NABIL EL-KADY, M.D.*; ZAKARIA SALAMA, M.D.*; IMAN HAMZA, M.D.*; AHMAD FOUAD, M.D.*; HEBA FADL, M.D.** and GAMAL ESMAT, M.D.*

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1 Med. J. Cairo Univ., Vol. 77, No. 3, December: 27-35, The Role of Duplex Color Doppler Ultrasonography in the Evaluation of Hepatic Arterial Flow and Arterial Resistance Indices in Patients with Liver Cirrhosis NABIL EL-KADY, M.D.*; ZAKARIA SALAMA, M.D.*; IMAN HAMZA, M.D.*; AHMAD FOUAD, M.D.*; HEBA FADL, M.D.** and GAMAL ESMAT, M.D.* The Department of Tropical Medicine and Liver, Faculty of Medicine, Cairo University* and Police Hospital**. Abstract Introduction: Color Doppler ultrasonography is an important breakthrough in the noninvasive evaluation of splanchnic hemodynamics. However, until present, there is no consensus on the role of Doppler parameters in grading the severity of chronic liver disease. Different studies performed in cirrhotic patients have yielded conflicting results due to differences in the selection of patients with different degrees of hepatic decompensation. Aim of the Work: The aim of this work is to evaluate hepatic and splenic arterial blood flow and arterial resistance indices by duplex color Doppler ultrasonography in patients with different grades of liver cirrhosis and portal hypertension. Patients and Methods: Sixty patients with liver cirrhosis and oesophageal varices were enrolled {44 males (73.4%), 16 females (26.6%), mean age 49.1 years ± 7.8 years} in addition to 20 healthy controls (14 males 70%, 6 females 30%, mean age 47.3 years ±7.0 years). Patients were divided into 4 groups. Child A, B and C patients were allocated to groups I, II and III respectively, group 4 patients comprised the control group (20 patients each). Calculated Doppler parameters included diameter, cross sectional area, velocity and flow volume for the hepatic artery splenic artery and portal vein in addition to the hepatic and splenic artery pulsatility and resistive indices and portal vein congestion index. Additionally the Liver vascular index (LVI) and Doppler perfusion index were calculated. Results: The hepatic artery mean diameter, cross sectional area, velocity and flow volume were comparable among patients and controls. The hepatic artery mean pulsatility and resistive indices (PI and RI) were significantly higher among patients as compared to controls (PI: 0.96 ±0.147, 1.66±0.25, 1.24±0.114 and 0.89±0.054 and RI: ±0.065, 0.734±0.054, 0.797±0.016 and ±0.024 in groups I-IV respectively) correlating with the Child-Pugh score and oesophageal variceal grading. The splenic artery mean diameter significantly increased among patients. The mean flow volume, PI and RI were significantly higher among patients as compared to the control group (PI: 1.03 ±0.127, 1.059±0.112, 1.07±0.091, 0.725±0.07, RI: 0.636±0.055, ±0.05, 0.685±0.04, ± 0.02 in groups I-IV respectively). Splenic impedance indices didn t correlate with the Child grade but correlated with the grade of varices. There is a highly significant decrease of liver vascular index (LVI) and a highly significant increase in Doppler perfusion index (DPI) in patients as compared to the control group. Conclusion: Doppler and color Doppler ultrasonography are valuable screening procedures for the assessment of the patient with cirrhosis and portal hypertension. The hepatic arterial resistance indices increase in cirrhosis and correlate with the severity of portal hypertension. While, the splenic artery resistance indices are increased in cirrhotic patients and do not correlate with the severity of portal hypertension although it correlates with the degree of oesophageal varices. Neither the portal venous blood flow nor the hepatic arterial blood flow are useful parameparameters for discriminating patients with cirrhosis from healthy subjects. Key Words: Portal hypertension liver cirrhosis Doppler of portal vein Hepatic artery and splenic artery. Introduction AN increase in hepatic resistance to blood flow is the initial phenomenon leading to portal hypertension accompanying liver cirrhosis. Additionally splanchnic vasodilatation with increased portal blood inflow, contributes to the maintenance and aggravation of portal hypertension [1-3]. Hepatic venous pressure gradient (HVPG) measurement is an established methodology to assess the severity of portal hypertension [4,5]. Although representing a gold standard, HVPG measurement is invasive, relatively expensive and available only in major centers. Therefore, there is an urgent need to develop reliable, non-invasive and widely available methods for the clinical assessment of portal hypertension in cirrhotic patients [6]. Ultrasonography has the advantages of low cost, easy opera- 27

