Liver biopsy is an important diagnostic tool in pediatrics because histopathologic analysis of hepatic tissue has the potential to definitively diagnose a plethora of congenital and acquired liver diseases, determine the disease stage, assess prognosis, and define treatment options. Choices for obtaining tissue in children include surgical biopsy obtained at laparotomy, transjugular biopsy, and a percutaneous needle biopsy (with or without image guidance). For most clinical scenarios, percutaneous biopsy is the safest, simplest, and preferred technical approach.
Historically, in North America, pediatric gastroenterologists have been the subspecialists most commonly trained in and practiced at percutaneous liver biopsy in children. Indeed, this technique is considered a core skill for board certification in pediatric gastroenterology (1). In experienced hands, the procedure is relatively easily accomplished at the bedside using procedural sedation. Ultrasonography to precisely localize the position of the liver and mark the optimal needle puncture site has been variably used from center to center (2). In most instances, because of the risk of hemorrhage and other complications postbiopsy, children are typically observed in an inpatient setting for close monitoring for up to 24 hours. Retrospective reviews of large numbers of procedures have concluded that, although generally considered safe, percutaneous biopsy performed by pediatric gastroenterologists is occasionally associated with potentially serious complications and even mortality (3–11).
In recent years, pediatric interventional radiology has become a recognized discipline in tertiary care medical centers. Many children's hospitals staff pediatric radiologists trained in interventional procedures, supported by state-of-the-art imaging modalities and greatly trained staff, and dedicated interventional and sedation suites for children. As a consequence, interventional radiologists have been asked increasingly to perform percutaneous liver biopsy under procedural sedation, typically guided by ultrasonography to precisely identify the biopsy path. A recent Web-based survey of pediatric gastroenterologists found that more than one-third of pediatric gastroenterologists had not performed a percutaneous liver biopsy in the last month, the majority of these referring their patients to an interventional radiology department to perform the biopsy (2). Despite this, documentation of the safety in children of percutaneous liver biopsy performed in the setting of an interventional radiology suite is limited to 2 current reports. The first is a large series from Rome, Italy, describing 421 biopsies performed under general anesthesia (9). The second is a report of 65 biopsies in infants younger than 1 year old (7). Neither of these clinical scenarios is fully applicable to the emerging practice in children up to age 21 years here in the United States, where procedural sedation is most often used. Herein, we report a retrospective medical record review of 294 consecutive percutaneous liver biopsies performed during a period of 11 years by an interventional radiology department in a tertiary care children's hospital.
PATIENTS AND METHODS
The Nationwide Children's Hospital institutional review board approved this retrospective medical record review with a waiver of informed consent. Ultrasound-guided liver biopsies done in the Nationwide Children's Hospital's interventional radiology suite were identified by a search of the department's procedure database. A total of 331 biopsies were performed between August 15, 1995 and May 24, 2007. Thirty-seven biopsies performed on adults were excluded, leaving 294 biopsies on 249 patients with age ≤21 years. Paper charts were reviewed for procedures performed before 1998. Thereafter, the majority of information collected in the present study was obtained from review of the electronic medical record.
Data recorded for each biopsy include age, sex, weight, pre- and postbiopsy hemoglobin, platelet count, prothrombin time, biopsy needle type, number of passes made, failed biopsies, number of samples obtained, use of Gelfoam slurry or pledgets, sedation technique, biopsy indication, final diagnosis, and complications. Complications were prospectively defined as pneumothorax, bleeding, blood transfusion, sepsis, death, operative intervention, bile leak, hospital readmission, and any other serious adverse event judged to be possibly related to liver biopsy. Minor complications such as pain at the biopsy site and superficial hematomas were not recorded as an adverse event, nor were issues related to procedural sedation. Readmissions within 1 week of the biopsy were reviewed carefully for potential clinical events related to the liver biopsy. Bleeding was defined by clinical signs such as tachycardia and hypotension as well as transfusion in the first 24 hours following biopsy or a decline in hemoglobin of 2 g/dL in the first 24 hours after biopsy. A separate database containing blood bank records on each patient was reviewed to ensure that no episodes of bleeding leading to transfusion were missed by medical record review.
