Liver disease is any disturbance of liver function that causes illness. The liver is responsible for many critical functions within the body and should it become diseased or injured, the loss of those functions can cause significant damage to the body. Liver disease is also referred to as hepatic disease.
Liver disease is a broad term that covers all the potential problems that may occur to cause the liver to fail to perform its designated functions. Usually, more than 75% or three quarters of liver tissue needs to be affected before decrease in function occurs.
The liver the largest solid organ in the body; and is also considered a gland because among its many functions, it makes and secretes bile. The liver is located in the upper right portion of the abdomen protected by the rib cage.
It has two main lobes that are made up of tiny lobules. The liver cells have two different sources of blood supply. The hepatic artery supplies oxygen rich blood that is pumped from the heart, while the portal vein supplies nutrients from the intestine and the spleen.
Normally, veins return blood from the body to the heart, but the portal vein allows chemicals from the digestive tract to enter the liver for "detoxification" and filtering prior to entering the general circulation. The portal vein also efficiently delivers the chemicals and proteins that liver cells need to produce the proteins, cholesterol, and glycogen required for normal body activities.
As part of its function, the liver makes bile, a fluid that contains among other substances, water, chemicals, and bile acids (made from stored cholesterol in the liver). Bile is stored in the gallbladder and when food enters the duodenum (the first part of the small intestine), bile is secreted into the duodenum, to aid in digestion of food.
The liver is the only organ in the body that can easily replace damaged cells, but if enough cells are lost, the liver may not be able to meet the needs of the body.
The liver can be considered a factory; and among its many functions include the:
- production of bile that is required in the digestion of food, in particular fats;
- conversion of the extra glucose in the body into stored glycogen in liver cells; and then converting it back into glucose when the need arises;
- production of blood clotting factors;
- production of amino acids (the building blocks for making proteins), including those used to help fight infection;
- the processing and storage iron necessary for red blood cell production;
- manufacture of cholesterol and other chemicals required for fat transport;
- conversion of waste products of body metabolism into urea that is excreted in the urine; and
- metabolization medications into their active ingredient in the body.
Cirrhosis is a term that describes permanent scarring of the liver. Normal liver cells are replaced by scar tissue that cannot perform any liver function.
Acute liver failure may or may not be reversible, meaning that is there is a treatable cause and the liver is able to recover and resume its normal functions.
What are the causes of liver disease?
The liver can be damaged in a variety of ways.
- Cells can become inflamed (such as in hepatitis: hepar=liver + itis=inflammation).
- Bile flow can be obstructed (such as in cholestasis: chole=bile + stasis=standing).
- Cholesterol or triglycerides can accumulate (such as in steatosis; steat=fat + osis=accumulation).
- Blood flow to the liver may be compromised.
- Liver tissue can be damaged by chemicals and minerals, or infiltrated by abnormal cells.
Alcohol abuse
Alcohol abuse is the most common cause of liver disease in North America. Alcohol is directly toxic to liver cells and can cause liver inflammation, referred to as alcoholic hepatitis. In chronic alcohol abuse, fatty accumulation (steatosis) occurs in liver cells causing the cells to malfunction.
Cirrhosis
Cirrhosis is a late-stage liver disease. Scarring of the liver and loss of functioning liver cells cause the liver to fail.
Drug-induced liver disease
Liver cells may become temporarily inflamed or permanently damaged by exposure to medications or drugs. Some medications or drugs require an overdose to cause liver injury while others may cause the damage even when taken in the appropriately prescribed dosage.
Taking excess amounts of acetaminophen (Tylenol, Panadol) can cause liver failure that is permanent. This is the reason that warning labels exist on many over-the-counter medications that contain acetaminophen and why prescription narcotic-acetaminophen combination medications (for example, Vicodin, Lortab, Norco, Tylenol #3) limit the numbers of tablets to be taken in a day.
Statin medications are commonly prescribed to control elevated blood levels of cholesterol. Even when taken in the appropriately prescribed dose, liver inflammation may occur and can be detected by blood tests that measure liver enzymes. Stopping the medication usually results in return of the liver function to normal.
Niacin is another medication used to control elevated blood levels of cholesterol, but liver inflammation for this medication is related to the dose taken. Similarly, patients with underlying liver disease may be at higher risk of developing liver disease due medications such as niacin.
There are numerous other medications that may cause liver inflammation, most of which will resolve when the medication is stopped. These include antibiotics such as nitrofurantoin (Macrodantin, Furadantin, Macrobid), amoxicillin and clavulanic acid (Augmentin, Augmentin XR), tetracycline (Sumycin), and isoniazid (INH, Nydrazid, Laniazid). Methotrexate (Rheumatrex, Trexall), a drug used to treat autoimmune disorders and cancers, has a variety of side effects including liver inflammation that can lead to cirrhosis. Disulfiram (Antabuse) used to treat alcoholics and can cause liver inflammation.
