Reuters Health Information: Pioglitazone improves advanced liver disease even in nondiabetics
Pioglitazone improves advanced liver disease even in nondiabetics
Last Updated: 2017-02-27
By Reuters Staff
NEW YORK (Reuters Health) - Treatment with pioglitazone
improves advanced fibrosis in patients with nonalcoholic
steatohepatitis (NASH), even in patients without diabetes,
according to results of a meta-analysis published today.
Clinical guidelines recommend identifying patients with
nonalcoholic fatty liver disease (NAFLD) with advanced fibrosis
to �target them for more intensive monitoring of the onset of
complications but acknowledge the lack of therapeutic options
that effectively reverse advanced stages of liver disease,�
write the authors from Turin, Italy, in JAMA Internal Medicine.
�The new finding in this meta-analysis is that treatment
with the antidiabetic drug pioglitazone reverses the more
advanced stages of liver disease in NASH regardless of the
presence of diabetes,� report Dr. Giovanni Musso and colleagues
from Humanitas Gradenigo Hospital and the University of Turin.
They pooled eight randomized controlled trials evaluating
the effect of thiazolidinedione therapy on histologic features
of the liver in a total of 516 patients with biopsy-proven NASH.
Five trials evaluated pioglitazone (average daily dose 30 or 45
mg) and three evaluated rosiglitazone (average daily dose 4 and
8 mg). The trials lasted for between six and 24 months.
In an analysis combining all eight trials, thiazolidinedione
therapy led to improvement in advanced fibrosis (odds ratio,
3.15; p=0.01), fibrosis of any stage (OR, 1.66; p=0.01), and
NASH resolution (OR, 3.22; p<0.001).
Analyses restricted to trials enrolling nondiabetic NASH
patients yielded similar results on all three outcomes (odds
ratios, 2.95, 1.76 and 3.40, respectively).
Pioglitazone use (and not rosiglitazone use) accounted for
all of the benefits observed with thiazolidinedione therapy, the
authors note, and they aren't sure why.
�Possible differences can be explained by the differential
effects of pioglitazone and rosiglitazone on inflammation and
fibrosis mechanisms, such as through up-regulation of
adiponectin, activation of adenosine monophosphate-activated
protein kinase, and induction of hepatic stellate cell
senescence,� they offer.
Aside from weight gain and lower limb edema, no major
adverse events were reported during the trials, the authors say.
However, due to the small number of trials and small sample size
of the trials they couldn't evaluate more serious adverse
effects of thiazolidinedione therapy.
This analysis, conclude Dr. Musso and colleagues, suggests
that pioglitazone use for up to 24 months can help reverse
advanced fibrosis stage in NASH �and may thus improve long-term
prognosis in this subgroup of patients who are at higher risk of
poor liver-related outcomes.�
In a linked editorial, Dr. Hal Yee Jr., of the University of
California, San Francisco, says this analysis makes a
�significant contribution� regarding the potential role
pioglitazone may have in the management of NASH, but several
�substantive questions� remain to be addressed before it can be
recommended as a treatment for patients with NASH.
Namely, �Does pioglitazone alter clinical outcomes, such as
development of ascites or encephalopathy, need for liver
transplantation, or liver-related death? What are the potential
risks associated with the use of pioglitazone? Should patients
with NASH be treated with pioglitazone? Might there be a
subpopulation of patients with NASH in whom pioglitazone could
be considered in their treatment?�
For now, Dr. Yee says, �it may make sense to consider the
use of pioglitazone in patients with type 2 diabetes who have
NASH and evidence of advanced fibrosis. Treating such patients
would not incur any incremental risk of adverse events because
they might already be taking pioglitazone as part of the
management of their diabetes, while potentially benefiting from
its putative benefits in NASH. For most patients with NASH,
prior guidance to reduce weight, exercise, and refrain from
heavy consumption of alcohol would seem prudent until we have
data showing therapies that improve clinical outcomes.�
The study had no commercial funding and the authors have
disclosed no conflicts of interest.
SOURCE: http://bit.ly/2mwPL6M and http://bit.ly/2mwLnVv
JAMA Intern Med 2017.