GENERAL LIVER INFORMATION

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[General]

The liver is a complex organ with interdependent metabolic,

excretory, and defense functions. No single or simple test assesses

overall liver function; sensitivity and specificity are limited. Use

of several screening tests improves the detection of hepatobiliary

abnormalities, helps differentiate the basis for clinically suspected

disease, and determines the severity of liver disease. Many tests are

available, but relatively few improve patient care.

Laboratory Tests

Among automatic analyses, the most useful are serum bilirubin,

alkaline phosphatase, and aminotransferase (transaminase).

Cholesterol and LDH are less valuable. The prothrombin time indicates

the severity of hepatocellular disease. Only a few biochemical and

serologic tests are diagnostic by themselves (eg, hepatitis B surface

antigen [HBsAg] for hepatitis B virus, serum copper and ceruloplasmin

for suspected 's disease, serum 1-antitrypsin for 1-antitrypsin

deficiency).

Bilirubin: Hyperbilirubinemia results from increased bilirubin

production, decreased liver uptake or conjugation, or decreased

biliary excretion (see Jaundice in Ch. 38). Increased bilirubin

production (eg, from hemolysis) or decreased liver uptake or

conjugation (eg, Gilbert's disease) causes unconjugated (or free)

bilirubin in serum to increase. Decreased bile formation and

excretion (cholestasis) elevates conjugated bilirubin in serum, and

the latter appears in urine.

The van den Bergh reaction measures serum bilirubin via

fractionation. A direct reaction measures conjugated bilirubin. The

addition of methanol causes a complete reaction, which measures total

bilirubin (conjugated plus unconjugated); the difference measures

unconjugated bilirubin (an indirect reaction).

Serum bilirubin may not be a particularly sensitive index of liver

dysfunction or disease prognosis, but it is an established test.

Total bilirubin is normally < 1.2 mg/dL (20 µmol/L). The only

value

of fractionating bilirubin into its components is to detect

unconjugated hyperbilirubinemia (present when the unconjugated

fraction is > 15% of total bilirubin). Fractionation is usually

required in cases of an isolated bilirubin elevation (ie, other

conventional liver tests are normal) or neonatal jaundice.

Sophisticated techniques to separate the various conjugates of

bilirubin have no clinical value.

Urine bilirubin is normally absent. Its presence, readily detected at

the bedside with a commercial urine test strip, indicates

hepatobiliary disease. Unconjugated hyperbilirubin is tightly bound

to albumin, not filtered by the glomerulus, and absent from urine

even with raised serum levels of unconjugated bilirubin. A positive

test for urine bilirubin confirms that any raised plasma levels are

from conjugated hyperbilirubinemia. There is no need to fractionate

the total plasma bilirubin. An early feature of hepatobiliary disease

can be bilirubinuria, which develops in acute viral hepatitis even

before clinical jaundice appears. It may be absent, however, under

other circumstances despite increased serum bilirubin. False-

negatives occur with prolonged storage of the urine specimen, which

may oxidize bilirubin, or in the presence of ascorbic acid (from

vitamin C ingestion) or nitrate in the urine (from urosepsis).

Urobilinogen is normally present in trace amounts in the urine (10

mg/L [17 µmol/L]) and can be assessed by commercial test strips.

This

intestinal metabolite of bilirubin becomes elevated from hemolysis

(excess pigment formation) or from mildly impaired liver uptake and

excretion (ie, when the enterohepatic circulation of this pigment

exceeds the liver's capacity to clear and excrete it). Failure of

bilirubin excretion into the small intestine reduces urobilinogen

formation so that the urine may test falsely low or absent. Thus,

although sensitive for mild liver disease, urobilinogen is too

nonspecific and too difficult to interpret.

Alkaline phosphatases: These isoenzymes can hydrolyze organic

phosphatase ester bonds in an alkaline medium, generating an organic

radical and inorganic phosphate. Their biologic function is unknown.

Alkaline phosphatase in serum normally comes from the liver and bone

and, during pregnancy, from the placenta. It is present in some

tumors (eg, bronchogenic carcinoma). Bone growth causes an age-

dependent rise in normal values, particularly in children < 2 yr and

adolescents. Thereafter, alkaline phosphatase activity declines,

reaching normal adult levels after a growth spurt during adolescence.

