Teruhiro Sakai

Portal-hypertensive gastropathy develops less in patients with cirrhosis and fundal varices

BACKGROUND/AIMS The aim of this prospective study was to examine the association of portal-hypertensive gastropathy and fundal varices in patients with cirrhosis. METHODS We carried out an endoscopic observation in 476 patients with cirrhosis (study 1), including 62 patients undergoing endoscopic obliteration of esophageal varices (study 2). In study 1, patients were classified into five subgroups: no esophagofundal varices (n=119), small esophagofundal varices (n=127), dominant esophageal varices (n=177), dominant fundal varices (n=27), and large esophagofundal varices (n=26). The severity of liver dysfunction was assessed by Pugh-Child classification: class A (n=222), class B (n=200), and class C (n=54). In study 2, two groups, poorly developed fundal varices (n=50) and well developed fundal (n=12), were distinguished and the follow-up endoscopic examinations were performed on the basis of 3-month intervals for 2 years. In each study, the severity of portal-hypertensive gastropathy was scored: 0 (absent), 1 (mild), 2 (severe), and 3 (bleeding). RESULTS Study 1: One-way ANOVA showed that both variceal pattern and Pugh-Child class significantly influenced portal-hypertensive gastropathy score. However, two-way ANOVA indicated that variceal pattern was the only significant variable. Portal-hypertensive gastropathy score was significantly higher in patients with dominant esophageal varices than in either patients with no esophagofundal varices or patients with small esophagofundal varices. In contrast, portal-hypertensive gastropathy score in patients with dominant fundal varices was similar to that in patients with no esophagofundal varices and was significantly lower compared with that in patients with dominant esophageal varices. Furthermore, portal-hypertensive gastropathy score was significantly lower in patients with large esophagofundal varices than in patients with dominant esophageal varices. Study 2: After the obliteration of esophageal varices, portal-hypertensive gastropathy score in patients with poorly developed fundal varices became significantly higher at 3-, 6-, 9-months while it was not modified in patients with well developed fundal varices during the follow-up period. Furthermore, the integrated incremental change in portal-hypertensive gastropathy score during the first 1-year follow-up period was significantly lower in patients with well developed fundal varices than in patients with poorly developed fundal varices. CONCLUSIONS These results indicate that both spontaneous and obliteration-induced portal-hypertensive gastropathy lesions develop less in patients with cirrhosis and fundal varices.

Effect of posture-induced blood volume expansion on systemic and regional hemodynamics in patients with cirrhosis

BACKGROUND/AIMS This study aimed to investigate the effects of posture-induced blood volume expansion on systemic and regional hemodynamics in patients with cirrhosis. METHODS The mean arterial pressure, cardiac index, peripheral vascular resistance index, and flow volume index of the superior mesenteric artery (SMA) and femoral artery (FA) were measured in 10 patients with cirrhosis and portal hypertension and 10 controls after they had been standing for 2 h. Plasma atrial natriuretic peptide, plasma renin activity, and plasma glucagon levels were also determined. These measurements were repeated after 30 min and 60 min when the patients were recumbent. RESULTS In the upright posture, systemic hemodynamics, FA blood flow index, plasma atrial natriuretic peptide level, and plasma renin activity level were similar in patients and controls. However, SMA blood flow index and plasma glucagon level were significantly higher in patients than in controls. On the assumption of the supine position, cardiac index and plasma atrial natriuretic peptide level significantly increased in the two groups, but the changes were greater in patients than in controls. Mean arterial pressure remained unchanged. The reduction in peripheral vascular resistance index was therefore greater in patients in controls. SMA and FA blood flow index increased significantly in the two groups, but the changes were greater in patients than in controls. Furthermore, SMA blood flow fraction (SMA blood flow index/cardiac index) was steady in controls, whereas it increased significantly in patients. In contrast, FA blood flow fraction (FA blood flow index/cardiac index) remained unchanged in the two groups. In patients, the change in peripheral vascular resistance index was correlated inversely with that of SMA blood flow index, but not with that of FA blood flow index. Plasma renin activity level dropped significantly, but the decline was similar in the two groups. Plasma glucagon level was not modified in either group. CONCLUSIONS In patients with cirrhosis, splanchnic vasodilation appears to be present, even in the upright position, and further abnormal vasodilation occurs on recumbency-induced blood volume expansion. This abnormal shear-stress phenomenon observed in the splanchnic circulation seems to be mediated by a local vasodilator rather than a general vasodilator.

