Non.Alcoholic Fatty Liver Disease Clinical Trial
Official title:
A Randomised Controlled Trial of Vitamin D Plus Plus Lifestyle Versus Lifestyle in Patients With Non-alcoholic Steatohepatitis:Effect on Liver Histology and Metabolic Parameters
Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of disorders characterized
by predominantly macrovesicular hepatic steatosis occurring in individuals in the absence of
significant alcohol consumption. In this context it is possible to distinguish a condition
of simple fatty liver, where the only histologic finding is the presence of steatosis, from
a state of non-alcoholic steatohepatitis (NASH), characterized by hepatocellular
injury/inflammation with or without fibrosis. The prevalence of NAFLD is around 20-30% in
the general population. With a rapid increase in the risk factors for metabolic syndrome,
NAFLD has become the most common cause of liver disease in Western countries. The clinical
relevance of NAFLD arises from the fact that a considerable proportion of subjects (20-30%)
develop NASH, and this condition can progress to cirrhosis in up to 15% of patients. In
addition NAFLD, and particularly NASH, represents a cardiovascular risk factor, independent
of other well-known conditions contributing to heart and vascular diseases.
Lifestyle modification is the effective medical treatment recommended for NASH, while there
is currently no pharmacologic therapy of proven benefit in these patients. Several pilot
studies, using insulin sensitizers (thiazolidinediones or metformin), and antioxidants, like
vitamin E, have provided inconclusive evidence that these drugs may improve clinical and
histological features of NASH.
In the complex and not completely understood pathogenic puzzle of NAFLD and NASH, also
vitamin D might have an important role. Vitamin D deficiency is associated with many common
pathological conditions frequently observed in NAFLD, like cardiovascular disease, and
insulin resistance. A recent paper by Targher and colleagues showed low vitamin D serum
levels in NAFLD patients, identifying an inverse relation between vitamin D levels and the
severity of liver disease. In keeping with the above data, recent experimental evidence also
suggested the potential ability of vitamin D, through interaction with its nuclear receptor
(vitamin D receptor - VDR), to interfere with inflammatory response, T cell function and
fibrogenesis. Therefore considering the link between vitamin D serum levels, severity of
NAFLD, and risk factors for NAFLD, we speculate that vitamin D might represent a new
therapeutic target in the management of NASH patients.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment