Value of Doppler Sonography in Assessing the Progression of Chronic Viral Hepatitis and in the Diagnosis and Grading of Cirrhosis

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1 Article Value of Doppler Sonography in Assessing the Progression of Chronic Viral Hepatitis and in the Diagnosis and Grading of Cirrhosis Alpay Haktanir, MD, Birsen Songül Cihan, MD, Çetin Çelenk, MD, Şener Cihan, MD Objective. The purpose of this study was to evaluate the value of Doppler sonography in assessing the progression of chronic viral hepatitis and in the diagnosis and grading of cirrhosis. Methods. Abdominal sonographic and liver Doppler studies were performed in 3 groups: 36 patients with chronic viral hepatitis, 63 patients with cirrhosis, and 30 control subjects with no evidence of liver disease. A series of Doppler indices of hepatic vascularity, including portal vein velocity, portal vein pulsatility score, flow volume of the portal vein, resistive and pulsatility indices of the hepatic artery, modified hepatic index, hepatic vascular index, waveform of the hepatic vein, and focal acceleration of flow, were measured and correlated with liver and spleen size, portal and splenic vein diameter, and presence of ascites and collateral vessels. These indices were compared across the 3 study groups and within the patient groups with respect to presence of inflammation, fibrosis, and steatosis, as determined by histologic evaluation. Results. The most useful indices were portal vein velocity, the modified hepatic index, and nontriphasic flow in the hepatic vein, which were helpful in distinguishing patients from control subjects. Hepatic vascular and modified hepatic indices were useful for differential diagnosis of cirrhosis and chronic viral hepatitis. However, all measurements were limited in their ability to determine the severity of chronic hepatitis. Conclusions. Doppler sonography is sensitive to hemodynamic alterations resulting from inflammation and fibrosis, and if sonography is the study of choice to follow the progression of hepatitis, it will not be adequate without Doppler imaging. Doppler sonography has high diagnostic accuracy in cirrhosis despite some false-positive conditions. However, it has a limited role in clinical grading. Key words: chronic hepatitis; cirrhosis; hepatic arterial index; hepatic vein; portal vein. Abbreviations CVH, chronic viral hepatitis; HAI, histologic activity index; HAPI, hepatic artery pulsatility index; HARI, hepatic artery resistive index; HVI, hepatic vascular index; MHI, modified hepatic index; PVP, portal vein pulsatility; PVV, portal vein velocity Received July 12, 2004, from the Department of Radiology, Ondokuz Mayis University Medical Faculty, Samsun, Turkey. Revision requested August 20, Revised manuscript accepted for publication October 27, Address correspondence and reprint requests to Alpay Haktanir, MD, Afyon Kocatepe Üniversitesi Tip Fakültesi, Kirmizi Hastane, Afyon, Turkey. dralpay@yahoo.com Chronic viral hepatitis (CVH) is a widespread disease in the world that causes serious disorders such as cirrhosis and hepatocellular cancer. Despite its limited value, sonography is still the most established method for diagnosis and follow-up of CVH primarily because of its availability. Although a coarse echo pattern of liver and periportal fibrosis may be detected, sonographic findings are normal in many cases. 1 Cirrhosis has to be closely investigated because of its important complications, including ascites, peritonitis, portal hypertension, and variceal bleeding. Sonography is helpful in the diagnosis and follow-up of patients who have classic findings of cirrhosis and portal hypertension such as ascites, varices, or increasing portal vein diameter by the American Institute of Ultrasound in Medicine J Ultrasound Med 2005; 24: /04/$3.50

2 Doppler Sonography in Chronic Viral Hepatitis and Cirrhosis However, B-mode sonography is incapable of examining cases with normal liver echogenicity and without any portal hypertension findings. The various histologic components of chronic liver inflammation and repair could theoretically affect hepatic circulation, by way of either dilatation or constriction, through effects of inflammatory cytokines and anatomic impairment. Hepatic fibrosis is a known cause of several regional hepatic hemodynamic changes, including the resistive index, hepatic blood flow, and the velocity of blood in the portal and hepatic arteries. 2 6 In cirrhosis, portal blood inflow, hepatic resistance, and portal venous pressure increase. Despite the initial increase, portal blood inflow decreases with increasing sinusoidal resistance and development of portosystemic collateral vessels. These hemodynamic changes influence the degree of portal hypertension and liver dysfunction. 