Influence of esophageal varices and spontaneous portal-systemic shunts on postprandial splanchnic hemodynamics.

OBJECTIVE: The aim of the study was to assess postprandial splanchnic hemodynamic changes in cirrhosis in relation to variceal status. METHODS: In 9 healthy controls and 56 patients with liver cirrhosis, stratified according to variceal status and presence of spontaneous portal-systemic shunts, the portal vein diameter and flow velocity, the congestion index of the portal vein, and the resistive index of the superior mesenteric artery (SMA-RI) were studied by Doppler ultrasound before and 30, 60, and 120 min after the intake of a standard meal. Comparison of postprandial parameters with basal ones was done within each group by paired t test and among groups by ANOVA and Duncan test. RESULTS: Healthy controls and cirrhotic patients without varices showed similar significant splanchnic hemodynamic changes, namely a reduction of SMA-RI (-13% at 30 min) and a consequent increase in portal vein diameter (respectively, +32% and +17% in the two groups) and velocity (+66% and +51%). A significant reduction of SMA-RI was also found in patients with varices, irrespective of the variceal size (range, -7 to -11%), but the expected portal vein dilation and velocity increase were progressively blunted with the increase of variceal size (range, 0-5% for diameter and 5-19% for velocity). Patients with spontaneous portal-systemic shunts showed a response similar to that of patients with large varices. Significant modification of the congestion index of the portal vein did not occur in any group. CONCLUSIONS: Our results show that the hemodynamic response to meal in patients with liver cirrhosis is influenced by the presence and size of esophageal varices and the presence of spontaneous portal-systemic shunts.

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 alpha 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$753 226, the cost per treatable HCC was US$17 934, and the cost for year of life saved was US$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.

Left ventricular volumes in liver cirrhosis.

BACKGROUND: Patients with alcoholic cirrhosis have left ventricular dimensions similar to controls. Few data have been reported in patients with cirrhosis of viral origin. AIM: To assess left ventricular dimensions in patients with pure viral cirrhosis. PATIENTS AND METHODS: Thirty patients with virus-related cirrhosis, 23 patients with alcoholic cirrhosis and 12 healthy controls were submitted to measurement of left ventricular volumes, cardiac output, mean arterial pressure and total peripheral resistance. RESULTS: Patients with cirrhosis showed a similar increase in cardiac index and heart rate and reduction of mean arterial pressure and peripheral vascular resistance in comparison to controls, irrespective of the aetiology. Left ventricular end systolic volume index was lower (p<0.01) and ejection fraction higher (p<0.01) in virus-related cirrhotic patients [mean +/- SD, respectively 12.4+/-4.1 ml/sqm and 77.9%) in comparison both to controls (21.5+/-6.3 ml/sqm and 66.8%) and alcoholics (20.6+/-7.0 ml/sqm and 68.8%). End diastolic volume index was not significantly different between the three groups. CONCLUSIONS: Our findings indicate smaller left ventricular volumes and higher ejection fraction in pure virus-related cirrhosis than in alcoholic cirrhosis and controls. Since peripheral haemodynamics proved similar in virus- and alcohol-related cirrhosis, a subclinical alcohol cardiomyopathy may be hypothesised to account for the absence of such left ventricular pattern in alcoholic patients.

Prognostic indicators of risk for first variceal bleeding in cirrhosis: a multicenter study in 711 patients to validate and improve the North Italian Endoscopic Club (NIEC) index.

OBJECTIVE: The best known indicator of risk for first bleeding in patients with cirrhosis without previous bleeding is the index devised by the North Italian Endoscopic Club for the Study and Treatment of Esophageal Varices (NIEC index), which results from the combination of size of esophageal varices, severity of red wale marks, and Child-Pugh class. Its efficiency is far from optimal, and validation studies have reported sensitivities and specificities markedly lower than those reported in the original study. In the present study we analyzed the efficiency of NIEC index in a large series of cirrhotic patients with varices without previous bleeding. In addition, we tried to improve the effectiveness of the index by modifying it, and to validate the modifications in an independent group of patients. METHODS: A total of 627 patients were enrolled and followed until either a variceal bleeding or for a maximum of 2 yr. During this time, 117 experienced a first variceal RESULTS: Using Cox's regression analysis, size of varices, severity of red wale marks, and Child-Pugh score were significant and independent predictors of first bleeding, as already noted in the original report of the NIEC group. However, coefficients and standard errors were markedly different, and the importance of size of esophageal varices in the regression was much larger, whereas that of Child-Pugh score was much lower. According to these data, a revised index was developed (Rev-NIEC). Using receiver operating characteristic (ROC) curve analysis, the revised index showed a larger efficiency, and the area under the curve was significantly larger (0.80 +/- 0.02 vs 0.74 +/- 0.02; p < 0.01). In particular, the curve showed that for a specificity of 75%, the new index had a sensitivity of 72% compared to that of 55% of the NIEC index. Validation in an independent sample of 84 patients showed good agreement between predicted and observed risk for bleeding. Validation with the bootstrap technique also showed adequate stability of the results. CONCLUSIONS: The revised index seems to be superior to the traditional index, and may turn out to be more useful in the selection of patients for different therapeutic procedures and in the stratification of patients in clinical trials.

