They say "A little knowledge is a dangerous thing". Most of the knowledge gained is based on what you
hear and what you see. Facts are mostly results of careful observation and interpretation, or are practically
proven and based on experience. "Alcohol damages liver" - A known fact worldwide. But how many of us
are familiar with liver damage being a consequence of other aspects of lifestyle than just alcohol consumption?
Liver- The largest organ of the body after skin, is an essential part of the organ system responsible for
a wide range of vital Tunctions required for smooth working of the body. Yet this very important organ
is vulnerable to the various habits we follow deviating away from healthy lifestyle The most common
diseases associated with liver due to unhealthy lifestyle are - Alcoholic liver disease and Non-alcoholic fatty liver disease.
Alcoholic Liver Disease
Alcoholic Liver Disease (ALD) is the cause of morbidity and mortality and occurs due to alcohol abuse i.e.
prolonged and excessive alcohol consumption. It is the leading cause of liver cirrhosis, liver failure both
acute and chronic, and at extreme cases increasing the risk of liver cancer as well. Approximately 3.8%
of global deaths are caused due to excessive alcohol consumption of alcohol dependence; about 1 in 7
men and 1 in 13 women in the age group of 15 to 64 years fall prey to liver damage due to alcohol abuse.
Alcohol Use Disorders (AUD) are responsible for liver cirrhosis while Alcohol Liver Diseases (ALD) are
the most important cause of death due to alcohol consumption. Consumption of alcohol in excess as
much as 40 g/day regularly can induce the formation of a range of liver lesions with variable degrees
of hepatic abnormalities. Alcoholic Liver Disease causes a great concern due to its contribution to the increasing risk of
liver conditions like inflammation and progressive fibrosis, liver cirrhosis, and also hepatocellular
carcinoma (HCC).
Pathogenesis
Although not completely understood, the complex interaction between the behavioral, environmental,
and genetic factors explains the mechanism of alcoholic liver diseases. Acetaldehyde, which is the
first metabolite of alcohol degradation is directly toxic to liver and responsible for the generation of
Alcoholic Liver Disease. Alcohol dehydrogenase and Cytochrome P450 2E1 (CYP2F1) are the two enzymes which are
responsible for processing of lower amounts of alcohol by metabolizing them to acetaldehydes via
oxidative degradation. While alcohol dehydrogenase is an enzyme that is found in the cytosol which
cannot be upregulated in alcoholics, the other enzyme cytochrome 1450 201 can be upregulated in
chronic drinkers. In Alcoholic Liver Disease, apart from generating.
acetaldehyde and CYP2E1 metabolites which are highly toxic and mutagenic, alcohol also produces
reactive oxygen species (ROS) such as superoxide anion and hydrogen peroxide which contributes
to oxidative damage of the liver.
The many conditions orchestrating for liver damage in alcoholics include disrupted liver turnover
(causing steatosis), decreased fatty acid oxidation, increased fat entry in to the liver from the peripheral
fat stores via fatty liver metabolism and increased fatty acid and triglyceride synthesis. Other aspects
instrumental in initiation of liver lesions include increased lipogenesis, peroxisome proliferator-activated
receptors and microsomal triglyceride transport proteins.
Inflammation is also an important feature of alcoholic steatohepatitis (Alcoholic fatty liver or ASH)
which may rise to be the underlying cause for fibrogenesis resulting to fibrosis, cirrhosis and at
extreme conditions leading to hepatocarcinogenesis.
Characteristic features of the ASH
1. Inflammatory infiltrates consisting of polymorphonuclear cells
2. Centrolobular hepatocyte ballooning
3. Mallory-Denk inclusion bodies
4. Chicken-Wire like fibrous networks
Following the gut-liver axis as the pathogenic pathway, the permeability of the gut increases
with the increase in ingestion of alcohol. It promotes the translocation of endotoxins from
lipopolysaccharides (gram-negative bacteria) which travels into the blood stream to reach the
Kupffer cells. Lipopolysaccharides bind to the endocrine receptors CD14, activating a signaling
pathway producing tumor necrosis factor a (inflammatory cytokine) which contributes to liver damage.
Fibrosis predominant in chronic liver diseases exhibits increased fibrogenesis and decreased
fibrolysis, mimicking the process of excessive wound healing. In progressive fibrosis,
damage to liver architecture and functional impairment is caused when liver parenchyma
is replaced by excess extracellular matrix. On activation of inflammatory cells such as Kupffer
cells, production of collagens, noncollagenous glycoproteins, proteoglycans and
glycosaminoglycans is regulated increasingly as compared to normal liver tissues. On the
contrary, downregulation of matrix degrading enzymes is initiated by the corresponding
tissue inhibitors.
Hepatocellular carcinoma (HCC) is another condition afflicting patients with alcohol cirrhosis.
Alcohol cirrhosis acts as precancerous condition, increasing the risk of HCC due to acetaldehyde,
which triggers the development of tumors. Acetaldehyde is also responsible for point mutations,
exchange of sister chromatids, inhibiting repair of DNA, a highly active mutagen converting
pro-carcinogens to carcinogens via CYP2E1 activity.
Non-Alcoholic Fatty Liver Diseases
Affecting about 25-35% of people around the globe, Non-alcoholic fatty liver disease (NAFLD) is
considered to be one of the most common chronic liver diseases in the recent studies especially
in relation to obesity. The disease is said to have a very close association with the metabolic
syndrome. The condition initiates from fat accumulation in the liver (fatty liver) which might then
progress to liver inflammation.
