Liver graft hyperperfusion in the early postoperative period promotes hepatic regeneration 2 weeks after living donor liver transplantation

Abstract

Hepatic regeneration is essential to meet the metabolic demands of partial liver grafts following living donor liver transplantation (LDLT). Hepatic regeneration is promoted by portal hyperperfusion of partial grafts, which produces shear stress on the sinusoidal endothelium. Hepatic regeneration is difficult to assess within the first 2 weeks after LDLT as the size of liver graft could be overestimated in the presence of postsurgical graft edema. In this study, we evaluated the effects of graft hyperperfusion on the rate of hepatic regeneration 2 weeks after LDLT by measuring hepatic hemodynamic parameters. Thirty-six patients undergoing LDLT were enrolled in this study. Hepatic hemodynamic parameters including peak portal venous flow velocity (PVV) were measured using spectral Doppler ultrasonography on postoperative day 1. Subsequently, we calculated the ratio of each velocity to 100 g of the initial graft weight (GW) obtained immediately after graft retrieval on the day of LDLT. Ratios of GW to recipient weight (GRWR) and to standard liver volume (GW/SLV) were also obtained. The hepatic regeneration rate was defined as the ratio of the regenerated volume measured using computed tomographic volumetry at postoperative week 2 to the initial GW. Correlations of the hemodynamic parameters, GRWR, and GW/SLV with the hepatic regeneration rate were assessed using a linear regression analysis. The liver grafts regenerated to approximately 1.7 times their initial GW (1.7 ± 0.3 [mean ± standard deviation]). PVV/100 g of GW (r2 = 0.224, β1 [slope coefficient] = 2.105, P = 0.004) and velocities of the hepatic artery and vein per 100 g of GW positively correlated with the hepatic regeneration rate, whereas GRWR (r2 = 0.407, β1 = –81.149, P < 0.001) and GW/SLV (r2 = 0.541, β1 = –2.184, P < 0.001) negatively correlated with the hepatic regeneration rate. Graft hyperperfusion demonstrated by increased hepatic vascular velocities and a small-sized graft in the early postoperative period contributes to hepatic regeneration 2 weeks after LDLT.

Multicollinearity and misleading statistical results

“…Hence, the graft weight relative to the recipient weight and standard liver volume is expected to be negatively correlated with the liver regeneration rate. The expected univariate correlations between each explanatory variable and liver regeneration rate were found in the above-cited paper [4]. Significant correlations between the hepatic hemodynamic parameters (PVV/GW, PSV/GW, EDV/GW, and HVV/GW) and between the relative graft weights (GRWR and GW/SLV) are anticipated because they share common characteristics.…”

“…In this section, multicollinearity is assessed from variance inflation factors, condition numbers, condition indices, and variance decomposition proportions, using data (Table 1) from a previously published paper [4]. The response variable considered, is the liver regeneration rate two weeks after living donor liver transplantation (LDLT).…”

“…While an increase in the PSV/GW leads to an increase in the liver regeneration rate, according to the results of the simple linear regression analysis [4] a unit increase in the PSV/GW reduces, albeit insignificantly, the regeneration rate by 0.05%. In addition, although the effect of a unit change in the GRWR on the regeneration rate is the strongest (37.954% decrease in the regeneration rate per unit increase), its regression coefficient is not statistically significant due to its inflated variance, which leads to a high standard error of 32.665 and a wide 95% confidence interval between –104.4 and 29.213.…”

Impact of Graft Weight Change During Perfusion on Hepatocellular Carcinoma Recurrence After Living Donor Liver Transplantation

“…After graft implantation, hepatocyte injury after reperfusion is mediated by release of reactive oxygen species with subsequent oxidative stress ( 8 ). In addition, when Kupffer cells and sinusoidal endothelial cells in the partial liver graft are exposed to high portal venous blood flow, shear stress caused by high portal venous blood flow induces hepatic regeneration ( 15 ). Decreased liver graft elasticity might affect early outcomes after LDLT.…”

“…Decreased liver graft elasticity might affect early outcomes after LDLT. Therefore, we tested liver function tests and INR repeatedly until one month after LDLT to compare levels between the two groups because the most appropriate time to evaluate graft regeneration in the early postoperative period is during the second postoperative week ( 15 , 16 ). However, there was no difference in aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin, or INR between the two groups.…”