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Latent Liver Disease in Persons Recovered from Catarrhal Jaundice *And in Otherwise Normal Medical Students As Revealed

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Latent Liver Disease in Persons Recovered from Catarrhal Jaundice *And in Otherwise Normal Medical Students As Revealed LATENT LIVER DISEASE IN PERSONS RECOVERED FROM CATARRHAL JAUNDICE *AND IN OTHERWISE NORMAL MEDICAL STUDENTS AS REVEALED BY THE BILIRUBIN EXCRETION TEST By ARTHUR KORNBERG (From the Department of Medicine, University of Rochester School of Medicine and Dentistry and the Medical Clinics, Strong Memorial and Rochester Municipal Hospitals, Rochester, New York) (Received for publication December 29, 1941) The frequency with which chronic non-hemoly- regarded as indicative of liver damage. Cholecystogram. tic jaundice occurs in otherwise healthy young A dose of tetraiodophenolphthalein was administered persons is not nor orally 18 and 12 hours before the test. Fragility of red commonly recognized, 'is it blood cells to hypotonic solutions of sodium chloride. usually appreciated how often an uncomplicated The method of Waugh and Asherman (4) was used attack of catarrhal jaundice is followed by residual with saline. Determinations were made with the Evelyn liver dysfunction which persists long after the colorimeter. Sedimentation rate. The Wintrobe method acute episode. was used. Values from 0 to 9 mm. per hour were re- The present study was the acci- garded as normal for males. Reticulocyte count. The prompted by "wet" method was used. A drop of capillary ear blood dental discovery of a relatively large number of was placed on a dry film of cresyl blue (in saturated medical students with chronic jaundice and a alcohol solution), and the reticulocytes in 1000 red blood history of a previous attack of catarrhal jaundice cells were counted. The normal range was considered to in two of them. A group of persons long recov- be 0 to 2.5 per cent. Urobilin. The Schlessinger reaction ered from catarrhal was and was used for the qualitative determination of urobilin in jaundice investigated the urine. A definite fluorescence in the filtrate was a also a control group of persons presumably nor- positive test. Urobilinogen. Ehrlich's aldehyde method mal. The bilirubin excretion test was used in all was employed for the detection of excess urobilinogen in cases because of its reliability in detecting lesser the urine. A red color in a dilution greater than 1: 10 degrees of liver dysfunction. was a positive test. Vitamin A absorption test and plant pigment determination. The method of Chesney and Mc- Coord was used. METHODS Fish liver oil containing 7000 U.S.P. vitamin A units for each kilogram of body weight was Bilirubin excretion test. The method of Von Bergmann given. The vitamin A content of the blood was measured and Eilbott (1, 2) was used with modifications. Bilirubin by the McCoord and Luce-Clausen (5) modification of (Eastman Kodak) was given under basal conditions in the Carr and Price technique. The analysis for the a dose of 1.5 mgm. per kilogram of body weight. No carotenoids or plant pigments (xanthophyll and carotene), untoward reactions were observed when fresh materials which was necessary for the correction of vitamin A were used. A retention at 4 hours in excess of 15 per results, was done by the method of Clausen and Mc- cent was regarded as abnormal. Coord (6). Bilirubin determination, qualitative and quantitative. The photoelectrometric method of Malloy and Evelyn (3) RESULTS was used. Hemolysis was avoided and analyses which 1. Persons presumed to be normal. For this failed to check within 2 per cent were rejected. The Evelyn colorimeter manual gives the range of normal group, subjects were selected who gave no indi- serum values for direct bilirubin as 0.1 to 0.4 mgm. per cation of liver dysfunction by history or physical cent and for indirect (total) bilirubin as 02 to 0.7 mgm. examination. They were in the younger age per cent. The ratio of the direct to indirect bilirubin is groups and were recovering from minor surgical given clinical significance when elevated values occur. The ratio is high (0.60 to 0.80) in obstructive jaundice, operations. intermediate (025 to 0.55) in diffuse parenchymal damage, The basal serum bilirubin concentrations which and low (0.15) in hemolytic jaundice. were generally below 0.8 mgm. per cent are in Bromsulphalein excretion test. A dose of 5 mgm. per Table I, and the individual values during the ex- kilogram of body weight was injected intravenously and cretion test are in Table II. Of 22 persons tested, a retention in excess of 10 per cent at 30 minutes was regarded as abnormal. Galactose tolerance test. Forty 95 per cent retained less than 15 per cent of the grams of the sugar were given orally; a urinary output injected bilirubin and 73 per cent retained less of more than 3 grams within 5 hours after ingestion was than 10 per cent. The sole person who retained 299 300 ARTHUR KORNBERG TABLE I TABLE III Distribution of basal bilirubin values in persons presumed to Mean bilirubin excretion test values in persons presumed to be normal be normal and others long recovered from catarrhal jaundice Range: 0.114 mgm. per cent to 0.900 mgm. per cent Mean concentration: 0.398 mgm. per cent The values at 0 minutes are the basal bilirubin levels. Standard deviation: 0.184 mgm. per cent Ci - Co = Concentration at time, "i," minus basal bilirubin concentration, "0". The mean bilirubin values are followed by their standard errors. The mean values Serum bilirubin Number of cases Per cent of total for the two groups were significantly different at each time mgm. per cent period except the one at 5 minutes. 0.000-0.199 3 10 0.200-0.399 11 38 "Post-catarrhal jaundice" 0.400-0.599 12 41 "Normal" group group 0.600-0.799 2 7 0.800-0.999 1 4 Time Num- Coef- Num- Coef- ber Mean value ficient ber Mean values ficient 100 of (Ci-Ce) of vari- of (C;-CG) of vari- Total 29 cases ation cases ation min- TABLE II utes 0 29 0.3964-0.034 0.460 17 0.616±k0.061 0.408 Individual bilirubin excretion test values in persons pre- 5 22 2.76040.106 0.181 16 2.940±4-0.080 0.109 sumed to be normal 30 29 1.32040.065 0.268 17 1.65040.085 0.212 Per cent retention at 240 minutes 60 29 0.710±0.048 0.366 17 1.120±0.085 0.312 C240 minutes - Co minutes X 100 90 26 0.490±40.039 0.408 17 0.870±40.085 0.402 C minutes- CO minutes 240 22 0.240±=0.030 0.584 17 0.540±40.073 0.506 Serum biLirubin in Table III. Figure 1 contains a composite Case~~Age-- - - - - -___ ~~~~~~~~~~~~~retention~~Per cent num- Age 0 5 30 60 90 240 ati240 curve of these mean bilirubin values, and Figure min- min- min- min- min- min- minutes utes utes utes utes utes utes 2 shows the linear relationship which is obtained when these values are plotted against the logarithm mgm. mgm. mgm. mgm. mgm. mgm. years per per per er per pe of time. cent cent cent cent cent cent 1 5 0.298 2.430 1.330 0.881 0.663 0.503 9.4 2. Persons long recovered from catarrhal jaun- 2 29 0.114 2.140 1.200 0.628 0.522 0.282 8.4 dice. The subjects for this group were chosen 3 28 0.114 2.610 1.220 0.700 0.556 0.332 8.8 4 31 0.264 2.810 1.240 0.863 0.628 0.503 9.4 completely at random from the hospital records 5 16 0.400 3.250 1.560 1.010 0.790 0.538 4.9 of adequately studied and confirmed cases of 6 16 0.645 3.920 2.400 1.590 1.300 0.975 10.1 7 14 0.522 3.860 2.160 1.360 1.070 0.682 4.8 acute catarrhal jaundice. They were generally 8 13 0.592 4.200 2.450 1.630 1.320 0.900 8.6 children or young adults who, during their acute 9 13 0.418 3.060 1.520 0.938 0.718 0.645 8.7 10 20 0.574 3.770 2.100 1.440 1.090 0.918 10.6 episode of jaundice, had symptoms of malaise, 11 14 0.490 3.350 2.030 1.340 1.070 0.790 10.5 nausea, and abdominal pain. There was a sudden 12 23 0.430 3.330 2.030 1.430 1.110 0.830 13.8 13 19 0.131 2.380 1.010 0.592 0.434 0.204 3.6 onset of jaundice which often coincided with 14 23 0.500 3.120 1.590 1.010 0.790 0.540 1.5 symptomatic improvement. A familial incidence 15 20 0.214 3.460 1.610 1.002 0.790 0.522 9.6 16 33 0.282 3.060 1.740 1.010 0.700 0.452 6.1 was noted in half of the cases. Fever, hepato- 17 25 0.503 4.610 2.590 1.730 1.350 0.955 11.0 megaly, leukopenia with an increase in the per- 18 23 0.900 4.320 2.960 2.430 2.080 1.560 19.6 19 24 0.538 3.770 2.170 1.420 1.120 0.790 7.7 centage of mononuclear cells, bilirubinuria, and 20 22 0.347 2.060 1.080 0.760 0.450 5.9 acholic stools were found in most cases. Hyper- 21 20 0.330 2.780 1.420 0.880 0.540 8.6 22 20 0.420 3.240 1.460 0.810 0.560 5.0 bilirubinemia was always present with an imme- 23 7 0.247 1.090 0.647 0.469 diate direct van den Bergh reaction when tested.
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