Diurnal changes of fibrinolysis in patients with liver cirrhosis and esophageal varices.

Variceal bleeding, whose triggering mechanisms are largely unknown, occurs with a circadian rhythmicity, with 2 peaks, one greater, in the evening, and one smaller, in the early morning. We assessed some clotting and hemodynamic parameters, possibly involved in variceal hemorrhage, over a 24-hour period, at 4-hour intervals, in 16 patients with cirrhosis and esophageal varices and in 9 controls. At each time interval, tissue plasminogen activator (tPA) and tPA inhibitor-1 (PAI-1) antigens and activities and total euglobulin fibrinolytic activity were determined and portal-vein flow velocity, volume, and congestion index were measured by duplex-Doppler. Significant circadian rhythms were searched for by least-squares and cosinor methods. tPA activity showed a circadian rhythm in cirrhosis, with a peak of 2.85 times the trough value, calculated at 18:42, and remained over 2.5-fold until shortly after 22:00. Total fibrinolytic activity showed a similar pattern, which was statistically significant also in controls. tPA and PAI antigens also showed significant circadian rhythm both in controls and cirrhotics, with higher values in the morning. Among the portal hemodynamic parameters only the congestion index showed significant rhythmic changes and only in cirrhosis, with the highest values in the late evening, but with limited diurnal excursion (+/- 5.5%). In conclusion, we showed the existence of a circadian rhythm of fibrinolysis in cirrhosis, whose temporal distribution might suggest a role of fibrinolysis in variceal hemorrhage on the basis of the comparison to the known chronorisk of variceal bleeding.

Assessment of vascular patterns of small liver mass lesions: value and limitation of the different Doppler ultrasound modalities.

OBJECTIVES: This study aimed to investigate the value and limitation of the different Doppler ultrasound modalities (spectral analysis, color, and power Doppler imaging) in the differential diagnosis of small liver tumors to identify the optimal diagnostic approach with the presently available Doppler technology. METHODS: Presence and distribution of color and power Doppler signals, Doppler peak frequency, resistive index, and systolic acceleration time were examined in 133 liver nodules (< or = 4 cm). RESULTS: Color and power Doppler did not identify specific diagnostic vascular patterns. By discriminant analysis, peak frequency (cut-off 1320 Hz) differentiates small hematocellular carcinoma (< or = 2 cm) from macroregenerative nodules and hemangiomas (accuracy 92.6%); resistive index (cut-off 0.65) differentiates malignancies from benign lesions (accuracy 83.8%); and systolic acceleration time (cut-off 105 ms) differentiates hepatocellular carcinoma from metastases (accuracy 80.9%). CONCLUSIONS: Power Doppler imaging is able to assess vascularity in the majority of small liver nodules, but the pattern distribution of tumoral vascular signals does not provide reliable differential diagnostic criteria. Using conventional Doppler technology, power Doppler should be used to detect vascular signals and spectral analysis, and subsequently to measure quantitative parameters such as high peak frequency and resistive index (which identify malignancy) and prolonged systolic acceleration time (which identifies primary from metastatic liver tumors).

Superior mesenteric artery impedance in chronic liver diseases: relationship with disease severity and portal circulation.

