Difference of hepatic circulation between alcoholic and non-alcoholic hepatic cirrhosis

Comparisons were made of hepatic circulation between alcoholic and non-alcoholic cirrhosis. The wedged hepatic venous pressure and per cent intrahepatic shunt measured by the method of continuous infusion of D-galactose-1-14C were similarly markedly increased. On the other hand, the wedged hepatic venography showed the main portal trunk and extrahepatic collaterals, namely, the tendency of reverse or stagnant portal flow, more frequently in alcoholic cirrhosis than in non-alcoholic cirrhosis. The nodules shown by slow low-pressure hepatic sinusoidography were larger in non-alcoholic cirrhosis than in alcoholic cirrhosis.     

Influence of somatostatin on splanchnic haemodynamics in patients with liver cirrhosis

Summary. The influence of intravenous somatostatin infusion (7·6 μag/min) on systemic and splanchnic haemodynamics was examined in 10 patients with liver cirrhosis and portal hypertension. The hepatic vein catheter technique was employed and indocyanine green dye was injected to evaluate hepatic blood flow. Mean wedged hepatic venous pressure fell from 24·9±2·8 in the basal state to 21·4±3·2 mmHg (P<0·2) at 60 min of infusion and the mean arterial pressure decreased from 87±5 to 80±6 mmHg (P<0·05). The rate of indocyanine green dye disappearance decreased from 8·7± 1·9 to 6·6±1·7 %/min (P<0·00l) during the infusion, indicating decreased hepatic blood flow. Arterial-hepatic venous oxygen differences rose from 69±11 to 78±11 ml/l. Blood glucose levels fell from 4·84±0·31 to 3·79± 0·33 mmol/l at 60 min of infusion (P<0·005). It is concluded that a continuous infusion of somatostatin in patients with liver cirrhosis and portal hypertension causes a decreased hepatic blood flow with augmented hepatic oxygen extraction and a modest reduction in mean wedged hepatic venous pressure. In view of the magnitude of the observed haemodynamic changes the findings do not suggest an important role for somatostatin in the treatment of patients with bleeding oesophageal varices.     

Hepatic insulin retention depends on influx in both diabetic and normal dogs

Hepatic retention of endogenous and exogenous insulin was investigated in normal and alloxanstreptozotocin diabetic dogs. An hour's peripheral venous infusion of insulin was preceded and followed by saline infusion. Blood samples were drawn simultaneously from the femoral artery and portal, hepatic and peripheral veins. Blood flow was measured electromagnetically in the portal vein and hepatic artery. Hepatic plasma flow was lower in diabetic dogs (p less than 0.001) so that prior to insulin infusion (basal hour) basal mean hepatic venous flux was diminished in them. Hepatic glucose production was higher (p less than 0.05) and arterio-venous glucose difference lower (p less than 0.01) in diabetics basally, but post-insulin infusion, these became similar in diabetics and normals. Although basal hour arterial and peripheral venous insulin concentrations were similar, portal venous insulin was 3.5-fold lower in diabetics. Mean insulin influx (hepatic arterial + portal venous fluxes) was four-fold lower in diabetics. The insulin net flux (influx - hepatic venous flux) was lower in diabetics (p less than 0.05) as was % extraction (p less than 0.001). During the insulin infusion hour the values remained lower for diabetics (p less than 0.05) for influx, net flux and % extraction. During the post-insulin infusion hour the influx, net flux and % extraction became similar. When the basal hour data in normals was restricted to the range of diabetic insulin influx values less than or equal to 10 mU X min-1, the differences in net flux and % extraction between normals and diabetics were no longer present.(ABSTRACT TRUNCATED AT 250 WORDS)     

Logistic-regression model for assessing portal hypertension by measuring hyaluronic acid (hyaluronan) and laminin in serum

We earlier observed a positive correlation between portal venous pressure (PVP) and the concentration of laminin in serum. Here we investigated whether the diagnostic efficacy could be improved by considering additional analytes and application of multivariate statistical analysis. In 102 patients with fibrotic liver disease of various etiologies we measured PVP as the gradient of the wedged and free hepatic venous pressures and determined the concentrations of hyaluronic acid and laminin in serum. Regression coefficients established by logistic regression in this group were subsequently used to predict portal hypertension (PVP greater than mmHg) in an independent group of 45 patients. By comparison with the known PVP, we obtained a sensitivity of 0.83 (confidence interval: 0.63-0.93) and a specificity of 0.82 (0.61-0.93) for diagnosis of portal hypertension by means of the concentrations of hyaluronic acid and laminin in serum. Application of the model is suggested as a tool for pre-screening and monitoring patients to be subjected to assessment of portal hypertension.     

