Primary care physicians and specialists alike often encounter patients with chronic liver disease. Fortunately, these days we need to resort to liver biopsy less often than in the past.
The purpose of this review is to provide a critical assessment of the growing number of noninvasive tests available for diagnosing liver disease and assessing hepatic fibrosis, and to discuss the implications of these advances related to the indications for needle liver biopsy.
WHEN IS LIVER BIOPSY USEFUL?
Needle liver biopsy for diagnosis remains important in cases of:
Diagnostic uncertainty (eg, in patients with atypical features)
Coexisting disorders (eg, human immunodeficiency virus [HIV] and hepatitis C virus infection, or alcoholic liver disease and hepatitis C)
An overlapping syndrome (eg, primary biliary cirrhosis with autoimmune hepatitis).
Fatty liver. Needle liver biopsy can distinguish between benign steatosis and progressive steatohepatitis in a patient with a fatty liver found on imaging, subject to the limitations of sampling error.
Because fatty liver disease is common and proven treatments are few, no consensus has emerged about which patients with suspected fatty liver disease should undergo needle biopsy. Many specialists eschew needle biopsy and treat the underlying risk factors of metabolic syndrome, reserving biopsy for patients with findings that raise the concern of cirrhosis.
Hereditary disorders, eg, hemochromatosis, alpha-1 antitrypsin deficiency, and Wilson disease.
Periodic needle biopsy is also valuable in the management of a few diseases.
In autoimmune hepatitis, monitoring the plasma cell score on liver biopsy may help predict relapse when a physician is considering reducing or discontinuing immunosuppressive therapy.1
After liver transplantation, a liver biopsy is highly valuable to assess for rejection and the presence and intensity of disease recurrence.
PROBLEMS WITH LIVER BIOPSY
Liver biopsy is invasive and can cause significant complications. Nearly 30% of patients report having substantial pain after liver biopsy, and some experience serious complications such as pneumothorax, bleeding, or puncture of the biliary tree. In rare cases, patients die of bleeding.2
Furthermore, hepatic pathology, particularly fibrosis, is not always uniformly distributed. Surgical wedge biopsy provides adequate tissue volume to overcome this problem. Needle biopsy, on the other hand, provides a much smaller volume of tissue (1/50,000 of the total mass of the liver).3
As examples of the resulting sampling errors that can occur, consider the two most common chronic liver diseases: hepatitis C and fatty liver disease.
Regev et al4 performed laparoscopically guided biopsy of the right and left hepatic lobes in a series of 124 patients with chronic hepatitis C. Biopsy samples from the right and left lobes differed in the intensity of inflammation in 24.2% of cases, and in the intensity of fibrosis in 33.1%. Differences of more than one grade of inflammation or stage of fibrosis were uncommon. However, in 14.5%, cirrhosis was diagnosed in one lobe but not the other.
In a study in patients with nonalcoholic fatty liver disease, Ratziu et al5 found that none of the features characteristic of nonalcoholic steatohepatitis were highly concordant in paired liver biopsies. Clearly, needle liver biopsy is far from an ideal test.
Increasingly, liver diseases can be diagnosed precisely with laboratory tests, imaging studies, or both. Thus, needle liver biopsy is playing a lesser role in diagnosis.
ADVANCES IN NONINVASIVE DIAGNOSIS OF LIVER DISEASE
Over the past 30 years, substantial strides have been made in our ability to make certain diagnoses through noninvasive means.
Blood tests can be used to diagnose viral hepatitis A, B, and C and many cases of hemochromatosis and primary biliary cirrhosis. For a detailed discussion of how blood tests are used in diagnosing liver diseases, see www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/guide-to-common-liver-tests/.
Imaging studies. Primary sclerosing cholangitis can be diagnosed with an imaging study, ie, magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP). The value of needle biopsy in these patients is limited to assessing the degree of fibrosis to help with management of the disease and, less often, to discovering other liver pathologies.6
Most benign space-occupying liver lesions, both cystic and solid, can be fully characterized by imaging, especially in patients who have no underlying chronic liver disease, and no biopsy is needed. Whether biopsy should be performed to investigate liver lesions depends on the clinical scenario; the topic is beyond the scope of this paper but has been reviewed in detail by Rockey et al.2