The Abnormal Hepatic Scan of Chronic Liver Disease: Its Relationship to Hepatic Hemodynamics and Colloid Extraction

71:210-213, 1976 Copyright ® 1976 by The William. &Wilkin. Co.

Vol. 71, No.2 Printed in U.S.A.

GASTROENTEROLOGY

THE 'ABNORMAL HEPATIC SCAN OF CHRONIC.LIVER DISEASE: ITS RELATIONSHIP TO HEPATIC HEMODYNAMICS AND COLLOID EXTRACTION MASUMASA HORISAWA, M.D., GREGORY GOLDSTEIN, M.D., ALAN WAXMAN, M.D., AND TELFER REYNOLDS, M.D.

Departments of Medicine and Nuclear Medicine of the University of Southern Cali/omia School of Medicine, and the Liver Service, John Wesley County Hospital; Los Angeles, California

To help explain the characteristic hepatic scan pattern of chronic liver disease, the degree of scan abnormality (scan score, SS) after administration of technetium-99m sulfur colloid (Tc) was compared with data obtained at hepatic vein catheterization in 28 patients. Although SS showed a correlation with wedged hepatic vein pressure (r = +0.491), the scan abnormality was not directly due to portal hypertension because it remained unchanged when the latter was relieved by portacaval shunt. Also, the scan abnormality was found to be unrelated to a low hepatic blood flow. Scan abnormality was not attributable primarily to hyperactivity of the reticuloendothelial (RE) cells of the spleen and bone marrow since fractional clearance (K) of Tc from the blood was decreased rather than increased in patients with abnormal scans. SS was inversely correlated with K of Tc (r = -0.575) and with hepatic extraction efficiency for Tc (r = -0.673), showing that the basic abnormality was poor extraction of the colloid by the RE cells of the liver with a resultant increase in the amount available for extrahepatic localization. Indirect evidence suggests that this poor extraction of colloid is due to intrahepatic shunts bypassing hepatic RE cells. Mottling and reduction in intensity of the hepatic peripheral vein every 3 min for 12 min, and analyzed for image with increased isotope uptake by spleen and bone content of ICG and Tc. Results were plotted on semilogarithmarrow are characteristic features of the scan in chronic mic paper, with time as the abscissa. Fractional clearances of liver disease.,·a Several studies·-· have suggested that lCG and Tc were calculated from the formula In 2/t .. , where In 2 is the natural logarithm of 2, or 0.693, and t .. is the time in min the scan abnormality is due to portal hypertension required for the concentration of leG or Tc to diminish by and/or portal collateral flow. However, it has been our 50%.1-11 ER values of lCG and Tc were calculated as the experience that the abnormal scan pattern does not difference between peripheral and hepatic venous levels of Tc change when portal hypertension is relieved by por- and lCG, expressed as a fraction of the peripheral vein level. tacaval shunt. Therefore, to understand better the HBF was calculated from the ICG data, using the formula pathogenesis of the abnormal scan pattern we have HBF = (KIER) x BV, where BV is blood volume. 10 If ER was compared it with hemodynamic measurements made at less than 0.05, HBF was not calculated. Blood volume was hepatic vein catheterization. These include wedged calculated by extrapolating the peripheral venous plasma leG hepatic vein pressure (WHVP), hepatic blood flow concentration to time zero, dividing this value into the dose of (HBF), hepatic extraction rate (ER), and fractional leG administered, and then multiplying by [100/(100 clearance (K) of" indocyanine green (leG) and techne- hematocrit) J. Liver scan was performed after hepatic vein catheterization was ended. The liver scan was scored on a 0 to 9 tium-99m sulfur colloid (Tel. Results indicate that the basis by the criteria of Castell and Johnson' as follows: for liver major reason for the abnormal scan pattern is poor mottling, 0 c none, +1 = mild, +2 = more marked with extraction of the radioactive colloid by the liver. scattered defects, and +3 - liver faintly visualized. For splenic Materials and Methods Twenty-eight patients with chronic liver disease underwent hepatic vein catheterization, at which time WHVP was measured by a technique previously described.' Then, 0.5 mg of lCG per kg and 2 mc of Tc were given intravenously and blood samples were drawn simultaneously from hepatic vein and Received June 12, 1974. Accepted February 28, 1976. Preliminary results were presented to the American Association for the Study of Liver Disease, Chicago, Illinois, October 30, 1974. Dr. Horisawa'. address is Nagoya University.School of Medicine, Nagoya, Japan. Dr. Goldstein's addresa is Newtown. Australia. No reprints available. 210