7 Doppler sonography is a noninvasive diagnostic modality based on hemodynamic parameters. Hemodynamic changes might have developed even in cases with normal findings on B-mode sonography. 8 Therefore, assessment of these alterations has importance for early diagnosis and for close follow-up of previously diagnosed cases. Alterations of liver hemodynamics in CVH and cirrhosis have been observed in various studies. Some authors evaluated these changes for CVH, some evaluated them for cirrhosis, and some did for both. Limitations of different values from many simple Doppler parameters of liver vasculature made observers use some new indices for more reliable evaluations, such as the modified hepatic index (MHI), congestion index, arterioportal ratio, 9 and portal hypertension index. 6,10 However, the reliability of these composite indices is not proved yet. In this study, we observed the role of Doppler sonography in cirrhosis and CVH. We aimed to determine the importance of Doppler sonography for detection of early changes in liver hemodynamics and the role of Doppler parameters for diagnosis and follow-up of CVH and cirrhosis. Materials and Methods The study prospectively included 99 patients and 30 control subjects. Color Doppler sonography was established for the evaluation of 36 patients with CVH (16 men and 20 women; age range, years; mean, 41 years), 63 patients with biopsy-proved cirrhosis (39 men and 24 women; age range, years; mean, 50 years), and 30 healthy control subjects (13 men and 17 women; age range, years; mean, 38 years). Written informed consent was obtained from each individual before the examinations. Diagnosis of CVH was made by histologic and serologic findings: 14 patients had B, 19 had C, 2 had B and C, and 1 had C and D hepatitis. Of 63 patients with cirrhosis, 40 had viral, 13 had alcoholic, and 10 had other (1 Wilson disease, 2 storage disease, and 7 idiopathic) origins. The modified Child-Pugh score, which ranks disease severity on the basis of signs and the findings of liver function tests, has been shown to predict survival. 11 On the basis of the total point score, patients are categorized into 1 of 3 stages: Child class A, 5 to 6 points; Child class B, 7 to 9 points; and Child class C, 10 to 15 points (Table 1). Patients with cardiac disease that may affect the hepatic vein waveform or receiving treatment with any drug known to alter portal and hepatic arterial hemodynamics were not included in the study. Liver functions of all control subjects were within normal limits. None of them had used any drug capable of altering the liver function tests for the previous 3 months. The possibility of chronic liver (infectious, metabolic, or autoimmune) or heart diseases was ruled out by appropriate tests. Sonographic Examination All measurements were done by a single radiologist without information about patient characteristics using color Doppler sonography with subjects in the supine or left lateral position. A PowerVision SSA-380A system (Toshiba Medical Systems Co, Ltd, Tokyo, Japan) with multihertz (3- to 5-MHz) convex and sector pulsed probes was used. Sonographic examinations were carried out 8 hours after the last meal. Liver and spleen sizes, portal and splenic vein diameters, degree of liver steatosis, portal vein velocity (PVV), portal vein pulsatility (PVP) score, flow volume of the portal vein, hepatic artery resistive index (HARI), hepatic artery pulsatility index (HAPI), MHI, hepatic vascular index (HVI), waveform of the hepatic vein, and focal acceleration of flow were evaluated in all subjects. Explanations of Doppler indices used in the study are presented in Table J Ultrasound Med 2005; 24:

3 Haktanir et al Table 1. Modified Child-Pugh Score Points Assigned to Laboratory Values and Signs* Parameter Laboratory value Total serum bilirubin level, mg/dl (µmol/l) <2 (34) 2 3 (34 51) >3 Serum albumin level, g/dl (g/l) >3.5 (35) (28 35) <2.8 International normalized ratio (prothrombin time) < >2.20 Signs Ascites None Controlled medically Poorly controlled Encephalopathy None Controlled medically Poorly controlled *On the basis of total points, a patient with cirrhosis is assigned to 1 of 3 classes: Child class A, 5 to 6 points; Child class B, 7 to 9 points; or Child class C, 10 to 15 points. Liver and Spleen Sizes Liver size was determined by measuring the longitudinal length from the dome of the right lobe to the inferior end on the midclavicular line. Splenic size was found by measurement of its longest diameter. Portal and Splenic Vein Diameters Measurement of portal vein diameter was performed from the hilar segment, which has least interobserver variability. 12 Splenic vein diameter was measured at the splenic hilum. Degree of Steatosis A diffuse increase in echogenicity was considered sonographic liver steatosis. 