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Background/aims: To realize the roles of peripheral vasodilatation and atrial natriuretic peptide in the formation of cirrhotic ascites, the effects of long-term administration of octreotide on carbon tetrachloride-induced cirrhotic rats were evaluated., Methods: Urine sodium excretion, hemodynamics, plasma atrial natriuretic peptide levels, renin activities and aldosterone concentrations were compared between cirrhotic and control rats (protocol 1); and between octreotide- (65 micrograms/kg, twice daily for 10 days, subcutaneously) and placebo-treated (5% dextrose) cirrhotic rats (protocol 2). In an in vitro experiment, right atrial tissue of cirrhotic rats was incubated with different concentrations of octreotide to evaluate the release of atrial natriuretic peptide (protocol 3)., Results: Cirrhotic rats had significantly lower urine sodium excretion and systemic vascular resistance, and significantly higher plasma atrial natriuretic peptide levels, renin activities and aldosterone concentrations than control rats. Compared with placebo-treated cirrhotic rats, octreotide caused increased urine sodium excretion (-10 +/- 4% vs. 13 +/- 8% from baseline values, p < 0.05) and systemic vascular resistance (2.6 +/- 0.1 vs. 3.3 +/- 0.3 mmHg.min.100 g.ml-1, p < 0.05); and decreased plasma atrial natriuretic peptide levels (166.7 +/- 24.8 vs. 234.0 +/- 19.2 pg/ ml, p < 0.05), renin activities (2.45 +/- 0.49 vs. 4.36 +/- 0.53 ng.ml-1.h-1, p < 0.01) and aldosterone concentrations (290.2 +/- 40.0 vs. 483.3 +/- 82.6 pg/ml, p < 0.05). In the in vitro experiment, right atrial release of atrial natriuretic peptide of cirrhotic rats was not significantly changed when incubated with different concentrations of octreotide., Conclusions: Octreotide ameliorates renal sodium retention and suppresses plasma levels of atrial natriuretic peptide of ascitic cirrhotic rats with a novel mechanism via, at least partly, the modification of peripheral vascular resistance.

Background/aims: Portal hypertension and hyperdynamic circulation (i.e. generalized vasodilation and increased cardiac output and regional organ blood flows) may play an important role in the development of portal hypertensive gastropathy. This study investigated the effect of chronic administration of aminoguanidine, a selective inducible nitric oxide synthase inhibitor, to portal hypertensive rats on hemodynamics and the development of portal hypertensive gastropathy., Methods: Partial portal vein-ligated or sham-operated rats were randomly assigned to receive either placebo (distilled water) or aminoguanidine (approximately 100 mg/kg per day subcutaneously) for 2 days prior to and 14 days. Hemodynamic studies with a thermodilution technique and gastric morphometric analysis were performed at 14 days after the operation., Results: In rats given placebo, portal vein-ligated rats had a significantly lower mean arterial pressure and systemic vascular resistance associated with a significantly higher cardiac index and portal pressure than sham-operated rats (p<0.05). In portal vein-ligated rats aminoguanidine induced a significant increase in mean arterial pressure and systemic vascular resistance accompanied by a significant decrease in cardiac index (p<0.05) without changes in portal pressure (p>0.05). Despite persistence of portal hypertension, the aminoguanidine-treated portal vein-ligated rats had similar mean arterial pressure, cardiac index, and systemic vascular resistance as seen in placebo-treated sham-operated rats. The mean cross-sectional area of gastric mucosal vessels was significantly higher in placebo-treated portal vein-ligated than in placebo-treated sham-operated rats (p<0.05). Treatment with aminoguanidine did not induce changes in the mean cross-sectional area of gastric mucosal vessels in either portal vein-ligated or sham-operated rats (p>0.05)., Conclusions: The results show that in portal hypertensive rats long-term aminoguanidine therapy corrects the hyperdynamic circulation without inducing changes in portal pressure and ameliorating the development of portal hypertensive gastropathy. This study suggests that, instead of correcting hyperdynamic circulation, treatment of portal hypertensive gastropathy should be aimed at reducing portal pressure.

