Natascia Celli

Characterization of small nodules in cirrhosis by assessment of vascularity : The problem of hypovascular hepatocellular carcinoma

In a prospective study, we examined the impact of arterial hypervascularity, as established by the European Association for the Study of the Liver (EASL) recommendations, as a criterion for characterizing small (1‐3 cm) nodules in cirrhosis. A total of 72 nodules (1‐2 cm, n = 41; 2.1‐3 cm, n = 31) detected by ultrasonography in 59 patients with cirrhosis were included in the study. When coincidental arterial hypervascularity was detected at contrast perfusional ultrasonography and helical computed tomography, the lesion was considered to be hepatocellular carcinoma (HCC) according to EASL criteria. When one or both techniques showed negative results, ultrasound‐guided biopsy was performed. In cases with negative results for malignancy or high‐grade dysplasia, biopsy was repeated when an increase in size was detected at the 3‐month follow‐up examination. Coincidental hypervascularity was found in 44 of 72 nodules (61%; 44% of 1‐2‐cm nodules and 84% of 2‐3‐cm nodules). Fourteen nodules (19.4%) had negative results with both techniques (hypovascular nodules). Biopsy showed HCC in 5 hypovascular nodules and in 11 of 14 nodules with hypervascularity using only one technique. All nodules larger than 2 cm finally resulted to be HCC. Not satisfying the EASL imaging criteria for diagnosis were 38% of HCCs 1 to 2 cm (17% hypovascular) and 16% of those 2 to 3 cm (none hypovascular). In conclusion, the noninvasive EASL criteria for diagnosis of HCC are satisfied in only 61% of small nodules in cirrhosis; thus, biopsy frequently is required in this setting. Relying on imaging techniques in nodules of 1 to 2 cm would miss the diagnosis of HCC in up to 38% of cases. Any nodule larger than 2 cm should be regarded as highly suspicious for HCC. (HEPATOLOGY 2005.)

Influence of liver fibrosis on hepatic artery Doppler resistance index in chronic hepatitis of viral origin

BACKGROUND Hepatic arterial Doppler sonography is increasingly being used in liver diagnostics. The determinants of the elevation of hepatic artery impedance indexes in chronic liver disease, however, have still not been fully clarified. The aim of the present study was to investigate the relationship between histological alterations and liver circulation in chronic hepatitis. METHODS Hepatic artery resistance index and portal flow velocity were measured using Doppler sonography in 47 patients with chronic hepatitis of viral origin diagnosed at histopathology. The patients were divided into two groups, those with mild and those with severe alterations, in accordance with the various histological parameters of the Knodell scoring system. RESULTS Hepatic artery resistance index and age were higher in patients with more severe liver fibrosis (respectively 0.638 +/- 0.084 and 39.0 +/- 10.9 (years) in mild fibrosis versus 0.687 +/- 0.060 and 49.4 +/- 14.4 (years) in severe fibrosis; P < 0.05 for both), whereas no difference between the two groups was found for the other histological features (degeneration, inflammation and necrosis), nor for portal flow velocity. CONCLUSIONS The increase in hepatic artery resistance index appears to be influenced by the extent of fibrous tissue deposition in the liver, determined by chronic inflammation and repair and, secondly, by ageing.Background: Hepatic arterial Doppler sonography is increasingly being used in liver diagnostics. The determinants of the elevation of hepatic artery impedance indexes in chronic liver disease, however, have still not been fully clarified. The aim of the present study was to investigate the relationship between histological alterations and liver circulation in chronic hepatitis. Methods: Hepatic artery resistance index and portal flow velocity were measured using Doppler sonography in 47 patients with chronic hepatitis of viral origin diagnosed at histopathology. The patients were divided into two groups, those with mild and those with severe alterations, in accordance with the various histological parameters of the Knodell scoring system. Results:

Percutaneous treatment of hepatocellular carcinoma

In early stage hepatocellular carcinoma (HCC), liver transplantation, surgical resection and percutaneous techniques are classified as radical treatments, and may be offered to about 25% of all patients with HCC evaluated in referral centres.

Influence of the Spleen on Portal Haemodynamics: a Non-invasive Study with Doppler Ultrasound in Chronic Liver Disease and Haematological Disorders

Background: Splanchnic haemodynamic parameters for the differential diagnosis of splenomegalies of different origins are still suboptimal and the role of spleen enlargement in cirrhosis remains controversial. In an attempt to elucidate these questions, we assessed splanchnic haemodynamics in chronic liver diseases and various other disorders with splenomegaly. Methods: Study groups comprised: (i) patients with chronic liver disease (89 with cirrhosis, 35 with chronic hepatitis), (ii) patients with splenomegaly without relevant portal hypertension (14 with haematological splenomegaly and 25 liver transplant recipients without complications), (iii) 15 patients with arterial hypertension, (iv) 22 healthy controls. In all subjects, spleen size, portal flow parameters and splenic artery resistance index were measured using duplex-Doppler ultrasound. Results: Splenic artery resistance index was significantly and selectively increased in patients with cirrhosis (0.63, whereas all other group means ranged between 0.53 and 0.56; P < 0.01). Portal flow velocity was significantly decreased in cirrhosis ( P < 0.01). The combination of these two parameters provided an accuracy of 87.5% in distinguishing portal hypertensive from haematological splenomegaly. In patients with cirrhosis, the degree of spleen enlargement was positively correlated with increasing portal flow volume, portal vein diameter and variceal size, whereas splenic resistance index and portal velocity did not differ in connection with spleen size. Conclusions: Splenoportal Doppler sonography provides specific findings in cirrhosis and may therefore be a useful tool in differentiating between splenomegaly of portal hypertensive or haematological origin. In patients with cirrhosis, the presence of splenomegaly is associated with the presence of larger oesophageal varices.

