Stefano Gaiani

Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis

BACKGROUND Hepatocellular carcinoma (HCC) is a major cause of death in cirrhotic patients. This neoplasm is associated with liver cirrhosis (LC) in more than 90% of cases. Early diagnosis and treatment of HCC are expected to improve survival of patients. AIMS To assess the cost effectiveness of a surveillance programme of patients with LC for the early diagnosis and treatment of HCC. PATIENTS A cohort of 313 Italian patients with LC were enrolled in the surveillance programme between March 1989 and November 1991. In the same period, 104 consecutive patients with incidentally detected HCC were referred to our centre and served as a control group. METHODS Surveillance was based on ultrasonography (US) and α fetoprotein (AFP) determinations repeated at six month intervals. Risk factors for HCC were assessed by multivariate analysis (Cox model). Outcome measures analysed were: (1) number and size of tumours; (2) eligibility for treatment; and (3) survival of patients. Economic issues were: (1) overall cost of surveillance programme; (2) cost per treatable HCC; and (3) cost per year of life saved (if any). Costs were assessed according to charges for procedures at our university hospital. RESULTS Surveillance lasted a mean of 56 (31) months (range 6–100). During the follow up, 61 patients (19.5%) developed HCC (unifocal at US in 49 cases), with an incidence of 4.1% per year of follow up. AFP, Child-Pugh classes B and C, and male sex were detected as independent risk factors for developing HCC. Only 42 (68.9%) of 61 liver tumours were treated by surgical resection, orthotopic liver transplantation, or local therapy. The cumulative survival rate of the 61 patients with liver tumours detected in the surveillance programme was significantly longer than that of controls (p=0.02) and multivariate analysis showed an association between surveillance and survival. The overall cost of the surveillance programme was US

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

753 226, the cost per treatable HCC was US

Measurement of gastric emptying time by real-time ultrasonography

17 934, and the cost for year of life saved was US

What is the criterion for differentiating chronic hepatitis from compensated cirrhosis? A prospective study comparing ultrasonography and percutaneous liver biopsy

112 993. CONCLUSION Our surveillance policy of patients with LC requires a large number of resources and offers little benefit in terms of patient survival. The decision whether to adopt a surveillance policy towards HCC should rely on the prevalence of the disease in the population and on the resources of a particular country.

Persistent hepatitis C viraemia without liver disease

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.)

Value of measurement of mean portal flow velocity by Doppler flowmetry in the diagnosis of portal hypertension

This paper describes an ultrasound method of assessing gastric emptying time based on measurements of the gastric antrum, which is visible in almost all subjects before and after meals. A total of 54 subjects were examined including 18 normal subjects and 36 subjects with idiopathic functional dyspepsia. The emptying time was determined in all subjects by measuring the changes in the cross-sectional area of the gastric antrum. In a subgroup of 34 subjects the volume of the whole antropyloric region was also considered. Measurements were taken by the same observer after fasting and at regular 30-min intervals after a standard 800-cal meal. Final emptying time (calculated in relation to the start of the meal) was considered to be the time at which the antral area or volume returned to basal value. Final emptying time (mean +/- SD) was 248 +/- 39 min in normal subjects and 359 +/- 64 min in patients with functional dyspepsia (p less than 0.001). A significantly higher degree of dilatation of the gastric antrum was found in dyspeptic patients than in control subjects. Barium x-ray of the stomach in 19 subjects always confirmed the ultrasound finding on the presence or absence of contents within the stomach. We conclude that this kind of ultrasound study of the antropyloric region allows accurate determination of total gastric emptying time.

Diagnosis of Budd-Chiari syndrome by pulsed Doppler ultrasound.

