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 LIVER DISEASES
There are over 100 types of liver diseases, and because of more than 200 functions that the Liver plays, many can be life-threatening unless treated.
The Liver diseases have been listed down in alphabetical order. Click on the alphabet to read more about the diseases.
 
 A B C D E F G H I J K L M
N O P Q R S T U V W X Y Z
 
Caroli Disease Chronic Hepatitis
Cancer of the Liver Cirrhosis
Crigler-Najjar Syndrome  
 

Caroli Disease

Disease condition

Caroli Disease is a rare inherited disorder characterized by abnormal widening (dilatation) of the ducts that carry bile from the liver (intrahepatic bile ducts).

There are two forms of Caroli Disease.

In most cases, the isolated or simple form Caroli Disease, affected individuals experience recurrent episodes of inflammation of the bile ducts (cholangitis) and unusual accumulation of pus (abscesses) on the liver.

A second form of Caroli Disease is associated with abnormal formation of bands of fibrous tissue in the portal area of the liver (congenital hepatic fibrosis). The portal area of the liver is a groove (fissure) where the portal vein and the hepatic artery enter the liver. The portal vein is the blood vessel that carries blood from the stomach, intestine, and spleen to the liver and the hepatic artery is the blood vessel that carries blood from the aorta. This form of Caroli Disease is also often associated with high blood pressure of the portal vein (portal hypertension), polycystic kidney disease, and, in severe cases, liver failure..

This is a rare congenital disorder that classically causes saccular ductal dilatation, which usually is segmental. Caroli disease is associated with recurrent bacterial cholangitis and stone formation.

Caroli disease also is known as communicating cavernous ectasia or congenital cystic dilatation of the intrahepatic biliary tree. It is distinct from other diseases that cause ductal dilatation caused by obstruction. It is not one of the many choledochal cyst derivatives.

Caroli disease is also called as Congenital Dilatation of Intrahepatic Bile Duct.

Disease Etiology

Caroli Disease is thought to be inherited as either an autosomal dominant or recessive genetic trait.

The precursor of the intrahepatic biliary tree is a double-layered sleeve of cells known as the ductal plate (DP). The DP first arises from hepatocyte precursors surrounding hilar portal vein vessels at 8 weeks' gestation, and peripheral regions of the DP then develop sequentially. During the remainder of gestation, a process of DP remodeling occurs in which small areas of the double layer separate to form tubules, which join to form the intrahepatic biliary tree, while the remaining regions of the DP become involuted. Caroli disease belongs to a subcategory of diseases thought to originate from failures of this process collectively known as ductal-plate malformation.

Symptoms

The patient may have a history of intermittent abdominal pain, which reflects episodes of bile stasis or the passage of bile stones.

Patients with cholangitis may report fever and pain in the right upper quadrant.

In Caroli syndrome, portal hypertension may result in hematemesis or melena.

Because Caroli syndrome is associated with ARPKD (autosomal dominant polycystic kidney disease) and because it appears to be inherited in an autosomal recessive manner, the patient may have a family history of kidney or liver disease.

Diagnosis

Lab Studies:

Bilirubin levels are usually in the reference range.

Transaminase levels may be slightly elevated.

The CBC may reveal thrombocytopenia and leukopenia if portal hypertension and hypersplenism are present. An elevated WBC count or erythrocyte sedimentation rate (ESR) may indicate cholangitis.

Creatinine and BUN values should be obtained to detect associated renal disease.

Imaging Studies:

Ultrasonography is the best initial imaging study because it reveals the irregular dilatation of the large intrahepatic bile ducts typical of Caroli disease or syndrome.

Extrahepatic biliary dilatation may also be present as a result of prior cholelithiasis.

Doppler evaluation of the liver can be used to detect portal hypertension.

The kidneys can also be assessed for evidence of polycystic kidney disease.

Magnetic resonance cholangiography is increasingly used to diagnose Caroli disease or syndrome.

It provides excellent images of the intrahepatic and extrahepatic biliary trees, and it can also depict renal involvement.

Its use is currently limited by the availability of the necessary equipment and expertise.