It is slightly increased in older people. During pregnancy, serum

levels rise two- to fourfold by the 9th mo and return to normal by 21

days' postpartum.

Alkaline phosphatase increases markedly in diseases that impair bile

formation (cholestasis) and to a lesser extent in hepatocellular

disease. Values in cholestasis, whether from intrahepatic causes

(primary biliary cirrhosis, drug-induced liver disease, liver

transplantation rejection) or graft-vs.-host disease or from

extrahepatic causes (bile duct obstruction from stricture, stone, or

tumor), rise similarly, up to fourfold. The elevation is not

discriminatory. In hepatocellular disease (eg, various forms of

hepatitis, cirrhosis, infiltrative disorders), alkaline phosphatase

levels tend to be somewhat lower, although overlap exists.

Isolated elevations (ie, other liver tests are normal) occur in

granulomatous hepatitis or focal liver disease (eg, abscess,

neoplastic infiltration, partial bile duct obstruction). In some

nonhepatic malignancies without liver metastasis, the mechanism is

obscure. For example, bronchogenic carcinoma may produce its own

alkaline phosphatase; hypernephroma in 15% of cases induces

nonspecific hepatitis as the presumed origin of the enzyme elevation.

For Hodgkin's lymphoma, the cause of the isolated alkaline

phosphatase elevation is unknown. Generally, an isolated alkaline

phosphatase elevation in an otherwise asymptomatic elderly adult is

not worth investigating. Most cases originate from the bone (eg, in

Paget's disease).

5´-Nucleotidase: Measurement of 5´-nucleotidase is simpler than

available techniques that assess elevated alkaline phosphatase to

distinguish bone from liver origin. 5´-Nucleotidase differs

biochemically from alkaline phosphatase and is more restricted to the

plasma membranes of the liver cell. Values are low in childhood, rise

gradually during adolescence, and plateau after age 50 yr. 5´-

Nucleotidase is normally elevated in some women during the last

trimester of pregnancy. This serum enzyme increases in hepatobiliary

but not in bone diseases. It is useful in assessing the anicteric

patient. Because of its specificity for liver disease, 5´-

nucleotidase offers some advantage over alkaline phosphatase, but

neither can differentiate obstructive from hepatocellular disease.

They may or may not rise and fall in parallel.

-Glutamyl transpeptidase (GGT): Also known as -glutamyltransferase,

GGT (present in the liver, pancreas, and kidney) transfers the -

glutamyl group from one peptide to another or to an L-amino acid. GGT

levels are elevated in diseases of the liver, biliary tract, and

pancreas when the common duct is obstructed. GGT levels parallel

those of alkaline phosphatase and 5´-nucleotidase in cholestatic

conditions. The extreme sensitivity of GGT (greater than that of

alkaline phosphatase) limits its usefulness, but it helps detect

hepatobiliary disease as the cause of an isolated rise in alkaline

phosphatase. GGT is normal in pregnancy and bone disease. Because it

is not physiologically elevated in pregnancy or childhood, GGT may

distinguish hepatobiliary disease in such cases. Drug use and alcohol

ingestion, which induce microsomal enzymes, also elevate GGT. As a

marker for alcoholic liver disease, GGT is poor when used alone but

more secure when combined with transaminases.

Transaminases: Aspartate transaminase (AST) and alanine

aminotransferase (ALT) are sensitive indicators of liver injury. AST

is present in the heart, skeletal muscle, brain, and kidney as well

as in the liver. AST levels thus rise in MI, heart failure, muscle

injury, CNS disease, and other nonhepatic disorders. AST is

relatively nonspecific, but high levels indicate liver cell injury.

ALT is reliable for routine screening for liver disease. Values > 500

IU/L suggest acute viral or toxic hepatitis and occur with marked

heart failure (ischemic hepatitis) and occasionally with common duct

stones. The magnitude of the elevation has no prognostic value and

does not correlate with the degree of liver damage. Serial testing

provides good monitoring: A fall to normal indicates recovery unless

associated with the end stages of massive hepatic necrosis.

