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Cirrhosis

Highlights

Causes of Cirrhosis

Cirrhosis is a liver disease characterized by permanent scarring of the liver that interferes with its normal functions. Causes include:

Complications

Cirrhosis can cause many serious complications including:

Dietary and Lifestyle Changes

Anyone who has cirrhosis can benefit from certain lifestyle interventions. These include:

Treatment

Cirrhosis is considered an irreversible condition. Treatment focuses on slowing the progression of liver damage and reducing the risk of further complications. Your doctor will treat any underlying medical conditions that are the cause of your cirrhosis.

If liver damage progresses to liver failure, some people may be candidates for liver transplantation. Liver donations can come from either a cadaver or from a living donor. People with cirrhosis who have a liver transplant have very good chances for survival.

Introduction

Cirrhosis is scarring of the liver and poor liver function. It results from various disorders that damage liver cells over time. Eventually, damage becomes so extensive that the normal structure of the liver is distorted and its function is impaired.

Cirrhosis of the liver
Cirrhosis is the end result of long-term liver damage. Alcohol abuse, and chronic hepatitis B and C, are the leading causes of cirrhosis.

Scarring: The main damage in cirrhosis is triggered by scarring that occurs from inflammation and injuries due to alcohol, viruses like hepatitis, or other damage. The scar tissue and other changes in liver cells gradually replace healthy liver tissue and act like small dams to alter the flow of blood and bile in and out of the liver. The initial stage of light to moderate scarring in the liver is called fibrosis. As the scarring becomes more severe and extensive, cirrhosis occurs.

Altered Blood and Bile Flow: Liver scarring causes changes in blood and bile flow that have consequences throughout the body. In cirrhosis:

The liver is the largest internal organ in the body. In a healthy adult, it weighs about 3 pounds. The liver is wedge-shaped, with the top part wider than the bottom. It is located below the diaphragm and occupies the entire upper right side of the abdomen.

The liver performs hundreds of vital functions. Some key functions include:

Gallbladder

Click the icon to see an image of the liver.

Causes

Chronic alcohol abuse causes alcoholic liver disease (also called alcohol-induced liver disease). Alcoholic liver disease includes fatty liver (build-up of fat cells in the liver), alcoholic hepatitis (inflammation of the liver caused by heavy drinking), and alcoholic cirrhosis. In the liver, alcohol converts to toxic chemicals that trigger inflammation and tissue injury. This process leads to cirrhosis.

Chronic viral hepatitis, both hepatitis B and hepatitis C, is another major cause of cirrhosis. Chronic hepatitis C is a more common cause of cirrhosis in developed countries, while hepatitis B is a more common cause of cirrhosis worldwide, especially in sub-Saharan Africa and parts of Asia. People with chronic hepatitis B who are co-infected with hepatitis D are especially at risk for cirrhosis. The longer a person has chronic hepatitis, the greater the risk for eventually developing cirrhosis.

Hepatitis viruses produce inflammation in liver cells, causing injury or destruction. If the condition is severe and long-term, the cell damage becomes progressive, leading to severe scarring of the liver.

Hepatitis C
Hepatitis C is a virus-caused liver inflammation which may lead to cirrhosis. The people most at risk for contracting and spreading hepatitis C are those who share needles for injecting drugs.

Autoimmune hepatitis, like other autoimmune disorders, develops when a misdirected immune system attacks the body's own cells and organs. People who have autoimmune hepatitis also often have other autoimmune conditions, including systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, scleroderma, inflammatory bowel disease, glomerulonephritis, and hemolytic anemia. Autoimmune hepatitis typically occurs in women ages 15 to 40.

Disorders that block or damage the bile ducts can cause bile to back up in the liver, leading to inflammation and cirrhosis. These diseases include primary biliary cirrhosis and primary sclerosing chlorangitis.

Primary Biliary Cirrhosis: Up to 95% of primary biliary cirrhosis (PBC) cases occur in women, usually around age 50. In people with PBC, the immune system attacks and destroys cells in the liver's bile ducts. Like many autoimmune disorders, the causes of PBC are unknown.

