Morphometric parameters of hepatocytes in experimental complete extrahepatic bile duct obstruction

Liver changes observed in complete extrahepatic bile duct obstruction (CEBDO) with consideration to its morphometric parameters, may reflect the upcoming decompensation of liver function and may serve as objective criteria for the disease prognosis.The aim. To study the morphological changes of hepatocytes in experimental CEBDO using macro- and micromorphometry.Materials and methods. In 41 rats, the CEBDO was done by ligation and transection of the common bile duct. The time points were on postoperative Day 1, 3, 7, 14, 21, 28 and 35. Control group included 10 non-operated rats. The total blood bilirubin (TB), liver volume (LV), the area of hepatocytes (AH), the hepatocyte nuclear-cytoplasmic ratio (HNCR), the hepatocyte bulk density (HBD) were investigated. The LV and HBD parameters were used to calculate the total volume of hepatocytes (TVH).Results. The highest mortality was recorded on Day 22-35 of the experiment (7 out of 11 animals). Bilirubin level was significantly higher than in the control group with its maximum on Day 1 (295±100 vs. 8±6, μmol/l, p<0.001). The highest LV value was observed on Day 14 (14.1±1.1 vs. 8.4±1.4cm³, p<0.01). The processes prevailing in the livers were cell proliferation, fibrosis with gradual displacement of hepatocytes by proliferating bile ducts, and complete loss of normal liver histostructure. The proportion of hepatocytes in the liver (HBD) was progressively decreasing from 0.94 (Control) to 0.44 (Day 35). In spite of that, the TVH level was initially increased (max 9.7±0.36cm³ on Day 3 vs. 8.3±0.26cm³ on Day 1, p<0.05), but after Day 14 it decreased, with no significant differences from the Control group on Day 21(8.2±1.2 vs. 7.9±1.6cm³, p>0.05), with its lowest level (5.0±0.9cm³) on Day 35 (p<0.05 compared with max value on Day 3). The HNCR index, which reflects proliferative activity of hepatocytes, had its maximum on Day 14 (0.53±0.01 vs. 0.21±0.05 in Control group, p<0.001).Conclusions. In experimental CEBDO, reduction of the HBD index less than 60 % and reduction of TVH less than the value of a normal liver are accompanied by highest mortality, i.e., are a sign of hepatic decompensation. That was preceded by the maximum proliferative activity of hepatocytes, the criterion of which is the HNCR index