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Thomas J. Bryce1 Benjamin M. Yeh1 Aliya Qayyum1 Preeyacha Pacharn2 Nathan M. Bass3 Ying Lu1 Fergus V. Coakley1
OBJECTIVE. We investigated whether CT signs can be used to predict hepatofugal ﬂow in the main portal vein in patients with cirrhosis. MATERIALS AND METHODS. We retrospectively identiﬁed 36 patients with cirrhosis, 18 with hepatopetal and 18 with hepatofugal ﬂow in the main portal vein, who underwent contemporaneous abdominal sonography and CT. Two independent observers evaluated the following features on the randomized CT studies: diameter of the portal, splenic, and superior mesenteric veins; spleen size; and the presence of ascites, varices, or arterial phase portal venous enhancement. These data were correlated with the ﬂow direction seen on sonography. RESULTS. A small main portal vein was the only sign signiﬁcantly (p ≤ 0.05) predictive of hepatofugal ﬂow by univariate and multivariate analyses. Observers 1 and 2 recorded a portal vein diameter of less than 1 cm in eight (44%) and seven (39%) of the 18 patients with hepatofugal ﬂow compared with one (6%) and none of the 18 patients with hepatopetal ﬂow, respectively (p < 0.02). Receiver operating characteristic analysis using the size of the portal vein to predict ﬂow direction revealed an area under the curve of 0.83 for observer 1 and 0.74 for observer 2. CONCLUSION. A diameter of less than 1 cm for the main portal vein is highly speciﬁc, although not sensitive, for hepatofugal portal venous ﬂow in patients with cirrhosis. This sign may be useful when sonography is limited, or this sign may prompt sonographic assessment in patients not known to have hepatofugal ﬂow. epatofugal portal venous ﬂow in patients with cirrhosis indicates advanced portal hypertension , and cirrhotic patients with hepatofugal ﬂow have greater hepatic dysfunction , a higher incidence of hepatic encephalopathy , an increased risk of variceal bleeding [2, 4, 5], poorer response of varices to endoscopic ligation , and higher mortality [2, 7], compared with cirrhotic patients with hepatopetal ﬂow. The detection of hepatofugal ﬂow in the main portal vein implies the liver is perfused solely by the hepatic artery, which is of therapeutic importance in planning chemoembolization of a hepatocellular carcinoma or placement of a transjugular intrahepatic portosystemic shunt (TIPS). CT arterioportography and portal venous angiography may be ineffective and therefore contraindicated in the presence of hepatofugal portal venous ﬂow . Doppler sonography is the principal technique used to determine the direction of ﬂow in the portal
Received April 10, 2003; accepted after revision June 26, 2003.
1 Department of Medicine and Department of Radiology, Abdominal Imaging Section, University of California at San Francisco, Box 0628, 505 Parnassus Ave., San Francisco, CA 94143-0628. Address correspondence to F. V. Coakley (email@example.com). 2
vein [9, 10], although MRI [11–13] and conventional angiography [14, 15] can also be used. To our knowledge, the role of CT in determining the direction of portal venous ﬂow has not been systematically examined, although patients with cirrhosis frequently undergo CT, particularly when hepatocellular carcinoma is a concern. The establishment of CT criteria for the detection of hepatofugal ﬂow in the main portal vein could be helpful in the evaluation of such patients. Therefore, we undertook this study to determine whether CT signs can be used to predict hepatofugal portal venous ﬂow in patients with cirrhosis.
Materials and Methods
Patients This study was a retrospective single-institution study approved by our institutional review board. Informed consent was not required. We searched our radiology information system (IDXrad [software version 9.7.1], IDX Systems, Burlington, VT)
Department of Radiology, Mahidol University, 2 Prannok Rd., Bangkok, 10700 Thailand.
