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LIVER DISEASES-AN OVERVIEW
*Dr. S. Sivakrishnan, M. Pharm, Ph.D.
Assistant Professor, Department of Pharmacy, Feat, Annamalai University, Tamilnadu, India.
ABSTRACT
Liver disease is the major cause of death every year. Approximately 29
million people suffer from a chronic liver condition (Blachier M, et al,
2013[1]) and more than 30 million Americans have liver diseases
(American liver foundation, 2017[2]). Liver diseases is the fifth big
killer in England after cancer, stroke and respiratory disease. The most
common causes of liver disease worldwide are chronic hepatitis B and
C, alcohol and non alcoholic steatohepatitis associated with obesity
and metabolic syndrome (HEPAMAP, 2007[3]). Around 10 lakh
patients of liver cirrhosis are newly diagnosed every year in India.
Liver disease is the tenth most common cause of death in India as per
the World Health Organization. Liver disease affect every one in five Indians. Liver disease
kills more people than diabetes and road deaths. Liver diseases does not usually cause any
obvious signs or symptoms until it’s fairly advanced and the liver is damaged. A number of
liver function test are available to test the proper function of the liver.
KEYWORDS: Liver, Hepatitis, Liver Cirrhosis.
INTRODUCTION
Liver is the second largest organ in human body, more than 5,000 separate bodily functions
including helping blood to clot, cleansing the blood of toxins to converting food into nutrients
to control hormone levels, fighting infections and illness, regenerating back after injury and
metabolizing cholesterol, glucose, iron and controlling their levels. Most people never give
their liver a thought until something goes wrong, yet, liver diseases on rise, affecting one in
ten. Liver diseases can be inherited or caused by a variety of factors that damage the liver. In
fact, there are many types of liver diseases that can be caused by a virus, damage from drugs
or chemicals, obesity, diabetes or an attack from own immune system, when the condition is
WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
SJIF Impact Factor 7.421
Volume 8, Issue 1, 1385-1395 Review Article ISSN 2278 – 4357
*Corresponding Author
Dr. S. Sivakrishnan
Assistant Professor,
Department of Pharmacy,
Feat, Annamalai University,
Tamilnadu, India.
Article Received on
20 Nov. 2018,
Revised on 10 Dec. 2018,
Accepted on 01 January 2019
DOI: 10.20959/wjpps20191-13036
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left untreated, it can become life threatening and can permanently damage the liver or the bile
duct. This damage leads to malignancy and cause liver cancer.
Liver Diseases
Numerous liver diseases are accompanied by jaundice caused by augmented levels of
bilirubin in the body. Bilirubin is the result of degradation of hemoglobin of dead red blood
cells which are normally removed by the liver and excreted via bile. In hepatitis,
inflammation of the liver, is caused by different viruses, but also some toxic substances,
autoimmune diseases and inherited conditions; Liver cirrhosis is the formation of fibrous
tissue in the liver to kill hepatocytes, respectively. Liver cell death can be caused by viral
hepatitis, alcohol poisoning or other toxic substances; Hemochromatosis is an inherited
disorder that causes iron accumulation in the body, leading to long-term liver damage;
Benign tumors such as adenoma, "angioma" focal nodular hyperplasia. Liver cancer as the
primary tumor or carcinoma cholangiocarcinoma or metastasis of cancer to other parts of the
digestive system; Wilson disease is an inherited disorder that causes copper accumulation in
the body; Primary sclerosing cholangitis, an inflammatory autoimmune disease carries bile;
Primary biliary cirrhosis, autoimmune disease of minute rage ducts; Budd-Chiari syndrome
or hepatic vein obstruction; Gilbert's syndrome, a genetic disorder of bilirubin metabolism.
There are also many pediatric liver diseases. Proper liver function can be verified by a
number of specialized clinical studies, which measure the presence or absence of typical
enzymes, metabolites or substances associated with the regular activities.
Acute Liver Failure ( Julie Polson et al., 2005[4])
Acute liver failure occurs when your liver rapidly loses its ability to function. More
commonly, liver failure develops slowly over the course of years. But acute liver failure,
develops in a matter of days. Acute liver failure can cause many complications, including
excessive bleeding and increasing pressure in the brain. Another term for acute liver failure is
fulminant hepatic failure. Acute liver failure is a medical emergency that requires
hospitalization. Some causes of acute liver failure can be reversed with treatment. But in
other situations, a liver transplant may be the only cure for acute liver failure.
Hepatitis (Dienstag JL, 2008[5])
Hepatitis is swelling and inflammation of the liver. The term is often used to refer to a viral
infection of the liver. Hepatitis can be caused by immune cells in the body attacking the liver
and causing autoimmune hepatitis, infections from viruses (such as Hepatitis A, B,C, D and
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E), bacteria or parasites, liver damage from alcohol, poisonous mushrooms or other poisons,
medications such as an overdose of acetaminophen, which can be deadly, Liver disease can
also be caused by inherited disorders such as cystic fibrosis or hemochromatosis, a condition
that involves having too much iron in our body (the excess iron deposits in the liver). Other
causes include Wilson's disease (excess copper deposits in the body). The symptoms of
hepatitis include: Abdominal pain or distention, breast development in males, dark urine, pale
or clay colored stools, fatigue, usually low-grade fever, general itching, jaundice (yellowing
of the skin and eyes), loss of appetite, nausea, vomiting and weight loss.
Hepatitis A
Hepatitis A is an inflammation (irritation and swelling) of the liver from the hepatitis A virus.
The hepatitis A virus is found mostly in the stools and blood of an infected person about 15 -
45 days before symptoms occur and during the first week of illness. Symptoms will usually
show up 2 - 6 weeks after being exposed to the hepatitis A virus. They are usually mild, but
may last for up to several months, especially in adults. Dark urine, fatigue, itching, loss of
appetite, low-grade fever, nausea, vomiting, anorexia, malaise(Koff RS,1998[6] & Elisabetta
Franco, Cristina Meleleo et al, 2012[7]), pale or clay-colored stools and yellow skin.
Hepatitis B
Hepatitis B is an irritation and swelling (inflammation) of the liver due to infection with the
hepatitis B virus (HBV). Hepatitis B spread by contact with the blood or body fluids (such as
semen, vaginal fluids, and saliva) of a person who has the virus. Symptoms of hepatitis B
may not appear for up to 6 months after the time of infection. Early symptoms include loss of
appetite, fatigue, low fever, muscle and joint aches, nausea and vomiting, jaundice, dark urine
right upper quadrant pain and hepatomegaly (Lee W, 1997[8]).
Hepatitis C
Hepatitis C is a viral disease that leads to swelling (inflammation) of the liver. Hepatitis C
infection is caused by the hepatitis C virus (HCV). Hepatitis C spreads by contact with the
blood of someone who has hepatitis C. The following symptoms may occur with hepatitis C
infection like pain in the right upper abdomen, abdominal swelling due to fluid (ascites),
clay-colored or pale stools, dark urine, fatigue, fever, itching, jaundice, loss of appetite,
nausea and vomiting.
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Delta Agent (Hepatitis D)
Delta agent is a type of virus called hepatitis D. It causes symptoms only in people who also
have a hepatitis B infection. Hepatitis D virus (HDV) is found only in people who carry the
hepatitis B virus. HDV may make a recent (acute) hepatitis B infection or an existing long-
term (chronic) hepatitis B liver disease which is worse. It can even cause symptoms in people
who carry hepatitis B virus but who never had symptoms. Risk factors include abusing
intravenous (IV) or injection drugs, being infected while pregnant (the mother can pass the
virus to the baby), carrying the hepatitis B virus, men having sexual intercourse with other
men, receiving many blood transfusions. Symptoms may include abdominal pain, dark-
colored urine, fatigue, jaundice, joint pain, loss of appetite, nausea and vomiting.
Hepatitis E
Hepatitis E is inflammation of the liver caused by infection with hepatitis E virus. It is one of
five known human hepatitis viruses. A,B,C,D and E. Heapatitis E Virus is a positive –sense,
single stranded non enveloped RNA icosahedral virus. HEV is predominantly transmitted by
faecal contamination of drinking water as a result of poor sanitation.( WHO. Hep. E Fact
Sheet. 2017[9] & Khuroo MS & Khuroo NS et al, 2016[10]) other routes of transmission
include consumption of contaminated food, such as raw or undercooked meat (eg: pork and
shellfish) derived from infected animals (Coloson P, Borentain P et al. 2010[11], Lewis Hc,
Wichmann O et al, 2010[12], Li TC, Chijiwa K et al. 2005[13] & Berto A, Martelli F et al,
2012[14]). and through transfusion of infected blood products which is more common in
highly endemic areas. (Khuro MS, Kamili S et al, 2004[15]). Symptoms may include jaundice,
malaise, anorexia nausea, vomiting, abdominal pain, hepatomegaly, pruritis and arthralgia.