Primary Sclerosing Cholangitis: Primary sclerosing cholangitis (PSC) is a chronic disease that mostly affects men, usually around age 40. The cause is unknown, but immune system defects, genetics, and infections may play a role.

Nonalcoholic fatty liver disease (NAFLD) resembles alcoholic liver disease, but it occurs in people who do not drink a lot of alcohol. NAFLD is the most common liver disease in the United States.

NAFLD is actually a progressive spectrum of liver diseases that include:

Obesity and type 2 diabetes are the two main causes of NAFLD. Metabolic syndrome is another major factor. Metabolic syndrome is a collection of risk factors that include:

Nonalcoholic fatty liver disease is usually benign and very slowly progressive. But, in certain people, it can lead to cirrhosis and eventual liver failure. NAFLD also increases the risk for heart disease, which is the leading cause of death for these people.

Hemochromatosis: Hemochromatosis is a disorder of iron metabolism. This disease interferes with the way the body normally handles iron. People with hemochromatosis absorb too much iron from the food they eat. The iron overload accumulates in organs in the body. When excess iron deposits accumulate in the liver, they can cause cirrhosis.

Other Hereditary Disorders: Other inherited diseases that can cause cirrhosis include Wilson's disease (which causes an accumulation of copper in the body), alpha-1 antitrypsin deficiency (a genetic disorder caused by defective production of a particular enzyme), and glycogen storage diseases (a group of disorders that cause abnormal amounts of glycogen to be stored in the liver).

Other causes of cirrhosis include:

Symptoms

Cirrhosis is divided into two stages: compensated and decompensated:

Early stages of compensated cirrhosis may cause few or no symptoms. When symptoms do begin, they may include:

As cirrhosis progresses to a decompensated stage, people may develop the following symptoms:

Some of these symptoms can lead to serious complications.

Jaundice
Jaundice is a condition produced when excess amounts of bilirubin circulating in the bloodstream dissolve in the layer of fat underneath the skin), causing a yellowish appearance of the skin and the whites of the eyes.

Complications

A damaged liver affects almost every bodily process, including the functions of the digestive, hormonal, and circulatory systems. Decompensated cirrhosis increases the risk of serious and potentially life-threatening complications.

The most serious complications of cirrhosis are those associated with portal hypertension. The portal vein carries blood from the intestine to the liver. High pressure in the portal vein develops when scarring in the liver blocks this flow of blood. This condition is called portal hypertension.

Portal hypertension causes some of the most serious complications of cirrhosis. Ascites, bleeding varices, hepatitis encephalopathy, and enlarged spleen are all associated with portal hypertension.

Ascites is fluid buildup in the abdominal cavity. It is caused by a combination of portal hypertension and low albumin levels. Albumin is a protein produced by the liver. Symptoms include:

If fluid accumulates in the lungs, it can cause problems with breathing. Although ascites itself is not fatal, it can lead to other more serious problems.

Spontaneous bacterial peritonitis: is a complication of ascites. It is a life-threatening bacterial infection of the membrane that lines the abdomen. Symptoms include confusion and altered mental status, fever, chills, and abdominal pain. Certain medications, such as proton pump inhibitors (used for treating acid reflux and gastroesophageal reflux disease), may increase the risk for spontaneous bacterial peritonitis in people with cirrhosis.

Ascites and portal hypertension can also cause kidney function to rapidly deteriorate.

Hepatorenal syndrome: occurs when the kidneys drastically reduce their own blood flow in response to the altered blood flow in the liver. It is a life-threatening complication that can be fatal unless liver transplantation is performed. Symptoms include:

Portal hypertension causes the development of varices, veins that enlarge to provide an alternative pathway for blood diverted from the liver. Varices usually form in the esophagus. They can also form in the upper stomach.

Varices pose a high risk for rupture and bleeding because they are thin-walled, twisted, and subject to high pressure. When varices rupture and bleed they can cause intestinal bleeding, a life-threatening event marked by black, tarry, or bloody stools or the vomiting of blood.