Background/aims: Vascular hyporesponsiveness in portal hypertension is well documented in the arterial tissue. The present study aimed to investigate the possible changes in the portal vein from portal hypertensive rats., Methods: Portal hypertension was induced by partial portal vein ligation. Fourteen days after surgery, portal veins were removed for contractile study and measurement of cAMP, cGMP and [Ca2+]i., Results: In vitro tension preparation showed a decreased maximum response to norepinephrine in portal vein of portal vein ligated rats (38.3 +/- 4.1 vs. 23.4 +/- 1.5 mN/mm2). The pA2 values of WB4101 and yohimbine (alpha1- and alpha2-adrenoceptor antagonist, respectively) were not different between the two groups. Tissue cAMP (14.4 +/- 0.9 vs. 12.2 +/- 0.7 pmol/mg protein), but not cGMP, content was increased and intracellular calcium [Ca2+]i levels (247 +/- 9 vs. 281 +/- 13 nM) were decreased in portal vein ligated rats., Conclusions: These results showed that in portal vein from portal vein ligated rats, vascular hyporesponsiveness and an increase in basal cAMP content and a decrease in basal [Ca2+]i were observed.

Background/aims: This study aimed to evaluate the effect of octreotide on total effective vascular compliance, measured during rapid volume expansion, in patients with posthepatitic cirrhosis., Methods: Twenty-nine patients with posthepatitic cirrhosis were randomly assigned to receive a 100-micrograms/h infusion of octreotide after a 100-micrograms bolus (n = 15), or a placebo (n = 14). Hemodynamic measurements were recorded before and 30 min after drug administration. Thereafter, rapid volume expansion was performed in each patient and hemodynamic measurements were repeated immediately after volume expansion., Results: Before volume expansion, placebo administration did not affect any of the hemodynamic values, while the hepatic blood flow was significantly decreased following octreotide administration. After volume expansion, the hemodynamic changes were similar between patients receiving octreotide and the placebo. However, the increase in right atrial pressure from the beginning to the end of volume expansion was higher and the total effective vascular compliance was lower in patients receiving octreotide (+3.5 +/- 0.3 mmHg, p = 0.05 and 1.69 +/- 0.16 ml.mmHg-1.kg-1, p < 0.05) compared to patients receiving placebo (+2.5 +/- 0.3 mmHg, 2.60 +/- 0.34 ml.mmHg-1.kg-1)., Conclusions: The present study suggests that octreotide decreased total effective vascular compliance in patients with posthepatitic cirrhosis. It is possible that, in patients with posthepatitic cirrhosis, venoconstriction was induced following octreotide administration.

Background/aims: Increased plasma endothelin levels have been reported in patients with cirrhosis. However, the relationship between plasma endothelin concentrations and hyperdynamic circulation or renal functions has not been documented., Methods: We measured the plasma endothelin-1 and endothelin-3 concentrations using radioimmunoassay in 96 patients with cirrhosis (Pugh's A in 26, Pugh's B in 45 and Pugh's C in 25) and compared these values to 56 age- and sex-matched healthy subjects. Systemic and portal hemodynamic measurements, effective renal plasma flow, creatinine clearance, plasma aldosterone concentration and plasma renin activity were recorded for each patient., Results: Plasma endothelin-1 and endothelin-3 levels were significantly increased in patients with cirrhosis compared to healthy subjects. Additionally, plasma endothelin-1 and endothelin-3 values were higher in patients with cirrhosis and ascites than in those without ascites. Moreover, plasma endothelin-1 levels increased in relation to the severity of cirrhosis. On the other hand, modest negative correlations were found between endothelin-1 and creatinine clearance or effective renal plasma flow., Conclusions: Plasma endothelin-1 and endothelin-3 levels are increased in patients with cirrhosis compared to healthy subjects. The increase in plasma endothelin-1 levels is related at least in part to the severity of cirrhosis. Increased endothelin-1 levels may possibly contribute to renal dysfunction in patients with cirrhosis.

