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Postprandial reversal of the portal venous flow in a patient with liver cirrhosis
The Netherlands
JOURNALOF MEDHXNE
Netherlands Journal of Medicine 47 (1995) 235-240
Brief report
Postprandial reversal of the portal venous flow in a patient with liver cirrhosis P.J. de Vries a,* , P. de Hooge b, J.B.L. Hoekstra ‘, J. van Hattum a a Department of Gastroenterology, University Hospital, Utrecht, Netherlands b Department of Diagnostic Imaging, Diakonessenhuis, Utrecht, Netherlands ’ Departmenf of Infernal Medicine, Diakonessenhuis, Utrecht, Netherlands
Received 5 August 1994; revised 13 February 1995; accepted 14 February 1995
Abstract The case of a 61-year-old man with alcoholic liver cirrhosis and a hepatoceilular carcinoma is presented. He was examined with duplex Doppler before and after a meal. In the fasting state a sluggish hepatopetal portal venous flow was found. After the meal a pendulating flow and then hepatofugal flow were found, The magnitude and direction of flow alternated synchronously with the action of the heart, suggesting a significant role for the hepatic artery in the postprandial reversal of portal venous flow. One year after this examination the patient died from the complications of decompensated cirrhosis and liver failure. At autopsy a large hepatocelhdar carcinoma was detected. Keywords:
Portal hypertension; Liver cirrhosis; Portal venous flow; Postprandial flow reversal; Hepatoceklar
carcinoma
1. Introduction
raised much debate in the past, but is well accepted nowadays [1,2]. The recent information on
The spontaneous reversal of portal venous flow is an intriguing phenomenon of portal hypertension. The pathophysiology of portal hypertension has not yet explained all the haemodynamic variables, many of which change during the evolution of liver disease. Hepatofugal portal flow can occur in end-stage liver disease with portal hyper-
portal venous flow mainly originates from duplex
tension. The question of its actual existence has * Corresponding author, current address: Department of Internal Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands. Tel.: (+ 31-20) 5662170; fax: ( + 31-20) 6972286.
Doppler
Qualitative
measure-
strated sluggish flow and hepatofugal flow in the portal vein in some patients. However, quantitative measurement of the portal venous flow does not distinguish between patients with cirrhosis in
general and healthy subjects 13-91. The driving force of spontaneous hepatofugal flow is the gradient between sinusoidal and portosystemic collateral blood pressure. A factor that may influence the sinusoidal pressure is the hepatic artery [lo].
0300-2977/95/$09.50 0 1995 Elsevier Science B.V. All rights reserved SSDl 0300-2977(95)00028-3
investigations.
ments in end-stage liver disease have demon-
Slight changes in the hepatic
236
P.J. de Vries et al. /Netherlands
Journal of Medicine 47 (1995) 235-240
artery are too small to be detected by duplex Doppler, but sometimes changes in portal haemodynamics may be found suggestive of hepatic artery influences. This report presents a patient with liver cirrhosis who was examined with duplex Doppler before and after a meal. Postprandial reversal of the direction of portal venous flow was found to be synchronous with the cardiac cycle. 2. Case report A 61-year-old man was examined with duplex Doppler before and after a meal. The patient was known for several years to have a histologically documented alcoholic liver cirrhosis and peripheral polyneuropathy. One year before examination he survived an episode of gastrointestinal haemorrhage. At the time of the examination he was admitted because he had recently evacuated about 9 litres of ascites via a ruptured umbilical hernia. Sodium intake was restricted and he was treated with spironolactone. There were no subjective complaints. Physical examination showed a man in poor nutritional state without any signs of encephalopathy. His weight was 60 kg and his height was 1.87 m . Blood pressure was 110/70 mmHg and the pulse rate was 70 bpm. The liver was enlarged with the edge palpable at 3 cm caudally from the right costal arch in the m idclavicular line. The spleen was not palpable. Ascites was not detected by physical examination. The peripheral neuropathy was present as before, with signs of muscular atrophy. Laboratory examination revealed the following: Hb 8.5 mmol/l, WBC 4.2.109/1, thrombocytes 90.109/1, creatinine 67 pmol/l (N: SO-120 pmol/l), sodium 125 mmol/l (N: 136-146
