Non alcoholic fatty liver disease (NAFLD) is the leading cause of liver dysfunction worldwide and is a rapidly growing health problem in regions such as the Middle East, Far East, Africa, the Caribbean, and Latin America. some of the developing countries like India.
NAFLD ranges from benign accumulation of fat droplets within liver cells (“steatosis”) to an inflammatory state causing fibrosis of the liver (Non Alcoholic Steatohepatitis, or NASH) to end stage liver cirrhosis. In NAFLD the excess fat accumulation is in the form of excessive triglycerides in the liver and they occupy more than 5% of liver cells called hepatocytes. This means that the fat forms 5% of the weight of the liver. Normally there is hardly any fat present in the liver.
In NASH there is injury to liver cells due to the fat and this causes the inflammation and fibrosis as stated earlier. Aside from the risk of liver failure, there is also an increased risk of developing liver cancer (hepatocellular carcinoma or HCC) with NASH.
Within the next five years, NASH cirrhosis will surpass Hepatitis C Virus cirrhosis as the leading indication for liver transplant in Western countries.
In 2008 there were at least 1.46 billion adults who were overweight or obese and another 170 million children who were obese and this number seems to be on the rise. Currently there seems to be a worldwide epidemic of diabetes and obesity. All this together contributes to the rising fatty liver problem. The incidence of NAFLD among the Indian population is estimated to be as high as 32%.
The two main causes of NAFLD are poor diet and sedentary lifestyle. NAFLD goes hand in hand with obesity and diabetes and is therefore a component of the Metabolic Syndrome, which consists of 3 or more of the following: obesity, hypertension, elevated fasting blood glucose, hypertriglyceridemia or low high-density lipoprotein levels.
Indians and NAFLD A recent study by Kalra and colleagues reported that among Indians with Type II Diabetes Mellitus, 56.5% also have NAFLD.
There are also genetic factors predisposing to NAFLD. For instance, simple steatosis is highly prevalent in the Indian population, even in people who are not overweight, are not diabetic, and don’t drink alcohol. So the unfortunate combination of a genetic predisposition, lack of exercise, and a diet rich in ghee, sugar, and oils, all conspire to make NAFLD a major health problem in India.
Other causes of fat accumulation within liver cells are excessive alcohol intake, many drugs (particularly chemotherapeutic agents and certain antiviral medications), pregnancy, and chemicals such as carbon tetrachloride.
The term NAFLD is used to distinguish fatty liver disease caused by the Metabolic Syndrome from these other causes. A fatty liver is reversible in its early stages if the offending causes are curtailed or ceased, but continued injury can ultimately cause progression to NASH, cirrhosis, and liver cancer.
NAFLD and NASH are asymptomatic in their early stages. As the disease progresses, fatigue, malaise, and right upper quadrant pain are the earliest symptoms. As NASH progresses to liver cirrhosis, classic symptoms of liver insufficiency can occur: swelling of the legs and abdomen, confusion, muscle wasting, etc.
Symptoms associated with the Metabolic Syndrome (obesity, diabetes, hypertension, and hyperlipidemia) such as frequent urination, excessive thirst, and headache, should alert treating physicians to the possibility of underlying, asymptomatic fatty liver disease.
The gold standard for diagnosing NAFLD is liver biopsy, but this procedure is invasive, painful, and carries risks of complications such as internal bleeding. So, doctors are reluctant to order a liver biopsy unless absolutely necessary.
Imaging tests such as ultrasound, CAT scan, and MRI can diagnose later stage NAFLD, but they are insensitive in detecting early disease. Combining these imaging techniques with other modalities such as elastography can improve sensitivity and there is active research promising that these procedures will soon be available.
Simple liver function tests, such as AST, ALT, INR, and GGT, can be slightly elevated in early NASH, but they are nonspecific in determining the severity of disease. Proprietary tests such as FibroTest (trademark) have been shown to be more sensitive and specific, but they are not routinely used due to expense.
The primary treatment for NAFLD is lifestyle modification. Eating a balanced diet, eating less, and increasing one’s physical activity all promote weight loss and improve or prevent diabetes and fatty liver. In severe cases of obesity, surgical or minimally invasive weight loss procedures may be considered, such as gastric bypass surgery (open, laparoscopic, or robotic) or endoscopy.
Basic research points to potential medical therapies the treat NAFLD, for example, the diabetes drug Metformin and inhibitors of the endocannabinoid pathway, but no human clinical trials exist as of yet that show efficacy. There is some evidence that treating diseases concomitant with NAFLD, such as diabetes and hyperlipidemia, can improve NAFLD and possibly prevent progression of liver disease.
References:1. Schuppan D, Schattenberg JM. Non-alcoholic steatohepatitis: pathogenesis and novel therapeutic approaches. Journal of gastroenterology and hepatology. 2013;28 Suppl 1:68-76. Epub 2013/07/24. doi: 10.1111/jgh.12212. PubMed PMID: 23855299.
2. Lam B, Younossi ZM. Treatment options for nonalcoholic fatty liver disease. Therapeutic advances in gastroenterology. 2010;3(2):121-37. Epub 2010/12/25. doi: 10.1177/1756283X09359964. PubMed PMID: 21180596; PubMed Central PMCID: PMC3002571.
3. Kalra S, Vithalani M, Gulati G, Kulkarni CM, Kadam Y, Pallivathukkal J, Das B, Sahay R, Modi KD. Study of prevalence of nonalcoholic fatty liver disease (NAFLD) in type 2 diabetes patients in India (SPRINT). J Assoc Physicians India. 2013 Jul;61(7):448-53.
Latest Publications and Research on Fatty Liver Disease: A Growing Health Problem in India
- Prognostic value of non-alcoholic fatty liver disease in the elderly patients. - Published by PubMed
- Impact of using different biomarkers of liver fibrosis on hepatologic referral of individuals with severe obesity and NAFLD. - Published by PubMed
- Erratum: FTY720/fingolimod decreases hepatic steatosis and expression of fatty acid synthase in diet-induced nonalcoholic fatty liver disease in mice. - Published by PubMed
- Iron-induced derangement in hepatic ?-5 and ?-6 desaturation capacity and fatty acid profile leading to steatosis: Impact on extrahepatic tissues and prevention by antioxidant-rich extra virgin olive oil. - Published by PubMed
- Maize extract rich in ferulic acid and anthocyanins prevents high-fat-induced obesity in mice by modulating SIRT1, AMPK and IL-6 associated metabolic and inflammatory pathways. - Published by PubMed