Effect of vasopressin on esophageal varices blood flow in patients with cirrhosis: comparisons with the effects on portal vein and superior mesenteric artery blood flow

BACKGROUND/AIMS Vasopressin reduces portal pressure which may be due to decreased portal inflow. However, it remains unclear whether vasopressin is able to selectively reduce esophageal varices blood flow. The aim of this study was to address this question. METHODS Fifteen patients with cirrhosis and esophageal varices were included in this prospective study. Portal vein and superior mesenteric artery flow velocity were measured with a percutaneous echo-Doppler. Esophageal varices flow velocity was measured using a transesophageal echo-Doppler technique. Mean arterial pressure and heart rate were also recorded. These measurements were performed at baseline condition and 15 min after observer blind drug administration. In this study, two groups, six patients receiving placebo and nine patients receiving 0.3 U/min of vasopressin, were randomized according to the coded number. RESULTS Placebo administration had no effect on systemic and splanchnic circulation. In contrast, vasopressin administration increased mean arterial pressure (p < 0.05) associated with a bradycardia (p < 0.01). In splanchnic circulation, vasopressin decreased portal vein (-32 +/- 3%, p < 0.01), superior mesenteric artery (-30 +/- 2%, p < 0.01), and esophageal varices flow velocity (-48 +/- 5%, p < 0.01). When the magnitude of these reductions was compared, ANOVA showed a significant difference (p < 0.01). Furthermore, the reduction in esophageal varices flow velocity was significantly higher than that in portal vein flow velocity (p < 0.01) and that in superior mesenteric artery flow velocity (p < 0.01). CONCLUSIONS These data support the view that vasopressin is able to selectively reduce esophageal varices blood flow. This effect, in addition to its well-established portal pressure reducing action, may play a role in its therapeutic efficacy in the treatment of variceal bleeding.

Influence of extravariceal collateral channel pattern on recurrence of esophageal varices after sclerotherapy

We investigated the influence of extravariceal collateral channel pattern on the recurrence of esophageal varices after sclerotherapy. One hundred and fifteen patients with cirrhosis and esophageal varices were studied. They were divided into four groups according to extravariceal collateral pattern on portal venography. Group 1 patients had neither paraesophageal veins nor gastrorenal veins (n-49); group 2 patients had paraesophageal veins only (n=30); group 3 patients had gastrorenal veins only (n=25); and group 4 patients had paraesophageal veins plus gastrorenal veins (n=11). Sclerotherapy was repeated to eradicate esophageal varices and follow-up endoscopic examination were performed. The overall recurrence-free rate at 36 months was 68%. The log-rank test showed the recurrence-free rate to be significantly higher in group 3 (76%) and group 4 patients (89%) than in group 1 patients (51%;P<0.05 andP<0.05, respectively). Although the recurrence-free rate was higher in group 4 than in group 2 patients (59%), this did not reach the level of significance (P=0.10). No significant differences were found between other pairs of groups. These results suggest that gastrorenal veins play an important role in the protection against recurrent esophageal varices after sclerotherapy, while the protective role of paraesophageal veins appears to be small.

Upright posture decreases esophageal varices flow velocity in patients with cirrhosis

BACKGROUND/AIMS Patients with cirrhosis tend to have esophageal variceal bleeding episodes at night, rather than during the day time. Since human beings carry on ordinary activities in the upright posture in the day time and are recumbent at night, we hypothesized that posture may be a factor related to a circadian variation of variceal bleeding. The aim of this study was to examine the effect of upright posture on esophageal varices hemodynamics in patients with cirrhosis. METHODS Nine patients with cirrhosis and esophageal varices were included in a crossover study performed on 2 separate days. On the non-endoscopic day, cardiac output, portal vein flow velocity, and superior mesenteric artery flow velocity were measured with percutaneous Doppler ultrasonography. Plasma renin activity and plasma norepinephrine concentrations were also determined. On the endoscopic day, in addition to the above measurements, esophageal varices flow velocity was measured using transesophageal Doppler ultrasonography. These measurements were performed in the supine position and 20 min after the assumption of the upright position. RESULTS On the non-endoscopic day, the upright posture significantly decreased cardiac output, portal vein flow velocity, and superior mesenteric artery flow velocity. Plasma renin activity and plasma norepinephrine concentration were significantly increased after assumption of the upright position. On the endoscopic day, similar hemodynamic and hormonal changes were observed. In addition, the upright posture significantly decreased esophageal varices flow velocity. Furthermore, the magnitude of the reduction in esophageal varices flow velocity (-42%) was significantly greater than that in portal vein flow velocity (-22%, p<0.01) and that in superior mesenteric artery flow velocity (-25%, p<0.01). Although the change in esophageal varices flow velocity was not significantly correlated with that in plasma renin activity (r=-0.28) and that in plasma norepinephrine concentration (r=-0.10), it was significantly correlated with the change in superior mesenteric artery flow velocity (r=0.73, p<0.05). CONCLUSIONS The upright posture decreases esophageal varices flow velocity mainly because of the reduction in splanchnic blood flow. This effect may contribute to a low prevalence of esophageal variceal bleeding in the day time in patients with cirrhosis.