ALT is found primarily in liver cells and thus has greater

specificity for liver disease but offers little other advantage. In

most liver diseases, the AST increase is less than that of ALT

(AST/ALT ratio < 1), but in alcohol-related liver injury, the ratio

frequently is > 2. The basis for this is the greater need of

pyridoxal 5´-phosphate (vitamin B6) as a cofactor for ALT; this

cofactor is deficient in the alcoholic, limiting the rise of ALT.

Although the practicality of the ratio is limited, an AST/ALT ratio >

3 with an inordinate increase in GGT (more than twice the alkaline

phosphatase) is highly suggestive of alcohol-related liver injury

(eg, alcoholic hepatitis).

Lactic dehydrogenase: LDH, commonly included in routine analysis, is

insensitive as an indicator of hepatocellular injury but is better as

a marker for hemolysis, MI, or pulmonary embolism. LDH can be quite

high with malignancies involving the liver.

Serum proteins: The liver synthesizes most serum proteins: - and -

globulins, albumin, and clotting factors (but not -globulin, which is

produced by B lymphocytes). Hepatocytes also make specific proteins:

1-antitrypsin (absent in 1-antitrypsin deficiency), ceruloplasmin

(reduced in 's disease), and transferrin and ferritin

(saturated with iron and greatly increased, respectively, in

hemochromatosis). These serum proteins and some others increase

nonspecifically in response to tissue injury (eg, inflammation) with

the release of cytokines. Such acute phase reactions may produce a

spuriously normal or elevated value.

Serum albumin, the main determinant of plasma oncotic pressure,

transports numerous substances (eg, unconjugated bilirubin). Its

serum concentration is determined by the relative rates of its

synthesis and degradation or loss, by its distribution between the

intra- and extravascular beds, and by the plasma volume. In adults,

the liver normally synthesizes 10 to 15 g (0.2 mmol) of albumin

daily, which represents about 3% of the total body pool. Its biologic

half-life is about 20 days; thus, serum levels do not reflect

hepatocellular function in acute liver disease. Serum albumin (and

its synthesis) is decreased in chronic liver disease (eg, cirrhosis,

ascites), largely because of the increased volume of distribution.

Alcoholism, chronic inflammation, and protein malnutrition depress

albumin synthesis. Hypoalbuminemia can result from excess albumin

loss from the kidney (nephrotic syndrome), gut (protein-losing

gastroenteropathies), and skin (burns).

Serum immunoglobulins rise in most cases of chronic liver disease

when the reticuloendothelial system is defective or bypassed by

portal venous shunts. The inability to clear portal venous blood of

transient bacteremias from normal colonic flora results in chronic

antigenic stimulation of extrahepatic lymphoid tissue and

hypergammaglobulinemia. Serum globulin levels rise slightly in acute

hepatitis and more markedly in chronic active hepatitis, particularly

of the autoimmune variety. The pattern of immunoglobulin increase

adds little: IgM is quite elevated in primary biliary cirrhosis, IgA

in alcoholic liver disease, and IgG in chronic active hepatitis.

Antibodies: Specific proteins may be diagnostic. Viral antigens and

antibodies are associated with specific causes of hepatitis (see

Acute Viral Hepatitis in Ch. 42 and Infectious Mononucleosis under

Viral Infections in Ch. 265).

Antimitochondrial antibodies are directed against antigens on the

inner mitochondrial membrane of several tissues. The M2 antigen is

most closely associated with primary biliary cirrhosis.

Antimitochondrial antibodies are positive, usually in high titers, in

> 95% of patients with primary biliary cirrhosis. These heterogeneous

antibodies are also present in 30% of cases of autoimmune chronic

active hepatitis and in some cases of drug hepatitis and collagen

vascular disease. They are absent in mechanical biliary obstruction

and primary sclerosing cholangitis; hence, they have important

diagnostic value, particularly when liver histopathology is equivocal.

Other antibodies occur in autoimmune chronic active hepatitis: Smooth

muscle antibodies directed against actin are found in 70%, and

antinuclear antibodies providing a homogenous (diffuse) fluorescence

are positive in high titers. Some patients with chronic active

hepatitis exhibit a different autoantibody, anti-liver-kidney-

microsome (LKM-1) antibody. However, none of these antibodies is

diagnostic by itself, and none reveals the pathogenesis of the

disease process.