CT may be used, particularly if sonograms cannot be obtained because of bowel gas or body habitus.

Hepatobiliary scintigraphy can be useful to document communication between cysts and the biliary system, a feature present in Caroli disease or syndrome but absent in polycystic liver disease and hepatic abscesses.

Invasive modalities, such as percutaneous transhepatic cholangiography (PTC) and endoscopic retrograde cholangiopancreatography (ERCP), enable excellent visualization of the biliary tree. However, these studies are limited by the risks of complications.

Procedures:

Liver biopsy and culture should be performed in cases of suspected chronic cholangitis.

ERCP has been used to identify and treat biliary stones in patients with Caroli disease or syndrome, but it is associated with a postprocedural risk of cholangitis.

Portosystemic shunting may be indicated in patients who have portal hypertension.

Histologic Findings:

Liver biopsy reveals the typical pattern of ductal-plate malformation, with bile-duct ectasia, portal-vein malformations, and fibrosis. In Caroli syndrome, ductal-plate malformation is evident throughout the liver, whereas only large intrahepatic ducts are affected in relatively rare Caroli disease.

Treatment – Medical, Surgical

Therapy depends on the clinical manifestations and the location of the biliary abnormality. Antibiotic treatment with broad-spectrum agents is extremely important. Prophylactic antibiotics have had poor and unpredictable results. The addition of oral agents such as ursodeoxycholic acid has no definite benefit. Prevention of the complications is ideal but no method has been proven effective.

Drainage procedures with endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) are important, and sphincterotomy can aid biliary drainage and stone removal or subsequent passage and may decrease bouts of cholangitis. If the process is confined to one lobe, lobectomy completely relieves the symptoms. Internal surgical bypass (choledochojejunostomy, Roux-en-Y, hepaticojejunostomy) is helpful in diffuse forms of the disease. No cure for the disease exists.

Extracorporeal shock-wave lithotripsy or intraductal electrohydraulic lithotripsy with biliary drainage, stent placement, and liberal sphincterotomy is advocated as an important but aggressive method to treat and prevent choledocholithiasis.

Ultimately, liver transplantation may be required. This is the best alternative when recurrent cholangitis is not present.

Chronic Hepatitis

Disease condition

Chronic Hepatitis (CAH) is ongoing injury to the cells of the liver with inflammation which lasts for longer than six months. The causes of chronic hepatitis are several: viruses, metabolic or immunologic abnormalities and medications.

Disease Etiology

Hepatitis B and C are the most common causes of chronic hepatitis. Together they account for more than 75 percent of the cases in the world. Hepatitis B is far more common in China and sub-Saharan Africa and among male homosexuals and IV drug users.

Chronic hepatitis C behaves differently from hepatitis B. The disease is generally mild, with fatigue being the main symptom. However, ten or more years later, the complications of cirrhosis appear in some patients, sometimes unexpectedly. By contrast with hepatitis B, the percentage of patients infected who develop cirrhosis is much greater. While primary liver cancer can also develop from hepatitis C, it appears to be much less common than after hepatitis B.

Autoimmune Chronic Hepatitis varies from mild to serious disease. The percentage of patients who develop cirrhosis is high and it may appear early. Most of the patients are young women but postmenopausal women and males may get the disease. Only a few cases of primary liver cancer have been reported with this disease. Twenty-five percent of the cases of chronic hepatitis result from damage to the liver by the immune system. The trigger for autoimmune chronic hepatitis is unknown, but the damage to the liver is caused by the individual's lymphocytes and by antibodies produced in the individual's own tissue. Autoimmune chronic hepatitis is usually a progressive disease ending in cirrhosis.

Hepatitis A and E (formerly called epidemic or enteric non-A, non-B) are rarely, if ever, responsible for causes of chronic hepatitis.

Hepatitis D infection needs the hepatitis B virus to multiply. Hepatitis D can cause acute hepatitis in someone who is a carrier of the hepatitis B virus and can cause acute hepatitis at the same time that the hepatitis B virus does. In any event, the combination of hepatitis B and D is worse then hepatitis B alone and is more likely to cause serious chronic hepatitis and cirrhosis. IV drug users have a high incidence of hepatitis D.

