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that HT inhibited the proliferation and induced with decreased frequency of development of HCC in
apoptosis in HCC in vitro and in a tumor model of obese patients with cirrhosis and hepatitis C virus
[87]
HCC, and exerted antiproliferative, antioxidant infection, significant reduction in HCC incidence
[74]
and anti-inflammatory effects on human hepatoma rate and improvement of event-free survival rate
HepG2 and Hep3B cell lines. [75,76] Oleuropein, a major in patients with cirrhosis, and reduced HCC
[88]
constituent of O. europaea, was shown to effectively recurrence after treatment with radiofrequency
inhibit cell viability and to induce apoptosis in HepG2 ablation in patients with cirrhosis. [84,89] Finally, BCAAs
human hepatoma cells in a dose -dependent manner, have been also shown to improve health-related
through activation of the caspase pathway. [77] quality of life [85,86] and sleep disturbances in patients
with cirrhosis. [90]
Oleanolic acid (3β-hydroxyolean-12-en-28-oic acid)
is a pentacyclic triterpenoid found in olive leaves. Milk thistle (Silybum marianum)
Antitumor effects of oleanolic acid have been Milk thistle is an herbal agent that has been used
investigated recently both in vitro and in vivo. It to treat liver diseases for centuries. Silymarin, the
exhibited inhibitory effect on HCC through induction main active constituent of milk thistle, is a mixture of
of apoptosis and cell cycle arrest both in transplanted polyphenols, including flavonolignans and flavonoids.
tumors in mice and in HepG2 cells, indicating that Despite a strong anticancer activity against human
oleanolic acid has significant antitumor activities on HCC cells are demonstrated in vitro, clinical studies
[91]
HCC both in vitro and in vivo models. Olive fruit supporting the use of silymarin as a hepatoprotective
[78]
pulp is a rich source of antioxidants and possesses agent have yielded conflicting results.
very good hepatoprotective activity against CCl -
4
induced hepatic damage in mice. [79] A Cochrane systematic review revealed that the
evidence supporting a role of milk thistle for the
Other foods and beverages treatment of patients with alcoholic and/or hepatitis B
Several other foods and beverages have been reported or C virus liver diseases is scanty, and that milk thistle
to have a protective role against HCC, including tea vs. placebo or no intervention had no significant
polyphenols (i.e. green and black tea), tomatoes effect on mortality, complications of liver disease
[80]
[92]
[81]
and tomato-based products (a rich source of or liver histology. Milk thistle was not associated
[92]
lycopene, an antioxidant carotenoid that has even with increased risk of adverse events. Silymarin
been shown to prevent HCC metastases in animal use in 1,049 patients with advanced fibrosis or
studies ), dietary fiber, green-yellow vegetables cirrhosis unsuccessfully treated with peginterferon
[18]
[82]
and fruit. [83] plus ribavirin has been associated with reduced
progression from fibrosis to cirrhosis. In a 24-week
[93]
Nutraceuticals and dietary supplements multicenter, double-blind, placebo-controlled trial
A large proportion of HCC patients use dietary that included 154 patients with chronic HCV infection
supplements. However, only in few cases their use and elevated serum alanine aminotransferase (ALT)
[3]
is supported by clinical evidence. unsuccessfully treated with interferon-based therapy,
silymarin did not significantly reduce serum ALT
Branched chain amino acids levels. Silymarin has also been used as an adjuvant
[94]
Branched chain amino acids (BCAA) may suppress therapy in conjunction with chemotherapy and other
hepatocarcinogenesis by several mechanisms, supplements (α-tocopheryl acetate and a product
including improvement of immune function, containing stem cell differentiation stage factors) in
reduction of oxidative stress and improvement of a case report of a patient with locally advanced HCC,
insulin resistance. Supplementation of BCAA for 2 with encouraging results. [95]
[84]
years in patients with cirrhosis (Child-Pugh class A)
has been associates with increases albumin synthesis Omega-3 fatty acids
in a multicenter, randomized controlled trial. [85] Preclinical data indicate that omega-3 polyunsaturated
However, another randomized controlled trial did not fatty acids (PUFAs) inhibit HCC cell growth and
find an improvement in serum albumin levels with might therefore be useful for the chemoprevention
[96]
BCAA supplementation, possibly due to different and treatment of human HCC. This hypothesis
patient characteristics (patients were Child-Pugh is supported by the results of a population-based
class B or C). Clinical trials have reported that long- prospective cohort study of 90,296 Japanese subjects,
[86]
term oral supplementation with BCAAs is associated in which consumption of omega-3 PUFAs, particularly

Hepatoma Research | Volume 2 | March 9, 2016 57