Kinetics and mechanisms of hepatic acute phase response to subtotal partial hepatectomy and cultural impact on environmental hepatic end-stage liver injury in the homeless

Intoxication and liver damage induced by carbon tetrachloride (CCI4), aflat oxin B1, diabetes, and subtotal partial hepatectomy (PH,,) in rats in which approximately 90% of the total hepatic tissue mass is surgically removed p roduces an acute-phase response (APR) whose initial stage prior to regressi on closely mimics the APRs associated with the life-threatening hepatic fai lure seen in the homeless. Rats treated by PH90 were either healthy, CCl4-intoxicated, diabetic, or al flatoxin B1 (AFB1) intoxicated to the point of 75% liver insufficiency. It is well documented that high rates of mortality following PH,, in aseptic r ats could be minimized by supplementing drinking water with 20% glucose, or ganic components of L-15 medium and housing animals in cages maintained at 33-35 degreesC. Aseptic rats showed a mild 20-30% decrease in APR proteins during the first 4-5 days following PH90, while a maximal APR was noted 9-1 2 days post PH90 and lasted for similar to 30 days when it returned to valu es close to those of healthy controls. This delay in hepatic APR of the rem nant caudate robe favoured replacement of lost basophilic clumps and riboso mes. The newly synthesized ribosomes of the nascent hepatocytes quantitativ ely maintained the APR signals of the injured caudate hepatocytes, and bios ynthesized and released a typical spectrum of APR proteins. We suggest that massively injured liver has decoded an already stored and irreversible DNA -biochemical sequence of events in which priority is given to recovery of l ost tissues by delaying an APR response to injury. In PH90 of diabetic and CCl4-intoxicated rats, the hepatic dual functions of regeneration and APR p rocesses associated with intoxication-initiated catabolic signals, created a heavy metabolic burden on the remnant caudate lobe leading to higher rate s of mortality. APR of healthy rats to AFB1 parallels that of alpha -amanit in-induced intoxication. Similarly, within shorter time scale proportional to the severity of surgery, livers undergoing 75% partially hepatectomy (PH 75) delayed both the onset and regression of APR. We are therefore led to believe that approaches other than liver transplant ation should be considered as viable alternatives in the treatment of vario us acute and chronic liver diseases to avoid rejection and retransplantatio n. Scarcity of cadaveric liver has forced the medical community to investig ate xenotransplantation with its unknown risks. Concomitantly, it is sugges ted that in view of the incalculable risks of indifference, the homeless mu st receive much improved medical care as we have found that two-dimensional immunoelectrophoretic assay of their serum is indicative of acute and chro nic liver injury. The scientific and moral interrelationships of related ma tters are illuminated. (C) 2001 Harcourt Publishers Ltd.