| Liver biopsy | |
|---|---|
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| ICD-9-CM | 50.1 |
| MedlinePlus | 003895 |
Liver biopsy is the biopsy (removal of a small sample of tissue) from the liver. It is a medical test that is done to aid diagnosis of liver disease, to assess the severity of known liver disease, and to monitor the progress of treatment. [1]
Liver biopsy is often required for the diagnosis of a liver problem (jaundice, abnormal blood tests) where blood tests, such as hepatitis A serology, have not been able to identify a cause. It is also required if hepatitis is possibly the result of medication, but the exact nature of the reaction is unclear. Alcoholic liver disease and tuberculosis of the liver may be diagnosed through biopsy. [1] Direct biopsy of tumors of the liver may aid the diagnosis, although this may be avoided if the source is clear (e.g. spread from previously known colorectal cancer). [1] Liver biopsy will likely remain particularly important in the diagnosis of unexplained liver disease. Non-invasive tests for liver fibrosis in alcoholic, nonalcoholic and viral liver diseases are likely to become more widely used. [2]
If the diagnosis is already clear, such as chronic hepatitis B or hepatitis C, liver biopsy is useful to assess the severity of the associated liver damage. The same is true for haemochromatosis (iron overload), although it is frequently omitted. Primary biliary cirrhosis and primary sclerosing cholangitis may require biopsy, although other diagnostic modalities have made this less necessary. [1]
Occasionally, liver biopsy is required to monitor the progress of treatment, such as in chronic viral hepatitis. [1] It is an effective way to measure changes in the Ishak fibrosis score. [3]
For the last century liver biopsy has been considered as the gold standard for assessing the stage and the grade of chronic liver disease. Consensus conference statements recommended liver biopsy in the management of almost all patients with hepatitis C and B.[ citation needed ]
Biopsy results show significant variability (up to 40% for fibrosis diagnosis) which can lead to a wrong diagnosis. The result depends on the representativity of the punctured sample. [4]
Only 5% of patients at risk of fibrosis have liver biopsy. In 2002, the consensus conferences in France and in the USA raised the possibility of treating patients with chronic hepatitis without liver biopsy. [5] [6] These conferences also underlined the necessity of developing reliable non-invasive tests that might be an alternative to liver biopsy both in hepatitis B and C.
Liver biopsy is generally a safe procedure, but it is invasive. Complications of liver biopsy are rare but potentially lethal. [7] The majority of complications (60%) occur within two hours, and 96% occur within 24 hours following the procedure. [7] Approximately 2–3% of patients undergoing liver biopsy require hospitalization for the management of an adverse event. [8] [9] Thirty percent of patients experience significant pain during the procedure. [10]
Significant bleeding after a liver biopsy occurs in 1–2 out of 100 patients who are biopsied. [11] [12] Bleeding usually becomes apparent within three to four hours. It often stops on its own, but if it persists, a blood transfusion may be needed. Surgery or angiography (a procedure in which the bleeding site is identified and treated) may be required if the bleeding is severe or does not stop on its own. Intraperitoneal hemorrhage is the most serious consequence of bleeding. Fatal complications have been reported in up to 0.01–0.3% of biopsied patients. [12] [13] [14]
Liver biopsies may be taken percutaneously (via a needle through the skin), transvenously (through the blood vessels), endoscopically (through endoscopic ultrasound fine needle biopsy), or directly during abdominal surgery. The sample is examined by microscope, and may be processed further by immunohistochemistry, determination of iron and copper content, and microbiological culture if tuberculosis is suspected [15]
For a percutaneous biopsy, it is recommended to use a Birmingham gauge 16 or wider cutting needle, and obtaining a length of 20–25 mm of liver tissue. The presence of 10–12 portal tracts within the specimen is considered sufficient for reliable analysis, ensuring that architectural relationships between structures are maintained. [16]
Liver biopsy results are limited by sampling error, [10] as abnormal findings may be missed if only normal tissue is retrieved. In addition, interpretation of liver biopsy results may vary. [10]
The first liver aspirate was performed by the German physician Paul Ehrlich in 1883. In 1923, the first report of percutaneous liver biopsy was described. [1] [10] The transjugular approach was pioneered by radiologist Charles Dotter in the 1970s. [17]
Non-invasive alternatives to liver biopsy in hepatitis C patients include both functional staging (quantitative liver function tests) and determination of fibrosis from non-invasive tests. These latter tests are described below and share the disadvantage of estimating fibrosis rather than function. Functional staging has the advantage of evaluating the whole liver and directly measuring hepatic function that determines many clinical outcomes. [18] The ability to predict clinical outcomes is the best proof of the value of a clinical test. Quantitative hepatic function tests were better than combinations of routine blood tests and Ishak fibrosis score in predicting clinical outcomes. The best of these were the perfused hepatic mass (PHM) by quantitative laparoscopic liver spleen scan (QLSS) and oral Cholate clearance and shunt, a blood test. The QLSS measurement of spleen volume per ideal body weight was nearly as good. [18]