1,5 Staging was performed as follows: (1) mild, a mild increase in echogenicity in which intrahepatic vessel walls and the diaphragm could be seen easily; (2) moderate, a moderate increase in echogenicity in which intrahepatic vessel walls and the diaphragm could hardly be seen; and (3) advanced, a substantial increase in echogenicity in which sound could not penetrate to the right liver lobe and the diaphragm and hepatic vessels also could not be seen. Flow Parameters of Liver Vasculature Portal Vein. Flow velocity was measured from the hilar segment with subjects in the supine position and during inspiration. All subjects were examined by the intercostal route because the hilar portal vein could not be shown by a subcostal approach in many instances, such as shrunken livers. Flow measurements consisted of peak, lowest, and mean venous velocity. The PVV was used for the evaluation of flow diminution. To evaluate the arterialization that may have been due to arterial portal shunting at the sinusoidal level, the PVP score was established. The mean venous velocity was used for flow volume calculations. Measurement of a cross-sectional area of the vessel lumen was done by showing it in a transverse plane. Flow direction was recorded from both the main portal vein and right and left branches of it. Flow direction of the splenic vein was established to evaluate the flow direction in the portal system. Hepatic Artery. The hepatic artery was evaluated via an intercostal approach by demonstration of right and left portal veins under a 60 angle. In some subjects, hepatic artery traces were seen at least 2 cm away from right or left portal vein bifurcations; therefore, measurements were done from there. In others whose distal hepatic artery traces could not be visualized, measurements were carried out by slight angulations of the ultrasound probe. At least 2 measurements from both branches were made, and averages were found in every subject. No measurement was done from the main hepatic artery. Resistive and pulsatility index values were calculated from obtained traces. With the use of PVV and the HAPI, the HVI was calculated (Table 2). In addi- Table 2. Indices, Their Explanations, and Units Used in the Study Index Explanation Unit PVV Peak venous velocity in portal vein cm/s PVP score Lowest portal venous velocity/peak * venous velocity Portal vein flow Mean venous velocity cross-sectional cm 3 /s volume area of portal vein HARI (peak systolic velocity end diastolic * velocity)/peak systolic velocity HAPI (peak systolic velocity end diastolic * velocity)/time-averaged peak velocity MHI PVV/HARI * HVI PVV/HAPI * * Rates without units. Time-averaged peak velocity is the velocity time integral of the spectral waveform trace. J Ultrasound Med 2005; 24:

4 Doppler Sonography in Chronic Viral Hepatitis and Cirrhosis tion, we used an MHI that was obtained from PVV divided by the HARI (Table 2). To our knowledge, it has rarely been used in previous studies. 10,13,14 Hepatic Vein. Waveforms were evaluated by the demonstration of the right and middle hepatic veins at a point 3-6 cm away from the inferior vena cava, under a degree of 60 both with intercostal and subcostal approaches. Measurements were done during mild inspiration and normal breathing in supine or 30 left lateral positions. When triphasic flow was recorded from 1 of these veins, it was taken into account as triphasic flow. Because of the motion artifacts of the heart and diaphragm, we did not recruit the left hepatic vein. Triphasic, biphasic, monophasic, and mixed (biphasic and monophasic) flow types were recognized by Doppler evaluation. Two groups were formed for statistical analysis: triphasic flow and nontriphasic flow, which is composed of 3 other flows. When the flow velocity increases by more than 100% along with the hepatic vein by going away from the inferior vena cava, it is considered focal acceleration of flow. Collaterals and Ascites Gray scale sonography was performed initially to determine collateral vascular structures. Thereafter, flow and flow direction of these vessels were recorded. Ascites was considered minimal if it was limited to the pelvic cul de sac or hepatorenal recess. When diffused to the intraperitoneal cavity, it was described as abundant. Histologic Evaluation Biopsies of all patients were carried out in the 4 weeks before or after sonographic examinations. Biopsy specimens were analyzed retrospectively by a single experienced pathologist uninformed about the radiologic examination results. Specimens were evaluated according to the suggestions of Desmet et al 15 with the use of the histologic activity index (HAI) scoring of Knodell et al. 16 In this respect, all specimens were evaluated for both inflammation degree and fibrosis stage. Inflammation degree, periportal necrosis, interlobular degeneration, and focal necrosis were all summed to yield total scores of portal