Liver biopsy

Last updated
Liver biopsy
Adenocarcinoma liver metastasis.jpg
Micrograph of a liver core needle biopsy showing cancer.
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]

Contents

Medical uses

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.

Risks and limitations

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]

Procedure and variants

A small quantity of tissue is sampled from the liver when doing a biopsy, which is then examined under a microscope Human liver biopsy sample.jpg
A small quantity of tissue is sampled from the liver when doing a biopsy, which is then examined under a microscope

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]

History

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

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 ]

Related Research Articles

<span class="mw-page-title-main">Gastroenterology</span> Branch of medicine focused on the digestive system and its disorders

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. The digestive system functions to move material through the GI tract via peristalsis, break down that material via digestion, absorb nutrients for use throughout the body, and remove waste from the body via defecation. Physicians who specialize in the medical specialty of gastroenterology are called gastroenterologists or sometimes GI doctors. Some of the most common conditions managed by gastroenterologists include gastroesophageal reflux disease, gastrointestinal bleeding, irritable bowel syndrome, inflammatory bowel disease (IBD) which includes Crohn's disease and ulcerative colitis, peptic ulcer disease, gallbladder and biliary tract disease, hepatitis, pancreatitis, colitis, colon polyps and cancer, nutritional problems, and many more.

<span class="mw-page-title-main">Hepatitis</span> Inflammation of the 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.

<span class="mw-page-title-main">Hepatocellular carcinoma</span> Medical condition

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.

<span class="mw-page-title-main">Alcoholic liver disease</span> Medical condition

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.

<span class="mw-page-title-main">Alcoholic hepatitis</span> Medical condition

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. Severe cases may be treated with glucocorticoids. The condition often comes on suddenly and may progress in severity very rapidly.

<span class="mw-page-title-main">Autoimmune hepatitis</span> Chronic, autoimmune disease of the liver

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.

<span class="mw-page-title-main">Primary biliary cholangitis</span> Autoimmune disease of the liver

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.

<span class="mw-page-title-main">Primary sclerosing cholangitis</span> Medical condition

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.

<span class="mw-page-title-main">Liver disease</span> Medical condition

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.

<span class="mw-page-title-main">Fatty liver disease</span> Medical condition related to obesity

Steatotic liver disease (SLD) a.k.a. fatty liver disease (FLD) or hepatic steatosis, 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.

<span class="mw-page-title-main">Hepatic encephalopathy</span> Brain disease resulting from liver failure

Hepatic encephalopathy (HE) is an altered level of consciousness as a result of liver failure. Its onset may be gradual or sudden. Other symptoms may include movement problems, changes in mood, or changes in personality. In the advanced stages it can result in a coma.

<span class="mw-page-title-main">Cholestasis</span> Medical condition

Cholestasis is a condition where bile cannot flow from the liver to the duodenum. The two basic distinctions are an obstructive type of cholestasis where there is a mechanical blockage in the duct system that can occur from a gallstone or malignancy, and metabolic types of cholestasis which are disturbances in bile formation that can occur because of genetic defects or acquired as a side effect of many medications. Classification is further divided into acute or chronic and extrahepatic or intrahepatic.

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.

<span class="mw-page-title-main">Non-alcoholic fatty liver disease</span> Excessive fat buildup in the liver not caused by alcohol use

Metabolic (dysfunction) associated fatty liver disease (MAFLD) was previously known as non-alcoholic fatty liver disease (NAFLD) until renamed in 2023 by a global consensus panel composed mostly of hepatology researchers and clinicians. The term metabolic dysfunction-associated steatotic liver disease (MASLD) is also used. MAFLD is excessive fat build-up in the liver without another clear cause such as alcohol use. There are two types; non-alcoholic fatty liver (NAFL) and metabolic dysfunction–associated steatohepatitis, with the latter indicating the presence of further liver inflammation. NAFL is less dangerous than MASH and usually does not progress towards it. When NAFL does progress to MASH, it may eventually lead to complications such as cirrhosis, liver cancer, liver failure, or 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.

<span class="mw-page-title-main">Liver cancer</span> Medical condition

Liver cancer is cancer that starts in the liver. Liver cancer can be primary or secondary. Liver metastasis is more common than that which starts in the liver. Liver cancer is increasing globally.

