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Clin Gastroenterol Hepatol. 2014 Jun;12(6):1012-8.e1. doi: 10.1016/j.cgh.2013.08.050. Epub 2013 Sep 10.

Branched-chain amino acids prevent hepatocarcinogenesis and prolong survival of patients with cirrhosis.

Author information

1
Division of Gastroenterology, Department of Medicine and Digestive Disease Information and Research, Kurume University School of Medicine, Kurume, Japan.
2
Department of Gastroenterology, Tokai University School of Medicine, Hachioji, Japan.
3
Department of Medicine and Gastroenterology, Osaka Kosei-Nenkin Hospital, Osaka, Japan.
4
Department of Gastroenterology and Hepatology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan.
5
Division of Gastroenterology and Hepatology, Kansai Medical University Takii Hospital, Moriguchi, Japan.
6
Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
7
Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Japan.
8
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan.
9
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
10
Third Department of Internal Medicine, Kyorin University School of Medicine, Mitaka, Japan.
11
Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan.
12
Department of Nutritional Medicine, Osaka City University Graduate School of Human Life Science, Osaka, Japan.
13
Department of Gastroenterology and Hepatology, NHO Beppu Medical Center, Beppu, Japan.
14
Miwa Clinic, Gastroenterology and Hepatology, Gifu, Japan.
15
Biostatistics Center, Kurume University, Kurume, Japan.
16
Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
17
Department of Hepato-biliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
18
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan. Electronic address: kasuzuki@morioka-u.ac.jp.

Abstract

BACKGROUND & AIMS:

Although a low plasma level of branched-chain amino acids (BCAAs) is a marker of cirrhosis, it is not clear whether BCAA supplements affect disease progression. We performed a multicenter study to evaluate the effects of BCAA supplementation on hepatocarcinogenesis and survival in patients with cirrhosis.

METHODS:

We enrolled 299 patients from 14 medical institutions in Japan in a prospective, multicenter study in 2009; 267 patients were followed through 2011. Patients were given BCAA supplements (5.5-12.0 g/day) for more than 2 years (n = 85) or no BCAAs (controls, n = 182). The primary end points were onset of hepatocellular carcinoma (HCC) and death. Factors associated with these events were analyzed by competing risk analysis.

RESULTS:

During the study period, 41 of 182 controls and 11 of 85 patients given BCAAs developed HCC. On the basis of the Cox and the Fine and Gray models of regression analyses, level of α-fetoprotein, ratio of BCAA:tyrosine, and BCAA supplementation were associated with development of HCC (relative risk for BCAAs, 0.45; 95% confidence interval, 0.24-0.88; P = .019). Sixteen controls and 2 patients given BCAAs died. Factors significantly associated with death were Child-Pugh score, blood level of urea nitrogen, platelet count, male sex, and BCAA supplementation (relative risk of death for BCAAs, 0.009; 95% confidence interval, 0.0002-0.365; P = .015) in both regression models.

CONCLUSIONS:

On the basis of a prospective study, amino acid imbalance is a significant risk factor for the onset of HCC in patients with cirrhosis. BCAA supplementation reduces the risk for HCC and prolongs survival of patients with cirrhosis.

KEYWORDS:

Hepatoma; Liver Cancer; Nutrition; Treatment Outcome

PMID:
24036055
DOI:
10.1016/j.cgh.2013.08.050
[Indexed for MEDLINE]

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