Portal hypertension can affect blood flow in the spleen causing it to become enlarged (splenomegaly). When the spleen cannot function properly, levels of blood platelets and white blood cells are reduced. These blood problems increase risks for infection and excessive bleeding.

Hepatic encephalopathy is impaired brain function due to liver damage. It is caused by a buildup in the blood of harmful intestinal toxins, particularly ammonia, which then accumulate in the brain.

Early symptoms of hepatic encephalopathy include confusion, forgetfulness, and trouble concentrating. Other symptoms may include fruity-smelling bad breath and tremor. In late stages, hepatic encephalopathy can result in coma.

People with cirrhosis have an increased risk for hepatocellular carcinoma, a type of liver cancer. Hepatitis B and C, alcoholism, hemochromatosis, and primary biliary cirrhosis, which are all causes of cirrhosis, are some of the major risk factors for liver cancer. Cirrhosis due to hepatitis C is the leading cause of hepatocellular carcinoma in the United States.

Diagnosis

Cirrhosis is diagnosed on the basis of physical exam, medical history, blood tests, and imaging tests. A liver biopsy may be performed to confirm a diagnosis of cirrhosis.

In a physical examination the doctor will evaluate:

A medical history will indicate risk factors for cirrhosis. People with a history of alcoholism, hepatitis B or C, or certain other medical conditions are at high risk.

Blood tests are used to measure liver enzymes associated with liver function. Enzymes known as aminotransferases, including aspartate (AST) and alanine (ALT), are released when the liver is damaged.

Blood tests may also measure:

Ultrasound or computed tomography (CT) scan may be used to determine the extent of scarring in the liver and to check for signs of liver cancer. A newer imaging method called transient elastography measures liver stiffness and may provide a non-invasive alternative to liver biopsy.

CT scan

Click the icon to see an image detailing a CT scan.

A liver biopsy is not always needed for diagnosis of cirrhosis. It may be performed for confirmation if other tests are inconclusive. A liver biopsy can also help determine the cause of cirrhosis, the extent of damage, and treatment options.

A biopsy involves a doctor inserting a thin biopsy needle, guided by ultrasound, to remove a small sample of liver tissue. Local anesthetic is used to numb the area. You may feel pressure and some dull pain. The procedure takes about 20 minutes.

The biopsy may be performed using various approaches, including:

Liver biopsy

Click the icon to see an image detailing liver biopsy.

Endoscopy:may be used to check for esophageal varices. In this test, a fiber-optic tube is inserted down the throat. The tube contains a tiny camera to view the inside of the esophagus, where varices are most likely to develop.

Paracentesis: is performed to determine the cause of ascites. This procedure involves using a thin needle to withdraw fluid from the abdomen.

Tests for Liver Cancer: Your doctor may recommend you have regular screening tests to check for the development of liver cancer (hepatocellular carcinoma). These tests include a blood test to check for levels of alpha-fetoprotein and an imaging test (MRI, or CT scan).

Treatment

If caught early enough, the early stages of liver scarring (fibrosis) can sometimes be treated to reduce inflammation and prevent the development of cirrhosis. Once cirrhosis occurs, it is generally considered an irreversible condition.

Treatment goals are to slow the progression of liver damage and reduce the risk of further complications. There are currently no drugs available to treat severe liver scarring, although researchers are investigating various anti-fibrotic drugs

Everyone with cirrhosis can benefit from certain types of lifestyle interventions. These include:

People with cirrhosis are susceptible to infections and bleeding, both of which can be life threatening. Contact your doctor's office or go to the emergency room if you experience any of the following symptoms:

Treatment for cirrhosis depends on the cause of cirrhosis. In some cases, treatment of an underlying condition may help reverse early-stage cirrhosis.

Chronic Hepatitis: Many types of antiviral drugs are used to treat chronic hepatitis B. Treatment for chronic hepatitis C depends on the genotype. Treatment options for hepatitis C are constantly evolving as new drugs are approved. Successful treatment of hepatitis can sometimes lead to regression of cirrhosis.

