Liver

Liver or hepatic disease that interrupts liver functions, such as converting food to energy or filtering toxins from the blood, affects tens of millions of Americans. At the Sherrie and Alan Conover Center for Liver Disease & Transplantation, our team explores the underlying causes of liver disease — viruses such as hepatitis and cirrhosis from drug or alcohol use – and liver cancer. This knowledge, combined with the latest surgical and nonsurgical treatments, allows us to deliver the best integrative care to you and your family.

One way we provide the best care possible is through educating you on your condition. The information here is designed to provide a concise overview of what you need to know about liver disease, liver cancers, treatments and transplant issues.

• About liver disease
• About liver cancer
• Treating liver disease
• Treating liver cancer
• The liver and your medications
• Signs of rejection after your transplant

 

About Liver Disease
Liver disease occurs when illness or injury creates a condition that interrupts the many critical functions your liver performs, which can cause significant damage to your body. Usually, more than 75 percent of liver tissue needs to be affected before a decrease in function occurs.

Causes of liver diseases can generally be grouped into five broad categories:

• Infection (from parasites like the liver fluke or viruses such as hepatitis)
• Immune system abnormalities in which your immune system attacks your body (such as primary biliary cirrhosis or sclerosing cholangitis)
• Genetics (such as hemochromatosis or Wilson’s disease)
• Cancer (such as bile duct cancer or liver adenoma)
• Other causes (such as nonalcoholic fatty liver disease or chronic alcohol abuse)

 

More than 100 diseases can be categorized as liver diseases or disorders; some are more common than others:

• Alagille syndrome (inherited disorder that causes progressive loss of bile ducts)
• Alpha 1 Anti-Trypsin deficiency (inherited disorder that breaks down liver tissue)
• Amyloidosis (multisystem disease in which abnormal proteins build up in the liver and other organs)
• Autoimmune hepatitis (chronic inflammation disorder that causes the immune system to attack the liver)
• Cirrhosis (scarring of the liver tissue from a variety of causes; reduces the ability of the liver tissue to function)
• Fatty liver disease (buildup of fat in the liver from a variety of causes; may result in inflammation and scarring)
• Gilbert’s syndrome (inherited disorder that causes bilirubin to build up in the liver and may cause discomfort)
• Hemochromatosis (inherited disorder in which the body absorbs too much iron; over-accumulation of iron can damage all organs)
• Liver cancer (see next section)
• Primary Biliary Cirrhosis (chronic disease that causes the body’s immune system to slowly attack the bile ducts)
• Primary Sclerosing Cholangitis (chronic inflammation and scarring cause the bile ducts to progressively reduce in diameter)
• Sarcoidosis (multisystem disease induces inflammation in the liver and other tissues that form lesions or hepatic granulomas)
• Toxic hepatitis (inflammation of the liver caused by chemicals)
• Type 1 Glycogen Storage disease (deficiency of the enzyme glucose-6-phosphatase can cause an enlarged liver)
• Viral hepatitis A, B, and C (viral infections that cause inflammation and can lead to cirrhosis, liver failure or cancer)
• Wilson’s disease (inherited disorder in which excess amounts of copper can accumulate in the liver)

 

About Liver Cancer
Primary liver cancer — when normal cells change and grow uncontrollably — is cancer that begins in the liver. It is more common for cancer to spread to the liver, or metastasize, than for it to start there, as it does with primary liver cancer. When metastatic cancer is discovered in the liver, the cancer is usually identified and treated according to the site of origin. For example, if liver cancer originated in the pancreas and spread to the liver, the disease would be identified and treated as pancreatic cancer.

There are three types of adult primary liver cancer; each is named for the type of cell from which it develops.

• Hepatocellular carcinoma (HCC) begins in the hepatocytes, the cells that make up the main tissue of the liver. HCC sometimes starts as a single tumor that spreads tentacle-like growths to other parts of the liver or it may develop as nodules at several different places in the liver. Hepatocellular carcinomas account for most adult primary liver cancers.
• Cholangiocarcinomas (also called bile duct cancer) grow from cells in the bile duct of the liver. Bile ducts are thin tubes that extend from the liver to the gall bladder and small intestine. A small percentage of adult primary liver cancers are cholangiocarcinomas.
• Angiosarcoma, a rare form of primary liver cancer, starts in the blood vessels of the liver and grows very quickly.

