How NAFLD is different from alcoholic liver disease

Is your liver safe if you don’t drink alcohol? A spectrum of diseases with a global prevalence of 25 per cent among non-alcoholics says otherwise. Meet non-alcoholic fatty liver disease, the teetotaller edition of fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a range of conditions associated with metabolic disorders such as type 2 diabetes, obesity, hypertension and dyslipidaemia. Today, doctors almost always recommend changes in lifestyle as a plan of action to reverse NAFLD.

“In alcoholic liver disease (ALD), ethanol is the aetiology (cause of a disease or condition),” says Dr Anurag Lavekar, consultant gastroenterologist at Galaxy Hospital of Digestive and Liver Diseases, Mumbai. “In non-alcoholic fatty liver disease, the aetiology is obesity, diabetes and increased triglycerides which cause deposition of fat in the hepatocytes. Pathologically, there is no difference. Only the aetiology is different.”

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The two conditions (ALD and NAFLD) range from simple hepatic steatosis (increased build-up of fat in the liver) to steatohepatitis (liver inflammation with fat accumulation), liver cirrhosis and hepatocellular carcinoma (a common type of primary liver cancer).

Most people with excess eating and alcohol consumption experience simple hepatic steatosis, which can either be benign or progress to hepatocyte injury and inflammation; and chronic liver inflammation leads to cirrhosis.

Heavy consumption of alcohol causes ALD, which is determined by the frequency and quantity of consumption. The fat accumulation caused by heavy drinking builds up in the liver becomes enlarged – this is known as fatty liver.

Fatty liver in NAFLD, on the other hand, is caused by unhealthy diet and lifestyle. NAFLD refers to a range of liver conditions caused by the accumulation of fat cells in the liver in people who consume little to no alcohol. Although studies have found that it is associated with obesity, cardiovascular diseases, diabetes mellitus and kidney disease, they haven’t found a specific cause yet.

Medicines in the market go through multiple, randomised control trials and meta-analyses (examining various studies on the same subject to understand the trends) to provide clear evidence of their benefit. While pharmacological treatment for NAFLD does exist, there is no evidence-based treatment available.

“I might give vitamin D to the patient for three months and levels of SGOT and SGPT enzymes [produced by the liver and its cells] might come down, but that isn’t what we are looking for,” says Dr Tharanath S, general physician at MS Ramaiah Memorial Hospital, Bengaluru. “Research becomes statistically significant when the majority of a population show clinical symptoms when the medicine is used on them.”

Why is fatty liver dangerous?

Once fat accumulates in the liver, it develops into inflammation in the liver, progressing to non-alcoholic steatohepatitis (NASH), an advanced form of NAFLD. After the liver becomes inflamed, the levels of the liver enzymes SGOT and SGPT increase which can also result in cirrhosis (liver tissue is replaced by scar tissue, permanently damaging the liver) and may even cause liver cancer.

“The function of the liver is to synthesise albumin (a chief protein). In NAFLD, the liver starts shrinking in size and its functioning is impaired. When there is less albumin in the body, it leads to oedema – accumulation of fluid in the interstitial space (intercellular spaces surrounding the cells which aid the delivery of materials to the cells and intercellular communication),” Dr Tharanath says. Swelling of the legs and abdomen, and facial puffiness are some symptoms of oedema.

Liver inflammation also impairs the synthesis of coagulation (blood clotting) factors. When the clotting factors are not synthesised properly, any bleed in the natural processes of the body will not stop in time, resulting in uncontrolled bleeding.

What causes NAFLD?

We don’t know the exact cause of NAFLD, but we understand the conditions associated with it. These are comorbidities (two or more conditions occurring at the same time) and have a bidirectional influence on NAFLD (they either cause or are caused by fatty liver).

Obesity

A body mass index (BMI) of over 30 can be classified as obese. A high BMI and waist circumference predict the presence of NASH and advanced fibrosis. In NAFLD, visceral fat (fat in the abdomen) as opposed to subcutaneous fat delivers excess free fatty acids to the liver and promotes insulin resistance. The amount of visceral fat is an indicator of fatty liver, inflammation and fibrosis. Visceral fat is indicated by abdominal obesity, which refers to a waist circumference of 40 inches in men and 35 inches in women.

Even polycystic ovary syndrome (PCOS), a hormonal disorder in reproductive women, is related to NAFLD because of obesity, Dr Lavekar says. “NAFLD has a positive correlation with obesity,” the doctor says. “Obesity occurs because of hypothyroidism and becomes the root cause of several conditions such as PCOS, NAFLD and diabetes.”

Type 2 diabetes mellitus

People with ultrasound-based evidence of NAFLD are two to five times more likely to develop type 2 diabetes mellitus. Liver steatosis (NASH) affects the production of glycogen induced by insulin. Therefore, the fat content in the liver determines the insulin dosage for people diagnosed with both NAFLD and diabetes.

“The fat cells will not allow the insulin to act normally, and the insulin will not be able to act on its receptor because of obesity. So, obesity is one of the important causes of insulin resistance,” Dr Tharanath says, explaining the relationship between obesity, diabetes and NAFLD. “That is why weight loss is an important non-therapeutic, non-pharmacological intervention in diabetes. If you achieve weight loss, the insulin will automatically start acting better on its receptors.”

Cardiovascular disease

The primary cause of death in people with NAFLD is related to cardiovascular disease (CVD). An association has been established between NAFLD and several subclinical features of CVD such as the following:

• Coronary-artery calcium score (measures the calcium-containing plaque in the arteries)
• Carotid artery intimal media thickness (extent of plaque build-up in the walls of the arteries supplying blood to the head)
• Arterial wall stiffness (thickness of the carotid artery wall measured by ultrasound).

Chronic kidney disease

People with NAFLD have twice the risk of chronic kidney disease (CKD). The worsening of NASH fibrosis is associated with the worsening of CKS also. The greater fat deposition in the walls of the artery may also contribute to kidney damage. There is evidence to suggest that improvement in NAFLD can lead to improved renal function.

Lifestyle modifications

“If patients come to us seeking treatment in the form of pharmacotherapy, we cannot discourage them,” Dr Lavekar says, referring to the lack of proven pharmacological treatment for NAFLD. “Some treatments come at the cost of great risks, like developing prostate cancer. For non-diabetics, vitamin E was recommended and pioglitazone for diabetics. But there are contraindications for everything, and we need to customise treatment for every patient. Every individual is different.”

Today, modifying lifestyle is the main choice of treatment for NAFLD. Weight loss increased physical activity and dietary changes are prescribed to manage and even reverse NAFLD. Making changes in lifestyle involves controlling blood glucose, blood pressure, triglycerides and HDL (high-density lipoprotein) cholesterol.

The American Association for the Study of Liver Diseases recommends a three to five per cent reduction of body weight to improve steatosis, and a seven to 10 per cent reduction if the condition has progressed to NASH, including fibrosis.

Physical activity

Physical activity prevents NAFLD from progressing. Increasing your physical activity helps reduce hepatic (liver) fat. Aerobic activity and resistance training are beneficial. Since there is no universal recommendation for physical activity, it should be tailored to the individual’s medical situation, clinical characteristics and fitness capacity.

“Low-carb, low-fat, high-fibre diet and good physical activity — it is as simple as this,” says Dr Tharanath, when asked about his recommended course of action. “Physical activity doesn’t have to be vigorous. Guidelines say five days a week at least, 30 minutes of brisk walk should be adequate. Apart from that, cycling, skipping rope and running on the treadmill are also beneficial.”

Dietary changes

“Around 15-20 per cent of your diet should consist of carbohydrates, 15-20 per cent of calories from fats. A dietitian or a nutritionist will help you tailor your diet according to your tastes and preferences,” says Dr Lavekar. “I recommend the Mediterranean diet for people with NAFLD. It hasn’t taken off in India because it is expensive and doesn’t suit the Indian taste buds.”

In the case of NAFLD, a hypocaloric (restricting caloric intake) diet of 500 to 100 kcal daily is recommended. For NASH and fibrosis, a Mediterranean diet is found to be beneficial along with a macronutrient-specific diet:

• Saturated fat: reduced to less than 7% of total calories consumed
• Dietary cholesterol: not exceeding 200mg per day
• Total fat: Between 25% and 35% of total caloric intake.

From the research on fatty liver so far, we know although it can be very dangerous when left alone, it is possible to reverse NAFLD and even take preventive measures. A sedentary lifestyle, greater waist circumference, heart diseases, diabetes and high levels of bad cholesterol are some indicators that tell us to watch out for fat accumulation in the liver. Highly restrictive diets and high-intensity physical activity may have favourable short-term results, but the goal is to make sustainable, long-term changes in lifestyle so that even when NAFLD has been reversed, you don’t fall back into old patterns.