Autoimmune Hepatitis: Autoimmune hepatitis is treated with the corticosteroid prednisone and also sometimes immunosuppressants, such as azathioprine (Imuran).

Bile Duct Disorders: Ursodeoxycholic acid (Actigall, generic), also known as ursodiol or UDCA, is used for treating primary biliary cirrhosis but does not slow the progression. Itching is usually controlled with drugs such as cholestyramine (Questran, generic) and colestipol (Colestid). Antibiotics for infections in the bile ducts and drugs that affect the immune system (prednisone, azathioprine, cyclosporine, and methotrexate) may also be used. Surgery may be needed to open up the bile ducts.

Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH): Weight reduction through diet and exercise, and diabetes and cholesterol management are the primary approaches to treating these diseases.

Hemochromatosis: Hemochromatosis is treated with phlebotomy, a procedure that involves removing about a pint of blood once or twice a week until iron levels are normal.

Treatment of Complications

First-line treatment of people with ascites (fluid accumulation in the abdomen) involves:

Treatment for Recurring or Refractory Ascites: People with ascites that do not respond to diuretics (refractory ascites) may be treated with the drug midodrine (Orvaten, generic) to reduce ascetic fluid. If they do not respond to this drug treatment, they may require other procedures to reduce fluid:

People with ascites who have high white blood cell counts should receive intravenous or oral antibiotic therapy. People who have had an episode of spontaneous bacterial peritonitis are usually treated with long-term antibiotic therapy to prevent further infection, but doctors must also consider the risk for drug resistance.

Hepatorenal syndrome can occur in patients with ascites. This is a life-threatening condition in which kidney failure develops because of altered blood flow in the liver. People with hepatorenal syndrome are usually treated with intravenous infusion of albumin or with the drug pentoxifylline.

The first step in managing encephalopathy (damage to the brain) is to treat any precipitating cause, such as:

Protein-restricted diets used to be recommended to lower ammonia production. However, extreme protein restriction can cause malnutrition and be harmful. Guidelines now recommend that people receive adequate protein intake and have small meals throughout the day including a late-night snack of complex carbohydrate.

Diets rich in vegetables and fiber are also important. The laxative lactulose, given as a syrup or enema, is used to empty the bowels and to help improve mental status. The antibiotic rifaxmin (Xifaxan) may be added for people who do not improve with lactulose alone. Sedatives and medications containing ammonium (such as certain antacids) should be avoided.

Other therapies may also be recommended. People who are hospitalized for hepatitis encephalopathy may need intravenous or tube feedings or require a shunt procedure.

Primary Prevention: Primary prevention means treating the varices before they have bled. Varices that are present in the esophagus, stomach, or intestines are always at risk of bleeding. Beta-blockers drugs, which are commonly used to treat high blood pressure, may be given to prevent bleeding.

People with medium-to-large varices that have not bled may be treated with a surgical procedure called endoscopic variceal ligation (EVL). EVL is also called band ligation. It involves inserting an endoscope down through the esophagus. Latex bands are wrapped around the bleeding varices to shut off the blood supply.

Treatment: When varices located in the digestive tract begin to bleed (variceal hemorrhage), it is considered an emergency situation. The first step is to immediately achieve normal blood clotting (hemostasis) in order to stop the current bleeding episode. Blood transfusions are usually required.

The main treatment for variceal hemorrhage is a drug that tightens blood vessels (vasoconstrictor) such as ocreotide (Sandostatin, generic). Medical procedures to stop bleeding include endoscopic variceal ligation (described above). An alternative procedure is endoscopic sclerotherapy. In endoscopic sclerotherapy, the endoscopic tube is inserted through the mouth and a sclerosant (a solution that toughens the tissue around the variceal blood vessels) is injected to stop the bleeding.

If these treatments do not control the bleeding, or bleeding recurs, a transjugular intrahepatic portosystemic shunt (TIPS) procedure is performed. (For more information on TIPS, see "Treatment of Ascites" above.) However, this procedure can increase the risk for encephalopathy.

