Center for Advanced Liver Diseases and Transplantation
Diseases of the Hepatobiliary System
The hepatobiliary system refers to the liver, gall bladder and bile ducts – organs that are involved with the production, storage, transport and release of bile, a secretion that prepared fats for further digestion.
There are numerous conditions that can harm the hepatobiliary system, some of which are life-threatening and ultimately, require surgery and/or liver transplantation. Liver damage can occur from a variety of sources: infections with viruses (hepatitis A, B, and C viruses), exposure to toxic drugs or chemicals, excessive use of alcohol, genetic disorders , diabetes, heart failure, cancer and shock. Some of the signs and symptoms of liver disease include:
- jaundice (yellowing of the skin and eye)
- pruritus (itching)
- dark, tea-colored urine
- weight loss
- muscle wasting
- ascites (swelling of the abdomen with fluid)
- easy bruising and bleeding (bleeding gums or frequent nosebleeds)
- vomiting blood
- blood in the stool (bright red blood or black, tar-like stool)
- mental confusion
In many cases, the liver is able to repair itself; in others, a variety of treatments may be effective. However, if liver damage is severe, the organ may not recover, resulting in liver failure which is life threatening. Once this happens, the patient may need a new liver.
Cirrhosis describes a condition in which damaged liver cells are replaced by scar tissue. Over time, the build-up of scar tissue becomes so great that it impacts blood flow through the liver, destroying more liver cells and ultimately leading to greater and greater loss of liver function.
Almost any liver disease can result in cirrhosis, but excessive use of alcohol remains the most common cause.
Inflammation of the liver is called hepatitis. Inflammation (or soreness) of the liver can be traced to many different causes, including viral infections, alcohol, fat accumulation in the liver, an incorrectly functioning immune system, exposure to chemicals and other toxins, and certain drugs.
The hepatitis C virus (formerly referred to as non-A, non-B hepatitis) is by far the leading indication for liver transplantation in the United States, accounting for between 30% and 50% of liver transplants, depending on the state where the patient lives. According to the American Liver Foundation, more than 4 million people in the U.S. have hepatitis C, but only about 30 percent who have the virus are aware that they do. The hepatitis C virus kills between 10,000 and 12,000 Americans each year, but the future holds even grimmer prospects. According to some estimates, about 10 million Americans will have hepatitis C within the next couple of decades.
Hepatitis C progresses very slowly, often over the course of 10-20 years, and does much of its damage without symptoms to indicate something might be wrong until liver failure sets in. When a person with hepatitis C does have symptoms, they typically are those associated with a damaged liver. The damage to the liver eventually takes the form of cirrhosis in about 25% of patients, in which healthy liver cells are injured and scar tissue forms in their place. Over time, cirrhosis impairs the liver’s ability to perform critical functions and reduces the amount of blood that flows through the vital organ. Alcohol use increases the progress of liver disease in Hepatitis C; further, the risk of liver cancer is increased in patients with the infection.
The hepatitis C virus, discovered in 1989, is transmitted via blood, so anyone who had a blood transfusion before 1992 or has used intravenous drugs could be at risk. It’s possible for an infected mother to pass along the virus to her child at birth. Researchers aren’t sure whether hepatitis C can be transmitted sexually. If so, it’s a rare occurrence, but people who’ve had multiple partners are encouraged to be tested for the virus. Certain groups of people have higher rates of hepatitis C than the general population, such as military veterans (especially those who served in Vietnam); prisoners; hemophiliacs; the homeless; and people with HIV.
The hepatitis B virus was once a major public health threat in the United States and it still is in some parts of the world, such as Asia and the Pacific. While the hepatitis B vaccine has become a valuable tool against the virus, those people who currently are infected or are not vaccinated and contract hepatitis B can face serious health problems, including liver cancer, the need for a liver transplant or even death. In the United States, 1.25 million people have chronic hepatitis B, and there are 5,000 to 6,000 hepatitis B-related deaths each year. Fortunately, the hepatitis B virus, which is transmitted via blood and bodily fluids, causes chronic infection in less than five percent of the cases.
The hepatitis A virus is an acute disease that typically is transmitted via contaminated water or food and resolves without becoming a chronic disorder in almost all cases. It is relatively uncommon in the United States, but international travelers (particularly those headed for developing countries or places with poor sanitation systems) are encouraged to be vaccinated against the hepatitis A virus.
Acute Fulminant Viral Hepatitis: This describes a sudden and catastrophic loss of liver function due to infection from any of the three previously described viruses. Fortunately, only a small percentage of patients (less than 1 percent) that have viral hepatitis develop this variety. The patient deteriorates rapidly from being healthy one day to possibly being comatose in 7-10 days. In addition to causing rapidly progressive liver failure there may be kidney failure, blood-clotting disorders, brain damage and coma.
