Liver biopsy
Encyclopedia
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.
physician Paul Ehrlich
in 1883. Percutaneous liver biopsy was first reported in the 1920s. The transjugular approach was pioneered by radiologist Charles Dotter in the 1970s.
ly (via a needle through the skin
), transvenously (through the blood vessel
s) 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
, abnormal blood tests) where blood test
s, 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. Direct biopsy of tumor
s 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
).
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.
Occasionally, liver biopsy is required to monitor the progress of treatment, such as in chronic viral hepatitis.
Liver biopsy is generally a safe procedure, but it is invasive. Complications of liver biopsy are rare but potentially lethal. The majority of complications (60%) occur within two hours, and 96% occur within 24 hours following the procedure. Approximately 2-3% of patients undergoing liver biopsy require hospitalization for the management of an adverse event. Thirty percent of patients experience significant pain during the procedure. Significant bleeding after a liver biopsy occurs in 1-2 out of 100 patients who are biopsied. 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.
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.
The cost of liver biopsy is estimated at USD$1,032 without complications and USD$2,745 with complications.
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. 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 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.
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 hepatits C. Other ultrasonic techniques used to characterize liver stiffness include Acoustic Radiation Force Impulse (ARFI) Imaging
.
APRI 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 Health Authorities. 50% of the results are unclassifiable. APRI may be useful for excluding significant fibrosis in hepatitis C.
Hepascore is an Australian blood test combining the following clinical and laboratory variables: age, gender, bilirubin, GGT, hyaluronic acid, alpha 2 macroglobin to create a score. The test has very few validations.
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
(removal of a small sample of tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
) from the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
. It is a medical test
Medical test
A diagnostic test is any kind of medical test performed to aid in the diagnosis or detection of disease. For example:* to diagnose diseases, and preferably sub-classify it regarding, for example, severity and treatability...
that is done to aid diagnosis
Medical diagnosis
Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...
of liver disease
Liver disease
Liver disease is a broad term describing any single number of diseases affecting the liver.-Diseases:* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons , autoimmunity or hereditary conditions...
, to assess the severity of known liver disease, and to monitor the progress of treatment.
History
The first liver aspirate was performed by the GermanGermany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
physician Paul Ehrlich
Paul Ehrlich
Paul Ehrlich was a German scientist in the fields of hematology, immunology, and chemotherapy, and Nobel laureate. He is noted for curing syphilis and for his research in autoimmunity, calling it "horror autotoxicus"...
in 1883. Percutaneous liver biopsy was first reported in the 1920s. The transjugular approach was pioneered by radiologist Charles Dotter in the 1970s.
Types
Liver biopsies may be taken percutaneousPercutaneous
In surgery, percutaneous pertains to any medical procedure where access to inner organs or other tissue is done via needle-puncture of the skin, rather than by using an "open" approach where inner organs or tissue are exposed .The percutaneous approach is commonly used in vascular procedures...
ly (via a needle through the skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
), transvenously (through the blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s) or directly during abdominal surgery
Abdominal surgery
The term abdominal surgery broadly covers surgical procedures that involve opening the abdomen. Surgery of each abdominal organ is dealt with separately in connection with the description of that organ Diseases affecting the abdominal cavity are dealt with generally under their own names The term...
. The sample is examined by microscope
Microscopy
Microscopy is the technical field of using microscopes to view samples and objects that cannot be seen with the unaided eye...
, and may be processed further by immunohistochemistry
Immunohistochemistry
Immunohistochemistry or IHC refers to the process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno," in reference to antibodies used in the procedure, and...
, determination of iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
and copper
Copper
Copper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...
content, and microbiological culture
Microbiological culture
A microbiological culture, or microbial culture, is a method of multiplying microbial organisms by letting them reproduce in predetermined culture media under controlled laboratory conditions. Microbial cultures are used to determine the type of organism, its abundance in the sample being tested,...
if tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
is suspected
Indications
Liver biopsy is often required for the diagnosis of a liver problem (jaundiceJaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
, abnormal blood tests) where blood test
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s, such as hepatitis A
Hepatitis A
Hepatitis A is an acute infectious disease of the liver caused by the hepatitis A virus , an RNA virus, usually spread the fecal-oral route; transmitted person-to-person by ingestion of contaminated food or water or through direct contact with an infectious person...
serology, have not been able to identify a cause. It is also required if hepatitis is possibly the result of medication
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
, but the exact nature of the reaction is unclear. Alcoholic liver disease
Alcoholic liver disease
Alcoholic liver disease is a term that encompasses the hepatic manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with hepatic fibrosis or cirrhosis. It is the major cause of liver disease in Western countries...
and tuberculosis of the liver may be diagnosed through biopsy. Direct biopsy of tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
s of the liver may aid the diagnosis, although this may be avoided if the source is clear (e.g. spread
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
from previously known colorectal cancer
Colorectal cancer
Colorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....
).
If the diagnosis is already clear, such as chronic hepatitis B or hepatitis C
Hepatitis C
Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...
, liver biopsy is useful to assess the severity of the associated liver damage. The same is true for haemochromatosis
Haemochromatosis
Haemochromatosis type 1 is a hereditary disease characterized by excessive intestinal absorption of dietary iron resulting in a pathological increase in total body iron stores. Humans, like most animals, have no means to excrete excess iron...
(iron overload), although it is frequently omitted. Primary biliary cirrhosis
Primary biliary cirrhosis
Primary biliary cirrhosis, often abbreviated PBC, is an autoimmune disease of the liver marked by the slow progressive destruction of the small bile ducts within the liver. When these ducts are damaged, bile builds up in the liver and over time damages the tissue. This can lead to scarring,...
and primary sclerosing cholangitis
Primary sclerosing cholangitis
Primary sclerosing cholangitis is a chronic liver disease caused by progressive inflammation and scarring of the bile ducts of the liver. The inflammation impedes the flow of bile to the gut, which can ultimately lead to liver cirrhosis, liver failure and liver cancer...
may require biopsy, although other diagnostic modalities have made this less necessary.
Occasionally, liver biopsy is required to monitor the progress of treatment, such as in chronic viral hepatitis.
Value and limitations
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.Liver biopsy is generally a safe procedure, but it is invasive. Complications of liver biopsy are rare but potentially lethal. The majority of complications (60%) occur within two hours, and 96% occur within 24 hours following the procedure. Approximately 2-3% of patients undergoing liver biopsy require hospitalization for the management of an adverse event. Thirty percent of patients experience significant pain during the procedure. Significant bleeding after a liver biopsy occurs in 1-2 out of 100 patients who are biopsied. 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.
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.
The cost of liver biopsy is estimated at USD$1,032 without complications and USD$2,745 with complications.
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. 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 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.
Non-invasive alternatives
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. 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.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 hepatits C. Other ultrasonic techniques used to characterize liver stiffness include Acoustic Radiation Force Impulse (ARFI) Imaging
Acoustic Radiation Force Impulse (ARFI) Imaging
Acoustic Radiation Force Impulse Imaging uses acoustic radiation force to generate images of the mechanical properties of soft tissue.-How it works:...
.
APRI 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 Health Authorities. 50% of the results are unclassifiable. APRI may be useful for excluding significant fibrosis in hepatitis C.
Hepascore is an Australian blood test combining the following clinical and laboratory variables: age, gender, bilirubin, GGT, hyaluronic acid, alpha 2 macroglobin to create a score. The test has very few validations.