suspected cases of liver cirrhosis, in order to confirm the diagnosis pathologically; establish etiology if possible (alcohol, alpha1-antitrypsin deficiency, primary biliary cirrhosis, Wilson's disease, hemochromatosis, etc); assess and stage level of activity; assess complications

chronic hepatitis, with or without cirrhosis, to identify cases of chronic activity hepatitis (liver biopsy mandatory for diagnosis) and differentiate this entity from chronic persistent hepatitis and lobular hepatitis

suspected liver disease in the known alcoholic patient, to confirm alcoholic liver disease, exclude alternative causes of liver disease (which may be present in 20% of cases), stage and assess disease activity

diagnosis of hepatoma or metastatic neoplasms

suspected multisystem disease with liver involvement, where traditional diagnostic techniques have not been fruitful (eg, sarcoidosis, amyloidosis, tuberculosis, glycogen storage disease)

staging of lymphoma

unexplained hepatomegaly

cholestasis of unknown etiology, where prior studies for biliary obstruction are negative

persistently elevated liver enzyme tests

selected cases of fever of unknown origin

selected cases of hepatitis of unknown etiology, in order to differentiate viral from drug-induced etiologies (not always possible) or to assess complications, such as cholestasis

evaluation of response to treatment

Liver biopsy is less useful in:

acute hepatitis A or B infection, unless the diagnosis is in question

extrahepatic biliary obstruction, where percutaneous transhepatic cholangiography and ERCP are considered first-line procedures

fluid-filled liver cysts detected on ultrasound or CT scan, probably more amenable to guided thin needle aspiration first

Contraindications Mahal et al (1979) noted that failure to heed accepted contraindications led directly to 22 bleeding episodes in 3800 percutaneous liver biopsies.¹ Contraindications include:

impaired hemostasis, accepted as prothrombin time more than 3 seconds over control, PTT more than 20 seconds over control, thrombocytopenia, and markedly prolonged bleeding time

severe anemia (Hgb <9.5 g/dL)

local infection near needle entry site, such as right sided pleural effusion or empyema, right lower lobe pneumonia, local cellulitis, infected ascites or peritonitis

tense ascites (low yield technically, risk of leakage)

high-grade extrahepatic biliary obstruction with jaundice (increased risk of bile peritonitis)

septic cholangitis

possible hemangioma

possible echinococcal (hydatid) cyst

lack of compatible blood for transfusion

uncooperative patient

Patient Preparation Procedures and risks of the procedure are explained and consent is obtained. Formal consultation with gastroenterology staff is usually required. Procedure entails overnight hospitalization in most cases but some patients may be candidates for a "same day" outpatient biopsy. This latter group is in good general health, not jaundiced, and displays no signs of liver failure (ascites, encephalopathy). They need to stay within several minutes of the hospital for 1-2 days postbiopsy and must have supervision from family or friends. Scheduling arrangements for both in-hospital and outpatient liver biopsies are handled by gastroenterology team. All aspirin products and nonsteroidal agents must be discontinued at least 5 days beforehand. If taking oral anticoagulants (Coumadin®), hospitalization is required to convert to heparin therapy before biopsy. Patient is NPO after midnight the evening prior. Daily medications may be taken on the day of procedure pending physician approval. In some hospitals, patient drinks one to two glasses of milk in the early AM on procedure day to empty the gallbladder. Screening laboratory studies ordered 24-48 hours in advance commonly include CBC, PT/PTT, BUN, bleeding time, and type and crossmatch for possible transfusion. Electrolytes and liver function tests are optional. If pneumonia or pleural effusion suspected on examination, PA and lateral chest x-ray is obtained. Premedication with meperidine and/or diazepam may be administered at physician discretion. This is not routine in some centers due to possible toxicity.

Aftercare Protocols are individualized for each hospital. In general, patient is monitored in a recovery area with frequent vital signs postbiopsy. If no complications are apparent, patient is transferred back to hospital room by cart. Strict bedrest is enforced for 24 hours; for the first 2 hours patient is positioned on his right side. After 5 hours, patient may be allowed to sit up. Vitals (blood pressure, pulse) are checked every 15-30 minutes for 2 hours, every 30 minutes for the next 2 hours, and then every hour for 8 hours. Following this, vitals every 4 hours are permissible. Physician should be immediately notified if hypotension, tachycardia, fever, or uncontrolled pain occurs. Diet is restricted to clear liquids for several hours, then full liquids as tolerated. Acetaminophen is usually sufficient for pain control. Some physicians recheck hematocrit 24 hours after procedure before approving hospital discharge.

Special Instructions In the appropriate high-risk patient, antibiotic prophylaxis for infective endocarditis may be considered. Little data exists regarding the risk of bacteremia, however, much less endocarditis.