Toxic hepatitis: Rarely, medications intended to help patients can cause the liver to become suddenly inflamed, causing toxic hepatitis. For that reason, acetaminophen (Tylenol™), isoniazid (a drug used to treat tuberculosis), and many anti-convulsants should not be taken by people with liver disease. Even with a healthy person, an excessive amount of acetaminophen could cause toxic hepatitis. In an occupational setting, toxic hepatitis can occur when workers are exposed to certain chemicals in a confined space and are not wearing or properly using respiratory protective gear.
Autoimmune Hepatitis: This is a condition in which a person’s immune system starts attacking their own organs, as if they did not belong to that individual. Autoimmune hepatitis primarily affects women and starts as early as adolescence. As the name suggests, autoimmune hepatitis can cause inflammation of the liver and other symptoms common to liver disease such as jaundice and itching as well as some associated with autoimmune disorders, namely, aching joints. Fatigue, common to both, is a frequently reported symptom. Lab tests show the presence of increased gamma globulin and smooth muscle antibodies in the blood.
Many people with autoimmune hepatitis respond well to prednisone treatment, which can relieve symptoms and cause elevated liver enzyme levels to return to normal. Autoimmune hepatitis is a condition that needs monitoring over the long term, as it can lead to cirrhosis and ultimately, the need for a liver transplant.
Alcoholic Liver Disease
Heavy drinking over a long period of time can take its toll on the liver by causing cirrhosis. Before the onset of cirrhosis the liver sometimes may accumulate an excessive amount of fat (known as fatty liver disease), which interferes with its proper functioning. Moreover, alcohol consumption can accelerate the rate at which other conditions, such as hepatitis C, damage the organ. According to the Scientific Registry of Transplant Recipients, alcoholic liver disease was the third leading indication for liver transplantation in 2003 (26 percent of the transplant recipients in this category also were infected with hepatitis C).
If alcoholic liver disease is identified in an early stage and if the person stops drinking, it is possible that his or her condition could improve. However, these are two major “ifs,” considering the often-silent nature of liver disease and the difficulty of breaking an addiction. Sometimes, the liver damage is advanced, and a liver transplant is needed.
Patients with alcoholic liver disease must meet the following criteria to be considered for liver transplantation at University Hospital: (1) abstinence from alcohol use; (2) ongoing participation in an alcohol treatment program or support group; and (3) presence of an adequate psychosocial support system. These patients must enter a formal contract with the transplant team outlining the parameters of abstinence from alcohol use.
Tumors found in the liver can be benign (non-cancerous) or malignant (cancerous). Some of the benign tumors can be left untreated, but sometimes they must be removed. Primary liver cancer (cancer that originates in the liver) is not as common in the United States as it is in other parts of the world, but there are still about 16,000 cases diagnosed in America each year. Most of the time, liver cancer begins in another organ and spreads to the liver. These tumors are called secondary liver tumors or metastases. Liver cancer usually is not diagnosed until it has reached an advanced stage, when removing a tumor surgically is less often a possible treatment choice.
Malignant (Cancerous) Liver Tumors
Primary liver cancer or hepatoma (Hepatocellular Cancer-HCC). While HCC is relatively rare in the United States, it is becoming more common as an unwanted consequence of the hepatitis C epidemic. About 80 percent of the time, HCC occurs in people who have cirrhosis, which can be the result of chronic hepatitis B or C, alpha-1-antitrypsin deficiency, or alcoholic or nonalcoholic fatty liver disease.
HCC is difficult to treat, especially when the patient also has cirrhosis. When the tumor is small or in only one lobe of the liver, surgeons may be able to remove it. This procedure is known as liver resection. If the liver cirrhosis is advanced, liver resection carries the risk of complete failure. In such instances liver transplantation is the only option left for a possible cure.
If either of the above surgeries is not an option, radiofrequency ablation or chemoembolization, two minimally invasive procedures, may be considered to shrink the size of the tumor (see Treatments for a complete description of these procedures).
Secondary Liver Cancer or Liver metastases: Cancer that begins in another part of the body and then spreads to the liver is by far the most common form of liver cancer. The usual cancers that spread to the liver originate in the colon (large intestine), breast and lung. Usually liver metastases do not cause symptoms in their early stages and when symptoms such as jaundice or pain do occur, it is often too late. That’s why it is important that patients with treated cancers have regular follow ups to discover any reoccurrence or spread of their tumors to the liver or other organs.
If there is only a single tumor or a few confined to one side of the liver, the best treatment is to remove them by liver resection. Sometimes, even when tumors are present in both sides of the liver (as long as they are not very large and too many), patients will benefit from a liver resection. If resection is not feasible then the best course of treatment is chemotherapy. Unlike in HCC or hepatoma, liver transplantation does not benefit patients with liver metastases, except in patients with metastases of a special type called neuroendocrine tumors. Metastatic neuroendocrine tumors (such as carcinoid tumors) originate in the pancreas or small bowel and then travel to the liver. Patients typically experience severe abdominal pain, nausea, and diarrhea. When chemotherapy or cryosurgery–which freezes the tumors as a method of destroying them–are ineffective, liver transplantation may be indicated.