Effect of chronic and progressive hepatic outflow blockade on renal function in rats

Systemic and splanchnic hemodynamics, plasma concentration, and urinary excretion of several hormones and the changes in renal function induced by saline infusion were studied in rats with a chronic and progressive model of postsinusoidal hypertension by hepatic vein ligation (HVL) and in a control group. HVL rats showed no differences in systemic hemodynamics compared with control rats, with the exception of decreased renal blood flow and increased renal vascular resistance. HVL rats showed increased portal and intrahepatic pressure, without other differences in splanchnic hemodynamics or in portal-systemic shunts. Clearance studies revealed that under basal conditions, HVL rats showed lower glomerular filtration rate, renal plasma flow, urinary flow, and sodium, chloride, and potassium excretion than control rats. After saline infusion (3% body weight, 15 ml/hr) differences in glomerular filtration rate became nonsignificant, but urinary flow and electrolyte excretion remained lower in HVL than in control rats. Under basal conditions, plasma norepinephrine and dopamine concentrations were higher and urinary prostaglandin E2 (PGE2) and prostaglandin F2 alpha levels were lower in HVL than in control animals. These results demonstrate that chronic and progressive hepatic congestion results in impaired renal function with decreased water and electrolyte excretion, and suggest the involvement of a hepatorenal sympathetic reflex in these alterations. Renal effects could also be mediated by the low levels of PGE.     

Effects of sodium nitroprusside, isosorbide dinitrate, isoproterenol, phentolamine and prazosin on hepatic venous responses to sympathetic nerve stimulation in the cat.

Hepatic blood volume was recorded by a plethysmographic technique in cats anesthetized with pentobarbital. The effects of three doses of each vasodilator drug were measured on arterial and portal pressures, hepatic blood volume in the denervated liver and on the portal pressure and hepatic venous responses to sympathetic nerve stimulation. Isosorbide dinitrate caused a small reduction in basal hepatic venous tone increasing hepatic blood volume by up to 15%; it had no effect on the responses to sympathetic nerve stimulation. Isoproterenol increased hepatic venous tone perhaps by stimulation of angiotensin formation and the responses to stimulation of the hepatic nerves were reduced because of this increased basal tone. Sodium nitroprusside produced a small decrease in basal venous tone and only large doses produced any reduction in the venous responses to hepatic nerve stimulation. The evidence that nitroprusside is a venodilator requires reexamination. Phentolamine had no effect on basal venous tone but markedly reduced the responses to sympathetic nerve stimulatiqn. When compared to phentolamine, prazosin produced comparable effects on arterial pressure but much less reduction in the hepatic venous responses to sympathetic stimulation. It is suggested that the alpha receptor blocking action of prazosin is selective for arterioles and this may explain the minor incidence of postural hypotension during clinical use.     

Alpha adrenoceptor subtype mediating sympathetic mobilization of blood from the hepatic venous system in anesthetized cats

Previous studies have suggested that sympathetic effects on hepatic blood volume may be mediated through alpha-2 adrenoceptors in anesthetized cats as prazosin did not block whereas phentolamine and phenoxybenzamine impaired these responses markedly. In this study we have shown that yohimbine blocks hepatic volume responses to both nerve stimulation and norepinephrine infusions. In comparison with norepinephrine, phenylephrine had much weaker effects on hepatic blood volume than on arterial and portal pressures. Clonidine produced a slow weak contraction of the hepatic venous bed which was blocked by yohimbine but not by prazosin. alpha-Methylnorepinephrine produced a norepinephrine-like contraction of the hepatic venous bed which was blocked by yohimbine but not by prazosin. Taken together, these data suggest that hepatic blood volume responses to both sympathetic nerve stimulation and infusions of catecholamines are mediated through alpha-2 adrenoceptors, whereas portal pressure responses are mediated through both alpha-1 and alpha-2 adrenoceptors.     

