxygen pressure/inspired oxygen fraction (PaO2/FiO2) ratio, and body temperature to predict COT failure, referred to as the Lactate, Oxygenation, and Temperature (LOT) score. The highest possible score was 17 points. The LOT score was associated with COT failure (area under the receiver operating curve or AUROC = 0.79, 95% CI 0.69 - 0.89, p < 0.001); the cut-off value of > 5 points had optimal predictive power and showed significantly higher 30-day mortality (log-rank χ2 = 28,828, p < 0.0001). The LOT score was able to effectively predict COT failure in COVID-19 patients with ARF. Patients with LOT score > 5 had a very high risk of therapy failure, and more advanced respiratory therapies must be considered in these patients.

CovHos, a New Score to Predict the Need of Hospitalization for Coronavirus Disease 2019 (COVID-19) Patients at the Emergency Department.

INTRODUCTION AND AIM: As first receivers of suspected coronavirus disease 2019 (COVID-19) patients, clinicians of the Emergency Department (ED) have to rapidly perform the first clinical assessment evaluating the intensity of care needed. So far, clear management guidelines still lack. We identified variables associated with hospitalization in order to give a quick tool to assist clinicians in stratifying cases based on the severity at their arrival at the ED and in predicting the need for hospital care.  Methods: This is a monocentric observational prospective study enrolling COVID-19 patients. A score for hospitalization prediction (CovHos Score) was created using variables associated with hospitalization at multivariate analysis and then validated on an internal subsequent cohort. RESULTS: A total of 667 patients were included; 465 (69.7%) were hospitalized and 108 (16.2%) died at 30-days follow-up. In a multivariate analysis, male sex, age>65, alveolar-to-arterial oxygen gradient percentage increase compared to that expected for age, neutrophils/lymphocytes ratio and C-reactive protein levels were significantly associated with a higher rate of hospital admission. A CovHos score cut-off of 12 points predicted hospitalization with 85% sensitivity and 82.4 % specificity (area under a receiver operating characteristic curve [AUROC] = 0.909, 95% CI 0.884 - 0.935). Similar results were obtained in the validation court. A cut-off of 22 has 79% sensitivity and 77% specificity in predicting mortality (AUROC = 0.824; 95% CI 0.782-0.866); sensitivity and specificity were respectively 71.4% and 71.3% in the validation group. CONCLUSIONS: Although medical judgment still remains crucial, the CovHos score is an effective tool to assist emergency clinicians in predicting the need for hospitalization or to optimize allocation in a shortage of hospital resources.

Role of ROX index in the first assessment of COVID-19 patients in the emergency department.

During the first outbreak of Coronavirus disease 2019 (COVID-19) Emergency Departments (EDs) were overcrowded. Hence, the need for a rapid and simple tool to support clinical decisions, such as the ROX index (Respiratory rate - OXygenation), defined as the ratio of peripheral oxygen saturation and fraction of inspired oxygen, to respiratory rate. The aim of the study was to evaluate the accuracy of the ROX index in predicting hospitalization and mortality in patients with a diagnosis of COVID-19 in the ED. The secondary outcomes were to assess the number of readmissions and the variations in the ROX index between the first and the second admission. This was an observational prospective monocentric study, carried out in the ED of Sant'Orsola-Malpighi Hospital in Bologna, Italy. Five hundred and fifty-four consecutive patients with COVID-19 were enrolled and the ROX index was calculated. Patients were followed until hospital discharge or death. A ROX index value < 25.7 was associated with hospitalization (area under the curve [AUC] = 0.737, 95% CI 0.696-0.779, p < 0.001). The ROX index < 22.3 was statistically related to higher 30-day mortality (AUC = 0.764, 95% CI 0.708-0.820, p < 0.001). Eight patients were discharged and returned to the ED within the subsequent 7 days, their mean ROX index was 30.3 (6.2; range 21.9-39.4) at the first assessment and 24.6 (5.5; 14.5-29.5) at the second assessment, (p = 0.012). The ROX index, together with laboratory, imaging and clinical findings, correlated with the need for hospital admission, mechanical ventilation and mortality risk in COVID-19 patients.

Criteria for diagnosing benign portal vein thrombosis in the assessment of patients with cirrhosis and hepatocellular carcinoma for liver transplantation.

Malignant portal vein thrombosis is a contraindication for liver transplantation. Patients with cirrhosis and early hepatocellular carcinoma (HCC) may have either malignant or benign (fibrin clot) portal vein thrombosis. The aim of this study was to assess prospectively whether well-defined diagnostic criteria would enable the nature of portal vein thrombosis to be established in patients with HCC under consideration for liver transplantation. Benign portal vein thrombosis was diagnosed by the application of the following criteria: lack of vascularization of the thrombus on contrast-enhanced ultrasound and on computed tomography or magnetic resonance imaging, absence of mass-forming features of the thrombus, absence of disruption of the walls of veins, and, if uncertainty persisted, biopsy of the thrombus for histological examination. Patients who did not fulfill the criteria for benign thrombosis were not placed on the transplantation list. In this study, all patients evaluated at our center during 2001-2007 with a diagnosis of HCC in whom portal vein thrombosis was concurrently or subsequently diagnosed were discussed by a multidisciplinary group to determine their suitability for liver transplantation. The outcomes for 33 patients who met the entry criteria of the study were as follows: in 14 patients who were placed on the transplantation list and underwent liver transplantation, no malignant thrombosis was detected when liver explants were examined histologically; 5 patients who were placed on the transplantation list either remained on the list or died from causes unrelated to HCC; in 9 patients, liver transplantation was contraindicated on account of a strong suspicion, or confirmation, of the presence of malignant portal vein thrombosis; and 5 patients who were initially placed on the transplantation list were subsequently removed from it on account of progression of HCC in the absence of evidence of neoplastic involvement of thrombosis. In conclusion, for a patient with HCC and portal vein thrombosis, appropriate investigations can establish whether the thrombosis is benign; patients with HCC and benign portal vein thrombosis are candidates for liver transplantation.

Widen NomoGram for multinomial logistic regression: an application to staging liver fibrosis in chronic hepatitis C patients.

The interpretation of regression models results can often benefit from the generation of nomograms, 'user friendly' graphical devices especially useful for assisting the decision-making processes. However, in the case of multinomial regression models, whenever categorical responses with more than two classes are involved, nomograms cannot be drawn in the conventional way. Such a difficulty in managing and interpreting the outcome could often result in a limitation of the use of multinomial regression in decision-making support. In the present paper, we illustrate the derivation of a non-conventional nomogram for multinomial regression models, intended to overcome this issue. Although it may appear less straightforward at first sight, the proposed methodology allows an easy interpretation of the results of multinomial regression models and makes them more accessible for clinicians and general practitioners too. Development of prediction model based on multinomial logistic regression and of the pertinent graphical tool is illustrated by means of an example involving the prediction of the extent of liver fibrosis in hepatitis C patients by routinely available markers.

Imaging Diagnosis of Hepatocellular Carcinoma: Recent Advances of Contrast-Enhanced Ultrasonography with SonoVue®.

Due to the ability to detect the typical contrast-imaging pattern for hepatocellular carcinoma (HCC), that is hyperenhancement in the arterial phase and hypoenhancement in the late phase on a cirrhotic background, contrast-enhanced ultrasonography (CEUS) was included in the American diagnostic algorithm for HCC in 2005. However, its role has been questioned because of the possibility of misdiagnosis of cholangiocarcinoma. The present review aims to describe the advantages and disadvantages of CEUS applications using Sonovue® for HCC. In particular there is focus on the accuracy of CEUS in detecting the typical HCC pattern, the CEUS patterns of intrahepatic cholangiocarcinoma (ICC), the risk of misdiagnosis with HCC, the diagnostic use of CEUS in cases of locoregional and systemic treatments, and the evaluation of response to antiangiogenic treatment using dedicated software.