Plasma endotoxin levels were investigated using a quantitative Limulus assay in patients with chronic liver diseases and correlated with the severity of liver diseases, the presence of esophageal varices, and hemodynamic parameters. The plasma endotoxin levels were significantly higher in chronic hepatitis patients with acute exacerbation (10.1 +/- 1.3 pg/ml, n = 13, p < 0.05) and patients with cirrhosis (7.0 +/- 0.7 pg/ml, n = 126, p < 0.05) than in healthy subjects (2.9 +/- 0.2 pg/ml, n = 45). Chronic hepatitis patients (n = 30) had plasma endotoxin levels which were similar to those in healthy subjects (4.6 +/- 0.5 vs. 2.9 +/- 0.2 pg/ml, p > 0.05) but lower than those in chronic hepatitis patients with acute exacerbation (4.6 +/- 0.5 vs. 10.1 +/- 1.3 pg/ml, p < 0.05). Endotoxemia (plasma endotoxin level > 5.7 pg/ml) was found in 27%, 85% and 41% of patients with chronic hepatitis, chronic hepatitis with acute exacerbation, and cirrhosis, respectively. In patients with cirrhosis, the plasma endotoxin levels progressively increased in relation to the severity of liver dysfunction (Pugh's class A/B/C = 4.9 +/- 0.5/7.9 +/- 1.4/10.2 +/- 2.0 pg/ml, p < 0.05). In contrast, plasma endotoxin levels were comparable between patients with cirrhosis with and without esophageal varices (p > 0.05). Chronic hepatitis patients with acute exacerbation (no collaterization) had much higher plasma endotoxin levels than those in patients with cirrhosis and large varices (p < 0.05), whereas compensated patients with cirrhosis and large esophageal varices had plasma endotoxin levels similar to those seen in chronic hepatitis patients (no collaterization) (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The preliminary results of a prospective double-blind controlled trial of colchicine in 100 patients with hepatitis B virus-related cirrhosis are reported. The patients, 94 males and 6 females, aged 32-80, were assigned to receive either 1 mg of colchicine or an identical placebo orally on a daily basis. The duration of the follow up ranged from 15 to 51 months (median 26 months). Seventy percent had histological proof of cirrhosis. On entry, 80 patients were in Child-Pugh class A, 19 were in class B, and one was in class C. Compared to the placebo group, there was no improvement in the colchicine group after a 24-month follow up in any of the biochemistry data, for example, serum albumin, alkaline phosphatase, alanine and aspartate aminotransferase, bilirubin, and prothrombin time. The difference in the cumulative survival rates at 51 months did not reach statistical significance (p = 0.8) in either group. There was no histological improvement in 30 patients who were willing to undergo repeated liver biopsies. No trend toward improvement of the hepatic pressure gradient was observed in these patients. The serum levels of aminopropeptide of type III procollagen increased significantly in patients in both groups after 24 months of therapy (1.07 +/- 0.06 vs. 1.36 +/- 0.06 U/ml in the colchicine group, 0.93 +/- 0.09 vs. 1.25 +/- 0.07 U/ml in the placebo group; p < 0.05). In addition, neither the clinical deterioration of cirrhosis nor death was prevented in patients receiving colchicine therapy. This report indicates that colchicine has no effect in the treatment of HBV-related postnecrotic cirrhosis.

The effects of octreotide on postprandial hemodynamic responses were evaluated in 20 patients with postnecrotic cirrhosis. They were randomly assigned to receive either a 100-micrograms bolus with a 100-micrograms/h infusion of octreotide or a placebo. Placebo administration did not affect any of the hemodynamic values. However, after a liquid meal of 500 kcal, postprandial increases in the hepatic venous pressure gradient and hepatic blood flow were observed in patients receiving placebo, while the systemic hemodynamic values remained unchanged. In contrast, in patients receiving octreotide, the hepatic blood flow was significantly decreased 30 min after administration, while the hepatic venous pressure gradient and the systemic hemodynamic values were not affected. After ingestion of a meal, the mean values of the hepatic blood flows were not significantly different from basal values. Moreover, the wedged hepatic venous pressure, the hepatic venous pressure gradient and the systemic hemodynamic values were not affected by meal ingestion. However, during octreotide infusion, hepatic blood flow 30 min after the meal had a tendency to increase compared to before the meal. In conclusion, octreotide inhibited the postprandial increase in portal pressure in patients with postnecrotic cirrhosis. In addition, octreotide decreased hepatic blood flow in the fasting state. When given before a meal, the increase in blood flow induced by the meal restored the hepatic blood flow to basal levels.

