Among the functions performed by the liver are
1. Release of bile as a part of digestion of fats, cholesterol and absorption of some vitamins, like vitamin K
2. Removal of toxins, including alcohol, from the body
3. metabolism of bilirubin, which is produced from the breakdown of hemoglobin ; after breakdown
of bilirubin, the iron is reused for synthesis of new blood cells
4. Carbohydrate metabolism, where stored carbohydrates are broken down in liver to glucose;
regulation of blood glucose and cholesterol levels
5. Home to a high number of Kupffer cells which are involved in immunity
6. Synthesis of proteins like albumin and hormones like angiotensin
Liver Diseases
Liver diseases are rising as one of the major lifestyle disorders in our country, and it adversely affects
the quality of life and also reducing life expectancy.
Hepatitis C
Hepatitis is the term used to describe inflammation of the liver. This condition may either resolve on its
own, or it may progress into fibrosis, cirrhosis, or even liver liver cancer. It can arise from several factors like
alcohol abuse, some drugs, autoimmune conditions and infections (caused by virus, bacteria, fungi and
parasites). If caused by a virus, it is known as viral hepatitis. There are 5 types of viral hepatitis and each
is caused by a different virus-Hepatitis A, B, C, D and E virus. Of these, HAV, HBV and HCV can cause
acute disease showing symptoms like nausea, abdominal pain, fatigue, malaise, and jaundice. In certain
cases, acute infection may also develop into chronic infection.
Hepatitis C is caused by the hepatitis C virus and can be acute or chronic hepatitis infection based on
the severity and duration of the infection. Acute HCV infection is usually asymptomatic while chronic
HCV infection is associated with a high risk of liver cirrhosis. Transmitted by infected blood, it is estimated
that 71 million people globally are infected by HCV. Some cases of HCV infections resolve themselves,
while some others develop into mild forms of the disease. In 60% of the cases, HCV infection develops
into the chronic progressive form. This depends upon the balance of several factors such as effectiveness,
specificity and rapidness of the immune response, and the replication rate of the virus.
The major complication of HCV infection is the development of fibrosis, which increases the morbidity and
mortality in chronic hepatitis by causing cirrhosis or hepatocarcinoma which can lead to death. After invasion
into a host, the virus multiplies in the bloodstream as well as various other tissues including the B and T
lymphocytes. While the liver is the principal site of replication, the virus also infects other tissues like those
of pancreas, thyroid, adrenal glands, spleen and bone marrow. HCV can also directly infect the lymphatic
tissue and can even lead to the development of B cell lymphoma. Since HCV variants develop when the
virus infects extrahepatic sites, immune recognition of the virus is also affected.
Alcoholic Liver Disease
Liver being the main site of alcohol metabolism, alcohol abuse leads to the development of alcoholic liver
disease. The metabolism of alcohol by the liver is done in three ways, by the alcohol dehydrogenase, by
cytochromes and by mitochondrial catalases. Of these, the first two enzymes convert alcohol to acetaldehyde
which is partly responsible for the damage to liver. Aside from this, the oxidative damage is caused to the
liver cells by simultaneous shortage of antioxidants in the liver cells and also by the alteration in the balance
of many cytokines, mainly tumor necrosis factor-alpha. Changes in lipid metabolism and in adipose tissue
can also promote injury to liver in alcoholic liver disease.
In chronic alcohol abusers, liver disease arises from chronic changes like steatohepatitis and fibrosis to
development of cirrhosis later in life. Simple steatosis is reversible through abstinence for a few weeks.
Steatohepatitis, while also reversible, is a fibrogenic process which induces changes that ultimately lead
to cirrhosis. Although simple steatosis is a relatively benign condition, with chronic alcohol abuse, it can
lead to the development of fibrosis and cirrhosis within 10 years. This progression also depends upon
other environmental factors. Severe alcoholic hepatitis can have a death rate of up to 50%.
Non-alcoholic Fatty Liver Disease (NAFLD)
Non-alcoholic fatty liver disease is a common term that is used to describe the condition in which adipose
tissue is deposited in the liver, and may sometimes manifest as progressive steatosis with associated
hepatitis, fibrosis, cirrhosis, and can progress to hepatocellular carcinoma (HCC). NAFLD is characterized
by steatosis of the liver without hepatocyte injury. Among the risk factors that can lead to the development
of NAFLD are metabolic syndrome, type 2 diabetes mellitus, high-fat diet, both passive and active smoke
exposure and reduced physical activity.