Some herbal remedies and excessive amounts of vitamins can cause hepatitis, cirrhosis and liver failure. Examples include vitamin A, kava kava, ma-huang, and comfrey.
Many mushrooms are poisonous to the liver and eating unidentified mushrooms gathered in the woods can be lethal.
Infectious hepatitis
The term "hepatitis" means inflammation, and liver cells can become inflamed because of infection.
Hepatitis A is a viral infection that is caused primarily through the fecal-oral route when small amounts of infected fecal matter are inadvertently ingested. Hepatitis A causes an acute inflammation of the liver which generally resolves spontaneously. The hepatitis A vaccine can prevent this infection.
Hepatitis B is spread by exposure to body fluids (needles from drug abusers, contaminated blood, and sexual contact) and can cause an acute infection, but can also progress to cause chronic inflammation (chronic hepatitis) that can lead to cirrhosis and liver cancer. The hepatitis B vaccine prevents this infection.
Hepatitis C causes chronic hepatitis. An infected individual may not recall any acute illness. Hepatitis C is spread by exposure to body fluids (needles from drug abusers, contaminated blood, and sexual contact). Chronic hepatitis C may lead to cirrhosis and liver cancer. At present, there is no vaccine against this virus.
Hepatitis D is a virus that requires concomitant infection with hepatitis B to survive, and is spread via body fluid exposure (needles from drug abusers, contaminated blood, and sexual contact).
Hepatitis E is a virus that is spread via contaminated food and water exposure.
Other viruses
Other viruses can also cause liver inflammation or hepatitis as part of the cluster of symptoms. Viral infections with infectious mononucleosis (Epstein Barr virus), adenovirus, and cytomegalovirus can inflame the liver. Non-viral infections such as toxoplasmosis and Rocky Mountain spotted fever are less common causes.
Cancers
Primary cancers of the liver arise from liver structures and cells. Two examples include hepatocellular carcinoma and cholangiocarcinoma.
Metastatic cancer (secondary cancer of the liver) begins in another organ and spreads to the liver, usually through the blood stream. Common cancers that spread to the liver begin in the lung, breast, large intestine, stomach, and pancreas. Leukemia and Hodgkin's lymphoma may also involve the liver.
What are the risk factors for liver disease?
Some liver diseases are potentially preventable and are associated with lifestyle choices. Hepatitis B and C are viral infections that are most often spread through the exchange of bodily fluids (for example, unprotected sexual intercourse, sharing unsterilized drug injecting equipment, using non-sterilized equipment for tattoos or body piercing). Alcohol related liver disease is due to excessive consumption of alcohol.
- Hereditary liver disease can be passed genetically from generation to generation. Examples include Wilson's disease and hemochromatosis.
- Chemical exposure may be toxic to the liver by irritating the liver cells causing inflammation (hepatitis), decreasing bile flow through the liver (cholestasis) and accumulation of triglycerides (steatosis). Chemicals such as anabolic steroids and vinyl chloride can cause liver cancers.
- Acetaminophen (Tylenol) overdose is a common cause of liver failure. It is important to review the dosing guidelines for all over-the-counter medications and to ask for guidance from your health care professional or pharmacist as to how much may be taken safely.
- Medications may irritate the blood vessels causing narrowing or formation blood clots (thrombosis). Birth control pills may cause hepatic vein thrombosis, especially in smokers.
What are the symptoms of liver disease?
Classic symptoms of liver disease include:
Fatigue, weakness and weight loss may also be occur.
However, since there are a variety of liver diseases, the symptoms tend to be specific for that illness until late-stage liver disease and liver failure occurs.
Examples of liver disease symptoms due to certain conditions or diseases include:
- A person with gallstones may experience right upper abdominal pain and vomiting after eating a greasy (fatty) meal. If the gallbladder becomes infected, fever may occur.
- Gilbert's disease have no symptoms.
- Individuals with cirrhosis will develop progressive symptoms as the liver fails. Some symptoms are directly related to the inability of the liver to metabolize the body's waste products. Others reflect the failure of the liver to manufacture proteins required for body function and may affect blood clotting function, secondary sex characteristics and brain function. Symptoms of cirrhosis of the liver include:
- easy bruising may occur due to decreased production of clotting factors;
- bile salts can deposit in the skin causing itching;
- gynecomastia or enlarged breasts in men may occur because of an imbalance in sex hormones; specifically an increase in estradiol;
- impotence (erectile dysfunction, ED), poor sex drive and shrinking testicles are due to decrease in function of sex hormones;
- confusion and lethargy may occur if ammonia levels rise in the blood stream (ammonia is a waste product formed from protein metabolism and requires normal liver cells to remove it);
- ascites (fluid accumulation within the abdominal cavity) occurs because of decreased protein production; and
- muscle wasting may occur because of reduced protein production.