2 28 Duplex Color Doppler Us in Liver Cirrhosis tion and high acceptability by the patients. It can provide not only valuable information on the morphological changes of the liver but also liver hemodynamics by color Doppler flow imaging [7-10]. The introduction of color Doppler ultrasonography has been an important breakthrough in the noninvasive evaluation of splanchnic hemodynamics. Both qualitative and quantitative evaluations of the portal systemic circulation are being widely used in patients with chronic hepatitis and cirrhosis [11-13]. However, until the present, there is no consensus on the role of Doppler parameters in grading the severity of chronic liver disease [14-19]. Moreover, different studies performed in cirrhotic patients have yielded conflicting and non conclusive results [20-25]. This is owing to differences in the selection of patients with different degrees of hepatic decompensation and/or to the inclusion of patients presenting confounding factors such as concomitant cardiovascular or renal diseases, or treatment with vaso-active agents or diuretics. Aim of the work: The aim of this work is to evaluate hepatic and splenic arterial blood flow and arterial resistance indices by duplex color Doppler ultrasonography in patients with different grades of liver cirrhosis and portal hypertension. Subjects and Methods Sixty consecutive patients with liver cirrhosis and oesophageal varices of whatever grade were enrolled in the study {44 males (73.4%), 16 females (26.6%), mean age 49.1 years ±7.8 years} in addition to 20 healthy controls (14 males 70%, 6 females 30%, mean age 47.3 years ±7.0 years). Patients with at least one of the following conditions were excluded: actual or previous hepatic encephalopathy, history of gastro-intestinal (GI) bleeding, hepatocellular carcinoma, cardiopulmonary disease, arterial hypertension, renal artery stenosis (ruled out by Doppler examination), diabetes mellitus, acute and chronic renal failure, previous treatments for portal hypertension, use of vaso-active drugs, diuretics or anti-inflammatory drugs, ongoing antiviral therapy, portal vein thrombosis and age <18 or >70 years. Routine laboratory tests were performed and reviewed in enrolled subjects before inclusion in this study. Patients underwent a complete abdominal ultrasonographic examination and upper GI endoscopy for grading of oesophageal varices (Table 1) using the Olympus videoscope GIF-XQ 240. Doppler Ultrasonography was done after an overnight fasting; patients were maintained in supine position for 15 min. Thereafter, Doppler measurements were obtained by an expert operator using an ultrasound equipment (Toshiba, SSA 320, Tokyo, Japan), with a MHz convex probe equipped with color and pulsed wave Doppler (range MHz). The Doppler sample volume, with a width of approximately half of the lumen, was placed in the middle of the vessel. Aliasing was avoided by using the best pulse repetition frequency in relation to the velocity of the vessel. A cutoff filter of 100 Hz was installed to eliminate possible artifacts from vessel wall motion. Calculated Doppler parameters included diameter, cross sectional area, velocity and flow volume for the hepatic artery splenic artery and portal vein in addition to the hepatic and splenic artery pulsatility and resistive indices and portal vein congestion index. Additionally the Liver vascular index (LVI) and Doppler perfusion index were calculated: LVI= DPI= Portal vein velocity Hepatic artery pulsatility index Hepatic artery flow Portal vein flow Patients were graded according to the child -pugh classification: Group I: Included 20 patients Child A. Group II: Included 20 patients Child B. Group III: Included 20 patients Child C. Healthy controls were grouped as Group IV. Statistical methods: The statistical tests used in this thesis are: Student t-test: T= X 1 = Mean of the first group. X 1 X 2 SD 2 SD n 1 n2 X2= Mean of the second group. SD 1= Standard deviation of the first group. SD2= Standard deviation of the second group. n1= Number of cases in the first group. n2= Number of cases the second group. X= Value. n= Number of cases X X= n

3 Nabil El-Kady, et al. 29 Standard deviation: x= Value. X= Mean. E= Sum. n= Number of cases. Chi-square test: E= Sum. O= Observed value. E= Expected value. Probability (P): S.D.= (X x) 2 n 1 (O E) 2 X 2 = E The significance level was set at p>0.05= Insignificant. p<0.05= Significant. p<0.01= Highly significant. The hepatic artery mean diameter, cross sectional area and velocity were comparable between patients and controls. The hepatic artery mean flow volume was higher among patients than controls but without statistical significant difference. The hepatic artery mean pulsatility and resistive indices were significantly higher among patients as compared to controls (Table 2, Picture 1). Furthermore, both parameters correlated significantly with the Child-Pugh score and the grading of oesophageal varices, so that the higher Child-Pugh grade or the grade of varices, the more significant increase in the hepatic arterial pulsatility and resistive indices (Table 3). The splenic artery mean diameter was significantly higher among patients. The mean flow volume and PI were significantly increased in the patients than the controls, also the RI was significantly higher among patients as compared to the control group (Table 2, Picture 2). Both the PI and RI didn t correlate with the Child grade while both parameters correlated significantly with the grade of varices, where the higher the grade of varices, the more the PI and RI (Table 3). Results All groups were age and sex-matched (73% of cases were males and 27% females, compared to 70% males and 30% females in the control group). Most cases and controls were in the 3 rd and 4 th decade of life and were comparable regarding their clinical and ultrasonographic findings. Endoscopically, all Child A patients (group I) had grade I varices without abdominal collaterals, while Child C patients (group III) had high grade varices (III and