-Fetoprotein (AFP): Synthesized by the fetal liver, AFP is normally

elevated in the mother and newborn. By 1 yr of age, infants achieve

adult values (normally < 20 ng/mL). Marked elevations develop in

primary hepatocellular carcinoma; the level correlates with tumor

size. AFP is a useful screening test because few other conditions

(embryonic teratocarcinomas, hepatoblastomas, infrequent hepatic

metastases from the GI tract, some cholangiocarcinomas) cause levels

> 400 ng/mL. In fulminant hepatitis, AFP can be > 1000 ng/mL; lesser

elevations (100 to 400 ng/mL) occur in acute and chronic hepatitis.

These values may represent hepatic regeneration.

Prothrombin time (PT): PT involves the interactions of factors I

(fibrinogen), II (prothrombin), V, VII, and X, which are synthesized

by the liver (see also discussion under Hemostasis in Ch. 131). PT

may be expressed in time (sec) or as a ratio of measured PT vs.

control PT, termed the INR. Vitamin K is necessary for prothrombin

conversion. The precursors of factors VII, IX, X, and possibly V

require it for activation through a carboxylation step, which is

essential for them to function as clotting factors. Vitamin K

deficiencies result from inadequate intake or malabsorption. Because

it is fat-soluble, vitamin K requires bile salts for intestinal

absorption and would therefore be deficient in cholestasis.

Malabsorption of vitamin K as a cause of a prolonged PT can be

differentiated by repeating the PT 24 to 48 h after administration of

vitamin K 10 mg sc. Little or no improvement occurs with parenchymal

liver disease.

PT is relatively insensitive for detecting mild hepatocellular

dysfunction. Because the biologic half-lives of the involved clotting

factors are short (hours to a few days), the PT has a high prognostic

value in acute liver injury. In acute viral or toxic hepatitis, PT >

5 sec above control is an early indicator of fulminant hepatic

failure.

Tests for hepatic transport and metabolism: Several tests can

determine the ability of the liver to transport organic material and

metabolize drugs. Bilirubin measurements are common; other tests,

although often very sensitive, are complex, costly, and nonspecific.

Bile acids are specific to the liver, being synthesized only in the

liver, constituting the driving force for bile formation and

exhibiting a 70 to 90% first-pass hepatic extraction. Serum bile acid

concentrations normally are extremely low (about 5 µmol/L).

Elevations are specific and very sensitive for hepatobiliary disease,

but they do not assist in differential diagnosis nor indicate

prognosis. Values are normal in isolated hyperbilirubinemia (eg,

Gilbert's syndrome). Sophisticated analysis of individual serum bile

acids may aid clinical research of bile acid therapy for gallstone

disease and primary biliary cirrhosis.

Imaging Studies

Radionuclide scanning, ultrasound (US), CT, and MRI have replaced

traditional imaging techniques (eg, oral cholecystogram, IV

cholangiogram). Invasive radiography (eg, ERCP) allows for

sophisticated instrumentation and treatment procedures.

Plain x-ray of the abdomen: The usefulness of x-rays is limited to

identifying calcifications in the liver or gallbladder, opaque

gallstones, and air in the biliary tract. Hepatic or splenic

enlargement and ascites may be detected.

Oral cholecystogram: This procedure is simple, reliable, and

relatively safe for visualizing the gallbladder; 25% of patients

experience diarrhea. Rarely, a patient has a hypersensitivity

reaction to the iodine in the contrast agent. An abnormal study

includes failure to visualize the gallbladder after a second dose of

contrast agent, provided the obvious has been excluded: vomiting,

gastric outlet obstruction, malabsorption, Dubin- syndrome,

and significant hepatocellular disease. Sensitivity for diagnosing

gallbladder disease (eg, cholelithiasis) is about 95%, but

specificity is much lower. Conversely, gallstones and tumors are

readily identified and differentiated. Besides defining gallbladder

anatomy, oral cholecystography also assesses the patency of the

cystic duct and, to a lesser extent, the concentrating function of

the gallbladder. Radiologic gallbladder filling is an important

criterion when assessing patients for gallstone dissolution therapy

with bile salts and for biliary lithotripsy. This technique is also

more useful than US for determining stone number and type (lucency

implies that the stones are composed of cholesterol). However, US and

biliary cholescintigraphy have largely replaced this former gold

standard because of their greater ease of use and lower false-

negative rates. Cholescintigraphy is also better at assessing

gallbladder filling and emptying.