Effect of transcatheter arterial chemoembolization on kidney hemodynamics and function in patients with cirrhosis and hepatocellular carcinoma

BACKGROUND/AIMS Transcatheter arterial chemoembolization (TACE) may have deleterious effect on the kidney in patients with cirrhosis and hepatocellular carcinoma. The aim of the study was to test this hypothesis. METHODS Twenty-four patients with cirrhosis and hepatocellular carcinomas were included. They consisted of 16 patients undergoing a single TACE and eight patients undergoing diagnostic angiography. Doppler ultrasonography was used to measure hepatic artery pulsatility index (HA-PI) and renal artery pulsatility index (RA-PI) before and 1 day and 10 days after the procedure. Similarly, kidney function was assessed by measuring creatinine clearance. In addition, plasma renin activity, noradrenaline, and endothelin-1 were also measured. RESULTS In patients receiving diagnostic angiography, no significant changes in HA-PI were observed after the procedure. In contrast, HA-PI increased significantly 1 day after the procedure (19%, p<0.01) in patients undergoing TACE, although it returned to baseline value 10 days after the procedure. In patients undergoing diagnostic angiography, no significant changes in RA-PI were observed after the procedure. Similarly, no detectable changes in RA-PI were noted in patients undergoing TACE. A transient small reduction in creatinine clearance was noted after the procedure in patients undergoing diagnostic angiography (-12%, p<0.05) and in those undergoing TACE (-11%, p<0.05). However, the effect was similar in the two groups (two-way ANOVA, p=0.72). No significant changes in plasma renin activity, noradrenaline, and endothelin-1 were observed after either diagnostic angiography or TACE. CONCLUSIONS These results suggest that TACE per se has no deleterious effect on the kidney hemodynamics and function in patients with cirrhosis and hepatocellular carcinoma.

UPRIGHT POSTURE BLUNTS POSTPRANDIAL SPLANCHNIC HYPEREMIA IN PATIENTS WITH CIRRHOSIS AND PORTAL HYPERTENSION

Abstract: The aim of this study was to compare postprandial hemodynamic changes observed during assumption of the recumbent posture and upright posture in patients with cirrhosis and portal hypertension. Eleven patients with cirrhosis and portal hypertension were studied. Echo-Doppler examinations were performed to measure flow volume in the portal vein (PV), superior mesenteric artery (SMA), and splenic artery (SA) in the fasting condition. Collateral blood flow was indirectly calculated by determining the difference between the sum of SMA, SA, and PV blood flows. After these measurements were done, each patient received a standardized liquid meal and was then randomly assigned to either maintain supine or upright posture, in a crossover design, on 2 different days (recumbent day and upright day). On each study day, the above-mentioned measurements were repeated 30 min and 60 min after the meal. PV blood flow increased significantly after the meal on the recumbent day (P < 0.01) but not on the upright day (P = 0.78). Although there were significant postprandial increases in SMA blood flow on both study days (P < 0.01, P < 0.01), the effect was less pronounced on the upright day than on the recumbent day (P < 0.01). Postprandial SA blood flow showed no change on the recumbent day (P = 0.64), but decreased significantly on the upright day (P < 0.01). The calculated postprandial collateral blood flow increased significantly on the recumbent day (P < 0.05), but showed no change on the upright day (P = 0.53). These results suggest that the upright posture blunts postprandial splanchnic hyperemia in patients with cirrhosis and portal hypertension.

High plasma cardiac natriuretic peptides associated with enhanced cyclic guanosine monophosphate production in preascitic cirrhosis

BACKGROUND/AIMS The initial abnormalities of renal sodium handling in cirrhosis remain unclear. The aim of this study was to characterize sodium metabolism in preascitic cirrhosis. METHODS Ten patients with preascitic cirrhosis and ten controls were studied. All subjects ate a diet providing 120 mmol sodium during an equilibration period lasting 5 days and the study day. On the study day, after remaining in bed, plasma levels of atrial natriuretic peptide, brain natriuretic peptide, renin activity, aldosterone, noradrenaline, and cyclic guanosine monophosphate were measured at 7 am. Thereafter, they were instructed to maintain an upright posture until dinner and the measurements were repeated at 9 am and 6 pm. After having dinner, all subjects were asked to remain in bed and the measurements were repeated at 11 pm. To measure renal sodium and cyclic guanosine monophosphate excretion, 24-h urine collections were performed, starting from 7 pm on the day before the experimental day. RESULTS Plasma levels of atrial natriuretic peptide, brain natriuretic peptide and cyclic guanosine monophosphate in patients with preascitic cirrhosis were significantly elevated compared with those in controls at every sampling time (p=0.03 or less, p= 0.04 or less, and p=0.01 or less). In contrast, plasma renin activities at every sampling time were significantly lower in patients than in controls (p= 0.04 or less). Plasma aldosterone and noradrenaline levels were not significantly different at every sampling time in the two groups. No significant differences in daily renal sodium excretion were found. However, urinary cyclic guanosine monophosphate excretion was significantly higher in patients than in controls (p<0.01). CONCLUSIONS The initial abnormalities of sodium metabolism in cirrhosis might be characterized by blunted renal responsiveness to natriuretic peptides. The results of the study also provide indirect evidence that the impairment is mainly located at postreceptor levels of signal transduction pathway to the peptides, if the activation of antinatriuretic factors other than renin-angiotensin or sympathoadrenergic systems does not play a role.