<span class="mw-page-title-main">Cirrhosis</span> Chronic disease of the liver, characterized by fibrosis

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 mau develop into spontaneous infections. More serious complications include hepatic encephalopathy, bleeding from dilated veins in the esophagus, stomach, or intestines, and liver cancer.

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.

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.

References

  1. 1 2 3 4 5 6 Grant A, Neuberger J (October 1999). "Guidelines on the use of liver biopsy in clinical practice". Gut. 45 (Suppl 4): IV1–IV11. doi:10.1136/gut.45.2008.iv1. PMC   1766696 . PMID   10485854.
  2. ↑ Manning DS, Afdhal NH (May 2008). "Diagnosis and quantitation of fibrosis". Gastroenterology. 134 (6): 1670–81. CiteSeerX   10.1.1.464.1263 . doi:10.1053/j.gastro.2008.03.001. PMID   18471546.
  3. ↑ Hoefs, JC; Shiffman, ML; Goodman, ZD; Kleiner, DE; Dienstag, JL; Stoddard, AM; HALT-C Trial, Group. (September 2011). "Rate of progression of hepatic fibrosis in patients with chronic hepatitis C: results from the HALT-C Trial". Gastroenterology. 141 (3): 900–908.e1–2. doi:10.1053/j.gastro.2011.06.007. PMC   3773843 . PMID   21699796.
  4. ↑ Regev A, Berho M, Jeffers LJ, et al. (October 2002). "Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection". Am. J. Gastroenterol. 97 (10): 2614–8. doi:10.1111/j.1572-0241.2002.06038.x. PMID   12385448. S2CID   25506596.[ dead link ]
  5. ↑ Agence Nationale d'Accréditation et d'Evaluation en Santé (ANAES) (April 2002). "Consensus conference. Treatment of hepatitis C". Gastroenterol. Clin. Biol. 26 (Spec No 2): B303–20. PMID   12180305.
  6. ↑ <Please add first missing authors to populate metadata.> (November 2002). "Recommendations from the National Institutes of Health consensus development conference statement: management of hepatitis C: 2002". Hepatology. 36 (5): 1039. doi: 10.1002/hep.510360502 . PMID   12395309.
  7. 1 2 Diagnostic Liver Biopsy at eMedicine
  8. ↑ Janes; Lindor, KD (1993). "Outcome of patients hospitalized for complications after outpatient liver biopsy". Ann Intern Med. 118 (2): 96–8. doi:10.7326/0003-4819-118-2-199301150-00003. PMID   8416324. S2CID   37740050.
  9. ↑ Pasha; et al. (1998). "Cost-effectiveness of ultrasound-guided liver biopsy". Hepatology. 27 (5): 1220–6. doi: 10.1002/hep.510270506 . PMID   9581674.
  10. 1 2 3 4 Lim, JK; Flamm, SL; Singh, S; Falck-Ytter, YT; Clinical Guidelines Committee of the American Gastroenterological, Association. (May 2017). "American Gastroenterological Association Institute Guideline on the Role of Elastography in the Evaluation of Liver Fibrosis". Gastroenterology. 152 (6): 1536–1543. doi: 10.1053/j.gastro.2017.03.017 . PMID   28442119.
  11. ↑ "Liver Biopsy: Learn How This Procedure Is Performed". medicinenet.com. Retrieved 22 April 2018.
  12. 1 2 Gilmore; et al. (1995). "Indications, methods, and outcomes of percutaneous liver biopsy in England and Wales: an audit by the British Society of Gastroenterology and the Royal College of Physicians of London". Gut. 36 (3): 437–41. doi:10.1136/gut.36.3.437. PMC   1382461 . PMID   7698705.
  13. ↑ Strassburg; Manns, MP (2006). "Approaches to liver biopsy techniques-revisited". Semin Liver Dis. 26 (4): 318–27. doi:10.1055/s-2006-951599. PMID   17051446. S2CID   260320814.
  14. ↑ Froehlich; et al. (1993). "Practice and complications of liver biopsy. Results of a nationwide survey in Switzerland". Dig Dis Sci. 38 (8): 1480–4. doi:10.1007/bf01308607. PMID   8344104. S2CID   21781162.
