How To Cure Fatty Liver?

Nonalcoholic fatty liver disease: Scientists identify trigger and treatment

Apart
from lifestyle changes and weight loss, there are currently no
effective or safe treatments for nonalcoholic fatty liver disease. Now,
for the first time, researchers find that a protein called cdk4 occurs
at higher levels in mouse models and human patients with the disease.
Also, when they blocked the protein in mice, using drugs, it
significantly reduced development of hepatic steatosis - the first stage
of the disease.

The study, by Cincinnati Children's Hospital Medical Center in Ohio, is published in the journal Cell Reports.

Senior
author Nikolai Timchenko, a professor in the department of surgery at
the University of Cincinnati and head of the Liver Tumor Biology Program
at Cincinnati Children's, says:

"This is the first study to show
that cdk4 triggers development of NAFLD [nonalcoholic fatty liver
disease] and that inhibiting this enzyme can both prevent and reverse
the first step of the disease."

NAFLD is the buildup of extra fat
in liver cells that is not caused by alcohol. It is normal for the
liver to contain some fat, but if 5-10 percent of its weight is fat,
then it is classed as fatty liver.

The first stage of NAFLD -
called hepatic steatosis - can progress to a condition called NASH
(nonalcoholic steatohepatitis) and eventually cirrhosis or liver cancer.

NAFLD
tends to develop in people who are overweight or obese, or who have
diabetes, high cholesterol, or high triglycerides. It can also result
from poor eating habits and rapid weight loss.

However, some
people can develop NAFLD even without these risk factors. Estimates
suggest up to a quarter of Americans have NAFLD.

Prof. Timchenko
says new safe and effective treatments for NAFLD are needed. Currently,
the only way to treat the disease is through weight loss and lifestyle
changes.

He explains that while new treatments currently
undergoing clinical trials are showing promising results, they are also
showing evidence of serious side effects.


Blocking cdk4 prevented hepatic steatosis
In
their study, the researchers found high levels of a protein called cdk4
- which is triggered by a high-fat diet - in mouse models of NAFLD and
in human patients with fatty livers.

The increase in cdk4 causes a
chain of events through certain pathways that result in hepatic
steatosis, fibrosis, and hepatocellular carcinoma (HCC or liver cancer),
note the researchers.

In another part of the study, the team
found blocking cdk4 disrupted the pathways and prevented the development
of hepatic steatosis in mice that would normally develop it when raised
on a high-fat diet.

They also found that inhibition of cdk4 in mouse livers with existing steatosis reversed the steatosis.

The inhibitors they used in the study were flavopiridol and PD-0332991.

The
authors conclude that the critical finding of their study was to
identify the elevation or activation of cdk4 as a key event in the
development of NAFLD.

They suggest this finding - together with
further work with cdk4 inhibitors - will likely offer strong evidence to
support use of cdk4 inhibitors as a treatment that stops the liver
developing steatosis, and even reverse existing steatosis.

"Both
of the cdk4 inhibitors we tested are approved by the FDA and in clinical
trials for liver cancer, so it should be possible to initiate clinical
trials for NAFLD with these drugs soon."

Prof. Nikolai Timchenko Said


Tag:

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Steatitis, Cirrhosis, Fibrosis, Fatty liver diseases, Fatty liver
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albumin, PT, INR, platelets, congestive heart failure, hepatitis,
cirrhosis, fatty liver, bile duct, gall bladder, alcoholic liver
disease, hepatitis C, hepatitis A, abdomen, intestines, first pass
metabolism, endocrine, exocrine, common bile duct, duodenum, 



















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