 

The most common risk factor for liver cancer is chronic hepatitis B or C. You can learn more about liver cancer here.

Treating Liver Disease
The treatment for liver disease often depends on its cause. Following are some common liver diseases, their causes and treatment options.

Acute Liver Failure
Acute liver failure is a rare condition in which patients with no prior history of liver disease suffer a sudden collapse of liver function. Symptoms include fatigue, nausea, pain in the abdomen, jaundice and mental confusion or mild memory loss. The most common cause of the condition occurs when a person takes too much acetaminophen (Tylenol®); hepatitis, herpes, shock, heat stroke and metabolic disorders can also cause acute liver failure.

A medical history, physical exam and blood and urine tests are used to diagnose this disease.

This condition is a medical emergency that requires immediate attention; there is no specific treatment for it. Our team will first treat the cause of the failure and may prescribe n-acetylcysteine to counteract the effects of an acetaminophen overdose.

Once the underlying cause has been treated, we will address complications and recommend ways to help your liver repair itself. Many people who experience acute liver failure require a transplant; because the condition is serious, you may be given the highest priority on the transplant waiting list.

Alcohol-induced Liver Disease
Alcohol-induced liver disease is a preventable disease, caused by over-consumption of alcohol. The most common symptoms of this disease include an enlarged liver and spleen, fever, jaundice, an increased white blood cell count, hypertension in the liver's portal vein system, fluid build-up in the abdomen (ascites), mental confusion, spider veins and kidney failure.

The three primary types of the disease are fatty liver, alcoholic hepatitis and alcoholic cirrhosis.

• Fatty liver, the most common form, is the excessive accumulation of fat in liver cells that causes the liver to enlarge and leads to discomfort on the upper right side of the abdomen.
• Alcoholic hepatitis is the acute inflammation of the liver that destroys liver cells and creates scar tissue; with this form you may experience fever, jaundice, increased white blood cells, an enlarged liver and spider-like veins.
• Alcoholic cirrhosis occurs when normal liver tissue is destroyed and non-functioning scar tissue is left in its place; you may experience the symptoms of alcoholic hepatitis plus portal hypertension, an enlarged spleen, ascites, kidney failure, confusion or liver cancer.

 

To diagnose alcohol-induced liver disease, our team will take a medical history, perform a physical exam and recommend blood and urine tests, liver function tests and a liver biopsy.

The goal of treatment will be to restore as much of the normal function to your liver as possible. When adverse conditions are removed, the liver can often restore and repair much of the damage done to it; we will require that you abstain from alcohol. Often, the only damage that cannot be repaired is scarring from cirrhosis.
Of special note, statistics show that women are more prone to suffer liver damage from drinking alcohol than men.

Autoimmune Liver Disease/Hepatitis
Autoimmune liver disease (autoimmune hepatitis) occurs when a patient’s immune system attacks liver and bile duct cells and can result in liver failure, cirrhosis or cancer; the condition often starts in childhood. Early in the progression of the disease, the symptoms may be few and may go unnoticed, including unexplained rashes or joint pain, abdominal discomfort, dark urine, light or gray-colored stool, vomiting or loss of appetite. As the condition progresses, you may experience jaundice, more severe joint pain and vomiting, spider veins and weight loss. Cirrhosis symptoms may also appear.

Several types of the condition exist; the common thread is that patients with the condition often suffer from other autoimmune diseases. The cause is unknown, but some researchers think it may be triggered by interaction between infections, medications and genetics.

To diagnose the condition, our team will take a medical history, perform a physical examination and recommend a series of blood tests to identify antibody markers for the disease. We may also perform a liver biopsy to rule out other possible conditions.

To treat the disease, we will suggest medications such as immunosuppressants to decrease the activity of your immune system and steroids to reduce swelling. With treatment, the condition often goes into remission within three years.

Benign Liver Lesions
Normally, noncancerous lesions in the liver do not pose a serious health risk and also do not spread to other areas of the body. You may experience no symptoms at all, some abdominal pain if the lesions grow large enough to compress other structures or some pain, nausea, vomiting or fever if the lesion is large enough (larger lesions have a tendency to bleed).

The three types of benign liver tumors are hemangioma, focal nodular hyperplasia and adenoma.

