Living Donor Liver Transplant

About live liver donation
Partial liver donation by relatives of the patient is becoming more and more common all over the world. More than 1000 live donations have been carried out globally. Though the liver is a single organ, the anatomical disposition of the organ allows it to be split into two useful portions safely. Moreover the liver has in excess of 300% reserver capacity and can theoretically survive with only 30% of the total liver volume. The liver is also very unique in its ability to regenerate. It is documented that the liver regenerates to 90% of the original liver volume within 3 months of removing > 50% of the liver for donation. Liver donation is a major surgery and will leave a large scar. At the author's center over 50 live donor operations have been performed with few minor complications. 60% of the patients did not require blood transfusion during surgery. The only notable complication was a bile leak from the raw area of the liver that settled spontaneously within 3 weeks. Most donors were discharged within 10 days of surgery and they can return to non-manual work 4-6 weeks after surgery and full active life within 3 months. The only long term morbidity seems to be wound pain which may persist beyond 3 months in about 30% of the donors. Occassional death has been reported after live donation which underlines the fact that the procedure should be carried out only by experts in this field in transplant centers with good track record, who can guarantee donor safety and low complication rate.

Factors in Donation Process
When an organ is donated from a person who has died, it is made available to an eligible patient on the waiting list. Before the transplant can take place, however, several things happen. Although a patient meets all the criteria and appears to be a good match for the organ, the organ still has to be accepted by the transplant center. The transplant team has a very short time to consider several factors before accepting that organ for the particular patient. If, in the physician's judgment, the organ offered presents undue risks to the patient, it may be refused. There are a number of reasons for refusing an organ, such as:

• Patient condition - The patient may currently be too ill to undergo surgery. Or, the patient may be out of town or otherwise unavailable for surgery at that time.
• Donor condition - The donor might have had high blood pressure, diabetes or some other illness that might have harmed the donated organ.
• Organ condition - If an organ has been outside the donor's body for too long it might not work as well and may not help the patient. Or, the organ might have been damaged during recovery from the donor or during transit to the transplant center. Sometimes, final examination of the organ shows previously unseen risks, such as too much fatty tissue or badly formed blood vessels.
• Donor/recipient compatibility - Critical "matching" tests, done just prior to surgery, sometimes reveal unknown incompatibilities that would result in failure of the transplant.
• Transplant center factors - Geography may be a factor, as it may not be possible to get the organ to the center within a desirable amount of time.

There are some differences among transplant centers overall in terms of how often organs are accepted or refused. But recent studies have found that how often a center accepts or refuses transplant organs does not seem to affect such important factors as how long patients wait for transplant or how well those patients do either before or after transplant.*

* From the United Network for Organ Sharing (UNOS') Summary of Key Findings 1113197. The UNOS 1997 Report on Center-Specific Organ Acceptance Rates.

Hepatitis Treatment

About Hepatitis
How do I get Hepatitis C | How do I keep it Myself

What is Hepatitis? 
Hepatitis is an inflammation of the liver. The different types of hepatitis are caused by different things, but they all produce inflammation of the liver. Viral hepatitis refers to several common contagious diseases caused by viruses that attack the liver. The most important types of viral hepatitis are hepatitis A, hepatitis B, and hepatitis C. Newly discovered forms of viral hepatitis also include hepatitis D, hepatitis E, and hepatitis G. Non-viral forms of hepatitis can be caused by toxic agents (drugs or chemicals), alcohol, or autoimmune processes. Another form of hepatitis is toxic hepatitis. Toxic hepatitis can be caused by viruses or by liver damage due to toxic substances. Toxic hepatitis is a deterioration of the liver cells caused by chemicals, alcohol, drugs, and industrial compounds. Alcohol abuse is a common cause of toxic liver damage.

Hepatitis C is a viral infection of the liver. Some patients have amild, acute infection that disappears without treatment. When the infection continues for six or more months, it is known as chronic hepatitis C, which can be marked by fatigue and liver function impairment. Those with chronic hepatitis C have an increased risk of later developing cirrhosis or liver cancer.