肝脏CT灌注成像与门静脉压力相关性的动物实验研究

目的:探讨正常比格犬门静脉压力与肝脏CT血流灌注参数的相关性。方法:采用螺旋CT对24只犬行肝脏灌注成像扫描,去卷积法计算肝脏血流灌注参数,包括血流量(blood flow,BF)、血容量(blood volume,BV)、平均通过时间(mean transit time,MTT)、肝动脉分数(hepatic arterial fraction,HAF)、肝动脉灌注量(hepatic arterial perfusion,HAP)、门静脉灌注量(portal venous perfusion,PVP)。扫描后3d内开腹,采用玻璃水柱法测定门静脉压力。利用直线回归与相关分析门静脉压力与肝脏CT血流灌注参数的相关性。结果:(1)正常比格犬实测门静脉压力值为(13.57±1.15)cmH2O。(2)正常比格犬门静脉压力与BF、PVP呈负相关,与HAF呈正相关,其中以PVP相关性最显著(r=-0.764,P<0.05),两者关系的直线回归方程为Y=16.507-0.037X。结论:肝脏CT灌注成像为无创、有效监测门静脉压力提供了一种新途径。     

The effect of increased inferior vena cava pressure on hepatic circulation in the dog

Inferior v. cava pressure (IVCP) was raised in the dog by a baloon catheter introduced via the jugular vein. Hepatic artery flow (HAF) and portal venous flow (PVF) were measured with the electromagnetic flow meter. The increase of IVCP reduced uniformly HAF and PVF, the relative contribution of the two vessels to the HBF did not change. The relationship between IVCP increase and HAF reduction and between the decrease of AP-IVCP and the reduction of HAF was linear. There was no sign of autoregulation or vasomotor regulation of HAF. The changes in IVCP are only partially transmitted to the portal venous pressure (PVP). There was no change in intrahepatic portal resistance with increased IVCP. The increase in PVP did not lead to resistance changes in the splanchnic circulation. As a sign of the autoregulation of splanchnic circulation of the AP-PVP versus PVF curve was concave to the pressure axis. It is concluded that as a result of opposing autoregulatory and vasomotor influences in the intact animal the hepatic circulation appears to react passively to the increased outflow pressure.     

Venous resistance increases during rat anaphylactic shock

Anaphylactic shock is a sudden, life-threatening allergic reaction associated with severe hypotension. The increased venous resistance accounts for the anaphylactic hypotension in anesthetized dogs. However, the change in peripheral vascular resistances during anaphylactic hypotension in other animals such as rats is not known. We measured the mean circulatory filling pressure using the mechanical occlusion method of inflation of the right atrial balloon along with systemic arterial pressure (Psa), central venous pressure, and portal venous pressure. Cardiac output was also measured with the thermodilution method. From these hemodynamic variables, we calculated the total peripheral and venous (Rv) resistances during anaphylactic hypotension in anesthetized rats. These hemodynamic variables were compared with those in the hemorrhagic shock. After an intravenous injection of 0.6 mg antigen ovalbumin in sensitized rats, Psa decreased from 119 +/- 4 to 43 +/- 2 mmHg, cardiac output decreased from 84.5 +/- 5.7 to 37.8 +/- 2.1 mL min, central venous pressure decreased from 0.9 +/- 0.1 to 0.1 +/- 0.1 mmHg, and mean circulatory filling pressure also decreased from 6.0 +/- 0.2 to 5.2 +/- 0.3 mmHg. Thus, the Rv increased from 0.06 +/- 0.05 to 0.15 +/- 0.02 mmHg mL(-1) min(-1), but total peripheral resistance did not significantly change. Portal venous pressure also increased from 5.6 +/- 0.5 to 21.5 +/- 0.9 mmHg. Hematocrit markedly increased from the baseline values of 43% +/- 1% to 55% +/- 1% at 15 min after antigen. During hemorrhagic shock, Psa decreased in the manner similar to anaphylactic shock; however, Rv did not significantly change, and portal venous pressure decreased. In conclusion, in rat anaphylactic shock, a substantial increase in Rv presumably due to hepatic venoconstriction may decrease venous return, resulting in systemic hypotension.     