Ultrasound: Findings obtained by US are morphologic and independent

of function. US is the most important investigative tool in screening

for biliary tract abnormalities and mass lesions in the liver. US is

better at detecting focal lesions (> 1 cm in diameter) than diffuse

disease (eg, fatty liver, cirrhosis). In general, cysts are echo-

free; solid lesions (eg, tumors, abscesses) tend to be echogenic. The

ability to localize focal lesions permits US-guided aspiration and

biopsy.

US is the least expensive, safest, and most sensitive technique for

visualizing the biliary system, especially the gallbladder. Accuracy

in detecting gallbladder or gallstone disease is close to 100%,

although an element of operator skill is needed. Gallstones cast

intense echoes with distal shadowing and may move with gravity. Size

can be accurately defined, but the number of stones may be difficult

to determine because of overlap when many are present. Criteria for

acute cholecystitis include a thickened gallbladder wall,

pericholecystic fluid, an impacted stone in the gallbladder neck, and

gallbladder tenderness on palpation ('s sign). Polyps of the

gallbladder are a frequent incidental finding. Carcinoma presents as

a nonspecific solid mass.

US is the procedure of choice for evaluating cholestasis and

differentiating extrahepatic from intrahepatic causes of jaundice.

Bile ducts stand out as echo-free tubular structures. The diameter of

the common duct is normally < 6 mm, increases slightly with age, and

can reach 10 mm after cholecystectomy. Dilated ducts are virtually

pathognomonic for extrahepatic obstruction, but normal bile ducts do

not exclude obstruction because it may be recent or intermittent. US

does not readily detect common duct stones, but they may be inferred

if the common duct is dilated and stones are identified in the

gallbladder. Visualization of the pancreas, kidney, and blood vessels

is an added bonus. Finding enlargement or a mass in the head of the

pancreas may reveal the cause of cholestasis or upper abdominal pain.

Doppler US measures the frequency change of a backscattered US wave

reflected from moving RBCs. This can show the patency of hepatic

vessels, particularly the portal vein, and the direction of blood

flow. Doppler US can reveal hepatic artery thrombosis after liver

transplantation. It also can detect unusual vascular structures (eg,

cavernous transformation of the portal vein).

Radionuclide scanning: This procedure involves hepatic extraction of

an injected radiopharmaceutical from the blood, most commonly

technetium 99m (99mTc).

Liver-spleen scanning uses 99mTc-sulfur colloid, which is rapidly

extracted from the blood by reticuloendothelial cells. Normally,

radioactivity is uniformly distributed. In a space-occupying lesion >

4 cm (eg, cyst, abscess, metastasis, hepatic tumor), the replaced

liver cells produce a cold spot. Generalized liver disease (eg,

cirrhosis, hepatitis) causes a heterogenous decrease in liver uptake

and increased uptake by the spleen and bone marrow. In hepatic vein

obstruction, there is decreased visualization of the liver except for

the caudate lobe because of its special drainage into the inferior

vena cava. US or CT has largely supplanted radionuclide scanning for

space-occupying lesions and diffuse parenchymal disease.

Cholescintigraphy: For scanning the hepatobiliary excretory system,

cholescintigraphy uses 99mTc-iminodiacetic acid derivatives. These

radiopharmaceuticals are organic anions, which the liver avidly

clears from plasma into bile much like bilirubin. A minimum 2-h fast

is necessary. A normal scan shows rapid, uniform liver uptake; prompt

excretion into the bile ducts; and a visible gallbladder and duodenum

by 1 h. In acute cholecystitis (with cystic duct obstruction), the

gallbladder is not visible by 1 h. Acute acalculous cholecystitis can

similarly be detected. Chronic cholecystitis is more problematic: It

can be reasonably diagnosed if gallbladder visualization is delayed

beyond 1 h, sometimes until 24 h, or if the gallbladder is never

visualized, but confounded by false-negatives and false-positives.

Several factors may contribute to nonvisualization of the gallbladder

(eg, significant cholestasis with markedly elevated bilirubin, a

nonfasting state, fasting > 24 h, certain drugs).

Cholescintigraphy also assesses hepatobiliary integrity (bile leaks

may be especially important after surgery or trauma) and anatomy

(from congenital choledochal cysts to choledochoenteric anastomoses).

After cholecystectomy, this biliary scan can quantitate biliary

drainage and assist in defining sphincter of Oddi dysfunction. In

neonatal jaundice, hepatobiliary imaging helps distinguish hepatitis

from biliary atresia.

Computed tomography: CT is sensitive to variations in density of

differing hepatic lesions. The addition of an IV contrast agent helps

differentiate more subtle differences between soft tissues and define

the vascular system and the biliary tract. CT shows liver structures

more consistently than US; neither obesity nor intestinal gas

obscures them. CT is especially useful for visualizing space-

occupying lesions (eg, metastases) in the liver and masses in the

pancreas. CT can detect fatty liver and the increased hepatic density

associated with iron overload. CT is expensive and necessitates

radiation exposure; both factors lessen its routine use compared with

US.

Magnetic resonance imaging: MRI is an exciting, although expensive,

technology that may prove advantageous for identification of tumors

and hepatic blood flow. Blood vessels are easily identified without

contrast agents. Although still evolving, MRI is comparable to CT for

detecting mass lesions and can visualize perihepatic vessels and the

biliary system. Magnetic resonance cholangiography is becoming an

increasingly useful screening tool before proceeding to more invasive

techniques.

Operative cholangiography: This procedure entails direct injection of

a contrast agent into the cystic duct or common bile duct at

laparotomy. Excellent visualization results. This diagnostic approach

is indicated for biliary stones when jaundice occurs or when a common

duct stone is suspected. Technical difficulties have limited its use

at laparoscopic cholecystectomy. Direct visualization of the common

duct can also be obtained by choledochoscopy. IV cholangiography for

identifying the common duct has been virtually abandoned because of

poor diagnostic yield, the risk of a hypersensitivity reaction, and

the advent of ERCP.

Endoscopic retrograde cholangiopancreatography: ERCP combines (1)

endoscopy (for upper GI endoscopy, see Ch. 19) for identifying and

cannulating the ampulla of Vater in the second portion of the

duodenum and (2) radiology after injection of a contrast agent into

the biliary and pancreatic ducts. This technique places a side-

viewing endoscope in the descending duodenum, identifies and

cannulates the papilla of Vater, and then injects a contrast agent to

visualize the pancreatic duct and the biliary duct systems. Besides

obtaining excellent images of the biliary tract and pancreas, ERCP

allows some visualization of the upper GI tract and the periampullary

area. Biopsies and interventional procedures may be performed (eg,

sphincterotomy, biliary stone extraction, placement of a biliary

stent in a stricture). ERCP is an outpatient procedure that, in

experienced hands, has relatively low risk (mainly pancreatitis in 3%

after sphincterotomy). It has revolutionized the diagnosis and

management of pancreaticobiliary disease. ERCP is especially valuable

in assessing the biliary tract in cases of persistent jaundice and in

seeking a lesion amenable to intervention (eg, stone, stricture,

sphincter of Oddi dysfunction). In jaundice and cholestasis, US to

assess duct size should precede ERCP.

Percutaneous transhepatic cholangiography (PTC): This procedure

involves puncture of the liver with a 22-gauge needle under

fluoroscopic or US control to enter the peripheral intrahepatic bile

duct system above the common hepatic duct. PTC has a high diagnostic

yield but only for the biliary system. Some therapeutic techniques

(eg, decompression of the biliary system, insertion of an

endoprosthesis) are possible. ERCP generally is preferred,

particularly if ducts are not dilated (eg, sclerosing cholangitis).

PTC is used after failed ERCP or when altered anatomy

(gastroenterostomy) precludes accessing the ampulla. It may

complement ERCP in hilar lesions at the porta hepatis. PTC is

generally safe but has a higher complication rate (eg, from sepsis,

bleeding, bile leaks) than ERCP. Local expertise often dictates the

choice between PTC and ERCP.

