Cirrhosis is the severe scarring of the liver and poor liver function seen at the terminal stages of chronic liver disease. The scarring is most often caused by long-term exposure to toxins such as alcohol or viral infections. The liver is located in the upper right side of the abdomen below the ribs. It has many essential body functions. These include:

·         producing bile, which helps your body absorb dietary fats, cholesterol, and vitamins A, D, E, and K

·         storing sugar and vitamins for later use by the body

·         purifying blood by removing toxins such as alcohol and bacteria from your system

·         creating blood clotting proteins

According to the National Institutes of Health (NIH), cirrhosis is the 12th leading cause of death due to disease in the United States. It’s more likely to affect men than women.

How Cirrhosis DevelopsThe liver is a very hearty organ and is normally able to regenerate damaged cells. Cirrhosis develops when the factors that damage the liver (such as alcohol and chronic viral infections) are present over a long period of time. When this happens, the liver becomes injured and scarred. A scarred liver can’t function properly, and ultimately this may result in cirrhosis.

Cirrhosis causes the liver to shrink and harden. This makes it difficult for nutrient-rich blood to flow into the liver from the portal vein. The portal vein carries blood from the digestive organs to the liver. The pressure in the portal vein rises when blood can’t pass into the liver. The end result is a serious condition called portal hypertension, in which the vein develops high blood pressure. The unfortunate consequence of portal hypertension is that this high-pressure system causes a backup, which leads to esophageal varices (like varicose veins), which can then burst and bleed.

Common Causes of CirrhosisThe most common causes of cirrhosis in the United States are long-term viral hepatitis C infection and chronic alcohol abuse. Obesity is also a cause of cirrhosis, although it is not as prevalent as alcoholism or hepatitis C. Obesity can be a risk factor by itself, or in combination with alcoholism and hepatitis C.

According to the NIH, cirrhosis can develop in women who drink more than two alcoholic drinks per day (including beer and wine) for many years. For men, drinking more than three drinks a day for years can put them at risk for cirrhosis. However, the amount is different for every person, and this doesn’t mean that everyone who has ever drunk more than a few drinks will develop cirrhosis. Cirrhosis caused by alcohol is usually the result of regularly drinking more than these amounts over the course of 10 or 12 years.

Hepatitis C can be contracted through sexual intercourse or exposure to infected blood or blood products. It’s possible to be exposed to infected blood through intravenous drug abuse and needle sharing or transfusions. Hepatitis C is rarely transmitted by transfusion in the United States due to blood bank screening.

ther causes of cirrhosis include:

·         Hepatitis B: Hepatitis B can cause liver inflammation and damage that can lead to cirrhosis.

·         Hepatitis D: This type of hepatitis can also cause cirrhosis. It’s often seen in people who already have hepatitis B.

·         Inflammation caused by autoimmune disease: Autoimmune hepatitis may have a genetic cause. According to the American Liver Foundation, about 70 percent of people with autoimmune hepatitis are women.

·         Damage to the bile ducts, which function to drain bile: One example of such a condition is primary biliary cirrhosis.

·         Disorders that affect the body’s ability to handle iron and copper: Two examples are hemochromatosis and Wilson’s disease.

·         Medications: Medications including prescription and over-the-counter drugs like acetaminophen, some antibiotics, and some antidepressants, can lead to cirrhosis.

Learn About Alcohol’s Effects on the Body »

Symptoms of CirrhosisThe symptoms of cirrhosis occur because the liver is unable to purify the blood, break down toxins, produce clotting proteins, and help with absorption of fats and fat-soluble vitamins. Often there are no symptoms until the disorder has progressed. Some of the symptoms include:

·         decreased appetite

·         nose bleeds

·         jaundice (yellow discoloration)

·         small spider-shaped arteries underneath the skin

·         weight loss

·         anorexia

·         itchy skin

·         weakness

More serious symptoms include:

·         confusion and difficulty thinking clearly

·         abdominal swelling (ascites)

·         swelling of the legs (edema)

·         impotence

·         gynecomastia (when males start to develop breast tissue)