Other Causes

Viruses of the herpes family, which cause cold sores, genital herpes, chicken pox, shingles and infectious mononucleosis, can cause acute hepatitis, especially when the immune system is not functioning properly. It is unlikely that they will produce chronic hepatitis. Other viruses, as yet undiscovered, may be responsible for some cases of chronic hepatitis.

Drug-Induced Hepatitis

Few medications still in use and several that have been withdrawn from the market can also cause chronic hepatitis. These include: isoniazid, used for tuberculosis; methyldopa, used for hypertension; nitrofurantoin, used for urinary tract infections; phenytoin, used for seizure disorders and selected other prescription medications. These medications must be taken for long periods of time and the number cases of chronic hepatitis produced by these medications is small.

Chronic hepatitis caused by drugs is usually recognized early. Stopping the medicine before cirrhosis has developed usually reverses the disease.

Inherited Disorders

Some inherited disorders of metabolism also can appear as chronic hepatitis. The most frequent of these conditions is Wilson's disease, a familial disorder of copper metabolism. Alpha-1-antitrypsin deficiency and tyrosinemia may appear as chronic hepatitis although other features help in distinguishing these rare conditions from those caused by viruses.


Symptoms

Symptoms result from the liver cell injury, the inflammation or from the resulting scarring which is called cirrhosis. Chronic hepatitis may follow acute hepatitis B or C (formerly called non-A, non-B) or may develop quietly without an acute illness.

Liver biopsy is helpful in that it confirms the diagnosis, aids in establishing the cause (etiology) and can demonstrate the presence of cirrhosis. It is less helpful in judging the response to treatment.

Fatigue, mild discomfort in the upper abdomen, loss of appetite and aching joints are the common symptoms of chronic hepatitis. Fatigue is by far the most common symptom and it might be quite disabling. Often it gets worse as the day wears on. Some patients, however, may have no symptoms. Others may have signs of liver failure, inducing jaundice, abdominal swelling (due to fluid retention called ascites), or coma, depending on the severity of the liver disease and whether or not cirrhosis has developed. Most complications are vague and may be mistaken for other diseases or simply a consequence of aging. Disorders of other organs like the thyroid, intestine, eyes, joints, blood, spleen, kidneys and skin may occur in about 20 percent of patients depending on the cause of the chronic hepatitis.

When the hepatitis is mild and limited in extent, it is called chronic persistent hepatitis (CPH). When it is more extensive and seems to be destroying the cells of the liver, it is called chronic active hepatitis (CAH).

Diagnosis

Treatment : Medical, Surgical

Interferon has been approved for the treatment of hepatitis B and C. The treatment has been shown to reduce the inflammation and liver damage caused by the virus in 25-30% of cases by eliminating the virus, thus reducing the development of scar tissue and avoiding the development of cirrhosis.

In people treated with interferon studies show that 50% will respond to treatment and 50% of those patients will relapse when interferon is stopped. Research is going on to address the relapse rate.

Additional clinical trials are being conducted to identify the most effective dose and duration of therapy with interferon. Studies are continuing in an attempt to reduce the side effects of the medication that exists. These include "flu-like" symptoms, and less often, fever, depression, hair loss, nausea and vomiting. Currently, the treatment consists of an injection three times a week over a period of six months. Blood tests are needed to monitor progress during treatment and a liver biopsy (retrieving a small specimen of the liver through a needle inserted into the liver) is an accepted procedure prior to and following treatment.

Fifty percent of the patients treated will experience remission of the disease. When the treatment is stopped 50 percent will relapse. However, only about 20 percent of untreated patients will go on to develop cirrhosis over a period of years. Research into the management of those who relapse is ongoing.

Interferon does not seem to work well in patients:

with substance abuse (alcohol or illegal drugs),

who are not very sick,

whose test results are not very abnormal,

whose immune system is not functioning well because of AIDS,

with hepatitis B who were infected from their mothers at birth,

carriers who are no longer contagious or infectious,

with significant heart, lung or kidney diseases,

or couples who are trying to conceive.

