Wah Kheong Chan of the University of
Malaya in Kuala Lumpur and colleagues conducted a randomised, double-blind,
placebo-controlled trial to evaluate silymarin for the treatment of NASH, or liver fat accumulation and
inflammation not associated with alcohol use. NASH and its less severe form,
non-alcoholic fatty liver disease (NAFLD), rival viral hepatitis and heavy
alcohol consumption as a cause of cirrhosis and liver cancer.
Silymarin, derived from the milk thistle
plant Silybum marianum, has been
shown to have anti-oxidant, anti-inflammatory and anti-fibrotic properties in
laboratory, animal and human studies.
This poster presentation included 64
participants with biopsy-confirmed NASH who had completed the study at the time
of the interim analysis. More than half were women and the average age was 50
years. A majority had grade 2 (moderate) steatosis and inflammation, followed
by stage 1 (mild), with a small number having stage 3 (severe). The average
NAFLD activity score – which incorporates steatosis, inflammation, and
swelling or 'ballooning' of hepatocytes – was 5, with two-thirds having scores
of 5-8. A majority of participants had absent or mild liver fibrosis (stage
F0-F1), but about one-third had advanced (F3) fibrosis.
Participants were randomly assigned to
receive 700mg silymarin three times daily or placebo for 48 weeks, along with
counselling about lifestyle factors such as diet and weight loss. Repeat liver
biopsies were performed at the end of the study.
More people in the silymarin group
experienced at least a 30% improvement in their NAFLD activity score after 48
weeks compared to the placebo group (33% vs 21%, respectively), but the
difference did not reach statistical significance. However, significantly more people in the silymarin arm experienced NASH resolution, defined as NAFLD
activity score <3 (13% vs 0%, respectively).
Similar proportions of participants in
both groups showed some improvement in their NAFLD activity scores (60% vs 59%),
and participants in both groups experienced significant improvement in these
scores relative to baseline (mean -0.733 with silymarin and -0.706 with
About the same proportion of people in
both the silymarin and placebo groups saw an improvement in steatosis (23% vs
24%). Fewer people in the silymarin group experienced improvement in
inflammation compared to the placebo group (27% vs 41%), but the difference was
not significant. Half of people in the silymarin group and 35% in the placebo
group saw an improvement in hepatocyte ballooning, again not a significant
Fibrosis scores decreased significantly in
the silymarin group (mean -0.367), while there was no notable change in the
placebo group (mean +0.147). A significantly higher proportion of people in the
silymarin group showed improvement in their fibrosis score (37% vs 15%,
respectively). Four people in the placebo group (12%) developed liver cirrhosis
during follow-up, while none in the silymarin group did so.
"A significantly higher percentage of
patients experienced NASH resolution and improvement in fibrosis stage after 48
weeks of treatment with silymarin compared to placebo," the researchers