Effect of histamine H3 receptor blockade on venous return and splanchnic hemodynamics in experimental bacteremia

OBJECTIVE: In the heart, histamine H3 receptors may function as inhibitory presynaptic receptors that decrease adrenergic neural norepinephrine release in conditions of enhanced sympathetic tone. In a previous study, we found that H3 receptor blockade improved cardiac contractility and systemic hemodynamics in experimental bacteremia in dogs. Because histamine H3 receptors have been found in the splanchnic circulation in other animal models, it was not clear the extent to which H3 receptor blockade may have altered splanchnic hemodynamics, and variables of venous return, that in turn contributed to the overall improvement in systemic hemodynamics observed in the previous experiment. In the present study, we examined splanchnic hemodynamics in the presence of H3 receptor blockade in a canine model of Escherichia coli bacteremia. DESIGN: Bacteremia was produced by intravenous infusion of live E. coli administered throughout the experiment. Variables of venous return included mean systemic pressure, resistance to venous return, and mean right atrial pressure. Splanchnic measurements included hepatic and portal pressures and flows. Measurements were obtained before and after H3 receptor blockade with thioperamide maleate. The animals were studied while ventilated and anesthetized. RESULTS: H3 receptor blockade caused a decrease in mean right atrial pressure from 5.9 mm Hg pretreatment to 3.5 mm Hg posttreatment (p < .05), although it did not affect mean systemic pressure or resistance to venous return. There were no changes in portal or hepatic flows after H3 receptor blockade. The cardiac function curve after H3 receptor blockade was shifted upward and to the left compared with the pretreatment curve. CONCLUSIONS: The results showed that the primary effect of H3 receptor blockade in experimental bacteremia was attributable to an increase in inotropy. There was no evidence to indicate that H3 receptor activation contributed to altered splanchnic hemodynamics in this model.     

Roles of endothelin-1 and nitric oxide in the mechanism for ethanol-induced vasoconstriction in rat liver.

This study was designed to investigate the mechanism for ethanol-induced hepatic vasoconstriction in isolated perfused rat liver. Upon initiation of ethanol infusion into the portal vein at concentrations ranging from 25 to 100 mM, portal pressure began to increase in a concentration-dependent manner and reached maximal levels in 2-5 min (initial phase), followed by a gradual decrease over the period of ethanol infusion (escape phenomenon). Endothelin-1 antiserum significantly inhibited this ethanol-induced hepatic vasoconstriction by 45-80%. Cessation of infusion of endothelin-1 antiserum was followed by a subsequent increase in portal pressure. On the other hand, when a nitric oxide synthesis inhibitor, NG-monomethyl-L-arginine (L-NMMA), was infused into the portal vein simultaneously with ethanol, the initial phase of the response of portal pressure to ethanol was not altered and the peak values of portal pressure remained unchanged. However, after the peak increase in portal pressure, the rate of decrease was less than in the absence of L-NMMA. Thus, L-NMMA diminished the escape phenomenon and sustained the vasoconstriction. This study supports the hypothesis that two endothelium-derived vasoactive factors, endothelin-1 and nitric oxide, regulate hepatic vascular tone in the presence of ethanol.     

Dogs with experimental cirrhosis of the liver but without intrahepatic hypertension do not retain sodium or form ascites.

Dogs with portal cirrhosis but without portal hypertension (end-to-side portacaval anastomosis) retain sodium and expand plasma volume before ascites formation. In our study, dogs were subjected to bile duct ligation and simultaneous side-to-side portacaval anastomosis (PCA) in order to create a canine model of hepatic cirrhosis without intrahepatic or portal hypertension. The effect of normalizing intrahepatic pressures in the face of venous outflow block on sodium handling was studied. 13 dogs survived the surgical procedures and were followed. Two dogs developed sodium retention and ascites at 5-6 wk (livers were cirrhotic) when the PCA spontaneously closed. 11 dogs were free of sodium retention and ascites for as long as 12 wks after surgery, while ingesting 35 meq/d of sodium. In this group glomerular filtration rate remained normal throughout the period of observation and there was no expansion of plasma volume. Nine of these dogs were then fed 85 meq/d of sodium; eight remained in sodium balance and one retained sodium and went on to develop ascites. When 10-15 mg i.m. of desoxycorticosterone acetate (DOCA) was given daily, five dogs developed sodium retention and ascites, while four escaped from DOCA. Dogs who developed ascites had either a partially occluded PCA (4/5) or a patent PCA, but with a significant portacaval pressure gradient of 9.5 cm H2O (1/5). In all four dogs who escaped from DOCA, the PCA was widely patent and the mean pressure gradient was only 1.6 cm H2O. Both groups were equally cirrhotic, as judged by histological and biochemical parameters. We conclude that normalizing intrahepatic pressure by providing an outflow tract for the cirrhotic liver will abolish that component of early renal tubular sodium retention not due to portal venous hypertension or ascites sequestration.     