Knowing the cause of the disease is helpful in estimating the prognosis. Only a small percentage of patients with chronic hepatitis B develop cirrhosis. In those patients, cirrhosis develops early in the course of the disease with complications appearing in the first few years. Chronic hepatitis often causes acute hepatitis or flare-ups and periods with no signs. Scarring becomes more extensive with each flare-up. Patients in the Orient have about a 15 percent chance of developing primary liver cancer, usually after the age of 50 with men more likely candidates than women. This complication is much less common in the Western World.

The disease becomes life-threatening only after cirrhosis has developed. More than half of all patients live at least 15 years from the time of the first diagnosis and this number is continuously improving. Previously, prognosis was thought to depend on what was found on liver biopsy. This is now only partly true. Prognosis is worse and complications more numerous and severe if cirrhosis has already developed. Much attention has been paid to the location and extent of the inflammation of the liver.

Steroid therapy remains the only useful treatment for autoimmune disease, but it may have to be given for a lifetime and may also not prevent the ultimate development of cirrhosis.

Liver transplantation has become an accepted form of therapy when chronic hepatitis becomes life-threatening, usually as a result of complications of cirrhosis. Recurrence of hepatitis C or autoimmune hepatitis does not seem to occur, but hepatitis B, if virus is still present and the patient is contagious, will recur in the new liver and often be acute. Attempts are being made to prevent this recurrence.

The most important treatment for hepatitis B is prevention. Hepatitis B vaccines should be given to all who are exposed to this disease on a regular basis. All pregnant women should be tested for hepatitis B. Carriers of hepatitis B, many of them unaware that they are infected, can pass it on to their babies as well as their sexual contacts. All newborns should be vaccinated against hepatitis B. Three injections are needed to provide adequate immunity.

An important aspect of treatment is supportive care. Diet should be well balanced. The use of high carbohydrate, high protein or low fat diets have no scientific basis, and in some instances, such diets may be harmful. Vitamin and mineral supplementation also has no place in the management of chronic hepatitis unless some deficiency is present. No substance is known that will help the main symptom, fatigue. However, a good physical fitness program may lessen this distressing symptom. Patients should be advised to limit the amount of salt that they use in an attempt to forestall the accumulation of fluids as ascites or ankle swelling. Since almost all drugs must be detoxified by the liver, and since the injured liver does not perform this task well, limiting the amount of drugs that a patient uses to only essential ones is important. This includes discouraging the use of sedatives and tranquilizers.

Life expectancy and Quality of Life

Learning more about the viruses responsible for chronic hepatitis and how to control them will occur in the next decade. Similarly, learning about the body's immune system and how to control it has already begun. Preventive efforts will be enhanced so that fewer cases of chronic hepatitis will develop. The goal of eliminating this group of diseases seems to be just over the horizon, and while our skills at transplantation are rapidly increasing, the form of therapy for chronic hepatitis, like the disease itself, will disappear.

Cancer of the Liver

Disease condition

Benign Tumors

The most common benign tumor of the liver is a cavernous hemangioma. This tumor, as well as other benign tumors, is typically found by chance on an imaging study of the liver, such as ultrasound or computed tomography (CT). Cavernous hemangioma can be diagnosed with reasonable accuracy by the use of various imaging tests. Unless it is extremely large, no specific therapy is usually required. This tumor may enlarge in women taking hormone pills; thus, physicians will often recommend discontinuing birth control pills or postmenopausal hormone replacement therapy.

The other common benign tumors of the liver are called hepatocellular adenoma and focal nodular hyperplasia. Both of these tumors are also usually found by chance, although hepatocellular adenoma has a substantial risk of bleeding within the tumor and into the peritoneal (abdominal) cavity. The use of a number of imaging tests, and occasionally hepatic arteriography or biopsy, may be required to make the diagnosis of this tumor. Hepatocellular adenomas are also quite sensitive to hormonal therapy and may regress when birth control pills or hormones are stopped. If feasible, removal of hepatic adenoma may be recommended if it is large in order to prevent the possibility of bleeding and/or rupture.

