Non Alcoholic Fatty Liver Disease

Running head: NON ALCOHOLIC FATTY LIVER DISEASE
NON ALCOHOLIC FATTY LIVER DISEASE
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Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) describes a range of hepatic complications
associated with inflammation and increased deposition of adipose tissue in the hepatic surface.
Due to its association with metabolic complications, NAFLD has been found to prevail
extensively across developed countries as well as developing countries. A number of metabolic,
nutritional, lifestyle and hormonal factors are associated with the underlying pathophysiology of
NAFLD. Considering the same, primary treatments for NAFLD aim to target changes in diet,
lifestyle as well as anthropometric characteristics. However, additional treatments in terms of
bariatric surgery, antioxidant therapy, incretin interventions and insulin sensitizing agents have
been found to be beneficial in NAFLD treatment.

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Introduction
Natural History
Non-Alcoholic Fatty Liver Disease (NAFLD) is a collective term implying the
occurrence of a range of hepatic disease conditions found to inflict individuals who avoid or
engage in negligible alcohol consumption(Pappachan et al. 2017). Taking insights from the self-
explanatory nature of the name itself, NAFLD is characterized by excessive deposition of
excessive lipid and adipose tissues in the liver (Younossi et al. 2016). While the specific
pathologies underlying NAFLD occurrence is unknown, obesity is implicated to be a key
causative factor. Indeed, NAFLD has been observed extensively in patient who are overweight
or obese (Bellentani 2017).
Epidemiology
NAFLD has been found to exist highest in developed countries as well as in some
developing nations like the United States (30%), Middle East (32%), South America (30%), Asia
(27%), Europe (24%) and Africa (13%) (Pappachan et al. 2017).
Overview
NAFLD is at present one of the most widely prevalent diseases worldwide considering
the association of its pathology with obesity and the alarming rates at which obesity is increasing
in the global population. Lack of timely treatment and management of NAFLD results in the
acquisition of increased metabolic complications such cardiovascular complications and type 2
diabetes mellitus which further results in hepatic mortality (Adams et al. 2017). While specific
pathologies associated with NAFLD is still left to be discerned, metabolic malfunctioning

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associated with decreased insulin sensitivity and increased insulin resistance is estimated to be
the major causative factor, coupled with additional factors in hormonal, lifestyle, humoral and
genetic platforms (Targher et al. 2016). Treatments aimed at management of metabolic
complications such as, reductions of weight, dietary modifications and lifestyle alterations have
been considered to be most beneficial in addition to antioxidant consumption, incretin based
drugs, insulin sensitizers and bariatric surgery (Angulo et al. 2015). The following essay will
hence aim to explore the various pathologies, diagnostic steps and treatment procedures
associated with the management of NAFLD.
Pathophysiology
Causes
Abnormalities associated with metabolic functioning such as impaired glucose
intolerance, diabetes mellitus, cardiovascular diseases such as atherosclerosis, due to excessive
levels of adiposity, hyperglycemia, dislipidemia and hypertension are considered to be the
primary causative factors underlying NAFLD incidence in the individuals. However, the
presence of metabolic complications may not always be associated with NAFLD incidence an
hence, alternative factors are being explored for the purpose of evaluating the true pathologies
underlying the disease (Hardy et al. 2016). A key causative factor which may be implicated for
NAFLD incidence is oxidative stress which is a resultant of the imbalance in the functioning pro-
inflammatory components in the human body hence leading to increased levels of inflammation,
especially across hepatocytes responsible for metabolic processes (Pirola et al. 2015).
Additionally, intrinsic defense mechanisms to combat the body’s acquisition with disease
conditions and lifestyle stress may be implicated to be a causative factor underlying NAFLD

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acquisition. Increased engagement with detrimental dietary and lifestyle disorders such as fatty
food consumption and sedentary lifestyle experiences coupled with psychological stresses as
well as disease infliction results in the hepatic stimulation of intrinsic defense mechanism such as
hepatic production of pro-inflammatory cytokines which results in hepatocyte damage and lipid
accumulation (Francque, van der Graaff and Kwanten 2016). Additional factors which may be
implicated as the causes of NAFLD include white blood cell inflammatory defense processes,
consequences of the metabolic products released by intestinal gut micro flora functioning and
hepatocyte necrosis or apoptosis caused due to detrimental disease conditions (Haas, Francque.
and Staels 2016).
Pathology
The exact cause of NAFLD is relatively unknown. However, obesity and associated
increased adiposity in the abdomen has been implicated to be a key causative factor. Increased
adiposity has been associated with emergence of metabolic complications such as insulin
resistance and diabetes, which results in altered lipid metabolism, increased circulatory levels of
lipids, endothelial fatty streak deposition and the progressive deposition of adipose tissues in the
hepatocytes (Rahmani et al. 2016). The following pathological processes have been associated
with NAFLD emergence.
Nutrition
The consumption of a diet rich in saturated fat, carbohydrates and deficient in dietary
fiber are considerd to be the primary pathologies underlying NAFLD emergence, especially the
high intake of sucrose and fructose associated excessive sugary food and soda consumption.
Such dietary patterns have been associated to exert a pre-biotic effect and hence often results in
intestinal dysbiosis - a major consequence of SIBO or small intestinal bacterial overgrowth

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(Asgharpour et al. 2016). It is worthwhile to remember that the intestinal microflora exerts key
functions in terms of carbohydrate, sugar and dietary fiber metabolism resulting in production of
short chain fatty acids (SCFA) such as propionic acid and butyric acid. While such SCFA are
associated with anti-inflammatory and anti-carcinogenic functioning, excessive production duo
increased microbial colonies characteristic in intestinal dysbiosis may result in alterations of lipid
metabolism and hence, increased adipose accumulation in the hepatic tissue and the emergence
of NAFLD (Jump et al. 2016). The resultant hepatic enlargement due to increased adiposity has
been associated with non-alcoholic steatohepatitis (NASH) – that is hepatic inflammation and
hepatocyte auto-immune damage. The links between intestinal gut microflora and NAFLD
associated damage are further established due to the characteristic presence of tight epithelial
junctions within such patients (Estes et al. 2018). The microbial overgrowth discussed earlier
enter such junction and hence gain accessibility to release pro-inflammatory cytokines through
the systemic circulatory processes (Kirpich, Marsano and McClain 2015).
Hormones
The associated hormonal pathologies underlying NAFLD are often a resultant of
detrimental lifestyle and dietary patterns such as high fat and high sugar consumption which
further disrupts hormonal equilibrium. The increased consumption of such foods have been
implicated to yield positive effects in the limbic areas of the brain - the cerebral sections for
reward perception and hypothalamic functioning (Chishima et al. 2017). Detrimental lifestyle
and dietary behaviors result in continuous hypothalamic functioning in terms of ghrelin and
leptin production – hormones associated with appetite and satiety. Increased reward center
activation may exert overproduction of appetite stimulating ghrelin resulting in a conundrum of
over eating and the increased adipose accumulation in hepatic tissues (Norheim et al. 2017).