The accumulation of free fatty acids and Triglycerides is the hallmark of this condition and is partly attributable
to insulin resistance and obesity. Two steps are proposed to be involved in the development of NAFLD. The
first step involves hepatic lipid accumulation due to sedentary lifestyle, high-fat diet, obesity and insulin
resistance. The second step is the activation of inflammation associated with fibrosis. Insulin resistance is
believed to play a key role in the development of steatosis which leads to increased de novo lipogenesis and
reduced lipolysis. This causes accumulation of fats in the liver, which further causes adipose tissue dysfunction
through alterations in the production and secretion of cytokines, brought about by insulin resistance.
Triglyceride deposition is also seen due to production of reactive oxygen species and mitochondrial
dysfunction that is associated with endoplasmic reticulum stress.
Hepatocellular Carcinoma (HCC)
The most common primary malignancy of the liver, HCC is often seen in patients with chronic liver
disease and cirrhosis. It is believed to originate from hepatic stem cells, and can progress with local
expansion, intrahepatic spread, and distant metastasis. While cirrhosis is the most important risk factor
for the development of HCC, inflammation, necrosis and fibrosis also contribute to development of HCC.
Chronic infection with both hepatitis B and C are independent risk factors for HCC. When arising from
HBV infection, HCC presents with underlying cirrhosis of the liver. Patients with HCV infection also show
cirrhosis of the liver.
HCC mediates liver damage through the development of inflammation and fibrosis of the liver. In livers
with cirrhosis, focal areas with abnormal immature hepatocytes are known as dysplastic foci and these
are considered as precancerous lesions. Dysplastic foci (or dysplastic nodules) can be both low grade
and high grade and both have the potential to develop into HCC, although high grade HCC has a much
greater risk. The common pathophysiology that is involved in HCC is the repeated damage to hepatocytes
that leads to cycles of cell death and regeneration which results in cirrhosis and instability in the genome
of these cells leading to initiation of HCC. Multiple genetic events accumulate step wise including gene
rearrangement, somatic mutations, alterations in copy number, epigenetic changes as well as alterations
in growth factor pathways. These steps lead to progression of tumor and its metastasis.
The Role of Poor Lifestyle Habits
Disease conditions like non-alcoholic fatty liver disease and hepatitis C also require lifestyle modifications,
as do those individuals who have undergone liver transplantation. These modifications include both dietary
intervention and increase in physical activity. Most liver diseases affect particular cells of the liver more
severely than others, for example, the damage caused by alcohol related liver disease affects cells which
are located in the low oxygen venous parts of the liver, where the expression of detoxification enzymes is
elevated.
Following are the liver diseases that have been recorded to occur due to lifestyle related causes:
Alcohol Abuse
Alcohol abuse has been linked with the development of liver disease. Its pathogenesis involve enzymes that
alter the levels of acetaldehyde and reactive oxygen species (ROS). Both of these are products of alcohol
metabolism. Higher levels of ROS reduce the antioxidative activity which allows oxidative damage to proteins,
lipids and
DNA. These molecules then serve as antigens that elicit an immune response in the host,
also leading to inflammation reaction. The damage that ensues in the form of mitochondrial
and autophagy dysfunction causes depletion of energy and the accumulation of cytotoxic
mediators, ultimately culminating in cell death. Acetaldehyde also promotes the translocation
of bacterial lipopolysaccharides to the liver; this stimulates the synthesis of cytokines involved
in inflammation reaction. It is also responsible for disruption of lipid levels by impacting the
transport of lipoproteins
from the liver, decreasing the fatty acid oxidation and increasing
its biosynthesis.
Alcohol influences production of hormones and cytokines by adipose tissues. Inflammatory state,
as well as insulin resistance that are commonly seen in Obesity are also involved in alcoholic
liver disease. Chronic alcoholism is also an important risk factor for development of HCC. There
is correlation between the amount of alcohol consumed over lifetime and development of liver disease.
Obesity and Poor Dietary Habits
Majority of the patients with non-alcoholic fatty liver are obese. This disease is characterized
by development of liver steatosis to non-alcoholic steatohepatitis. The distribution of the fat is
also essential as people with higher levels of visceral fat are more likely to suffer from non-alcoholic
fatty liver disease. In some human trials, it was seen that the consumption of beverages containing
high fructose corn syrup is associated with development of liver cirrhosis. The ingested carbohydrates
are a major stimulus for de novo synthesis of lipids in the liver High levels of free fatty acids that
are derived from visceral adipose tissues, as well as chronic low grade inflammation that is often
seen in obesity are two of the most important contributing factors to progression of liver injury.