  15. ↑ Silva MA, Hegab B, Hyde C, Guo B, Buckels JA, Mirza DF (November 2008). "Needle track seeding following biopsy of liver lesions in the diagnosis of hepatocellular cancer: a systematic review and meta-analysis". Gut. 57 (11): 1592–6. doi:10.1136/gut.2008.149062. PMID   18669577. S2CID   20355451.
  16. ↑ Boyd, Alexander; Cain, Owen; Chauhan, Abhishek; Webb, Gwilym James (2020). "Medical liver biopsy: background, indications, procedure and histopathology". Frontline Gastroenterology. 11 (1): 40–47. doi: 10.1136/flgastro-2018-101139 . ISSN   2041-4137. PMC   6914302 . PMID   31885839.
  17. ↑ Rösch J, Lakin PC, Antonovic R, Dotter CT (August 1973). "Transjugular approach to liver biopsy and transhepatic cholangiography". N. Engl. J. Med. 289 (5): 227–31. doi:10.1056/NEJM197308022890501. PMID   4713761.
  18. 1 2 Gregory T Everson, Mitchell L Shiffman, John C Hoefs, Timothy R Morgan, Richard K Sterling, David A Wagner, Shannon Lauriski, Teresa M Curto, Anne Stoddard, Elizabeth C Wright Quantitative liver function tests improve the prediction of clinical outcomes in chronic hepatitis C: results from the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis Trial. 2011 Hepatology 55(4):1019-29
  19. ↑ Tapper, Elliot B.; Lok, Anna S.-F. (2017-08-24). Longo, Dan L. (ed.). "Use of Liver Imaging and Biopsy in Clinical Practice". New England Journal of Medicine. 377 (8): 756–768. doi:10.1056/NEJMra1610570. ISSN   0028-4793. PMID   28834467. S2CID   205117722.
  20. ↑ "Scientific Publications". 2008-10-18. Archived from the original on 2008-10-18.
  21. ↑ Poynard T, Imbert-Bismut F, Munteanu M, et al. (2004). "Overview of the diagnostic value of biochemical markers of liver fibrosis (FibroTest, HCV FibroSure) and necrosis (ActiTest) in patients with chronic hepatitis C". Comp Hepatol. 3 (1): 8. doi: 10.1186/1476-5926-3-8 . PMC   522750 . PMID   15387887.
  22. ↑ Castéra L, Vergniol J, Foucher J, et al. (February 2005). "Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C". Gastroenterology. 128 (2): 343–50. doi: 10.1053/j.gastro.2004.11.018 . PMID   15685546.
  23. ↑ Yoneda M, Suzuki K, Kato S, et al. (August 2010). "Nonalcoholic fatty liver disease: US-based acoustic radiation force impulse elastography". Radiology. 256 (2): 640–7. doi: 10.1148/radiol.10091662 . PMID   20529989.
  24. ↑ Adams LA, Bulsara M, Rossi E, DeBoer B, Speers D, George J, Kench J, Farrell G, McCaughan GW, Jeffrey GP (October 2005). "Hepascore – An Accurate Validated Predictor of Liver Fibrosis in Chronic Hepatitis C Infection". Clinical Chemistry. 51 (10): 1867–73. doi: 10.1373/clinchem.2005.048389 . PMID   16055434.
  25. ↑ Raftopoulos SC, George J, Bourliere M, Rossi E, de Boer WB, Jeffrey GP, Bulsara M, Speers DJ, Macquillan G, Ching HL, Kontorinis N, Cheng W, Flexman J, Fermoyle S, Rigby P, Walsh L, McLeod D, Adams LA (April 2012). "Comparison of noninvasive models of fibrosis in chronic hepatitis B". Hepatology International. 6 (2): 457–467. doi:10.1007/s12072-011-9296-5. PMID   21748376. S2CID   22215786.
  26. ↑ Adams LA, George J, Bugianesi E, Rossi E, De Boer WB, van der Poorten D, Ching HL, Bulsara M, Jeffrey GP (October 2011). "Complex non-invasive fibrosis models are more accurate than simple models in non-alcoholic fatty liver disease". Journal of Gastroenterology and Hepatology. 26 (10): 1536–43. doi:10.1111/j.1440-1746.2011.06774.x. PMID   21950746. S2CID   205467096.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.