Malignant Tumors

The most common primary malignant tumor of the liver is a hepatocellular carcinoma. Primary liver cancer accounts for less than 1 percent of all cancers in this country. However, in other parts of the world such as Africa, Southeast Asia, and China, it is a major health problem, causing up to 50 percent of cancer cases seen in those areas. This difference is thought to be due to the much higher percentage of the population who are carriers of the hepatitis B virus, which predisposes to the development of hepatocellular carcinoma.

Disease Etiology

It was recognized a number of years ago that chronic carriers of the hepatitis B virus, particularly those with chronic hepatitis or cirrhosis, are at substantially increased risk to develop hepatocellular carcinoma. Recent evidence indicates that patients who have long-standing chronic hepatitis C virus infection are also at increased risk for the development of hepatocellular carcinoma, although the exact risk is uncertain.

Certain toxins and chemicals are also rarely associated with liver cancer. In Africa, aflatoxin, a product of mold found in badly stored peanuts or other foods, has been recognized as a cause of liver cancer. Finally, certain diseases other than chronic hepatitis B or C are associated with an increased risk of hepatocellular carcinoma. Iron overload cirrhosis (hemochromatosis) is associated with a substantial risk of hepatocellular carcinoma once cirrhosis has developed. Patients with long-standing alcoholic cirrhosis are also at risk for developing this tumor. Two congenital disorders, alpha-1-antitrypsin deficiency and tyrosinemia, may also be complicated by the development of hepatocellular carcinoma.


Symptoms

Metastatic or secondary tumors of the liver come from cancers originating elsewhere in the body. Because the liver filters blood from all parts of the body, it is often the site in which cancer cells will lodge and develop into metastatic nodules. An enlarged liver secondary to cancer may be an early sign of cancer in other organs. Secondary or metastatic cancer should not be confused with primary cancer of the liver.

Diagnosis

Primary liver cancer may be detected by screening high risk patients or by chance on an imaging study of the abdomen performed for another reason, or it may be detected because of symptoms such as abdominal pain. Studies performed in several countries have demonstrated that the periodic use of abdominal ultrasound and a blood tumor marker, called alpha-fetoprotein, may lead to the early detection of small hepatocellular carcinomas in patients at high risk. This screening strategy has not been widely adopted because its cost-effectiveness has yet to be proven. In patients who develop symptoms from more advanced hepatocellular carcinoma, weight loss, periodic severe pain and other generalized symptoms may occur. Health may deteriorate rapidly and jaundice (yellow skin) may appear.

The diagnosis of primary cancer of the liver is typically made by liver imaging tests, such as abdominal ultrasound and CT scan in combination with the measurement of blood levels of alpha-fetoprotein. The final diagnosis is confirmed by needle biopsy, which is typically performed by a radiologist who can direct the biopsy needle to the exact position of the tumor. It may be necessary to also examine the arteries and veins of the liver by hepatic arteriography, particularly if surgery is considered.

Treatment : Medical, Surgical

Treatment of primary cancer of the liver may be directed towards a cure, or focused at palliation (the relief of symptoms and prolongation of life). When the tumor is small and limited to one lobe of the liver, surgical removal offers a chance of cure. If the tumor is larger or involves more than one lobe of the liver such that it cannot be removed, liver transplantation has also been performed. In either case, the cure rate averages only 20-30 percent, which has limited somewhat the use of liver transplantation for this problem.

There are a number of newer therapies that offer good palliation for hepatocellular carcinoma. In particular, the direct injection of alcohol into the tumor via a small needle or the embolization at the time of hepatic arteriography of a specific chemotherapeutic agent (chemo-embolization) has resulted in prolonged survivals. These measures may also be used together with either surgical resection or liver transplantation.

Cirrhosis

Disease condition

Cirrhosis is a term that refers to a group of chronic liver diseases in which normal liver cells are damaged and replaced by scar tissue, decreasing the amount of normal liver tissue. The distortion of the normal liver structure by the scar tissue interferes with the flow of blood through the liver. It also handicaps the function of the liver which, with the loss of normal liver tissue, leads to failure of the liver to perform some of its critically important functions. Cirrhosis and other liver diseases take the lives of over 25,000 Americans each year and rank eighth as a cause of death.