Benign (Non-Cancerous) Liver Tumors
Hepatic Hemangioma: A hemangioma is a cluster of tiny blood vessels that form a non-cancerous tumor. A hepatic hemangioma is a common, benign tumor found in the liver, occurring more frequently in women than in men. They are often found when patients undergo ultrasound or CT scans for other problems. Most of the time, hepatic hemangiomas do not cause any problems and do not require treatment. When they do, it often is because of their size and/or their proximity to other organs. Large hepatic hemangiomas can cause pain or enlargement of the liver, and in rare cases, they can rupture. In those instances when the tumor is causing problems or thought to be in a troublesome location, surgical removal is indicated. In most instances surgeons are able to peel out the hemangioma without removing much of the normal liver.
Hepatic Adenoma: A hepatic adenoma is an uncommon, benign tumor that on rare occasion becomes a malignant hepatocellular carcinoma. Adenomas usually do not have any symptoms but are more likely to rupture than any of the liver tumors and therefore patients with these tumors need to seek medical advice. The long-term use of oral contraceptives is associated with the development of adenomas, and sometimes if a woman stops using that form of birth control, the adenoma may shrink. If the tumors do not shrink quickly surgical removal is indicated.
Focal Nodular Hyperplasia (FNH)
With this type of benign tumor, a nodule (often containing central scar tissue) grows in the liver. An FNH tumor usually does not present any symptoms, but if it is unusually large or causing pain, surgical removal often is recommended. This is because in rare instances these tumors can rupture; removing the ones that are large and most likely to cause problems can be prudent. They are found more frequently in women than in men, and it is thought that hormones “feed” FNH tumors
Other Liver Diseases
Alpha 1-Antitrypsin (AAT) Deficiency. AAT (also known as alpha1 proteinase inhibitor) is a protein that is made primarily in the liver. AAT belongs to a group of proteins which help prevent certain white blood cell enzymes (proteinases) from going beyond their regular infection-fighting functions to attack healthy body tissue. When the body doesn’t make enough AAT, the lungs often don’t work as efficiently (patients tend to develop emphysema) and the liver may be adversely affected, leading to cirrhosis. AAT deficiency is an inherited condition with two defective genes passed along–one by each parent. This rare deficiency affects fewer than 100,000 Americans.
Familial Amyloidosis Polyneuropathy
This inherited disease, which occurs most often in people of Swedish and Portuguese descent, is a mutation of the transthyretin (TTR) molecule. Instead of the TTR protein being formed, an incorrect protein - amyloid - is produced. With this condition, amyloids are found throughout the body, destroying nerves and interfering with other organs. Neurological symptoms, low blood pressure, and muscle wasting are common manifestations of the disease, which can run a course of several years but has no cure. Because TTR is made in the liver, liver transplantation has been used as treatment.
Eating wild mushrooms can make a person severely ill, or in the worst-case scenario, cause a painful death. One particular type of mushroom, the Amanita phalloides, causes about 90 percent of all mushroom eating-related deaths. Mushroom poisoning typically involves a latent period of as long as 24 hours, when no symptoms are felt, followed by extreme gastrointestinal upset; damage to several organs, including the liver; heart failure; seizures; and coma.
The mushrooms’ toxins can have an especially severe effect on the liver, attacking the organ’s cells and shutting down some of its key functions. When the liver begins to fail but there is medical reason to believe the patient could survive the poisoning, that person may be a candidate for liver transplantation.
Fatty liver and Non-Alcoholic Steatohepatitis
In this condition an excessive amount of fat accumulates in the liver due to a variety of reasons. The most common reasons are excess weight, diabetes, excessive use of alcohol and hepatitis C. Because of the rapid rise in obesity in America, including among children, the number of individuals with fatty liver is rapidly rising. Most patients with fatty liver related to obesity or diabetes retain normal liver function and do not experience any problems during their lifetime. However, in some patients the excess fat causes inflammation in the liver known as Nonalcoholic steatohepatitis or NASH, as the condition sometimes is called. The damage is similar to that which occurs with alcoholic liver disease, but with NASH, the patients have consumed little or no alcohol. Like other liver diseases, NASH is typically “silent” in its early stage, and the first indication of the disease often comes from a routine blood test. Elevated liver enzymes indicate to a physician that something is irregular, leading to more tests and elimination of other conditions. It takes a liver biopsy to confirm a diagnosis of NASH; if there is only fat in the liver, but no inflammation or damage, that’s indicative of a simple fatty liver.