mmol/l), potassium 4.8 mmol/l (N: 3.8-5.0 mmol/l), bilirubin 42 pmol/l (N: < 17 pmol/l ) with a direct fraction of 0.72, alkaline phosphatase 132 IU/l (N: 27-93 IU/l), y-glutamyl transpeptidase 68 U/l (N: 8-46 IU/l), ASAT 58 IU,‘l (N: < 30 II-J/l), ALAT 35 IU,‘l (N: < 30 B-J/l), ammonia 95 kmol/l (N: < 50 pmol/l), serum protein 74 g/l, prothrombin time 15.6 s (contro1:ll.S s), factor V activity 38% (N: 70130%). cu-Fetoprotein was normal. Endoscopic examination showed large oesophageal varices classified as grade 4 according to Paquet, and gastric varices. The patient was examined with a mechanical sector scanner (Technicare AutosectorTM) integrated with pulsed Doppler (Technicare Auto DIIT, Technicare, USA). This system has been calibrated in vitro using a flow phantom [ll]. The examination technique has been described previously. In short, the portal vein was visualised on the real-time two-dimensional image and the Doppler-beam marker was directed at the portal vein. When holding the breath after a normal expiration the image was frozen and the Doppler signal was sampled. Thereafter the two-dimensional image was updated very briefly. The latter procedure reduces the aesthetic quality of the two-dimensional image, but enables revision of correct probe positioning after flowmetry. Duplex Doppler examination was performed in the early morning hours after an overnight fast. After the first measurement the patient took a liquid meal according to Lundh [121, and thereafter measurements were repeated for 60 m in at 5 m in intervals. The Doppler signal could be received adequately, but the best signal was received at an insonation angle of ca. 60”. The morphological image of the liver showed increased reflections
Fig. 1. The top part of the figure shows a longitudinal ultrasound view of the portal vein. The lower part shows the Doppler recordings 5, 24 and 38 min after the intake of a meal (A, B and C, respectively). The arrows indicate the systole. The Doppler graphs show the flow velocity (cm/s, y-axis) over 4 s (x-axis). Hepatopetal flow is shown by the signals above the horizontal, hepatofugal flow by the signals below the horizontal. (A) 5 min after the intake of the meal: hepatopetal flow in the portal vein with a slight pulsatile flow pattern. The cross indicates the beginning of a portal flow wave. (B) 24 min after the intake of the meal: portal venous flow is hepatopetal during diastole; during systole no flow is recorded. The cross indicates the beginning of a portal flow wave. (C) 38 min after the intake of the meal. The portal flow is hepatofugal during systole. During diastole no flow is recorded.
P.J. de Vies et al. /Netherlands Journal of Medicine 47 (199.5)235-240
237
238
P.J. de Vries et al. /Netherlands
Journal of Medicine 47 (1995) 235-240
suggestive of cirrhosis. There was still much ascites and the portal vein diameter was of small caliber (5.1 cm). A large coronary vein with a diameter of 7.6 mm was seen, branching from the portal vein in the lesser omentum and running cranially. The Doppler signal of the portal vein was sampled on the hepatic side of the branching coronary vein. The spleen size was normal. In the fasting state and during the first postprandial measurement the direction of portal venous flow was hepatopetal with a pulsatile flow pattern (Fig. 1A). Ten minutes after the meal an undulating pattern of the flow synchronous with the action of the heart was seen. When hepatic artery signals or systolic artefact signals were recorded simultaneously with the portal venous flow, the portal venous flow occurred in a hepatofugal direction during systole, with undetectable flow during diastole. This pattern alternated with a pattern of diastolic hepatopetal flow and systolic undetectable flow (Fig. 1B). The pattern of systolic hepatofugal and diastolic undetectable flow persisted (Fig. 1C) for 1.5 h. At that time the measurements were ended. During the examination the direction of flow was confirmed at different insonation angles. For reasons of comparability the photographs were taken using the same insonation angles. The direction of flow in the splenic vein was always splenofugal. In the coronary vein it was always hepatofugal. One year after this examination the patient died after an episode of massive irretractable ascites and liver failure. In the intervening period there had been no follow-up of the patient. Although the (Yfetoprotein in serum was never elevated, the suspicion of a hepatocellular carcinoma was confirmed at autopsy. Centrally in the liver a large hepatocellular carcinoma was found with extensive intravascular growth. 