Title:Statins: An Under-Appreciated Asset for the Prevention and the Treatment of NAFLD or NASH and the Related Cardiovascular Risk
Volume: 16
Issue: 3
Author(s): Vasilios G. Athyros*, Chrysa Boutari, Konstantinos Stavropoulos, Panagiotis Anagnostis, Konstantinos P. Imprialos, Michael Doumas and Asterios Karagiannis
Affiliation:
- Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki,Greece
Keywords:
Non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, cardiovascular disease, statins, metabolic syndrome,
diabetes mellitus.
Abstract: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease (30% of the
general population) and up to 40% of cases advance to the more severe form of the disease: nonalcoholic
steatohepatitis (NASH), which is causally related to cirrhosis and cardiovascular disease
(CVD). There is no generally accepted effective treatment for NAFLD/NASH. The joint guidelines of
the European Association for the Study of the Liver (EASL), the European Association for the Study of
Diabetes (EASD) and the European Association for the Study of Obesity (EASO) suggest the “off label”
use of pioglitazone in patients without type 2 diabetes mellitus (T2DM) and pioglitazone in subjects
with T2DM or vitamin E or their combination for the treatment of NASH; however pioglitazone
has considerable limitations: weight gain, bone fractures in women, and heart failure.
The aim of this narrative review is to assess the existing evidence supporting statin use for the treatment
of NASH and the reduction of the high CVD risk of these patients. Animal data suggest that there is
some benefit from statin use in liver histology in models of NASH. In humans, 3 post hoc analyses of
randomised controlled trials (n=1,600, n=1,123, n=8,864) suggest that the use of atorvastatin (even in 80
mg/day) has a beneficial effect on NAFLD/NASH, in terms of liver enzyme reduction and ultrasonographic
amelioration. Moreover, and most importantly, statin treatment halved CVD morbidity and
mortality in statin-treated NAFLD/NASH patients compared with statin-treated participants with normal
liver structure and function and reduced by 2/3rds CVD events in comparison with NAFLD/NASH patients
that were not on a statin (90% of this population is not on statins because of the unjustified fear
for liver damage). Three biopsy studies (n=20, n=107 and n=356) showed that statin treatment had a
protective effect on steatosis, steatohepatitis and fibrosis.
Data suggest that statin treatment in humans substantially improve or cure NAFLD/NASH, but above
all substantially reduce CVD morbidity and mortality. Administration of potent statins appears safe and
effective in saving lives in NAFLD/NASH patients.
