Quantitative Assessment of Hepatic Function During Liver Regeneration in a Standardized Rat Model

Abstract

Reliable assessment of hepatic function during liver regeneration is crucial after liver surgery or liver transplantation. 99m Tcgalactosyl human serum albumin ( 99m Tc-GSA) scintigraphy, 99m Tc-mebrofenin hepatobiliary scintigraphy (HBS), the indocyanine green (ICG) clearance test, and the galactose elimination capacity (GEC) are common quantitative liver function tests. However, to our knowledge, comparative analysis between these tests has never been performed during liver regeneration. The aim of this study was therefore to compare 99m Tc-GSA scintigraphy, 99m Tc-mebrofenin HBS, the ICG clearance test, and GEC in the assessment of hepatic function during liver regeneration in rats. Methods: Rats were subjected to 70% partial hepatectomy (PHx). Liver function and functional volume were determined at predefined times after PHx and expressed as a percentage of baseline (pre-PHx) values. Results: During liver regeneration, functional liver volume measured by 99m Tc-GSA SPECT correlated strongly with conventional liver volume based on wet weight. One day after 70% PHx, conventional liver volume overestimated liver function as measured by 99m Tc-mebrofenin uptake and excretion rates, 99m Tc-GSA uptake rate, and ICG clearance. On days 5 and 7, 99m Tc-mebrofenin uptake and ICG clearance had recovered to levels similar to conventional liver volume, whereas 99m Tc-GSA uptake reflected a reduced liver function in relation to conventional liver volume and 99m Tc-mebrofenin uptake. The GEC measurements consistently overestimated liver function during regeneration. Conclusion: Volumetric assessment of the liver should be complemented by liver function-specific assays. Functional regeneration is impaired, compared with volumetric regeneration, in the early phase of liver regeneration. In later stages of liver regeneration, 99m Tc-GSA uptake underestimates hepatic regeneration in comparison to liver volume and 99m Tc-mebrofenin uptake. GEC is of less value because it is only minimally affected by 70% PHx and is influenced by factors not related to liver function. 99m Tc-mebrofenin HBS has the advantage of providing visual and quantitative information regarding both uptake and excretory liver function.

New Perspectives in the Assessment of Future Remnant Liver

“…Several studies have reported a more advanced increase in liver function versus increase in volume [68,69,70], although the available studies do not deliver clear evidence for this statement due to methodological and analytical errors, leaving this question to be answered in the future. Moreover, the 99m Tc-GSA uptake may underestimate hepatic regeneration in the later stages of liver regeneration, as shown by de Graaf et al [71] in a rat model.…”

Transporters involved in the hepatic uptake of 99mTc-mebrofenin and indocyanine green

“…We recently compared the ICG clearance test with 99m Tc-mebrofenin HBS in rats after ischemia-reperfusion injury combined with a partial hepatectomy(7) and during liver regeneration after major hepatectomy (40). In both models a differential decrease in OATP isoforms was observed, contributing to the difference in hepatic uptake between ICG and 99m Tc-mebrofenin after ischemia-reperfusion injury and during regeneration.…”

Somatostatin Therapy Protects Porcine Livers in Small-for-Size Liver Transplantation

“…Therefore, it follows that the smaller the graft, the greater is the proportion of hepatocytes entering the replicative process to form these islands, decreasing the amount of functional liver tissue available even as gross mass is restored (44). This helps explain why multiple studies, including our own, have reported that functional regeneration does not correlate with volumetric regeneration during the early stages of liver regrowth (4,5,(51)(52)(53)(54) and that strategies that decelerate regeneration can actually lead to better preservation of normal hepatic microarchitecture and improved survival during the regenerative process (43).…”