uptake,O = none, +1 = less than liver uptake. +2 - equal to liver uptake, and +3 - greater than liver uptake. For bone marrow uptake, 0 - none, + 1 = faint visualization. +2 = more marked but less than liver uptake, and +3 = equal to liver uptake. Scan score (SS) was compared with all of the hemodynamic measurements, with prothrombin, which reflects hepa· tocellular function, and with serum globulin. which has been thought to reflect bypass of intrahepatic reticuloendothelial (RE) cells. 12• 11

Results Results of the study are summarized in Table 1. All patients except one had portal hypertension, as indi-

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LIVER SCAN PATTERN AND HEPATIC HEMODYNAMICS TABLE 1

Caoe

WHVP-

ss·

2 3 4 4' 5 6 7 8 9 10 11 12 13 14 15 15' 16 17 18 19 20 21 22 23 24 25 26 27 28

13 11 20 19 16 12 19 10 15 4 19 )3 17 19 5 18 20 19 26 20 15 14 7 19 10 7 8 12 13 12

6 5 9 9 9 8 6 3 5 2 6 6 7 5 7 8 7

leG"

ER'

K'

0.220 0.530 0.020 0.070 0.100 0.090

0.074 0.071 0.007 0.030 0.024 0.024

0.048 0.440 0.200 0.210

0.024 0.182 0.043 0.022

0.226 0.720 0.077 0.060 0.170 0.143 0.690 0.250 0.099 0.387 0.134 0.336 0.643 0.712 0.053 0.123 0.022

0.124 0.063 0.037 0.026 0.042 0.043 0.167 0.060 0.028 0.107 0.058 0.068 0.220 0.173 0.038 0.035 0.017

HBF"

Tc' ER

K

0.460 0.730 0.100 0.270 0.133 0.120

0.165 0.151 0.065 0.107 0.107 0.112 0.090 0.124 0.126 0.248 0.060 0.043 0.082 0.182 0.204 0.103 0.090 0.107 0.077 0.173 O.llS 0.099 0.173 0.135 0.095 0.231 0.131 0.128 0.082 0.099

mllm;n

5 5 4 7 5 1 7 3 1 6 7 9

1005 529 1866 1201 1810

1336 389 2356 530 1831 1291 1012 918 1046 1346 1689 755 1215

990 2522 891

Globulin

Prothrombin'

g/lOOml

0.250

0.640 0.350 0.790 0.200 0.160 0.280 0.244 0.562 0.111 0.137 0.115 0.321 0.596 0.490 0.192 0.517 0.322 0.344 0.638 0.600 0.382 0.229 0.245

4.0 4.3 3.6 2.9 3.8 3.4 3.6 4.6 4.2 4.7 3.6

54 43 38 40 23 68 100 31 100 70 36

4.2 3.7 2.8 3.5

80 36 72

6.7 3.1 4.3 4.6 4.7 4.2 4.4

50 100 52 90 92 52 100 90

44

5.7 4.0

• WHVP, wedged hepatic vein pressure in mm Hg above inferior vena cava pressure. • SS, scan score. c ICG. indocyanine green. d HBF. hepatic blood flow by fractional clearance method with lCG . • Tc, technetium-99m sulfur colloid. I Per cent of control (Owren-Ware method, normal values of over BO). , ER. hepatic extraction .ate. • K, fractional clearance. I After portacaval shunt. j HBF not calculated because of failure to measure hematocrit on the day of the hepatic vein catheterization.