HEPATITIS C (HCV)
Hepatitis C (HCV) is a form of hepatitis caused by an RNA virus. HCV accounts for the majority of the hepatitis cases previously referred to as non-A, non-B hepatitis. The hepatitis C virus was first identified and described in 1987, and in 1990 a hepatitis C antibody test (anti-HCV) became commercially available to help identify individuals exposed to HCV. In mid-1995 the hepatitis C virus was seen for the first time ever by scientists with the aid of an electron microscope. It is a linear single-strand RNA (ribonucleic acid) virus 40-50 nanometers in size. It is covered with a lipid envelope and is encased with glycoprotein peplomers or "spikes".

Patient Information - What is Hepatitis C?
Hepatitis C is a disease of the liver caused by a virus that was first discovered in 1989. Unlike hepatitis A which is caused by fecal contamination of food and water; or hepatitis B which is spread through contact with infected blood or other body fluids; hepatitis C is spread by direct contact with the blood of an infected person. Prior to the discovery of the virus, it was known that some agent caused hepatitis or inflammation of the liver in people who had been given blood, and it was known that the agent could be transmitted to patients and to experimental animals in blood. Before the virus was identified, this form of hepatitis was called non A non B hepatitis because the viruses causing hepatitis A and hepatitis B were already identified and could be tested for. Patients with hepatitis following exposure to blood who had negative tests for hepatitis A and for hepatitis B were said to have non A non B hepatitis. It is now known that the majority of these patients were infected with the virus identified and named hepatitis C virus or HCV for short. As tests for this virus have improved over the years since 1989, more and more people who have hepatitis which could not be diagnosed with accuracy are now being correctly diagnosed as infected with the hepatitis C.

Is the new hepatitis A vaccine effective and who needs it? 
Yes, the new hepatitis A vaccine (Havrix) is very effective. It induces protective titres of anti-bodies in greater than 95%, and 99% of people after the first and second doses, respectively. If time does not permit two doses six months apart, then a single Havrix-1440 (double strength) dose may be given. The first dose of the vaccine probably requires at least three weeks to induce significant antibodies, so those travellers who did not have the foresight to have the first dose administered at least three weeks before departure to a high-endemic area should also have standard gammaglobulin to assure protection. Protective antibody titres to the vaccine last at least three years. At this time the need for booster doses is unclear, but it's likely that, similar to hepatitis B, they will be unnecessary. The vaccine should be administered as an IM injection into the deltoid. Children can be given half-strength (0.5 mL) doses.

Although the manufacturer has suggested a very broad range of people to be targeted for vaccination, the National Advisory Committee on Immunization (NACI) only recommends vaccinating:

1) long-term or frequent travellers to endemic regions (which means basically everywhere except Canada, USA, Western Europe, Japan, Australia, and New Zealand).
2) residents of communities with high endemic rates of recurrent outbreaks of hepatitis A, and
3) residents and staff of institutions for the mentally handicapped.

Who Should Receive Hepatitis A Vaccination? 
Long-term or frequent travellers to endemic regions. Residents of communities with high endemic rates of hepatitis A. Residents and staff of institutions for the mentally handicapped

Is there any role for standard gammaglobulin in viral hepatitis prophylaxis?
Basically no. (See the answer above for one last small indication.) Development of highly effective hepatitis A vaccines has obviated the need for gammaglobulin. Note that standard gammaglobulin is useless for immunoprophylaxis against hepatitis B and hepatitis C.

What is universal hepatitis B vaccination? 
This refers to vaccination of the entire population, usually at the neonatal or childhood level. The rationale for this is that targeted vaccination of high-risk groups has failed to achieve its aims, because most people in these risk groups are unaware or unwilling to be vaccinated. Moreover, 30% to 40% of hepatitis B virus (HBV) infections occur in people who deny any known risk factor.

What are the immunoprophylaxis recommendations for household contacts if an individual is found to be positive for HBsAg or develops acute hepatitis B?
All household contacts should be screened for HBsAg and anti-HBs. If the spouse or sexual partner is negative for both, then he or she should be given 5 mL of HBIG and a course of vaccine, if the index case has acute hepatitis B, whereas vaccine alone should suffice for partners of chronic HBsAg carriers. Other household contacts, if serologically negative, require only a course of vaccination. In Canada, almost all public health units will carry out the above or slightly variant programs when notified of a positive HBsAg result.