OBJECTIVE: The increase of splanchnic blood flow volume in liver cirrhosis is attributed to decreased arterial resistance. The aim of this study was to noninvasively investigate superior mesenteric artery impedance in patients with chronic liver diseases and to assess its relationship with portal hemodynamics and with clinical parameters. METHODS: Superior mesenteric artery (SMA) pulsatility (SMA-PI) and resistance (SMA-RI) indices and portal vein flow parameters (velocity, volume, and congestion index) were measured by duplex-Doppler ultrasound in 14 patients with chronic hepatitis, in 73 cirrhotics, in 30 liver transplant recipients, and in 31 control subjects. RESULTS: SMA-PI significantly differed among the five groups (p < 0.0001), being lower in cirrhotics (2.55+/-0.70) and transplanted patients (2.77+/-0.69) than in chronic hepatitis (3.28+/-0.57) and control subjects (3.42+/-0.92). SMA-PI was lower in ascitic cirrhosis (2.40+/-0.71) than in compensated cirrhosis (2.71+/-0.70) (p < 0.01) and in cirrhotics with large varices (2.30+/-0.67) than in those without varices (2.75+/-0.65) (p < 0.05). Moreover SMA-PI correlated with numeric Child-Pugh score (r=-0.28) and portal vein congestion index (r=-0.36). CONCLUSION: Hyperdynamic splanchnic circulation, noninvasively assessed by a decrease of mesenteric artery impedance, occurs in cirrhosis since the early stage of the disease and tends to worsen in relation to liver failure and the severity of portal hypertension. Furthermore, the persistent SMA-PI decrease in transplant recipients suggests a consistent contribution to this circulatory alteration from a patent portosystemic collateral circulation.

Duplex-Doppler evaluation of the effects of propranolol and isosorbide-5-mononitrate on portal flow and splanchnic arterial circulation in cirrhosis.

BACKGROUND: A decrease in portal flow is an important pharmacological effect of drugs used for the prophylaxis of variceal bleeding. AIM: To assess the acute and chronic effects of propranolol, and the effect of the acute addition of isosorbide-5-mononitrate, on splanchnic circulation. METHODS: Measurements of portal blood flow volume (PBFV) and of Doppler ultrasound pulsatility index of the superior mesenteric, femoral and interlobar renal arteries were performed in 10 cirrhotic patients with varices at baseline, 90 min after propranolol or placebo, after 30 days of chronic propranolol treatment and 45 min after the addition of isosorbide-5-mononitrate. RESULTS: The mean PBFV was significantly lower at all times than at baseline, with the greatest mean percentage decrease achieved after the addition of isosorbide-5-mononitrate (> or = 20% in all patients). Acute changes, however, did not predict the chronic effects in many patients. Isosorbide-5-mononitrate significantly increased the mesenteric and femoral pulsatility indices, whereas no significant change was observed in the kidney. CONCLUSIONS: Propranolol significantly decreases PBFV, but chronic effects cannot be reliably predicted by the acute change. All patients achieved a decrease in PBFV of > or = 20% after the acute addition of isosorbide-5-mononitrate to chronic propranolol treatment.

High prevalence of Helicobacter pylori in liver cirrhosis: relationship with clinical and endoscopic features and the risk of peptic ulcer.

In 153 consecutive patients with cirrhosis we assessed: (1) the prevalence of IgG to Helicobacter pylori and compared it with that found in 1010 blood donors resident in the same area; and (2) the relationships of IgG to Helicobacter pylori with clinical and endoscopic features and with the risk of peptic ulcer. The IgG to Helicobacter pylori prevalence of cirrhotics was significantly higher than in blood donors (76.5% vs 41.8%; P < 0.0005) and was not associated with sex, cirrhosis etiology, Child class, gammaglobulins and hypertensive gastropathy. In both groups, the prevalence of IgG to Helicobacter pylori was significantly higher in subjects over 40. Among patients with cirrhosis a significantly higher prevalence of Helicobacter pylori was found in patients with previous hospital admission (P = 0.02) and/or upper gastrointestinal endoscopy (P = 0.01) and patients with peptic ulcer (P = 0.0004). Multivariate analysis identified increasing age and male sex as risk factors for a positive Helicobacter pylori serology and no independent risk factors for peptic ulcer. The high prevalence of Helicobacter pylori-positive serology found in the present series is related to age and sex and might also be explained by previous hospital admissions and/or upper gastrointestinal endoscopy. Our results do not confirm the role of Helicobacter pylori as risk factor for peptic ulcer in patients with liver cirrhosis.

Relationship between splanchnic, peripheral and cardiac haemodynamics in liver cirrhosis of different degrees of severity.