3. Discussion The principal finding of this report is that the direction of portal venous flow may be reversed in the early postprandial phase in a patient with severe decompensated liver cirrhosis and portal hypertension. The reversal of portal venous flow appears to be induced by the hepatic arterial
flow. This phenomenon has not been observed before. The reversal of the direction of flow in our patient was unequivocal. The limitations of our ultrasound equipment have been evaluated and at the current settings the equipment was shown to perform well [ll]. Quantitative flow measurements are subject to non-systematic intra-observer variance. A mean coefficient of variation for this intra-observer variability of 14% was found. The direction of flow determined with duplex Doppler has been shown to correspond with cineangiographic results [13]. Visualisation of the caval and portal veins was adequate; they could be clearly distinguished. The portal vein could also be distinguished adequately from other vessels such as the coronary vein. Spontaneous hepatofugal flow is associated more frequently with hepatocellular carcinoma than with cirrhosis without carcinoma [141. The haemodynamic significance of the hepatocellular carcinoma at the time of examination of our patient is indeterminate. At that time the hepatocellular carcinoma was not detected and the blood a-fetoprotein level was normal, also shortly before death, 1 year later. The reversal of the direction of portal venous flow is a significant feature of portal hypertension. In the past the existence of spontaneous reversal of the flow was regarded with scepticism. The reason was that spontaneous reversal was demonstrated with non-physiological measurement techniques. Nowadays, after the development of duplex Doppler techniques, spontaneous hepatofugal flow is a well-recognised phenomenon. The reported incidence of hepatofugal flow in the portal vein ranges from 3 to 15% depending on patient selection and technique of investigation [2,5,15,16]. In end-stage liver disease, hepatofugal flow is detected more often than in earlier stages. The actual reversal of the direction of flow has never been observed, although a stagnant flow with a “to and fro” motion during the respiratory cycle after side-to-side portocaval anastomosis has been reported [ll. The pathophysiology of portal hypertension is described by the classical backward flow theory,
P.J. de Vries et al. /Netherlands
Journal of Medicine 47 (1995) 235-240
which explains elevated portal pressure by an increase in portal venous resistance, and the forward flow theory [17]. The latter is based on the finding of an increased splanchnic inflow. This may sustain the elevated portal pressure in the presence of substantial portal systemic collateral blood flow. The role of the hepatic artery in this hyperdynamic splanchnic circulation is not completely elucidated. By its inflow into hepatic sinusoids it has the potential to modulate sinusoidal pressure and thus portal venous pressure and flow. In liver cirrhosis the influence of the hepatic artery may be relatively large. Small changes in hepatic arterial pressure induced by physiological stimuli may have large effects on portal venous haemodynamics. Sinusoidal pressure may increase as a result of postprandial changes in the hepatic artery. In end-stage liver cirrhosis with sluggish portal flow this may initiate reversal of the direction of flow. The findings in our patient indicate the hepatic artery as the driving force directing blood towards the collateral vascular system. In contrast, it seems unlikely that portosystemic collateral vascular pressure decreases. After a meal the splanchnic inflow and azygos flow increase, the collateral vascular system receiving the major part of the increase in blood flow [4,9,18-221. The