I have a general practice with very little ER work; why should I be vaccinated for HBV? 
If your practice involves no work in emergency rooms, hospital wards, institutions for the handicapped and no administration of needles or minor surgery, and you never have hangnails, minor cuts and abrasions on your hands, then it is likely that you would not be susceptible to occupationally-acquired hepatitis B. There are very few practices that fit this description, and all other physicians would benefit from this safe and effective vaccine. Or, put another way, there has been several cases of unvaccinated physicians who died from occupationally-acquired acute hepatitis B; isn't your life worth the $150.00 cost of a course of vaccine?

I had a standard course of three deltoid injections of full-dose hepatitis B vaccination, but failed to make protective antibody titres.

What does this mean and what should I do now?
Lesser response rates to HBV vaccination are associated with age, increased body mass and smoking. For example, only 60% to 80% of those aged over 60 years make protective antibody titres. No one can reverse aging, but it you are overweight and smoke, losing weight and quitting smoking, followed by revaccination, might be effective. Even in healthy immunocompetent adults, about 5% will not develop protective antibodies after a course of vaccination. Recent work has discovered that the immune response to hepatitis B surface epitopes is genetically determined. For your interest, you probably have HLA haplotypes B8, DR3, SCO1; or B44, DR7, FC31. If a second complete course of vaccinations fails to induce protective titres, you will have to sadly accept that you are not protected against hepatitis B. You can blame your parents for giving you these bad genes.

Is a booster dose needed after five or ten years for recipients of hepatitis B vaccination? 
No. If you originally demonstrated an adequate antibody response, even though anti-HBs titres may gradually fall below the critical 10 IU/L level, the immune system will mount a sufficiently protective anamnestic response if rechallenged with hepatitis B.

Is there anything on the horizon for a vaccine against hepatitis C? 
No. Effects to develop an effective HCV vaccine have been frustrated by:

• initial difficulties in actually identifying the virus responsible for hepatitis C (although we knew its molecular structure in 1989, it was not until 1996 that a putative HCV was identified),
• difficulties in establishing stable cultures of the virus in a cell line, and
• high mutability of the HCV, which like HIV, mutates at a high rate.

What should be done in case of a needlestick injury? 
Management will slightly differ depending on whether the recipient (usually a health care worker) has previously been vaccinated for HBV. If vaccinated, then the recipient (as a baseline) and the source patient, should be tested for anti-HCV and anti HIV. If not vaccinated, then HBsAg should be added to the tests for the source patient, and both HBsAg and anti-HBs added to the recipient's bloodwork. Since this article is focussed on hepatitis, we will only deal with the HBV and HCV-positive scenarios.

1) Source is HBsAg-positive, recipient unvaccinated (and negative for both HBsAg and HBs): give recipient HBIG, 5 mL, i.m., and first dose of hepatitis B vaccine. Complete the standard dosing protocol of vaccine at zero, one, and six months. Without intervention, there is about a 20% chance of the recipient contracting acute hepatitis B, and this figure is a composite of approximately a 50% to 80% chance if the source is HBeAg-positive (replicating, with high viral load), and a 10% to 15% chance if the source is HBeAg-negative. 2) Source is anti-HCV-positive, recipient anti-HCV-negative: test the recipient for ALT at baseline (as soon as possible after needlestick), and HCV-RNA by polymerase chain reaction and ALT at six to eight weeks after exposure. If HCV RNA is negative at this time, the chance of contracting acute hepatitis C is essentially zero. If the HCV-RNA test is not available locally, then the ALT should be repeated at three and six months, and the anti-HCV at six months. If they remain normal or negative at six months, the likelihood of developing HCV will be nil. If HCV-RNA turns positive at six to eight weeks, this heralds the onset of acute hepatitis C, and these patients should be treated with a- interferon at a dose of three million units s.c. thrice weekly for 24 weeks. In centres where HCV-RNA is not available, the diagnosis of acute HCV can be made using a combination of the ALT and anti-HCV serology, realizing that the development of anti-HCV-positivity, even with third generation enzyme immunoassays, sometimes lags behind the acute hepatitis by a month or more. Therefore, before embarking on interferon therapy with its cost and side effects, I would recommend confirming the diagnosis by HCV-RNA which can be sent out to a lab in a larger centre.

Fortunately, acute HCV developing after needlestick injury is uncommon. Several series have indicated that the risk of this occurring is approximately 5% to 10%.