These adipose tissues also secrete adipokines which, along with accumulation of lipids in the liver,
further promote inflammation.
Obesity and the metabolic syndrome are recognized as independent risk factors for reduced response
to therapy and greater severity of the disease in Hepatitis C infection. Higher body mass index is
associated with increased steatosis in patients who suffer from chronic HCV. With increasing severity
of steatosis, there is a positive correlation with disease progression, worsening liver damage
and fibrosis in patients with chronic HCV. The increased levels of circulating insulin that is found
in obese individuals is considered to be associated with higher levels of fibrosis. Obesity also
increases the severity of alcohol induced liver damage. Further, research has shown that excess
of macro-components as well as deficiency in micronutrients are linked to increased severity of
liver diseas in overweight and obese individuals. Thus, the treatment of this condition mainly
includes anti-obesity medication and modification of lifestyle.
Heavy Smoking
In addition to harming the organs directly in contact with the smoke, smoking can also cause damage
to other organs including the liver. Three major effects of cigarette smoking on the liver are direct and
indirect toxic effects, immunological effects and oncogenic effects. The substances produced in the
body have cytotoxic effects which increase necroinflammation and fibrosis. It also results in increase
in the production of pro-inflammatory cytokines which can damage the liver. Smoking also causes
polycythemia and increases red cell mass and turnover. This in turn causes iron overload disease
which promotes oxidative stress in liver cells.
Smoking affects both branches of the immune systemhumoral and cell mediated. It acts by
blocking the proliferation and by induction of apoptosis in lymphocytes. The elevated iron
levels which induce oxidative stress and lipid peroxidation can activate stellate cells leading
to the development of fibrosis.
Oncogenic substances produced by smoking increase the risk of hepatocellular carcinoma in
patients who suffer from viral hepatitis and are independent of viral infection as well. Smoking
tobacco also suppresses the tumor suppressor gene p53, while also suppressing Tcell response.
Among the indirect toxic effects of smoking are increase in carboxyhemoglobin and decrease
in oxygen carrying capacity of red blood cells. It also increases the risk of developing hepatocellular
carcinoma in patients with chronic liver disease
Diagnosis of Liver Disorders
Liver disorders can be diagnosed by blood tests, imaging tests, and tissue analysis.
Among the biochemical tests, the four major tests that are done to check for liver abnormalities
are proteins, enzymes and other substances that are eliminated or processed by the liver and
whose levels are altered in the case of liver injury. These tests can indicate the potential severity
of liver injury as well as any changes in the status of liver health over time.
1. Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST)
Elevation in the levels of these enzymes indicates cellular damage from inflammation or cell
death. ALT levels are higher than AST in case of acute liver damage as seen in hepatitis.
2. Gamma-glutamyl transferase (GGT)
It is useful for detecting liver damage due to drugs and alcohol. It is also useful for follow up
of chronic alcoholism and helps for detecting early rejection after liver transplantation.
3. Alkaline phosphatase (ALP)
Elevated levels can indicate hepatobiliary disease and blockage of bile ducts, the pressure of
the blockage stimulates the liver to produce more ALP.
4. Albumin
Extensive loss of liver tissue which occurs in a long-standing disease can cause decrease in
albumin levels. It is also reduced in case of malnutrition, malabsorption, nephrotic syndrome,
chronic infections and alcoholic liver disease.
Tissue examination can include biopsy, wherein a part of the liver is sampled and assessed
microscopically for damage to liver, as well as for diagnosis of cancer.
Following imaging tests can be performed for detection and diagnosis of
liver diseases
Abdominal Ultrasound
A technique which uses ultrasound to create pictures of the liver, it can allow the evaluation
of blood flow to and from the liver.
Abdominal Computed Tomography (CT) scan
A procedure that combines X-ray equipment with computers that produce digital images of the
liver. It can help determine the severity of liver cirrhosis.
Magnetic Resonance Imaging (MRI)
In this technique, a strong magnetic field is used to obtain detailed images of the liver which
can detect the damage caused by various liver disorders.
Many liver disorders are asymptomatic; it is easy to fall into the sway of creature comforts and
ignore the fact that our actions have consequences unseen. Our liver is an organ that tirelessly
functions in systems as diverse as digestion and immunity. The silver lining to this cloud is the
fact that for a very long time, damage to liver caused by lifestyle is reversible. This is indeed the
best example that mending our ways in time can avert a greater calamity in the future.
