Wang Ss

Prognostic value of Plasma endotoxin levels in patients with cirrhosis

BACKGROUND Endotoxemia has frequently been observed in patients with cirrhosis. Previous studies have shown that cirrhotic patients with endotoxemia have a higher mortality than those without. We evaluated the clinical value of plasma endotoxin level in predicting short-term (3 months) and long-term (2 years) survival among cirrhotic patients and compared it with the Child-Pugh score. METHODS Plasma endotoxin levels were determined in 102 cirrhotic patients without clinical evidence of infection by a quantitative Limulus assay. The patients were followed up for 3 months to assess short-term survival and for 2 years for long-term survival. RESULTS Plasma endotoxin levels increased progressively as liver function deteriorated. In short-term survival analysis, plasma endotoxin levels were significantly higher in non-survivors than those in survivors (10.6 +/- 2.2 pg/ml versus 5.8 +/- 0.5 pg/ml; P < 0.05). Both plasma endotoxin and serum bilirubin levels, but not the Child-Pugh score, were significant factors in predicting short-term survival in multivariate analysis. In long-term survival analysis, plasma endotoxin levels did not differ significantly between survivors and non-survivors (6.1 +/- 0.6 pg/ml versus 7.3 +/- 1.1 pg/ml; P > 0.05) and was not an independent predictor of long-term survival. In contrast, both Child-Pugh score and serum bilirubin levels were significant predictors of long-term survival in multivariate analysis. CONCLUSIONS In patients with cirrhosis, plasma endotoxin levels progressively increase as liver function deteriorates and may be useful in predicting short-term survival.

C-reactive protein and lactate dehydrogenase isoenzymes in the assessment of the prognosis of acute pancreatitis

The value of serum C‐reactive protein, lactate dehydrogenase isoenzymes and erythrocyte sedimentation rate in predicting the outcome of acute pancreatitis was evaluated for 57 episodes in 54 patients. Serum C‐reactive protein levels on day 2, 4 and 7 after admission were significantly higher in 19 episodes of severe attacks than in 38 episodes of mild attacks (13.71±9.68, 9.00±7.54, 6.02±3.83 vs 4.78±3.91, 3.30±3.61, 1.43±2.08 mg/dL; P < 0.0001, P < 0.005, P < 0.0001, respectively). The sensitivity, specificity and accuracy of predicting a severe attack were 94, 76 and 82% using C‐reactive protein ≥ 8 mg/dL on day 2; 67, 92 and 84% using C‐reactive protein ≥ 5 mg/dL on day 7; and 59, 76 and 70% using Ransons criteria ≥ 3. Increases in LDH‐4 and LDH‐5 isoenzymes were found in both groups, with LDH‐4 being slightly higher in severe attacks than in mild attacks. There was no significant difference of erythrocyte sedimentation rate between both groups. When compared with Ransons criteria, lactate dehydrogenase isoenzymes and erythrocyte sedimentation rate, C‐reactive protein is more valuable in the early assessment of the severity of acute pancreatitis.

Serum pancreas-specific protein in acute pancreatitis. Its clinical utility in comparison with serum amylase.

To compare the clinical utility of serum pancreas-specific protein and serum amylase in the diagnosis of acute pancreatitis, the study was conducted in 134 normal subjects and 70 patients (36 with acute pancreatitis and 34 with other acute abdominal diseases as control group). The serum level of pancreas-specific protein in 134 healthy adults was 29.6 +/- 1.6 micrograms/l, with 95% within 7.3-67.2 micrograms/l. The upper reference limit was set at 70 micrograms/l. Serum levels of pancreas-specific protein and amylase within 12 h of arrival were significantly higher in patients with acute pancreatitis than in the control group (647.3 +/- 79.3 versus 33.8 +/- 4.8 micrograms/l (p < 0.0001) and 2536 +/- 344 versus 175 +/- 35 IU/l (p < 0.0001)). No significant difference in the levels of pancreas-specific protein was noted between biliary and alcoholic pancreatitis or between severe and mild attacks. The sensitivity, specificity, and accuracy of diagnosing acute pancreatitis were 100%, 94.1%, and 97.1% with serum pancreas-specific protein > 70 micrograms/l and 97.2%, 91.2%, and 94.3% with serum amylase > 360 IU/l. The result demonstrated that pancreas-specific protein may be a good serum marker in the diagnosis of acute pancreatitis.