IV) with the presence of abdominal collaterals (3 cases 15%). Only one patient in group II (5%) had abdominal collaterals on ultrasonography. Although the portal vein diameter was not significantly altered in patients with cirrhosis, its cross sectional area significantly increased in the studied patients as compared to the controls. On the other hand the mean portal vein velocity was significantly reduced in cirrhotic patients without significant change in the mean portal vein flow volume, the latter was found comparable between patients and controls. The portal vein congestion index was significantly higher in studied patients as compared to the control group (Table 1). Picture (1): Hepatic artery velocity and resistive index in a normal subject. Picture (2): Splenic artery velocity and resistive index in a normal subject.

4 30 Duplex Color Doppler Us in Liver Cirrhosis Group I Group II Group III Group IV Group I Group II Group III Group IV Fig. (1): Liver Vascular index (LVI) of the studied groups ( p< 0.01): There is a highly significant decrease of LVI in cases when compared to the control group Fig. (2): Doppler perfusion index (DPI) of the studied groups (p<0.01): There is a highly significant increase in DPI in patients as compared to the control group. Table (1): Endoscopic findings and portal hemodynamics of the studied groups. Group I Group II Group III No % No % No % Group IV Varices: Grade I NS Grade II Grade III Grade IV Portal hemodynamics Mean STD Mean STD Mean STD Mean STD Diameter (mm) NS Cross sectional area (cm 2 ) S Velocity cm/sec HS Flow volume (ml/min) NS Congestion index HS p Table (2): Hepatic and splenic arteries hemodynamics in the studied groups. Variables Group I Group II Group III Group IV Mean SD Mean SD Mean SD Mean SD Hepatic artery: Diameter (mm) NS Cross sectional area (cm 2 ) NS Velocity (cm/sec) NS Flow volume (ml/min) NS Pulsatility index (PI) HS Resistive index (RI) HS Splenic artery: Diameter (mm) S Cross sectional area (cm 2 ) S Velocity (cm/sec) NS Flow volume (ml/min) HS Pulsatility index HS Resistive index HS p

5 Nabil El-Kady, et al. 31 Table (3): Correlation of each of the hepatic and splenic arteries pulsatility and resistive indices (PI and RI) with child-pugh classification and grading of oesophageal varices. Hepatic artery Child groups Hepatic artery PI Hepatic artery RI A & B A & C B & C p value p value p value Grade of varices Hepatic artery PI Hepatic artery RI No varices a Mean a Mean SD SD Grade I ab Mean ab Mean SD SD Grade II abc Mean abc Mean SD SD p value P value Grade III abcd abcd Mean Mean SD SD Grade IV abcd Mean abcd Mean SD SD Splenic artery Child groups Splenic artery PI Splenic artery RI A&B p value A&C p value B&C p value Grade of varices Hepatic artery PI Hepatic artery RI No varices a Mean a Mean 501 SD SD Grade I ab Mean ab Mean SD SD Grade II abc abc Mean Mean SD SD Grade III abcd abcd Mean Mean SD SD Grade IV abcd Mean abcd Mean SD SD Discussion Measuring disease progression represents a key challenge in the different stages of chronic liver disease (CLD). Indeed, a correct and reliable mea- surement of the stage of the disease has relevant implications for assessing the effectiveness of the current therapeutic regimens and predicting the occurrence of complication. This appears particularly relevant for advanced stages of CLDs characterized by the presence of portal hypertension and its complications. In this specific context, a current major challenge is to identify non-invasive or minimally invasive methodologies able to substitute or integrate the standard invasive methods, i.e. the measurement of the hepatic venous pressure gradient (HVPG). At the present state of technological development, ultrasonography (US) has a complementary role in the diagnosis of advanced fibrosis/cirrhosis. Studies aimed at assessing the usefulness of Doppler ultrasonography (DUS) for the prediction of portal hypertension in cirrhotic patients have provided conflicting results [20-25]. It is likely that these discrepant findings are at least in part owing to different cirrhotic populations in terms of aetiology, clinical score and chronologic relationship with portal hypertension-related complications. Moreover, information about current medications, concomitant diseases and mean arterial pressure were not always available in previous studies. Finally, it should be stressed that the DUS technique is equipment and operator dependent [27]. Therefore, to be reliable, measurements should be performed by an experienced operator carefully adhering to strict methodology. Most patients in our study were in the third and fourth decade of life while in the other trials most patients were in the fifth and sixth decade of life. It seems that Egyptians have an earlier onset of liver disease than other populations because schistosomal infection occurs early in the Egyptians, whereas alcoholic cirrhosis have developed at a later age among the western population [27]. Derangement of the splanchnic circulation is initiated by the increase of portal resistance in cirrhosis, leading to a reduction of flow velocity in the portal system, often accompanied by a dilation of portal vessels and development of collateral portosystemic pathways. Other hemodynamic consequences are observed in the splanchnic arterial system, in particular in the splenic and hepatic arteries [28]. Cirrhotic patients have an increased splenic artery blood flow which is explained by an increase in its diameter [29-31]. In this study, both the splenic artery mean diameter and flow volume were significantly increased in patients than controls. Also,