During the time frame covered by this study, a variety of pre- and postliver biopsy protocols were used. In most instances, outpatients were admitted the morning of the biopsy and prebiopsy blood studies including a baseline complete blood cell count and prothrombin time were obtained. Biopsies were performed using procedural sedation in the interventional radiology suite, except in 17 instances when general anesthesia was used because a concurrent surgical procedure was being performed or the patient could not be satisfactorily sedated using procedural sedation techniques. Procedural sedation with intravenous pentobarbital or midazolam in combination with fentanyl was used in most instances. Hepatic ultrasonography was conducted to identify the optimal site and biopsy approach in all of the cases. Under direct ultrasound guidance, the biopsy needle was advanced to the liver capsule and then advanced into the hepatic parenchyma using biopsy needles ranging from 14 to 22 gauge. The biopsy needles most frequently used were Bioprince 16 or 18 gauge (Angiotech, Vancouver, Canada) or Quick-Core 16 gauge (Cook, Bloomington, IN). Core lengths range from 9 to 29 mm with adjustable throw lengths. Serial biopsies were obtained by separate needle passes through the hepatic capsule or with the use of a guiding needle and a single transcapsular pass at the discretion of the interventional radiologist. In the setting of coagulopathy in which tract embolization was planned, all of the patients had a single puncture with a guiding needle through which multiple biopsy specimens were obtained. Gelfoam torpedoes or slurry was injected in the biopsy tract for 30 biopsies because of coagulopathy, a history of bleeding complications, or at the attending interventional radiologist's discretion. Pressure to the biopsy site was applied for approximately 10 minutes. A limited ultrasound was performed at the end of the procedure to evaluate for bleeding or other complications.
Two hundred ninety-four biopsies were performed on 249 patients. The patients’ ages ranged from 8 days to 20 years with a mean of 10.2 years. The patients’ weights ranged from 2.1 to 157.8 kg. The number of male and female patients were similar. Seventy-five percent of the patients were managed by the gastroenterology service, with the remainder being predominantly from the hematology/oncology service.
In patients for whom data was recorded, 1 pass was made in 6 patients, 2 passes in 118, 3 passes in 136, and 4 passes in 32. More than 2 passes were done at the request of the clinician when tumor was suspected or more tissue was needed for analysis. Two biopsy attempts failed, both in the same patient. This patient, weighing more than 100 kg, could not be sedated using intravenous medications. A repeat attempt under general anesthesia also failed because biopsy needles were not long enough to reach the targeted liver lesion because of morbid obesity.
Preoperative biopsy indications included a known or suspected mass lesion or neoplastic disorder (n = 35), a known or suspected metabolic liver disease (n = 79), known or suspected autoimmune disease (n = 44), unexplained elevation in liver enzymes (n = 31), hepatitis C (n = 25), follow-up for orthotopic liver transplant (n = 28), neonatal cholestasis (n = 31), cholestasis beyond the neonatal interval (n = 11), and suspected infectious disease involving the liver other than hepatitis C (n = 10). During the interval encompassed by this medical record review, liver transplantation was not performed at Nationwide Children's Hospital and outpatient liver biopsies were not performed; however, we include biopsies performed at our institution on liver transplant patients in cases in which the transplantation was performed at outside institutions. Twenty-nine patients received prebiopsy blood products, typically for prebiopsy anemia or coagulopathy. These were administered at the discretion of the attending physician. Fourteen received fresh frozen plasma, 11 received platelets, 9 received packed red blood cells, and 2 received factor concentrates. All 9 patients who received prebiopsy packed red blood cells had primary hematological or oncologic diseases for which the patient previously had received transfusion. Of the patients receiving prebiopsy blood products, 13 required them because of cancer or primary hematological disease, 13 because of primary liver disease, and 3 because of complications from liver transplantation.