Chronic inhibition of nitric oxide ameliorates splanchnic hyposensitivity to glypressin in a hemorrhage-transfused rat model of portal hypertension

BACKGROUND Vasopressin given during hemorrhage is less effective than when given during a stable state in experimental portal hypertension or patients with cirrhosis (the so-called hyposensitivity phenomenon). This study investigated whether chronic inhibition of nitric oxide (NO) synthesis by NG-nitro-L-arginine methyl ester (L-NAME), a non-selective NO synthase inhibitor, could potentiate the portal-hypotensive effect of glypressin (a long-acting vasopressin analogue) in portal-hypertensive rats during acute bleeding status. METHODS Portal hypertension was induced by partial portal vein ligation (PVL). Rats were divided to receive either L-NAME (approximately 25 mg/kg/day in tap water) or placebo (tap water) treatment orally from 2 days prior to until 14 days after the operation. At the end of treatment, L-NAME-and placebo-treated PVL rats were subdivided into without-bleeding and with-bleeding groups to assess the effects of glypressin (0.07 mg/kg) on systemic and portal hemodynamics. In rats with a hypotensive hemorrhage, 4.5 ml of blood was withdrawn and 50% of the withdrawn blood was reinfused before the administration of glypressin. RESULTS As compared with placebo-treated rats, chronic treatment with L-NAME in PVL rats significantly increased mean arterial pressure (P < 0.001) without modulating portal pressure (P > 0.05). In placebo-treated PVL rats, glypressin resulted in a less decrease in portal pressure in rats with bleeding than in those without bleeding (P < 0.05). For PVL rats with bleeding, the portal-hypotensive effect of glypressin was significantly potentiated after chronic L-NAME treatment (P < 0.05). CONCLUSIONS Chronic inhibition of NO alleviates the splanchnic hyposensitivity to glypressin observed in bleeding PVL rats, suggesting the pathophysiological role of nitric oxide in mediating this splanchnic hyposensitivity.Background: Vasopressin given during hemorrhage is less effective than when given during a stable state in experimental portal hypertension or patients with cirrhosis (the so-called hyposensitivity phenomenon). This study investigated whether chronic inhibition of nitric oxide (NO) synthesis by NG-nitro-L-arginine methyl ester (L-NAME), a non-selective NO synthase inhibitor, could potentiate the portal-hypotensive effect of glypressin (a long-acting vasopressin analogue) in portal-hypertensive rats during acute bleeding status. Methods: Portal hypertension was induced by partial portal vein ligation (PVL). Rats were divided to receive either L-NAME (~25 mg/kg/day in tap water) or placebo (tap water) treatment orally from 2 days prior to until 14 days after the operation. At the end of treatment, L-NAME-and placebo-treated PVL rats were subdivided into without-bleeding and with-bleeding groups to assess the effects of glypressin (0.07 mg/kg) on systemic and portal hemodynamics. In rats with a hypotensive hemorrhage, 4.5 ml of blood was withdrawn and 50% of the withdrawn blood was reinfused before the administration of glypressin. Results: As compared with placebo-treated rats, chronic treatment with L-NAME in PVL rats significantly increased mean arterial pressure (P < 0.001) without modulating portal pressure (P > 0.05). In placebo-treated PVL rats, glypressin resulted in a less decrease in portal pressure in rats with bleeding than in those without bleeding (P < 0.05). For PVL rats with bleeding, the portal-hypotensive effect of glypressin was significantly potentiated after chronic L-NAME treatment (P < 0.05). Conclusions: Chronic inhibition of NO alleviates the splanchnic hyposensitivity to glypressin observed in bleeding PVL rats, suggesting the pathophysiological role of nitric oxide in mediating this splanchnic hyposensitivity.