prognostic value of reversal of prandial portal flow and increased azygos flow can only be speculated on. Previous studies have not shown any additional risk of variceal haemorrhage in patients with spontaneous hepatofugal flow [2,10]. The significance of our findings is twofold. First it shows that in the early postprandial phase a reversal of portal venous flow can occur. This implies that encephalopathy may be aggravated not only by nutrition-derived humoral substances but also by increased postprandial portosystemic shunting. Secondly, the findings suggest a significant role for the hepatic artery as the driving force behind this postprandial reversal of portal venous flow. References [l] Moreno AH, Burchell AR, Reddy RV, Steen JA, Panke WF, Nealon TF. Spontaneous reversal of portal blood
flow: the case for and against its occurrence in patients with cirrhosis of the liver. Ann Sug 1975;181:346-358. [2] Gaiani S, Bolondi L, Li Bassi S, Zironi G, Siring0 S, Barbara L. Prevalence of spontaneous hepatofugal portal flow in liver cirrhosis. Clinical and endoscopic correlation in 228 patients. Gastroenterology 1991;100:16@-167 [3] Ohnishi K, Saito M, Nakayama T et al. Portal venous hemodynamics in chronic liver disease: effects of posture change and exercise. Radiology 1985;155:757-761. [4] Okazaki K, Miyazaki M, Onishi S, Ito K. Effects of food intake and various extrinsic hormones on portal blood flow in patients with liver cirrhosis demonstrated by pulsed Doppler with the Octoson. Stand J Gastroenterol 1986;21:1029-1038. 151Zoli M, Marchesini G, Cordiani MR et al. Echo-Doppler measurement of splanchnic blood flow in control and cirrhotic subjects. J Clin Ultrasound 1986;14:429-435. [61Ohnishi 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 flowmetty. Am J Gastroenterol 1987;82:507-511. [71 Gaiani S, Bolondi L, Li Bassi S, Santi V, Zironi G, Barbara L. Effect of a meal in healthy humans and in patients with chronic liver disease. Hepatology 1989;9: 815-819. WI Sabba C, Weltin GG, Cicchetti DV et al. Observer variability in echo-Doppler measurements of portal flow in cirrhotic patients and normal volunteers. Gastroenterology 1990;98:1603-1611. [91 Gaiani S, Bolondi L, Fenyves D, Zironi G, Rigamonti A, Barbara L. Effect of propranolol on portosystemic collateral circulation in patients with cirrhosis. Hepatology 1991;14:824-829. UOl Rector WG, Hoefs JC, Hossack KF, Everson GT. Hepatofugal portal flow in cirrhosis: observations on hepatic hemodynamics and the nature of the arterioportal communications. Hepatology 1988;8:16-20. 1111 De Vries PJ. Van Hattum J, Hoekstra JBL, De Hooge P. Duplex Doppler measurements of portal venous flow in normal subjects. Inter- and intra-observer variability. J Hepatol 1991;13:358-363. W-1 Lundh G. Pancreatic exocrine function in neoplastic and inflammatory disease: a simple and reliable new test. Gastroenterology 1962;42:275-280. [I31 Ohnishi K, Saito M, Koen H, Nakayama T, Nomura F, Okuda K. Pulsed Doppler flow as a criterion of portal venous velocity: comparison with cineangiographic measurements. Radiology 1985;154:495-498. [141 Okuda K, Moriyama M. Yasumoto M, et al. Roentgenologic demonstration of spontaneous reversal of portal blood flow in cirrhosis and primary carcinoma of the liver. Am J Roentgen01 1973;119:419-428. [151 Ohnishi K, Saito M, Sato S, et al. Direction of splenic venous flow assessed by pulsed Doppler flowmetry in patients with a large splenorenal shunt. Relation to spontaneous hepatic encephalopathy. Gastroenterology 1985;89:180-185. 1161Burcharth F, Aagaard J. Total hepatofugal portal blood
240
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Journal of Medicine 47 (1995) 235-240
flow in cirrhosis demonstrated by transhepatic portography. Fortschr Rontgenstr 1988;148:47-49. [17] Benoit JN, Womack WA, Hernandez L, Granger DN. “Forward” and “backward” flow mechanisms of portal hypertension. Gastroenterology 198.5;89:1092-1096. [18] Sabba C, Ferraioh G, Buonamico P, et al. A randomized study of propranolol on postprandial portal hyperemia in cirrhotic patients, Gastroenterology 1992;102:1009-1016. [19] Moneta GL, Taylor DC, Helton WC, Mulholland MW, Strandness DE. Duplex ultrasound measurement of postprandial intestinal blood flow: effect of meal composition. Gastroenterology 1988;95:1294-1301.
