Metabolic effects of liver transplantation in cirrhotic patients

Livio Luzi, Gianluca Perseghin, Enrico Regalia, Lucia Piceni Sereni, Alberto Battezzati, Dario Baratti, Elda Bianchi, Ileana Terruzzi, Hannele Hilden, Leif C. Groop, Andrea Pulvirenti, Marja Riitta Taskinen, Leandro Gennari, Vincenzo Mazzaferro

Research output: Contribution to journalArticlepeer-review

Abstract

To assess whether liver transplantation (LTx) can correct the metabolic alterations of chronic liver disease, 14 patients (LTx-5) were studied 5±1 mo after LTx, 9 patients (LTx-13) 13±1 mo after LTx, and 10 patients (LTx- 26) 26±2 months after LTx. Subjects with chronic uveitis (CU) and healthy volunteers (CON) were also studied. Basal plasma leucine and branched-chain amino acids were reduced in LTx-5, LTx-13, and LTx-26 when compared with CU and CON (P <0.01). The basal free fatty acids (FFA) were reduced in LTx-26 with respect to CON (P <0.01). To assess protein metabolism, LTx-5, LTx- 13, and LTx-26 were studied with the [1-14C]leucine turnover combined with a 40-mU/m2 per rain insulin clamp. To relate changes in FFA metabolism to glucose metabolism, eight LTx-26 were studied with the [1-14C]palmitate and [3-3H]glucose turnovers combined with a two-step (8 and 40 mU/m2 per min) euglycemic insulin clamp. In the postabsorptive state, LTx-5 had lower endogenous leucine flux (ELF) (P <0.005), lower leucine oxidation (LO) (P <0.004), and lower non-oxidative leucine disposal (NOLD) (P <0.03) with respect to CON (primary pool model). At 2 yr (LTx-26) both ELF (P <0.001 vs. LTx-5) and NOLD (P <0.01 vs. LTx-5) were normalized, but not LO (P <0.001 vs. CON) (primary and reciprocal pool models). Suppression of ELF by insulin (Δ-reduction) was impaired in LTx-5 and LTx-13 when compared with CU and CON (P <0.01), but normalized in LTx-26 (P <0.004 vs. LTx-5 and P 0.3 vs. CON). The basal FFA turnover rate was decreased in LTx-26 (P <0.01) and CU (P <0.02) vs. CON. LTx-26 showed a lower FFA oxidation rate than CON (P <0.02). Tissue glucose disposal was impaired in LTx-5 (P <0.005) and LTx-13 (P <0.03), but not in LTx-26 when compared to CON. LTx-26 had normal basal and insulin-modulated endogenous glucose production. In conclusion, LTx have impaired insulin-stimulated glucose, FFA, and protein metabolism 5 mo after surgery. Follow-up at 26 mo results in (a) normalization of insulin-dependent glucose metabolism, most likely related to the reduction of prednisone dose, and, (b) maintenance of some alterations in leucine and FFA metabolism, probably related to the functional denervation of the graft and to the immunosuppressive treatment.

Original languageEnglish
Pages (from-to)692-700
Number of pages9
JournalJournal of Clinical Investigation
Volume99
Issue number4
Publication statusPublished - Feb 15 1997

Keywords

  • FFA turnover
  • glucose turnover
  • insulin resistance
  • leucine turnover
  • liver transplantation

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Metabolic effects of liver transplantation in cirrhotic patients'. Together they form a unique fingerprint.

Cite this