High risk factors of Non-Alcoholic Fatty Liver Diseases
Clinical studies reveal that Non-Alcoholic Fatty Liver Diseases patients suffer from a higher threat to following conditions,
1. 19-42% of all the Non-Alcoholic Fatty Liver Diseases cases expressed increasing levels of LDL (Low Density Lipoprotein)
cholesterol, even in the absence of significant degree of dyslipidaemia,
2. 66-83% incidences exhibit markers of insulin resistance with 18-33% of the cases possessing
type 2 diabetes mellitus,
3. In approximately 46% cases, increase in incidence of the disease is directly proportional to
the age, with higher mortality rates particularly in older age groups
Pathogenesis
Polymorphisms of genes such as PNPLA3, TMOSF2,FTO, LIPA, IFNA4 HFE, and HMOX-1 predisposes one for
the development and progression of Non-Alcoholic Fatty Liver Diseases.
High risk factors associated with development of Non-Alcoholic Fatty Liver Diseases are
1. Obesity
2. Diabetes mellitus
3. Hypertension
4. Metabolic syndrome
In patients with metabolic syndrome, Non-Alcoholic Fatty Liver Diseases and type 2 diabetes mellitus coexist because
the pathophysiology of alterations in carbohydrate and fat metabolism is similar to that of
alterations in hyperinsulinemia lead by insulin resistance. Type 2 diabetes mellitus contributes
to liver fibrosis and cirrhosis, also increases the risk of hepatocellar carcinoma in individuals
with Non-Alcoholic Fatty Liver Diseases. In cases of insulin resistance and hyperinsulinemia,
Complex metabolic pathways are initiated due to increase in adipocyte lipolysis and circulating
free fatty acids (taken up by the liver cells). Insulin resistance lowers the level of adiponectin
in the plasma which is responsible for insulin sensitivity and to reduce inflammation in individuals
with Non-Alcoholic Fatty Liver Diseases. Whereas, it increases leptin hormone concentration that regulates body weight and
fat mass. The increased free fatty acids produced due to insulin resistance are taken up by the
liver from circulation. The free fatty acids which are not oxidized are either stored in the liver
or are exported as very low density lipoproteins (VLDLs). This increases the risk of atherosclerosis
as well because high VLDL will elevate the level of circulating triglycerides and LDL, and reduce
the level of HDL.
Gastrointestinal hormones and adipokines which are responsible for controlling appetite also
contribute to Non-Alcoholic Fatty Liver Diseases pathogenesis. Glucagon levels elevated with altered insulin/glucagon
ratio is found in Non-Alcoholic Fatty Liver Diseases patients.
Insulin resistance is the risk factor in Non-Alcoholic Fatty Liver Diseases patients with type 2 diabetes mellitus, majority
of them are obese. Obesity is the aftermath of unhealthy lifestyle, physical inactivity and over
nutrition. In case of non-obese patients, high dietary intake of fructose and cholesterol as
well as genetic risk factors are predisposing aspects of Non-Alcoholic Fatty Liver Diseases.
Factors responsible for mortality, are listed below
In Alcoholic Liver Disease incidences -
1. When progresses to simple hepatic steatosis showing lower albumin levels,
2. When advanced fibrosis/cirrhosis occurs due to persistant alcohol intake or due to older
age, showing lower albumin levels,
3. In situations of compensated cirrhosis due to persistant alcohol intake,
4. Also in cases of decompensated cirrhosis caused either due to old age or alcohol abuse showing
elevated levels of alkaline phosphatase (ALP).
In Non-Alcoholic Fatty Liver Diseases incidences
1. When progressed to simple hepatic steatosis showing lower albumin levels,
2. When the risk of simple hepatic steatosis/ steatohepatitis increases due to older age
and becomes complex due to intervention of type 2 diabetes mellitus,
3. When advanced fibrosis/cirrhosis occurs due to older age, showing decreased level of
aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ratio.
Diagnosis
1. Non-Alcoholic Fatty Liver Diseases can be diagnosed with the liver function tests. Variations in the normal levels of the liver
enzymes will help diagnose the condition.
2. Non-Alcoholic Fatty Liver Diseases is usually suspected in obese patients and radiologic tests are performed such as
ultrasound and CT scan in order to detect swelling in abdomen.
3. Ultrasound imaging test can be performed which can show the accumulation of fat in the liver.
4. Biopsy is another major diagnostic technique used to confirm Non-Alcoholic Fatty Liver Diseases. In this procedure, fine
needle is inserted through the skin, collecting small tissue of liver and observing under microscope
for presence of fatty infiltration, inflammation and scarring.
5. Alcoholic Liver Disease can also be diagnosed with the help of LFT Blood Test. Apart from this, liver biopsy can
also be performed to confirm the disease. Its microscopic features will showcase classically ballooned
hepatocytes, inflamed cell infiltrate, necrosis, polymorphonuclear and mononuclear cells.
Both liver diseases are associated with improper lifestyle habits, over intake of alcohol or unhealthy
foods are the underlying cause for the abnormalities in liver functioning. What you feed your body,
is exactly what your body will give you in return. This simple relationship is understood from the liver
diseases discussed above where food and alcohol consumed affect the liver health and function and
its consequence is pronounced throughout the body.