[20] O’Brien S, Keogan M, Patchett S, McCormick PA, Afdha1 N, Hegarty JE. Postprandial changes in portal haemodynamics in patients with cirrhosis. Gut 1992;33:364-367. 1211Lee SS, Hadengue A, Moreau R, Sayegh R, Hilton P, Lebrec D. Postprandial hemodynamic responses in patients with cirrhosis. Hepatology 1988;8:647-651. 1221Bendtsen F, Simonsen L, Henriksen JH. Effect on hemodynamics of a liquid meal alone and in combination with propranolol in cirrhosis. Gastroenterology 1992;102: 1017-1023.
JOURNALOF MEDHXNE
Netherlands Journal of Medicine 47 (1995) 235-240
Brief report
Postprandial reversal of the portal venous flow in a patient with liver cirrhosis P.J. de Vries a,* , P. de Hooge b, J.B.L. Hoekstra ‘, J. van Hattum a a Department of Gastroenterology, University Hospital, Utrecht, Netherlands b Department of Diagnostic Imaging, Diakonessenhuis, Utrecht, Netherlands ’ Departmenf of Infernal Medicine, Diakonessenhuis, Utrecht, Netherlands
Received 5 August 1994; revised 13 February 1995; accepted 14 February 1995
Abstract The case of a 61-year-old man with alcoholic liver cirrhosis and a hepatoceilular carcinoma is presented. He was examined with duplex Doppler before and after a meal. In the fasting state a sluggish hepatopetal portal venous flow was found. After the meal a pendulating flow and then hepatofugal flow were found, The magnitude and direction of flow alternated synchronously with the action of the heart, suggesting a significant role for the hepatic artery in the postprandial reversal of portal venous flow. One year after this examination the patient died from the complications of decompensated cirrhosis and liver failure. At autopsy a large hepatocelhdar carcinoma was detected. Keywords:
Portal hypertension; Liver cirrhosis; Portal venous flow; Postprandial flow reversal; Hepatoceklar
carcinoma
1. Introduction
raised much debate in the past, but is well accepted nowadays [1,2]. The recent information on
The spontaneous reversal of portal venous flow is an intriguing phenomenon of portal hypertension. The pathophysiology of portal hypertension has not yet explained all the haemodynamic variables, many of which change during the evolution of liver disease. Hepatofugal portal flow can occur in end-stage liver disease with portal hyper-
portal venous flow mainly originates from duplex
tension. The question of its actual existence has * Corresponding author, current address: Department of Internal Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands. Tel.: (+ 31-20) 5662170; fax: ( + 31-20) 6972286.
Doppler
Qualitative
measure-
strated sluggish flow and hepatofugal flow in the portal vein in some patients. However, quantitative measurement of the portal venous flow does not distinguish between patients with cirrhosis in
general and healthy subjects 13-91. The driving force of spontaneous hepatofugal flow is the gradient between sinusoidal and portosystemic collateral blood pressure. A factor that may influence the sinusoidal pressure is the hepatic artery [lo].
0300-2977/95/$09.50 0 1995 Elsevier Science B.V. All rights reserved SSDl 0300-2977(95)00028-3
investigations.
