Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases
worldwide.(1) The prevalence of NAFLD is estimated to be about 20%-30% in the Western world
(2) and increasing in Asia. The prevalence of NAFLD across Asia varies from 5% to 40%.(3,4)
In one study with a sample of 922 subjects using proton-magnetic resonance spectroscopy and
transient elastography, 252 subjects had intrahepatic triglyceride content ≥5%, and the
population prevalence of NAFLD in Hong Kong Chinese was 27.3%.1 NAFLD may progress to
non-alcoholic steatohepatitis (NASH), cirrhosis, liver failure and liver cancer, and is
believed to be the leading etiology for cryptogenic cirrhosis.(5,6) NAFLD is also strongly
associated with obesity and metabolic syndrome and is shown to be an independent
cardiovascular risk factor.(7,8)
At present, there is no standard pharmacologic therapy available for NAFLD currently. Current
management for NAFLD includes diet and lifestyle changes, management of underlying metabolic
risk factors and pharmacological therapies. Insulin-sensitizing medication such as
Pioglitazone has been shown to improve histological NASH in terms of steatosis, inflammation,
ballooning, NAFLD Activity Score (NAS score) and resolution of NASH. (9) However, the
long-term efficacy and safety of Pioglitazone are unknown, and not all patients respond to
Pioglitazone. Vitamin E is a fat-soluble compound which prevents liver injury by blocking
intrinsic apoptotic pathways and by protecting against mitochondrial toxicity. (10) It also
improves histological NASH in terms of steatosis, inflammation, ballooning, NAS score, and
resolution of NASH at a dose of 800 IU/day. (9) However, the long-term safety of vitamin E is
also an issue, because doses of 400 IU/day or higher have been associated with increased
all-cause mortality. (11) While lifestyle management is often advocated, it is difficult to
maintain. (12) Thus, it is important to explore new treatment strategies.
In general, NAFLD prevalence is higher in men compared to women. However, the prevalence of
NAFLD in women is increasing in women over the past 10 years, (13) especially postmenopausal
women who have greater NAFLD risk and higher rates of severe hepatic fibrosis relative to
premenopausal women, and older women with NAFLD experience greater mortality than men. (14) A
cohort study in Japan reported that women after the age of 70 had a higher prevalence of
fatty liver than men (19.4% vs 14.9%). (15) Another cohort showed that gradual age-related
increases in NAFLD prevalence were also observed in women (3.9% in the 21-39 age group; 7.6%
in the 40-49 age group; 14.0% in the 50-59 age group; 18.9% in 60-69 age group), but not men.
(15)
NAFLD is more prevalent in overweight and obese individuals; gut microbiota also plays a role
in the development of insulin resistance, hepatic steatosis, necroinflammation and fibrosis.
(16) On the other hand, probiotics can strengthen the intestinal wall, reducing its
permeability, bacterial translocation, and endotoxemia according to animal and human studies.
Recently, it has been reported that NAFLD might be linked to small intestinal bacterial
overgrowth (SIBO), which induces liver injury by gut-derived lipopolysaccharides (LPS) and
TNF- α production. (17) Probiotics have several anti-inflammatory effects that can contribute
to their clinical benefits in NAFLD. (18)
The use of probiotics, prebiotics and synbiotics has been considered a potential and
promising strategy to regulate the gut microbiota. (19, 20) Some clinical studies have been
conducted to investigate the effects of probiotics on liver functions in NAFLD and NASH
subjects. In general, the results of the trials (21-28) showed that the use of probiotics can
reduce BMI, total fat percentage, total cholesterol, triglycerides, fasting insulin, alanine
aminotransferase (ALT), aspartate transaminase (AST), tumour necrosis factor (TNF-α),
interleukin (IL-6), liver stiffness et cetera.
This is a single-arm, open-label clinical trial for evaluating the efficacy of SIM01 on the
reduction of liver biochemistry in 40 female subjects with NAFLD. All subjects will take 2
sachets of SIM01 daily for 3 months with monthly assessment on adverse event observation, and
adherence to the study product throughout the study period. The change in CAP scores measured
by the fibroscan, BMI, liver function and interleukin-6 will also be evaluated.