Five patients received blood products after the biopsy. Two patients received transfusions before discharge because of baseline anemia and transfusion dependence and not because there was concern for bleeding from the biopsy or a drop in hemoglobin values. One patient received a transfusion after having a liver biopsy and concomitant multiple abdominal procedures with no evidence of bleeding from the liver biopsy. Two patients required blood products because of suspected bleeding from the liver biopsy. One patient with aplastic anemia had a 2-g hemoglobin drop postbiopsy. In this instance, prebiopsy laboratory studies showed a hemoglobin of 10.2, a platelet count of 93,000, and an international normalized ratio of 1.27. There were no clinical signs of bleeding. Another patient with leukemia had a 3.8-g hemoglobin drop, but no clinical signs of bleeding. Prebiopsy studies showed a hemoglobin of 12.3 and an international normalized ratio of 1.24. No prebiopsy platelet count was done. Seventeen patients had Gelfoam placed at biopsy sites. None had bleeding. One liver transplant recipient had a positive blood culture for Klebsiella pneumonia 2 days after biopsy. One patient with Hodgkin disease had a small pneumothorax seen on x-ray immediately after biopsy of a subdiaphragmatic lesion. A computed tomography scan 4 hours later showed complete resolution of the pneumothorax without therapy. There were no bile leaks, exploratory laparotomies, other unexpected operative procedures, or deaths.
National trends indicate an increasing number of percutaneous liver biopsies are now being done by interventional radiologists with imaging guidance (2), and anecdotal evidence suggests fewer pediatric gastroenterologists are being trained to perform this procedure. For this reason, the Accreditation Council for Graduate Medical Education's statement on program requirements for fellowship requirements in pediatric gastroenterology was recently modified to state that “fellows must understand the principles, indications, contraindications, risks, and interpretation of results of procedures.” No longer is there a requirement for technical expertise in actually performing the procedure for pediatric gastroenterology. Notwithstanding this shift in practice, there is a paucity of information about the safety of percutaneous biopsy performed by interventional radiology staff. Our retrospective study was performed to assess the safety and effectiveness of percutaneous liver biopsy by interventional radiologists in a large, tertiary care children's hospital.
All of the biopsies performed by interventional radiologists in patients younger than 21 years old were analyzed. During the interval of our analysis, no percutaneous biopsies were performed by pediatric gastroenterologists. Twenty-eight biopsies were performed in patients who had received orthotopic liver transplantation and 8 in patients who had undergone bone marrow transplantation. Fifty-one patients had cancer and 8 had known clotting disorders.
The most commonly reported complication of percutaneous liver biopsy is hemorrhage. In existing reports of large numbers (n > 50) of biopsies performed by pediatric gastroenterologists, the occurrence of bleeding requiring blood transfusion ranges from 0% to 4.5%. Table 1 summarizes selected information relating to blood transfusion, death and other serious complications from 10 such reports. The 3 most recent reports, including our own, describe procedures performed by interventional radiologists, and the remaining 7 studies report biopsy results from pediatric gastroenterologists.
In our series, a ≥2-g drop in hemoglobin occurred in 2 of 294 (0.7%) biopsies. Both patients had bone marrow failure (aplastic anemia and leukemia) and neither had evidence of coagulopathy or apparent increase in bleeding risk. In a prior report of 469 percutaneous liver biopsies performed by a pediatric gastroenterologist, 2.8% had bleeding requiring transfusion with a mortality rate of 0.6%, and patients with neoplastic disorders and bone marrow transplantation were also found to be at highest risk for postbiopsy complications (3). Thus, our retrospective review indicates that liver biopsy performed by an interventional radiologist is at least as safe as that reported in existing studies in the literature. Because some of the studies summarized in the table were performed several decades ago and under variable circumstances (eg, imaging by ultrasound), it is probably not valid to statistically compare bleeding rates when the procedure was performed by a pediatric gastroenterologist (1.9% for all of the manuscripts reviewed in the table) versus an interventional radiologist (0.6% for all of the manuscripts reviewed in the table); however, in either instance, the occurrence of bleeding is low.
No patient died as a result of the procedure in our series. Indeed, death is a rare complication regardless of the age group or the type of proceduralist. In our series, 1 patient had a positive blood culture after liver biopsy. Liver pathology revealed a posttransplant bile duct lesion not seen on prebiopsy ultrasound. This is a known complication of biopsy in posttransplant patients and is probably not affected by biopsy technique. One patient had a transient pneumothorax. This was anticipated because of the location of the subdiapragmatic tumor being biopsied. Four hours after biopsy, the pneumothorax could not be seen on computed tomography scan and required no therapy. Isolated episodes of anecdotal complications such as these are reported in nearly all of the existing reports, as depicted in the table.
Biopsy specimens were obtained in all passes except 1 patient in whom obesity precluded the needle reaching the targeted liver lesion. Tissue obtained in all of the other cases was considered adequate for diagnosis. Given this high success rate, it can be concluded that adequate biopsy material in biopsies can be obtained by interventional radiologists with virtual certainty. As shown in the table, this is also the case for existing reports of biopsies obtained by pediatric gastroenterologists, in which the success rate ranged from 87% to 100%.
In summary, complications of percutaneous liver biopsy performed by interventional radiologists, including bleeding, are rare. We conclude that liver biopsy can be safely and effectively performed in pediatric patients by an experienced interventional radiologist in the radiology suite using clinical judgment about the use of prebiopsy clotting factors and other techniques such as Gelfoam administration. Given the paucity of complications of percutaneous liver biopsy in children, whether performed by pediatric gastroenterologists or interventional radiologists, it is unlikely that specific measures to prevent such rare complications, such as the use of Gelfoam or transfused factors, can be identified in a hypothesis-driven interventional clinical trial.
1. Rudolph CD, Winter HS. NASPGN guidelines for training in pediatric gastroenterology. NASPGN Executive Council, NASPGN Training and Education Committee. J Pediatr Gastroenterol Nutr
1999; 29 (Suppl 1):S1–26.
2. Banerjee S, Bishop W, Valim C, et al. Percutaneous liver biopsy practice patterns among pediatric gastroenterologists in North America. J Pediatr Gastroenterol Nutr
3. Cohen MB, HH AK, Lambers D, et al. Complications of percutaneous liver biopsy in children. Gastroenterology
4. Lichtman S, Guzman C, Moore D, et al. Morbidity after percutaneous liver biopsy. Arch Dis Child
5. Lachaux A, Le Gall C, Chambon M, et al. Complications of percutaneous liver biopsy in infants and children. Eur J Pediatr
6. Scheimann AO, Barrios JM, Al-Tawil YS, et al. Percutaneous liver biopsy in children: impact of ultrasonography and spring-loaded biopsy needles. J Pediatr Gastroenterol Nutr
7. Amaral JG, Schwartz J, Chait P, et al. Sonographically guided percutaneous liver biopsy in infants: a retrospective review. AJR Am J Roentgenol
8. Azzam RK, Alonso EM, Emerick KM, et al. Safety of percutaneous liver biopsy in infants less than three months old. J Pediatr Gastroenterol Nutr
9. Pietrobattista A, Fruwirth R, Natali G, et al. Is juvenile liver biopsy unsafe? Putting an end to a common misapprehension. Pediatr Radiol
10. Walker WA, Krivit W, Sharp HL. Needle biopsy of the liver in infancy and childhood. A safe diagnostic aid in liver disease. Pediatrics
11. Kader HA, Bellah R, Maller ES, et al. The utility of ultrasound site selection for pediatric percutaneous liver biopsy. J Pediatr Gastroenterol Nutr