Effect of Phenobarbitone on Plasma [14C]Bilirubin Clearance in Patients with Unconjugated Hyperbilirubinaemia

1. The clearance of a tracer dose of [14C]bilirubin from the plasma was studied in patients with Gilbert's syndrome, congenital non-haemolytic jaundice, haemolytic jaundice and in normal subjects. Clearance was significantly impaired in the patients with Gilbert's syndrome and in those with congenital non-haemolytic jaundice when compared with the normal subjects, and was normal in the patient with haemolytic jaundice. 2. Treatment for 2 weeks with phenobarbitone (180 mg/day) lowered the plasma bilirubin concentration and improved all indices of plasma clearance of the isotope in patients with Gilbert's syndrome, so that they became indistinguishable from those of normal subjects. The improvement in plasma [14C]bilirubin clearance in these patients was associated with modest increases in hepatic bilirubin glucuronyl transferase in some subjects. 3. Phenobarbitone treatment improved plasma bilirubin concentrations and plasma [14C]bilirubin clearance in patients with congenital non-haemolytic jaundice, so that they resembled those seen in patients with untreated Gilbert's syndrome. Despite this improvement hepatic bilirubin glucuronyl transferase activity remained undetectable. 4. These results are compatible with the hypothesis that Gilbert's syndrome is a manifestation of a relative deficiency of hepatic bilirubin glucuronyl transferase, and differs from congenital non-haemolytic jaundice only in severity.

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Effect of An Intraluminal Food-Bulk on Low Calorie Induced Hyperbilirubinaemia

Clinical Science ◽

10.1042/cs0660493 ◽

1984 ◽

Vol 66 (4) ◽

pp. 493-496 ◽

Cited By ~ 2

Author(s):

Giovanni L. Ricci ◽

Riccardo R. Ricci

Keyword(s):

Caloric Restriction ◽

Serum Bilirubin ◽

Bilirubin Concentration ◽

Gilbert’S Syndrome ◽

Absorbable Material ◽

Low Calorie ◽

Gilbert's Syndrome ◽

Normal Individuals ◽

Plasma Bilirubin

1. To test the hypothesis that the presence of food in the intestine plays a role in the control of serum bilirubin levels, the effect of a 1674 kJ (400 kcal) diet, including non-absorbable material able to produce an intestinal bulk, was compared with the effect of caloric restriction alone. 2. In normal individuals (n = 10) the rise of plasma bilirubin was comparable after the two trials. In patients with Gilbert's syndrome (n = 18), bilirubin concentration rose to a much greater extent during the caloric restriction as compared with controls, and to a lesser extent (P<0.001) after the bulky diet, as compared with caloric restriction alone in the same patient. 3. It is proposed that a factor originating from the intestine, perhaps a hormone, the release of which is dependent on the presence of food-bulk, plays a role in the control of hyperbilirubinaemia associated with caloric restriction.

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Definition of a Conjugation Dysfunction in Gilbert's Syndrome: Studies of the Handling of Bilirubin Loads and of the Pattern of Bilirubin Conjugates Secreted in Bile

Clinical Science ◽

10.1042/cs0550063 ◽

1978 ◽

Vol 55 (1) ◽

pp. 63-71 ◽

Cited By ~ 5

Author(s):

C. A. Goresky ◽

Ellen R. Gordon ◽

E. A. Shaffer ◽

P. Paré ◽

D. Carassavas ◽

...

Keyword(s):

Caloric Intake ◽

Normal Subjects ◽

Hepatic Uptake ◽

Gilbert’S Syndrome ◽

Pigment Pattern ◽

Gilbert's Syndrome ◽

Plasma Bilirubin ◽

Average Proportion ◽

Conjugation Process ◽

Biliary Pigment

1. Intravenous doses of bilirubin (3.4 μmol/kg) were given to normal subjects and patients with Gilbert's syndrome. Both groups displayed an identical initial disappearance of a substantial proportion of the bilirubin but, late in time, the Gilbert's patients exhibited reduced clearance with a sustained elevation of the plasma bilirubin and no reflux into the plasma space of conjugated bilirubin. Increasing the dose in normal subjects (by factors of 3 and 6) failed to reproduce the response found in the Gilbert's patients. 2. In the bile-containing duodenal aspirates of Gilbert's patients the average proportion of bilirubin found as bilirubin diglucuronide was 68% (normal 88%) and of bilirubin monoglucuronide, 23% (normal 7%). Both differences were significant at the P < 0.001 level. In the Gilbert's patients restriction of caloric intake to 1569 kJ/day for 2 days characteristically raised the serum bilirubin with no modification of the biliary pigment pattern; phenobarbital (180 mg/day for 2 weeks) decreased the plasma bilirubin to the normal range with, concomitantly, a reversion of the biliary pigment pattern towards normal. 3. We conclude that there is no hepatic uptake defect in Gilbert's syndrome but that there is decreased activity in the conjugation process underlying the addition of the second glucuronic acid moiety to bilirubin, to form bilirubin diglucuronide.

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Jaundice

10.1093/med/9780199568741.003.0031 ◽

2018 ◽

Author(s):

Satish Keshav ◽

Alexandra Kent

Keyword(s):

Pancreatic Cancer ◽

Clinical Approach ◽

Bilirubin Concentration ◽

Gilbert’S Syndrome ◽

Gilbert's Syndrome ◽

Mucous Membranes ◽

Plasma Bilirubin

Jaundice, also known as icterus, is the yellowish discolouration seen in skin, mucous membranes, and sclerae when the plasma bilirubin concentration is >40 μ‎mol/l. Jaundice may arise from increased production of bilirubin, for instance, in haemolysis; from reduced conjugation in the liver, as in Gilbert’s syndrome; or from reduced excretion via bile, as in intra-hepatic cholestasis. Jaundice also occurs when the flow of bile is obstructed, for instance, by gallstones or pancreatic cancer (extra-hepatic cholestasis). The clinical approach to the jaundiced patient is described in this topic.

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Hepatic Bilirubin UDP-Glucuronyl Transferase Activity in Liver Disease and Gilbert's Syndrome

New England Journal of Medicine ◽

10.1056/nejm196906052802303 ◽

1969 ◽

Vol 280 (23) ◽

pp. 1266-1271 ◽

Cited By ~ 190

Author(s):

Martin Black ◽

Barbara H. Billing

Keyword(s):

Liver Disease ◽

Transferase Activity ◽

Gilbert’S Syndrome ◽

Glucuronyl Transferase ◽

Gilbert's Syndrome

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An Evaluation of Bilirubin Kinetics with Respect to the Diagnosis of Gilbert's Syndrome

Clinical Science ◽

10.1042/cs0540539 ◽

1978 ◽

Vol 54 (5) ◽

pp. 539-547

Author(s):

L. Okolicsanyi ◽

O. Ghidini ◽

R. Orlando ◽

S. Cortelazzo ◽

G. Benedetti ◽

...

Keyword(s):

Storage Capacity ◽

Hepatic Clearance ◽

Normal Subjects ◽

Tolerance Test ◽

Gilbert’S Syndrome ◽

Transfer Rates ◽

Essentially Normal ◽

Gilbert's Syndrome ◽

Relative Storage Capacity ◽

Kinetics Of

1. The kinetics of the plasma disappearance of bilirubin (2 mg/kg intravenously) were studied in 106 patients with Gilbert's syndrome and in 13 normal subjects. 2. All patients had significant decreases in hepatic bilirubin clearance and transfer rates from plasma to liver, resulting in increased values for plasma retention at 4 h. The calculated value for unconjugated bilirubin production was normal in 40% of patients and increased in the remainder. 3. In 29 of the Gilbert's patients their bromosulphthalein kinetics were studied 1 week before the bilirubin test. These results were essentially normal and it was concluded that the hepatic clearance mechanisms for bilirubin and bromosulphthalein are different. 4. In 10 patients the bilirubin transport maximum (Tm) was found to be low whereas the relative storage capacity (S) was normal. Phenobarbitone treatment in four patients resulted in an increase in Tm, and S decreased in two patients and remained unchanged in the other two. 5. These results support the hypothesis that there are several variants of Gilbert's syndrome and that the bilirubin tolerance test is a useful diagnostic test.

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