liver facts

8/11/2019 Liver Facts

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Liver facts

The liver is the largest solid organ in the body, weighing on average about 3.5 pounds.

The liver carries out a large number of critical functions, including manufacture of essential proteins, and

metabolism of fats and carbohydrates.

The liver also serves to eliminate harmful biochemical waste products and detoxify alcohol, certain drugs,

and environmental toxins.

The liver forms and secretes bile that contains bile acids to aid in the digestion and intestinal absorption

(taking in) of fats and the fat-soluble vitamins A, D, E, and K.

Diseases that may affect the liver include hepatitis (inflammation of the liver),cirrhosis(scarring),fatty

liver,andliver cancer(hepatocellular carcinoma).

Symptoms ofliver diseasemay include bleeding oreasy bruising,swelling,fatigue,andjaundice(yellow

coloring to the skin and whites of the eyes).

Liver overview

The liver is the largest solid organ in the body. People may not know that the liver is also the largest gland in

the body. The liver is actually two different types of gland. It is a secretory glandbecause it has a specialized

structure that is designed to allow it to make and secrete bile into the bile ducts. It also is an endocrine

glandsince it makes and secretes chemicals directly into the blood that have effects on other organs in the

body. Bile is a fluid that both aids in digestion and absorption of fats as well as carries waste products into the

intestine.

There are all sorts of glands in the body that make and secrete substances, including the pancreas (digestive

enzymes), thyroid and other endocrine glands (hormones), gastric glands in the stomach (acid), andlymph

glands or nodes(lymph).

Reviewed by William C. Shiel Jr., MD, FACP, FACR on 10/7/2011
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How large is the liver?

The liver weighs about three and a half pounds (1.6 kilograms). It measures about 8 inches (20 cm) horizontally

(across), and 6.5 inches (17 cm) vertically (down), and is 4.5 inches (12 cm) thick.

Where is the liver located (liver anatomy)?

The liver is located just below the diaphragm (the muscular membrane separating the chest from the

abdomen), primarily in the upper right part of the abdomen, mostly under the ribs. However, it also extends

across the middle of the upper abdomen and part way into the left upper abdomen. An irregularly shaped,

dome-like solid structure, the liver consists of two main parts (a larger right lobe and a smaller left lobe) and two

minor lobes. As you can see in the diagram below, the upper border of the right lobe is at the level of the top of

the 5th rib (a little less than 1/2 inch below the nipple), and the upper border of the left lobe is just below the 5th

rib (about 3/4 inch below the nipple). During inspiration (breathing in), the liver is pushed down by the

diaphragm and the lower edge of the liver descends below the margin of the lowest rib (costal margin).

What is the function of the liver?

The liver has a multitude of important and complex functions. Some of these functions are to:

Manufacture (synthesize) proteins, includingalbumin(to help maintain the volume of blood) and blood

clotting factors

Synthesize, store, and process (metabolize) fats, including fatty acids (used for energy) andcholesterol

Metabolize and store carbohydrates, which are used as the source for the sugar (glucose) in blood that

red blood cells and the brain use

Form and secrete bile that contains bile acids to aid in the intestinal absorption (taking in) of fats and the

fat-solublevitamins A, D, E, and K.
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Eliminate, by metabolizing and/or secreting, the potentially harmful biochemical products produced by the

body, such asbilirubinfrom the breakdown of old red blood cells, and ammonia from the breakdown of

proteins

Detoxify, by metabolizing and/or secreting, drugs, alcohol, and environmental toxins


What special features enable the liver to do so much?

The liver has many special features. For example, in order to carry out its secretory functions, ducts (tubes)

closely connect it to the gallbladder and intestines. Thus, bile made by the liver travels through these tubes to

the gallbladder. The bile is stored in the gallbladder between meals, and then is discharged into the intestines

at mealtime to aid in digestion.

For another example, the liver is appropriately situated in the body to directly receive the blood that comes from

the intestines (portal blood). With this arrangement, the liver can readily process (metabolize) nutrients

absorbed from food as well as other contents of the portal blood. Indeed, because of its numerous biochemical

functions, the liver is considered the biochemical factory of the body.

What's more, the liver is organized strategically to coordinate its structure, including its blood circulation, with

its functions. Four key features of this organization of the liver are as follows.

1. The basic unit of the liver is called an acinus (pronounced as' i-nus: plural acini). (There are numerous

acini in the liver.) In each acinus, the liver cells (hepatocytes) are grouped into three zones that are

anatomically related to the liver's blood supply and drainage. Thus, the blood enters zone one first, and

then travels through the second and third zones before leaving the liver. Each zone has its own special

functions to perform. (Moreover, because of these different functions, as well as the different relationships

to the flow of blood, the zones have different susceptibilities to injury.)

2. Specialized areas of the walls of adjacent liver cells (hepatocytes) join to form bile canaliculi (pronounced

kan" ah-lik' u-li). The canaliculi are microscopic tubes that transport bile that is produced by the liver cells

(hepatocytes). Then, meeting with other canaliculi, they ultimately empty into tiny bile ducts. These bile

ducts join with other bile ducts to form larger bile ducts that ultimately leave the liver.

3. The liver has a unique, dual blood supply. One comes from the portal vein, as already mentioned, and theother from the hepatic artery. The hepatic artery brings to the liver oxygenated blood that comes from the

lungs, heart, and branches of the aortic artery. So, finally, tiny branches of the portal vein and hepatic

artery travel in the liver together with the tiny bile ducts in tracts called portal tracts (triads).

4. The hepatic artery supplies blood to nourish the bile ducts and the liver cells (hepatocytes). This blood

joins with the portal vein blood in tiny blood vessels called sinusoids. Now, these sinusoids are situated on

each side of single-cell-thick plates of liver cells (hepatocytes), and they have an exceptionally porous
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(hole-filled) lining (epithelium). This unique arrangement enables passage of even large molecules (for

example, lipoproteins) through the sinusoidal lining to and from the liver cells (hepatocytes). The blood

travels in the sinusoids through the three acinar zones. Finally, the blood is drained from the liver by the

hepatic veins and then heads back to the heart and lungs.


What diseases affect the liver?Comment on thisRead 1 CommentShare Your Story

The most common liver diseases are various types of acute (sudden) hepatitis (inflammation), chronic (long

duration) hepatitis,fatty liver,cirrhosis(scarring), andcancer.Cancers that affect the liver are most commonly

metastatic cancers that have spread via the bloodstream to the liver from other sites in the body. However,

primary cancers (cancers that arise in the liver) can also occur. The most common type of primary liver cancersare known ashepatocellular carcinomas.Viruses, drugs, and alcohol, as well as metabolic, immune (defense)

system, and genetic (hereditary) abnormalities are the common causes of many liver diseases. But note that,

contrary to a popular misconception,alcoholis only one of the many causes of liver disease. Moreover,

sometimes the cause of the liver disease is not known.

How do liver diseases cause symptoms?Comment on thisRead 1 CommentShare Your Story

Acute and chronic liver diseases can interfere with the functions of the liver and thereby cause symptoms.

However, the liver has a hefty reserve capacity. In other words, it usually takes substantial damage to the liver

before a disease interferes with the functions of the liver and causes symptoms. Examples of such symptoms

are:

Jaundice(yellow skin) that can occur when the liver is unable to properly metabolize or secrete the yellow

pigment bilirubin in bile

Bleeding or easy bruising that can occur when the liver is unable to make enough of the normal blood

clotting proteins

Swelling of the legs with fluid (edema)that can occur when the liver is unable to make enough albumin

and the serum albumin gets too low

Fatiguethat is of unknown cause, but may be related to some impaired metabolic function of the liver

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What about blood tests for the diagnosis of liver disease?Comment on thisShare Your Story

Damage to the liver often gives rise to telltale abnormalities in certain blood tests (suggesting liver disease), the

so-calledliver blood tests(for example, ALT, AST, and alkaline phosphatase enzymes). As a matter of

convenience, the liver blood tests often are collectively referred to as liver function tests. But, abnormalities in

only some of them (i.e., elevated bilirubin, low albumin, and prolonged prothrombin time) actually reflect, atleast in part, abnormal function of the liver. And, it turns out that abnormalities of the other liver blood tests may

reflect the actual injury to the liver. For example,viral hepatitiscan cause the ALT or AST enzymes in injured

liver cells to spill into the blood stream and increase their level in the blood.

Sometimes, the pattern of liver blood test abnormalities provides a clue as to the type of liver disease. For

example, an AST to ALT ratio greater than two (as long as both are less than nine times normal) suggests

alcoholic hepatitis or cirrhosis of any type.

Other blood tests are more specific for the diagnosis of particular liver diseases. For example, there are

serological tests for most of the different types of viral hepatitis and immunological tests forprimary biliary

cirrhosis(antimitochondrial antibodies)or chronic autoimmune hepatitis (smooth muscle antibody). Additionally,

there are special tests forhemochromatosis(iron-related tests), Wilson's disease (copper-related tests), and

liver cancer (tumor markers).


Why does the doctor examine the liver?

The doctor examines the liver as part of the abdominal physical examination to try to gain helpful diagnosticinformation about a patient's liver condition. For example, the liver can be tender (painful to touch) with acute

hepatitis or feel hard and irregular (bumpy) with cancer of the liver. Also, some conditions can cause the liver to

enlarge (fatty liver or certain types of chronic hepatitis or cirrhosis), while others can make the liver smaller

(advanced cirrhosis).

