The rate of serious adverse events related to liver biopsy is approximately 1% in patients with advanced chronic hepatitis C, which is comparable to the overall rate of biopsy complications, Dr. Leonard B. Seeff and his colleagues reported in an article appearing in the October issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2010.03.025).
Although the risks of liver biopsy in general are well documented, few studies have specifically examined adverse effects of the procedure in patients with advanced hepatitis C. It was not known until now whether they are at greater risk for complications than are patients with more mild chronic liver disease, said Dr. Seeff of the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Md., and his associates.
The investigators assessed these risks using data from the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) study, a large clinical trial evaluating the safety and efficacy of peginterferon alfa-2a and ribavirin. The study protocol mandated that serial liver biopsies be performed at baseline, 1.5 years, and 3.5 years. The trial was conducted at 10 clinical centers during 2000-2006.
Adverse events were defined as serious if they necessitated hospitalization, costly investigations such as ultrasound or CT, or blood transfusion, or if they led to perforation of an organ, surgery, or death.
Approximately 90% of the biopsies were outpatient procedures. In 80% of the procedures, bedside ultrasound guidance was utilized, and all included anesthetizing the subcutaneous tissue and liver capsule. Sixty percent of the procedures involved conscious sedation with short-acting benzodiazepines.
Most of the needles used were 16 gauge. Sixty percent of the biopsies utilized a cutting needle and the other 40% used an aspiration needle. At six of the medical centers, two passes usually were used to obtain adequate, unfragmented samples, whereas a single pass was routine at the remaining four medical centers.
All the medical centers required that a complete blood count, platelet count, and prothrombin time (PT) or international normalized ratio (INR) be performed before biopsy. Six centers allowed biopsies to proceed in patients with low platelet counts, four of them when the platelet count was as low as 50,000/mm3. The other four centers required platelet counts of at least 70,000/mm3 before permitting biopsy.
There were 2,740 biopsies: 1,187 at baseline, 852 at 1.5 years, and 701 at 3.5 years. A total of 63 complications developed, 29 of them serious, for an overall 1.1% rate of serious complications.
Slightly more than half of the serious adverse events (16) were bleeding events: hemoperitoneum (8 patients), subcapsular hematoma (4 patients), hemobilia (3 patients), and hemothorax (1 patient). Four patients required transfusions, and eight underwent embolization of the bleeding vessel and/or surgery to evacuate the blood.
Bleeding events are “the most commonly reported and concerning” major complication, and numerous studies have reported typical rates of 0.8%-1.7% related to liver biopsies. The 1.1% rate in this population of patients with advanced disease falls within that range, Dr. Seeff and his colleagues noted.
Other serious complications included severe pain (seven patients), punctured gall bladder (two patients), and marked hypotension, pneumothorax, syncope, and dehydration in one patient each. There were no deaths related to the biopsy procedure.
Serious complications were significantly related to a platelet count of 60,000/mm3 or lower, an INR of 1.3 or greater, and the presence of any esophageal varices on upper endoscopy.
“If liver biopsies had been avoided when platelet counts were less than or equal to 60,000/mm3, bleeding as a complication would have been reduced by 25% while eliminating only 2.8% of the biopsies,” the researchers said.
The complication rate did not differ significantly across treatment centers and was not significantly associated with patient body mass index, length of the biopsy specimen, fragmentation of the liver tissue, the presence or absence of splenomegaly, the use or nonuse of peginterferon alfa-2a or ribavirin, the type of biopsy needle, the use or nonuse of ultrasound guidance, or the presence of cirrhosis versus bridging fibrosis.
“A trend was observed, however, toward a greater risk of a nonbleeding serious adverse event if more than one pass was made or an inexperienced operator performed the procedure,” they noted.
This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Additional support was provided by the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, the National Center for Minority Health and Health Disparities, the National Center for Research Resources, and Hoffmann-La Roche. Several of Dr. Seeff’s associates also reported financial ties to Hoffmann-La Roche.