• Hemangiomas are the most common form and the small ones (under 6 cm) produce no symptoms and usually require no treatment. Surgery is recommended for the larger lesions if they are symptomatic.
• Focal nodular hyperplasia is the second most common type; treatment options are the same as with hemangiomas.
• Adenomas are less common and occur primarily in women of childbearing age who use oral contraception. Larger tumors (more than 5 cm) may cause discomfort, pain, nausea, vomiting or fever and have a higher tendency to bleed. They also have a relatively small potential to become cancerous (about 10 percent). We will usually recommend surgery to remove them.

Individuals with a history of diabetes, obesity, hepatitis C or malnutrition may experience focal fatty change, a condition in which the fat in the liver is not evenly spread out so pockets of fat accumulate. This is normally diagnosed with an MRI but often no treatment is required.

Biliary Duct Atresia
Biliary atresia is a rare congenital condition, affecting newborn babies, in which the ducts that transport bile from the liver to the gallbladder do not develop normally; the ducts are either blocked or absent. Since bile cannot leave the liver, damage and cirrhosis may occur.

Symptoms usually occur within the first two to three weeks of birth and include:

• Jaundice
• Dark urine
• Enlarged spleen
• Pale or gray-colored stools
• Slow growth and weight gain

 

Our team will perform a physical exam to check for an enlarged spleen; we will recommend blood, urine, and stool tests to look for signs of problems with liver function. We may also suggest ultrasounds and liver scan X-rays to get a clear picture of the liver and bile ducts. A liver biopsy is also a diagnostic option.

Our team may recommend a surgery known as the Kasai procedure in which the liver is connected directly to the small intestine (where the bile drains); this procedure is most successful if done before the baby reaches eight weeks. If there is already severe damage to the liver or the ducts within the liver are blocked, a liver transplant may be the only option.

Cirrhosis
Liver disease, chronic hepatitis, nonalcoholic fatty liver disease and other conditions can cause a scarring of liver tissue known as cirrhosis. In this condition, scar tissue from cell damage replaces healthy tissue and the flow of blood through the organ becomes partially blocked. This interferes with the liver’s ability to remove bacteria and toxins from your blood, control infections and process nutrients.

Once cirrhosis has started to interfere with your liver function, symptoms can include swelling in your feet and abdomen, vomiting (sometimes blood), difficulty sleeping at night (and increased daytime sleep), jaundice, easy bruising, tremors in your hands when extended (asterixis), hepatic encephalopathy and progressive memory loss, muscle loss and bloody, purple or black bowel movements.

Cirrhosis can compromise your ability to fight infection, increase your chances of malnutrition and make it difficult for you to reason and concentrate.

To diagnose cirrhosis, our team will obtain your medical history and discuss your symptoms and specific risk factors (especially alcohol use). In a physical examination, we will check for such signs of the condition as an enlarged or hard liver. We may recommend blood tests for high bilirubin (the substance that causes the yellow color in jaundice), low albumin, low cholesterol, low platelets and low clotting factors. We will most likely suggest CT and MRI scans as well as ultrasound to obtain a complete picture of your liver. A biopsy is another possible diagnostic tool.

At Houston Methodist, we use a tool to help build a model of your end-stage liver disease (MELD); the MELD score will measure the severity of your cirrhosis and is an important factor in determining your position on a waiting list if you should need a transplant.

Our treatment plan for you will vary depending on the cause of your condition and your symptoms, but will most likely include several lifestyle changes including the elimination of alcohol and over-the-counter medications such as acetaminophen or ibuprofen and starting a low-sodium diet. To relieve symptoms, we may recommend antibiotics, diuretics and other medications.

If the scarring has caused a pressure build-up that is likely to lead to blood vessel rupture, our team may recommend a transjugular intrahepatic portosystemic shunt (TIPS), a metal mesh stint that connects the portal and hepatic veins to improve blood flow and reduce the risk of bleeding. A liver transplant is an option if we cannot control your complications with other procedures or medications.

If you have cirrhosis, it is important to be screened for liver cancer on a regular basis; approximately 30 percent of people with cirrhosis will develop liver cancer within a 20-year period.

Drug-induced Hepatitis
When drugs or other chemical substances have damaged your liver, this is known as drug-induced hepatitis (hepatoxicity or drug-induced liver injury). In mild cases, you may have no noticeable symptoms; for more severe cases, you may experience symptoms similar to viral hepatitis, including malaise, anorexia, nausea, vomiting, upper-right-side abdominal pain, jaundice, light or gray-colored stools and dark urine.