What is a liver biopsy?Comment on thisRead 1 CommentShare Your Story

The most accurate way to diagnose the type of liver disease is by doing aliver biopsy,although a biopsy is not

necessary in most cases. This procedure involves removing, with a thin hollow needle, a small piece of liver

tissue for microscopic study. What's interesting about a liver biopsy is that the tiny sample is usually

representative of the disease (pathology) in the rest of this large organ. Put another way, most liver disease

involves the entire liver. When the disease is localized to only a small part of the liver, as for example, cancer

usually is, the biopsy can be done with ultrasonic visual guidance to be certain that the small, involved area is

biopsied.

What else is important about the liver?
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There's one other interesting point about this remarkable organ. The liver has an extraordinary capacity to

regenerate (reproduce itself). For example, damage the liver, and it will soon regenerate in an attempt to

restore its functions. Cut out a part of the liver, and it likewise will grow back (regenerate) rapidly. In fact, when

a person donates a part of her or his liver for transplantation, much of the part that is removed will soon grow

back.

There's a famous story in Greek and Roman mythology that testifies to the liver's great capacity to regenerate.

Witness Prometheus chained to a rock on a mountain. This confinement was his punishment because he had

displeased the ruler Zeus (Jupiter, if you prefer Latin to Greek) by providing fire (and other benefits) to

humankind. Picture a vulture pecking away at the liver of the helpless Prometheus. He survived, however,

according to the legend, because his liver renewed itself as fast as the vulture devoured it.

REFERENCE: Fauci, Anthony S., et al. Harrison's Principles of Internal Medicine. 17th ed. United States: McGraw-Hill

Professional, 2008.

Previous contributing author:Leslie J. Schoenfield, MD, PhD

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Comment from: Anne, 55-64 Female (Patient)Published: June 05
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I was just advised by my doctor that I have a cyst on my liver.I'm not sure what that means. She is sending me for aCT

scanwithin the next few weeks.

I had pains under my leftbreast.

I had aliverbiopsy today. It was not as bad as I had thought it would be. After the happy juice, I felt a small pinch while

numbing the liver area for puncture and the site where the sample would be taken. Then, poof, it was over. So don't worry,

and don't let others' experiences scare you.
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What is cirrhosis?

Cirrhosis is a complication of manyliver diseasesthat is characterized by abnormal structure and function of

the liver. The diseases that lead to cirrhosis do so because they injure and kill liver cells, and the inflammation

and repair that is associated with the dying liver cells causes scar tissue to form. The liver cells that do not die

multiply in an attempt to replace the cells that have died. This results in clusters of newly-formed liver cells

(regenerative nodules) within the scar tissue. There are many causes of cirrhosis; they include chemicals (suchas alcohol, fat, and certain medications),viruses,toxic metals (such as iron and copper that accumulate in the

liver as a result ofgeneticdiseases), andautoimmuneliver diseasein which the body'simmune systemattacks

the liver.

Why does cirrhosis cause problems?Comment on thisRead 9 CommentsShare Your Story

The liver is an important organ in the body. It performs many critical functions, two of which are producing

substances required by the body, for example, clotting proteins that are necessary in order for blood to clot,

and removing toxic substances that can be harmful to the body, for example, drugs. The liver also has an

important role in regulating the supply to the body ofglucose(sugar) andlipids(fat) that the body uses as fuel.

In order to perform these critical functions, the liver cells must be working normally, and they must have an

intimate relationship with the blood since the substances that are added or removed by the liver are transported

to and from the liver by the blood.

The relationship of the liver to the blood is unique. Unlike most organs in the body, only a small amount of

blood is supplied to the liver by arteries. Most of the liver's supply of blood comes from the intestinal veins as

the blood returns to the heart. The main vein that returns blood from the intestines is called the portal vein.As

the portal vein passes through the liver, it breaks up into increasingly smaller and smaller veins. The tiniest

veins (called sinusoids because of their unique structure) are in close contact with the liver cells. In fact, the

liver cells line up along the length of the sinusoids. This close relationship between the liver cells and blood

from the portal vein allows the liver cells to remove and add substances to the blood. Once the blood has

passed through the sinusoids, it is collected in increasingly larger and larger veins that ultimately form a single

vein, thehepatic veinthat returns the blood to the heart.

In cirrhosis, the relationship between blood and liver cells is destroyed. Even though the liver cells that survive

or are newly-formed may be able to produce and remove substances from the blood, they do not have the

normal, intimate relationship with the blood, and this interferes with the liver cells' ability to add or remove

substances from the blood. In addition, the scarring within the cirrhotic liver obstructs the flow of blood through

the liver and to the liver cells. As a result of the obstruction to the flow of blood through the liver, blood "backs-

up" in the portal vein, and the pressure in the portal vein increases, a condition calledportal hypertension.

Because of the obstruction to flow and high pressures in the portal vein, blood in the portal vein seeks other

veins in which to return to the heart, veins with lower pressures that bypass the liver. Unfortunately, the liver isunable to add or remove substances from blood that bypasses it. It is a combination of reduced numbers of

liver cells, loss of the normal contact between blood passing through the liver and the liver cells, and blood

bypassing the liver that leads to many of the manifestations of cirrhosis.