ments in end-stage liver disease have demon-
Slight changes in the hepatic
236
P.J. de Vries et al. /Netherlands
Journal of Medicine 47 (1995) 235-240
artery are too small to be detected by duplex Doppler, but sometimes changes in portal haemodynamics may be found suggestive of hepatic artery influences. This report presents a patient with liver cirrhosis who was examined with duplex Doppler before and after a meal. Postprandial reversal of the direction of portal venous flow was found to be synchronous with the cardiac cycle. 2. Case report A 61-year-old man was examined with duplex Doppler before and after a meal. The patient was known for several years to have a histologically documented alcoholic liver cirrhosis and peripheral polyneuropathy. One year before examination he survived an episode of gastrointestinal haemorrhage. At the time of the examination he was admitted because he had recently evacuated about 9 litres of ascites via a ruptured umbilical hernia. Sodium intake was restricted and he was treated with spironolactone. There were no subjective complaints. Physical examination showed a man in poor nutritional state without any signs of encephalopathy. His weight was 60 kg and his height was 1.87 m . Blood pressure was 110/70 mmHg and the pulse rate was 70 bpm. The liver was enlarged with the edge palpable at 3 cm caudally from the right costal arch in the m idclavicular line. The spleen was not palpable. Ascites was not detected by physical examination. The peripheral neuropathy was present as before, with signs of muscular atrophy. Laboratory examination revealed the following: Hb 8.5 mmol/l, WBC 4.2.109/1, thrombocytes 90.109/1, creatinine 67 pmol/l (N: SO-120 pmol/l), sodium 125 mmol/l (N: 136-146
mmol/l), potassium 4.8 mmol/l (N: 3.8-5.0 mmol/l), bilirubin 42 pmol/l (N: < 17 pmol/l ) with a direct fraction of 0.72, alkaline phosphatase 132 IU/l (N: 27-93 IU/l), y-glutamyl transpeptidase 68 U/l (N: 8-46 IU/l), ASAT 58 IU,‘l (N: < 30 II-J/l), ALAT 35 IU,‘l (N: < 30 B-J/l), ammonia 95 kmol/l (N: < 50 pmol/l), serum protein 74 g/l, prothrombin time 15.6 s (contro1:ll.S s), factor V activity 38% (N: 70130%). cu-Fetoprotein was normal. Endoscopic examination showed large oesophageal varices classified as grade 4 according to Paquet, and gastric varices. The patient was examined with a mechanical sector scanner (Technicare AutosectorTM) integrated with pulsed Doppler (Technicare Auto DIIT, Technicare, USA). This system has been calibrated in vitro using a flow phantom [ll]. The examination technique has been described previously. In short, the portal vein was visualised on the real-time two-dimensional image and the Doppler-beam marker was directed at the portal vein. When holding the breath after a normal expiration the image was frozen and the Doppler signal was sampled. Thereafter the two-dimensional image was updated very briefly. The latter procedure reduces the aesthetic quality of the two-dimensional image, but enables revision of correct probe positioning after flowmetry. Duplex Doppler examination was performed in the early morning hours after an overnight fast. After the first measurement the patient took a liquid meal according to Lundh [121, and thereafter measurements were repeated for 60 m in at 5 m in intervals. The Doppler signal could be received adequately, but the best signal was received at an insonation angle of ca. 60”. The morphological image of the liver showed increased reflections
Fig. 1. The top part of the figure shows a longitudinal ultrasound view of the portal vein. The lower part shows the Doppler recordings 5, 24 and 38 min after the intake of a meal (A, B and C, respectively). The arrows indicate the systole. The Doppler graphs show the flow velocity (cm/s, y-axis) over 4 s (x-axis). Hepatopetal flow is shown by the signals above the horizontal, hepatofugal flow by the signals below the horizontal. (A) 5 min after the intake of the meal: hepatopetal flow in the portal vein with a slight pulsatile flow pattern. The cross indicates the beginning of a portal flow wave. (B) 24 min after the intake of the meal: portal venous flow is hepatopetal during diastole; during systole no flow is recorded. The cross indicates the beginning of a portal flow wave. (C) 38 min after the intake of the meal. The portal flow is hepatofugal during systole. During diastole no flow is recorded.
