Long-term hypolipidemic effect of portacaval transposition and distal intestinal resection without change in liver function tests

Partial ileal bypass and end-to-side portacaval shunt (PCS) have significantly reduced serum cholesterol levels in clinical use. PCS can cause deterioration of liver function. Portacaval transposition (PCT) may induce plasma cholesterol lowering equivalent to PCS without deleterious side effects. We have followed four dogs with PCT, two with 50% distal ileal resection (IR), and five with PCT + IR for 3 years, as well as four control animals for 1 year, and have measured their hepatic cholesterol synthesis, hepatic lipid concentration, and cholesterol turnover rates. The dogs at 3 years postoperatively are in good health without deterioration of liver function tests (BSP retention, bilirubin, GGT, SGOT, alkaline phosphatase) and BUN. Dogs with IR had 25% reduction of plasma cholesterol and 58% reduction of triglycerides; dogs with PCT had 36% reduction of plasma cholesterol (P < 0.01) and 39% reduction of triglycerides (P < 0.01); those with PCT + IR had 43% reduction of plasma cholesterol (P < 0.01) and 68% reduction of triglycerides (P < 0.001). Compared to normal dogs, IR dogs have increased cholesterol turnover rate (P < 0.05), hepatic total lipid (P < 0.02), free cholesterol (P < 0.01), and cholesterol esters (P < 0.01). PCT + IR dogs have increased hepatic cholesterol synthesis (P < 0.05), increased cholesterol turnover (P < 0.001), and increased hepatic free cholesterol (P < 0.05), and cholesterol ester (P < 0.05). Neither PCT nor IR alone affected the cholesterol-exchangeable pool sizes. However, the PCT + IR dogs, compared to normal dogs, have larger slowly (P < 0.05) and rapidly (P < 0.01) exchangeable cholesterol pool sizes. The rapidly exchangeable cholesterol pool size of PCT + IR was also larger than that after PCT alone (P < 0.01). In summary, there is significant and lasting 35+% reduction of plasma cholesterol and triglyceride for 36+ months after either PCT or PCT + IR without deterioration of liver function parameters. Combining the IR and PCT in euthyroid dogs does not significantly improve the cholesterol lowering and causes increased cholesterol pool sizes and hepatic cholesterol content. PCT dogs remained in good health, without deterioration of liver function, for 3 years. It is suggested that PCT may be an attractive clinical alternative to PCS, at least for lipid reduction.