A second reason for the problems caused by cirrhosis is the disturbed relationship between the liver cells and

the channels through whichbileflows. Bile is a fluid produced by liver cells that has two important functions: to

aid in digestion and to remove and eliminate toxic substances from the body. The bile that is produced by liver
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cells is secreted into very tiny channels that run between the liver cells that line the sinusoids, called canaliculi.

The canaliculi empty into small ducts which then join together to form larger and larger ducts. Ultimately, all of

the ducts combine into one duct that enters thesmall intestine.In this way, bile gets to the intestine where it

can help with the digestion of food. At the same time, toxic substances contained in the bile enter the intestine

and then are eliminated in thestool.In cirrhosis, the canaliculi are abnormal and the relationship between liver

cells and canaliculi is destroyed, just like the relationship between the liver cells and blood in the sinusoids. Asa result, the liver is not able to eliminate toxic substances normally, and they can accumulate in the body. To a

minor extent, digestion in the intestine also is reduced.

What are the symptoms and signs of cirrhosis?Comment on thisRead 29 CommentsShare Your Story

Patients with cirrhosis may have few or no symptoms and signs of liver disease. Some of the symptoms may

be nonspecific, that is, they don't suggest that the liver is their cause. Some of the more common symptoms

and signs of cirrhosis include:

Yellowing of the skin (jaundice)due to the accumulation ofbilirubinin the blood

Fatigue

Weakness

Loss of appetite

Itching

Easy bruisingfrom decreased production of blood clotting factors by the diseased liver.

Patients with cirrhosis also develop symptoms and signs from the complications of cirrhosis that are discussed

next.

What are the complications of cirrhosis?

Edema and ascites

Ascirrhosis of the liverbecomes severe, signals are sent to the kidneys to retain salt and water in the body.

The excess salt and water first accumulates in the tissue beneath the skin of the ankles and legs because of

the effect of gravity when standing or sitting. This accumulation of fluid is called edema or pitting edema.

(Pitting edema refers to the fact that pressing a fingertip firmly against an ankle or leg with edema causes an

indentation in the skin that persists for some time after release of the pressure. Actually, any type of pressure,

such as from the elastic band of a sock, may be enough to cause pitting.) The swelling often is worse at theend of a day after standing or sitting and may lessen overnight as a result of the loss of the effects of gravity

when lying down. As cirrhosis worsens and more salt and water are retained, fluid also may accumulate in

theabdominal cavitybetween the abdominal wall and the abdominal organs. This accumulation of fluid

(calledascites) causes swelling of the abdomen, abdominal discomfort, and increased weight.

Spontaneous bacterial peritonitis (SBP)
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Fluid in the abdominal cavity (ascites) is the perfect place for bacteria to grow. Normally, the abdominal cavity

contains a very small amount of fluid that is able to resist infection well, and bacteria that enter the abdomen

(usually from the intestine) are killed or find their way into the portal vein and to the liver where they are killed.

In cirrhosis, the fluid that collects in the abdomen is unable to resist infection normally. In addition, more

bacteria find their way from the intestine into the ascites. Therefore, infection within the abdomen and the

ascites, referred to as spontaneous bacterial peritonitis or SBP, is likely to occur. SBP is a life- threateningcomplication. Some patients with SBP have no symptoms, while others havefever,chills,abdominal painand

tenderness,diarrhea,and worsening ascites.

Bleeding from esophageal varices

In the cirrhotic liver, the scar tissue blocks the flow of blood returning to the heart from the intestines and raises

the pressure in the portal vein (portal hypertension). When pressure in the portal vein becomes high enough, it

causes blood to flow around the liver through veins with lower pressure to reach the heart. The most common

veins through which blood bypasses the liver are the veins lining the lower part of theesophagusand the upper

part of thestomach.

As a result of the increased flow of blood and the resulting increase in pressure, the veins in the lower

esophagus and upper stomach expand and then are referred to as esophageal andgastricvarices; the higher

the portal pressure, the larger the varices and the more likely a patient is to bleed from the varices into the

esophagus or stomach.

Bleeding from varices usually is severe and, without immediate treatment, can be fatal. Symptoms of bleeding

from varices includevomiting blood(thevomituscan be red blood mixed with clots or "coffee grounds" in

appearance, the latter due to the effect of acid on the blood), passing stool that is black and tarry due to

changes in the blood as it passes through the intestine (melena), and orthostaticdizzinessorfainting(caused

by a drop inblood pressureespecially when standing up from a lying position).

Bleeding also may occur from varices that form elsewhere in the intestines, for example, the colon, but this is

rare. For reasons yet unknown, patients hospitalized because of actively bleeding esophageal varices have a

high risk of developing spontaneous bacterial peritonitis.