OBJECTIVE: To investigate the relationships between changes in splanchnic and systemic haemodynamics in liver cirrhosis. DESIGN AND METHODS: Abdominal and peripheral duplex-Doppler sonography and Doppler echocardiography were performed in 42 cirrhotic patients with (group A, ascitic) or without ascites (group NA, non-ascitic) and in a control group of 36 healthy volunteers. RESULTS: There were significant differences (P < 0.05 at ANOVA) between the three groups in portal vein flow velocity (controls, groups NA and A, respectively, 29.2, 21.4 and 20.0 cm/s), portal diameter (9.3, 12.2 and 12.0 mm), superior mesenteric artery (SMA) resistance index (RI) (0.889, 0.854 and 0.816), femoral artery RI (0.988, 0.974 and 0.945), mean arterial pressure (MAP) (101.4, 102.0 and 87.3 mmHg), peripheral vascular resistance (1579, 1404 and 1094 dyn/cm5/s) and cardiac index (CI) (2.91, 3.46 and 3.77 l/min/m2). Multiple regression analysis identified renal interlobular- and SMA RI (respectively, r = -0.58 and r = 0.51) in group A as the two regional vascular beds correlated to MAP. CONCLUSION: The deterioration of the cirrhotic hyperdynamic circulation in the presence of ascites and the correlation between MAP and mesenteric and renal resistances are consistent with the peripheral arterial vasodilation hypothesis. The positive correlation between MAP and SMA RI in ascitic patients shows a link between this region and the general circulation. This seems to suggest that splanchnic hyperafflux plays a part in the formation of ascites.

Peptic ulcer in patients with liver cirrhosis: a retrospective endoscopic and clinical study.

AIM: It has been showed that peptic ulcer is more frequent in patients with liver cirrhosis, is associated with the severity of cirrhosis, and occurs without upper abdominal pain in up to 70% of patients and with complications in 29%. The aim of this study was to retrospectively assess the characteristics of peptic ulcer in a large series of patients with liver cirrhosis. MATERIALS AND METHODS: In this retrospective study the consecutive records of 1,748 endoscopies, performed in patients with liver cirrhosis during a period of 14 years, were reviewed to evaluate the frequency and clinical characteristics of peptic ulcer. RESULTS: The ulcer prevalence was 6.3%, and 77.5% of the ulcers were asymptomatic. Complications from ulcer were present in 29% of all patients and in 32% of those who has the first diagnosis of ulcer during the study. Patients with asymptomatic ulcer had a more decompensated cirrhosis. After healing, 20%-25% of the recurrent ulcers had complications while patients were on standard maintenance treatment. CONCLUSIONS: This retrospective study confirms the high frequency of peptic ulcer in patients with liver cirrhosis. It also confirms that the peptic ulcer in these patients is very often asymptomatic and associated with concurrent complications, especially in those with more severe liver disease. The complication rate in recurrent ulcers was 20%-25%. However, due to the retrospective nature of this study, after ulcer healing the endoscopic follow-up was irregular. Regularly repeated endoscopy should be carried out in patients with liver cirrhosis and peptic ulcer to diagnose new and recurrent ulcers and to prevent related complications.

Intra- and extrahepatic arterial resistances in chronic hepatitis and liver cirrhosis.

Thirty patients with chronic hepatitis (CH), 84 with liver cirrhosis (LC) and 42 controls, underwent noninvasive measurement of hepatic artery resistance index (RI) by means of Doppler ultrasound (US), at the porta hepatis and in the intrahepatic branches, in order to investigate possible changes related to: (a) the liver disease; (b) the site of measurement; and (c) ageing. The intrahepatic RI differed among LC, CH and controls (0.731, 0.690 and 0.643, p < 0.05), whereas the RI at the porta hepatis did not (0.754, 0.748 and 0.729, respectively). Intrahepatic RI correlated with age in LC (r = 0.51, p < 0.0001) and in controls (r = 0.49, p < 0.001). In LC, it correlated also with the presence and size of esophageal varices (r = 0.32, p < 0.05). In conclusion, an increase of hepatic artery RI in chronic liver diseases can be demonstrated when assessed in the intraparenchymal branches. The increase of hepatic artery RI with ageing should be considered in future studies.

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

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.

Circadian occurrence of variceal bleeding in patients with liver cirrhosis.