P.J. de Vies et al. /Netherlands Journal of Medicine 47 (199.5)235-240
237
238
P.J. de Vries et al. /Netherlands
Journal of Medicine 47 (1995) 235-240
suggestive of cirrhosis. There was still much ascites and the portal vein diameter was of small caliber (5.1 cm). A large coronary vein with a diameter of 7.6 mm was seen, branching from the portal vein in the lesser omentum and running cranially. The Doppler signal of the portal vein was sampled on the hepatic side of the branching coronary vein. The spleen size was normal. In the fasting state and during the first postprandial measurement the direction of portal venous flow was hepatopetal with a pulsatile flow pattern (Fig. 1A). Ten minutes after the meal an undulating pattern of the flow synchronous with the action of the heart was seen. When hepatic artery signals or systolic artefact signals were recorded simultaneously with the portal venous flow, the portal venous flow occurred in a hepatofugal direction during systole, with undetectable flow during diastole. This pattern alternated with a pattern of diastolic hepatopetal flow and systolic undetectable flow (Fig. 1B). The pattern of systolic hepatofugal and diastolic undetectable flow persisted (Fig. 1C) for 1.5 h. At that time the measurements were ended. During the examination the direction of flow was confirmed at different insonation angles. For reasons of comparability the photographs were taken using the same insonation angles. The direction of flow in the splenic vein was always splenofugal. In the coronary vein it was always hepatofugal. One year after this examination the patient died after an episode of massive irretractable ascites and liver failure. In the intervening period there had been no follow-up of the patient. Although the (Yfetoprotein in serum was never elevated, the suspicion of a hepatocellular carcinoma was confirmed at autopsy. Centrally in the liver a large hepatocellular carcinoma was found with extensive intravascular growth. 3. Discussion The principal finding of this report is that the direction of portal venous flow may be reversed in the early postprandial phase in a patient with severe decompensated liver cirrhosis and portal hypertension. The reversal of portal venous flow appears to be induced by the hepatic arterial
flow. This phenomenon has not been observed before. The reversal of the direction of flow in our patient was unequivocal. The limitations of our ultrasound equipment have been evaluated and at the current settings the equipment was shown to perform well [ll]. Quantitative flow measurements are subject to non-systematic intra-observer variance. A mean coefficient of variation for this intra-observer variability of 14% was found. The direction of flow determined with duplex Doppler has been shown to correspond with cineangiographic results [13]. Visualisation of the caval and portal veins was adequate; they could be clearly distinguished. The portal vein could also be distinguished adequately from other vessels such as the coronary vein. Spontaneous hepatofugal flow is associated more frequently with hepatocellular carcinoma than with cirrhosis without carcinoma [141. The haemodynamic significance of the hepatocellular carcinoma at the time of examination of our patient is indeterminate. At that time the hepatocellular carcinoma was not detected and the blood a-fetoprotein level was normal, also shortly before death, 1 year later. The reversal of the direction of portal venous flow is a significant feature of portal hypertension. In the past the existence of spontaneous reversal of the flow was regarded with scepticism. The reason was that spontaneous reversal was demonstrated with non-physiological measurement techniques. Nowadays, after the development of duplex Doppler techniques, spontaneous hepatofugal flow is a well-recognised phenomenon. The reported incidence of hepatofugal flow in the portal vein ranges from 3 to 15% depending on patient selection and technique of investigation [2,5,15,16]. In end-stage liver disease, hepatofugal flow is detected more often than in earlier stages. The actual reversal of the direction of flow has never been observed, although a stagnant flow with a “to and fro” motion during the respiratory cycle after side-to-side portocaval anastomosis has been reported [ll. The pathophysiology of portal hypertension is described by the classical backward flow theory,
P.J. de Vries et al. /Netherlands
Journal of Medicine 47 (1995) 235-240
