Non-alcoholic Fatty Liver Disease (NAFLD) & Non-alcoholic Steatohepatitis (NASH)

1 February 2, 2017

Nonalcoholic Fatty Liver Disease (NAFLD) is a term used for a wide range of conditions occurring from the build-up of fat within the liver cells in the liver of people who drink little or no alcohol.It is usually seen in people who are overweight or obese.The most common form of NAFLD is a non-serious condition called fatty liver. In fatty liver, fat accumulates in the liver cells.if more than 5% – 10% percent of the liver’s weight is fat, then it is called a fatty liver (steatosis).

There are 4 stages of NAFLD –

  1. Simple Fatty Liver ( Steatosis)
  2. Non-alcoholic Steatohepatitis (NASH)
  3. Fibrosis
  4. Cirrhosis

The liver is the second largest organ in the body and is located under the rib-cage on the right side and weighs about 3 pound. Its shape is like a football and is flat on one side. The liver is responsible for processing the food and drinks into energy for the body. It also removes harmful substances from the blood. A healthy liver should contain little or no fat.

A small group of people with NAFLD may have a more serious condition named Non-alcoholic steatohepatitis (NASH). NASH is often known to be a ‘silent’ liver disease. In NASH, fat accumulation (similar to NAFLD), is associated with liver cell inflammation and different degrees of scarring. It’s a potential serious condition that may possibly lead to severe liver scaring and cirrhosis.

NASH is a more aggressive form of the condition, when the liver has become inflamed. Inflammation is part of the body’s response to injury, which suggests that cells in the liver are being damaged and that some liver cells are dying.

NASH cirrhosis is now one of the leading indications for liver transplantation in the United States. NASH is diagnosed most often in patients between 40 yr and 60 yr but can occur in all age groups. Many affected patients have obesity, type 2 diabetes mellitus (or glucose intolerance), dyslipidemia, and/or metabolic syndrome.


Causes of NAFLD/NASH

NAFLD is a part of the metabolic syndrome characterized by diabetes, or pre-diabetes (insulin resistance), being overweight or obese, elevated blood lipids such as cholesterol and triglycerides, as well as high blood pressure.

Both NASH and NAFLD have become more common, because of the greater number of Americans with obesity. In the past 10 years, the rate of obesity has doubled in adults and tripled in children. Obesity also contributes to diabetes and high blood cholesterol, which can further complicate the health of someone with NASH. Diabetes and high blood cholesterol are also becoming more common among Americans.

Moreover, some patients with NASH are not obese, do not have diabetes, and have normal blood cholesterol and lipids. NASH can occur without any of the possible parent risk factor and can even occur in children. Thus, NASH is not simply obesity that affects the liver.

  • Oxidative Stress – Imbalance between pro-oxidant and anti-oxidant chemicals that lead to liver cell damage.
  • Cytokines– Production and release of cytokines – toxic inflammatory proteins, by the patient’s own inflammatory cells, liver cells, or fat cells.
  • Liver cell necrosis or death, called apoptosis.
  • Adipose tissue (fat tissue) inflammation and infiltration by white blood cells.
  • Gut microbiota –Intestinal bacteria which may play a role in liver inflammation.


In most cases of NAFLD, there are no symptoms and have a normal examination. Children may exhibit symptoms such as abdominal pain, which may be in the center or the right upper part of the abdomen, and sometimes fatigue.When symptoms occur, they may include fatigue, weakness, weight loss, loss of appetite, nausea, abdominal pain, spider-like blood vessels, yellowing of the skin and eyes (jaundice), itching, fluid build up and swelling of the legs (edema) and abdomen (ascites), and mental confusion.

In case of NASH, patients generally feel well in the early stages and only begin to have symptoms—such as fatigue, weight loss, and weakness and those in NAFLD—once the disease is more advanced or cirrhosis develops. However, the progression of NASH can take years. NASH can slowly worsen, causing scarring or “fibrosis” to appear and accumulate in the liver.As fibrosis worsens, the liver becomes seriously scarred, hardened, and unable to function normally.



The aim of treatment is to improve steatosis and prevent the development of fibrosis, which can lead to cirrhosis and its complications. Because the prognosis of NASH depends on risk factors (eg, obesity, insulin resistance, type 2 diabetes), these conditions have been the focus of treatment. Treatment proposed for NAFLD has been based on the 2-insult hypothesis; the first being fatty liver infiltration (linked to obesity and insulin resistance) and the second being oxidative stress. Patients should avoid alcohol and other hepatotoxins.

The treatment includes –

  • Treatment of Obesity – In adults with NASH, weight reduction has been widely studied and has been successful to improve not only the biochemical results but also the histology. Numerous drugs have been suggested, including – sibutramine, a serotonin reuptake inhibitor, and orlistat; which reduces fat absorption. Both of these have been shown to improve liver enzyme levels and sonographic signs of fatty liver. A meta-analysis of rimonabant, a cannabinoid-1-antagonist, showed that it is associated with increased adverse events and currently it cannot be recommended for NAFLD.Pharmacologic treatment of obesity in NASH is still experimental.
  • Lipid Lowering Agents – Oxidative stress has been hypothesized to contribute to the progression of NAFLD to NASH and to worsen insulin resistance. For this reason, antioxidant treatment to reduce this stress and slow the progression of the disease has been studied.
  • Insulin Sensitizing Agents -NASH patients with diabetes are at higher risk of developing more-aggressive disease. Insulin-sensitizing agents have been tested in adults. Metformin, a biguanide oral anti-diabetic agent, lowers hepatic glucose production and promotes glucose uptake in the muscles.

Peroxisome proliferator-activated receptor gamma (PPARg) agonists (thioglitazones) have been shown to improve insulin resistance, a surrogate marker of fatty liver, and histology by promoting redistribution of triglycerides from the liver and muscle into proliferating adipocytes.

  • Hepatoprotective Therapy – Several therapeutic agents believed to offer hepatocyte protection have been evaluated.Pentoxifylline inhibits a number of proinflammatory cytokines and may have hepatoprotective effects.
  • Others -The renin-angiotensin system may induce fibrosis in NAFLD. Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers (ARBs) can improve insulin sensitivity. ARBs, in small studies including a randomized controlled trial, have shown improvement in histologic inflammation and fibrosis.L-carnitine was found to improve steatosis, NAFLD histologic activity score and aminotransferases. Pilot studies based on the theory that NAFLD may be linked to small bowel bacterial overgrowth have shown some promise with the use of probiotics and prebiotics.
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