Cardiac abnormalities in Cirrhosis

TO THE EDITOR: Valeriano and coworkers discussed modifications of cardiac function in cirrhotic patients in the November issue (1). Their data are fairly interesting, but whether the reported modifications are purely the expression of cirrhotic cardiomyopathy, as thought by the authors, or are influenced by the etiology of liver disease, particularly of alcohol abuse, still remains open to discussion, at least in our opinion. Blendis and Wong correctly noted the presence of a wide variety of etiologies in the Valerianoet al. study group (2) and suppose that previous alcohol abuse has no influence at all on cardiac function after 6 months of abstinence. We are not so confident that the effect of previous long-lasting heavy alcohol consumption is completely cleared after 6 or even more months of abstinence. To date no study has reported, to our knowledge, a direct comparison of diastolic cardiac function between patients with pure viral cirrhosis and those with alcoholic cirrhosis. Pozzi and coworkers (3) tried to separate alcoholic patients from viral ones, finding no difference, but nine of 24 patients with viral cirrhosis had a mixed etiology (viral plus alcohol) in their study, so that a confounding effect of alcohol in the viral group cannot be excluded with certainty. The same is true for the Valeriano article (1), where eight of 40 patients had postalcoholic cirrhosis; seven, cryptogenic liver disease; and two, primary biliary cirrhosis. In the latter case chronic elevation of bile acids may also affect cardiac function (4, 5), and in the event of cryptogenic disease, a subclinical cardiac involvement also cannot be excluded with certainty. We recently reported on the presence of differences in left ventricular systolic function when patients with cirrhosis are accurately grouped according to previous alcohol consumption (pure viral cirrhosisvs cirrhosis with previous heavy alcohol intake) (6). In that article and in two others (7, 8) selectively assessing pure viral cirrhotics a significant increase of ejection fraction was found, which is not the case in practically all studies assessing patients with mixed etiologies, including the recent one by Valeriano and colleagues (1). We believe, therefore, that a subgrouping for etiology should be applied also to studies on left ventricular diastolic function. Accordingly, we present here the data of the E/A ratio, an index of diastolic compliance of the left ventricle (where E and A represent the peak flow velocities across the mitralic valve during early and presystolic diastole, detected by Doppler ultrasound at echocardiography) taken from an ongoing study on cardiac function under exercise testing in cirrhosis. We analyzed 29 patients with cirrhosis (mainly nonascitic) divided into two groups: group A (mean age 6 SD 5 52 6 9 yr) had 15 patients, 14 with alcohol-related cirrhosis and one with primary biliary cirrhosis, and group B (53 6 12 yr) had 14 patients with a pure viral etiology (hepatitis B virus or hepatitis C virus, with patients currently abstinent and reporting a previous alcohol consumption below 20 g/day). Fourteen healthy subjects (48 6 12 yr) were studied as a control group (group C). The E/A ratio appeared significantly different (Fig. 1) in controls and cirrhotics (Student’st test, p , 0.002) and among the three groups (analysis of variance, p , 0.01), with a significant difference between group C and group A ( p , 0.002) (also after the Bonferroni correction). Group B showed lower values than group C and higher values than group A, with marginal significance ( ps 5 0.07 and 0.09, respectively). In conclusion, our present data appear to go in the direction of a diastolic dysfunction in cirrhosis (1, 2), but show that nonviral etiologies likely bear an additional cardiac damage, raising the question whether case series of cirrhotic

Effect of levovist® on splanchnic hemodynamics in cirrhotic patients

This study was aimed to assess the effect of Levovist on Doppler parameters of splanchnic hemodynamics. A total of 12 patients with cirrhosis and 12 healthy subjects underwent Doppler ultrasound (US) examination of the portal vein and of the hepatic, splenic and superior mesenteric arteries before, 5 to 8 and 12 to 15 min after the start of an 8-min long IV infusion of 2.5 g of Levovist. Mean velocity and mean diameter were calculated for the portal vein. Resistance index was determined for the arteries. A significant increase of resistance index was observed in the hepatic (0.80 +/- 0.07 vs. 0.71 +/- 0.06; p < 0.01) and splenic arteries (0.72 +/- 0.06 vs. 0.64 +/- 0.06; p < 0.01) 5 to 8 min after contrast agent injection in patients with cirrhosis, but not in controls. Neither portal vein diameter nor portal flow mean velocity changed during the test in both controls and cirrhotic patients. This effect might be related to a selective trapping of microbubbles in the altered hepatic and splenic microvasculature in patients with cirrhosis rather than being artefactual. It might have implications on harmonic imaging US protocols designed to image the cirrhotic liver in the early arterial phase.