Disease Etiology

There are a number of conditions that can lead to cirrhosis:

Alcohol consumption While almost everyone who drinks excessive amounts of alcohol sustains some liver damage, it does not necessarily develop into cirrhosis. In those individuals who drink one-half to one pint (8 to 16 ounces) of hard liquor per day (or the equivalent in other alcoholic drinks), for 15 years or more, about one-third develop cirrhosis. Another third develop fatty livers, while the remainder have only minor liver problems. In general, the more you drink, the greater the frequency and regularity of excessive intake, the more likely that cirrhosis will result. A poor diet, long considered to be the main factor in the development of cirrhosis in the alcoholic, is probably only a contributing factor. Alcohol by itself, in large amounts, is a poison which can cause cirrhosis.

Acute hepatitis A and acute hepatitis E do not lead to chronic hepatitis. Acute hepatitis B leads to chronic infection in approximately 5 percent of adult patients. In a few of these patients, the chronic hepatitis B progresses to cirrhosis.

Acute hepatitis D infects individuals already infected by hepatitis B.
Acute hepatitis C becomes chronic in approximately 80 percent of adults. A minority of these patients (20-30 percent) will progress to cirrhosis, typically over many years.

Hemochromatosis - abnormal accumulation of iron in the liver and other organs because of the increased absorption of iron from the intestine.

Wilson's disease - abnormal accumulation of copper in the liver and other organs due to the decreased excretion of copper from the liver.
Alpha1-antitrypsin deficiency--inherited absence of a specific enzyme in the liver.

Glycogen storage diseases - inability to properly utilize sugars.

Autoimmune hepatitis prolonged obstruction or other diseases of the bile ducts (biliary cirrhosis, sclerosing cholangitis) prolonged exposure to environmental toxins

Some forms of heart disease (cardiac cirrhosis) severe reaction to drugs schistosomiasis (parasitic infection)

Symptoms

The onset of cirrhosis is often "silent" with few specific symptoms to identify what is happening in the liver. As continued scarring and destruction occur, the following signs and symptoms may appear:

Loss of appetite

Nausea and vomiting

Weight loss

Enlargement of the liver

Jaundice--yellow discoloration of the whites of the eyes and skin occurs because bile pigment can no longer be removed by the liver

Itching - due to the retention of bile products in the skin

Ascites--abdominal swelling due to an accumulation of fluid caused by    the obstruction of blood flow through the liver

Vomiting of blood--frequently occurs from swollen, ruptured varices   (veins that burst) in the lower end of the esophagus due to the   increased pressure in these vessels caused by scar tissue formation

Increased sensitivity to drugs--due to inability of the liver to    inactivate them

Encephalopathy (impending coma) - subtle mental changes advancing    to profound confusion and coma.

Many patients may have no symptoms and are found to have cirrhosis by physical examination and laboratory tests, which may have been performed in the course of treatment for unrelated illnesses.



Diagnosis

In alcoholic cirrhosis

History of regular and excessive alcoholic intake physical and behavioral changes examination of liver tissue obtained by needle biopsy under local anesthesia

In active viral hepatitis infection

blood tests

liver biopsy

Treatment : Medical, Surgical

Treatment depends on the type and stage of the cirrhosis. It aims at stopping the progress of the cirrhosis, reversing (to whatever extent possible) the damage which has already occurred, and treating complications that are disabling or life-threatening. Stopping or reversing the process requires removal of the cause.

In alcoholic cirrhosis

abstinence from alcohol

an adequate, wholesome diet

In cirrhosis caused by viral hepatitis

an approved approach is the use of interferon to improve immune    responses to viral infection.

Experts estimate that more than half of all liver diseases could be prevented if people acted upon the knowledge we already have.