To define patients with an ascitic fluid polymorphonuclear cell count > or = 250 cells/mm3 or > or = 500 cells/mm3 but without spontaneous bacterial peritonitis, 166 patients with sterile cirrhotic ascites, 46 patients with spontaneous bacterial peritonitis, 123 patients with hepatocellular carcinoma, 67 patients with peritoneal carcinomatosis or massive liver metastasis and 12 patients with other miscellaneous diseases were studied. The sensitivity, specificity and accuracy of the diagnosis of spontaneous bacterial peritonitis were 100, 86 and 88% with the cut-off value of an ascitic fluid polymorphonuclear cell count > or = 250 cells/mm3; and were 93, 91 and 92% with that value > or = 500 cells/mm3, respectively. With the cut-off value > or = 250 cells/mm3 or > or = 500 cells/mm3, the prevalence was 18% or 14% in hepatocellular carcinoma; and 30% or 19% in peritoneal carcinomatosis or massive liver metastasis. The ascitic fluid lactate concentration was insensitive and nonspecific. Among the patients with an ascitic fluid polymorphonuclear cell count greater than the cut-off values, an ascitic fluid erythrocyte count > or = 10,000 cells/mm3, a ratio of ascitic fluid erythrocyte to total leukocyte count > or = 100, and the ratio of ascitic fluid polymorphonuclear cell to total leukocyte count < or = 75% indicated hepatocellular carcinoma, while serum to ascites albumin gradient < or = 1.1 g/dl and a ratio of ascitic fluid polymorphonuclear cell to total leukocyte count < or = 75% indicated peritoneal carcinomatosis or massive liver metastasis.

The effects of reserpine were investigated in two models of portal hypertension in rats. Twenty-four hours after 1 mg/kg of reserpine was administered intraperitoneally to normal and portal vein stenosed rats, the cardiac index, mean arterial pressure, heart rate, and portal pressure were significantly decreased compared with normal and portal vein stenosed rats receiving placebo. In addition, the portal tributary blood flow was significantly decreased in portal vein stenosed rats receiving reserpine, but was unchanged in normal rats. In cirrhotic rats receiving a single dose of reserpine, 0.1 mg/kg intraperitoneally for 24 h, there were significant decreases in cardiac index, mean arterial pressure and heart rate compared with cirrhotic rats receiving placebo, while the portal pressure and portal tributary blood flow followed a decreasing trend after reserpine administration. The degree of hemodynamic change was similar in the groups of rats receiving reserpine, even though cirrhotic rats received lower doses than either normal or portal vein stenosed rats. This study suggests enhanced sympathetic nervous activity observed in cirrhotic rats.

One hundred and fifty cirrhotic patients with or without esophageal varices and/or gastric varices were investigated by endoscopy and hepatic venous catheterization to evaluate differences in the degree of portal hypertension, main portal venous diameter and frequency of portal systemic encephalopathy. Hemodynamic values were correlated with varices size as assessed by endoscopy. Patients with large gastric varices had wedged hepatic venous pressures and hepatic venous pressure gradients which were lower than patients with esophageal varices only, but similar to patients without varices. In addition, in patients with large gastric varices, a decrease in the diameter of the main portal vein and an increase in the incidence of chronic portal systemic encephalopathy were noted. Our results implied that patients with large gastric varices presented different hemodynamic features including the degree of portal hypertension and the incidence of portal systemic encephalopathy from patients with esophageal varices only.