Another procedure, called balloon tamponade, may be used to temporarily control bleeding prior to the TIPS procedure. Balloon tamponade is performed only for bleeding that cannot be controlled by drugs or endoscopy. It involves inserting a tube through the nose and down through the esophagus until it reaches the upper part of the stomach. A balloon at the tube's end is inflated and positioned tightly against the esophageal wall. It is usually deflated in about 24 hours. Balloon tamponade poses a risk for serious complications, the most dangerous being rupture of the esophagus.

Secondary Prevention: People who survive an episode of variceal bleeding need to be treated with drugs to prevent bleeding recurrence. They are prescribed either a combination of a nitrate drug beta-blocker or a beta-blocker alone. Several sessions of endoscopic variceal ligation may also be performed over the course of several months. The TIPS procedure may be recommended if bleeding recurs despite drug and endoscopic therapy. Liver transplantation may also be an option.

Septic shock is a life-threatening condition that occurs when severe bacterial infection causes extreme low blood pressure. It is very important that people with cirrhosis and septic shock receive immediate and appropriate antibiotic treatment.

Liver Transplantation

When cirrhosis progresses to end-stage liver disease, liver transplantation may be an option. Transplantation is not necessary or appropriate for all people with cirrhosis.

A scoring system called Model for End-Stage Liver Disease (MELD) is used to determine which patients are most in need of a donor liver. A MELD score predicts 3-month survival based on laboratory tests of creatinine, bilirubin, and blood-clotting time. Priority is given to people who are most likely to die without a liver transplant.

Unfortunately, there are many more patients waiting for liver transplants than there are available organs. Living-donor liver transplantation is an option. In living-donor transplantation, surgeons replace the person's diseased liver with a part of the liver taken from a donor. The donor's liver regenerates to full size within a few weeks of surgery, and the recipient's liver also regrows. This procedure produces excellent results, but there are some risks for the donor.

Transplantation surgery generally takes 4 to 12 hours to perform, and patients stay in the hospital for up to 3 weeks after the surgery. Most people return to normal or near-normal activities 6 to 12 months following the transplant. For the rest of their lives, they will need to take immunosuppressive medication to prevent rejection.

Current 5-year survival rates after liver transplantation are about 80%, depending on various factors. People report improved quality of life and mental functioning after liver transplantation. In researching transplant centers, ask how many transplants they perform each year and their survival rates. Compare those numbers to those of other transplant centers.

Liver Transplantation for People with Viral Hepatitis: One of the primary problems with performing liver transplantation in patients with viral hepatitis is recurrence of the virus after transplantation. Recurrence occurs more often with hepatitis C than hepatitis B. Pretreatment with antiviral drugs, along with life-long immune globulin injections after transplant, is very successful in reducing the risk of recurrence in hepatitis B. Pretreatment with new drugs such as sofosbuvir is showing promise in preventing recurrence in hepatitis C.

Liver Transplantation for People with Alcoholic Liver Disease: Liver transplantation is controversial for people with alcoholic liver disease. Most transplant centers recommend that people achieve at least 6 months of sobriety before being considered for a transplant. People with alcohol dependence who may need a liver transplant should meet with a mental health professional for evaluation of psychological problems, and to get help setting goals for addiction treatment.

Liver transplant - series

Click the icon to see an illustrated series detailing a liver transplant.

Resources

References

Amodio P, Bemeur C, Butterworth R, Cordoba J, Kato A, Montagnese S, et al. The nutritional management of hepatic encephalopathy in patients with cirrhosis: International Society for Hepatic Encephalopathy and Nitrogen Metabolism Consensus. Hepatology. 2013 Jul;58(1):325-36. Epub 2013 May 31.

Arabi YM, Dara SI, Memish Z, Al Abdulkareem A, Tamim HM, Al-Shirawi N, et al. Antimicrobial therapeutic determinants of outcomes from septic shock among patients with cirrhosis. Hepatology. 2012 Dec;56(6):2305-15.

