What Is Known
- Image-guided liver biopsy is used in managing pediatric liver disease.
- Percutaneous liver biopsy is generally considered to be a minor procedure, although is not without risk.
- Transjugular liver biopsy is often favored in adult high-risk patients; however, transjugular liver biopsy is more challenging in small children due to equipment and patient size mismatch.
What Is New
- Gelatin sponge pledgets in solid form can be loaded into the coaxial needle using 16 G angiocaths for percutaneous liver biopsy tract embolization.
- Our study demonstrated no statistically significant difference in complications between transjugular liver biopsy and percutaneous liver biopsy with tract embolization.
- Percutaneous liver biopsy with gelatin sponge pledget tract embolization may be considered as first-line approach in children.
Image-guided liver biopsy is often used to obtain tissue samples for diagnosis, prognosis, and management of hepatic diseases in children (1). The role of biopsy has evolved with the recent development of noninvasive diagnostic tools, such as magnetic resonance imaging (MRI) elastography and ultrasound (US) elastography (2). If the decision is made to proceed with liver biopsy, 4 techniques are available: blind needle biopsy without imaging guidance, image-guided percutaneous needle biopsy (using US or computed tomography), transjugular liver biopsy (TJLB) with US and fluoroscopic guidance, or surgical biopsy during laparoscopy or laparotomy (3). Image-guided percutaneous biopsy may also be performed with or without coaxial needle technique, which allows for tract embolization following the biopsy. In the pediatric population, percutaneous liver biopsy (PLB) with or without tract embolization is currently considered the most favorable approach in many clinical situations (1).
PLB is generally considered to be a minor procedure, although is not without risk. There have been multiple reported complications after PLB procedures, including abdominal wall pseudoaneurysm, pneumothorax, sepsis, and severe hemorrhage (1,4–7). Prior studies also report higher complication rates after PLB in children compared to adults (8,9).
The optimal diagnostic approach remains controversial in high-risk patients with coagulopathy or ascites which may preclude standard PLB. In many practices, patients at higher risk for complications who require liver biopsy are often referred for TJLB. In high-risk adult patients, TJLB has been found to have a relatively low morbidity and mortality (10). Although TJLB is often favored in high-risk adult patients, this approach is more challenging in small children. Downsides for this approach in children include radiation exposure, equipment and patient size mismatch, risk of inadvertent capsular puncture, and risk of arrhythmia with wire manipulation in the right atrium. In addition, TJLB specimens have historically been considered inferior to PLB specimens owing to their smaller size and excessive fragmentation (11).
Image-guided PLB with gelatin sponge embolization of the biopsy tract has been suggested as a strategy to minimize bleeding complications in high-risk patients (12). This technique has theoretical advantages because biopsy specimens are often larger, real-time US imaging guidance is possible, and there is deployment of a physical barrier that can expand within the biopsy tract (13). The gelatin sponge pledgets remain in solid form when deployed during tract embolization as opposed to the liquid slurry (consisting of a gelatin sponge sheet suspended in 5–10 mL saline) that can be injected into the biopsy tract. The purpose of this study is to compare the safety and efficacy of TJLB and PLB with tract embolization in pediatric patients with liver disease in our tertiary care pediatric interventional radiology practice.
MATERIALS AND METHODS
This study is a retrospective review of liver biopsies performed by interventional radiologists at a tertiary care pediatric institution from December 2009 and October 2015. All consecutive patients aged <19 years at time of procedure were included. Institutional review board approval and a waiver of consent were granted for this retrospective study. All procedures were performed by 1 of 3 interventional radiology physicians ranging in experience from 3 to 28 years. Informed consent was obtained in all cases. Patient age, weight, pre- and postbiopsy laboratory values (including hemoglobin, hematocrit, international normalized ratio [INR], platelets), procedural records (including biopsy approach, gauge of biopsy needle, number of cores), adequacy of biopsy sample in pathology reports, and intra- and postprocedural complications were recorded after review of the electronic medical record and imaging.
Transjugular Liver Biopsy Technique
TJLB was performed according to the previously reported techniques using US and fluoroscopic guidance (14). A 19 G Cook TJLB set (Cook, Bloomington, IN) was used in all cases. The number of passes obtained was at the discretion of the interventional radiologist, typically between 3 to 5 samples.
Percutaneous Biopsy Technique With Gelatin Sponge Pledget Tract Embolization
Preprocedure focused US of the abdomen was performed to determine optimal percutaneous access site for biopsy. Under real-time US guidance (8–12 MHz curved or 15 MHz linear transducer), a 17 or 15 G coaxial guide needle (Argon, Temno, Bard, Cook) was advanced into the liver parenchyma (Fig. 1A). The stylet was removed and an 18 or 16 G cutting biopsy needle was advanced into the liver parenchyma through the coaxial guide needle. Color Doppler was often used to assist in avoiding large vascular structures. The number of passes obtained was at the discretion of the interventional radiologist, typically between 2 and 5 samples. For tract embolization, gelatin sponges were cut into thin strips and loaded into 16 G angiocaths. The preloaded gelatin sponge pledgets were placed into the coaxial guide needle using the angiocaths and deployed along the biopsy tract using the coaxial stylet. Using real-time US guidance, deployment of individual gelatin sponge pledgets was repeated until the entire biopsy tract, including liver capsule, was lined with pledgets as the coaxial guide needle was gradually withdrawn (Fig. 1B) (13). In the setting of ascites, a 5-French sheathed Yueh needle was placed near the planned access site for PLB and paracentesis was performed before biopsy.
All outpatients were admitted overnight and all inpatients remained inpatient for at least 24 hours of observation, according to routine practice at our institution. Our postbiopsy observation policy is consistent with the position statement on outpatient liver biopsy by the European Society for Pediatric Gastroenterology Hepatology and Nutrition from 2015 and per provider preference our patients were admitted for observation for at least 1 overnight stay (2). Postbiopsy labs and imaging were not performed consistently.
Procedure-related complications were classified according to the reporting standards and recommendations of the Society of Interventional Radiology (15). Technical success was defined as obtaining liver core biopsy tissue samples. Diagnostic quality was defined as obtaining adequate sampling for a pathologic diagnosis.
Analysis of nominal variables was performed with Chi-square test and analysis of continuous variables was performed with Mann-Whitney U test. Statistical significance was determined at the 95% confidence interval. P values <0.05 were considered statistically significant.
During the study period, there were 39 TJLB and 120 PLB performed. The patient characteristics are outlined in Table 1. In general, the TJLB patients were older and heavier and had lower platelets and higher INR as compared with the PLB patients.
Coaxial approach was used for all PLB. The PLB were performed with 18-gauge biopsy needle through 17-gauge coaxial needle in 69.2% procedures and 16-gauge biopsy needle through 15-gauge coaxial needle in 30.8% procedures. For the PLB, the left lobe was accessed via a subxiphoid approach in 72.5%, right lobe via subcostal or intercostal approach in 21.7%, and other approach in 5.8% procedures. There were 11 high-risk patients undergoing PLB who had INR >1.5. Subxiphoid approach was used in 7 patients, subcostal approach in 3 patients, and right lateral approach in 1 patient.
The TJLB procedures were performed via the right internal jugular vein access in 94.8% patients and the left internal jugular vein in 5.2% patients. Pressure measurements were documented in 20.5% of TJLB procedures.
In our series, 74 of 120 (61.7%) of percutaneous biopsies were performed on liver transplants and 7 of 39 (17.9%) of transjugular biopsies were performed on liver transplants. There was a mixture of split left lobe grafts and whole liver transplants in the study population.
The postbiopsy laboratory values, samples obtained, diagnostic quality, and complication rates are outlined in Table 2. All TJLB and PLB procedures were technically successful and yielded liver core samples. Complication rates were 2.6% for the TJLB group and 3.3% for the PLB group (P value = 0.81).
The TJLB group had 1 (2.6%) complication of supraventricular tachycardia in a 16.3-year-old male with native liver and elevated LFTs, requiring adenosine cardioversion and intensive care unit (ICU) admission. The PLB group had 4 (3.3%) complications. A 14.3-year-old boy underwent subxiphoid approach PLB 2 weeks after liver transplant for methylmalonic acidemia, and developed postbiopsy hemoperitoneum on US and CT with decreased hemoglobin by 4.8, requiring transfusion. A 2-year-old girl underwent subxiphoid approach PLB, 2 weeks after liver transplant for acute liver failure of unknown etiology, and developed hypotension after biopsy and received transfusion despite minimally decreased hemoglobin by 0.9. A 2-month-old girl (weight 3.5 kg) with intrauterine growth restriction/small for gestational age and jaundice underwent native liver right subcostal approach PLB and developed postbiopsy decrease in hemoglobin by 3.2 and received transfusion. A 9-year-old boy with elevated LFTs underwent subxiphoid approach PLB approximately 7 years after liver transplant for unknown etiology liver disease, and developed bilious drainage from the access site.
The PLB complications did not occur in high-risk coagulopathic patients, as the patients with complications had platelets >80 and INR <1.7. The patient (<5 kg) who had a postbiopsy decreased hemoglobin did have small volume ascites; however, no hemorrhage was found on 2 postbiopsy US examinations. No patient who developed complications after PLB had moderate or large-volume ascites.
There was no statistically significant difference between the TJLB and PLB groups in technical success rate, diagnostic quality, or complication rate.
Liver biopsy is often used in the diagnostic workup for hepatic disease in children because of its high reliability and overall low mortality and morbidity (16). The optimal diagnostic approach in high-risk patients with coagulopathy or ascites which may preclude standard PLB is still controversial. Although some patients may be referred for TLB in this setting, image-guided PLB with gelatin sponge pledget tract embolization has also been suggested as a strategy to minimize bleeding complications in high-risk patients. The purpose of the present study was to evaluate the safety and efficacy of TJLB compared to PLB with gelatin sponge pledget tract embolization in pediatric patients.