What is the treatment of Acute Alcoholic Hepatitis?
General measures for treatment of acute alcoholic hepatitis include abstinence from alcohol, nutritive support, relief of vitamin deficiencies and dietary adjustments if ascites or hepatic encephalopathy are present. Gastrointestinal bleeding and infections, particularly spontaneous bacterial peritonitis, are potential complications that can be specifically treated. Patients with mild alcoholic hepatitis may have marked improvement with abstinence and supportive care while those with deep jaundice, hepatic encephalopathy and marked abnormality in prothrombin have a 30-50% mortality and will almost certainly develop severe hepatic fibrosis or cirrhosis if they survive. A discriminant function developed by Maddrey and Colleagues (4.6 x prothrombin time-control prothrombin time + serum bilirubin in mg/dl) of >32 indicates a poor prognosis.

Since we have lacked knowledge of the pathogenesis of alcoholic liver injury, specific treatment of acute alcoholic hepatitis has been necessarily empirical. Potential objectives of treatment in severe cases have been suppression of hepatic inflammation, reduction of collagen formation, stimulation of hepatocyte regeneration and interruption of possible immunologically mediated or cytokine-induced hepatocyte damage.

A large number of randomized controlled trials (RCT) of a number of different treatments have been published. These include propylthiouracil, insulin and glucagon, anabolic-androgenic steroids, colchicine, penicillamine, and parenteral nutrition. None have shown unequivocal benefit. Much attention has been directed toward corticosteroid therapy, with 14 published RCTs. Most have shown no benefit, including three from our USC Liver Unit ( 2 published, 1 unpublished). However, in 3 of 14 trials there was a significantly better survival in a subgroup of patients with the most severe illness as indicated by the presence of spontaneous hepatic encephalopathy or a high Maddrey discriminant function. Three meta-analyses of these trials have been published. Two concluded that there was modest benefit from corticosteroid treatment in a subgroup of patients with spontaneous hepatic encephalopathy. The third and most recent meta-analysis concluded that there was no statistically significant benefit from corticosteroid, including the subgroup with encephalopathy.

In our Liver Unit we have recently completed a 4-year RCT of pentoxiphylline treatment designed to inhibit synthesis of tumor necrosis factor, a potentially harmful cytokine. This trial, not yet published, showed significant benefit from the treatment with short-term death rate of 23/52 in control patients vs. 12/49 in those treated with pentoxifylline. Currently we are considering a trial of monoclonal antibody to tumor necrosis factor.

Liver Cancer

Liver cancer rarely occurs in a normal liver. Non cancerous tumours are rare. It is common in livers infected with hepatitis B or C viruses and in cirrhotic livers. These do not produce much symptoms until late stages and are picked up on random scans. In more advanced stages it causes pain, jaundice, swelling of abdomen, loss of weight and appetite. Cancers that occur from liver cells are primary liver cancers and those that spread from other organs are secondary liver cancers. The differentiation is important, as the treatment differs widely. The diagnosis is made by ultrasound, MRI or CT scans along with fine needle biopsy. Some of these tumours can produce cancer markers such as Alpha fetoprotein (AFP) or Carcinoembryonic antigen (CEA). These markers are more useful for follow up after treatment than for the diagnosis, when raised. Most primary cancers that are restricted to the liver are best treated surgically irrespective of size, whenever possible. Surgery or liver transplant offers the best shot at survival. Survival after liver transplant is as good (85%) as non tumour patients when the tumour volume or number is low (Milan criteria). Liver cancers can spread outside the liver to the lymph nodes, lungs or locally to the adjacent tissues like diaphragm. More commonly primary cancers are known to grow rapidly through the blood vessel like the portal vein, forming tumour thrombus. Tumours that are not treatable surgically can be treated by chemo-embolization(TACE) or radio-embolization (theraspheres), Ethanol injection (PEI), Radiofrequency ablation(RFA) or by Cryoablation.

Secondary liver tumours are usually treated on the same lines as the primary tumours with the difference that the source of the primary tumour is also treated at the same time, provided the disease has not spread to the lungs and bones. Secondary cancers from primary tumour in colon, ovary or neuroendocrine origin are particularly suited for aggressive surgical removal as it improves survival. Liver transplants are not indicated for secondary liver cancers with the exception of a special group of tumours called neuroendocrine tumors.

Cancer of the Liver.
This National Cancer Institute (NCI) booklet has important information about cancer that begins in the liver. It discusses possible causes, symptoms, diagnosis, and treatment of liver cancer. It also has information to help patients cope with this disease. Information specialists at the NCI's Cancer Information Service at 1-800-4-CANCER can help people with questions about cancer and can send NCI publications.