Hepatic encephalopathy

Some of the protein in food that escapes digestion and absorption is used by bacteria that are normally present

in the intestine. While using the protein for their own purposes, the bacteria make substances that they release

into the intestine. These substances then can be absorbed into the body. Some of these substances, for

example,ammonia,can have toxic effects on the brain. Ordinarily, these toxic substances are carried from the

intestine in the portal vein to the liver where they are removed from the blood and detoxified.

As previously discussed, when cirrhosis is present, liver cells cannot function normally either because they are

damaged or because they have lost their normal relationship with the blood. In addition, some of the blood in

the portal vein bypasses the liver through other veins. The result of these abnormalities is that toxic substances

cannot be removed by the liver cells, and, instead, the toxic substances accumulate in the blood.

When the toxic substances accumulate sufficiently in the blood, the function of the brain is impaired, a condition

calledhepatic encephalopathy.Sleeping during the day rather than at night (reversal of the
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normalsleeppattern) is among the earliest symptoms of hepatic encephalopathy. Other symptoms include

irritability, inability to concentrate or perform calculations, loss of memory,confusion,or depressed levels of

consciousness. Ultimately, severe hepatic encephalopathy causescomaand death.

The toxic substances also make the brains of patients with cirrhosis very sensitive to drugs that are normally

filtered and detoxified by the liver. Doses of many drugs that normally are detoxified by the liver have to bereduced to avoid a toxic buildup in cirrhosis, particularly sedatives and drugs that are used to promote sleep.

Alternatively, drugs may be used that do not need to be detoxified or eliminated from the body by the liver, for

example, drugs that are eliminated by the kidneys.

Hepatorenal syndrome

Patients with worsening cirrhosis can develop the hepatorenal syndrome. This syndrome is a serious

complication in which the function of the kidneys is reduced. It is a functional problem in the kidneys, that is,

there is no physical damage to the kidneys. Instead, the reduced function is due to changes in the way the

blood flows through the kidneys themselves. The hepatorenal syndrome is defined as progressive failure of the

kidneys to clear substances from the blood and produce adequate amounts ofurineeven though some other

important functions of thekidney,such as retention of salt, are maintained. If liver function improves or a

healthy liver is transplanted into a patient with hepatorenal syndrome, the kidneys usually begin to work

normally. This suggests that the reduced function of the kidneys is the result of the accumulation of toxic

substances in the blood when the liver fails. There are two types of hepatorenal syndrome. One type occurs

gradually over months. The other occurs rapidly over a week or two.

Hepatopulmonary syndrome

Rarely, some patients with advanced cirrhosis can develop the hepatopulmonary syndrome. These patients

can experience difficulty breathing because certain hormones released in advanced cirrhosis cause the lungs

to function abnormally. The basic problem in the lung is that not enough blood flows through the small blood

vessels in the lungs that are in contact with thealveoli(air sacs) of the lungs. Blood flowing through the lungs is

shunted around the alveoli and cannot pick up enough oxygen from the air in the alveoli. As a result the patient

experiencesshortness of breath,particularly with exertion.

Hypersplenism

Thespleennormally acts as a filter to remove olderred blood cells,white blood cells, and platelets (small

particles that are important for the clotting of blood.). The blood that drains from the spleen joins the blood in

the portal vein from the intestines. As the pressure in the portal vein rises in cirrhosis, it increasingly blocks the

flow of blood from the spleen. The blood "backs-up" and accumulates in the spleen, and the spleen swells in

size, a condition referred to assplenomegaly.Sometimes, the spleen is so swollen that it causesabdominal

pain.

As the spleen enlarges, it filters out more and more of the blood cells and platelets until their numbers in the

blood are reduced. Hypersplenism is the term used to describe this condition, and it is associated with a low

red blood cell count (anemia), lowwhite blood cell count(leucopenia), and/or a low platelet count

(thrombocytopenia). The anemia can cause weakness, the leucopenia can lead to infections, and the

thrombocytopenia can impair the clotting of blood and result in prolonged bleeding.

Liver cancer (hepatocellular carcinoma)
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Cirrhosis due to any cause increases the risk of primaryliver cancer(hepatocellular carcinoma). Primary refers

to the fact that the tumor originates in the liver. A secondary liver cancer is one that originates elsewhere in the

body and spreads (metastasizes) to the liver.

The most common symptoms and signs of primary liver cancer are abdominal pain and swelling, an enlarged

liver,weight loss,and fever. In addition, liver cancers can produce and release a number of substances,including ones that cause an increased inred blood cellcount (erythrocytosis), low blood sugar

(hypoglycemia), and high blood calcium (hypercalcemia).

What are the common causes of cirrhosis?