Systemic and splanchnic haemodynamic effects of pentifylline in rats with portal hypertension.

1. The systemic and splanchnic haemodynamic effects of pentifylline (40 mg/kg body weight intravenously) were assessed in rats with portal hypertension associated either with CCl4-induced cirrhosis (n = 13) or portal vein ligation (n = 13). 2. Heparinized catheters were placed into the portal vein, inferior vena cava, aorta and left ventricle with exits from the neck. Haemodynamic studies were performed 4 h after consciousness was regained. Cardiac output and regional blood flows were measured using radiolabelled microspheres and the reference sample method in seven rats in each group; portal-systemic shunting was measured using microsphere injection in the ileo-colic vein in six rats in each group. 3. Forty-five minutes after injection, pentifylline had no effect on mean arterial pressure, cardiac output, peripheral resistance, portal venous flow, hepatic artery flow or portal-systemic shunting in either group of rats with portal hypertension. The drug lowered portal pressure (-18%) in cirrhotic rats, but not in portal-vein-ligated rats. 4. These data demonstrate that pentifylline lowers portal pressure in cirrhotic rats without affecting portal venous flow and portal-systemic shunting; this effect is possibly mediated by changes in intrahepatic resistance related to the effects of pentifylline on blood viscosity and/or on intrahepatic vasomotor tone.     

Vasoactive intestinal peptide down-regulates the intrahepatic renin-angiotensin system in the anaesthetized rat.

Gastric sodium loading results in an increase in the portal venous concentration of vasoactive intestinal peptide (VIP) and down-regulation of both the intrahepatic and circulating renin-angiotensin systems. In the present study we sought to determine whether an increase in the concentration of VIP in the portal circulation might act to down-regulate the intrahepatic and/or circulating renin-angiotensin systems. Male Sprague-Dawley rats were infused intraportally with haemaccel vehicle or VIP in haemaccel for 60 min. Livers were harvested and blood was sampled. Angiotensin-converting enzyme (ACE) activity and angiotensinogen, angiotensin I, angiotensin II and renin concentrations were measured. VIP infusion decreased hepatic ACE activity (P < 0.05), the hepatic angiotensinogen concentration (P < 0.001) and the hepatic angiotensin I concentration (P < 0.05). The plasma angiotensinogen concentration and serum ACE activity were also decreased by intraportal VIP infusion (P < 0.05 for each). Plasma renin, angiotensin I and angiotensin II concentrations were unchanged by VIP infusion. We conclude that an increase in the portal venous VIP concentration down-regulates the intrahepatic renin-angiotensin system. These changes are similar to those reported after gastric sodium loading, and we suggest, therefore, that the increase in portal venous VIP that occurs after gastric sodium is the means by which the gastric sodium sensor signals the liver to effect these changes in the renin-angiotensin system.     

Effect of calcium antagonists on basal and digitalis-dependent changes in splanchnic and systemic hemodynamics

We investigated the effects of the calcium antagonists verapamil and tiapamil on basal splanchnic and systemic hemodynamics and digoxin-induced vasoconstriction in 16 healthy men, using the hepatic venous catheter technique, the thermodilution method, and systolic time intervals. After a baseline period, verapamil or tiapamil were given by a primed-constant infusion in six of 16 subjects each, and hemodynamic changes were determined. Thereafter digoxin (1 mg) was concomitantly infused and hemodynamic changes were observed over 105 minutes. Control trials with digoxin alone were performed in seven of 16 subjects. Four of 16 subjects received only placebo. Digoxin provoked an increase in systolic blood pressure and splanchnic vascular resistance. Estimated splanchnic blood flow, mean pulmonary artery pressure, and total electromechanical systole decreased. Verapamil did not change basal hemodynamic parameters. Tiapamil decreased diastolic blood pressure and systemic and splanchnic vascular resistance. Both drugs attenuated the vasoconstricting effect of digoxin on the splanchnic vascular bed. Results indicate that calcium antagonists might be beneficial in treatment of digitalis-induced splanchnic vasospasm.     

Differential response of normal and cirrhotic liver to vasoactive agents. A study in the isolated perfused rat liver

In cirrhosis, endogenous vasoactive agents could act as modulators of intrahepatic resistance and thus portal pressure. The aim of this work was to study the effects of norepinephrine, angiotensin II and arg8-vasopressin on intrahepatic portal resistance in isolated perfused livers from normal rats and rats with carbon tetrachloride-induced cirrhosis. Livers were perfused at a constant pressure and the measured variable was portal blood flow. Dose-response curves were obtained by cumulative addition of agonists to the perfusate. The three vasoactive agents increased resistance in normal and cirrhotic livers. The maximal amplitude of response was similar in normal and cirrhotic livers. The cirrhotic livers exhibited an increased sensitivity to norepinephrine, a decreased sensitivity to angiotensin II but an unchanged sensitivity to arg8-vasopressin. The shape of the dose-response curve for norepinephrine and arg8-vasopressin, but not for angiotensin II, was modified in cirrhotic livers. We conclude that the cirrhotic liver retains a strong vascular reactivity to vasoactive agents and particularly to norepinephrine.     

Clinical value of hepatic vein catheterization

Techniques of hepatic vein catheterization, hepatic venous pressure measurement, and occlusion phlebography using a balloon catheter are described.Hepatic venous pressure measurements (n=95) and hepatic occlusion phlebography were combined in 32 cases.In patients with liver cirrhosis (n-63) a significant elevation of hepatic venous pressure gradients was found. A decrease of the pressure gradient was seen after portacaval and splenorenal shunt operations.Hepatic occlusion phlebography showed alterations of hepatic veins only in patients with cirrhosis. A rough correlation between pressure gradients and the extent of changes in the liver veins was found. Hepatic occlusion phlebography, in patients who had undergone shunt procedure, demonstrated various collaterals.Combined hepatic vein pressure measurements and hepatic occlusion phlebography using a balloon catheter are proposed as a very suitable method for the evaluation of chronic liver disease and portal hypertension.     

Decreased arteriovenous flow resistance in the left gastric venous area in cirrhotic patients

Abstract. To assess the relationship between the fluid mechanics in the left gastric venous area and the portal trunk, manometric measurements were made in patients with or without cirrhosis of the liver. In ten normal subjects, temporary portal vein occlusion produced comparable elevation in both the occluded left gastric venous pressure (OLGP) and the portal vein pressure (PVP); 152–4129 mm of water in OLGP and 115–452 mm of water in PVP. In sixty cirrhotic patients, however, the portal vein occlusion resulted in far less increase in OLGP than that in PVP; 281–365 mm of water in OLGP and 281–540 mm of water in PVP. In other words, regarding pressure measurements, the relationship was 'separated' in cirrhotics, but 'continuous' in normal subjects. Mathematical analysis of the data using a modification of Wheat-stone bridge model suggested that the arteriovenous flow resistance in the left gastric venous area of cirrhotics was reduced to less than one fifth of that in the controls. It would appear that the increased flow capacity as a result of a reduced arteriovenous flow resistance is responsible for the functional 'separation' from the portal trunk.     

Hepatofugal portal flow in advanced liver cirrhosis with spontaneous portosystemic shunts: effects on parenchymal hepatic enhancement at dual-phase helical CT

BACKGROUND: We investigated whether spontaneous hepatofugal portal flow in advanced cirrhosis affects hepatic enhancement on dual-phase helical computed tomography. METHODS: Fifteen patients with hepatofugal portal flow on Doppler sonography and angiography (group 1) and 15 age- and sex-matched patients with hepatopetal portal flow (control; group 2) underwent dual-phase helical computed tomography. Vascular and liver attenuation values were measured on unenhanced scans and scans obtained during hepatic arterial (HAP; 25 s) and portal venous (PVP; 70 s) phases. RESULTS: Portal vein enhancement was lower during PVP in group 1 than in group 2 ( p < 0.0001). Liver enhancement was higher during HAP and lower and delayed during PVP in group 1 versus group 2 ( p < 0.0001). CONCLUSION: In hepatofugal portal flow, liver enhancement is increased during HAP and compensating for decreased and delayed liver enhancement during PVP, resulting in potential decreased hypervascular tumor conspicuity.