Department of Medicine, Division of Gastroenterology, University of California at San Francisco, Box 0538, 505 Parnassus Ave., San Francisco, CA 94143-0538. AJR 2003;181:1629–1633 0361–803X/03/1816–1629 © American Roentgen Ray Society
AJR:181, December 2003
In these patients. Mountain View. Acuson Solutions). the lag was 37 and 62 days. Thus. ﬂow in the portal vein was hepatopetal on sonography 1 day before CT (Fig. 0–148 days) in the hepatopetal group and 3 days (range.5-mm slice collimation) in 20 of these patients. If sonography had been performed more than 48 hr before or after the CT examination (hepatopetal group. 17–73 years) in the hepatofugal group. and large varices. Thirty-four of the 36 patients received 150 mL of IV iohexol (Omnipaque 350. All patients received oral diatrizoate meglumine (Hypaque. and coagulopathy. Alternatively. for multiphase CT examinations (n = 20). Observer 2 found that the main portal vein measured less than 1 cm in seven (39%) of 18 patients with hepatofugal ﬂow and 0 of 18 patients with hepatopetal ﬂow (p < 0. hepatofugal group. Acuson Solutions. arterial phase) enhancement of the main portal vein was recorded. The causes for cirrhosis in the group with hepatopetal ﬂow and in the group with hepatofugal ﬂow. if CT had not been performed between the sonographic examinations. measured on the ﬁrst image that was clearly inferior to the splenoportal conﬂuence. recorded as the maximum axial diameter. 3). 4). the diagnosis of cirrhosis was established by histology in six patients and on clinical grounds in 12. Nycomed Amersham).01). n = 5).1. Both observers recorded the following CT signs: short-axis diameter of the main portal vein. hepatofugal group. We then randomly selected an additional 18 patients with hepatopetal ﬂow who also met these criteria to form the ﬁnal study population of 36 patients. Continuous data (vessel diameters and spleen size) were examined by univariate analysis using the two-tailed Cochran t test. Results The CT signs recorded by each observer showed high interobserver consistency for all measurements other than the presence of varices and the size of the spleen. Arterial phase enhancement of the portal vein was seen in only one patient. Cirrhosis was cryptogenic in two patients with hepatopetal ﬂow. None of the patients was assigned a Child-Pugh class because not all required data were available retrospectively.to 4-MHz sector transducer (4V1. given that both observers measured the main portal vein at or slightly above 1 cm in several patients with hepatopetal ﬂow (Fig. absence of TIPS or thrombosis of the main portal vein. and the hepatofugal group comprised seven men and 11 women. December 2003 . No other signs achieved signiﬁcance by either method. primary sclerosing cholangitis. viral hepatitis and ethanol abuse. Images were also acquired in the arterial phase of enhancement (45-sec scan delay with 2. 1).01) with hepatofugal ﬂow by univariate and multivariate analyses (Fig. presence or absence of ascites. measured adjacent to the midportion of the pancreatic tail. which was measured midway between the splenoportal conﬂuence and the portal vein bifurcation in the porta hepatis. Interobserver agreement for continuous data was assessed using Bland-Altman regression  with Bradley-Blackwood p values . and spleen size. ROC analysis using the diameter of the main portal vein to predict hepatofugal ﬂow revealed an Az of 0. NC). All p values of 0. n = 2). the presence or absence of early (i. 44–80 years) versus 51 years (range. The 1-cm measurement was the largest (most sensitive) threshold that could be used to predict hepatofugal ﬂow without signiﬁcantly reducing speciﬁcity.74 for observer 2 (Fig. 0 and six patients. Observers were unaware of clinical and sonographic ﬁndings. We identiﬁed 18 patients with hepatofugal ﬂow in the main portal vein who met these criteria. and cystic ﬁbrosis. 