Complications Based on several large series, serious morbidity has been estimated at 0.1% to 0.2%. Fatality rates have ranged from 0% to 0.17%, both figures being derived from studies involving >20,000 biopsies each. The more commonly seen complications are:

pain - the most common adverse event, noted in 50% of cases. Usually it is confined to the right shoulder, probably referred pain from diaphragmatic pleura. Analgesia is required in approximately 20% of patients with acetaminophen sufficient in most cases. Symptoms resolve in 1-2 days.

hemorrhage - minor episodes are common. Self-limited oozing from the puncture site may persist for approximately 1 minute, but with loss of only 5-10 mL blood. Significant hemorrhage is less frequent but is the most common cause of death from liver biopsy. Several series have estimated an incidence of approximately 0.2%, but Sherlock (1984) reported 40 patients out of 6379 required transfusion for intraperitoneal bleeding.2 She felt these statistics may even underestimate the incidence since those with severe coagulopathies were excluded. Bleeding usually results from a tear of a distended portal or hepatic vein. Specific sites include the abdominal cavity (hemoperitoneum), liver capsule (capsular hematoma), liver parenchyma (intrahepatic hematoma), or biliary tree (hemobilia). Postulated risk factors are coagulopathy, amyloid liver, hepatocellular injury, hemangioma, and vascularized tumor. However, bleeding may be massive when no risk factors are present. Not all episodes require surgery. In a study 4 of 7532 patients needed surgical intervention while 12 others with severe hemorrhage were transfused and observed.

bile leakage with peritonitis - associated with severe obstruction of the larger bile ducts. This is felt to result from laceration of a small, distended duct or from puncture of the gallbladder. With the widespread use of noninvasive imaging, the size of the bile ducts is known prebiopsy and the complication rate has declined.

laceration of internal organs and viscera - right kidney, gallbladder, colon, pancreas, and others

others: right-sided pneumothorax, arteriovenous fistula - 5.4% of all biopsies, drug toxicity

Equipment Several biopsy needles are available.

Menghini needle - 1.9 mm diameter steel shaft with sharpened beveled tip and syringe; specimen is obtained using suction/aspiration into a 10 mL syringe. Requires only 1 second within the liver ("1-second technique") and patient need not hold his breath. Disadvantages are small samples and fragmentation of biopsy specimens.

"Trucut" needle - disposable 2.05 mm diameter needle designed to cut out cores of tissue. Specimens are less fragmented, even in the cirrhotic liver, and thus a high success rate. However, dwell time in liver is longer (5-10 seconds), patient must cooperate more, and several steps are necessary.

Vim-Silverman needle - sheath with inner cutting blade (similar to a "punch" biopsy). Trucut needle is a modernized Vim-Silverman.

Technique Patient lies supine in bed with right hand behind his head. Liver margins are estimated by percussion. Two approaches are popular, transthoracic (intercostal) or subcostal (anterior). With the former, biopsy site is identified along the midaxillary line in the center of hepatic dullness, usually the eighth or ninth intercostal space. This approach avoids other abdominal organs but always penetrates the pleura. With the subcostal approach, the biopsy site lies below the bottom rib anteriorly, and is used when a liver mass is easily palpable below the right costal margin. The risk of visceral laceration is higher and this approach is infrequently used; fine needle aspiration under CT guidance has become more popular. A wide area is prepped and draped in sterile fashion with operators in gowns, gloves, and masks. The skin is anesthetized with 1% lidocaine, then deeper structures are infiltrated - subcutaneous tissue, intercostal muscles, and diaphragm. Some operators make a small superficial incision with a No 11 blade at the needle entry site to facilitate needle insertion. Techniques differ with the type of biopsy needle selected. In general, the biopsy needle is advanced as far as the diaphragm (depth estimated by a finder needle). If a Menghini needle is used, suction is applied to the syringe, the needle is pushed rapidly through the pleura and into the liver parenchyma. A 2.5 cm core of liver is aspirated and needle withdrawn, all within 1 second. If other needles are used, patient may need to hold his breath at end expiration to decrease the risk of pneumothorax. Several passes of the biopsy needle are performed to minimize sampling bias.

Specimen At least two to three liver cores, each >2 cm in length. Initial specimen processing and transportation handled by gastroenterology team. A typical protocol would be as follows:

tissue fixation - for light microscopy, specimen is routinely fixed in 10% buffered formalin within 1 minute. For transmission electron microscopy, 1 mm cubes of specimen are fixed immediately in glutaraldehyde with further processing in Pathology Laboratory.

routine tissue stains including: H & E - general liver histology stain; reticulin stain - for connective tissue, especially cirrhosis, fibrosis, bridging necrosis; trichrome - fibrosis; iron stain - useful for hemosiderosis, hemochromatosis, bile pigments; diastase PAS stain - useful for alpha1-antitrypsin globules, bile ducts, iron; orcein - for hepatitis B surface antigen (if present, fine granular brown material stains in hepatocytes). Also for copper-binding protein in Wilson's disease.

cytologic preparation - fluid from aspirating syringe may be smeared on clean microscope slide, fixed, and sent to Cytology Laboratory

microbiological culture - specimen sent without fixative in sterile container. Special stains (AFB, KOH, etc) and cultures (tuberculosis, viral, Brucella, parasites, fungi) as needed

optional special stains (ie, congo red for amyloidosis, immunohistochemistry)

Footnotes

References