BACKGROUND/AIMS/METHODS The diagnosis of cirrhosis is currently based on percutaneous liver biopsy, although this procedure may give rise to false negative results. This prospective study blindly investigates the accuracy of an ultrasonographic score, derived from liver, spleen and portal vein features, in predicting the final diagnosis in 212 patients with compensated chronic liver disease undergoing percutaneous liver biopsy. RESULTS Taking biopsy as the standard, the ultrasonographic score differed significantly between chronic hepatitis (39+/-33) and cirrhosis (100+/-35) (p<0.0001). Discriminant analysis with stepwise forward selection of the variables identified liver surface nodularity and portal flow velocity as independently associated with the diagnosis of cirrhosis (p<0.005), and a score based on these two variables correctly identified cirrhosis in 82.2% of cases. One or both of these abnormalities were also found in 27/32 patients who were diagnosed as having cirrhosis at ultrasound, but were not cirrhotic histologically. Eight of these 32 cases developed signs of decompensated liver disease and/or portal hypertension in the subsequent 6-month follow-up, thus supporting the diagnosis of cirrhosis. CONCLUSIONS Our data suggest that ultrasound is accurate in predicting the final diagnosis in patients with compensated chronic liver disease and may identify cirrhosis even in the absence of a typical histopathological pattern. However, neither percutaneous liver biopsy nor ultrasonography can be assumed to be the definitive criterion for the diagnosis of compensated cirrhosis.

Interobserver and interequipment variability of hepatic, splenic, and renal arterial Doppler resistance indices in normal subjects and patients with cirrhosis

In viral infections persistence of the virus is not always associated with virus-induced disease. To find out if active hepatitis C virus (HCV) infection can persist without liver disease we selected four symptom-free individuals with antibodies to HCV but normal aminotransferase levels. They were followed up for 3 years by monthly serology and a liver biopsy was done. At presentation, all four had both antibodies to HCV and circulating HCV RNA. During follow-up their sera remained persistently positive for all HCV antibodies and RNA yet aminotransferase levels did not increase and liver biopsy was normal. These findings indicate that persistent hepatitis C viraemia is not invariably associated with liver damage.

Gall bladder sludge formation during prolonged fasting after gastrointestinal tract surgery.

To establish the sensitivity and specificity of the mean portal flow velocity in the diagnosis of portal hypertension, a population of 304 consecutive cirrhotic patients, in whom 246 abdominal Doppler examinations were performed, was prospectively analysed between June 1988 and December 1990. To avoid equipment-related variability only examinations performed using the same equipment were considered. Further inclusion criteria were the absence of portal vein thrombosis or reversed flow in the portal vessels and the absence of spontaneous, ultrasonographically detectable, portosystemic shunts. The parameter evaluated was mean portal flow velocity calculated directly from the Doppler trace by specific, operator-independent, software. 123 patients satisfied the inclusion criteria. As a control group 60 healthy age- and sex-matched subjects were examined. Mean portal flow velocity was significantly lower in cirrhotic patients than healthy subjects (13.0 +/- 3.2 cm/s vs. 19.6 +/- 2.6 cm/s; p < 0.001). There was also a decrease in mean portal flow velocity in cirrhotics in each Child-Pugh category (13.8 +/- 2.8 cm/s in Child-Pugh A class; 12.1 +/- 3.5 cm/s in Child-Pugh B class and 11.0 +/- 2.4 cm/s in Child-Pugh C class) with a statistically significant difference between each Child-Pugh category and healthy subjects (p < 0.001), between Child-Pugh A and B (p < 0.01) and between Child-Pugh A and C (p < 0.005). The sensitivity and specificity of mean portal flow velocity in the detection of portal hypertension was then analyzed with the receiver operating characteristic curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in Splanchnic Hemodynamics in Inflammatory Bowel Disease Non-Invasive Assessment by Doppler Ultrasound Flowmetry

Computed tomography and real-time ultrasonography may not be conclusive for the diagnosis of the Budd-Chiari syndrome; in many cases more information may be needed, especially on vascular alterations. Doppler ultrasonography provides qualitative data on flow direction and pattern, thereby contributing significantly to diagnosis. Eight cases in which hepatic vein patency was unclear and presence of intrahepatic vessels resembling hepatic veins raised problems of interpretation in real-time ultrasonography are described. In some cases, patency or occlusion of the upper portion of the inferior vena cava were difficult to identify with real-time ultrasonography. Doppler ultrasonographic investigation showed flow in the hepatic veins to be completely absent in two cases and reversed in another two. In the remaining four cases, a flat waveform was evident. Flow in the inferior vena cava was reversed in four cases and showed a flat waveform in three other cases. Portal vein thrombosis was detected in only one case, whereas the remaining seven patients showed slow hepatopetal flow. These findings demonstrate that absent or reversed flow in the hepatic veins and/or flat flow in the hepatic veins associated with reversed flow in the inferior vena cava may be considered diagnostic for the Budd-Chiari syndrome. For this series the sensitivity of Doppler ultrasonography was 87.5%.