No specific diagnostic tests exist for drug-induced hepatitis, so we will rely on your own description of the type, dosage and frequency of the medications you are taking.

Our team may suggest tests to eliminate the possibility of other liver-related conditions like viral hepatitis or hemochromatosis. We may suggest a liver biopsy to assess the general damage to your liver.

Fatty Liver Disease
Fatty liver disease (also known as nonalcoholic fatty liver disease or NAFLD) is a chronic liver disease in which fat is deposited within the liver cells (a condition known as steatosis). NAFLD presents few symptoms in the early stages; you may experience a dull pain in the upper right side of your abdomen, an enlarged liver and skin discoloration around the neck and armpits. As the condition progresses, symptoms of liver cirrhosis may develop (weakness, fatigue and jaundice).
NAFLD is linked to the conditions of being obese, diabetic or insulin-resistant, high lipid counts and high blood pressure. Steatosis may also be caused by excessive alcohol consumption.

NAFLD occurs in three forms -- simple steatosis, NASH and NRC.

• Nonalcoholic fatty liver, or simple steatosis, is the mildest form; the liver contains up to five percent fat but has not experienced any damage. Weight loss through diet and exercise is the preferred treatment.
• In NASH (nonalcoholic steatohepatitis), the excess fat has resulted in inflammation, liver cell damage and some scarring. The inflammation response is caused by the increased production of oxidants by the liver cells which cause cells to degenerate and increased release of toxic inflammatory mediators such as cytokines from the fat cells which heightens immune reactions. Weight loss and controlling diabetes, high blood pressure and high lipid levels are lifestyle changes we would recommend to reduce the effect of this condition.
• NRC (NASH-related cirrhosis) is characterized by organ-wide scarring that affects your liver's function and may lead to liver failure. Transplant is an option.

Weight loss is one of the most powerful tools we have to help you treat NAFLD; even a modest loss of 5 to 10 percent of body weight can decrease the amount of fat in the liver by 40 percent.

Hemochromatosis
Hemochromatosis occurs when your body absorbs too much iron from the gastrointestinal tract. With this disorder, you may experience such symptoms as joint pain, fatigue, loss of sex drive or impotence, lack of normal menstruation and pain in the upper-right abdomen. Hemochromatosis can result from a genetic defect or other non-hereditary conditions.

• Primary hemochromatosis is due to a genetic defect that causes your body to absorb too much iron; iron builds up in liver tissues, causing the organ to swell. This form of the condition is one of the most common genetic disorders in the United States.
• Secondary (acquired) hemochromatosis may be caused by such conditions as blood disorders, alcoholism or frequent blood transfusions.

We will recommend blood tests to diagnose hemochromatosis, including a serum transferrin saturation test to measure the amount of iron in your blood and a serum ferritin test to measure the amount of iron in your liver. A liver biopsy may be necessary to check for iron in the liver and to gauge the amount of damage that may have occurred. We can test for the gene mutation that causes hemochromatosis to determine if your condition might be hereditary.

To treat the condition, our team may recommend phlebotomy, regular withdrawal of blood that will normalize your body's iron levels. We may also suggest a medication that causes the body to expel excess iron, as well as low-iron diets and the elimination of alcohol.

Hepatic Encephalopathy
In hepatic encephalopathy, your brain function is disrupted due to liver failure. When the liver's ability to process and filter toxins and waste products (such as ammonia) is compromised, more of these substances enter the bloodstream and reach the brain. The extent of symptoms of hepatic encephalopathy depend on the severity of damage to the liver and range from mild cognitive impairment to coma. They can also include personality changes, changes in sleep patterns, confusion, irritability, forgetfulness, poor concentration and judgment, lethargy, drowsiness, jerky limb movements and a musty or sweet odor on your breath.

To diagnose this condition, our team will ask about your memory and sleep habits. We may recommend testing your blood for elevated levels of ammonia and zinc.
 
The symptoms of hepatic encephalopathy can be treated; the underlying cause, the liver damage, may be serious and may require a transplant.