Several clinical events have a rhythmicity over the 24 h period. We assessed the presence of periodic rhythm in the occurrence of haematemesis in patients with liver cirrhosis under different daylight regimens, namely during standard time and during daylight savings. Over a 48 month period there were 212 consecutive admissions of 118 cirrhotics with variceal bleeding. Complete data were available for 181 episodes of bleeding: 121 (66.9%) started with haematemesis and 60 (33.1%) started with melaena. One hundred and two (56%) episodes occurred during daylight savings and 79 (44%) occurred during standard time. The cosinor test showed a 24 h biphasic peak for the occurrence of haematemesis (09.45 and 21.45 h). Moreover, a biphasic diurnal asymmetric frequency was also found by multiple component rhythmometry. The time peaks of onset of variceal haemorrhage did not change significantly during standard time and daylight savings. Patients with more than one haematemesis episode significantly bled over the same time interval. The present study confirms that over the 24 h period variceal bleeding in cirrhotic patients occurs with a predictable rhythmicity that does not seem to be under the control of the light-dark cycle. The finding of a chronorisk for variceal haemorrhage addresses specific questions for pathophysiological studies as well as for new treatment strategies.

Short- and long-term hemodynamic response to octreotide in portal hypertensive patients: a double-blind, controlled study.

This randomized, double-blind, placebo-controlled study on the hemodynamic effect of two different doses of octreotide administered subcutaneously was conducted among 20 cirrhotic portal hypertensive patients. The wedged hepatic venous pressure, the hepatic venous pressure gradient, the mean portal venous flow velocity, the resistive index of the superior mesenteric artery, the heart rate and the mean arterial pressure were simultaneously evaluated by hepatic vein catheterization and Doppler flowmetry at baseline, 30 and 45 min after a subcutaneous injection of octreotide [0.10 mg (7 patients), 0.05 mg (7 patients)] and of a placebo (6 patients). The portal blood flow velocity, the resistive index of the superior mesenteric artery, the heart rate and the mean arterial pressure were also measured 2, 4, 6 and 8 h after the injection. The hemodynamic changes observed 30 min after the injection did not differ from those at 45 min and the changes at 2, 4, and 6 h were similar to those at 8 h. A statistically significant decrease, in comparison to the placebo group, was observed 45 min after the injection of the two doses of octreotide in the wedged hepatic venous pressure (cumulative median decrease: -10%, p < 0.005), in the hepatic venous pressure gradient (cumulative median decrease: -10%, p < 0.005) and in the mean portal flow velocity (cumulative median decrease: -11%, p < 0.005). A significant increase in the resistive index of the superior mesenteric artery was observed 45 min after the injection of the two doses of octreotide (cumulative median increase: +10%, p < 0.005). Lower, but significant changes in the mean portal flow velocity and in the resistive index of the superior mesenteric artery persisted until 8 h after the injection of the two doses of octreotide (cumulative median decrease of mean portal flow velocity: -7%, p < 0.005 and cumulative median increase of resistive index of the superior mesenteric artery: +4%, p < 0.005). Changes in the wedged hepatic venous pressure, the hepatic venous pressure gradient, the mean portal flow velocity and the resistive index of the superior mesenteric artery showed a great variability among patients. These changes were more pronounced in patients injected with the lower dose with no relationship with the plasma drug concentrations. Responder patients showed a significant higher baseline mean portal flow velocity in comparison with nonresponders (15.2 +/- 1.7 cm/s vs 11.3 +/- 1.3 cm/s; p < 0.005).

In hepatocellular carcinoma AgNOR protein expression correlates with tumour mass doubling time.

AIMS/METHODS: The relationship between AgNOR protein expression and doubling time was evaluated in 20 untreated nodules of hepatocellular carcinoma arising in cirrhotic liver. AgNOR protein quantity within the lesion was defined by image cytometry on histological sections from frozen biopsies obtained under ultrasound-guidance, selectively stained for AgNOR proteins. Tumour doubling time was calculated 6 months after diagnosis by measuring the volume variations of the nodules over a fixed period by "real time" ultrasonography. RESULTS: The doubling time of nodules characterized by high AgNOR protein area values (> 5.50 microns2, corresponding to the median AgNOR protein value) was shorter than that of nodules with low AgNOR protein area values (< 5.50 microns2). A highly significant difference in the mean doubling time values between the two groups (6.31 +/- 2.68 (E.S.) versus 15.92 +/- 3.03 (E.S.) months, respectively; p = 0.009) was found. Moreover, when the relationship between AgNOR protein and doubling time values was tested by linear regression analysis, a significant inverse correlation was observed (r = -0.68; p < 0.005). CONCLUSIONS: Our results indicate that AgNOR protein quantity represents a reliable parameter for predicting the tumour growth rate of untreated hepatocellular carcinoma nodules. Among the procedures commonly employed for the assessment of cell proliferation, the evaluation of the AgNOR parameter seems to be particularly suitable for kinetic analysis of ultrasound-guided fine-needle liver biopsies.

