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Milk Thistle Shines Hope in the Treatment of Non-Alcoholic Fatty Liver Disease

Researchers from University of Malaya discover that herbal supplement (milk thistle) may be useful for improving liver damage in patients with fatty liver disease.

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A comparison between normal liver with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.
Credit : 2016 MAYO Foundation for Medical Education and Research

Non-alcoholic fatty liver disease (NAFLD), commonly referred to as “fatty liver”, is a liver condition characterized by the accumulation of fat in the liver in persons who do not consume alcohol heavily. The prevalence of NAFLD has been increasing in recent years and parallels the increase in prevalence of obesity and other obesity-related diseases. NAFLD on its’ own is benign. However, a significant number of people with NAFLD progress to a condition known as Non-Alcoholic SteatoHepatitis (NASH), whereby the fat in the liver causes inflammation and damage, eventually leading to scarring (fibrosis) and permanent damage (cirrhosis). Cirrhosis ultimately leads to liver failure and death.

NASH patients are also at increased risk of developing liver cancer, especially in the presence of excessive scarring in the liver. NAFLD is now recognized as one of the most common causes of chronic liver disease worldwide, including in Malaysia. The impact of the disease is big in countries such as Malaysia where the prevalence of obesity is high. NAFLD is also closely related to diabetes mellitus, hypertension and dyslipidemia, and patients with NAFLD are more susceptible to cardiovascular diseases as well as certain cancers.

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Milk thistle.
Credit : Google image.

A group of dedicated clinical researchers from the Gastroenterology Unit, Department of Medicine, Faculty of Medicine at the University of Malaya have been actively conducting research work on NAFLD over the last decade. Their effort has contributed to most of the published work on NAFLD in Malaysia found in the literature today. Their work focused on the epidemiology of the disease as well as non-invasive methods for the assessment of the severity of liver disease in patients with NAFLD. The prevalence of NAFLD in the general population was estimated to be 22.7% based on a study using ultrasonography conducted on health check individuals in a private medical centre in Petaling Jaya about a decade ago. Recently, the prevalence of NAFLD was found to be 57.4% based on a study using Fibroscan conducted on health check individuals in a public medical facility in Kuala Lumpur. The study also found that 17.5% of the individuals had liver stiffness measurement consistent with excessive scarring in the liver.

Apart from documenting the extent and risk of NAFLD in Malaysians, the same research group from the Gastroenterology Unit have worked on novel treatment options for NAFLD. No specific medical treatment (drugs) has been developed for improving NASH. Recently, the group found that silymarin may be useful for the treatment of NASH. Silymarin is an extract from the milk thistle plant Silybum marianum and has been used for centuries as a herbal remedy for chronic liver disease. Its anti-oxidant, anti-inflammatory and anti-fibrotic activities have been demonstrated in basic scientific experiments and some human clinical trials, but without very objective measures such as liver biopsy, have also suggested that silymarin may be useful for the treatment of NAFLD. “Our work provides primary histological data on the potential efficacy of silymarin in improving liver fibrosis in patients with NASH,” said Associate Professor Dr. Chan Wah Kheong, one of the main investigators of this research project.

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Associate Professor Dr. Chan Wah Kheong sharing information about their study on silymarin for the treatment of NASH during poster presentation at the International Liver Congress 2015 in Vienna, Austria.
Credit : Associate Professor Dr. Chan Wah Kheong

The study randomized biopsy-proven NASH patients to silymarin 700 mg three times daily or placebo for 48 weeks, and a repeat liver biopsy was performed at the end of the study. All patients received lifestyle advice. The original aim of the study was to demonstrate an improvement in NASH based on histology, which the researchers could not demonstrate. However, the researchers found, to their surprise, that a significantly higher proportion of patients who received silymarin had fibrosis improvement compared with those who received placebo (22.4% vs. 6%, p-value = 0.023).

The improvement in fibrosis on biopsy was further supported by improvement in liver stiffness measurement by Fibroscan. Silymarin was also found to be safe and well tolerated by most patients in the study. “There are currently limited treatment options for NASH. Although weight loss through diet restriction and physical exercise has been shown to improve NASH, only a minority of patients are able to achieve the desired amount of weight loss to have a significant impact on the disease. The findings from our study should prompt further work to better define the role of silymarin in the treatment of NAFLD,” he added.

The full report of the study has been published in Clinical Gastroenterology and Hepatology, the prestigious journal of the American Gastroenterological Association, and was immediately highlighted by NEJM Journal Watch. “We are happy that our research work has received the recognition from our peers and hope to continue to contribute in the field of NAFLD. We would like to take this opportunity to thank our collaborator, Dr. Nik Raihan Nik Mustapha, Consultant Pathologist from Hospital Sultanah Bahiyah, Alor Setar, and all others who have contributed to the success of this research project, especially the patients and their family members,” said Professor Sanjiv Mahadeva, the other main investigator of the research project. The group is currently actively conducting further research in NAFLD, including a study on the prevalence of NAFLD and advanced fibrosis in patients with diabetes mellitus, a pilot study on the use of empaglifozin for the treatment of NASH in patients with diabetes mellitus, the use of a novel magnetic resonance imaging-based technology for staging of liver fibrosis in NAFLD patients, etc., and welcomes collaboration for further advancement in the field of NAFLD.