Development and validation of a nomogram based on clinical factors and standard laboratory tests for prediction of clinically significant liver fibrosis in chronic hepatitis C virus infection.

OBJECTIVES: Staging liver fibrosis in chronic viral hepatitis C (HCV) patients is essential for prompting surveillance and treatment. The aim of this study was to develop a nomogram, on the basis of simple clinical and laboratory variables, to predict three clinically significant stages of fibrosis (nil-mild, moderate, advanced/cirrhosis), using histology as reference, and to compare its performance with that of FibroTest, a widely used noninvasive fibrosis score. MATERIALS AND METHODS: Nomograms are graphical representations of a mathematical formula, used as predictive tools. The study retrospectively recruited 406 HCV patients undergoing liver biopsy. Nomogram was developed in a training set of 252 patients and tested in a validation set of 154 patients. Histology was staged according to the Metavir system. Fibrosis stages were subgrouped as follows: advanced fibrosis/cirrhosis (F3/F4, 24%), nil-mild (F0/F1, 36%), and moderate (F2, 40%). Age at biopsy, aspartate aminotransferase, γ-glutamyl transpeptidase, albumin, platelet count, and prothrombin activity formed the basis for the so-called Fibro-Nomogram, which, in one graphical representation, estimates probability for different stages of fibrosis. RESULTS: Areas under the receiver-operating characteristic curves for advanced fibrosis/cirrhosis were similar for training (0.86) and validation sets (0.87). For nil-mild fibrosis, area under the receiver-operating characteristics were 0.81 and 0.79. Compared with FibroTest, Fibro-Nomogram performed slightly better at predicting severe fibrosis (F3/F4) with positive likelihood ratio (LR+) 5.07 (95% confidence interval 3.08-8.37) versus LR+ 3.82 (95% confidence interval 2.56-5.71) for FibroTest. For nil-mild fibrosis, the two tests showed limited but comparable performances. CONCLUSION: In HCV patients, Fibro-Nomogram, an inexpensive and readily available predictive tool, could enable clinicians to interpret patients' profile, concurrently stratifying patients into three clinically relevant probability categories with good overall performance.

Quantification of enhancement of focal liver lesions during contrast-enhanced ultrasound (CEUS). Analysis of ten selected frames is more simple but as reliable as the analysis of the entire loop for most parameters.

The aim of the study was to evaluate the reliability of the analysis of only 10 frames rather than of a whole clip in performing quantitative assessment of tumor enhancement of focal liver lesions (FLLs) following ultrasound contrast injection. Contrast-enhanced ultrasonography (CEUS) examinations of 31 FLLs (median diameter: 30mm) were performed. All clips were analyzed and quantified with an early prototype of the SonoLiver software (TomTec GmbH, Munich and Bracco Research SA, Geneva), first evaluating the entire clip then selecting only 10 frames at different time intervals. Enhancement measurements obtained from the analysis of the entire clip or of only 10 frames were closely correlated (r=0.931 and p<0.0001 for Area Under the Curve; r=0.944 and p<0.0001 for Perfusion Index). In conclusion, enhancement quantification of FLLs can be reliably obtained from only 10 frames, rather than the entire clip, at least for most parameters, making such procedure easier for potential routine use.

Liver AL amyloidosis as a possible cause of high liver stiffness values.

The liver is a common site of amyloid deposition in primary systemic amyloidosis. We report the case of a 52-year-old white woman complaining of hepatomegaly, high levels of alkaline phosphatase and serum gamma-glutamyl transferase. Other laboratory tests showed proteinuria with light-chain type lambda. Color Doppler ultrasonography showed an enlarged bright liver with hepatopetal portal blood flow. Fine-needle aspiration biopsy of abdominal fat, with Congo red stain, was positive for amyloid. No liver biopsy was performed, but transient elastography showed high liver stiffness values (75 kPa), suggestive of amyloid infiltration, as other causes of elevation had been ruled out by clinical, laboratory and radiological findings. Bone marrow morphology and immunoistochemistry confirmed low-grade plasmacytoma with amyloidosis.