Functional elements associated with hepatic regeneration in living donors after right hepatic lobectomy

Abstract

We quantified the rates of hepatic regeneration and functional recovery for 6 months after right hepatic lobectomy in living donors for liver transplantation. Twelve donors were studied pre-donation (baseline); 8 were retested at a mean ± SD of 11±3 days after donation (T1), 10 were retested at a mean of 91±9 days after donation (T2), and 10 were retested at a mean of 185±17 days after donation (T3). Liver and spleen volumes were measured with computed tomography (CT) and single-photon emission computed tomography (SPECT). Hepatic metabolism was assessed with caffeine and erythromycin, and hepatic blood flow (HBF) was assessed with cholates, galactose, and the perfused hepatic mass (PHM) by SPECT. The regeneration rates (mL kg(-1) of body weight day(-1)) by CT were 0.60±0.22 mL from the baseline to T1, 0.05±0.02 mL from T1 to T2, and 0.01±0.01 from T2 to T3; by SPECT they were 0.54±0.20, 0.04±0.01, and 0.01±0.02, respectively. At T3, the liver volumes were 84%±7% of the baseline according to CT and 92%±13% of the baseline according to SPECT. Changes in the hepatic metabolism did not achieve statistical significance. At T1, the unadjusted clearance ratios with respect to the baseline were 0.75±0.07 for intravenous cholate (P<0.001), 0.88±0.15 for galactose (P=0.07), 0.84±0.08 for PHM (P=0.002), and 0.83±0.19 for the estimated HBF (P=0.06). At T1, these ratios adjusted per liter of liver were up to 50% greater than the baseline values, suggesting recruitment of HBF by the regenerating liver. Increased cholate shunt, increased spleen volume, and decreased platelet count, were consistent with an altered portal circulation. In conclusion, initial hepatic regeneration is rapid, accounts for nearly two-thirds of total regeneration, and is associated with increases in HBF and cholate uptake. Right lobe donation alters the portal circulation of living donors, but the long-term clinical consequences, if there are any, are unknown.

Trial registration: ClinicalTrials.gov NCT00096733.

Copyright © 2013 American Association for the Study of Liver Diseases.

Figures

Figure 1. Example of clearances of cholates before and after donation

This figure displays the clearance curves for intravenously- (solid line) and orally-(dashed line) administered cholate isotopes in a single donor at baseline, prior to donation (upper Panel) and at T1 after donation (lower Panel). The increase in systemic concentrations of the orally-administered [2,2,4,4-D] cholate reflects the altered portal circulation and reduced hepatocyte mass after resection.

Figure 2. Liver and spleen volume ratios (compared with baseline pre-donation) by time since donation

Panel A. Liver volumes relative to the volume of the liver at baseline prior to donation are shown for each donor (n=10). Panel B. Spleen volumes relative to the volume of the spleen at baseline prior to donation are shown for each donor (n=10).

Figure 3. Platelet count and spleen volume per kg body weight before and after donation

The relationship of platelet count to spleen volume is shown with the cutoff for normal platelet count at 150 μL-1. Results for studies performed at baseline, and at T1, T2, and T3 after donation are indicated by separate markers. In general, regardless of study period, there was an inverse relationship of platelet count to spleen volume.