Symptoms.
Liver cancer is sometimes called a "silent disease" because in an early stage it often does not cause symptoms. But, as the cancer grows, symptoms may include:

• Pain in the upper abdomen on the right side; the pain may extend to the back and shoulder
• Swollen abdomen (bloating)
• Weight loss
• Loss of appetite and feelings of fullness
• Weakness or feeling very tired
• Nausea and vomiting
• Yellow skin and eyes, and dark urine from jaundice
• Fever

These symptoms are not sure signs of liver cancer. Other liver diseases and other health problems can also cause these symptoms. Anyone with these symptoms should see a doctor as soon as possible. Only a doctor can diagnose and treat the problem.

Treatment.
Many people with liver cancer want to take an active part in decisions about their medical care. They want to learn all they can about their disease and their treatment choices. However, the shock and stress that people often feel after a diagnosis of cancer can make it hard for them to think of everything they want to ask the doctor. Often it helps to make a list of questions before an appointment. To help remember what the doctor says, patients may want to take notes or ask whether they may use a tape recorder. Some patients also want to have a family member or friend with them when they talk to the doctor -- to take part in the discussion, to take notes, or just to listen.

At this time, liver cancer can be cured only when it is found at an early stage (before it has spread) and only if the patient is healthy enough to have an operation. However, treatments other than surgery may be able to control the disease and help patients live longer and feel better. When a cure or control of the disease is not possible, some patients and their doctors choose palliative therapy. Palliative therapy aims to improve the quality of a person's life by controlling pain and other problems caused by the disease.

The doctor may refer patients to doctors who specialize in treating cancer, or patients may ask for a referral. Specialists who treat liver cancer include surgeons, transplant surgeons, gastroenterologists, medical oncologists, and radiation oncologists.

Liver Coma (Encephalopathy)

Liver is the most important organ that helps in clearing waste products of metabolism from the blood stream. All the food that is eaten is assimilated in the intestines and absorbed into the blood stream and is carried to the liver by the portal vein. In the liver the cells are active round the clock and break down the absorbed nutrients into energy yielding forms, storage forms and body building forms of basic products. The waste produced as the end result is also made non toxic and excreted either as bile or through the urine. When liver cell failure occurs the waste products accumulate in the blood, slowing down the brain function. The coma can progress through four stages, the earliest being slowness of speech or altered sleep wake cycle and the last stage being deep state of coma. In most occasions coma is reversible completely unless the liver failure is very advanced.

One of the several toxins that is measurable is ammonia. As most toxins are waste products of protein metabolism (aromatic aminoacids), this state is also called protein intolerance, this is directly proportional to the degree of liver failure. Thus treatment of liver coma involves reducing intake of protein in the diet and clearing the large bowel of faecal matter. Oral antibiotics also help by reducing the bacterial load in the gut, indirectly reducing the ammonia production from waste matter. Coma can also be a result of low sodium level in the blood or due to intake of drugs with sedative action. In this case correction of sodium level will restore normalcy. Infections in the body of patients with cirrhosis of liver can predispose to liver coma.

Portal Hypertension

Portal vein carries blood with nutrients from the intestines to the liver, for further processing. In normal state the pressure in the portal vein is around 9 mm of mercury, about twice the pressure in other veins in the body. This pressure gradient is required to push the blood across the liver tissues, into the heart. However when the liver shrinks from disease, the resistance to blood flow increases several fold. This state is called portal hypertension. This results in accumulation of fluid in the abdomen (ascites) and diversion of blood flow through some narrow bypass vessels, which results in varices. Variceal veins are thin walled and found lining the upper stomach and lower food pipe. When the pressure increases beyond a threshold, the wall can break, resulting in severe bleeding. Hence, ascites, GI bleed, hypersplenism and portal hypertensive gastropathy are the result of portal hypertension. Since resitance to blood flow can only be altered by a liver transplant, certain mechanical and medical strategies are used to avert the problems. Drugs like beta blockers (propronolol) used to reduce PHT. The dosage starts at 20 mg thrice a day and titrated to reduce the heart rate to less than 60. Glue injection and elastic banding (EVL) of variceal veins is another approach to prevent bleeding. In severe bleed, an oesophageal balloon is used to stop bleeding followed by glue injection, band ligation or TIPS procedure. Increased portal pressure also causes enlargement of the spleen, as they are connected to the same venous drainage. The enlarged spleen hyperfunctions, causing a fall in all the cell types in the blood like white and red cells as well as platelets. This state is called hypersplenism. Extreme hyper-splenism is treated by partial embolization of spleen or create a shunt (TIPS) to reduce portal pressure. Removal of spleen in a patient with cirrhosis is not advisable and can be dangerous.