How Cirrhosis Is DiagnosedA diagnosis of cirrhosis begins with a detailed history and physical exam. Your doctor will take a complete medical history. The history may reveal long-term alcohol abuse, exposure to hepatitis C, family history of autoimmune diseases, or other risk factors. The physical exam can show signs such as:

·         pale skin

·         yellow eyes (jaundice)

·         reddened palms

·         hand tremors

·         an enlarged liver or spleen

·         small testicles

·         excess breast tissue (in men)

·         decreased alertness

Tests can reveal how damaged the liver has become. Some of the tests used for evaluation of cirrhosis are:

·         complete blood count (to reveal anemia)

·         coagulation blood tests (to see how quickly blood clots)

·         albumin (to test for a protein produced in the liver)

·         liver function tests

·         alpha fetoprotein (a liver cancer screening)

Additional tests that can evaluate the liver include:

·         upper endoscopy (to see if esophageal varices are present)

·         ultrasound scan of the liver

·         MRI of the abdomen

·         CT scan of the abdomen

·         liver biopsy (the definitive test for cirrhosis)

Part 6 of 8: Complications

Complications from CirrhosisIf your blood is unable to pass through the liver, it creates a backup through other veins such as those in the esophagus. This backup is called esophageal varices. These veins are not built to handle high pressures, and begin to bulge from the extra blood flow.

Other complications from cirrhosis include:

·         bruising (due to low platelet count and/or poor clotting)

·         bleeding (due to decreased clotting proteins)

·         sensitivity to medications (the liver processes medications in the body)

·         kidney failure

·         liver cancer

·         insulin resistance and type 2 diabetes

·         hepatic encephalopathy (confusion due to the effects of blood toxins on the brain)

·         gallstones (interference with bile flow can cause bile to harden and form stones)

·         esophageal varices

·         enlarged spleen (splenomegaly)

·         edema and ascites

·         Cirrhosis is a complication of liver disease which involves loss of liver cells and irreversible scarring of the liver.

·         Alcohol and viral hepatitis B and C are common causes of cirrhosis, although there are many other causes.

·         Cirrhosis can cause weakness, loss of appetite, easy bruising, yellowing of the skin (jaundice), itching, and fatigue.

·         Diagnosis of cirrhosis can be suggested by history, physical examination and blood tests, and can be confirmed by liver biopsy.

·         Complications of cirrhosis include edema andascites, spontaneous bacterial peritonitis, bleeding from varices, hepaticencephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, hypersplenism, and liver cancer.

·         Treatment of cirrhosis is designed to prevent further damage to the liver, treat complications of cirrhosis, and preventing or detecting liver cancer early.

·         Transplantation of the liver is becoming an important option for treating patients with advanced cirrhosis. 

·         Alcohol is 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 ounces of hard liquor or the equivalent for fifteen or more years will develop cirrhosis. Alcohol causes a range of liver diseases; from simple and uncomplicated fatty liver (steatosis), to the more serious fatty liver with inflammation (steatohepatitis or 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 of NAFLD have 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 called insulin resistance, which, in turn, is associated withmetabolic syndrome and diabetes mellitus type 2. Obesity is the most important cause of insulin resistance, metabolic syndrome, and type 2 diabetes. NAFLD is the most common liver disease in the United 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 health officials are worried that the current epidemic of obesity will 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, and insulin resistance. 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 a high occurrence of NASH in the new livers of patients undergoing liver transplant for 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 with hepatitis 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 hepatitis is a condition where hepatitis B or hepatitis C virus infects the liver for years. Most patients with viral hepatitis will not develop chronic hepatitis and cirrhosis. For example, the majority of patients infected with hepatitis A recover completely within weeks, without developing chronic infection. In contrast, some patients infected withhepatitis B virus and most patients infected withhepatitis C virus develop chronic hepatitis, which, in turn, causes progressive liver damage and leads to cirrhosis, and, sometimes, liver cancers.

