Fatty Liver (cont.)
In this Article
How are NAFLD and NASH treated?
While the natural clinical history and the
processes involved in the development of NAFLD are beginning to slowly unravel,
no single truly effective treatment has been found to date. However, common
sense dictates that weight loss, if overweight, and correcting elevated
cholesterol, triglycerides, and blood sugar should be beneficial in NAFLD.
Yet, very little data exist on the effects of weight loss and exercise on the
progression of fatty liver disease. One retrospective study (looking back in
time) showed that in obese individuals with initially elevated transaminases,
weight gain lead to a further increase in the liver enzymes. In contrast, a 10%
weight loss lead to a significant decrease in the enzymes and even normal
transaminases in some patients. The enzyme decrease occurred at the rate of 8%
per 1% loss of body weight.
In studies of patients undergoing stomach (gastric) reduction operations for
morbid obesity, substantial weight loss is accompanied by a marked reduction in
transaminases and a regression of fatty liver. However, rapid weight loss in
this situation can also induce the occurrence of a fatty liver with liver
inflammation. Perhaps inflammatory cytokines (the small hormones mentioned
earlier) and the fat that produce the fatty liver and inflammation come from the
body fat (adipose tissue), especially the remaining abdominal fat.
There are
little published data on the use of glucose lowering (hypoglycemic) agents or
lipid lowering agents in the treatment of NASH. Troglitazone (Rezulin) is a
PPARg (peroxisome proliferator activating receptor gamma) compound that, as
indicated above, enhances the effects of insulin. The FDA, however, withdrew
this drug from the market because it caused cases of severe liver injury
(hepatotoxicity). Before the drug was withdrawn, however, a small trial of
troglitazone in patients with NASH was conducted for 6 months. The study showed
a significant decrease in transaminases, but only moderate improvement in
microscopic (histological) severity in the liver biopsies.
Troglitazone, as does
other medications in its class (thiazolidinediones), increases insulin
sensitivity and perhaps decreases inflammation and scarring in the liver. A
short trial with gemfibrozil (Lopid), a drug that lowers blood fats
(antilipidemic agent), showed some positive effects. It lowered transaminases
and serum triglycerides, but follow-up liver biopsies were not performed. A
one-year trial of clofibrate (Atromid-S), another drug that lowers blood fats,
however, had no positive effect whatsoever. Metformin (Glucophage),
is an insulin-enhancing (sensitizing) agent used extensively to treat DM2. The
drug was studied in a small series of NASH
patients and showed beneficial effects on transaminases and decreased fatty
infiltration in the liver. A larger trial is ongoing. Recent data also suggest that
lowering cholesterol and triglycerides using medications such as statins help decrease fatty
liver.
In one published trial, a one-year course of ursodiol (Actigall,
Urso) in patients with NASH decreased transaminases and improved the liver
biopsies. The way
that this bile acid molecule works in NASH remains unclear, but
it may involve effects on the immune system that decrease inflammation. But recent data
cannot confirm efficacy of Actigall in treating fatty liver.
In view of the multiple processes involved in causing
NASH, it may well be that many different classes of medications, as well as
weight loss, will have beneficial effects. These drugs could conceivably
include:
- Insulin-sensitizing agents, such as the two new thiazolidinediones, pioglitazone
(Actos) and rosiglitazone
(Avandia), and metformin (Glucophage)
- Medications that lower lipids such as statin drugs and
Lopid
- Drugs that improve blood flow, such as pentoxifylline
(Trental)
Presumably, weight loss through exercise and diet modification along with
insulin-sensitizing agents will help reverse fatty infiltration of the liver.
The other therapies might be beneficial in slowing the processes of inflammation
and scarring. A combination of therapies will probably be the most
beneficial.
Next: What is the future of NAFLD and NASH? »
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