Primary Biliary Cirrhosis
Primary biliary cirrhosis occurs when the bile ducts through and out of the liver are blocked due to swelling and irritation. The obstruction damages liver cells and can lead to cirrhosis. Symptoms present gradually and may include fatigue, jaundice, itchy skin, dry eyes and mouth, dark urine and abdominal pain and swelling. The cause of this condition is not known and primarily affects middle-aged women.

A routine blood test to check liver function may be the first indication of primary biliary cirrhosis. We may also recommend several other tests, including blood tests for anti-mitochondrial antibodies, alkaline phosphatase and cholesterol; an abdominal ultrasound to obtain a picture of your liver and bile duct system; and a liver biopsy to determine the extent of the damage.

Our team may recommend treatment with medications such as ursodeoxycholic acid and vitamin therapy to relieve your symptoms and prevent further complications. If your liver has been severely damaged, we may recommend a liver transplant.

Primary Sclerosing Cholangitis
Primary sclerosing cholangitis occurs when inflammation causes scars in the bile ducts, making them harden and narrow and unable to remove bile from the liver. Early symptoms may include fatigue and itching, and as the disease progresses, you may experience pain in your upper-right abdomen, fever, chills, night sweats, jaundice, weight loss and an enlarged liver. It can lead to liver failure.

It is not known what causes the condition, but it could be a combination of genetic predisposition and a trigger such as a toxin or infection. A large percent of people with the condition also suffer with inflammatory bowel disease.

To diagnose primary sclerosing cholangitis, we may recommend blood tests to determine your liver function and level of enzymes, an MRI or X-ray of your bile ducts to examine blockage and a liver biopsy to determine the extent of damage to your liver. (Some people discover the disease via a routine blood test or an X-ray that shows liver abnormalities.)

To treat the disease, our team may suggest managing complications and monitoring your liver for further damage. We may recommend antihistamines to relieve itching, antibiotics to control the bacterial infections that result from bile backing up into the liver and vitamins and supplements to counter nutritional deficiencies.

To keep your bile ducts open, our team may recommend balloon dilation via catheter to open blockages in the larger bile ducts outside the liver or stent placement into a duct to keep it open. Transplant may be an option if the damage to your liver is severe.

Viral Hepatitis
Hepatitis occurs when the liver swells due to inflammation; in the case of viral hepatitis, the inflammation is caused by a viral infection. The most common symptoms of hepatitis include loss of appetite, fatigue, mild fever, muscle and joint aches, nausea, vomiting and abdominal pain.

Each type of hepatitis is named for the virus that causes it: A, B, C and D.

Hepatitis A is the least serious form and can be contracted when you come in contact with blood or stool from someone who has the virus. In addition to the common symptoms, you may also experience jaundice. No specific treatment exists, but the majority of people with this condition recover on their own within about three months with no permanent liver damage.

Hepatitis B spreads through contact with the bodily fluids of a person with the virus. You may experience the common symptoms or no symptoms at all. If your case is acute, our team would recommend monitoring liver and other body functions through blood tests.

Some hepatitis B patients can fight off the disease on their own or with the help of antiviral medications, usually within a few months. If you cannot get rid of the infection completely (chronic hepatitis), you may develop liver damage and cirrhosis. We may recommend oral medications to help keep the virus from replicating and if your liver damage is severe, we may suggest a transplant.
 
Regardless of the outcome, our team would strongly recommend continued monitoring to detect potential liver cancer.

Hepatitis C, contracted through contact with body fluids, appears in both acute and chronic forms. Many patients with this virus experience no symptoms, although they can experience the common symptoms as well as abdominal swelling (ascites) and dark urine.

Our physicians may recommend medications designed to remove the virus from the blood and reduce the risk of cirrhosis and liver cancer. Some people are excellent candidates for the virus-removal therapy, and, even if it does not totally remove the virus, it does reduce the chance of you developing severe liver disease.

Hepatitis D (or "delta hepatitis") is caused by the hepatitis D virus but can only develop if you are already infected with the hepatitis B virus. The symptoms of hepatitis D are the same as those for hepatitis B. You can only get hepatitis D in two ways: coinfection or superinfection.

• In coinfection, you become infected with both B and D at the same time. This form is usually acute and resolves on its own. Treatment for a coinfected person is usually not needed.
• In superinfection, you become infected with B then get infected with D. In this form, the D virus makes the B symptoms worse and can lead to liver failure. Our team may suggest antiviral treatments to help you fight off this version of the disease; if liver failure results, a transplant may be necessary.