Liver Cirrhosis

Cirrhosis of the Liver
When the liver gets damaged uniformly by toxins, bile, drugs, alcohol, hepatitis infections or by certain genetic conditions, the normal tissue gets replaced with scars. As the disease progresses the scars coalesce to forming ‘bridging fibrosis’. Several islands of normal liver get trapped within the sea of scar and struggle to regenerate, forming nodules. This state is called cirrhosis and is the final pathway for all progressive chronic liver diseases. The liver cirrhosis is also a progressive state that leads to gradual shrinking of the size of the liver. As the volume of normal functioning liver cells reduce, a state of liver failure ensues. This is manifested as lower levels of the protein albumin and prothrombin, that can be measured by blood tests (serum albumin and prothrombin time). The shrinkage of liver also causes mechanical resistance to flow of blood in the main vein that runs through the liver (portal vein), resulting in the state of portal hypertension. This manifests in patients as fluid accumulation in the belly (ascites) and enlargement of some bypass blood channels in the food pipe (called varices). These enlarged vessels are not built to withstand high pressures and can rupture spontaneously, resulting in life threatening bleeding. Cirrhosis also predisposes the liver to cancer risk. When the liver failure advances it becomes incompatible with life and will need liver replacement. Patients with cirrhosis can be without symptoms for a long time and only suffer when the liver failure advances. Most symptomatic patients will need liver replacement within 4 years and have a death rate of 98% without liver transplant during that period. The symptoms of cirrhosis include severe itching, altered sleep wake cycle, change in hand writing, jaundice, swelling of the legs or abdomen, loss of hair from the body in men, darkening of skin, and bleeding from mouth and nose. The diagnosis is confirmed by blood tests and liver scan.

Causes
Cirrhosis has many causes. In the United States, chronic alcoholism and hepatitis C are the most common causes.

Alcoholic liver disease. To many people, cirrhosis of the liver is synonymous with chronic alcoholism, but in fact, alcoholism is only one of the causes. Alcoholic cirrhosis usually develops after more than a decade of heavy drinking. The amount of alcohol that can injure the liver varies greatly from person to person. In women, as few as two to three drinks per day have been linked with cirrhosis and in men, as few as three to four drinks per day. Alcohol seems to injure the liver by blocking the normal metabolism of protein, fats, and carbohydrates.

Chronic hepatitis C. The hepatitis C virus ranks with alcohol as the major cause of chronic liver disease and cirrhosis in the United States. Infection with this virus causes inflammation of and low grade damage to the liver that over several decades can lead to cirrhosis.

Chronic hepatitis B and D. The hepatitis B virus is probably the most common cause of cirrhosis worldwide, but in the United States and Western world it is less common. Hepatitis B, like hepatitis C, causes liver inflammation and injury that over several decades can lead to cirrhosis. The hepatitis D virus is another virus that infects the liver, but only in people who already have hepatitis B.

Autoimmune hepatitis. This typef of hepatitis is caused by a problem with the immune system.

Inherited diseases. Alpha-1 antitrypsin deficiency, haemochromatosis, Wilson's disease, galactosemia, and glycogen storage diseases are among the inherited diseases that interfere with the way the liver produces, processes, and stores enzymes, proteins, metals, and other substances the body needs to function properly.

Nonalcoholic steatohepatitis (NASH). In NASH, fat builds up in the liver and eventually causes scar tissue. This type of hepatitis appears to be associated with diabetes, protein malnutrition, obesity, coronary artery disease, and corticosteroid treatment.

Blocked bile ducts. When the ducts that carry bile out of the liver are blocked, bile backs up and damages liver tissue. In babies, blocked bile ducts are most commonly caused by biliary atresia, a disease in which the bile ducts are absent or injured. In adults, the most common cause is primary biliary cirrhosis, a disease in which the ducts become inflamed, blocked, and scarred. Secondary biliary cirrhosis can happen after gallbladder surgery, if the ducts are inadvertently tied off or injured.