cated by a WHVP level more than 4 mm Hg above inferior vena caval pressure. 7 K and ER of leG were generally decreased, often markedly so, from the usual normal values of 0.207 ± 0.052 and 0.698 ± 0.199, respectively. 10. II Also, K and ER for Tc were markedly reduced in most patients from the normal values quoted by Mundschenk et a1." SS showed a poor positive correlation with HBF (r = 0.262), indicating that the abnormal scan pattern was not due to decreased HBF. There was positive correlation between WHVP and SS (r = 0.491) (fig. I), but SS Was not directly related to portal hypertension, since SS remained unchanged when portal hypertension was relieved by end-to-side portacaval shunt (table 1, cases 4 and 15). Portal pressure at surgery fell from 56 to 32 cm saline in case 4, and from 53 to 25 em saline in case 15

after completion of the shunt.· Significant negative correlation between SS and K ofTc (r = -0.575) (fig. 2) indicates that the scan abnormality was not primarily due to increased activity of extrahepatic RE cells but rather to decreased total hepatic clearance of Tc. Negative linear correlation between SS and ER of Tc (r = -0.673) (fig. 3) indicates that decreased hepatic clearance was due to inefficient hepatic extraction rather than to decreased HBF. Also, there were negative linear correlations between ER of leG and SS (r = -O.612); • Lack of definite dP4'l'f!8se in WHVP after portacavaishunt in these two patients presumably was due to failure to decompress the liver. which is surprising in view of the measured fall in HBF. The shunt was shown to be patent at the time of hepatic transplantation 1 year later in case 15. and there have been no further episodes of variceal bleeding over a 2-year period in case 4.

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HORISA WA ET AL.

varices. Millette et a1. 11 found that the extrahepatic uptake of radioactive colloidal gold conelated positively with the portohepatic pressure gradient and negatively ·6 with the fractional clearance of ICG . 7 • Although we found a positive correlation between SS 6 and WHVP, our experience has been that the abnormal scan pattern persists after portal hypertension is relieved 5 • by portacaval shunt. Mean SS was 6.3 in 30 patients 4 • hospitalized in our Liver Unit who had had prior 3 portacaval shunts. In 12 patients, including the 2 in table 1, who had scans performed both before and after 2 • portacaval shunt, mean SS was 5.8 preoperatively and I. WHVP 6.4 postoperatively, when the scans were read "blindly" by two of the authors (A. W. and T. R.). When the 12 25 15 20 10 5 pairs of scans were compared, with the dates concealed, FIG. 1. Correlation between wedged hepatic vein pressure (WHVP) the postoperative scan was judged to be more abnormal and scan score (S8); r - 0.491; n - 30; P < 0.01; regression line, y 0.223% + 2.419. WHVP is el
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LIVER SCAN PATTERN AND HEPATIC llEMODYNAMICS

function using heat-denatured albumin labeled with "'I. From observing fractional clearance with increasing doses of the colloid, they concluded that the phagocytic capacity of the RE system is only modestly reduced in cirrhosis. Poor extraction of the colloid, even with tracer doses, was found in the few patients in both studies who underwent hepatic vein catheterization. Shaldon et al." also found reduced extraction of colloid in cirrhosis, which improved after portacaval shunt. They ascribed the poor extraction to intrahepatic shunting. The significant correlations between K of leG and K of Tc (+0.781), and ER of leG and ER of Tc (+0.780), are of interest and could be explained by intrahepatic shunts that result in decreased extraction both by hepatocytes and RE cells. It has been proposed that measurement of intrahepatic shunting of portal blood might prove useful in selection of patients for portacaval shunt." The liver scan pattern may provide a rough assessment of this measurement. Bj0rneboe et al. U have proposed that the hyperglobulinemia of chronic liver disease might be due to intrahepatic shunts that allow gut antigens to bypass hepatic RE cells, and evidence favoring this concept was also found by Triger et al. 13 However, in our patients there was no positive correlation between SS and serum globulin (r = -0.231), and between ER of Tc and serum globulin (r = 0.037), providing no support for this theory. Our results further emphasize previous observations'S. u. "." that calculation of HBF from fractional clearance of various radioactive colloids without measurement of hepatic extraction rate gives erroneous results in patients with chronic liver disease. Even if hepatic extraction is measured, HBF calculation will be inaccurate if there is substantial uptake of colloid by the bone marrow. '8

213

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