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“The only thing necessary for these diseases to the triumph is for good people and governments to do nothing.”


Liver Biopsy - Just Think About It

Emmet B. Keeffe, MD

Liver Biopsy: Indications, Contraindications, and Complications

I'd like to convince you that we should do liver biopsy in many patients but not all patients.

The historical role of liver biopsy was critical in the diagnosis of all patients with acute and chronic liver diseases. However, in our current practices the diagnosis of chronic liver disease is now made by very sophisticated virological, immunological, and genetic testing. For example, we have serologic and virologic tests that diagnose hepatitis A through E, we have antimitochondrial antibody (AMA) that allows the easy diagnosis of primary biliary cirrhosis. We have antinuclear antibody and smooth muscle antibody for autoimmune hepatitis and we have both standard laboratory studies and genetic tests to diagnose all of our genetic liver diseases.

Thus, today in our practice, liver biopsy is reserved primarily for staging and in certain special situations like in allograft dysfunction after transplantation or when we need to analyze a specimen for iron or copper content.

I would now like to review the usual indications for a liver biopsy. Firstly, to evaluate chronically elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels of uncertain cause; to confirm the diagnosis of chronic liver disease, although as we'll see we can now diagnose most liver diseases without the biopsy based on good biochemical tests; to grade and stage chronic hepatitis, which is the prime indication we use biopsy today; and to determine the etiology of hepatic neoplasms when the imaging studies are equivocal or uncertain.


We need to evaluate the response to treatment in certain circumstances, such as autoimmune hepatitis or when we are doing pharmaceutically funded clinical trials, and we need to look at the outcome of a course of treatment. And then there are special circumstances. We need to evaluate liver transplant allograft dysfunction; to measure iron or copper in certain circumstances; and rarely, to culture for organisms.

There are also less certain indications for liver biopsy. One is to evaluate the cause of acute hepatitis. In acute viral hepatitis the diagnosis is usually obvious based on serologic and virologic tests. However, there are other circumstances, for example, acute hepatitis as a presentation of autoimmune hepatitis that requires a biopsy for confirmation of diagnosis or sometimes in suspected acute drug-induced hepatitis, a liver biopsy may be helpful.

In typical primary biliary cirrhosis (PBC) with an elevated alpha phosphatase and a positive AMA, liver biopsy is less often used than it had in the past. In typical primary sclerosing cholangitis (PSC) with a diagnostic cholangiogram, liver biopsy likewise is less often used. To stage PBC and PSC is less important because therapy is relatively standard and we will know when there's cirrhosis and a need for liver transplantation. And finally, Budd-Chiari syndrome is typically diagnosed by imaging studies and does not usually require a biopsy.

Other less certain indications include a typical hepatocellular carcinoma (HCC) or hepatic metastasis. We do not want to biopsy certain focal lesions, such as a cavernous hemangioma, and I would put forth, although it's a bit controversial, that we probably do not want to biopsy all patients who have nonalcoholic fatty liver disease (NAFLD) particularly if we suspect there's only simple steatosis, and, I do not think we need to biopsy all chronic hepatitis B (HBV) and Hepatitis C (Hepatitis C Virus) patients.

I'd like to address the contraindications to liver biopsy starting with the absolute contraindications. We cannot do a liver biopsy if a patient is not cooperative. We must also have satisfactory coagulation and the usual rules for impaired coagulation that make liver biopsy a risk for bleeding such as a prothrombin time (PT) of equal to or more than four seconds over control, or an International Normalized Ratio (INR) equal to or greater than 1.5, a platelet count according to different rules less than 50,000 or less than 60,000, or a bleeding time - although we do not do this routinely any longer - of equal to 10 minutes or more. We don't want to do a biopsy if we presume there's a vascular tumor such as a hemangioma, echinococal disease, which does not come up very often, or high-grade biliary obstruction from imaging studies.

Relative contraindications to a liver biopsy include ascites, severe chronic lung disease, infections either in the right pleural cavity or below the right diaphragm, amyloidosis, myeloproliferative diseases, and hereditary hemorrhagic telangiectasia. The latter 3 have been reported in some studies to be associated with an increased tendency for bleeding. Thus, these are relative and not absolute contraindications.


I would now like to review the known complications of liver biopsy, which we have to take in context of decisions in our practice regarding performance of biopsy. First of all pain. Pain occurs in .06% to 22% of patients in the literature. Although in my own practice I must say, pain occurs routinely in from 15% to 30% of the patients, and it may be pleuritic, peritoneal, or diaphragmatic. Some patients may have a vasovagal reaction with a faint. Hemorrhage is our most feared complication which occurs in .2% to .3% and bleeding may be in the peritoneal cavity (.03% to .7%), within the liver or in the subcapsular space (.06% to 23%), or within the biliary tree (.06% to .2%). And once in a while, in .001% to .4% of the cases we may biopsy another organ. And the one we particularly fear is the gallbladder although the lung, kidney, and colon may also present problems if they are hit rather than the liver (Reddy and Jeffers. Schiff's Diseases of the Liver, 8th ed. 1999).

Other complications include bile peritonitis (.03% to .2%), infectious problems including bacteremia, sepsis (.09%), or abscess, pneumothorax or pleural effusion (.08% to .3%), hemothorax (.2% to .5%), arteriovenous fistula (5.4%), and reactions to the anesthetic agent (.03%) (Reddy and Jeffers. Schiff's Diseases of the Liver, 8th ed. 1999).


Slide 1. Percutaneous Liver Biopsy Complications -- "Bottom Line"

I've given you a laundry list of all of the complications of liver biopsy. This is now the bottom line. This is what I tell my patients as I approach them before a liver biopsy. You can expect pain in 20% or 30% of biopsies, severe complications occur in 3 per 1000 and the ones that we worry about are hemorrhage or perforation of another organ, and a death rate occurs with a frequency of about 3 per 10,000.