inflammation, and the scores were divided into 3 subgroups: (1) 0 to 5, minimal inflammation; (2) 5 to 10, mild inflammation; and (3) 10 and greater, severe inflammation. Fibrosis was estimated as stage 0 to 3 according to the HAI scoring. Because the fourth stage of fibrosis means cirrhosis, it was included in the cirrhosis group. Intrahepatic fat accumulation was subjectively evaluated. Statistical Analysis Pearson correlation analysis, analysis of variance, Tukey honestly significant difference, Kruskal- Wallis variance analysis, Mann-Whitney U, χ 2, and Fisher exact tests were used for statistical analysis. Results were recorded as mean ± SD. When a significant difference was observed by Kruskal-Wallis variance analysis, the Mann- Whitney U test was performed to determine which particular group was responsible for the difference. Therefore, the P significance level was lowered to adjust for such multiple comparisons. Statistically analyzed variables have been classified as follows: Significant differences were sought between control, CVH, and cirrhosis groups for HARI, HAPI, PVV, MHI, HVI, PVP score, portal vein flow volume, portal and splenic vein diameters, and spleen and liver sizes. This attempt was performed by independent pairwise comparisons. In the CVH group, relationships of inflammation degree and fibrosis stage with afferent (inflow at porta) and efferent (outflow at the hepatic veins) vascular components were separately evaluated. Relationships of increased echogenicity with the hepatic vein waveform were also observed. In the cirrhosis group, statistical analysis was performed for Doppler parameters of subgroups formed according to Child-Pugh scoring (Table 1) and existence of ascites and collaterals. Results Results of Control, CVH, and Cirrhosis Groups The HARI, HAPI, MHI, and HVI values of all groups are presented in Table 3. In the cirrhosis group, mean HARI and HAPI values were significantly larger than those in the CVH and control groups, and those in the CVH group were also greater than those in the control group. The MHI and HVI in the CVH group were significantly smaller than those in the control group, and those in the cirrhosis group were also smaller than those in the CVH and control groups (P <.05/3 =.017). Statistically different values for the cirrhosis group compared with the other 2 groups are presented in Table 4. Portal and splenic vein diame- 314 J Ultrasound Med 2005; 24:

5 Haktanir et al ters and spleen sizes of patients with cirrhosis were significantly greater than those of the CVH and control groups. Mean PVV of the cirrhosis group was smaller than those in the control and CVH groups (P <.001). No statistical difference was found for these values between CVH and control groups (P >.05/3 =.017). There was no statistical difference for the size, portal vein flow volume, and PVP score between all 3 groups (P >.05). Results of CVH Group Afferent Vasculature Values of afferent vasculature according to inflammation degree are presented in Table 5. The HARI and HAPI in group 2 were significantly greater than those in group 1, and the HARI in group 3 was also greater than that in group 1. The MHI in group 1 was greater than that in group 3 (P <.05/3 =.017). No significant difference was found between all 3 groups with respect to PVV and HVI. Relationships between fibrosis stage and afferent vasculature Doppler parameters were observed. No patients in the CVH group had stage 2 fibrosis. Statistical analysis could not be performed in subgroup stage 0 because of the insufficient case number (n = 3). The mean MHI of 21 cases in stage 1 fibrosis was 31.8 ± 4.4 cm/s, and it was 28 ± 7.5 cm/s in 12 cases of stage 3 fibrosis. Mean PVV in stage 1 was 23 ± 3 cm/s, and it was 20.5 ± 5.7 cm/s in stage 3. There was a significant difference between stage 1 and 3 fibrosis for MHI and PVV (P <.05). Other Doppler Table 3. Values of HARI, HAPI, MHI, and HVI for All Groups Values by Group HARI HAPI MHI, cm/s HVI, cm/s Control (n = 30) Minimum Maximum Mean ± SD* 0.63 ± ± ± ± 5.5 CVH (n = 36) Minimum Maximum Mean ± SD* 0.73 ± ± ± ± 0.01 Cirrhosis (n = 63) Minimum Maximum Mean ± SD* 0.77 ± ± ± ± 4.1 Results were compared for each group with both other groups independently. *P <.05/3 =.017. parameters of afferent vasculature were not found to be related to fibrosis stages. Efferent Vasculature The relationships of hepatic vein waveforms with inflammation, fibrosis, and sonographic steatosis (increased echogenicity) are presented in Table 6. With respect to nontriphasic flow, no significant difference was found between subgroups that formed according to the degree of inflammation. Nontriphasic flow frequency in stage 3 fibrosis was statistically larger than in stage 1 fibrosis (P <.01, Fisher exact test). No subjects had grade 3 sonographic steatosis. The number of cases was insufficient for statistical analysis when grade 1 and 2 subgroups were considered separately. Therefore, we united all increased echogenicity subgroups. In this Table 4. Significantly Different Values for the Cirrhosis Group Compared With the Other 2 Groups Portal Vein Splenic Vein Values by Group PVV, cm/s Diameter, mm Diameter, mm Spleen Size, mm Control (n = 30) Minimum Maximum Mean ± SD* 25 ± ± ± ± 12 CVH (n = 36) Minimum Maximum Mean ± SD* 22 ± ± ± ± 12 Cirrhosis (n = 63) Minimum Maximum Mean ± SD* 16 ± 4 12 ± 2 12 ± ± 33 Results were compared for the cirrhosis group with each other group separately. *P <.001. J Ultrasound Med 2005; 24:

6 Doppler Sonography in Chronic Viral Hepatitis and Cirrhosis Table 5. Values of Afferent Vasculature According to the Degree of Inflammation HAI Group 1 (Inflammatory 2 (Inflammatory 3 (Inflammatory Degree: 0 5) Degree: 5 10) Degree: >10) Index (n = 6) (n = 17) (n = 13) HARI Minimum Maximum Mean ± SD 0.67 ± 0.02* 0.74 ± 0.06* 0.73 ± 0.05* HAPI Minimum Maximum Mean ± SD 1.11 ± 0.08* 1.5 ± 0.5* 1.36 ± 0.2 MHI, cm/s Minimum Maximum Mean ± SD 34 ± 2.5* 31 ± 4 28 ± 7.3* HVI, cm/s Minimum Maximum Mean ± SD 20 ± ± 4 16 ± 5 PVV, cm/s Minimum Maximum Mean ± SD 23 ± 2 23 ± 3 21 ± 5.5 HAI degree: less than 5, minimal inflammation; 5 to 10, moderate inflammation; and greater than 10, severe inflammation. *P <.05/3 =.017. respect, the frequency of nontriphasic flow in fatty livers was significantly greater than that of others (P <.01, Fisher exact test). Results of Cirrhosis Group Of 63 patients with cirrhosis, 17 had Child A, 24 had Child B, and 22 had Child C cirrhosis. Abundant ascites was detected in 32 patients. There was minimal ascites in 8 patients, whereas there was none in the remaining 23. Portal venous flow was hepatofugal in 7 cases. It was hepatofugal during inspiration and hepatopetal during expiration in 3 patients. Collateral neovascularization was seen in 1 or more sites in 33 patients, and there were no collaterals in 13. In the other 17, observation of collaterals could not be done because of excessive ascites. The hepatic vein waveform was triphasic in 8 patients and nontriphasic in 55. Focal acceleration of velocity was recorded in 10 patients. For Doppler findings according to Child classification and presence of collaterals or ascites, there was no statistical relationship between Doppler parameters, spleen size, and splenic or portal vein diameter and Child classification. However, liver sizes in Child C cirrhosis were smaller than in A and B cirrhosis (P <.001). No statistical difference was found between patients with and without collaterals for Doppler and gray scale sonographic parameters except from hepatic vein waveforms (Table 7). The frequency of nontriphasic flow was greater in patients with collaterals than others (P <.05, Fisher exact test). No difference was found for the flow direction in the portal vein. In 17 of 63 patients with cirrhosis, exact knowledge of collaterals could not be gained because of ascites. Therefore, these patients were not included in statistical analysis. There were no significant differences between patients with abundant, minimal, and no ascites for the measured parameters except liver size and hepatic vein waveform. Liver sizes in the abundant ascites group were smaller than others (P <.05/3 =.017). The relationship of hepatic venous waveforms with ascites is presented in Table 7. Nontriphasic flow was more frequent in the group with abundant ascites than in that with no ascites (χ 2 = 0.39; P <.05). Because 1 patient with cirrhosis had portal vein thrombosis, it was not possible to get PVV, HVI, and MHI values. The HARI was 0.95 in that patient. Figure 1 shows normal and pathologic waveforms of portal and hepatic veins in some of our subjects. Table 6. Relationship of Hepatic Venous Waveforms With Inflammation, Fibrosis, and Steatosis in the CVH Group Inflammation Fibrosis Steatosis Hepatic Vein Waveform None Present Triphasic Nontriphasic * 0 8* 5* 6* Total No subjects had grade 2 fibrosis or sonographic grade 3 steatosis. Because of the insufficient number of cases for statistical analysis, grade 1 and 2 steatosis groups are considered as 1 group having steatosis. *P < J Ultrasound Med 2005; 24:

7 Haktanir et al Discussion Certain hemodynamic disruptions in liver vessels go along with chronic hepatic diseases. These alterations are generally the result rather than the cause of hepatic dysfunction and structural changes. Resistance and pulsatility indices, hepatic blood flow, waveforms in hepatic veins, and blood velocity of the portal vein and hepatic arteries are parameters susceptible to pathologic and morphologic changes. 2 6,17 These parameters can reliably be evaluated by Doppler sonography. Many reports confirmed the clinical usefulness of this technique in the diagnosis of portal hypertension and liver cirrhosis. 4,5,18 22 Cirrhosis is characterized by the presence of extensive fibrosis and numerous regenerative nodules replacing the normal liver parenchyma. Elevated vascular resistance and increased portal blood inflow are 2 principal mechanisms that have been reported to be involved in the development of portal hypertension secondary to cirrhosis. 23 Our findings support the results of Koda et al 5 that a decrease in PVV is more sensitive than portal vein flow volume for the advancement of fibrosis stage. Contrary to this, Piscaglia et al 6 found no significant correlation between portal flow velocity and liver fibrosis in their study of 47 patients with CVH. The hepatic vein waveform is triphasic in all healthy subjects. 24 Morphologic alterations in the liver parenchyma may impair the compliance of the walls of the hepatic veins. 25 Damped waveforms have been attributed to the stiffness of the liver parenchyma in patients with various liver diseases. 17,26 There are limited reports concerning the relationship between histologic changes in chronic hepatitis and nontriphasic flow. 17,27,28 Our result about an increase in the frequency of nontriphasic flow with more severe fibrosis is not in contradiction with a report by Dietrich et al, 28 who found a weak relationship between nontriphasic flow and the fourth stage of fibrosis. 28 Colli et al 17 also suggested that abnormal waveforms of the hepatic vein correlate with fibrosis and steatosis in the surrounding parenchyma. We found no association between waveforms of hepatic veins and the degree of inflammation. This result supports the above-mentioned findings. 17,28 Another entity concerning the alteration of the hepatic vein waveform is steatosis. We observed Table 7. Relationship of Hepatic Venous Waveforms With Collateral and Ascites Formation in the Cirrhosis Group Collaterals Ascites Hepatic Vein Waveform Present None None Minimal Abundant Triphasic Nontriphasic 30* 8* Total *P <.05 (Fisher exact test). P <.05 (χ 2 = 0.39). a significant difference of nontriphasic flow between healthy subjects and patients having increased echogenicity. This result is also concordant with previous observations. 17,28 In our study, the increase of the HARI and HAPI was significantly greater in patients with moderate or severe inflammation than in those with mild inflammation and in control subjects. To our knowledge, there are few studies concerning HARI and HAPI values in CVH. Piscaglia et al 6 concluded that the HARI of patients with CVH seems to be significantly influenced by the degree of fibrous tissue deposits. It is important to disclose the increase of the HARI and HAPI in mildly inflamed cases of CVH and in hepatitis B and C virus carriers because this increase can be used as an indicator for progression and also for biopsy decision. Once the inflammatory degree exceeds the mild phase, the increase of hepatic artery resistance varies independent of inflammation. This means that hepatic arterial resistance indices in moderate inflammation can be higher than those in severe inflammation. To the best of our knowledge, there is no report in the literature about the association of the MHI with increasing fibrosis. A decreasing MHI for the progression of inflammation and fibrosis (inflammatory HAI of >10 and third stage of fibrosis) and decreasing PVV for the progression of fibrosis can be used to indicate an additional biopsy. Nontriphasic flow in the hepatic vein can be established as an indicator for fibrosis stage in cases without sonographic steatosis. In this respect, if B-mode sonography is performed for follow-up alone, no findings may be seen in patients with CVH or hepatitis B and C virus carriers until cirrhosis and portal hypertension take place. Because Doppler sonography can show early hemodynamic changes, it must be established for the follow-up of CVH. Nontriphasic flow in the hepatic vein is a considerable determinant for liver disease, especially for cirrhosis. J Ultrasound Med 2005; 24:

8 Doppler Sonography in Chronic Viral Hepatitis and Cirrhosis Figure 1. Examples of normal and pathologic waveforms in portal and hepatic veins. Top left, Normal hepatopetal flow showing a slight undulation in the hilar portal vein obtained during mild inspiration. Top right, Monophasic flow or loss of undulation in a patient with early stage cirrhosis. Middle left, Biphasic arterialized flow detected in a patient with cirrhosis. Middle right, Normal triphasic flow in the hepatic vein during normal breathing. Bottom left, Abnormal biphasic flow. Bottom right, Abnormal monophasic flow in the hepatic vein. 318 J Ultrasound Med 2005; 24:

9 Haktanir et al Portal/splenic vein diameters, spleen size, and Doppler parameters were not significantly different between Child subgroups. This result is in agreement with the literature. 29,30 However, liver sizes in the Child C subgroup were significantly lower than in the A and B subgroups. Although various classifications for hepatic waveforms in liver diseases have been improved by some observers, 31 we preferred using nontriphasic flow to avoid confusion. Nontriphasic flow was significantly more frequent in patients with collaterals than others in our study. Gorka et al 32 observed the relationship of esophageal varices grades and waveform characteristics of the hepatic vein, and they found monophasic flow in 92% of cases with advanced varices. We did not detect any relationship between portal and splenic vein diameters, liver and spleen sizes, or Doppler parameters of afferent vasculature and collaterals. This result is parallel with those of previous studies. 14,29,30,32,33 No relationship was found between cases with and without ascites for Doppler parameters of afferent vasculature, portal and splenic vein diameters, or spleen size. This result is in agreement with the observation of Haag et al. 29 A significant difference of nontriphasic flow in the hepatic vein between these groups was found in our study. However, we evaluated subjects with ascites without considering the existence of collaterals. It is necessary to show the association of nontriphasic flow with refractoriness of ascites independent of collateral formation. Liver sizes were significantly lower in subjects with abundant ascites. Piscaglia et al 22 reported significant differences of the HARI in patients with CVH and cirrhosis and healthy subjects. Our results also showed significant differences of the HARI, HAPI, HVI, and MHI between control, CVH, and cirrhosis groups (Table 3). To our knowledge, no previous observation has been made in the literature about the differences of HVI and MHI values between patients with CVH and cirrhosis. Studies suggesting the significant difference of PVV between CVH and cirrhosis are limited. 21 We found significant differences of PVV, portal and splenic vein diameters, and spleen size between the CVH and cirrhosis groups: PVV was significantly lower in the cirrhosis group, whereas the others were significantly lower in the CVH group. For liver size, PVP score, and portal flow volume, there were no significant differences between the 3 groups. The relative abundance of patients with Child A and B cirrhosis (n = 41) may explain the indifference of liver size in the cirrhosis group. The smallest PVP score was 0.48 for the control group, and it was 0.40 for the cirrhosis group in our study. The lower limit of the PVP score for cirrhosis is quite variable in the literature Arterialization of the portal vein was found in only 1 of 62 patients with cirrhosis (Figure 1). In our opinion, this finding has limited value in the diagnosis. We did not find any significant difference of portal vein flow volume between groups. Because of the association of the PVV decrease and portal vein dilatation in portal hypertension, flow volume remained within normal limits. Moriyasu et al 37 also found no relationship between portal pressure and portal flow volume. Some mistakes can be made when measuring portal vein flow volume with Doppler sonography. It is generally recognized that flow volume measurements have limited reliability in this modality. In conclusion, alterations of liver hemodynamics resulting from inflammation at the tissue level are detectable on Doppler sonography. This noninvasive technique is helpful for assessment of the degree of liver inflammation and the stage of fibrosis, and it should be used to follow the progression of CVH. Doppler sonography has high diagnostic value for cirrhosis. However, its value in clinical staging is limited. References 1. Withers CE, Wilson SR. The liver. In: Rumack CM, Wilson SR, Charboneau JW (eds). Diagnostic Ultrasound. 2nd ed. St Louis, MO: CV Mosby Co; 1998: Zoli M, Magalotti D, Bianchi G, et al. Functional hepatic flow and Doppler-assessed total hepatic flow in control subjects and in patients with cirrhosis. J Hepatol 1995; 23: Ohnishi K, Saito M, Nakayama T, et al. Portal venous hemodynamics in chronic liver disease: effect of posture change and exercise. Radiology 1985; 155: J Ultrasound Med 2005; 24:

10 Doppler Sonography in Chronic Viral Hepatitis and Cirrhosis 4. Zironi G, Gaiani S, Fenyves D, Rigamonti A, Bolomdi L, Barnara L. Value of measurement of mean portal flow velocity by Doppler flowmetry in the diagnosis of portal hypertension. J Hepatol 1992; 16: Koda M, Murawaki Y, Kawasaki H, Ikawa S. Portal blood velocity and portal blood flow in patients with chronic viral hepatitis: relation to histological liver fibrosis. Hepatogastroenterology 1996; 43: 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 2001; 36: Bosch J, Garcia-Pagan JC. Complications of cirrhosis. I. Portal hypertension. J Hepatol 2000; 32(suppl): S141 S Shapiro RS, Stancato-Pasik A, Glajchen N, Zalasin S. Color Doppler applications in hepatic imaging. Clin Imaging 1998; 22: Hirata M, Akbar SM, Horiike N, 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 2001; 31: Piscaglia F, Donati G, Serra C, et al. Value of splanchnic Doppler ultrasound in the diagnosis of portal hypertension. Ultrasound Med Biol 2001; 27: Propst A, Propst T, Zangerl G, Ofner D, Judmaier G, Vogel W. Prognosis and life expectancy in chronic liver disease. Dig Dis Sci 1995; 40: Tai DI, Chuah SK, Chen CL, Lo SK, Changchien CS, Li IT. Inter-observer variability of portal hemodynamics measured by Doppler ultrasound on three different locations of portal vein. J Clin Ultrasound 1996; 24: Bolognesi M, Sacerdoti D, Merkel C, Bombonato G, Gatta A. Noninvasive grading of the severity of portal hypertension in cirrhotic patients by echo-color- Doppler. Ultrasound Med Biol 2001; 27: Annet L, Materne R, Danse E, Jamart J, Horsmans Y, Van Beers BE. Hepatic flow parameters measured with MR imaging and Doppler US: correlations with degree of cirrhosis and portal hypertension. Radiology 2003; 229: Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 1994; 19: Knodell RG, Ishak KG, Black WC, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981; 1: Colli A, Cocciolo M, Riva C, et al. Abnormalities of Doppler waveform of the hepatic veins in patients with chronic liver disease: correlation with histologic findings. AJR Am J Roentgenol 1994; 162: Ohnishi K, Sato S, Pugliese D, Tsunoda T, Saito M, Okuda K. Changes of splanchnic circulation with progression of chronic liver disease studied by echo- Doppler flowmetry. Am J Gastroenterol 1987; 87: Gorka W, Kagalwalla A, McParland BJ, Kagalwalla Y, al Zaben A. Diagnostic value of Doppler ultrasound in the assessment of liver cirrhosis in children: histopathological correlation. J Clin Ultrasound 1996; 24: Sacerdoti D, Merkel C, Bolognesi M, Amodio P, Angeli P, Gatta A. Hepatic arterial resistance in cirrhosis with and without portal vein thrombosis: relationships with portal hemodynamics. Gastroenterology 1995; 108: 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 1997; 92: Piscaglia F, Gaiani S, Zironi G, et al. Intra- and extrahepatic arterial resistances in chronic hepatitis and liver cirrhosis. Ultrasound Med Biol 1997; 23: Benoit JN, Womack WA, Hernandez L, Granger DN. Forward and backward flow mechanisms of portal hypertension. Gastroenterology 1985; 89: Coulden RA, Lomas DJ, Farman P, Britton PD. Doppler ultrasound of the hepatic veins: normal appearances. Clin Radiol 1992; 45: Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973; 60: Arda K, Ofelli M, Calikoglu U, Olcer T, Cumhur T. Hepatic vein Doppler waveform changes in early stage (Child-Pugh A) chronic parenchymal liver disease. J Clin Ultrasound 1997; 25: J Ultrasound Med 2005; 24:

11 Haktanir et al 27. O donohue J, Ng C, Catnach S, Farrant P, Williams R. Diagnostic value of Doppler assessment of the hepatic and portal vessels and ultrasound of the spleen in liver disease: Eur J Gastroenterol Hepatol 2004; 16: Dietrich CF, Lee JH, Gottschalk R, et al. Hepatic and portal vein flow pattern in correlation with intrahepatic fat deposition and liver histology in patients with chronic hepatitis C. AJR Am J Roentgenol 1998; 171: Haag K, Rossle M, Ochs A, et al. Correlation of duplex sonography findings and portal pressure in 375 patients with portal hypertension. AJR Am J Roentgenol 1999; 172: Erden A, Altuntas B, Olcer T, Cumhur T. Presinusoidal portal hypertension does not affect hepatic artery resistance index. Eur Radiol 1999; 9: Farrant P, Meire HB. Hepatic vein pulsatility assessment on spectral Doppler ultrasound. Br J Radiol 1997; 70: Gorka W, al Mulla A, al Sebayel M, Altraif I, Gorka TS. Qualitative hepatic venous Doppler sonography versus portal flowmetry in predicting the severity of esophageal varices in hepatitis C cirrhosis. AJR Am J Roentgenol 1997; 169: Zoli M, Marchesini G, Cordiani MR, et al. Echo- Doppler measurement of splanchnic blood flow in control and cirrhotic subjects. J Clin Ultrasound 1986; 14: Duerinckx AJ, Grant EG, Perrella RR, Szeto A, Tessler FN. The pulsatile portal vein in cases of congestive heart failure: correlation of duplex Doppler findings with right atrial pressures. Radiology 1990; 176: Abu-Yousef MM, Milam SG, Farner RM. Pulsatile portal vein flow: a sign of tricuspid regurgitation on duplex Doppler sonography. AJR Am J Roentgenol 1990; 155: Hosoki T, Arisawa J, Marukawa T, et al. Portal blood flow in congestive heart failure: pulsed duplex sonographic findings. Radiology 1990; 174: Moriyasu F, Ban N, Nishida O, et al. Clinical application of an ultrasonic duplex system in the quantitative measurement of portal blood flow. J Clin Ultrasound 1986; 14: J Ultrasound Med 2005; 24: