Several studies have validated the effectiveness of Ursodeoxycholic acid (UDCA), as an anti-apoptotic agent lowering serum TNF-α concentrations, decreasing endoplasmic reticulum stress and improving hepatic insulin sensitivity, suggesting that UDCA may be effective in the treatment of non-alcoholic steatohepatitis (NASH).
Non-alcoholic fatty liver disease (NAFLD) is the term for a range of conditions caused by a build-up of fat in the liver in people without significant history of alcohol use/abuse. It’s usually seen in people who are overweight or obese, but can also be seen in persons with normal BMI.
As the name implies, the main characteristic of NAFLD is too much fat stored in liver cells. NAFLD is one of the most common forms of chronic liver disease which may progress to NASH and eventually develops into cirrhosis or liver cancer.
The role of Ursodeoxycholic Acid in NAFLD
Sanjeev R. Mehta, in a research published on Therapeutic Advances in Endocrinology and Metabolism found that UDCA monotherapy significantly improved liver function in five studies and improved steatosis and fibrosis in two studies.
All five studies assessing UDCA combination therapy (especially with Vitamin E) showed significant improvements in liver function, while two studies also improved steatosis and inflammation.
One study of high-dose UDCA showed significant improvements in ALT, γGT and liver fibrosis, whereas the other study showed no significant change in ALT and liver pathology.
Another finding as published on pubmed.gov found that the combination of UDCA with vitamin E significantly improves liver function tests in long-term and is very well tolerated.
NAFLD is said to be developed by a 2-hit hypothesis where the first hit is the presence of fat in the liver (Steatosis) and the second hit is the presence of free radicals capable of inducing oxidative stress.
A retrospective study published on BMC Gastroenterology shows that 41 per cent of patients with NASH progressed to liver fibrosis and 5.4 per cent to end-stage liver diseases.
The systematic review of 224 articles according to the format of PRIMSA revealed that the prevalence of NASH has increased with obesity and type 2 diabetes topping the list of conditions.
The lead investigators of the team Zun Xiang, Yi-peng Chen and Kui-fen Ma, assessed the study eligibility and methodological quality to ensure that no quality compromise exists in the research.
According to them, “despite the “two hit hypothesis” for NAFLD, the mechanism by which it progresses to NASH is still vague, but may include oxidative stress, free fatty acid induced lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, dysregulated cytokines and gut bacteria overgrowth.
“However, due to its yet undetermined pathogenesis, NASH therapy remains empirical and is limited to treating associated conditions, including diabetes, obesity and hyperlipidemia. The current standard of care in the treatment of NASH involves weight loss and increased physical activity, which, while useful in treating simple steatosis, is difficult for patients to achieve”, they stated.
There are four stages involved in the development of NAFLD. They are :
Simple fatty liver (steatosis) – occurs when there is a buildup of fat in the liver cells. This stage is mainly harmless, and is often diagnosed during tests carried out for another reason.
Non-alcoholic steatohepatitis (NASH) – A more serious form of NAFLD, where the fat globules in the liver cells cause inflammation of the liver. NASH occurs in about one quarter of patients with NAFLD.
Fibrosis – where continuous inflammation causes scarring of the tissue around the liver and nearby blood vessels.
Cirrhosis – the most severe stage, occurring after years of inflammation, where the liver shrinks and becomes scarred and lumpy; this damage is permanent and can lead to liver failure (where the liver stops working properly) and liver cancer.
In a chat with Pharm. Makuo Muobike, product manager, Mega Lifesciences Nigeria Ltd., marketers of Ursoliv, a brand of Ursodeoxycholic acid, he said clinical observations have revealed that NAFLD is seen in 80 per cent of patients with metabolic syndrome consisting of type II diabetes, obesity and hyperlipidaemia.
He stated further that being a secondary bile acid, produced by intestinal bacteria as metabolic byproduct, UDCA has shown to be effective in non-surgical treatment of cholesterol gallstones and primary biliary cholangitis (PBC).
“The clinical properties of UDCA are as follows: widely used in the treatment of patients with PBC, primary sclerosis cholangitis (PSC) and has an excellent safety profile”, he asserted.