6 32 Duplex Color Doppler Us in Liver Cirrhosis the splenic artery resistive index is significantly and selectively increased in patients with cirrhosis [31-33]. Splenic impedance indices are generally higher in cirrhotic patients than in normal subjects, and among cirrhotics, they tended to be higher in patients with more severe oesophageal varices [29]. As the rule is with all Doppler parameters, variations exist between studies, sometimes studies are even conducted by the same authors. Piscaglia et al., reported that no significant difference could be found in splenic artery RI between patients and controls. Splenic artery pulsatility index significantly increased in a similar study population [34]. Moreover, the splenic artery PI correlates with portal pressure providing a good accuracy for the prediction of portal hypertension [35]. We reported a significant increase (p<0.01) in splenic artery resistive and pulsatility indices in cirrhotic patients as compared to the healthy controls. Also, there was significant correlation (p<) of these impedance parameters with the degree of oesophageal varices but no significant correlation (p>0.05) of SA-PI and SA-RI with Child-Pugh score. In our patients there was increase in splenic artery blood flow. This finding together with the associated increased splenic impedance may seem to be contradictory, while it is not. Indeed, in these patients, arterial vascular resistance is probably not the main determinant of splenic impedance indices. Why splenic impedance indices are sensitive to portal resistance, in contrast with other organs in which they mainly reflect arterial resistance, is not known. A possible explanation for the particular sensitivity of splenic impedance indices to venous hemodynamics could be the peculiar venous circulation of the spleen. The blood supply and the route of blood flow are unique in the spleen, which has a venous circulation different from that of any other organ, i.e., the presence of the red pulp, with two coexisting circulation systems, the red pulp sinuses, and the red cords. In portal hypertension, congestive splenomegaly is manifested histologically by red pulp congestion with accumulation and concentration of erythrocytes in widened pulp cords and sinuses. It is possible that the presence and the structure of the red pulp make the spleen impedance indices sensitive to venous haemodynamics and that velocity in arterial splenic vessels. This could be an interpretation of our results, because vascular impedance indices are sensitive to congestion of the organ too [36]. Our interpretation is further reinforced by the dramatic decrease of splenic indices after portosystemic shunt or liver transplantation, conditions in which the increased splenic inflow does not change much, although there is a clear decrease in resistance to splenic outflow. It is possible that, in organs in which a normal capillary net is present, impedance indices mainly reflect arterial resistance, where as the presence of a peculiar venous structure makes splenic impedance indices more sensitive to venous blood congestion [33]. The portal flow velocity is significantly decreased in cirrhosis (p<0.01). It is worth noting that the absolute values of portal flow velocity in both healthy subjects and cirrhotic patients vary considerably. Errors in Doppler measurements, observer variability and collateral pathways contribute to these variations. The combination of PVV with the increase in splenic artery resistive index provided an accuracy of 87.5% in diagnosing portal hypertension [32]. We reported a highly significant reduction of the portal vein mean velocity in patients as compared to controls. The least value was reported in Child C patients (10.3 cm/sec) and the highest was in Child A (11.0 cm/sec). Vyas and co-workers [37] reported similar results where portal vein velocity was significantly lower in patients with cirrhosis than in controls, and was significantly lower in patients in Child class B and C than those in class A. This confirms the finding that a mean portal vein velocity less than 16 cm/sec is 91% sensitive in the diagnosis of portal hypertension (mean velocity in the control group was 16.7 cm/sec) [38]. Our results showed that the mean portal vein flow volume was higher in patients than control, but without statistically significant difference reaching a highest value of 880 ml/min in Child B patients and 790 ml/min among controls. Liu and colleagues reported an increased flow volume in the portal vein in Child A+B group than normal (p<0.05) and the volume of PVF was less in Child C group than Child A+B (p<0.01) [39]. On the other hand in other study portal blood flow was significantly lower in patients with cirrhosis than in controls and significantly lower in patients in Child class B and C than those in class A [37]. This variation is in agreement with what was reported that in patients with diffuse liver disease, the (PVF) varies markedly in accordance with disease progression and from patient to patient depending upon the presence of extra-hepatic shunting and compensatory venous dilatation [40].

7 Nabil El-Kady, et al. 33 The congestion index of the portal vein was variable in most clinical, biochemical and endoscopic subgroups and that several factors can affect it: portal venous pressure, portal vascular resistance in the liver, portal blood flow, and the development of portosystemic collateral pathways [41]. Thus some studies found that there was no significant difference in CI between patients with and without cirrhosis [42,43], while our results and others found that congestion index was significantly higher in cirrhotic patients than in controls [44]. In cirrhotic patients Doppler sonography of the hepatic artery reveals enlarged, tortuous hepatic arteries with high velocity flow [45]. The diameter of the proper hepatic artery, was significantly larger (p<0.05) than seen in the control group [46]. In this study, the mean hepatic artery diameter was higher in cases than controls but without statistically significant difference. In our study, no significant difference was found (p>0.05) in hepatic artery blood flow in cirrhotic patients when compared to the controls. The same findings were described by others [42]. It is believed that hepatic arterial vasodilatation occurs in response to reduced portal venous flow and hepatic arterial flow reserve is high in patients with cirrhosis [47] without significant difference in hepatic artery blood flow in Child-Pugh classes A, B and C respectively when compared to the control group [48]. As regards the resistive index of hepatic artery, this study revealed significantly higher resistive index in cirrhotic patients as compared to control group (p<0.05) which was the same finding in other studies [33,50-52]. We also reported a significantly higher hepatic artery pulsatility index in cirrhotic patients as compared to the control group ( p<0.05). These results are in agreement with other studies that reported that the most specific Doppler criterion of liver cirrhosis with portal hypertension was increase in hepatic artery pulsatility index [34,52]. Since pulsatility index reflects vascular impedance, patients with cirrhosis have increased hepatic arterial vascular resistance. Pathological changes such as distortion of hepatic vascular bed by fibrosis, regeneration nodules, collagenization of Disse space and hepatocyte swelling may contribute to increased hepatic artery pulsatility index [53]. There is a significant correlation of the HA-RI and HA-PI with Child-Pugh classes A, B and C (p< 0.01). Thus, our results suggest that the pathophysiology of the increase in hepatic arterial resistance in cirrhosis is parallel to that of portal resistance. We further examined the relationship between hepatic arterial indices and the degree of oesophageal varices and found that there re was a highly significant correlation between HA-PI, HA-RI and the degree of oesophageal varices ( p<0.05), this was the same results obtained by other studies which found that HA-PI significantly correlated with either the size of oesophageal varices or the degree of hepatic dysfunction [54,55]. One of our goals was to examine the value of integrated assessment of PVV and HA-PI in the diagnosis of cirrhosis and portal hypertension as well as the hepatic arterial and total liver blood flow. For this purpose we used liver vascular index which was derived from the ratio of PVV to HA- PI and studied as well the Doppler perfusion index (DPI) which is the ratio of hepatic arterial to total liver blood flow. We demonstrated highly significant decrease (p<0.01) in LVI in cirrhotic patients than in controls and a highly significant increase in DPI in patients than controls. Iwao and co-workers who found that LVI was significantly lower in cirrhotic patients than in controls and it was a highly sensitive and specific Doppler US parameter in the diagnosis of cirrhosis and portal hypertension, and the best cut off value of LVI was 12 cm/sec with a sensitivity and specificity of 97 and 93% respectively in the diagnosis of cirrhosis and portal hypertension [54]. While Edward and co-workers found that DPI is elevated in patients with liver cirrhosis and hepatic metastasis [56]. Conclusion: It is finally concluded that Doppler and color Doppler ultrasonography are valuable, rapid, non invasive screening procedure for the assessment of the patient with cirrhosis and portal hypertension. The hepatic arterial resistance indices increase in cirrhosis and correlate with the severity of portal hypertension. While, the splenic artery resistance indices are increased in cirrhotic patients and do not correlate with the severity of portal hypertension although it correlates with the degree of oesophageal varices. Neither the portal venous blood flow nor the hepatic arterial blood flow are useful parameters for discriminating patients with cirrhosis from healthy subjects. It is recommended that Duplex color Doppler ultrasonography has its place and should be done in the assessment and management protocol of patients with cirrhosis and portal hypertension. Further studies including more patients with various chronic liver diseases are needed to observe the determinants of splenic artery resistance indices that allow a better definition of their pathophysiology and clinical significance. Further

8 34 Duplex Color Doppler Us in Liver Cirrhosis studies are needed to determine the prognostic value of the hepatic arterial resistance indices in liver cirrhosis and their role in other chronic liver diseases. References 1- BOSCH J., PIZCUETA M.P., FERNÁNDEZ M., et al.: Hepatic, splanchnic and systemic haemodynamic abnormalities in portal hypertension Baillieres Clin. Gastroenterol. Sep., 6 (3): , WIEST R. and GROSZMANN R.J.: The paradox of nitric oxide in cirrhosis and portal hypertension: too much, not enough. Hepatology, 35: , GUPTA T.K., TOURNER M., CHUNG M.K. and GROSZ- MANN R.J.: Endothelial dysfunction and decreased production of nitric oxide in the intrahepatic microcirculation of cirrhotic rats. Hepatology, 28: , PERELLO A., ESCORSELL A., BRU C., et al.: Wedged hepatic venous pressure adequately reflects portal pressure in hepatitis C virus-related cirrhosis. Hepatology, 30: , GROSZMANN R.J. and WONGCHARATRAWEE S.: The hepatic venous pressure gradient: anything worth doing should be done right. Hepatology, 39: 280-2, FRANCESCO VIZZUTTI, UMBERTO ARENA, LUIGI REGA, ROBERTO GIULIO ROMANELLI, et al.: Performance of Doppler Ultrasound in the Prediction of Severe Portal Hypertension in Hepatitis C Virus-Related Chronic Liver Disease. Liver Int. Dec., 27 (10): , TCHELEPI H., RALLS P.W., RADIN R. and GRANT E.: Sonography of diffuse liver disease. J. Ultrasound Med., 21: , MARTINEZ-NOGUERA A., MONTSERRAT E., TOR- RUBIA S. and VILLALBA J.: Doppler in hepatic cirrhosis and chronic hepatitis. Semin Ultrasound CT MR, 23: 19-36, ARDA K., OFELLI M., CALIKOGLU U., et al.: Hepatic vein Doppler waveform changes in early stage (Child- Pugh A) chronic parenchymal liver disease. J. Clin. Ultrasound, 25: 15-19, GORKA W., AL MULLA A., AL SEBAYEL M., et al.: Qualitative hepatic venous Doppler sonography versus portal flowmetry in predicting the severity of esophageal varices in hepatitis C cirrhosis. AJR Am. J. Roentgenol. 169: , IWAO T., TOYONAGA A., OHO K., et al.: Value of Doppler ultrasound parameters of portal vein and hepatic artery in the diagnosis of cirrhosis and portal hypertension. Am. J. Gastroenterol., 92: , ZHENG R.Q., WANG Q.H., LU M.D., et al.: Liver fibrosis in chronic viral hepatitis: an ultrasonographic study. World J. Gastroenterol., 9: , ZHONG-ZHEN S.U., HONG SHAN, WEI-MIN K.E., et al.: Portalsystemic hemodynamic changes in chronic severe hepatitis B: An ultrasonographic study. World J. Gastroenterol. February, 7; 14 (5): , BERNATIK T., STROBEL D., HAHN E.G. and BECKER D.: Doppler measurements: a surrogate marker of liver fibrosis? Eur. J. Gastroenterol. Hepatol., 