The effect of portal hypertension on plasma sex steroid levels was studied in 49 patients with hepatitis B virus-related postnecrotic cirrhosis. In accordance with the Child-Pugh classification, 18 patients were classified as grade A, 15 grade B and 16 grade C. At the same time, 25 males who were admitted for physical check-up served as normal controls. Serum testosterone levels decreased (3.31 +/- 2.03 vs. 5.65 +/- 0.13 ng/ml) and estrone levels increased (0.16 +/- 0.08 vs. 0.09 +/- 0.02 ng/ml) significantly in patients with cirrhosis compared to the levels obtained in the controls. Moreover, these changes were associated with an increased severity of cirrhosis (P < 0.05 when severity increased from grade A to C). Hemodynamic values regarding hepatic venous pressure gradient and cardiac output demonstrated significant differences in patients from grade A to C, but the correlation between these two parameters was poor (r = 0.3242). The hepatic venous pressure gradient, the only direct measurement of portal hypertension, did not correlate with any of the measured hormone levels in patients with cirrhosis. There was, however, a highly significant negative correlation between cardiac output and testosterone levels (r = -0.8754, P < 0.01) and a positive correlation between cardiac output and estrone levels (r = 0.7522, P < 0.05) in grade C patients. On the basis of these results, we concluded that gonadal dysfunction is a common finding in patients with hepatitis B related postnecrotic cirrhosis, especially in those with decompensated liver function. The relationship between cardiac output and severity of liver disease suggests that the degree of portosystemic shunting probably increases as liver disease worsens.(ABSTRACT TRUNCATED AT 250 WORDS)

This randomized controlled trial was conducted to compare the efficacy of intravenous infusion of octreotide (a synthetic long-acting somatostatin analogue) with vasopressin in 48 cirrhotic patients with endoscopically proven bleeding esophageal varices. Twenty-four patients received a continuous infusion of octreotide 25 micrograms/h for 24 h after an initial bolus of 100 micrograms and another 24 patients received a continuous infusion of vasopressin 0.4 U/min for 24 h. Bleeding was initially controlled after 6 h of drug infusion in 88% (21/24) and 54% (13/24) of the patients treated with octreotide and vasopressin respectively (p = 0.03). Complete control of bleeding after 24 h of drug infusion was achieved in 15 (63%) patients receiving octreotide and in 11 (46%) patients receiving vasopressin (p > 0.05). Side effects during drug infusion such as headache, chest pain and abdominal pain were significantly lower in the octreotide group (3/24) than in the vasopressin group (11/24). Serum gastrin and insulin levels fell significantly following octreotide infusion, but plasma glucose levels remained unchanged. Mortality related to bleeding esophageal varices was no different between the two groups. This report showed that octreotide infusion was more effective and had fewer side effects than vasopressin in initial controlling of acute esophageal variceal bleeding until an elective endoscopic sclerotherapy could be performed.

In a prospective study of 103 consecutive cirrhotic patients a high prevalence (43%) of anorectal varices was found compared with only 2% in 103 age- and sex-matched control subjects (p less than 0.001). However, there was no significant difference between the prevalences of hemorrhoids in cirrhotic patients and in control subjects (79% vs. 83%, p greater than 0.05). The hepatic venous pressure gradient of cirrhotic patients with anorectal varices was similar to cirrhotic patients without anorectal varices (14 +/- 6 mmHg, n = 22, vs. 16 +/- 7 mmHg, n = 39, p greater than 0.05. There was no significant difference in the hepatic venous pressure gradient between cirrhotic patients with and without hemorrhoids (15 +/- 6 mmHg, n = 47, vs. 16 +/- 8 mmHg, n = 14, p greater than 0.05). The prevalence of anorectal varices and hemorrhoids in cirrhotic patients had no relation to Child-Pugh's grading, esophageal varices with and without sclerotherapy and ascites. We conclude that anorectal varices are common in cirrhotic patients. Anorectal varices and hemorrhoids are not related to the degree of portal pressure.

