Laura Riccardi

Thrombotic risk factors in patients with liver cirrhosis: correlation with MELD scoring system and portal vein thrombosis development.

BACKGROUND/AIMS Prognostic scores currently used in cirrhotic patients do not include thrombotic risk factors (TRFs). Predicting factors of portal vein thrombosis (PVT) development are still unknown. We wanted to describe TRFs as a function of liver disease severity using the MELD score and assess the role of local and systemic TRFs as predictors of PVT development in cirrhotic patients. METHODS One hundred consecutive patients with liver cirrhosis were included in the study. TRFs, D-dimers, MELD score, portal vein patency and flow velocity were evaluated in all subjects at baseline and every 6 months thereafter. Variables able to predict PVT development within 1 year were identified by means of multiple logistic regression. RESULTS The plasma levels of protein C and antithrombin were lower and the concentration of D-dimers was higher in patients with advanced disease. Plasma levels of antithrombin, protein C and protein S resulted significantly lower in PVT group at univariate analysis, but reduced portal vein flow velocity was the only variable independently associated with PVT development. CONCLUSIONS Lower concentrations of natural coagulation inhibitors are frequently detected in patients with liver cirrhosis. A reduced portal flow velocity seems to be the most important predictive variable for PVT development in patients with cirrhosis.

Contrast‐enhanced power Doppler of the intestinal wall in the evaluation of patients with Crohn disease

Background: Crohn disease (CD) manifests with highly variable signs and symptoms, and assessment of the status of the disease in the single patient can be difficult. This study was conducted to evaluate the efficacy of power colour Doppler ultrasonography, with and without echo‐enhancement, in distinguishing active from quiescent CD. Methods: Resistance Index (RI) of the superior mesenteric artery (SMA), bowel thickness of the affected loops and the presence of colour signals at power Doppler analysis prior to and after ultrasonography contrast agent injection (Levovist®) were evaluated in 48 patients with CD. Results: In our series, 26/48 patients had active and 22/48 had quiescent CD. A CDAI score ≥150 and a pathological (>5 mg/dL) C reactive protein were significantly correlated with active disease (P < 0.001 and P = 0.004, respectively). Intestinal wall thickness showed no significant correlation with disease status (7.5 ± 1.3 mm in active disease versus 6.8 ± 1.3 mm in quiescent disease; P = 0.11). Vascular signals in the affected loops were revealed in 11/22 patients (50%) with active disease and in 5/26 (20%) with quiescent disease (P = 0.052). After Levovist injection, colour signals were found in 22/22 with active and in 8/26 with quiescent CD (P < 0.001). SMA RI was significantly lower in active CD patients (0.81 ± 0.01 versus 0.83 ± 0.02; P = 0.001). Conclusions: Our data suggest that in patients with CD a finding of a SMA RI ≤ 0.81, or the presence of a colour signal in the wall of the affected loops, at power Doppler sonography, is indicative of active disease. Utilization of echo‐enhancer media can greatly improve the diagnostic sensitivity of intestinal wall power Doppler scan. A finding of intestinal wall thickening is not associated with active disease in our series.

Early prediction of response to sorafenib in patients with advanced hepatocellular carcinoma: The role of dynamic contrast enhanced ultrasound

BACKGROUND & AIMS Sorafenib has become the standard first-line treatment for patients with advanced HCC and acts by inducing alterations in tumor vascularity. We wanted to evaluate the feasibility of dynamic CEUS (D-CEUS) as a predictor of early tumor response to sorafenib and to correlate functional parameters with clinical efficacy end points. METHODS Twenty-eight HCC patients treated with sorafenib 400mg bid were prospectively enrolled. CEUS was performed at baseline (T0) and after 15 (T1) and 30 (T2) days of treatment. Tumor vasculature was assessed in a specific harmonic mode associated with a perfusion and quantification software (Q-Lab, Philips). Variations between T1/T2 and T0 were calculated for five D-CEUS functional parameters (peak intensity, PI; time to PI, TP; area under the curve, AUC; slope of wash in, Pw; mean transit time, MTT) and were compared for responders and non-responders. The correlation between D-CEUS parameters, overall survival (OS), and progression-free survival (PFS) was also assessed. A p value <0.05 was considered statistically significant. RESULTS The percentage variation at T1 significantly correlated with response in three D-CEUS parameters (AUC, PI and Pw; p=0.002, <0.001, and 0.003, respectively). A decrease of AUC (p=0.045) and an increased/unchanged value of TP (p=0.029) and MTT (p=0.010) were associated with longer survival. Three D-CEUS parameters (AUC, TP, Pw) were significantly associated with PFS. CONCLUSIONS D-CEUS provides a reliable and early measure of efficacy for anti-angiogenic therapies and could be an excellent tool for selecting patients who will benefit from treatment.