14: , LIM A.K., PATEL N., ECKERSLEY R.J., et al.: Doppler sonography grade the severity of hepatitis C-related liver disease? AJR Am. J. Roentgenol., 184: , HORNG M.H.: An ultrasonic image evaluation system for assessing the severity of chronic liver disease. Comput Med. Imaging Graph, 31: , MACÍAS RODRÍGUEZ M.A., RENDÓN UNCETA P., NAVAS RELINQUE C., et al.: Ultrasonography in patients with chronic liver disease: its usefulness in the diagnosis of cirrhosis. Rev. Esp. Enferm Dig., 95: , , HIRATA M., AKBAR S.M., HORIIKE N. and ONJI M.: Noninvasive diagnosis of the degree of hepatic fibrosis using ultrasonography in patients with chronic liver disease due to hepatitis C virus. Eur. J. Clin. Invest., 31: , PISCAGLIA F., GAIANI S., CALDERONI D., et al.: Influence of liver fibrosis on hepatic artery Doppler resistance index in chronic hepatitis of viral origin. Scand J. Gastroenterol., 36: , CHOI Y.J., BAIK S.K., PARK D.H., et al.: Comparison of Doppler ultrasonography and the hepatic venous pressure gradient in assessing portal hypertension in liver cirrhosis. J. Gastroenterol. Hepatol., 18: 424-9, BAIK S.K., KIM J.W., KIM H.S., et al.: Recent variceal bleeding: DUS hepatic vein waveform in assessment of severity of portal hypertension and vasoactive drug response. Radiology, 240: , TAOUREL P., BLANC P., DAUZAT M., et al.: Doppler study of mesenteric, hepatic, and portal circulation in alcoholic cirrhosis: relationship between quantitative Doppler measurements and the severity of portal hypertension and hepatic failure. Hepatology, 28: 932-6, MERKEL C., SACERDOTI D., BOLOGNESI M., et al.: Doppler sonography and hepatic vein catheterization in portal hypertension: assessment of agreement in evaluating severity and response to treatment. J. Hepatol., 1998; 28: SCHEPKE M., RAAB P., HOPPE A., et al.: Comparison of portal vein velocity and the hepatic venous pressure gradient in assessing the acute portal hemodynamic response to propranolol in patients with cirrhosis. Am. J. Gastroenterol., 95: , BERZIGOTTI A., CASADEI A., MAGALOTTI D., et al.: Renovascular impedance correlates with portal pressure in patients with liver cirrhosis. Radiology, 240: 581-6, ZAKARIA M.S., THAKEB F., LABIB S., et al.: Incidence of oesophageal varices as a cause of upper gastrointestinal bleeding among patients subjected to upper gastrointestinal endoscopy: In Takeb, F. and Zakaria, S. (3eds). Gastrointestinal endoscopy: An Egyptian View, MARTINS R.D., SZEJNFELD J., LIMA F.G., et al.: Endoscopic, ultrasonographic, and US-Doppler parameters as indicators of variceal bleeding in patients with schistosomiasis. Dig. Dis. Sci., 45 (5): , BOLOGNESI M., SACERDOTI D., MERKEL C., et al.: Splenic Doppler impedance indices:influence of different

9 Nabil El-Kady, et al. 35 portal hemodynamic conditions. Hepatology, , WILLIAM J., ZWIEBEL M.D., RICHARD A., et al.: Splanchnic blood flow in patients with cirrhosis and portal hypertension: investigation with duplex Doppler US. Radiology March, , DINC H., SARI A., RESIT GUMELE H., et al.: Portal and splanchnic haemodynamics in patients with advanced post hepatic cirrhosis and healthy adults. Assessment with duplex Doppler US. Radiology, 39 (2): , PISCAGLIA F., DANATI G., CECILIANI L., et al.: Influence of the spleen on portal haemodynamics: a non invasive study with Doppler ultrasound in chronic liver disease and haematological disorders". Scand. J. Gastroenterol., 37 (10): , SORESI M., BASCONE F., MAGLIARISI C., et al.: Haemodynamic changes in splanchnic circulation after orthotopic liver transplantation in patients with liver cirrhosis". Abdom. Imaging, 27 (5): 451-5, BORISOV A.E., KASHCHENKO V.A., VASIUKOVA E.L., et al.: Evaluation of the effectiveness of Doppler sonography in patients with diffuse liver disease with portal hypertension syndrome". Vestn Khir Im II Grek, 161 (2): 26-31, BOLOGNESI M., SCERDOTI D., MERKEL C., et al.: Non invasive