Berg CL, Gillespie BW, Merion RM, Brown RS Jr, Abecassis MM, Trotter JF, et al Improvement in survival associated with adult-to-adult living donor liver transplantation. Gastroenterology. 2007 Dec;133(6):1806-13. Epub 2007 Sep 14.

Brown RS Jr. Live donors in liver transplantation. Gastroenterology. 2008 May;134(6):1802-13.

Cárdenas A, Ginès P. Management of patients with cirrhosis awaiting liver transplantation. Gut. 2011 Mar;60(3):412-21. Epub 2010 Dec 30.

Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012 Jun;55(6):2005-23.

Chandok N, Watt KD. Pain management in the cirrhotic patient: the clinical challenge. Mayo Clin Proc. 2010 May;85(5):451-8. Epub 2010 Mar 31.

Garcia-Tsao G, Bosch J. Management of varices and variceal hemorrhage in cirrhosis. N Engl J Med. 2010 Mar 4;362(9):823-32.

Garcia-Tsao G, Lim JK; Members of Veterans Affairs Hepatitis C Resource Center Program. Management and treatment of patients with cirrhosis and portal hypertension: recommendations from the Department of Veterans Affairs Hepatitis C Resource Center Program and the National Hepatitis C Program. Am J Gastroenterol. 2009 Jul;104(7):1802-29. Epub 2009 May 19

Garcia-Tsao G, Sanyal AJ, Grace ND, Carey WD; Practice Guidelines Committee of American Association for Study of Liver Diseases; Practice Parameters Committee of American College of Gastroenterology. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Am J Gastroenterol. 2007 Sep;102(9):2086-102.

Ginès P, Schrier RW. Renal failure in cirrhosis. N Engl J Med. 2009 Sep 24;361(13):1279-90.

Gonzalez R, Zamora J, Gomez-Camarero J, Molinero LM, Bañares R, Albillos A. Meta-analysis: Combination endoscopic and drug therapy to prevent variceal rebleeding in cirrhosis. Ann Intern Med. 2008 Jul 15;149(2):109-22.

Leise MD, Poterucha JJ, Kamath PS, Kim WR. Management of hepatic encephalopathy in the hospital. Mayo Clin Proc. 2014 Feb;89(2):241-53. Epub 2014 Jan 8. PMID 24411831 www.ncbi.nlm.nih.gov/pubmed/24411831.

Lewis JH, Stine JG. Review article: prescribing medications in patients with cirrhosis - a practical guide. Aliment Pharmacol Ther. 2013 Jun;37(12):1132-56. Epub 2013 May 3.

Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ; American Association for Study of Liver Diseases. Primary biliary cirrhosis. Hepatology. 2009 Jul;50(1):291-308.

Marchesini G, Moscatiello S, Di Domizio S, Forlani G. Obesity-associated liver disease. J Clin Endocrinol Metab. 2008 Nov;93(11 Suppl 1):S74-80.

Martin P, DiMartini A, Feng S, Brown R Jr, Fallon M. Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Hepatology. 2014 Mar;59(3):1144-65. PMID 24716201 www.ncbi.nlm.nih.gov/pubmed/24716201.

Runyon BA; AASLD. Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis 2012. Hepatology. 2013 Apr;57(4):1651-3.

Sohrabpour AA, Mohamadnejad M, Malekzadeh R. Review article: the reversibility of cirrhosis. Aliment Pharmacol Ther. 2012 Nov;36(9):824-32.

Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis. Lancet. 2014 May 17;383(9930):1749-61. Epub 2014 Jan 28. PMID 24480518 www.ncbi.nlm.nih.gov/pubmed/24480518.

Udell JA, Wang CS, Tinmouth J, FitzGerald JM, Ayas NT, Simel DL, et al. Does this patient with liver disease have cirrhosis? JAMA. 2012 Feb 22;307(8):832-42.



Review Date: 12/26/2014
Reviewed By: Todd Eisner, MD, Private practice specializing in Gastroenterology, Boca Raton, FL. Clinical Instructor, Florida Atlantic University School of Medicine. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team. Author: Julia Mongo, MS.
The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997- A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.
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