Contrast‐enhanced gray‐scale harmonic ultrasound in the efficacy assessment of ablation treatments for hepatocellular carcinoma

Abstract: Background. The aim of this study was to compare contrast‐enhanced gray‐scale harmonic ultrasound with multiphasic spiral computed tomography in the assessment of treatment efficacy of non‐surgically treated HCC.

Hepatocellular carcinomas <2 cm in diameter complicating cirrhosis: ultrasound and clinical features in 153 consecutive patients

Abstract: Purpose: To determine the frequencies of various echogenicity patterns in 153 consecutive unifocal hepatocellular carcinomas (HCCs) <2 cm detected in cirrhotic livers and to identify their relationships with clinical, laboratory, and microscopic features.

Nonalcoholic fatty liver disease is associated with increased GHBP and reduced GH/IGF-I levels

Introduction  Nonalcoholic fatty liver disease (NAFLD) has been described in adult GH deficiency syndrome. Furthermore, chronic liver disease can be associated with significant changes in levels of IGF‐I, GH‐binding protein (GHBP), IGF‐binding proteins (IGFBPs) and acid‐labile subunit (ALS). However, the effect of liver steatosis on the GHBP production has not been investigated yet.

A phase II study of sunitinib in advanced hepatocellular carcinoma

BACKGROUND In 2007, sorafenib was the first drug able to improve overall survival in patients with advanced hepatocellular carcinoma. AIM In 2005 we designed a phase II study to assess safety and efficacy of sunitinib. METHODS This is a single arm, open-label, single-centre phase II trial. Eligibility criteria were advanced hepatocellular carcinoma; no prior chemotherapy, performance status 0-1; and Child≤B8. The treatment schedule was 50mg each day orally, 4 weeks on, 2 weeks off. RESULTS Between 10/2007 and 10/2010, 34 patients were enrolled. A significant worsening of liver functional reserve after sunitinib was observed. Grade 3/4 adverse effects occurred in 80% of patients and included fatigue (47%), nausea (15%), liver failure (15%), encephalopathy (12%) and upper gastrointestinal bleeding (12%). Six patients (18%) died within 60 days of enrolment. A partial response was observed in 4 patients (12%). Median time to tumour progression was 2.8 months and median overall survival was 5.8 months. CONCLUSION A dose of 50mg/d induces a high rate of severe adverse events. Toxicity remains a key concern also at the dose of 37.5mg/d. However, sunitinib is able to induce a prolonged response in some patients. Positron Emission Tomography/Computed Tomography scans may select good responders.

Elastography assessment in patients with chronic HCV infection

Introduction:  Liver fibrosis (LB) assessment plays an important role in hepatology. A common characteristic of all chronic liver diseases is the occurrence and progression of fibrosis towards cirrhosis. Besides its plain interest for prognosis purposes, determining the fibrosis reveals the natural history of the disease and the risk factors associated with its progression to guide the antifibrotic action of different treatments.

Usefulness of contrast enhanced ultrasound in monitoring therapeutic response after hepatocellular carcinoma treatment

In the last years, the development in the oncology field has been huge and rapid. In particular, the evaluation of response to anti-tumour treatments has been being object of intense research, producing significant changes. Response assessment after therapy in solid neoplasias has always used radiological imaging techniques, with tumour size reduction representing a presumed therapeutic efficacy. However, with the introduction of anti-angiogenetic drugs the evaluation of tumour size has become unsuitable because some tumours, under treatment, show only tumour perfusion changes rather than lesion shrinkage. Between different imaging techniques with contrast-enhancement, contrast-enhanced ultrasound (CEUS) and, in particular, dynamic CEUS have arisen as a promising and non-invasive device for monitoring cancer treatments. Moreover, the introduction of perfusion software has even more refined the technique since it is able to provide quantitative parameters related to blood flow and blood volume that can be associated with tumour response and clinical outcome such as the progression free survival and the overall survival. Here, we give an overview of the current status of CEUS in monitoring hepatocellular carcinoma response to different kind of treatments.

