URINARY COPROPORPHYRIN ISOMERS IN CONGENITAL AND ACQUIRED LIVER CHOLESTASIS

E. Rocchi1, P. Ventura2, G. Casalgrandi1, S. Marchini2

1Post Critical Care Unit and 2Medicine II Unit, Department of Medicines and Medical Specialities, University of Modena and Reggio Emilia; Modena, Italy

Proven the key role of liver in heme synthesis and porphyrin metabolism and excretion, urinary porphyrin (and their metabolites) concentrations and/or profiles may result altered in the presence of liver impairment and cholestasis. The present study was aimed at comparing coproporhyrin isomer (CPI) urinary excretion profiles (measured by HPLC methods) in congenital and acquired liver cholestatic syndromes in order to assess the possible diagnostic-functional significance of these assays. The table resumes urinary CPI values and cholestasis parameters in controls and in patients affected by different acquired cholestatic  and Dubin-Johnson syndromes.

Total Plasma

Bilirubin (mg/dl)

Alkaline Fosfatase

(mU/ml)

-GT

(mU/ml)

Urinary Total Coproporhyrin

(nnmol/mmol creatinine)

Urinary Coproporphyrin I/III ratio

Plasma Tri-oh / Di-oh Bile acid ratio

Controls

(n=16)

0.8 ± 0.4

142 ± 37

13 ± 1.7

71 ± 29

0.53 ± 0.1

3.5 ± 0.6

Intrahepatic Cholestasis of Pregnancy  (n=12)

1.6 ± 1.2*

250 ± 26**

80 ± 7.5**

169 ± 50**

1.9 ± 0.2**

3.3 ± 1.2°

Viral Chronic Hepatitis

(n=13)

6.5 ± 1.9**

249 ± 58**

351 ± 58**

248 ± 90**

1.5 ± 0.2**

2.3 ± 1.2*

Liver

Cirrhosis

(n=21)

5.7 ± 1.0**

377 ± 86**

85 ± 16**

268 ± 163*

1.23 ± 0.4**

0.9 ± 0.6**

Primary Biliary Cirrhosis

(n=8)

4.9 ± 1.3**

386 ± 54**

479 ± 94**

304 ± 136**

1.9 ± 0.7**

3.7 ± 1.3°

Extrahepatic

Biliary Obstruction (n=20)

17  ± 2.3**

382 ± 42**

435 ± 74**

311 ± 102**

1.4 ± 0.4**

4.2 ± 1.8°

Drug-Induced Cholestasis

(n=10)

7.2 ± 3.4**

247 ± 36*

88 ± 8.1**

286 ± 86*

1.7 ± 0.2**

2.9 ± 1.6°

Dubin-Johnson Syndrome

(n= 4)

2.7 ± 0.2**

167 ± 53°

15 ± 3.1°

106 ± 11*

5.1 ± 1.5**

2.6 ± 0.9*

 

Statistical vs. control group : ° p=ns; *p<.05; **p<.01. Anova for independent samples.

The abnormal distribution of urinary CP isomers in different cholestatic diseases is suggested to be the consequence of a retention effect due to biliary excretion impairment, nevertheless a new synthetic active response to cholestasis may be also relevant and particularly important especially in Dubin-Johnson Syndrome. In cholestastic diseases the inversion of urinary CP isomers ratio may be also considered an early signal of entero-hepatic circulation derangement even in those conditions known as “dissociated cholestasis” (moderate or no jaundice), such as pregnancy cholestasis. The amount of isomer I production and secretion rate, seems also to be correlated to the functional status of hepatocyte: the higher tri-oh/di-oh ratio (an extremely sensible functional test) and the greater increase of copro I/copro III ratio in pregnancy cholestasis , in primary biliary cirrhosis and in obstructive forms (scanty liver derangement) with respect to liver cirrhosis, chronic hepatitis and drug-induced cholestasis, supports this hypothesis.