·         Inherited (genetic) disorders that result in the accumulation of toxic substances in the liver, which leads to tissue damage and cirrhosis. Examples include the abnormal accumulation of iron (hemochromatosis) or copper (Wilson's disease). In hemochromatosis, 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 muscle damage leading to heart 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). In Wilson 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, psychiatric disturbances and other neurological difficulties occur if the condition is not treated early. Treatment is with oral medication, which 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 and destruction 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 of hemoglobin from old red blood cells.). Along with the gallbladder, the bile ducts make up the biliary tract. In PBC, 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 frequently found in patients withCrohn's disease and ulcerative 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, eventually causing 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 hepatitis is a liver diseasefound more commonly in women that is caused by an abnormality of the immune system. 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 chronic heart 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. The single best test for diagnosing cirrhosis is biopsy 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 of intravenous drug 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 the enlarged spleen below the left rib 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. However, these spider telangiectasias also can be seen in individuals without liver disease.

§  Jaundice (yellowness of the skin and of the whites of the eyes due to elevated bilirubin in the blood) is common among patients with cirrhosis, but jaundice can occur in patients with liver diseases without cirrhosis and other conditions such as hemolysis (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, although other diseases can cause them commonly, for example, congestive heart failure.

§  Patients with abnormal copper deposits in their eyes or certain types of neurologic disease may have Wilson's disease, a genetic disease in which there is abnormal handling and accumulation of copper throughout the body, including the liver, which can lead to cirrhosis.

§  Esophageal varices may be found unexpectedly during upper endoscopy(EGD), strongly suggests cirrhosis. 

§  Computerized tomography (CT or CAT) or magnetic resonance imaging (MRI) scans and ultrasoundexaminations 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, which suggest cirrhosis.

§  Advanced cirrhosis leads to a reduced level of albumin in 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 as ALT and AST) 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, a genetic disease of 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 or primary biliary cirrhosis, both of which can lead to cirrhosis.

§  Liver cancer (hepatocellular carcinoma) may be detected by CT and MRI scans or ultrasound of 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. 

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Rev

·         Cirrhosis is a complication of many liver diseases characterized by abnormal structure and function of the liver. The diseases that lead to cirrhosis do so because they injure and kill liver cells, after which 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 including chemicals (such as alcohol, fat, and certain medications), viruses, toxic metals (such as iron and copper that accumulate in the liver as a result of genetic diseases), and autoimmune liver disease in which the body's immune system attacks the liver.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 of glucose(sugar) and lipids (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, the hepatic vein, which 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 called portal 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 is unable 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 which bile flows. Bile is a fluid produced by liver cells that has two important functions: to aid indigestion and to remove and eliminate toxic substances from the body. The bile that is produced by liver 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 the small 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 the stool. 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. As a 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.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 of bilirubin in the blood

§  Fatigue

§  Weakness

§  Loss of appetite

§  Itching

§  Easy bruising from 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. As cirrhosis of the liver becomes 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 the end 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 the abdominal cavity between the abdominal wall and the abdominal organs. This accumulation of fluid (called ascites) causes swelling of the abdomen, abdominal discomfort, and increased weight.

Spontaneous bacterial peritonitis (SBP)

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- threatening complication. Some patients with SBP have no symptoms, while others have fever, chills, abdominal pain and 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 (portalhypertension). 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 the esophagus and the upper part of the stomach.

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 and gastric varices; 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 include vomiting blood (the vomitus can 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 orthostatic dizziness or fainting (caused by a drop in blood 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 called hepatic encephalopathy. Sleeping during the day rather than at night (reversal of the normal sleep pattern) 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 causes coma and 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 be reduced 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 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, meaning 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 of urine while other important functions of the kidney, 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 again. 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 hepatopulmonary syndrome. These patients can experience difficulty breathing because certain hormones released in advanced cirrhosis cause thelungs 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 the alveoli (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 experiences shortness of breath, particularly with exertion.

Hypersplenism

The spleen normally acts as a filter to remove older red 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," accumulating in the spleen, and the spleen swells in size, a condition referred to as splenomegaly. Sometimes, the spleen is so enlarged 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), low white 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)

Cirrhosis due to any cause increases the risk of primary liver cancer(hepatocellular carcinoma). Primary refers to the fact that the tumororiginates 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 in red blood cell count (erythrocytosis), low blood sugar(hypoglycemia), and high blood calcium (hypercalcemia ).