Although the published adult liver biopsy literature suggests bleeding rate of 1% and diagnostic yield of 98%, pediatric studies have described complication rates ranging from 5% to 20% and diagnostic accuracy of 86% (1,3,9). In a large series of 213 pediatric liver biopsy patients (average weight 22 kg) a complication rate of 10% for PLB was described; however, the gelatin sponge tract embolization technique was not used (8). Another series of 67 high-risk pediatric patients who underwent PLB with tract embolization (average weight 6 kg) included patients with additional risk factors for complications including coagulopathy, thrombocytopenia, and ascites (13). That study found no bleeding complications and suggested that the use of gelatin sponge pledget tract embolization technique likely contributed to the lack of complications. In the adult population, TJLB has been found to have a low major morbidity and mortality compared with PLB; however, PLB with gelatin sponge tract embolization has also been described as an alternative to TJLB in adult patients at high risk of bleeding (17–22). In our study the complication rates were not statistically significantly different between the TJLB and PLB groups, 2.6% and 3.3%, respectively. One of our PLB patients developed hemoperitoneum on imaging requiring transfusion and another PLB patient had a decrease in hemoglobin without imaging abnormalities and received blood products.
There was a mixture of split left lobe grafts and whole-liver transplants in our series. Our biopsy approach was typically subxiphoid for both types of allografts. The authors do not feel that the type of graft substantially changed our biopsy approach. We generally favor subxiphoid approach in pediatric patients due to the small size of intercostal spaces and often excellent sonographic window in subxiphoid approach due to the superficial position of the liver.
TJLB specimens have historically been considered inferior to PLB specimens due to their smaller size and excessive fragmentation (23). In our study, statistically significantly more biopsy passes were obtained in the TJLB group than the PLB group, possibly due to small size or fragmentation of samples. We, however, found no statistically significant difference in diagnostic accuracy between PLB and TJLB groups, with each group having 1 nondiagnostic specimen.
There are more than 64 series totaling more than 7000 TJLB in the adult literature (10). In contrast, TJLB has not been well studied in the pediatric population. Ours is one of the largest series of TJLB patients in the pediatric literature to date. We found that both TJLB and PLB with tract embolization proved to be safe and effective for obtaining adequate liver tissue, and both were appropriate for high-risk patients with contraindications for standard PLB approach. We did not observe any bleeding complications in the TJLB group. The only complication in the TJLB group was cardiac arrhythmia related to wire manipulation in the right atrium during catheter selection of the inferior vena cava and hepatic vein, which resolved following adenosine cardioversion and ICU admission.
There are 2 large published studies in adult patients comparing TJLB and PLB. In the first study comparing 100 patients, they found that the TJLB samples were on average smaller than those obtained by PLB. Complications were higher in the PLB group (3.5%) compared to no complications in the TJLB group. The PLB were not performed with tract embolization in this study (21). In the second adult series of 329 patients comparing TJLB and PLB, they found no major complications in either group and both techniques yielded sufficient tissue diagnosis. The PLB technique in this series used gelatin sponge tract embolization which was credited for the lack of bleeding complications (18).
There are limitations to our retrospective study. It is a retrospective analysis with a limited number of patients, particularly in the TJLB group. There was an unequal number of patients in the TJLB and PLB groups. The study population was not fully matched statistically, with the TJLB group patients being older, larger, and more coagulopathic than the PLB group. Several operators with variable levels of experience performed the biopsy procedures. There was also operator preference in selecting PLB versus TJLB approach. Throughout the study period, more PLB and fewer TJLB were performed once the authors recognized that the gelatin sponge pledget tract embolization technique was successful in patients with coagulopathy and/or ascites. If hepatic vein pressures measurements were requested, then transjugular biopsy approach was typically selected (Although the authors do recognize that hepatic vein pressure measurements can be performed through internal jugular or femoral access with a small 4- or 5-French sheath and then liver biopsy can subsequently be performed percutaneously in small patients.). Transjugular approach would also be favored in patients with poor sonographic window or in patients undergoing subsequent cardiac catherization requiring full heparinization immediately after biopsy. In addition, postbiopsy laboratory values and imaging were not performed routinely on all cases. Nevertheless, this is one of the largest pediatric liver biopsy comparative series in the medical literature. Further prospective studies are needed to confirm our results.
In conclusion, TJLB and PLB with gelatin sponge pledget tract embolization are both safe and effective for the diagnosis of hepatic disease in pediatric patients. Our study demonstrated no statistically significant difference between TJLB and PLB with tract embolization in technical success rate, diagnostic quality, or complication rate. We confirmed that PLB with tract embolization in pediatric patients has a lower complication rates than the published pediatric liver biopsy literature even in high-risk patients. PLB avoids radiation exposure and can be performed quickly at the bedside in critical ICU settings. Therefore, PLB with gelatin sponge pledget tract embolization may be considered as first-line approach in the pediatric population, even in the setting of coagulopathy.
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