We measured the hemodynamic effects of intravenous vasopressin, ketanserin (a 5-hydroxytryptamine-2 receptor blocker), and vasopressin plus ketanserin in 33 patients with hepatitis B-related cirrhosis. Thirteen patients received vasopressin alone (0.66 units/min), ten patients ketanserin alone (10 mg), and ten patients vasopressin followed by vasopressin plus ketanserin. Vasopressin alone reduced the hepatic venous pressure gradient (from 18 +/- 5, mean +/- S.D., to 9 +/- 3 mmHg, p less than 0.0001) and cardiac output (p less than 0.0001), but increased mean arterial pressure (p less than 0.005), mean pulmonary arterial pressure (p less than 0.0001), pulmonary capillary wedge pressure (p less than 0.0001), and systemic vascular resistance (p less than 0.001). There was no significant change in heart rate. Ketanserin alone produced a significant fall in the hepatic venous pressure gradient (from 16 +/- 4 to 13 +/- 3 mmHg, p less than 0.0001), mean arterial pressure (p less than 0.005), mean pulmonary arterial pressure (p less than 0.005), and pulmonary capillary wedge pressure (p less than 0.005). Heart rate, cardiac output, and systemic vascular resistance were not significantly changed. The addition of ketanserin to vasopressin corrected most of the systemic hemodynamic disturbances produced by vasopressin. This combination did not lead to a further reduction in the hepatic venous pressure gradient. We conclude that intravenous ketanserin reduces portal pressure in patients with hepatitis B-related cirrhosis. The addition of ketanserin to vasopressin improves the detrimental systemic hemodynamic effects of vasopressin without further reducing the portal pressure.

Des-gamma-carboxy prothrombin (DCP) assay was performed by a staphylocoagulase method in 35 consecutive patients with small (less than 5 cm), resectable hepatocellular carcinoma (HCC). They also simultaneously received serum alpha-fetoprotein (AFP) assay. According to diagnostic strategy, patients were divided into two groups. Group I consisted of eight patients who were candidates for a mass screening project for HCC with elevated AFP levels (greater than 20 ng/ml). Five of these patients had an increased DCP level (greater than 6 U/l). Group II included 27 victims of chronic hepatitis B or cirrhosis whose tumors were detected by ultrasonography during regular follow-up. In this group, increased DCP and AFP levels were observed in 11 and 16 cases, respectively. Of 14 patients with smaller HCC (less than 3 cm), only three had elevated DCP levels, while eight patients had an abnormal AFP level. When these two assays were combined, 18 of 27 patients in group II and nine of 14 patients with smaller HCC (less than 3 cm) revealed elevation of one or both of the two markers. A total of 16 out of 35 patients with small HCC had abnormal DCP levels. In conclusion, DCP assay is less sensitive than AFP assay in the detection of small HCC, and the combination of both markers has little complementary effect.

In an attempt to evaluate the effect of quinidine in the treatment of patients with cirrhosis and muscle cramps, 31 cirrhotic patients with muscle cramps were randomly divided into two groups and given orally 400 mg of quinidine sulfate per day or placebo, respectively. Baseline clinical and laboratory data for these two groups were similar. Four weeks after oral administration of quinidine, the number of cramps significantly decreased from 14.4 +/- 1.7 (mean +/- S.E.) to 4.4 +/- 1.1 episodes (p less than 0.0001), but it remained unchanged in the placebo group (from 11.8 +/- 1.0 to 11.5 +/- 1.5 episodes, p greater than 0.05). In addition, 88% of the 16 patients on quinidine and 13% of the 15 patients on a placebo showed a greater than 50% reduction in the number of cramps during a 4-week treatment period (p less than 0.0001). The peak and trough serum levels of quinidine in patients having received quinidine for 2 weeks were 1.3 +/- 0.1 and 0.7 +/- 0.1 mg/l, respectively. There was a significant relationship between serum quinidine concentrations and attenuation of cramps. No significant adverse effect was observed during the study, except for five (31%) patients who developed mild diarrhea after quinidine therapy. Diarrhea subsided spontaneously or was controlled by medications without the interruption of quinidine therapy. It was concluded that quinidine is a safe and effective drug for the treatment of cirrhotic patients with muscle cramps.

