(5) in Diseases

Jugoro Takeuchi and Akira Takada .The First Department of Internal Medicine, School of Medicine KanazawaUniversity

It has been widely recognized that hypoproteinemia, especially , due to the decrease of albumin synthesis is frequently found in liver diseases. HyperƒÁ-globulinemia has also been encountered in liver diseases. In this study, an attempt has been made to elucidate the abnormality of albumin and clinical sig- nificance of hypoalbuminemia, compared with that of ƒÁ-, in liver diseases. Clinical significance of hypoalbuminemia Hypoalbuminemia was encountered in over 90%of the patients with liver diseases. The level of albumin decreased with the progression of the stage of liver disease. There was no correlation between the level and various , except between the serum albumin level and B.S.P. retention test (P<0.05) in liver cirrhosis. Intensity of hypoalbuminemia was not different between chronic active and inactive liver diseases. Differences of the serum albumin level in liver with and without , and with and without portal hypertension were not statistically significant, although the ascites group showed a lower serum albumin level than the non-ascites group. Amongthree types of cirrhosis (type A: multilobular cirrhosis with broad fibrous band, type B : multilobular cirrhosis with narrow fibrous band, type C : sublobular cirrhosis), types A and B showed lower serum albumin levels than those of type C, but A and B showed almost the same serum albumin levels. The significance of various hepatic tests in judging the prognosis of liver cirrhosis was studied. Only abnormality in the serum albumin level and B. S. P. test correlated to poor prognosis in liver cirrhosis. These results suggest that the lowering of the serum albumin level reflects some special type of liver injury which is not detected by the other hepatic tests. Estimation of the serum albumin level gives the advantage of evaluating the severity and progression of liver injury, especially prognosis of liver cirrhosis. 131I-albumin turnover 13I-albumin turnover was studied by the method of Berson et al. The half-life time of the albumin (T1/2) was 10.5 days in the control group, 10.1 days in acute , ll.3 days in chronic hepatitis and 15.9 days in liver cirrhosis, respectively. Liver cirrhosis showed a significantly longer half-life time than the control group. The degradation rate (D. R.) of albumin, expressed by g./kg./day in acute and chronic hepatitis was not different from that in the control group, but cirrhosis showed a significantly lower D. R. than the control group. However, the difference between 306 Takeuchi and Takada Jap. J. Med. 1968

D.R. in the control and chronic hepatitis was significant, when D. R. was expressed as g./cm./day. The exchangeable albumin pool (E.A.P.) significantly decreased in three liver diseases and the circulating albumin (C: A.) decreased in chronic hepatitis and liver cirrhosis. On the other hand, the extravascular albumin (E. V.A.) showed a tendency to decrease in three liver diseases, but the decrease was not statistically significant. The correlation coefficients between the serum albumin level and each variation of the albumin turnover were higher in order of D.R., E.A.P,, C.A. and E.V.A. The migration rate of albumin from the intravascular to extravascular compartment inclined to decrease in the liver diseases. Judged histologically, the turnover rate of albumin did not correlate to the activity of the liver diseases. Although differences of TV2 and D. R. of albumin, between cirrhosis with and without portal hypertension were not observed, the ascites group showed a lower T72 and D. R. of aLbuminthan the non-ascites group. Therefore, the abnormality of albumin turnover is considered to be characterized by a decrease of D.R. and E,V.A. The changes of serum albumin sharply reflect the changes of D.R, of albumin. The turnover changes of albumin are well correlated with the severity or progression of liver disease, but not the activity of liver injury. 131I-ƒÁ-globulin turnover The turnover changes of ƒÁ-globulin were studied using 131I-labelled IgG by the method of Berson et al. T1/2 of ƒÁ-globulin was 9.6 days in the control, 9.7 days in acute hepatitis, 8.1 days in chronic hepatitis and 7.9 days in cirrhosis respectively. A decreasing tendency of T1/2 witn tne progression of liver diseases was observed, but the difference among each group was not statistically significant. D.R. of ƒÁ- globulin increased with the progression of liver injury. D. R. of ƒÁ-globulin in cirrhosis wassignificantly higher than that of the control group. Almost the same changes as in D.R. were found in the exchangeable ƒÁ-globulin pool (E.G.P.) and circulating globulin (C. G.). However, no significant increase of extravascular ƒÁ-globulin (E. V. G.) in the liver diseases was observed. Compared to the control group the migration rate of ƒÁ-globulinfrom intra- to extravascular compartmentincreased more than that of the extra- to intravascular compartment in the liver diseases. Increasing of the ƒÁ-globulin turnover in the liver diseases was more prominent in the active group than in the inactive group. However, presence of ascites and portal hypertension in liver cirrhosis did not affect turnover changes of ƒÁ-globulin. The changes of the serum ƒÁ-globulin level correlated well with the changes of C.G., D.R., E.G.P. and E.V.G., respectively. It can be said that ƒÁ-globulin turnover rates increase in liver diseases, especially in active liver injury. Interrelation between albumin and j-globulin Changes of the albumin and ƒÁ-globulin concentration in the serum were not correlated with each other, nor were turnover changes of albumin and ƒÁ-globulin. In the control group, the Al/G1 ratio was influenced more strongly by the changes of ƒÁ-globulin than those of the albumin concentration, while the influence of the albumin concentration on the Al/G1 ratio became increasingly evident in acute and chronic Vol. 7, No. 4 HYPOPROTEINEMIA IN LIVER DISEASES 307

hepatitis and in cirrhosis, the Al/Gl ratio was affected more strongly by the albumin concentration than the serum ƒÁ-globulin level. Gastroenteric clearance of 51Cf-albumin Although hypoalbuminemia in liver diseases is due mainly to the decrease of albumin synthesis in the liver, the possibility of pre- and post-hepatic factors playing some additional roles in the pathogenesis of hypoalbuminemia in liver diseases was studied. In liver cirrhosis, no decrease in absorption of 131I-RISA was found, excluding the prehepatic factor. Concerning the post-hepatic factor, fecal excretion of 131_pYpancj 51Cr-albumin injected intravenously did not increase and suggested that there was no increase in loss to the gastrointestinal (G.I.) tract. However, gastroenteric clearance of the 51Cr-albumin tended to increase in liver cirrhosis and when the daily excretion rate of albumin to the G.I. tract was compared with the daily degradation rate of albumin, the percentage of G. I. excretion to the degradation was clearly higher in cirrhosis than in the control group. Therefore, it is suggested that the protein loss to the G. I. tract might be partially attributed to hypoalbuminemia in liver cirrhosis and that liver cirrhosis might be a relative protein-losing gastroenteropathy.