Nonalcoholic fatty liver disease (NAFLD) is now one of the most common causes of chronic liver disease. It is associated with lipid deposition in hepatocytes. It varies from simple steatosis, to nonalcoholic steatohepatitis- NASH, with inflammation and hepatocellular injury, to advanced fibrosis and cirrhosis. When it is simple fatty liver it is reversible but once NASH set up, it progresses to advanced fibrosis and cirrhosis.
EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease in 2016 has given following definition of NAFLD.^[1]
NAFLD is characterized by excessive hepatic fat accumulation, associated with insulin resistance, and defined by the presence of steatosis in >5% of hepatocytes according to histological analysis or by a proton density fat fraction >5.6% assessed by proton magnetic resonance spectroscopy (1HMRS) or quantitative fat/water selective magnetic resonance imaging (MRI).^[1]
According to EASL guideline ultrasound is the preferred first-line diagnostic procedure for imaging of NAFLD, as it provides additional diagnostic information.
Whenever imaging tools are not available or feasible serum biomarkers and scores are an acceptable alternative for the diagnosis of steatosis.
A quantitative estimation of liver fat can only be obtained by 1H-MRS. This technique is of value in clinical trials and experimental studies, but is expensive and not recommended in the clinical setting.^[1]
NASH has to be diagnosed by a liver biopsy showing steatosis, hepatocyte ballooning and lobular inflammation.^[1]
Most lean persons with NAFLD display insulin resistance and altered body fat distribution even though they have less severe metabolic disturbance than overweight NAFLD.^[1]
This malady is initially silent with or without right hypochondriac discomfort. It is often an incidentalitis-with raised transaminases on routine liver panel, or ultrasonogram done for other conditions. It is strongly associated with obesity and insulin resistance and is a constituent of the metabolic syndrome. NASH cirrhosis is now one of the leading indications for liver transplantation in the United States.^[2] So it is clear how it has been designated as a silent killer. Development of NASH may be the result of two stage liver insults. Initially, macrovesicular steatosis occurs which is a manifestation of excessive triglyceride accumulation in the liver.
Insulin resistance and subsequent hyperinsulinemia, due to obesity or mere sedentary life style appear to lead to alterations in the hepatocyte uptake, synthesis, degradation, and metabolism of free fatty acids and ultimately to accumulation of lipids in the hepatocytes. These changes seem to make the liver susceptible to an inflammatory response and progression of liver damage. Oxidative stress, mainly caused by mitochondrial dysfunction, and proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), Interleukin 1, are believed to play an important role in the progression of liver damage in NAFLD.
Several recent research have shown oxidative stress is caused by hepatic iron, leptin, and intestinal bacteria. Hepatocyte apoptosis is the final component involved in NAFLD progression.^[2]
Overall, mortality have been shown to be significantly higher in NASH patients. Incidence of Coronary artery disease and malignancy increases. Liver cirrhosis and carcinoma are the most common causes of death in NASH patients.
Data suggest that the natural history of NAFLD is determined by the severity of the histologic damage. Most patients with NAFLD have pure steatosis without nflammation and are reported to have a benign clinical course.
Of patients with NASH 15% to 25% progress to cirrhosis over 10 to 20 years.
At the time of initial biopsy, as many as 30% of NASH patients have advanced hepatic fibrosis, whereas 10% to 15% have well-established cirrhosis.^[2]
It is now recognized that a large portion of patients with cryptogenic cirrhosis is due to NASH.
NASH cirrhosis is a risk factor for development of hepatocellular carcinoma (HCC). Some studies report a prevalence of HCC in NAFLD patients of 0% to 0.5% and 0% to 2.8% in NASH patients over a 20-year period.^[2]

Importance of Diet :
Dietary habits and nutrients are the importan contributors to the development, progression, and treatment of NAFLD. Generally,hypercaloric diet, especially rich in Trans-Fatand Saturated fat and cholesterol, and fructosesweetenedbeverages seem to increase visceraladiposity and stimulate hepatic lipid accumulationand progression into Non-alcoholic Fatty LiverDisease, whereas reducing caloric intake,increasing soy protein and whey consumption,and food supplement of monounsaturated fattyacids, omega-3 fatty acids, and probiotics havepreventive and therapeutic effects.
Based on available data, at least 3-5% of weight loss, achieved by hypocaloric diet alone or in conjunction with exercise and life style modification, generally reduces hepatic steatosis, and up to 10% weight loss may be needed to improve hepatic inflammation. Moderate physical activity without weight loss also improves fatty liver as we have shown in a study published in this journal.^[3]
A sustained adherence to diet rather than the actual diet type is a major predictor of successful weight loss. Moreover, a healthy diet has benefits beyond weight reduction on NAFLD patients whether obese or of normal weight. Therefore, nutrition serves as a major route of prevention and treatment of NAFLD.^[4]
Ingestion of monounsaturated fatty acids (MUFAs) lowers the risk of development of cardiovascular disease and contributes to the improvement of lipid profile.
Food products rich in MUFAs include olive oil, rapeseed oil, sunflower, soy, nuts and avocado.
Replacement of dietary saturated fatty acids by monounsaturated fatty acids in a diet causes amelioration of serum glucose level and blood pressure. A diet rich in MUFAs increases the level of HDL-cholesterol and decreases the level of total cholesterol in subjects with diabetes.
Monounsaturated fatty acids inhibit oxidation of LDL-cholesterol and decrease the serum level of triglycerides by activation of peroxisome proliferator-activated receptor a (PPARa). A study conducted on humans with NASH confirmed the beneficial effect of a MUFA-rich diet on oxidative stress.
A food product notably rich in MUFAs is olive oil (74 g of MUFAs per 100 g) and rapeseed oil (cheaper). Numerous clinical trials confirm the favorable effect of olive oil on the prevention and treatment of metabolic syndrome. Unrefined, extra virgin olive oil contains a number of bioactive constituents with antioxidative properties. A diet enriched with olive oil improves endothelial function and inhibits pro inflammatory cytokine like TNF-a production.^[5]
Trans fatty acids occur naturally in dairy products. They are synthesized by bacterial microbiota in the gastrointestinal tract of ruminants. Trans fatty acids can also be made commercially during the production of margarine. They are formed during the hydrogenation of plant oils. Conjugated linoleic acid (isomer cis-9 trans-11) contained in dairy products does not negatively influence the human organism. On the other hand, trans fatty acids present in hydrogenated margarine exhibit the opposite effect. The intake of conjugated linoleic acid (isomer trans-10 cis- 12) in the form of hydrogenated margarine promotes proinflammatory cytokines, intensifies endothelium dysfunction and predisposes towards lipid profile disturbances.
Dietary recommendations in NAFLD suggest avoidance of the trans fatty acids contained in highly processed food products.^[5]
A number of studies have shown a significant relationship between high consumption of soft drinks and risk for obesity and diabetes development, especially in children and adolescents. Highly processed food is often rich in fructose and saccharose. These simple carbohydrates are very often used in the production of food.
Fructose is used as a sweetener in the production of juices, jellies and jams. Consumption of soft drinks and juices rich in high-fructose corn syrup (HFCS) has increased from 3.9% of total calories in 1977 to 9.2% of total calories in 2001. In addition, soft drinks contain considerably high amounts of aspartame and caramel colorant.
Caramel colorant is a high source of advanced glycation end products (AGEs) which exhibit pro-inflammatory properties. Consumption of soft drinks rich in fructose contributes to insulin resistance and furthermore stimulates NAFLD development. Fructose intensifies lipogenesis and triglycerides synthesis. Studies conducted on ducks and rats revealed that a high-fructose diet causes liver steatosis . In a study conducted on adult men it was proven that a normo-caloric diet with a 3 g of fructose per kg of body mass per day (about 41 of high-fructose soft drink) contributes to increased accumulation of lipids within hepatocytes, decreased insulin sensitivity and increased triglycerides serum level.
Consumption of more than one serving of a highfructose soft drink (about 360 ml) per day significantly increases the risk of metabolic syndrome development. That risk is not observed in subjects who do not consume any high-fructose soft drinks.^[5]

Remedy
Prebiotics
Prebiotics were first defined as “nondigestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, thus improving host health”.
This definition was later refined to include other areas that may benefit from selective targeting of particular microorganisms “a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora, that confer benefits.”
Lactobacilli and bifidobacteria are the usual target genera for prebiotics; Changes in bifidobacteria are more likely to be seen compared to lactobacilli. This may be due to the fact that more bifidobacteria usually reside in the human colon than lactobacilli, and they exhibit a preference for oligosaccharides.^[6] Prebiotics occur naturally in foods such as leeks, asparagus, chicory, Jerusalem artichokes, garlic, onions, wheat, oats, and soybeans.^[6] They should be included in the diet to prevent and reverse fatty liver.

Fiber :
Dietary fiber consists of nondigestible carbohydrates and lignin that are intrinsic and intact in plants.
Functional fiber consists of isolated, nondigestible carbohydrates that have beneficial physiological effects in humans.^[6]
Traditionally, dietary fiber was classified according to its solubility in an attempt to relate physiological effects to chemical types of fiber.
Soluble fibers were considered to have benefits on serum lipids, while insoluble fibers were linked with laxation benefits. But this is not always true.^[6]
Also, additional properties of fiber, such as viscosity and fermentability, may be more important characteristics in terms of physiological benefits. Viscous fibers are those that have gelforming properties in the intestinal tract, and fermentable fibers are those that can be metabolized by colonic bacteria. In general, soluble fibers are more completed fermented and have a higher viscosity than insoluble fibers.^[6] Water-soluble fibers (specifically, beta-glucan, psyllium, pectin, and guar gum) were most effective for lowering serum LDL cholesterol concentrations, without affecting high density lipoprotein (HDL) concentrations.^{[ 6 ]}
A multi-ethnic cohort followed 75,000 people for 14 years. People who ate more than 15g of fiber per day had significantly lower diabetes risk. People who ate high amounts of insoluble fiber (more than 17 g/day) or cereal fiber (more than 8 g/day) had less type II diabetes risk than people who had lower intakes.^[7]

Usually 25 g of fiber recommended daily for a 2000 calorie diet.^[6]
– Legumes including kidney, pinto, navy, lima and baked beans.
– Whole Grains wheat bran and oat bran are present in a variety of cereals and breads. Lentils, Flaxseeds or Linseed (Tishi, Alsi.), Chia seeds, Aples, Pears, Broccoli,spinachs, – Whole Fresh Fruits the valuable pectin fibre is found in the skin and pulp.^[7]

Oligofructose :
Oligofructose is an indigestible fructose oligomer that is found in plant food. Food products rich in oligofructose include chicory, artichoke, leek, asparagus and garlic. Clinical trials conducted on humans showed that oligofructose ingestion causes a reduction in triglycerides and glucose serum levels. Oligofructose supplementation in overweight and obese patients contributes to a decrease in postprandial glucose levels and it beneficially influences glycaemia control.
A diet rich in oligofructose stimulates satiety through bacterial fermentation and the increase in free fatty acid concentrations in the large intestine. In a study conducted on rats it was proven that oligofructose supplementation causes a reduction in the amount of consumed food and increases serum glucagon-like peptide 1 concentration (GLP-1). Oligofructose supplementation reduces the risk of insulin resistance, diabetes and obesity development in animals fed a high-fat diet (fat content : 72% of total calories). Additionally, oligofructose consumption attenuates the inflammation within hepatocytes. The influence of oligofructose is allegedly related to the action of GLP-1 and its concentration in brain cells and serum.
Oligofructose intake also causes a decrease in a ghrelin concentration. Ghrelin is an orexigenic hormone which stimulates food ingestion.^[8]
Food products rich in oligofructose include chicory, artichoke, leek, asparagus and garlic. They should be cosumed to reduce fatty liver.

Treatment Guidelines (Easl, Easd, Easo) :
While no firm recommendations can be made, pioglitazone (most efficacy data, but off-label outside T2DM) or vitamin E (better safety and tolerability in the short-term) or their combination could be used for NASH.^[1]
In the PIVENS trial, vitamin E (800 IU/day) improved steatosis, inflammation and ballooning and induced resolution of NASH in 36% of patients (21% in the placebo arm.^{[ 9 ]}
– The optimal duration of therapy is unknown; in patients with increased ALT at baseline, treatment should be stopped if there is no reduction in aminotransferases after 6 months of therapy; in patients with normal ALT at baseline, no recommendations can be made.^[1]
– Statins may be confidently used to reduce LDLcholesterol and prevent cardiovascular risk, with no benefits or harm on liver disease.
Similarly n-3 polyunsaturated fatty acids reduce both plasma and liver lipids, but there are no data to support their use specifically for NASH.^[1]