Alcoholis a very common cause of cirrhosis, particularly in the Western world. The development of

cirrhosis depends upon the amount and regularity of alcohol intake. Chronic, high levels of alcohol

consumption injure liver cells. Thirty percent of individuals who drink daily at least eight to sixteen ouncesof hard liquor or the equivalent for fifteen or more years will develop cirrhosis. Alcohol causes a range of

liver diseases; from simple and uncomplicatedfatty liver(steatosis), to the more serious fatty liver with

inflammation (steatohepatitisor alcoholic hepatitis), to cirrhosis.

Nonalcoholic fatty liver disease (NAFLD)refers to a wide spectrum of liver diseases that, like alcoholic

liver disease, ranges from simple steatosis, to nonalcoholic steatohepatitis (NASH), to cirrhosis. All stages

ofNAFLDhave in common the accumulation of fat in liver cells. The term nonalcoholic is used because

NAFLD occurs in individuals who do not consume excessive amounts of alcohol, yet, in many respects,

the microscopic picture of NAFLD is similar to what can be seen in liver disease that is due to excessive

alcohol. NAFLD is associated with a condition calledinsulin resistance,which, in turn, is associated with

themetabolic syndromeanddiabetesmellitus type 2.Obesityis the most important cause of insulin

resistance, metabolic syndrome, and type 2 diabetes. NAFLD is the most common liver disease in theUnited States and is responsible for 24% of all liver disease. In fact, the number of livers that are

transplanted for NAFLD-related cirrhosis is on the rise.Public healthofficials are worried that the

currentepidemicofobesitywill dramatically increase the development of NAFLD and cirrhosis in the

population.

Cryptogenic cirrhosis(cirrhosis due to unidentified causes)is a common reason for liver

transplantation. It is termed cryptogenic cirrhosis because for many years doctors have been unable to

explain why a proportion of patients developed cirrhosis. Doctors now believe that cryptogenic cirrhosis is

due to NASH (nonalcoholic steatohepatitis) caused by long standing obesity, type 2 diabetes,

andinsulinresistance. The fat in the liver of patients with NASH is believed to disappear with the onset of

cirrhosis, and this has made it difficult for doctors to make the connection between NASH and cryptogenic

cirrhosis for a long time. One important clue that NASH leads to cryptogenic cirrhosis is the finding of ahigh occurrence of NASH in the new livers of patients undergoingliver transplantfor cryptogenic cirrhosis.

Finally, a study from France suggests that patients with NASH have a similar risk of developing cirrhosis

as patients with long standing infection withhepatitis Cvirus. (See discussion that follows.) However, the

progression to cirrhosis from NASH is thought to be slow and the diagnosis of cirrhosis typically is made in

patients in their sixties.

Chronic viral hepatitisis a condition wherehepatitis Borhepatitis Cvirus infects the liver for years. Most

patients withviral hepatitiswill not develop chronic hepatitis and cirrhosis. For example, the majority of
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patients infected withhepatitis Arecover completely within weeks, without developing chronic infection. In

contrast, some patients infected with hepatitis B virus and most patients infected with hepatitis C virus

develop chronic hepatitis, which, in turn, causes progressive liver damage and leads to cirrhosis, and,

sometimes, liver cancers.

Inherited (genetic) disordersresult in the accumulation of toxic substances in the liver which lead to

tissue damage and cirrhosis. Examples include the abnormal accumulation of iron (hemochromatosis) orcopper (Wilson's disease). Inhemochromatosis,patients inherit a tendency to absorb an excessive

amount of iron from food. Over time, iron accumulation in different organs throughout the body causes

cirrhosis,arthritis,heart muscledamage leading toheart failure,and testicular dysfunction causing loss of

sexual drive. Treatment is aimed at preventing damage to organs by removing iron from the body through

bloodletting (removing blood). InWilson disease,there is an inherited abnormality in one of the proteins

that controls copper in the body. Over time, copper accumulates in the liver, eyes, and brain.

Cirrhosis,tremor,psychiatricdisturbances and otherneurologicaldifficulties occur if the condition is not

treated early. Treatment is with oral medication that increases the amount of copper that is eliminated from

the body in the urine.

Primary biliary cirrhosis (PBC)is a liver disease caused by an abnormality of the immune system that is

found predominantly in women. The abnormal immunity in PBC causes chronic inflammation anddestruction of the small bile ducts within the liver. The bile ducts are passages within the liver through

which bile travels to the intestine. Bile is a fluid produced by the liver that contains substances required for

digestion and absorption of fat in the intestine, as well as other compounds that are waste products, such

as the pigment bilirubin. (Bilirubin is produced by the breakdown ofhemoglobinfrom old red blood cells.).

Along with thegallbladder,the bile ducts make up thebiliarytract. InPBC,the destruction of the small bile

ducts blocks the normal flow of bile into the intestine. As the inflammation continues to destroy more of the

bile ducts, it also spreads to destroy nearby liver cells. As the destruction of the hepatocytes proceeds,

scar tissue (fibrosis) forms and spreads throughout the areas of destruction. The combined effects of

progressive inflammation, scarring, and the toxic effects of accumulating waste products culminates in

cirrhosis.