Sonographic assessment of the distal end of the thoracic duct in healthy volunteers and in patients with portal hypertension.

OBJECTIVE: Our study assessed the feasibility of detecting and measuring by sonography the diameter of the thoracic duct in healthy subjects and in patients with cirrhosis and portal hypertension. We also evaluated the relationship of thoracic duct size with age and with clinical, endoscopic, and sonographic signs of portal hypertension. SUBJECTS AND METHODS: The left supraclavicular area of 24 patients with cirrhosis and 23 healthy subjects was examined with high-frequency probes using transverse and oblique scans to visualize the distal end of the thoracic duct. All patients with cirrhosis, diagnosed by liver biopsy or clinical and biochemical data, had endoscopic or sonographic signs of portal hypertension. The severity of the liver disease was determined by Child-Pugh's criteria; the diameter of portal vessels and the size of esophageal varices were also considered. RESULTS: The thoracic duct was visualized in 19 of 24 patients with cirrhosis and in 18 of 23 control subjects (percent of visualization was 79% and 78%, respectively). The diameter of the duct was larger in patients with cirrhosis than in healthy subjects (3.1 +/- 1.2 mm versus 1.9 +/- 0.5 mm; p < .0001), but no relationship was found among clinical, endoscopic, and sonographic signs of portal hypertension. A direct relationship between age and the size of the thoracic duct was found only among healthy subjects. CONCLUSION: This is the first report of the sonographic visualization of the distal end of the thoracic duct. Its diameter is small in healthy young subjects, whereas in patients with cirrhosis its increased diameter seems to be associated only with the presence of portal hypertension and not with its severity.

Peptic ulcer and its course in cirrhosis: an endoscopic and clinical prospective study.

The epidemiological and clinical characteristics of peptic ulcer were studied in 324 of 368 consecutive patients with cirrhosis of the liver during a mean period of 1.2 (+/- 0.61) years. Peptic ulcer prevalence rates in patients with cirrhosis were as follows: point prevalence 11.7%, period prevalence 15.1%, and life-time prevalence 24.2%. The annual incidence rate observed in 140 patients with cirrhosis undergoing endoscopic follow up was 4.3%. Ulcers were asymptomatic in more than 70% of patients. The peptic ulcer complication rate at entry was 20% in the whole group and 40% in those who had not a previous diagnosis of peptic ulcer when admitted to the study. Peptic ulcer was more frequent among HBsAg+ cirrhotics (p = 0.05). Patients with more severely decompensated cirrhosis also had a higher frequency of asymptomatic ulcers (p = 0.04), gastric ulcers (p = 0.01) and asymptomatic gastric ulcers (p = 0.005). After diagnosis, during endoscopic follow up, gastric ulcer in patients with cirrhosis tended to heal slowly and recurred with higher frequency than in controls without cirrhosis (p = 0.04). Seventy-nine per cent of peptic ulcer recurrences were asymptomatic in patients with cirrhosis. There were no complications during the follow-up period: this could be due to the regular timing of endoscopy, which permitted early detection and treatment of the recurrences, thus preventing further complications.

Timing of the first variceal hemorrhage in cirrhotic patients: prospective evaluation of Doppler flowmetry, endoscopy and clinical parameters.

We followed 87 cirrhotic patients with esophageal varices and without previous hemorrhage for a mean period of 24 mo to prospectively evaluate the occurrence of variceal bleeding within (early) or after (late) 6 mo from entry and the contribution of portal Doppler ultrasound parameters to the prediction of early and late hemorrhage. Clinical, biochemical, endoscopic and portal Doppler ultrasound parameters were recorded at entry. Variceal bleeding occurred in 22 patients (25.3%). Nine (40.9%) bled within the first 6 mo. Cox regression analysis identified variceal size, cherry-red spots, serum bilirubin and congestion index of the portal vein (the ratio of portal vein [cross-sectional area] and portal blood flow velocity) as the only independent predictors of first variceal hemorrhage. Discriminant analysis was used to find the prognostic index cut off points to identify patients who bled within 6 mo (prognostic group 1) or after 6 mo (prognostic group 2) or remained free of bleeding (prognostic group 3). The cumulative proportion of patients correctly classified was 73% in prognostic group 1, 47% in prognostic group 2 and more than 80% in prognostic group 3. The addition of Doppler ultrasound flowmetry to clinical, biochemical and endoscopic parameter only improved the classification of patients with early bleeding.