CASE REPORT: Portal vein thrombosis associated with hereditary protein C deficiency: A report of two cases

Protein C deficiency is one of the causes of curable or preventable portal vein thrombosis. We report two patients of portal vein thrombosis associated with hereditary protein C deficiency. The first patient presented with continuous right upper quadrant pain and high fever. The abdominal sonography revealed normal liver parenchyma but portal vein and superior mesenteric vein thrombosis. Based on a 55% (normal 70–140%) plasma protein C level, he was diagnosed as having protein C deficiency. A trace of his family history showed that his elder brother also had protein C deficiency with a 50% plasma C level. Both patients received anticoagulant therapy. The younger brother showed good response. Unfortunately, the elder one suffered from recurrent episodes of variceal bleeding and received a life‐saving splenectomy and devascularization. We herein remind clinicians that early screening and therapy are helpful in preventing late complications of protein C deficiency with portal vein thrombosis.

Effects of endothelin‐1 on portal‐systemic collaterals of common bile duct‐ligated cirrhotic rats

Background/Aims  Endothelin‐1 (ET‐1) may induce intrahepatic vasoconstriction and consequently increase portal pressure. Endothelin‐1 has been shown to exert a direct vasoconstrictive effect on the collateral vessels in partially portal vein‐ligated rats with a high degree of portal‐systemic shunting. This study investigated the collateral vascular responses to ET‐1, the receptors in mediation and the regulation of ET‐1 action by nitric oxide and prostaglandin in cirrhotic rats with a relatively low degree of portal‐systemic shunting.

Effects of prostacyclin inhibition on splanchnic Hyposensitivity to glypressin in a hemorrhage-transfused rat model of Portal hypertension

Background: Hyposensitivity to vasopressin is a well-documented phenomenon in animals with portal hypertension and patients with cirrhosis and hemorrhage. Similar findings exist with infusion of glypressin (a long-acting vasopressin analogue), and this phenomenon could be ameliorated by inhibition of nitric oxide (NO) synthase. Besides NO, excessive formation of prostacyclin (PGI2) has been shown to play an important role in the development of hyperdynamic circulation and the mediation of hyporeactivity to vasoconstrictors in portal-hypertensive states. This study was designed to investigate whether the blockade of PGI2 activity by indomethacin infusion could enhance the portal-hypotensive effect of glypressin in portal-hypertensive rats with bleeding. Methods: Portal hypertension was induced by partial portal vein ligation (PVL). Fourteen days after operation systemic and portal hemodynamics were measured in stable or bleeding PVL rats receiving intravenous glypressin (0.07 mg/kg) or indomethacin (5 mg/kg) followed by glypressin infusion. In rats with a hypotensive hemorrhage 4.5 ml of blood was withdrawn, and 50% of the withdrawn blood was reinfused before the administration of glypressin or indomethacin. Results: Splanchnic hyposensitivity to glypressin was shown in hemorrhage-transfused PVL rats. Indomethacin infusion did not cause significant systemic and portal-hemodynamic changes in bleeding PVL rats (P > 0.05). The addition of indomethacin significantly enhanced the portal-hypotensive effects of glypressin and potentiated the increases in mean arterial pressure induced by glypressin infusion in bleeding PVL rats. Conclusions: The improvement of splanchnic hyposensitivity to glypressin in a hemorrhage-transfused rat model of portal hypertension by the administration of indomethacin suggests that PGI2 has in the development of this hyposensitivity.

Hyperdynamic circulation of cirrhotic rats: role of substance P and its relationship to nitric oxide.

