Clinical analysis of liver function: development of a novel method for the detection of portosystemic shunts.

Abstract

A portosystemic shunt (PSS) is defined as a congenital or acquired abnormal blood vessel that redirects blood around the liver without being filtered through hepatic parenchyma. PSS are thought to contribute to the distribution of isolated secondary metastases beyond the liver in 1.7 - 7.2% of all colorectal cancer patients without cirrhosis of the liver. No standardised clinical test for PSS yet exists and subsequently, the majority of PSS cases are detected incidentally through radiological means. To better identify PSS, a simple standardised clinical test for its detection is needed. The aim of this thesis was to develop a cost effective, non-invasive technique that can detect and measure PSS in a healthy liver model. Methods An artificial 8mm diameter PSS was created between the portal vein and the inferior vena in a pig model with a catheter inserted in the confluence of the hepatic veins for sample collection. A spectrum of compounds including indocyanine green (ICG), ¹³C-methacetin, sorbitol and lignocaine, were injected into the portal system. To analyse the pharmacokinetic nature of the shunt and liver, Evans blue dye and ¹⁴C-sucrose were also administered. ICG was measured via a LiMON® spectrometer attached to the pig’s snout, while levels of the other indicators were measured by serial blood and breath sample collection over a 40 minute period. The process was repeated with the PSS clamped as the control. Results Of the administered compounds, only ICG had the potential to clearly identify and quantify the shunt due to the rapid serial sampling via the LiMON®. Further simulations using ICG demonstrated that the shunted fraction can be calculated using the transit times, including mean residence time, lag time and pharmacokinetic modelling. Conclusion Although this study has not yet provided a concise method for PSS detection available for immediate clinical use, it does provide a large foundation for further exploration into a quantitative technique. A future PSS test would allow an added risk assessment for secondary cancer, and consequently individual cancer therapy may be better targeted for individual patient care.