which explains elevated portal pressure by an increase in portal venous resistance, and the forward flow theory [17]. The latter is based on the finding of an increased splanchnic inflow. This may sustain the elevated portal pressure in the presence of substantial portal systemic collateral blood flow. The role of the hepatic artery in this hyperdynamic splanchnic circulation is not completely elucidated. By its inflow into hepatic sinusoids it has the potential to modulate sinusoidal pressure and thus portal venous pressure and flow. In liver cirrhosis the influence of the hepatic artery may be relatively large. Small changes in hepatic arterial pressure induced by physiological stimuli may have large effects on portal venous haemodynamics. Sinusoidal pressure may increase as a result of postprandial changes in the hepatic artery. In end-stage liver cirrhosis with sluggish portal flow this may initiate reversal of the direction of flow. The findings in our patient indicate the hepatic artery as the driving force directing blood towards the collateral vascular system. In contrast, it seems unlikely that portosystemic collateral vascular pressure decreases. After a meal the splanchnic inflow and azygos flow increase, the collateral vascular system receiving the major part of the increase in blood flow [4,9,18-221. The prognostic value of reversal of prandial portal flow and increased azygos flow can only be speculated on. Previous studies have not shown any additional risk of variceal haemorrhage in patients with spontaneous hepatofugal flow [2,10]. The significance of our findings is twofold. First it shows that in the early postprandial phase a reversal of portal venous flow can occur. This implies that encephalopathy may be aggravated not only by nutrition-derived humoral substances but also by increased postprandial portosystemic shunting. Secondly, the findings suggest a significant role for the hepatic artery as the driving force behind this postprandial reversal of portal venous flow. References [l] Moreno AH, Burchell AR, Reddy RV, Steen JA, Panke WF, Nealon TF. Spontaneous reversal of portal blood
flow: the case for and against its occurrence in patients with cirrhosis of the liver. Ann Sug 1975;181:346-358. [2] Gaiani S, Bolondi L, Li Bassi S, Zironi G, Siring0 S, Barbara L. Prevalence of spontaneous hepatofugal portal flow in liver cirrhosis. Clinical and endoscopic correlation in 228 patients. Gastroenterology 1991;100:16@-167 [3] Ohnishi K, Saito M, Nakayama T et al. Portal venous hemodynamics in chronic liver disease: effects of posture change and exercise. Radiology 1985;155:757-761. [4] Okazaki K, Miyazaki M, Onishi S, Ito K. Effects of food intake and various extrinsic hormones on portal blood flow in patients with liver cirrhosis demonstrated by pulsed Doppler with the Octoson. Stand J Gastroenterol 1986;21:1029-1038. 151Zoli M, Marchesini G, Cordiani MR et al. Echo-Doppler measurement of splanchnic blood flow in control and cirrhotic subjects. J Clin Ultrasound 1986;14:429-435. [61Ohnishi 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 flowmetty. Am J Gastroenterol 1987;82:507-511. [71 Gaiani S, Bolondi L, Li Bassi S, Santi V, Zironi G, Barbara L. Effect of a meal in healthy humans and in patients with chronic liver disease. Hepatology 1989;9: 815-819. WI Sabba C, Weltin GG, Cicchetti DV et al. Observer variability in echo-Doppler measurements of portal flow in cirrhotic patients and normal volunteers. Gastroenterology 1990;98:1603-1611. [91 Gaiani S, Bolondi L, Fenyves D, Zironi G, Rigamonti A, Barbara L. Effect of propranolol on portosystemic collateral circulation in patients with cirrhosis. Hepatology 1991;14:824-829. UOl Rector WG, Hoefs JC, Hossack KF, Everson GT. Hepatofugal portal flow in cirrhosis: observations on hepatic hemodynamics and the nature of the arterioportal communications. Hepatology 1988;8:16-20. 1111 De Vries PJ. Van Hattum J, Hoekstra JBL, De Hooge P. Duplex Doppler measurements of portal venous flow in normal subjects. Inter- and intra-observer variability. J Hepatol 1991;13:358-363. W-1 Lundh G. Pancreatic exocrine function in neoplastic and inflammatory disease: a simple and reliable new test. Gastroenterology 1962;42:275-280. [I31 Ohnishi K, Saito M, Koen H, Nakayama T, Nomura F, Okuda K. Pulsed Doppler flow as a criterion of portal venous velocity: comparison with cineangiographic measurements. Radiology 1985;154:495-498. [141 Okuda K, Moriyama M. Yasumoto M, et al. Roentgenologic demonstration of spontaneous reversal of portal blood flow in cirrhosis and primary carcinoma of the liver. Am J Roentgen01 1973;119:419-428. [151 Ohnishi K, Saito M, Sato S, et al. Direction of splenic venous flow assessed by pulsed Doppler flowmetry in patients with a large splenorenal shunt. Relation to spontaneous hepatic encephalopathy. Gastroenterology 1985;89:180-185. 1161Burcharth F, Aagaard J. Total hepatofugal portal blood
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