BACKGROUND It has been suggested that excessive formation of nitric oxide (NO) is responsible for the hyperdynamic circulation observed in portal hypertension. Substance P is a neuropeptide partly cleared by the liver and causes vasodilatation through the activation of the endothelial NO pathway. However, there are no previously published data concerning the plasma level of substance P in cirrhotic rats and its relationship to NO. METHODS Plasma concentrations of substance P and nitrate/nitrite (an index of NO production) were determined in control rats and cirrhotic rats with or without ascites using an enzyme-linked immununosorbent assay and a colorimetric assay, respectively. In addition, systemic and portal hemodynamics were evaluated by a thermodilution technique and catheterization. RESULTS Cirrhotic rats with and without ascites had a lower systemic vascular resistance (2.6 +/- 0.2 and 3.9 +/- 0.4 mmHg ml(-1) x min x 100 g body weight, respectively) and higher portal pressure (14.6 +/- 0.6 and 11.3 +/- 1.8 mmHg) than control rats (6.5 +/- 0.3 mmHg x ml(-1) x min x 100 g BW and 6.8 +/- 0.2 mmHg, respectively, P < 0.05), and cirrhotic rats with ascites had the lowest systemic vascular resistance. Plasma levels of nitrate/nitrite progressively increased in relation to the severity of liver dysfunction (control rats, 2.7 +/- 0.5 nmol/ml; cirrhotic rats without ascites, 5.6 +/- 1.3 nmol/ml; cirrhotic rats with ascites, 8.3 +/- 2.2 nmol/ml; P < 0.05). Cirrhotic rats with ascites displayed higher plasma values of substance P (57.7 +/- 5.9 pg/ml) than cirrhotic rats without ascites (37.9 +/- 3.1 pg/ml, P < 0.05) and control rats (30.1 +/- 1.0 pg/ml, P < 0.05). There was no significant difference in plasma substance P values between control rats and cirrhotic rats without ascites (P > 0.05). No correlation was found between plasma levels of substance P and nitrate/nitrite (r = 0.318, P > 0.05). CONCLUSIONS Excessive formation of NO may be responsible, at least partly, for the hemodynamic derangements in cirrhosis. Although substance P may not participate in the initiation of a hyperdynamic circulation in cirrhosis, it may contribute to the maintenance of the hyperdynamic circulation observed in cirrhotic rats with ascites.

Cyclooxygenase expression in splanchnic hyposensitivity to glypressin of bleeding portal hypertensive rats.

Background Prostacyclin mediates, at least partly, the splanchnic vascular hyporesponsiveness to glypressin in bleeding portal hypertensive rats. This study investigated the relative contribution of cyclooxygenase‐1 (COX‐1) and cyclooxygenase‐2 (COX‐2) in the splanchnic hyposensitivity to glypressin in rats with portal hypertension induced by partial portal vein ligation (PVL).

Changes of hepatic and systemic haemodynamics following somatostatin administration in patients with hepatitis B‐related cirrhosis

Abstract Somatostatin has been used to effectively control acute variceal haemorrhage, with conjectured mechanisms on portal hypertension. We, therefore, evaluated the effects of somatostatin on hepatic and systemic haemodynamics in 15 patients with hepatitis B‐related cirrhosis and portal hypertension. All patients received an intravenous, continuous infusion of somatostatin 250 μg/h, following a bolus injection of 250 μg. In systemic haemodynamics, the mean arterial pressure (MAP) increased (P < 0.05), associated with a reflex bradycardia within 3 min following bolus injections, compared with basal values. The right atrial pressure, pulmonary capillary wedge pressure, inferior vena cava pressure, cardiac index, and systemic vascular resistance remained unaffected after drug infusion. In hepatic haemodynamics, the wedge hepatic vein pressure remained unchanged after drug administration. However, there was an increase in free hepatic vein pressure (FHVP; P < 0.05), and a trend toward a decrease in the hepatic vein pressure gradient (HVPG; P= 0.063), within 3 min after bolus injection. Furthermore, the hepatic blood flow decreased significantly at 10 and 30 min after somatostatin infusion (P < 0.05). The effective sinusoidal perfusion assessed by indocyanine green infusion also decreased progressively at 10 min (P= 0.057) and 30 min (P < 0.05). We concluded that somatostatin, at the dose used in this study, caused a transient and bolus‐related vasoconstrictive effect, resulting in increases in MAP and FHVP, a decrease in heart rate, and a trend toward lower HVPG. In addition, somatostatin reduced the hepatic blood flow and effective sinusoidal perfusion which may be hazardous to cirrhotic patients during variceal haemorrhage.