Treating Liver Cancer
Liver cancer can seldom be successfully treated with traditional chemotherapy or radiation like other types of cancer, although these treatments may be used to shrink tumors before surgery. With metastatic cancers, your physician will determine where the cancer originated, then follow the treatment for that type of cancer. Your physician will evaluate several factors to determine the appropriate treatment, including the number and size of the tumors, how well your liver is functioning, whether the cancer has spread to other areas and your overall health.

Surgical Treatment
For early-stage cancers that have not spread, your physician may recommend a partial hepatectomy and remove the cancerous portion of the liver; as much as 80 percent of your liver can safely be removed. Factors such as underlying liver disease and cirrhosis can make you ineligible for this treatment. The surgery is performed under general anesthesia and takes between three and four hours. Patients normally stay in the hospital for about five days after surgery to be monitored.

Liver Transplant
If a partial hepatectomy is not an option, your physician may consider a liver transplant . To be eligible for liver transplant, your cancer must be contained within the liver. If the cancer has already spread, a liver transplant will not cure the cancer and could make it worse due to the required immune suppression medications taken after liver transplant.

Other Treatments
Several other treatments for liver cancer may be effective.

• Intra-Arterial Liver Tumor Treatment/Locoregional Therapy involves a small puncture in a groin artery through which a catheter is inserted then navigated into the liver to deliver either chemotherapy or radiation. This first-line approach may be used for some patients of primary or metastatic cancer and can be coupled with other treatments.
• Radiofrequency Ablation is a procedure in which probes are placed into liver tumors (up to 5 cm in diameter), electricity is directed into the tissue and the resulting heat destroys the tumor cells; this may sometimes be performed either without making incisions or laparoscopically. This first-line approach may be used for some patients of primary or metastatic cancer.
• TheraSphere (Yttrium Therapy) is a liver cancer treatment in which small beads containing radioactive Yttrium-90 are injected into the main artery of the liver and directed through the blood vessels to the tumor; the radiation destroys the tumor cells. Most of the radioactivity is gone within 10 to 12 days following treatment.
• Transcatheter Arterial Chemoembolization (TACE) with Drug Eluting Beads is a palliative treatment in which tiny beads carrying chemotherapy agents are guided by X-ray into the tumor to cut off its blood supply and deliver an extended dose of cancer-killing drugs. This treatment is for patients with primary hepatocellular carcinoma.
• Sorafenib (brand name Nexavar®) is an oral chemotherapy drug designed to treat inoperable hepatocellular carcinoma; it is a multikinase inhibitor that slows the spread of cancer cells.

The Liver and Your Medications
One of the liver's key functions is to remove toxic substances from your blood; this is a vital step in processing medications. Taking certain medications can cause further damage as an already-weakened liver works to break down the toxins.

The following drugs have been classified as hepatotoxic, or potentially damaging to the liver. Discuss these medications with your doctor before taking them.

Signs of Rejection
Most transplant recipients experience at least one episode of organ rejection. This does not mean you will lose your new liver; rejection is almost always reversible if caught in time. It is natural for your immune system to see your new liver as a foreign object and try to attack it. To help your body accept your new organ, we give you immunosuppressive medications. To keep your body from rejecting the new organ, these medications weaken your immune system.
You should always take your anti-rejection medications as directed and report any changes in your health as soon as possible. Early detection and prevention are essential to reversing the process of rejection, which can occur at any time. There are several signs that may occur to signal possible liver rejection:

• Elevated liver enzymes, verified with a blood test
• Jaundice or yellowing of your eyes or skin
• Flu-like symptoms such as chills, aches, pains, headache, fatigue, nausea and vomiting
• Fever over 101°F
• Darker, cola- or tea-colored urine
• Clay-colored stools
• Pain or fullness over your incision site

There are cases where you may experience rejection without having any symptoms at all. That is why it is important to keep your follow-up appointments — the blood tests taken during these appointments may reveal the first signs of rejection.
To find out if your liver is being rejected, we may ask that you repeat your lab tests and have an ultrasound or biopsy. If the tests detect rejection, you will probably be admitted to the hospital for treatment and receive medication through an intravenous (IV) feed for a specific amount of time.