0 and one patient. Nycomed Amersham. Additional studies were not available for the remaining three hepatopetal and two hepatofugal patients. Interobserver agreement for categorical data was measured with kappa statistics . contemporaneous (within 5 months) abdominal CT. but in only one (6%) of 18 patients with hepatopetal ﬂow (p < 0. cirrhosis was diagnosed by a gastroenterologist in all but two. ascites. ethanol abuse alone.75. the sensitivity of this sign for predicting hepatofugal ﬂow was 44% and the speciﬁcity was 94%. The median time between sonography and CT was 23 days (range. and histologic diagnosis of cirrhosis (n = 11) or a clear clinical diagnosis of cirrhosis documented in the medical record (n = 25). Observer 1 found that the main portal vein measured less than 1 cm in eight (44%) of 18 patients with hepatofugal ﬂow. n = 9). and medical records for the period of October 1998 to March 2002 to identify patients meeting the following sequential criteria: abdominal sonography report containing the term “cirrhosis”. presence or absence of varices. SAS. and images were acquired in the portal venous phase of enhancement (70-sec scan delay with 5-mm slice collimation). we identiﬁed a second Doppler sonographic study of ﬂow direction in the main portal vein for each patient so that sonography occurred before and after the CT examination (hepatopetal group.Bryce et al. Imaging Technique All CT examinations were performed on multidetector scanners (LightSpeed or HiSpeed. the time lag between CT and sonography for the two patients with hepatopetal ﬂow was 3 and 31 days. cirrhosis was established by histology in ﬁve patients and on clinical grounds in 13.to 4-MHz sector transducer (4V2. CT Interpretation Two radiologists independently reviewed the randomized CT images of all 36 patients on a PACS (picture archiving and communication system) workstation (Impax DS 3000 [release 4. 11 and four patients. 2). cirrhosis was diagnosed on the basis of clinical evidence including a history of severe alcohol abuse. 0–97 days) in the hepatofugal group.e. and for the two patients with hepatofugal ﬂow. nonalcoholic steatotic hepatitis. NJ). and a higher threshold would greatly reduce speciﬁcity with only mildly increasing sensitivity (Fig. both of whom had hepatofugal portal venous ﬂow. n = 9.02). diameter of the splenic vein. 1). Multivariate analysis was performed using logistic regression with a generalized linear model to account for the presence of two observers.1]. WI). The hepatopetal group comprised 10 men and eight women. Parameters were selected in a stepwise fashion with a type 3 signiﬁcance level of 0. Two patients (one with hepatopetal and one with hepatofugal ﬂow) did not receive IV contrast material. Princeton. hypoalbuminemia. 2). Mortsel. Receiver operating characteristic (ROC) analysis and area under the ROC curve (Az) calculations were performed to evaluate predictive models.83 for observer 1 and 0. All additional sonographic studies evaluated conﬁrmed the ﬂow direction seen on the initial study. In these two patients. Acuson Solutions) or a 2. A small main portal vein correlated strongly (p < 0. CA) with a 1. Data Analysis Statistical analysis was performed using statistical analysis software (SAS version 8. direction of ﬂow in the main portal vein described in the sonography report. we identiﬁed the two sonographic examinations closest in time to the CT examination (hepatopetal group. Cary.5.. The univariate analyses were performed separately for the data for each observer. in that patient. autoimmune hepatitis. in the hepatofugal group. respectively. Of those patients without histologic conﬁrmation. one patient and 0 patients. maximum short-axis diameter of the superior mesenteric vein. Agfa.05 or less required for factors to remain in the model. one and three patients. Noncontinuous data (all other categories) were examined using Fisher’s exact test. All images were contiguous. In the hepatopetal group.05 or less were considered signiﬁcant. 1630 AJR:181. n = 14. Milwaukee. The mean age of patients in the hepatopetal group was 59 years (range. A representative case illustrates the ﬁnding of a small portal vein in a patient with hepatofugal ﬂow (Fig. gross ﬁndings of cirrhosis on imaging studies. one and three patients. n = 2. hepatofugal group. two patients and one patient. included the following: chronic viral hepatitis. Color Doppler sonography of the direction of ﬂow in the main portal vein was performed using a scanner (Sequoia 512. A lower threshold would reduce sensitivity without signiﬁcantly increasing speciﬁcity. General Electric Medical Systems. In addition. Belgium). for a sensitivity of 39% and a speciﬁcity of 100%.