grading of the severity of portal hypertension in cirrhotic patients by echo-color-doppler". Ultrasound Med. Biol., 27 (7): 901-7, BARBARA L., OKUDA K., TAYLOR K.J.W., et al.: The value of Doppler US in the study of hepatic haemodynamics (Consensus conference). J. Hepatol., 10: , VYAS K., GALA B., SAWANT P., et al.: Assessment of portal hemodynamics by ultrasound color Doppler and laser Doppler velocimetry in liver cirrhosis. Gastroenterol., 21 (5): , BOLONDI L., GAIANI S.L., PISCAGLIA F., et al.: Doppler ultrasound in portal hypertension". Ultrasound in Medicine and Biology, 20 (1): 131 (abstr.), LUI Y., LI L., YU Z., et al.: Correlative study between portal vein pressure and portal vein haemodynamics in patients with portal hypertension. Zhong Gan. Zang Bing Za. Zhi., 10 (2): 135-7, (Eng. Abst.), KASHITANI N., KIMOTO S., TSUNODA M., et al.: Portal blood flow in the presence or absence of diffuse liver disease: Measurement by phase contrast MR Imaging. Abd. Imaging, 20 (3): 197, SIRINGO S., BOLONDI L., GAIANI S., et al.: The relationship of endoscopy, portal Doppler ultrasound flowmetry and clinical and biochemical tests in cirrhosis. J. Hepatol., 20 (1): 11, ANNET L., MATERNE R., DANSE E., et al.: Hepatic flow parameters measured with MR imaging and Doppler US: correlations with degree of cirrhosis and portal hypertension. Department of Radiology and the Laboratory of Gastroenterology, St. Luc University Hospital, Radiology Sep., 11, PISCAGLIA F., DANATI G., SERRA C., et al.: Value of splanchnic Doppler ultrasound in the diagnosis of portal hypertension. Ultrasound Med. Biol., 27 (7): 893-9, SACERDOTI D., MERKEL C., BOLOGNESI M., et al.: Hepatic arterial resistance in cirrhosis with and without portal vein thrombosis: relationships with portal hemodynamics. Gasteroenterol., 108 (4): 1152, ZIMMERMAN P., FAROOKI S., DAVID S.K., et al.: Doppler sonography of the hepatic vasculature.freedom of Information Act. Disclaimer, 3 (6): 53-19, TONI R., BOLONDI L., GAIANI S., et al.: Accessory ultrasonographic findings in chronic liver disease diameter of splenic and hepatic arteries, fasting gallbladder volume and course of left portal vein. J. Clin. Ultrasound, 13 (9): 611-8, ZIPPRICH A., STEUDEL N., BEHRAMANN C., et al.: Functional significance of hepatic arterial flow reserve in patients with cirrhosis. Hepatology, 37 (2): , KLEBER G., STEUDEL N., BEHRMANN C., et al.: Hepatic arterial flow volume and reserve in patients with cirrhosis: use of intra-arterial Doppler and adenosine infusion. Gastroenterology, 117 (5): , BORSE N., SAWANT P., GALA B., et al.: Assessment of renal and hepatic haemodynamics in cirrhosis of liver. Indian J. Gastroenterol., 21 (6): 213-5, KOK T., JAGT E.J., HAGGSMA E.B., et al.: The value of Doppler ultrasound in cirrhosis and portal hypertension. Scand J. Gastroenterol., Suppl; 230: 82-8, PISCAGLIA F., ZIRONI G., MAZZIOTTI A., et al.: Systemic and splanchnic hemodynamic changes after liver transplantation for cirrhosis: a long term prospective study. Hepatology, 30: 58-64, SCHNEIDER A.W., KALK J.F. and LLEIN C.P.: Effect of lostartan, an angiotensin II receptor antagonist, and portal pressure in cirrhosis. Hepatology, 29 (2): , IWAO T., OHO K., SAKAI, et al.: Noninvasive hemodynamic measurements of superior mesenteric artery in the prediction of portal pressure response to propranolol. J. Hepatol., 28 (5): , IWAO T., TOYONAGA A., OHO K., et al.: Value of Doppler ultrasound parameters of portal vein and hepatic artery in the diagnosis of cirrhosis and portal hypertension. Gastroenterology, 92: , SACERDOTI D., MERKEL C., BOLOGNESI M., et al.: Hepatic arterial resistance in cirrhosis with and without portal vein thrombosis: relationships with portal hemodynamics. Gasteroenterol., 108 (4): 1152, EDWARD L., WILSON J., JAGERSON D., et al.: Detection of colo-rectal liver metastasis: comparison of laparotomy, CT, US and Doppler perfusion index. Radiol., 195: , 1994.