Forty-one hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA positive Chinese patients with chronic active hepatitis B were randomized to receive either prednisolone or placebo oral for 8 weeks. The prednisolone group received 60 mg daily for 2 weeks, 40 mg for 2 weeks, 20 mg for 2 weeks, 10 mg for 1 week and 5 mg for 1 week. In 18 patients receiving prednisolone, serum HBV DNA levels rose during the course of therapy, but dropped abruptly within 1 month of cessation of treatment. Conversely, their serum alanine aminotransferase (ALT) levels decreased during high doses of prednisolone therapy, and then became transiently elevated during the period of withdrawal of prednisolone. At 1 year from initial treatment, the serum HBV DNA and ALT levels were similar between the groups of patients treated with prednisolone or placebo. In the prednisolone treated group, 66.7% of patients became HBV DNA negative, 50% became HBeAg negative, and 33.3% seroconverted to antibody to HBeAg (anti-HBe). In the placebo treated group, 60.9% of patients became HBV DNA negative, 60.9% became HBeAg negative, and 56.5% seroconverted to anti-HBe. Hepatic decompensation was not noted in any of the prednisolone-treated patients. Thus, the effects of the withdrawal prednisolone therapy on serum ALT and HBV DNA levels was temporary, and no differences in serum viral markers or biochemical parameters of liver inflammation between these two groups were noted at the 1 year follow-up period.

We measured the haemodynamic changes following triglycyllysine vasopressin administration and after addition of nitroglycerin in twelve patients with portal hypertension due to hepatitis B-related cirrhosis. A bolus i.v. injection of triglycyllysine vasopressin at a dose of 2 mg reduced the hepatic venous pressure gradient from 18.5 +/- 3.7 (mean +/- S.D.) to 15.6 +/- 4.0 mmHg, p less than 0.001. However, the cardiac index decreased from 4.8 +/- 1.0 to 3.7 +/- 0.8 l/min m2, p less than 0.001; the heart rate decreased from 79 +/- 15 to 71 +/- 13, p less than 0.01; the right atrial pressure increased from 3.2 +/- 1.9 to 5.3 +/- 2.3 mmHg, p less than 0.001; the mean arterial pressure increased from 92 +/- 13 to 103 +/- 13 mmHg, p less than 0.05; and the systemic vascular resistance rose from 939 +/- 182 to 1367 +/- 310 dyn/s cm-5, p less than 0.001. Furthermore, both mean pulmonary arterial pressure and pulmonary capillary wedge pressure showed a significant increase following triglycyllysine vasopressin administration as compared with baseline values (p less than 0.005). The addition of sublingual nitroglycerin at a dose of 0.6 mg returned all the systemic haemodynamic parameters to baseline levels. On the other hand, nitroglycerin administration caused no further change in the hepatic venous pressure gradient. We concluded that although triglycyllysine vasopressin significantly reduced portal pressure in patients with hepatitis B-related cirrhosis, it produced untoward systemic haemodynamic changes similar to those seen with vasopressin. The addition of nitroglycerin improved the detrimental systemic haemodynamic effects produced by triglycyllysine vasopressin without further reducing the hepatic venous pressure gradient.

Portal vein pressure and wedged hepatic vein pressure were measured simultaneously in 21 patients with hepatitis B-related cirrhosis of the liver and were compared to pressure measured in six patients with idiopathic portal hypertension. No significant difference in the portal venous pressure gradient was found between patients with cirrhosis and those with idiopathic portal hypertension (17.3 +/- 4.3 mmHg (mean +/- S.D.) vs. 19.7 +/- 3.1 mmHg, P greater than 0.05). However, the difference between the portal and the hepatic venous pressure gradient was significantly smaller in patients with cirrhosis than in idiopathic portal hypertension patients (1.3 +/- 1.7 vs. 10.8 +/- 2.1 mmHg, P less than 0.001). An excellent correlation was found between portal vein pressure and wedged hepatic vein pressure in hepatitis B-related cirrhosis (r = 0.94, P less than 0.001). There was no linear relationship between the portal venous pressure gradient and varix size or bleeding episodes. We concluded that a close agreement existed between portal vein pressure and wedged hepatic vein pressure in hepatitis B-related liver cirrhosis. Therefore, measurement of wedged hepatic vein pressure reliably reflects portal vein pressure in these patients.