There is currently no treatment for NASH, but studies indicate that by losing weight, getting more exercise, and eating a healthy diet, patients can stop or even reverse the damage caused by NASH.
Polycystic liver disease
This is a congenital (individuals are born with this problem) condition, which may not be recognizable until adulthood. When large cysts form in the liver, the condition is known as polycystic liver disease. It’s common for patients with polycystic liver disease to also have cysts in their kidneys, or polycystic kidney disease. When polycystic liver disease is severe, the liver looks like a sponge. Polycystic liver disease rarely causes liver failure, despite the presence of hundreds of cysts. The most common symptoms are enlargement of the abdomen and pain, which sometimes require treatment. Treatment consists of either aspiration under x-ray guidance or “unroofing” by creating an opening in the cyst wall for drainage, a procedure known as fenestration. The relief from aspiration is less durable than with fenestration. Rarely, the severity of the pain calls for liver transplantation.
Wilson’s disease: Normally, the liver helps the body rid itself of copper. In people with Wilson’s disease, the gene responsible for this process is defective, and copper builds up in the liver, the brain, and other organs. Over time, too much copper in the liver can lead to symptoms such as jaundice and swelling of the abdomen and, untreated, lead to acute liver failure, a need for liver transplantation, or death. Many patients, when diagnosed early on, respond well to the drugs that help remove copper from the bloodstream. They must take the medicine for the rest of their lives. There is an acute form of Wilson’s disease in which the copper overload is swift and the organ damage is rapid. In these cases with liver failure, liver transplantation is life-saving.
Bilary & Pancreatic Conditions
Laparoscopic removal of the gall bladder has many benefits, but one of its possible complications is injury to the bile ducts. In as much as 1 percent of these procedures, there is unintentional trauma to the bile ducts, which may cause bile to leak or the bile ducts to become narrow (bile duct stricture). There are other causes of bile duct stricture, such as cancer, but people who have persistent pain or discomfort 10-14 days after laparoscopic gall bladder surgery might have had a bile duct injury during the procedure. Some patients have fever or develop jaundice related to the injury, as well.
Bile duct repair involves surgery that can be relatively simple or complex; if infection has occurred, that must be treated, also. The earlier a bile duct injury is detected and repaired, the better. Over time, an untreated injured duct will not drain properly, leading to a build-up of bile in the liver.
Primary Sclerosing Cholangitis (PSC)
This slow, progressive
disease affects the bile ducts both inside and outside
the liver. Inflammation and scarring cause the ducts
to narrow, and bile accumulates in the liver. Many times,
patients also have inflammatory bowel disease. Patients
with PSC have an increased risk of developing cancer
in the bile ducts. More common in men than in women,
PSC carries symptoms of itching, jaundice, fatigue and
bouts of fever. Sometimes blocked bile ducts can be
opened through surgery or other procedures, improving
the bile flow. When the ducts remain affected, liver
failure may occur after several years. Liver transplantation
is the only apparent cure.
Primary biliary cirrhosis (PBC) is caused by chronic inflammation of the bile ducts inside the liver, which progressively destroy the bile ducts. It is an autoimmune condition of unknown cause that leads to cirrhosis. PBC has a long and protracted course of progression. Some medicines are available for PBC in the early stages, but when cirrhosis has set in and symptoms of liver failure begin to show, liver transplantation is the best treatment option.
Cancer of the bile ducts, or cholangiocarcinoma, is slow-growing, but also not usually diagnosed until it is in an advanced stage. The malignant tumors block the bile ducts, which causes jaundice. The best possible treatment is to remove the tumor-containing bile ducts. If the tumor is situated in the bile ducts as they come out of the liver, removal of a portion of the liver along with the bile duct may be required to remove the tumor. Even if the tumors cannot be removed, there are endoscopic and surgical techniques that can unblock the obstructions. When surgery is not possible, radiation either alone or with chemotherapy is a course of treatment.
Cancer of the pancreas, the fourth leading cause of cancer death in America, is typically aggressive, hard to treat and metastasizes (spread) to other organs, including the liver. In relatively few cases, a complex surgery known as the Whipple procedure is performed to remove the cancer. Most patients are not candidates for the surgery and receive a combination of chemotherapy and radiation. Unfortunately, the prognosis for patients at this stage of the disease is very poor.
Pancreatic cancer can be very painful, so while there might not be a cure in sight, there are procedures that can help to keep the patient comfortable. For example, the bile ducts of patients with pancreatic cancer can become blocked, leading to jaundice and related lack of appetite and itching. By stent placement, gastroenterologists can open the blocked bile ducts and relieve the symptoms of jaundice. To ease the pain of pancreatic cancer, a celiac nerve block can be used to inject certain agents, such as alcohol or a steroid, into the identified nerve or nerves. The numbness brings pain relief that narcotic medications cannot match.