Alagille Syndrome (Kamath BM et al., 2007[16])
Alagille syndrome is sometimes an autosomal dominant disorder, meaning a person inherits it
from one parent who has the disorder. In other cases, a gene mutation develops
spontaneously, meaning neither parent carries a copy of the mutated gene. A child who has a
parent with Alagille syndrome has a 50 percent chance of developing the disorder. Most
people with Alagille syndrome have a mutation or defect, in the Jagged1 (JAG1) gene.
Mutations in the NOTCH2 gene are seen in less than 1 percent of people with Alagille
syndrome. Infants with Alagille syndrome may have symptoms of liver disease and poor bile
drainage from the liver in the first few weeks. These symptoms can also occur in children and
adults with Alagille syndrome.
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Alcohol-Related Liver Disease (O'Shea RS et al., 2010[17] & Choi G et al., 2012[18])
Alcohol can damage or destroy liver cells. The liver breaks down alcohol so it can be
removed from body. Liver can become injured or seriously damaged if drink more alcohol
than it can process. There are three main types of alcohol-related liver disease: fatty liver
disease, alcoholic hepatitis and alcoholic cirrhosis. Many heavy drinkers will progress from
fatty liver disease to alcoholic hepatitis to alcoholic cirrhosis over time. However, some
heavy drinkers may develop cirrhosis without having alcoholic hepatitis first. Others may
have alcoholic hepatitis but never have symptoms.
Figure. 1: Normal liver and Alcohol affected liver.
Fatty Liver
Fatty liver disease is the build up of extra fat in liver cells. It is the earliest stage of alcohol-
related liver disease. There are usually no symptoms. If symptoms do occur, they may
include fatigue, weakness, and weight loss. Almost all heavy drinkers have fatty liver disease.
However, if they stop drinking, fatty liver disease will usually go away.
Alcoholic Hepatitis
Alcoholic hepatitis causes the liver to swell and become damaged. Symptoms may include
loss of appetite, nausea, vomiting, abdominal pain, fever and jaundice. Up to 35 percent of
heavy drinkers develop alcoholic hepatitis. Alcoholic hepatitis can be mild or severe. If it is
mild, liver damage may be reversed. If it is severe, it may occur suddenly and quickly lead to
serious complications including liver failure and death.
Alcoholic Cirrhosis
Alcoholic cirrhosis is the scarring of the liver (hard scar tissue replaces soft healthy tissue). It
is the most serious type of alcohol-related liver disease. Symptoms of cirrhosis are similar to
those of alcoholic hepatitis. Between 10 to 20 percent of heavy drinkers affect by cirrhosis.
The damage from cirrhosis cannot be reversed and can cause liver failure. Stoping alcohol
consumption can help to prevent further damage.
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Enlarged Liver (Ferri FF, 2012[19] & Goldman L et al., 2012[20])
Figure. 2: Enlarged liver.
An enlarged liver is one that's bigger than normal. The liver is a large, football-shaped organ
found in the upper right portion of abdomen. The medical term for enlarged liver is
hepatomegaly (hep-uh-to-MEG-uh-le). Enlarged liver isn't a disease. It's a sign of an
underlying problem, such as liver disease, congestive heart failure or cancer. Treatment for
enlarged liver involves identifying and controlling the underlying cause of the condition.
Many diseases and conditions can cause an enlarged liver, including: Liver diseases,
Cirrhosis, Hepatitis caused by a virus (including hepatitis A, B and C) or caused by infectious
mononucleosis, Non alcoholic fatty liver disease, Alcoholic fatty liver disease, amyloidosis (a
disorder that causes abnormal protein to accumulate in liver), Wilson's disease (a disorder
that causes copper to accumulate in liver), hemochromatosis (a disorder that causes iron to
accumulate in liver), Gaucher's disease (a disorder that causes fatty substances to accumulate
in liver), liver cysts (Fluid-filled pockets in the liver), Noncancerous liver tumors, including
hemangioma and adenoma, Obstruction of the gallbladder or bile ducts and toxic hepatitis.