Each year more than 25 million Americans are afflicted with liver and gallbladder diseases and more than 25,000 die of chronic liver disease and cirrhosis. There are few effective treatments for most life-threatening liver diseases, except for liver transplants. Meanwhile, patients and their families must cope with medical, financial and emotional problems.

Research has recently opened up exciting new paths for investigation, but much more remains to be done to find cures for more than 100 different liver diseases and help millions of Americans who are suffering. To increase the number of liver researchers, the American Liver Foundation encourages young scientific investigators to pursue careers in liver research by supporting bright, highly trained men and women in their quest for answers. Research and education have made a difference. When the Foundation first became operational in 1979, reported deaths due to chronic liver diseases and cirrhosis exceeded 50,000 each year. By 1992, that figure was reduced to 26,000.

Concerned contributors like you have enabled us to increase Foundation-supported research tenfold since 1980.

In the past year the Foundation has counselled, encouraged, and informed over 35,000 anxious victims of liver disease. We distributed two million brochures to patients and referred hundreds to medical specialists. We thank you for your thoughtful support and confidence in our efforts. You have enabled us to touch the lives of millions of Americans who look to the American Liver Foundation for guidance, support and encouragement.

In certain types of cirrhosis caused by autoimmune hepatitis

corticosteroids alone or with azathioprine may be an effective treatment

In cirrhotic patients with jaundice

supplemental fat soluble vitamins may be helpful

Wilson's disease

removal of excessive copper by drugs that deplete the body's copper

Hemochromatosis

removal of excess iron by phlebotomy (removal of one pint of blood    per week)

Most types of cirrhosis

liver transplantation with replacement of the diseased organ when advanced liver failure occurs

Life expectancy and Quality of Life

Complications of cirrhosis include ascites, coma and hemorrhage from esophageal varices.

Ascites is treated by reducing the intake of salt and the administration of drugs to improve excretion of salt and water (diuretics). In some instances, large amounts of fluid are removed by direct catheter drainage through the abdominal wall (large volume paracentesis)

Treatment of coma, or impending coma (encephalopathy), includes specific medications, reducing the intake of protein foods, and control of intestinal hemorrhage.

Treatment of hemorrhage from varices (internal varicose veins) includes sclerotherapy (injection of the enlarged vein with a chemical that causes scarring). Other treatments include: drugs to reduce the likelihood of bleeding or rebleeding, compression of the bleeding varices with a specially constructed balloon, and a new radiological procedure called transjugular intrahepatic portosystemic shunt (TIPS).

Treatment at this stage, with proper adherence to the physician's recommendations, leads to improvement in the majority of cases and the patient is able to pursue a normal life and activities.

When cirrhosis is not discovered until extensive damage has resulted, the outlook may be less favorable for improvement, and complications such as ascites and hemorrhage are more likely to be encountered.

The liver is a large organ and is able to perform its vital functions despite some damage. It also has the ability to repair itself to a limited degree. Cells that die are replaced by new cells. If the cause of cirrhosis can be removed, these factors provide hope for both improvement and carrying on a normal life.

An increasing number of scientific investigators conducting liver research give hope for new breakthroughs in treatment, management and cures for liver diseases in the foreseeable future.



Crigler-Najjar Syndrome

Disease condition

Crigler-Najjar syndrome (CNS) is an inherited disorder in which bilirubin (a substance made by the liver) cannot be changed into its water-soluble form, bilirubin glucuronide. This causes jaundice (yellow discoloration of skin and eyes) and organ malfunctions.

Alternative names to CNS are Glucuronyl transferase deficiency (type I Crigler-Najjar) and Arias syndrome (type II Crigler-Najjar).

Type 1 CNS is associated with neonatal jaundice and neurologic manifestations, whereas type 2 CNS manifests as a lower serum bilirubin level. Affected individuals may survive to adulthood without any neurological impairment.

Crigler-Najjar is a very rare disease. There are less than 50 known cases in the USA, and less than 200 worldwide. It is named after Dr. Crigler and Dr. Najjar who discovered the disease.

Disease Etiology

Crigler-Najjar syndrome is caused by an abnormal gene which fails to produce a functional enzyme (bilirubin glucuronyltransferase) capable of converting bilirubin into a water-soluble and therefore, easily excreted form. As a result, bilirubin can build up in the body, which can damage the brain and other organs.