Primary sclerosing cholangitis (PSC)is an uncommon disease found frequently in patientswithulcerative colitis. In PSC, the large bile ducts outside of the liver become inflamed, narrowed, and

obstructed. Obstruction to the flow of bile leads to infections of the bile ducts and jaundice and eventually

causes cirrhosis. In some patients, injury to the bile ducts (usually as a result of surgery) also can cause

obstruction and cirrhosis of the liver.

Autoimmune hepatitisis a liver disease caused by an abnormality of the immune system that is found

more commonly in women. The abnormal immune activity in autoimmune hepatitis causes progressive

inflammation and destruction of liver cells (hepatocytes), leading ultimately to cirrhosis.

Infants can be born without bile ducts (biliary atresia)and ultimately develop cirrhosis. Other infants

are born lacking vital enzymes for controlling sugars that leads to the accumulation of sugars and

cirrhosis. On rare occasions, the absence of a specific enzyme can cause cirrhosis and scarring of the

lung (alpha 1 antitrypsin deficiency). Less common causes of cirrhosis include unusual reactions to some drugs and prolonged

exposure to toxins, as well as chronicheart failure(cardiac cirrhosis). In certain parts of the world

(particularly Northern Africa), infection of the liver with a parasite (schistosomiasis)is the most common

cause of liver disease and cirrhosis.
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How is cirrhosis diagnosed and evaluated?Comment on thisRead 2 CommentsShare Your Story

The single best test for diagnosing cirrhosis isbiopsy of the liver.Liver biopsies, however, carry a small risk for

serious complications, and, therefore, biopsy often is reserved for those patients in whom the diagnosis of the

type of liver disease or the presence of cirrhosis is not clear. The possibility of cirrhosis may be suggested by

the history, physical examination, or routine testing. If cirrhosis is present, other tests can be used to determine

the severity of the cirrhosis and the presence of complications. Tests also may be used to diagnose the

underlying disease that is causing the cirrhosis. The following are some examples of how doctors discover,

diagnose and evaluate cirrhosis:

In taking a patient's history, the physician may uncover a history of excessive and prolonged intake of

alcohol, a history ofintravenousdrug abuse,or a history of hepatitis. These pieces of information suggest

the possibility of liver disease and cirrhosis.

Patients who are known to have chronic viral hepatitis B or C have a higher probability of having cirrhosis.

Some patients with cirrhosis have enlarged livers and/or spleens. A doctor can often feel (palpate) the

lower edge of an enlarged liver below the right rib cage and feel the tip of theenlarged spleenbelow the

leftrib cage.A cirrhotic liver also feels firmer and more irregular than a normal liver.

Some patients with cirrhosis, particularly alcoholic cirrhosis, have small red spider-like markings

(telangiectasias) on the skin, particularly on the chest, that are made up of enlarged, radiating blood

vessels. These spider telangiectasias also can be seen in individuals without liver disease, however.

Jaundice (yellowness of the skin and of the whites of the eyes due to elevated bilirubin in the blood) iscommon among patients with cirrhosis, but jaundice can occur in patients with liver diseases without

cirrhosis and other conditions such ashemolysis(excessive break down of red blood cells).

Swelling of the abdomen (ascites) and/or the lower extremities (edema) due to retention of fluid is

common among patients with cirrhosis though other diseases can cause them commonly, e.g., congestive

heart failure.

Patients with abnormal copper deposits in their eyes or certain types of neurologic disease may have

Wilson's disease, agenetic diseasein which there is abnormal handling and accumulation of copper

throughout the body, including the liver, that can lead to cirrhosis.

Esophageal varices may be found unexpectedly duringupper endoscopy(EGD), and they stronglysuggesting cirrhosis.

Computerized tomography(CT or CAT) ormagnetic resonance imaging(MRI) scans

andultrasoundexaminations of the abdomen done for reasons other than evaluating the possibility of liver

disease may unexpectedly detect enlarged livers, abnormally nodular livers, enlarged spleens, and fluid in

the abdomen that suggest cirrhosis.
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Advanced cirrhosis leads to a reduced level ofalbuminin the blood and reduced blood clotting factors due

to the loss of the liver's ability to produce these proteins. Thus, reduced levels of albumin in the blood or

abnormal bleeding suggest cirrhosis.

Abnormal elevation of liver enzymes in the blood (such asALTandAST)that are obtained routinely as

part of yearly health examinations suggests inflammation or injury to the liver from many causes as well as

cirrhosis.

Patients with elevated levels of iron in their blood may have hemochromatosis, agenetic diseaseof the

liver in which iron is handled abnormally and which leads to cirrhosis.

Auto-antibodies (antinuclear antibody, anti-smooth muscle antibody and anti-mitochondrial antibody)

sometimes are detected in the blood and may be a clue to the presence of autoimmune hepatitis

orprimary biliary cirrhosis,both of which can lead to cirrhosis.

