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

Authors


  • This article is publication 20 from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study, which is registered with ClinicalTrials.gov (NCT00096733).

  • In addition to the institutions affiliated with the authors, the Adult-to-Adult Living Donor Liver Transplantation Cohort Study includes Northwestern University (Chicago, IL), the University of California Los Angeles (Los Angeles, CA), Columbia University Health Sciences, NY, NY, University of Virginia, Charlottesville, VA, and Virginia Commonwealth University (Richmond, VA).

  • Gregory T. Everson and Claus U. Niemann were the principal investigators at the 2 clinical centers at the University of Colorado and the University of California San Francisco, respectively. John C. Hoefs and Norah Milne were responsible for the analyses of single-photon emission computed tomography liver-spleen scans. Kim M. Olthoff participated in the preparation of the manuscript. Robert Dupuis analyzed the erythromycin breath tests, and Shannon Lauriski analyzed the cholate clearances and shunt and the caffeine and galactose samples. Andrea Herman was the study coordinator in Colorado. Brenda W. Gillespie and Nathan P. Goodrich performed the statistical analyses. James E. Everhart was the project officer from National Institute of Diabetes and Digestive and Kidney Diseases.

  • Gregory T. Everson has intellectual property rights related to the filing (by the University of Colorado Denver) of US patent application 60/647,689 (Methods for Diagnosis and Intervention of Hepatic Disorders) on January 26, 2005 and International Application PCT/US2006/003132 as published under the Patent Cooperation Treaty, World Intellectual Property Organization, International Patent Classification A61K 49/00 (2006.01), International Publication Number WO 2006/081521 A2 on August 3, 2006. Everson also has an equity interest in HepQuant LLC. The other authors have no financial relationships to disclose.

  • This study was supported by the National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases (grants U01-DK62536, U01-DK62444, U01-DK62467, U01-DK62483, U01-DK62484, U01-DK62494, U01-DK62496, U01-DK62498, U01-DK62505, and U01-DK62531) and by the University of California Irvine (contract 38643).

Address reprint requests to Gregory T. Everson, M.D., Section of Hepatology, Division of Gastroenterology and Hepatology, University of Colorado Denver, 1635 Aurora Court, B-154, Aurora, CO 80045. Telephone: 720-848-2245; FAX: 720-848-2246; E-mail: greg.everson@ucdenver.edu

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. Liver Transpl 19:292–304, 2013. © 2013 AASLD.

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