Drugs, toxins, and infections. Severe reactions to prescription drugs, prolonged exposure to environmental toxins, the parasitic infection schistosomiasis, and repeated bouts of heart failure with liver congestion can each lead to cirrhosis.

Symptoms
Many people with cirrhosis have no symptoms in the early stages of the disease. However, as scar tissue replaces healthy cells, liver function starts to fail and a person may experience the following symptoms:

• Exhaustion
• Fatigue
• Loss of appetite
• Nausea
• Weakness
• Weight loss.

As the disease progresses, complications may develop. In some people, these may be the first signs of the disease.

Treatment
Liver damage from cirrhosis cannot be reversed, but treatment can stop or delay further progression and reduce complications. Treatment depends on the cause of cirrhosis and any complications a person is experiencing. For example, cirrhosis caused by alcohol abuse is treated by abstaining from alcohol. Treatment for hepatitis-related cirrhosis involves medications used to treat the different types of hepatitis, such as interferon for viral hepatitis and corticosteroids for autoimmune hepatitis. Cirrhosis caused by Wilson's disease, in which copper builds up in organs, is treated with medications to remove the copper. These are just a few examples--treatment for cirrhosis resulting from other diseases will depend on the underlying cause. In all cases, regardless of the cause, following a healthy diet and avoiding alcohol are essential because the body needs all the nutrients it can get, and alcohol will only lead to more liver damage.

Treatment will also include remedies for complications. For example, for ascites and edema, the doctor may recommend a low-sodium diet or the use of diuretics, which are drugs that remove fluid from the body. Antibiotics will be prescribed for infections, and various medications can help with itching. Protein causes toxins to form in the digestive tract, so eating less protein will help decrease the buildup of toxins in the blood and brain. The doctor may also prescribe laxatives to help absorb the toxins and remove them from the intestines.

For portal hypertension, the doctor may prescribe blood pressure medication such as a beta-blocker. If varices bleed, the doctor may either inject them with a clotting agent or perform a rubber-band ligation, which uses a special device to compress the varices and stop the bleeding.

When complications cannot be controlled or when the liver becomes so damaged from scarring that it completely stops functioning, a liver transplant is necessary. In liver transplantation surgery, a diseased liver is removed and replaced with a healthy one from an organ donor. About 80 to 90 percent of people survive liver transplantation. Survival rates have improved over the past several years because of drugs such as cyclosporine and tacrolimus, which suppress the immune system and keep it from attacking and damaging the new liver.

Alcoholic Liver Disease

Alcoholic Liver Disease
This is the most common cause of liver cirrhosis in most parts of the world. Alcohol related liver injury passes through three distinct clinical phases such as acute fatty liver, alcoholic hepatitis and alcoholic cirrhosis. In a given patient these may occur in varying combinations. Acute fatty change of alcohol abuse may progress to cirrhosis in 20% of patients. Alcoholic hepatitis develops only in a small proportion of patients after decades of abuse. This condition may progress to cirrhosis. Once cirrhosis develops it is irreversible and progress at the rate of 10% annum if there is no further insult. Liver cancer can develop in 20% of these cirrhotics.

Alcoholic fatty liver disease:
Fatty change occurs after consumption of large amounts of alcohol over a short period of time. The liver tests and clinical liver swelling returns to normal after abstaining from alcohol. The fat clearance fro the liver takes place in 2-6 weeks. With continued abuse of alcohol this may progress to hepatitis and cirrhosis. Fatty change may persist in some after abstaining from alcohol when they have obesity, diabetes or pancreatitis.

Alcoholic Hepatitis:
This is a state with a wide spectrum of presentation ranging from mild swelling of the liver to severe jaundice, fluid in the abdomen including hepatic coma. The symptoms include lethargy, anorexia, fatigue, vague abdominal pain and rarely jaundice. Women tend to have more florid illness. Approximately 50% may have fluid collection in the abdomen. Bleeding tendency may manifest as easy bruising of skin. Blood tests will reveal a rise in liver enzymes, bilurubin and alkaline phosphatase. Low haemoglobin and high white cell counts are common. In the more severely ill, platelet count will be low and the prothrombin time will be elevated and incompletely corrected with treatment.