Fig.5 0. 1.8 1 Observer 1 Observer 2 False-Positive Fraction Fig. 2.6 0. Note that main portal vein diameter of less than 1 cm is highly speciﬁc for hepatofugal ﬂow.CT Signs of Hepatofugal Portal Venous Flow 2.83 for observer 1 and 0.5 1 Diameter of Main Portal Vein (cm) 2 0.—Diagram shows receiver operating characteristic (ROC) values achieved using small main portal vein diameter to predict hepatofugal ﬂow in main portal vein in patients with cirrhosis.4 0.4 0.74 for observer 2. Operating points achieved by predicting hepatofugal ﬂow when main portal vein diameter was less than 1 cm are shown for observer 1 (×) and observer 2 (Δ). Axial CT scan obtained during portal venous phase shows small (8 mm in diameter) main portal vein (arrow). Area under ROC curve (Az) was 0.6 1 0. Note that at appropriate operating points. A Fig.8 True-Positive Fraction Hepatopetal Hepatofugal Hepatopetal Hepatofugal 1. Sonogram shows hepatofugal ﬂow in main portal vein.5 0.2 0 0 0 0. this sign is highly speciﬁc for hepatofugal ﬂow. 3. this ﬁnding strongly correlates with hepatofugal ﬂow. A. December 2003 1631 . B. B AJR:181.—73-year-old woman with cirrhosis due to alcohol abuse.2 0.—Diagram shows diameters of main portal vein in patients with hepatopetal ﬂow versus hepatofugal ﬂow.
Such ﬂow changes can occur spontaneously in cirrhotic patients . CT and sonography were not immediately contemporaneous. In our study. CT scan obtained during arterial phase shows contrast enhancement of portal vein. a phenomenon that would also be expected to reduce hepatic portal venous perfusion. This decrease in ﬂow volume could explain the decreased diameter of the portal vein. These factors might exhibit an association with hepatofugal ﬂow in a larger study. a main portal vein of less than 1 cm can be considered relatively small in a cirrhotic patient because portal hypertension tends to increase portal vein size . B 1632 AJR:181. reveals hepatopetal ﬂow. This sign is thought to indicate hepatofugal portal venous ﬂow. however. B. it is reasonable to expect that the direction of ﬂow at the time of CT would be accurately predicted by the contemporaneous sonographic examination that was evaluated. although the possible effects of the time difference would be expected to apply to both hepatopetal and hepatofugal groups of patients. the portal vein is supplied only by the hepatic artery. For example. 4. 22]. The lag between the examinations may have lowered the sensitivity of the study for additional predictors of hepatofugal ﬂow. 25]. Disturbance of baseline physiology during abdominal CT. despite a reduction or reversal in ﬂow. Normally. For example. in the postprandial state [24. and Doppler sonography of this patient 1 day before CT showed hepatopetal ﬂow. which also supplies the hepatic veins.) Although speciﬁc for hepatofugal ﬂow. but these differences did not achieve statistical signiﬁcance.—49-year-old man with cirrhosis due to chronic hepatitis C infection. Discussion Our ﬁnding that a relatively small main portal vein in patients with cirrhosis indicates hepatofugal ﬂow is consistent with the physiology of hepatofugal ﬂow in the cirrhotic liver.Bryce et al. and the subsequent increased shunting of hepatic arterial blood into the portal venous system may result in temporary hepatofugal ﬂow. Analysis of additional sonography examinations of the study population provided evidence that the direction of portal venous ﬂow in our subjects was stable. this sign was of only moderate sensitivity in our study group. Doppler sonogram obtained 1 day earlier than A. The lag between studies would not be expected to generate spurious associations and should not detract from the ﬁnding that a small portal vein size is associated with hepatofugal portal venous ﬂow. Therefore. such as due to breath-hold technique or bolus administration of IV contrast material. (A small main portal vein in cirrhotic patients has been associated with spontaneous splenorenal shunts . Our study has several limitations. A Fig. this sign was present in only one of 20 patients undergoing CT with arterial phase contrast enhancement. may alter portal venous hemodynamics. and during hepatic arteriography . Possible explanations for the limited sensitivity may include a tendency for the vein to remain patulous after enlarging in earlier stages of portal hypertension and the possibility that portal hypertension may provide a continuing impetus for venous enlargement.0 cm . The sample size was small and may have restricted the power of the study to detect differences between the hepatopetal and hepatofugal groups. A. contrast administration might elevate right heart and hepatic vein pressures. Arterial phase enhancement of the portal vein has been reported as a sign of hepatofugal ﬂow [1. the prevalence of ascites and varices was higher in patients with hepatofugal ﬂow. the portal vein receives ﬂow from the superior mesenteric vein and the splenic vein. December 2003 . The average size of the main portal vein in healthy adults has been found to be 1. In patients with cirrhosis and hepatofugal ﬂow in the main portal vein. The ﬁnding of arterial phase enhancement of the portal vein on CT in a patient with hepatopetal portal venous ﬂow on sonography is puzzling but might be explained by transient changes in ﬂow direction in the portal venous system.
