ERYTHROCYTE AND LIVER PORPHOBILINOGEN DEAMINASE ACTIVITY IN CIRRHOSIS AND CLINICAL OR EXPERIMENTAL CHOLESTASIS

Yalouris A, Manganas D, Yannakos G, Triantafyllou G, Danias P, Kantartzis K, Raptis S

 

Second Department of Internal Medicine, Athens University, Evangelismos Hospital, Athens, Greece

 

 

Porphobilinogen deaminase (PBG-D), the third enzyme in the haem synthetic process, mainly expressed in the erythrocytes and the liver, has a key role in the pathogenesis of the acute porphyrias. In the present study we investigated the effect of cirrhosis or cholestasis on this enzyme. We have found that: 1) Erythrocyte PBG-D activity was significantly increased (p=0.0003) in 27 patients with non-alcoholic liver cirrhosis (19.89±6.65 nmoles/h.l) and in 24 patients with extrahepatic cholestasis (20.69±11.17 nmoles/h.l) as compared to 30 healthy controls (12.77±4.76 nmoles/h.l). The enzymic activity was positively correlated to the prothrombin time in both patient groups and negatively to the alkaline phosphatase in the cholestatic group. 2) Erythrocyte PBG-D activity in blood samples from normal subjects significantly increased when their homologous plasma was substituted by that of patients with cholestasis (p<0.001) or cirrhosis (p=0.05) although it remained lower than that of the respective patients' blood samples. 3) In 8 rabbits, after ligation of the common bile duct, PBG-D activity significantly increased both in the erythrocytes (from 30.26±10.33 to 48.87±15.82 nmoles/h.l, p=0.002) and the liver (from 13.27±4.79 to 17.68±5.42 nmoles/h.g, p=0.035). In 8 sham-operated rabbits erythrocyte PBG-D also increased (from 29.60±9.85 to 33.32±12.23 nmoles/h.l, p=0.016) but in a significantly lower degree than in the "cholestatic" group (111.10±10.95% versus 167.96±41.64%, p=0.006) while the hepatic enzyme remained unchanged (from 13.40±3.85 to 13.83±7.21 nmoles/h.g, p=0.80). 4) In 5 patients operated for extrahepatic cholestasis the mean hepatic PBG-D activity was higher than in other 5 who underwent cholecystectomy without having cholestasis (12.63±3.24 versus 9.64±1.17 nmoles/h.g) but the difference was not statistically significant (p=0.11). In conclusion, erythrocyte and liver PBG-D activity is considerably increased in cholestasis and cirrhosis and plasma factors seem to play a role in it