OBJECTIVE: To investigate the morphological changes in the liver in patients with organ failure and hyperbilirubinemia and to correlate them to the outcome. DESIGN: A case series prospective study. SETTING: Intensive care units of two general hospitals. PATIENTS: Twelve patients in organ failure with predominant hepatic involvement, aged 16 to 69 years (mean 56 years). INTERVENTIONS: Liver biopsy was performed on all patients 3-15 days after organ failure. A second biopsy was also performed on all four surviving patients, as well as on 3 patients just before death at a mean time of 16 days (6-32) and 31 days (14-55), respectively, after the first biopsy. The samples were studied by electron microscopy and findings were assessed according to Rappaport's designation. MEASUREMENTS AND MAIN RESULTS: In the first biopsy it was shown that in zone III there was complete degeneration of bile canaliculi and hepatocytes in contrast to zone I. The grade of histological severity for zone III is positively correlated to the bilirubin concentration (p = 0.001). In the specimens from the second biopsy, it was shown that numerous, newly formed secondary bile canaliculi per 20 consecutive hepatocytes had developed in zone III in the surviving patients, whereas there was a complete absence of such canaliculi in the patients who died (mean +/- SD: 9.6 +/- 3.2 vs 0). CONCLUSIONS: It appears that the destruction of primary bile canaliculi is a striking anatomical defect in patients with organ failure and impaired bilirubin excretion. The restoration of liver function coincides with adequate formation of new secondary bile canaliculi in zone III, giving credence to the hypothesis that this formation is an important structural change responsible for the improvement in liver function.
OBJECTIVE: To investigate the morphological changes in the liver in patients with organ failure and hyperbilirubinemia and to correlate them to the outcome. DESIGN: A case series prospective study. SETTING: Intensive care units of two general hospitals. PATIENTS: Twelve patients in organ failure with predominant hepatic involvement, aged 16 to 69 years (mean 56 years). INTERVENTIONS: Liver biopsy was performed on all patients 3-15 days after organ failure. A second biopsy was also performed on all four surviving patients, as well as on 3 patients just before death at a mean time of 16 days (6-32) and 31 days (14-55), respectively, after the first biopsy. The samples were studied by electron microscopy and findings were assessed according to Rappaport's designation. MEASUREMENTS AND MAIN RESULTS: In the first biopsy it was shown that in zone III there was complete degeneration of bile canaliculi and hepatocytes in contrast to zone I. The grade of histological severity for zone III is positively correlated to the bilirubin concentration (p = 0.001). In the specimens from the second biopsy, it was shown that numerous, newly formed secondary bile canaliculi per 20 consecutive hepatocytes had developed in zone III in the surviving patients, whereas there was a complete absence of such canaliculi in the patients who died (mean +/- SD: 9.6 +/- 3.2 vs 0). CONCLUSIONS: It appears that the destruction of primary bile canaliculi is a striking anatomical defect in patients with organ failure and impaired bilirubin excretion. The restoration of liver function coincides with adequate formation of new secondary bile canaliculi in zone III, giving credence to the hypothesis that this formation is an important structural change responsible for the improvement in liver function.