Coronary vein diameter and ﬂow direction in patients with portal hypertension: evaluation with duplex sonography and correlation with variceal bleeding. AJR 1994. Gastroenterology 1991. The interobserver variation regarding spleen size may have resulted from the complex and partly subjective methodology used.33:159–174 17.55:465–470 23.43:234–235 19.2:267–273 24. Matsui T. Hamamoto N.29:255–275 15. Hoevels J. Gastrointest Endosc 1999. However. AJR 1990. Johansen K. Dick R.161:989–994 14. Duplex ultrasonography of the portal vein. Peterson MS. CT arterial portography and dual phase spiral CT. Koch GG. Paun M. this sign may be useful when sonography is limited or may prompt sonographic assessment in patients not known to have hepatofugal ﬂow. Nishiuma S. The measurement of observer agreement for categorical data. References 1. Komatsuda T.177:1109–1112 26. Eur J Ultrasound 1997. Restricting the analysis to only those patients with a histologic diagnosis would have selected for substantially more diseased or symptomatic patients. Kane RA.32:766–772 13. Biometrics 1977. Park CM. Wachsberg RH.1:307–310 18.CT Signs of Hepatofugal Portal Venous Flow High interobserver consistency was not seen for the measurement of spleen size and assessment for the presence or absence of varices. Direction of splenic venous ﬂow assessed by pulsed Doppler ﬂowmetry in patients with a large splenorenal shunt: relation to spontaneous hepatic encephalopathy. Kudo M. von Herbay A. Edelman RR. Landis JR. Lunderquist A. Clin Radiol 2000. Erckenbrecht JF. our data suggest that a main portal vein diameter of less than 1 cm is highly speciﬁc for hepatofugal portal venous ﬂow in cirrhotic patients. Li Bassi S. de Vries PJ. Merkel C. Radiology 2001. and had either histologic conﬁrmation of cirrhosis or had been assigned the diagnosis of cirrhosis at a tertiary care center (by a gastroenterologist in all but two cases).78:197–205 4. we believe that the probability of noncirrhotic patients existing within the study population is low.149:77–81 16. Magnetic resonance angiography for monitoring prophylactic endoscopic treatment of high risk esophageal varices. Siringo S. et al. Lancet 1986. AJR 2001. Haussinger D. Reverse ﬂow in intrahepatic portal vessels and liver function impairment in cirrhosis. but not vice versa. Camilo ME. Finucci G. AJR 1993.149:537–540 20.100:160–167 28. Barbara L. Altman DG. Okabe Y. possibly harming the generalizability of our results. Sato S. Blackwood LG. the diagnosis of cirrhosis was conﬁrmed histologically in only about one third of the study subjects. Carr BI. Bland JM. Scholten T.1–3. Hepatic arterioportal shunts not directly related to hepatocellular carcinoma: ﬁndings on CT during hepatic arteriography. Hoekstra JB. Am Stat 1989. Dodd GD 3rd. Federle MP. Imaging of the portal venous system in patients with cirrhosis: MR angiography vs duplex Doppler sonography. et al. Color Doppler ﬁndings of gastrointestinal varices. Endoscopy 2000. Color Doppler sonographic evaluation of spontaneous portosystemic shunts and inversion of portal venous ﬂow in patients with cirrhosis. Color Doppler sonography of the hepatic artery and portal venous system. Barone A. Chezmar JL. Leﬂeur RS. Arterioportography. Wachsberg RH. de Hooge P. 28]. Tochio H. Raghavendra BN.187:407–412 12. and diagnostic pitfalls. et al.220:321–328 22. Pealer K. Ehman RL. This study did not seek to measure the prevalence of hepatofugal ﬂow in the entire population of cirrhotic patients. Sonographic measurements of the normal liver.26:951–960 8. Tylen U. van Hattum J. Bolondi