Multiphasic MRI is useful in diagnosing various types of liver lesions such as hepatocellular carcinoma, cholangiocarcinoma, hepatocellular adenoma, focal nodular hyperplasia, and hemangioma. [19]
FibroTest (FibroSure in the USA) and FibroMax are non-invasive tests using a blood sample and an algorithm. The test results correspond to stages F0-F4 and grades A0-A3 of the METAVIR scoring system. [20] In 2007 FibroTest was validated by French Health Authorities as a first-line diagnosis of liver injury before biopsy. It was recommended to be a better predictor than biopsy staging for hepatitis C complications and death. [21]
FibroScan is a type of ultrasound machine that uses transient elastography to measure liver stiffness. Its diagnostic performance for fibrosis is similar to that of methods based on serologic markers. Combined use of Fibroscan and Fibrotest could avoid a liver biopsy in most patients with chronic hepatitis C. [22] Other ultrasonic techniques used to characterize liver stiffness include Acoustic Radiation Force Impulse (ARFI) Imaging. [23]
Hepascore is a blood test developed in Australia combining the following clinical and laboratory variables: age, gender, bilirubin, GGT, hyaluronic acid, alpha 2 macroglobin to create a score. The test has been validated for patients with hepatitis B, [24] hepatitis C [25] and non-alcoholic fatty liver disease. [26]
APRI (AST to platelet ratio index) is a quick serum biomarker for fibrosis assessment from Italy. This simple index is made up of routine laboratory tests. The test has not been validated by any health authorities. 50% of the results are unclassifiable. APRI may be useful for excluding significant fibrosis in hepatitis C.[ citation needed ]
Gastroenterology is the branch of medicine focused on the digestive system and its disorders. The digestive system consists of the gastrointestinal tract, sometimes referred to as the GI tract, which includes the esophagus, stomach, small intestine and large intestine as well as the accessory organs of digestion which include the pancreas, gallbladder, and liver.
Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pain, and diarrhea. Hepatitis is acute if it resolves within six months, and chronic if it lasts longer than six months. Acute hepatitis can resolve on its own, progress to chronic hepatitis, or (rarely) result in acute liver failure. Chronic hepatitis may progress to scarring of the liver (cirrhosis), liver failure, and liver cancer.
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide.
Alcoholic liver disease (ALD), also called alcohol-related liver disease (ARLD), is a term that encompasses the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosis or cirrhosis.
Alcoholic hepatitis is hepatitis due to excessive intake of alcohol. Patients typically have a history of at least 10 years of heavy alcohol intake, typically 8–10 drinks per day. It is usually found in association with fatty liver, an early stage of alcoholic liver disease, and may contribute to the progression of fibrosis, leading to cirrhosis. Symptoms may present acutely after a large amount of alcoholic intake in a short time period, or after years of excess alcohol intake. Signs and symptoms of alcoholic hepatitis include jaundice, ascites, fatigue and hepatic encephalopathy. Mild cases are self-limiting, but severe cases have a high risk of death. Severity in alcoholic hepatitis is determined several clinical prediction models such as the Maddrey's Discriminant Function and the MELD score.
Autoimmune hepatitis, formerly known as lupoid hepatitis, plasma cell hepatitis, or autoimmune chronic active hepatitis, is a chronic, autoimmune disease of the liver that occurs when the body's immune system attacks liver cells, causing the liver to be inflamed. Common initial symptoms may include fatigue, nausea, muscle aches, or weight loss or signs of acute liver inflammation including fever, jaundice, and right upper quadrant abdominal pain. Individuals with autoimmune hepatitis often have no initial symptoms and the disease may be detected by abnormal liver function tests and increased protein levels during routine bloodwork or the observation of an abnormal-looking liver during abdominal surgery.
Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune disease of the liver. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to build up in the liver, a condition called cholestasis. Further slow damage to the liver tissue can lead to scarring, fibrosis, and eventually cirrhosis.
Primary sclerosing cholangitis (PSC) is a long-term progressive disease of the liver and gallbladder characterized by inflammation and scarring of the bile ducts, which normally allow bile to drain from the gallbladder. Affected individuals may have no symptoms or may experience signs and symptoms of liver disease, such as yellow discoloration of the skin and eyes, itching, and abdominal pain.
Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.
Fatty liver disease (FLD), also known as hepatic steatosis and steatotic liver disease (SLD), is a condition where excess fat builds up in the liver. Often there are no or few symptoms. Occasionally there may be tiredness or pain in the upper right side of the abdomen. Complications may include cirrhosis, liver cancer, and esophageal varices.