Alpha-1 Antitrypsin Deficiency (Czaja AJ, 1998[21])
Alpha-1 antitrypsin deficiency (Alpha-1) is a hereditary genetic disorder which may lead to
the development of lung and/or liver disease. It is the most common genetic cause of liver
disease in children. Adults can also be affected by Alpha-1 and may develop lung conditions
such as emphysema as well as liver problems. Fortunately, many persons diagnosed with
Alpha-1 never develop any of the associated diseases.
Budd-Chiari Syndrome (Eldon A. Shaffer, 2007[22])
Budd-Chiari syndrome is caused by blood clots that completely or partially block the large
veins that carry blood from the liver (hepatic veins) into the inferior venacava. Usually, the
cause is a disorder that makes blood more likely to clot, such as excess red cells
(polycythemia), sickle cell disease, inflammatory bowel disease and connective tissue
disorders.
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Gilbert's Syndrome ( Claridge LC et al., 2011[23]): Gilbert's syndrome is a common, mild
liver condition in which the liver doesn't properly process a substance called bilirubin.
Bilirubin is produced by the breakdown of red blood cells. Gilbert's (zheel-BAYRZ)
syndrome typically is harmless and doesn't require treatment. Gilbert's syndrome is caused by
an inherited gene mutation. Person born with Gilbert's syndrome, may often goes
undiscovered for many years. Gilbert's syndrome is often discovered by accident, such as a
person have a blood test that shows elevated bilirubin levels. Gilbert's syndrome is also
known as constitutional hepatic dysfunction and familiar non hemolytic jaundice.
Liver-Hemangioma (Assy N et al., 2009[24])
Figure. 3: Liver Hemangioma.
Liver hemangioma (he-man-jee-O-muh) is a noncancerous (benign) mass that occurs in the
liver. Liver hemangioma is made up of a tangle of blood vessels. Most cases of liver
hemangioma are discovered during a test or procedure for some other condition. Most people
who have a liver hemangioma never experience signs and symptoms and don't need
treatment. There's no evidence that an untreated liver hemangioma can lead to liver cancer.
Nonalcoholic Steatohepatitis (American Liver Foundation, 2006[25])
Nonalcoholic steatohepatitis or NASH is a common, often “silent” liver disease. It resembles
alcoholic liver disease, but occurs in people who drink little or no alcohol. The major feature
of NASH is fat in the liver, along with inflammation and damage. Most people with NASH
feel well and are not aware that they have a liver problem. Nevertheless, NASH can be severe
and can lead to cirrhosis, in which the liver is permanently damaged and scarred and no
longer able to work properly. Although having fat in the liver is not normal, by itself it
probably causes little harm or permanent damage. If fat is suspected based on blood test
results or scans of the liver, this problem is called nonalcoholic fatty liver disease (NAFLD).
If liver biopsy is performed in this case reports will show that some people have NASH while
others have simple fatty liver.
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Portal Hypertension (Steven K. Herrine, 2012[26])
Portal hypertension is abnormally high blood pressure in the portal vein (the large vein that
brings blood from the intestine to the liver) and its branches. Cirrhosis (scarring that distorts
the structure of the liver and impairs its function) is the most common cause in Western
countries. Portal hypertension can lead to a swollen abdomen, abdominal discomfort,
confusion, and bleeding in the digestive tract.
Hepatic Encephalopathy: Hepatic encephalopathy (portosystemic encephalopathy, liver
encephalopathy or hepatic coma) is deterioration of brain function that occurs because toxic
substances normally removed by the liver build up in the blood and reach the brain. Hepatic
encephalopathy may be triggered by bleeding in the digestive tract, an infection, failure to
take drugs as prescribed, or another stress in people who have a long-standing (chronic) liver
disorder. People become confused, disoriented, drowsy with changes in personality, behavior,
and mood.
Ascites: Ascites is the accumulation of protein-containing (ascitic) fluid within the abdomen.
