Bleeding Complication With Liver Biopsy

Bleeding Complication With Liver Biopsy: Is It Predictable?

Stephen Caldwell, MD,
Patrick G. Northup, MD

Liver biopsy remains a cornerstone of diagnosis and disease staging and an important measure of natural history and therapeutic outcomes in many forms of liver disease. The major limitations of biopsy are the risk of procedure-related complications especially bleeding and adequacy of the sample to ensure accurate histologic interpretation. In the current issue of Clinical Gastroenterology and Hepatology, Seeff et al report liver biopsy complication rates in 1 of the largest cohorts of patients with histologically advanced disease.1

The study involved 2740 percutaneous biopsies performed over 7 years at 10 centers as part of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial. The study assessed the efficacy of low dose maintenance peginterferon alfa-2a therapy in patients with histologically advanced hepatitis C—related fibrosis undergoing biopsy at baseline (n = 1187), 1.5 years (n = 852), and 3.5 years (n = 701) of treatment. Eighty percent of the biopsies were performed with ultrasound guidance, 40% used an aspiration needle, and 60% used a cutting needle. Single passes were reported in 40% and 2 passes in 60%. Complication rates were determined prospectively with no difference between baseline and follow-up biopsies.

Overall, serious adverse events (AE) occurred in 29 of the biopsies with no deaths. Severe bleeding was the most common cause seen in 16 (0.6%) of the biopsies including hemoperitoneum in 8, subcapsular hematoma in 4, hemobilia in 3, and hemothorax in 1. About one fourth of the adverse events were due to severe pain and one fourth were due to other causes including punctured gallbladder in 2, pneumothorax in 1, syncope in 1, and hypotension in 2. Because of its higher frequency and potential severity, the authors focused on bleeding risk assessment. No difference in those who bled versus those who did not was seen between 2 passes versus a single pass, use of a cutting needle versus an aspiration needle, or performance by a fellow as opposed to an attending physician.

Factors that were statistically different between those with bleeding and those without were lower albumin, presence of varices, platelets less than 60,000 and INR ≥ 1.3 although it should be noted that among the 8 patients with international normalized ratio (INR) > 1.5, none had bleeding. Moreover, while these variables were statistically significant, the clinical differences were not clinically dramatic as is evident in Tables 6 and 7 of the report. The relationship to varices and albumin levels suggests that the variation in risk may be due to changes in hepatic vasculature in more advanced disease rather than changes in hemostatic mechanisms.

Although several other factors limit interpretation of the data including preset study inclusion criteria (based in part on conventional coagulation parameters) and the retrospective acquisition of procedure details by questionnaire as discussed by the authors, the study raises the interesting and challenging issue of bleeding risk assessment with percutaneous liver biopsy. Reassuringly, the mortality was zero although the incidence of nonfatal severe bleeding was higher in this cohort of advanced fibrosis stage patients, 1 in 200, compared with about 1 in 500 biopsies from a compilation of past reports of patients of all stages.2

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