Additionally, there is increased pressure within the cirrhotic liver affecting blood flow through the liver. Increased pressure in the portal vein causes blood flow to the liver to slow and blood vessels to swell. Swollen veins (varices) form around the stomach and esophagus and are at risk for bleeding.
When to seek medical care for liver disease
Often, the onset of a liver disease is gradual and there is no specific symptom that brings the affected individual to seek medical care. Fatigue, weakness and weight loss that cannot be explained should prompt a visit for medical evaluation.
Jaundice or yellow skin is never normal and should prompt an evaluation by a medical professional.
Persisting fever, vomiting, and abdominal pain should also prompt medical evaluation as soon as possible.
How is liver disease diagnosed?
The precise diagnosis of liver disease involves a history and physical examination performed by the health care professional. Understanding the symptoms and the patient's risk factors for liver disease will help guide any diagnostic tests that may be considered.
Liver disease can have physical findings in almost all body systems including the heart, lungs, abdomen, skin, cognitive function, and other parts of the nervous system. The physical examination can require evaluation of the entire body.
Blood tests are helpful in assessing liver inflammation and function.
Specific liver function blood tests include:
- AST and ALT ( transaminase chemicals released with liver cell inflammation);
- GGT and alkaline phosphatase (chemicals released by cells lining bile ducts);
- bilirubin; and
- protein and albumin levels.
Other blood tests may be considered, including the following:
- complete blood count (CBC), patients with end stage liver disease may have bone marrow suppression and low red blood cells, white blood cells and platelets;
- INR blood clotting function may be impaired due to poor protein production,
- lipase to check for pancreas inflammation;
- electrolytes, BUN and creatinine to assess kidney function; and
- ammonia blood level assessment is helpful in patients with mental confusion.
Imaging studies may be used to visualize, not only the liver, but other organs nearby that may be diseased. Examples of imaging studies include:
- CT scan (computerized axial tomography),
- MRI (magnetic resonance imaging), and
- ultrasound (sound wave imaging, which is especially helpful in assessing the gallbladder and bile ducts.
Liver biopsy may be considered to confirm a specific diagnosis for liver disease. Under local anesthetic, a long thin needle is inserted through the chest wall into the liver, where a small sample of liver tissue is obtained for examination under a microscope.
What is the treatment for liver disease?
Each liver disease will have its own specific treatment regimen. For example, hepatitis A requires supportive care to maintain hydration while the body's immune system fights and resolves the infection. Patients with gallstones may require surgery to remove the gallbladder. Other diseases may need long-term medical care to control and minimize the consequences of their disease
In patients with cirrhosis and end-stage liver disease, medications may be required to control the amount of protein absorbed in the diet. The liver affected by cirrhosis may not be able to metabolize the waste products, resulting in elevated blood ammonia levels and hepatic encephalopathy. Low sodium diet and water pills (diuretics) may be required to minimize water retention.
In those with large amounts of ascites fluid, the excess fluid may have to be occasionally removed with a needle and syringe (paracentesis). Using local anesthetic, a needle is inserted through the abdominal wall and the fluid withdrawn.
Operations may be required to treat portal hypertension and minimize the risk of bleeding.
Liver transplantation is the final option for patients whose liver has failed.
What are the complications of liver disease?
Except for gallstone disease and some viral infections such as Hepatitis A and infectious mononucleosis, most liver diseases are managed and not cured.
Liver disease can progress to cirrhosis and liver failure. Associated complications may include increased risk of bleeding and infection, malnutrition and weight loss, and decreased cognitive function.
Some liver diseases are associated with an increased risk for developing liver cancer.
Can liver disease be prevented?
- Alcohol abuse is the most common cause of liver disease in North America. Consuming alcohol in moderation may help minimize the risk of alcohol-related liver disease.
- The risk of contracting Hepatitis B and C can be decreased by minimizing the risk of exposure to other person's bodily fluids.
- Vaccination is available for Hepatitis A and B.
- Fatty liver disease is a preventable illness with the promotion of a healthy lifestyle including a well balanced diet, weight control, avoiding excess alcohol consumption and routine exercise program. These lifestyle modifications do not guarantee success in disease prevention in that some people will develop fatty liver disease anyway.
What is the outlook for a patient with liver disease?
The outlook and outcome for a patient depends upon the underlying diagnosis.
Interestingly, in patients with cirrhosis, there may be little correlation between the amount of damage found on liver biopsy and the ultimate outcome. A patient may never develop symptoms and have a normal life-span or may develop significant symptoms.
Liver Disease At A Glance
- The liver has an important role in many bodily functions from protein production and blood clotting to cholesterol, glucose and iron metabolism.
- A variety of illnesses can affect the liver.
- Cirrhosis occurs when normal liver cells are replaced by scar tissue as a result of chronic liver disease.
- Symptoms of liver diseases include weakness and fatigue, weight loss, nausea, vomiting, and yellow discoloration of the skin (jaundice).
- The treatment of a particular liver disease depends on its specific cause.
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