Gastroenterology

Gastroenterology

Volume 124, Issue 7, June 2003, Pages 1792-1801
Gastroenterology

Clinical-liver, pancreas, and biliary tract
Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial

https://doi.org/10.1016/S0016-5085(03)00323-8Get rights and content

Abstract

Background & aims:

The role of oral supplementation with branched-chain amino acids (BCAA) in advanced cirrhosis is far from settled. A nutritional approach might prevent progressive liver failure and improve nutritional parameters and quality of life.

Methods:

A multicenter, randomized study comparing 1-year nutritional supplementation with BCAA against lactoalbumin or maltodextrins was performed in 174 patients with advanced cirrhosis. Primary outcomes were the prevention of a combined end point (death and deterioration to exclusion criteria), the need for hospital admission, and the duration of hospital stay. Secondary outcomes were nutritional parameters, laboratory data and Child-Pugh score, anorexia, health-related quality of life, and need for therapy.

Results:

Treatment with BCAA significantly reduced the combined event rates compared with lactoalbumin (odds ratio, 0.43; 95% confidence interval, 0.19–0.96; P = 0.039) and nonsignificantly compared with maltodextrins (odds ratio, 0.51; 95% confidence interval, 0.23–1.17; P = 0.108). The average hospital admission rate was lower in the BCAA arm compared with control treatments (P = 0.006 and P = 0.003, respectively). In patients who remained in the study, nutritional parameters and liver function tests were, on average, stable or improved during treatment with BCAA and the Child-Pugh score decreased (P = 0.013). Also, anorexia and health-related quality of life (SF-36 questionnaire) improved. Long-term compliance with BCAA was poor.

Conclusions:

In advanced cirrhosis, long-term nutritional supplementation with oral BCAA is useful to prevent progressive hepatic failure and to improve surrogate markers and perceived health status. New formulas are needed to increase compliance.

Section snippets

Study design

The study, planned in 1996 by a steering committee, was a multicenter, randomized, controlled study involving 15 centers with a specific interest in patients with liver disease. Each center was to recruit 12 patients with advanced liver cirrhosis of any etiology in a 6-month period. Inclusion criteria were (1) a diagnosis of liver cirrhosis documented by histology and confirmed by laboratory data, (2) Child-Pugh score21 ≥7 (class B or C), and (3) sonographic and endoscopic evidence of portal

Clinical course

In individual patients, the study period lasted from 1 to 15.5 months; only one of the 174 patients was lost to follow-up after withdrawal from the study for adverse effects at 1 month (see following text). A total of 1809 patient-months (657 on BCAA, 551 on L-ALB, and 601 on M-DXT) was available for analysis. Forty-three events were recorded (Table 2). Twenty-five patients died during the study period (5 in the BCAA group, 11 in the L-ALB group, and 9 in the M-DXT group). In 4 cases, death

Discussion

After 2 decades of debate, the potential benefits of nutritional supplementation with BCAA are still an unsettled issue. This is particularly true for oral supplementation, for which a meta-analysis on the 9 available trials (a total of 165 patients) was not possible17 because of conflicting results as well as differences in study design, duration of treatment, and type of nutritional supplementation. Most studies were also exceedingly short; even considering the crossover design of a few

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    Supported by Divisione Medica Europa, Bracco Imaging spa, Milano, Italy. Data collection and statistical analyses were performed by 2 principal investigators (G.M. and G.B.) at the University of Bologna independently of the sponsor.

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    Participating centers and investigators: Cattedra di Gastroenterologia, Università di Bari (F. Guglielmi, C. Panella, and L. Pietrini); Dipartimento di Medicina Interna, Cardioangiologia, Epatologia, and Cattedra di Malattie del Ricambio, Università di Bologna (M. Bertelli, G. Bianchi, S. Loffreda, G. Marchesini, B. Rossi, and G. Zoli); Dipartimento di Medicina Interna e Gastroenterologia, Università di Bologna (G. Danesi, R. Mimmo, C. Morelli, and C. Sama); Divisione di Gastroenterologia, Azienda Ospedaliera S. Orsola-Malpighi, Bologna (P. Leo and R. Muratori); Divisione di Gastroenterologia, Azienda AUSL Città di Bologna, Bologna (F. Sarti); Divisione Medica Europa, Bracco Imaging spa, Milano (R. Abbiati and E. Grossi); Divisione di Epatologia e Gastroenterologia “Crespi,” Ospedale Ca’ Granda - Niguarda, Milano (C. Vai); Cattedra di Gastroenterologia, II Università di Napoli (A. Federico and C. Loguercio); Dipartimento di Medicina Clinica e Sperimentale - Clinica Medica II, Università di Padova (P. Amodio and G. Campo); II Cattedra di Gastroenterologia, Università “La Sapienza,” Roma (M. Merli and O. Riggio); Cattedra di Medicina Interna, Università Cattolica, Roma (G. L. Rapaccini and L. Puglisi); Dipartimento di Medicina Clinica, Università “La Sapienza,” Roma (C. Cangiano, A. Laviano, and F. Rossi-Fanelli); Cattedra di Gastroenterologia, Università di Torino (B. Lavezzo and A. Ottobrelli); Dipartimento di Medicina III, Ospedale S. Bortolo - USL 6, Vicenza (E. Ambrosini and M. Salvagnini).

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