L. Morton MJ. Portal venous thrombosis or sclerosis in liver transplantation candidates: preoperative CT ﬁndings and correlation with surgical procedure. Sonographic evaluation of patients with portal hypertension. pancreas.164:333–337 9. et al. If validated in prospective studies. Ohnishi K. RadioGraphics 2002. de Stefano G. Simmons MZ. Saito M. Gaiani S. et al. AJR 1987. which involved identifying the maximal single dimension of the spleen on any axial image. Kim DH. Oliver JH 3rd. Postprandial reversal of the portal venous ﬂow in a patient with liver cirrhosis. Neth J Med 1995. Bahramipour P.89:180–185 27. Gastroenterology 1985. Percutaneous transhepatic portography in the assessment of portal hypertension: clinical correlations and comparison of radiographic techniques. Finn JP. Baron RL. Smith-Laing G. Left gastric vein hemodynamics and variceal recurrence in patients undergoing prophylactic endoscopic ligation of high-risk esophageal varices. Frieling T. Herlinger H. et al. Johnson CD. Noguchi R. Bradley EL. Clin Radiol 1978. Comparison of pulsed Doppler sonography and angiography in patients with portal hypertension. Nelson RC. Ishida H.28:332–333 AJR:181. although the sensitivity of this sign is limited. December 2003 1633 . had imaging features consistent with cirrhosis. Cardiovasc Radiol 1979. and portal vein. Finally. Scand J Gastroenterol 1991. Balthar EJ. Gastroenterology 1980. Spontaneous intermittent reversal of blood ﬂow in intrahepatic portal vein branches in cirrhosis of the liver. Given that all patients in this study had signiﬁcant risk factors for cirrhosis. Radiology 1993. Intrahepatic spontaneous retrograde portal ﬂow in patients with cirrhosis of the liver: reversal by food intake. 27]. Statistical methods for assessing agreement between two methods of clinical measurement.70:181–190 11. Imazu H. although this information would be required to determine predictive values. The discrepancy in identiﬁcation of varices between observers could be explained by a greater sensitivity of observer 2 for varices in borderline cases. spleen. Matsumoto A. Lovett KE. Ohnishi A.155:517–525 10. Ralls PW.47:235–240 25. This is important given that our sign. et al. The prevalence of hepatofugal ﬂow in unselected cirrhotic patients has been previously estimated at 3. Am J Gastroenterol 1983.162:637–641 5. Giorgio A.50:768–774 7. Sonnenberg A. imaging ﬁndings. Geller DA. Fritsch WP. Niederau C. Sherlock S. although highly speciﬁc. et al.4% [2. et al. Bellon S. Zironi G.22:123–140 2. Comparing paired data: a simultaneous test of means and variances. Sofocleous CT.6:171–177 3. Subramanyam BR.23:45–50 6. rising to 9% or more in patients with advanced cirrhosis [2. Brancatelli G. Surg Clin North Am 1990. Muller JE. Tarantino L. Burkart DJ. Phase-contrast cine MR angiography in chronic liver disease. Abdom Imaging 1998. Does advanced cirrhosis with portosystemic shunting affect the value of CT arterial portography in the evaluation of the liver? AJR 1995. J Clin Ultrasound 2000. In conclusion. Radiology 1983. Konno K. Evaluation of splanchnic angiography as a prognostic index of survival in patients with cirrhosis. Prevalence of spontaneous hepatofugal portal ﬂow in liver cirrhosis: clinical and endoscopic correlation in 228 patients. given that all cases identiﬁed as positive by observer 1 were also called positive by observer 2. is of limited sensitivity. most patients with a diagnosis of cirrhosis do not undergo histologic conﬁrmation.78:369–373 21. Hepatofugal ﬂow in the portal venous system: pathophysiology. Cha SH.