Many disorders can cause ascites, but cirrhosis is the most common. If large amount of fluid
accumulates, the abdomen becomes very large, sometimes making people lose their appetite
and feel short of breath and uncomfortable. Analysis of the fluid can help to determine the
cause. Usually, a low-sodium diet and diuretics can help to eliminate excess fluid. The
symptoms may include sudden weight gain, distended abdomen, abdominal pain, heart burn,
nausea and vomiting.
Cholestasis: Cholestasis is reduction or stoppage of bile flow. Disorders of the liver, bile
duct or pancreas can cause cholestasis. The symptoms of cholestatis is like skin and sclera of
the eyes look yellow, itching of skin, dark coloured urine, light-coloured and foul smelling
stool. With cholestasis, the flow of bile (the digestive fluid produced by the liver) is impaired
at some point between the liver cells (which produce bile) and the duodenum (the first
segment of the small intestine). When bile flow is stopped, the pigment bilirubin (a waste
product formed when old or damaged red blood cells are broken down) escapes into the
bloodstream and accumulates. Normally, bilirubin binds with bile in the liver, moves through
the bile ducts into the digestive tract and it is eliminated from the body via stool.
Jaundice: In jaundice, the skin and sclera of the eyes look yellow. Jaundice occurs when
there is too much bilirubin (a yellow pigment) in the blood (a condition called
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hyperbilirubinemia). Bilirubin is formed when hemoglobin (the part of red blood cells that
carries oxygen) is broken down as part of the normal process of recycling old or damaged red
blood cells. These symptoms may include nausea, vomiting, abdominal pain, and small spider
like blood vessels that are visible in the skin (spider angiomas). Men may have enlarged
breasts, shrunken testes, and pubic hair that grows as it does in women.
Primary Sclerosing Cholangitis (PSC): PSC is a disease that damages and blocks bile ducts
inside and outside the liver. Bile is a liquid secreted by liver. Bile ducts are tubes that carry
bile out of the liver to the gallbladder and small intestine. In the intestine, bile helps in break
down of fat in food. In PSC, inflammation of the bile ducts leads to scar formation and
narrowing of the ducts over time. As scarring increases, the ducts become blocked. As a
result, bile builds up in the liver and damages liver cells. Eventually, scar tissue can spread
throughout the liver, causing cirrhosis and liver failure.
Biliary Atresia (Hartley JL et al., 2009[27])
Biliary atresia is a life-threatening condition in infants in which the bile ducts inside or
outside the liver do not have normal openings. The two types of biliary atresia are, fetal and
perinatal. Fetal biliary atresia appears while the baby is in the womb. Perinatal biliary atresia
is much more common and does not become evident until 2 to 4 weeks after birth. Some
infants, particularly those with the fetal form, also have birth defects in the heart, spleen or
intestines. Symptoms may include weight loss, irritability, jaundice, liver may become harden
and distended abdomen, pale grey stools and dark urine.
Test For Liver Diseases: A number of liver function test are available to test the proper
function of the liver, (serum proteins, serum albumin, bilirubin (direct and indirect), ALT,
AST, GGT, ALP, PT and PTT). Imaging tests such as transient elastography, ultrasound and
magnetic resonance imaging can be used to examine the liver tissue and bile ducts. Liver
biopsy can be performed to examine liver tissue to distinguish between various conditions;
tests such as elastography may reduce the need for biopsy in some situations (Tapper EB,
Lok AS, 2017.[28]). Liver Biomarkers as well as the related in vitro diagnostic antibodies used
for diagnosis being provided.
CONCLUSION
Liver diseases can be inherited or caused by a variety of factors that damage the liver (virus,
drugs or chemicals, obesity, diabetes or an attack from own immune system), when the
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condition is left untreated, it can become life threatening and can permanently damage the
liver or the bile duct. This damage can then become malignant. The liver disease prognosis
depends on how quickly the condition was diagnosed and treated. In beginning stages, liver
disease usually responds to treatment, but in advanced liver disease, the damage done by
fibrosis, cirrhosis and liver failure cannot be reversed. This advanced stage leads to eventual
death. While diagnosing liver disease, the condition causing the disease must be treated. If
caught early, and are treated correctly, the damage to the liver may heal. In the middle stages
of disease, treatment may work to help heal the damage, but as the disease progresses,
treatments focus on managing the disease and prolonging the diagnosis.
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