Liver Biopsy

Percutaneous liver biopsy provides valuable diagnostic information

with relatively small risk and little patient discomfort. Performed

with the patient under local anesthesia, this bedside procedure

entails aspiration (using the Menghini needle or the disposable and

therefore always sharp Jamshidi needle) or cutting (using the

disposable Trucut--a variation of the Vim-Silverman needle). The

needle is inserted through an anesthetized intercostal space anterior

to the midaxillary line, just below the point of maximal dullness on

expiration. The patient lies still and maintains expiration. The

liver is rapidly entered with either suction applied (Jamshidi) or a

cutting sheath advanced (Trucut). The result is a procedure that

takes 1 to 2 sec and yields a liver specimen 1 mm in diameter and 2

cm long. Occasionally, a second pass is necessary; if a second or

third attempt is unsuccessful, then needle biopsy should be guided by

ultrasound (US) or CT. US-guided biopsies using a biopsy gun, whose

spring mechanism fires a modified Trucut needle, are less painful and

provide a high yield. US guidance is particularly useful for sampling

focal lesions or avoiding vascular lesions (eg, hemangiomas).

At biopsy, the liver's texture can be ascertained on needle

insertion: a hard, gritty feel suggests cirrhosis. The biopsy is

examined routinely for histopathology. Cytology, frozen section, and

culture may be useful in selected cases. In suspected 's

disease, copper content should be measured. Gross inspection provides

information: fragmentation suggests cirrhosis; a fatty liver is pale

yellow and floats in formaldehyde; carcinoma is whitish.

Liver biopsy is sufficiently safe to perform as an outpatient

procedure. After biopsy, the patient is monitored for 3 to 4 h,

during which complications (eg, intra-abdominal hemorrhage, bile

peritonitis, lacerated liver) are most likely. Because delayed

bleeding can occur as long as 15 days later, discharged patients

should remain within 1 h of the hospital. Mild right upper quadrant

discomfort, sometimes radiating from the diaphragm to the shoulder

tip, is common and responds to mild analgesics. Mortality is low at

0.01%; major complications are reportedly about 2%.

Indications for percutaneous liver biopsy are listed in Table 37-1.

Fine-needle biopsy under US guidance detects metastatic carcinoma in

at least 66% of cases and may establish the diagnosis despite

negative scanning techniques; cytologic examination of the biopsy

fluid yields positive findings in an additional 10% of cases. Results

are less valuable in lymphoma and correlate poorly with the clinical

impression of hepatic involvement. Biopsy is especially valuable in

detecting TB or other granulomatous infiltrations and can clarify

graft problems (ischemic injury, rejection, biliary tract disease,

viral hepatitis) after liver transplantation.

Limitations of the procedure include (1) the need for a skilled

histopathologist (many pathologists have little experience with

needle specimens); (2) sampling error (nonrepresentative tissue

seldom occurs in hepatitis and other diffuse conditions but can be a

problem in cirrhosis and space-occupying lesions); (3) inability to

differentiate hepatitis etiologically (eg, viral vs. drug-induced);

and (4) occasional errors or uncertainty in cases of cholestasis.

Relative contraindications include a clinical bleeding tendency or a

coagulation disorder (prothrombin time > 3 sec over control values

[iNR > 1.2] despite giving vitamin K, bleeding time > 10 min), severe

thrombocytopenia (50,000/µL), severe anemia, peritonitis, marked

ascites, high-grade biliary obstruction, and subphrenic or right

pleural infection or effusion.

Transvenous liver biopsy is performed by threading a modified Trucut

needle through a catheter inserted into the right internal jugular

vein and through the right atrium into the inferior vena cava and

hepatic vein. The needle is advanced through the hepatic vein into

the liver. Hepatic vein and wedge pressures can also be obtained.

Although the specimen obtained is relatively small and the operator

must be skilled in angiography, this technique can be used even when

the patient has a significant coagulation disorder. It is

surprisingly well tolerated and requires minimal sedation, if any,

except in the case of an uncooperative patient. The yield for liver

tissue is > 95% in experienced hands. The complication rate is very

low: 0.2% bleed from puncture of the liver capsule. One center

reported no mortality in > 1000 transvenous biopsies.