The syndrome is inherited as an autosomal recessive trait. This means that the child must get the defective gene from both parents to develop the severe form of the condition. Parents who are carriers (with just one defective gene) have about half the enzyme activity of a normal adult.

Infants who inherit the trait from both parents (this is called being homozygous for the abnormal gene) develop severe jaundice (hyperbilirubinemia) beginning a few days after birth. If these infants are not treated, they may develop kernicterus, which is bilirubin toxicity of the brain and can be fatal.

In such infants, the jaundice will persist into adult life and may require daily treatment. The constantly elevated levels of bilirubin may eventually produce an adult form of kernicterus despite treatment. If left untreated, this severe infant-onset form of the disease will lead to death in childhood.

Milder forms of the disease (type II) are not associated with severe toxicity, liver damage, or changes in thinking during childhood. Affected individuals still have jaundice, but they have fewer symptoms and less organ damage.

Symptoms

A family history of Crigler-Najjar syndrome

Yellow skin (jaundice) and eyes (icterus) that begins on the 2nd or 3rd day of life and progressively worsens

Jaundice that persists beyond 2 weeks of life without an obvious cause

Confusion and changes in thinking (resulting from brain toxicity of bilirubin)

Type 1 is associated with the production of little or no UGT, which causes very high levels of bilirubin to build up in the body. Jaundice, the yellowish appearance of the skin and eyes due to the excess bilirubin, is present at or soon after birth.

Type 2 is associated with low UGT activity, and therefore lower levels of bilirubin in the body than in type 1. Jaundice may not appear until later in infancy or childhood.

If Crigler-Najjar syndrome type 1 is not identified and treated at birth, the excess bilirubin may cause brain damage, known as bilirubin encephalopathy or kernicterus. Symptoms of kernicterus are low muscle tone (hypotonia), deafness, and lethargy; death or permanent brain damage may result.

Diagnosis


Tests used to evaluate the liver function include: Unconjugated bilirubin in blood (would be highly elevated)

Total bilirubin level (would be high)

Conjugated bilirubin (would be low to absent)

Liver biopsy, enzyme assay for low-absent Glucuronyl transferase activity

A family history of Crigler-Najjar syndrome

Infants with Type 1 will be jaundiced and have bilirubin levels of 17-50 mg/dL.

Crigler-Najjar syndrome Type 2 may be suspected in infants and children who are jaundiced and have bilirubin levels of 6-22 mg/dL.

Treatment - Medical, Surgical

Medical Treatment :

Patients with type 2 CNS may not require any treatment or can be managed with phenobarbital. By contrast, prompt treatment of kernicterus is required in patients with type 1 CNS to avoid the potentially devastating neurological sequelae.
Emergent management of bilirubin encephalopathy involves plasma exchange transfusion, which acts by removing the bilirubin-saturated albumin and provides free protein, which draws bilirubin from the tissues.

Plasma exchange should be accompanied by long-term phototherapy, which helps in the conversion of bilirubin to more soluble isoforms that can be excreted in the urine. Oral calcium phosphate may be a useful adjuvant to phototherapy in type 1 CNS.

Therapies based on gene and cell transfer techniques, although largely experimental at the present time, are likely to play an important role in the management of CNS in the future.

Inhibitors of heme oxygenase, such as tin protoporphyrin or tin-mesoporphyrin, may be helpful in reducing bilirubin levels emergently, but the effect is short-lived.

Phototherapy is needed on an ongoing basis throughout life. In infants this is done using bilirubin lights (bili or 'blue' lights)

Phototherapy becomes less successful after 4 years because thickened skin blocks the light.

Surgical Treatment:


Liver transplantation has been attempted in select patients with type 1 CNS and has achieved good success rates.

Life expectancy and Quality of Life

Genetic counseling is recommended for prospective parents with a family history of Crigler-Najjar syndrome. People who carry the gene can be recognized by blood testing.

The majority die with kernicterus in the first year of life.

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