Contrast ultrasound LI-RADS LR-5 identifies hepatocellular carcinoma in cirrhosis in a multicenter restropective study of 1,006 nodules

Background & Aims. The use of contrast enhanced ultrasound (CEUS) for the diagnosis of hepatocellular carcinoma (HCC) in cirrhosis was questioned for the risk of false positive diagnosis in case of cholangiocarcinoma. The American College of Radiology has recently released a scheme (CEUS LI-RADS) classifying lesions at risk for HCC investigated by CEUS. Aim of the present study was to validate this LI-RADS scheme for the diagnosis of HCC. Methods. A total of 1006 nodules in 848 patients with chronic liver disease at risk for HCC collected in 5 Italian centers were retrospectively analyzed. Nodules were classified as LR-5, (HCC) if ≥ 1 cm with arterial phase hyperenhancement, and late washout (onset ≥60 seconds after contrast injection) of mild degree. Rim enhancement and/or early and/or marked washout qualified lesions as LR-M (malignant, but not specific for HCC). Other combinations qualified lesions at intermediate risk for HCC (LR-3) or probable HCC (LR-4). Diagnostic reference standard was CT/MRI diagnosis of HCC (=506) or histology (n=500). Results. Median size was 2 cm. Of 1006 nodules, HCC were 820 (81%), cholangiocarcinoma 40 (4%), regenerative nodules (±dysplastic) 116 (11%). The LR-5 category (52% of all nodules) was 98.5% predictive of HCC, with no risk of misdiagnosis for pure cholangiocarcinoma. Sensitivity for HCC was 62%. All LR-M nodules were malignant and the majority of non-hepatocellular origin. Over 75% of cholangiocarcinomas were LR-M. The LR-3 category included 203 lesions (HCC 96=47%) and the LR-4 202 (HCC 173=87%). Conclusions. The CEUS LI-RADS class LR-5 is highly specific for HCC, enabling its use for a confident non invasive diagnosis.BACKGROUND & AIMS The use of contrast enhanced ultrasound (CEUS) for the diagnosis of hepatocellular carcinoma (HCC) in cirrhosis was questioned because of the risk of a false positive diagnosis in cases of cholangiocarcinoma. The American College of Radiology has recently released a scheme (CEUS Liver Imaging Reporting and Data System [LI-RADS®]) to classify lesions at risk of HCC investigated by CEUS. The aim of the present study was to validate this LI-RADS scheme for the diagnosis of HCC. METHODS A total of 1,006 nodules from 848 patients with chronic liver disease at risk of HCC were collected in five Italian centers and retrospectively analyzed. Nodules were classified as LR-5, (HCC) if ≥1 cm with arterial phase hyperenhancement, and late washout (onset ≥60 s after contrast injection) of mild degree. Rim enhancement and/or early and/or marked washout qualified lesions as LR-M (malignant, but not specific for HCC). Other combinations qualified lesions at intermediate risk for HCC (LR-3) or probable HCC (LR-4). Diagnostic reference standard was CT/MRI diagnosis of HCC (n = 506) or histology (n = 500). RESULTS The median nodule size was 2 cm. Of 1,006 nodules, 820 (81%) were HCC, 40 (4%) were cholangiocarcinoma, 116 (11%) regenerative nodules (±dysplastic). The LR-5 category (52% of all nodules) was 98.5% predictive of HCC, with no risk of misdiagnosis for pure cholangiocarcinoma. Sensitivity for HCC was 62%. All LR-M nodules were malignant and the majority of non-hepatocellular origin. Over 75% of cholangiocarcinomas were LR-M. The LR-3 category included 203 lesions (HCC 96 [47%]) and the LR-4 202 (HCC 173 [87%]). CONCLUSIONS The CEUS LI-RADS class LR-5 is highly specific for HCC, enabling its use for a confident non-invasive diagnosis. LAY SUMMARY This is a retrospective study of approximately 1,000 focal lesions at risk for hepatocellular carcinoma (HCC). Herein, we demonstrate that the refined definition of the typical contrast enhanced ultrasound pattern of HCC introduced by the Liver Imaging Reporting and Data System (LI-RADS®) practically abolishes the risk of misdiagnosis of other malignant entities (e.g. cholangiocarcinoma) for HCC with negligible reduction in sensitivity. These data support the use of contrast enhanced ultrasound to diagnose HCC in cirrhosis.