Liver cancer (hepatocellular carcinoma) may be detected by CT and MRI scans orultrasoundof the

abdomen. Liver cancer most commonly develops in individuals with underlying cirrhosis.

If there is an accumulation of fluid in the abdomen, a sample of the fluid can be removed using a long

needle. The fluid then can be examined and tested. The results of testing may suggest the presence of

cirrhosis as the cause of the fluid.

How is cirrhosis treated?

Comment on thisRead 15 CommentsShare Your StoryTreatment of cirrhosis includes 1) preventing further damage to the liver, 2) treating the complications of

cirrhosis, 3) preventing liver cancer or detecting it early, and 4) liver transplantation.

Preventing further damage to the liver

Consume a balanced diet and one multivitamin daily. Patients with PBC with impaired absorption of fat

soluble vitamins may need additional vitamins D and K.

Avoid drugs (including alcohol) that cause liver damage. All patients with cirrhosis should avoid alcohol.

Most patients with alcohol induced cirrhosis experience an improvement in liver function with abstinence

from alcohol. Even patients with chronic hepatitis B and C can substantially reduce liver damage and slow

the progression towards cirrhosis with abstinence from alcohol.

Avoidnonsteroidal anti-inflammatory drugs(NSAIDs, e.g.,ibuprofen). Patients with cirrhosis can

experience worsening of liver and kidney function with NSAIDs.

Eradicate hepatitis B and hepatitis C virus by using anti-viral medications. Not all patients with cirrhosis

due to chronic viral hepatitis are candidates for drug treatment. Some patients may experience serious

deterioration in liver function and/or intolerableside effectsduring treatment. Thus, decisions to treat viral
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hepatitis have to be individualized, after consulting with doctors experienced in treating liver diseases

(hepatologists).

Remove blood from patients with hemochromatosis to reduce the levels of iron and prevent further

damage to the liver. In Wilson's disease, medications can be used to increase the excretion of copper in

the urine to reduce the levels of copper in the body and prevent further damage to the liver.

Suppress the immune system with drugs such asprednisoneandazathioprine(Imuran) to decrease

inflammation of the liver in autoimmune hepatitis.

Treat patients with PBC with a bile acid preparation, ursodeoxycholic acid (UDCA), also

calledursodiol(Actigall). Results of an analysis that combined the results from several clinical trials

showed that UDCA increased survival among PBC patients during 4 years of therapy. The development

ofportal hypertensionalso was reduced by the UDCA. It is important to note that despite producing clear

benefits, UDCA treatment primarily retards progression and does not cure PBC. Other medications such

ascolchicineandmethotrexatealso may have benefit in subsets of patients with PBC.

Immunize patients with cirrhosis against infection with hepatitis A and B to prevent a serious deteriorationin liver function. There are currently no vaccines available for immunizing against hepatitis C.

Treating the complications of cirrhosis

Edema and ascites.Retention of salt and water can lead to swelling of the ankles and legs (edema) or

abdomen (ascites) in patients with cirrhosis. Doctors often advise patients with cirrhosis to restrict dietary salt

(sodium) and fluid to decrease edema and ascites. The amount of salt in the diet usually is restricted to 2

grams per day and fluid to 1.2 liters per day. In most patients with cirrhosis, however, salt and fluid restriction is

not enough, and diuretics have to be added.

Diuretics are medications that work in the kidneys to promote the elimination of salt and water into the urine. A

combination of the diureticsspironolactone(Aldactone) andfurosemidecan reduce or eliminate the edema and

ascites in most patients. During treatment with diuretics, it is important to monitor the function of the kidneys by

measuring blood levels ofblood urea nitrogen(BUN) andcretonneto determine if too muchdiureticis being

used. Too much diuretic can lead to kidney dysfunction that is reflected in elevations of the BUN and creatinine

levels in the blood.

Sometimes, when the diuretics do not work (in which case the ascites is said to be refractory), a long needle or

catheter is used to draw out the ascitic fluid directly from the abdomen, a procedure called abdominal

paracentesis. It is common to withdraw large amounts (liters) of fluid from the abdomen when the ascites is

causing painful abdominal distension and/or difficulty breathing because it limits the movements of the

diaphragms.

Another treatment for refractory ascites is a procedure called transjugular intravenous portosystemic shunting(TIPS, see below).

Bleeding from varices.If large varices develop in the esophagus or upper stomach, patients with cirrhosis are

at risk for serious bleeding due to rupture of these varices. Once varices have bled, they tend to rebleed and

the probability that a patient will die from each bleeding episode is high (30%-35%). Therefore, treatment is

necessary to prevent the first (initial) bleeding episode as well as rebleeding. Treatments include medications

and procedures to decrease the pressure in the portal vein and procedures to destroy the varices.
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