Cholestasis is a condition where the flow of bile from the liver to the duodenum is impaired. The two basic distinctions are:
Chronic liver disease in the clinical context is a disease process of the liver that involves a process of progressive destruction and regeneration of the liver parenchyma leading to fibrosis and cirrhosis. "Chronic liver disease" refers to disease of the liver which lasts over a period of six months. It consists of a wide range of liver pathologies which include inflammation, liver cirrhosis, and hepatocellular carcinoma. The entire spectrum need not be experienced.
Metabolic dysfunction–associated steatotic liver disease (MASLD) is the name adopted in 2023 for the condition previously known as non-alcoholic fatty liver disease (NAFLD). This condition is diagnosed when there is excessive fat build-up in the liver, and at least one metabolic risk factor. When there is also moderate alcohol intake, the term MetALD is used, and differentiated from alcoholic liver disease (ALD) when this is the sole cause of steatotic liver disease. The terms non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis have been used to describe different severities, the latter indicating the presence of further liver inflammation. NAFL is less dangerous than NASH and usually does not progress to it, but this progression may eventually lead to complications, such as cirrhosis, liver cancer, liver failure, and cardiovascular disease.
Acute fatty liver of pregnancy is a rare life-threatening complication of pregnancy that occurs in the third trimester or the immediate period after delivery. It is thought to be caused by a disordered metabolism of fatty acids by mitochondria in the fetus, caused by long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency. This leads to decreased metabolism of long chain fatty acids by the feto-placental unit, causing subsequent rise in hepatotoxic fatty acids in maternal plasma. The condition was previously thought to be universally fatal, but aggressive treatment by stabilizing the mother with intravenous fluids and blood products in anticipation of early delivery has improved prognosis.
Liver cancer, also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy, is cancer that starts in the liver. Liver cancer can be primary in which the cancer starts in the liver, or it can be liver metastasis, or secondary, in which the cancer spreads from elsewhere in the body to the liver. Liver metastasis is the more common of the two liver cancers. Instances of liver cancer are increasing globally.
Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage to the liver leads to repair of liver tissue and subsequent formation of scar tissue. Over time, scar tissue can replace normal functioning tissue, leading to the impaired liver function of cirrhosis. The disease typically develops slowly over months or years. Early symptoms may include tiredness, weakness, loss of appetite, unexplained weight loss, nausea and vomiting, and discomfort in the right upper quadrant of the abdomen. As the disease worsens, symptoms may include itchiness, swelling in the lower legs, fluid build-up in the abdomen, jaundice, bruising easily, and the development of spider-like blood vessels in the skin. The fluid build-up in the abdomen may develop into spontaneous infections. More serious complications include hepatic encephalopathy, bleeding from dilated veins in the esophagus, stomach, or intestines, and liver cancer. Stages of cirrhosis include compensated cirrhosis and decompensated cirrhosis.
FibroTest, known as FibroSure in the US, is a biomarker test that uses the results of six blood serum tests to generate a score that is correlated with the degree of liver damage in people with a variety of liver diseases. FibroTest has the same prognostic value as a liver biopsy. FibroSure uses quantitative results of five serum biochemical markers, α2-macroglobulin, haptoglobin, apolipoprotein A1, bilirubin, gamma glutamyl transpeptidase (GGT), with a patient’s age and gender to generate a measure of fibrosis and necroinflammatory activity in the liver.
Bile acid malabsorption (BAM), known also as bile acid diarrhea, is a cause of several gut-related problems, the main one being chronic diarrhea. It has also been called bile acid-induced diarrhea, cholerheic or choleretic enteropathy, bile salt diarrhea or bile salt malabsorption. It can result from malabsorption secondary to gastrointestinal disease, or be a primary disorder, associated with excessive bile acid production. Treatment with bile acid sequestrants is often effective. It is recognised as a disability in the United Kingdom under the Equality Act 2010
Thomas D. Schiano is an American specialist in liver transplantation, intestinal transplantation and in the diagnosis and treatment of acute and chronic liver disease. He serves as associate editor for the journals Hepatology and Liver Transplantation and has published more than 200 peer-reviewed articles and abstracts and more than 20 book chapters.
Detlef Schuppan is a German biochemist and physician. He focuses on the diagnosis and treatment of coeliac disease and wheat sensitivity, fibrotic liver diseases and the immunology of chronic diseases and cancer. He is the director of the Institute of Translational Immunology and a professor of internal medicine, gastroenterology, and hepatology at the Medical Center of the Johannes Gutenberg University of Mainz in Germany. He directs the outpatient clinic for coeliac disease and small intestinal diseases. He is also a professor of medicine and a senior visiting scientist at Harvard Medical School.
