Despite emerging technologies, such as noninvasive methods of assessment of liver fibrosis with transient elastography, percutaneous liver biopsy (PLB) continues to be an important tool for the diagnostic evaluation of liver diseases in pediatric patients. Its most known and feared complication is major bleeding, reported in about 1% of the biopsies performed in adults (1), and higher rates (3%–4%) of bleeding-related complications are reported in children (2), particularly in infants younger than 3 months (3). A variety of biopsy techniques are described, including the use of different types of needles or automated devices and the use of routine ultrasound guidance real-time vs prebiopsy (4,5). In a limited-resource scenario, with no availability of real-time ultrasound guidance, we hypothesized that PLB can be safely performed by pediatric gastroenterology trainees. The aim of this study was to compare the effectiveness and safety of PLB in children according to training level (trainees vs staff physicians).
A retrospective review of all children (younger than 18 years) undergoing PLB at a single institution between July 2010 and April 2018 was performed. Our primary objective was to compare the frequency PLB complications among physicians with different training levels. Secondarily, we aimed to assess effectiveness of the biopsies—a biopsy was considered effective if it was considered representative on histological assessment, helping to elucidate the diagnosis of the underlying liver disease. This study was exempt by our institutional review board.
Demographics, preprocedural diagnoses/indications, procedural details, laboratory data, pathologic diagnosis, and complications were recorded. For the purpose of this study, complications recorded included bleeding (minor and major), infection, bile leak or hemobilia, arteriovenous fistula, pneumothorax or hemothorax, and death. Minor bleeding was defined as the finding a hemoglobin drop >1.5 (g/dL), while major bleeding was defined by hemodynamic changes and/or the need for transfusion. Control ultrasound evaluation was not performed routinely, only in selected circumstances as per physician's discretion—in cases of persistent pain, changes in vital signs, and/or significant drop in hemoglobin performed 6 hours after procedure.
Continuous data were analyzed by the Student t test and categorical data by the Fisher exact test for the comparisons between groups—fellows vs staff physicians. All data were analyzed using software R 3.2.1 (R Core Team, 2015). Statistical tests were 2-sided, with a P value < 0.05 considered statistically significant.
The procedures were performed under sedation with midazolam and dextroketamine immediately after the puncture site was demarcated with ultrasonography. Biopsies were performed either by first-year pediatric gastroenterology fellows or by experienced staff, using suction needle (Menghini) technique. For the purposes of this study outcome analysis, all biopsies that were initiated by fellows were accounted for in the trainee's group, with rational of not artificially increasing complications in the staff group. Staff performed biopsies either in situations when a fellow was unavailable or per treating physician's discretion.
A total of 212 PLB were performed, 205 were included in this analysis (07 were excluded because the level of training of the physician who completed the biopsy was not recorded). Approximately 54.6% of patients were women, with a median age of 3.3 years (0.3; 10.6). The main indication for the biopsy was neonatal cholestasis (27.9%), followed by unexplained nonspecific elevation in liver enzymes (22%), suspected autoimmune hepatitis (17%), suspected inborn error of metabolism (6%), after liver transplant (5%), and known chronic viral hepatitis (5%). Other indications, each representing <5% of the total included Alagille syndrome, progressive familial intrahepatic cholestasis and benign recurrent intrahepatic cholestasis, focal liver lesions, and hemophagocytic lymphohistiocytosis. The biopsy was performed by trainees in 81.5% (167/205) of cases. The number of needle passes ranged from 1 to 5, with decreasing frequencies of 52.5%, 32.9%, 20.6%, 2.7%, and 1.1%, respectively. Fragments were considered appropriate for histological diagnosis in 95.6% of the biopsies performed. Drop in hemoglobin greater than 1.5 and 2.0 g/dL was registered in 14.1% and 6.3% of patients, respectively, while bleeding with clinical repercussion occurred in 0.9%–02 of the 205 cases reviewed. Both events of major bleeding occurred in the trainee group and in patients who were submitted to less than 3 punctures to obtain an adequate fragment. One of these patients needed a surgical intervention as a branch of the right hepatic vein was punctured, while the second patient was managed conservatively.
No differences were observed between the groups (fellows vs staff physicians) regarding the number of attempts/biopsy passes, drop in hemoglobin, major bleeding, technical difficulties reported during the procedure, or sampling of nonrepresentative biopsies. Table 1 summarizes the number of attempts, target laboratory data before biopsy, and hemoglobin drop after biopsy according to experience of performing physician, while frequency of imaging performed after biopsy, success rate/representative biopsy, major complications, and technical difficulties divided by groups are presented in Table 2.
There is broad spectrum of practices among different centers in respect to who is the specialist (gastroenterologists or interventional radiologists) and how percutaneous liver biopsies should be performed—in regards to the type of needle and use ultrasound guidance or not. And, although there is an increasing trend toward ultrasound-guided biopsies completed by interventional radiologists (4), previous studies do not support the conclusion that ultrasound-guided biopsies are superior in terms of safety or adequacy when compared with the use of ultrasound to mark the puncture (5), a finding that was reproducible in the pediatric population (6), or even when compared with percussion approach—but, this latest finding was reported in a study where only a very small minority of patients (50/1,011) underwent biopsy under ultrasound guidance (7).
In light of the current knowledge, the premise that experienced gastroenterologists can safely continue to perform liver biopsies without real-time ultrasound guidance is accepted (8). There is limited and controversial evidence related to the experience of the physician performing the biopsy (9). Using a relatively large pediatric study cohort of patients submitted to liver biopsies, in our institution executed by gastroenterologists without real-time ultrasound guidance, we sought to evaluate the main outcomes of the procedure in children according to level of training of the performing physician. Interestingly, the number of biopsy passes did not differ with the level of expertise, and the major complications were seen in patients who had only 1 or 2 attempts. A large observational study (n > 1800) that assessed risk factors of complication after liver biopsy including the number of biopsy passes found that performing multiple biopsy passes was not associated with severe complications (10). On the other hand, Bilreiro et al. (11) have shown that increased numbers of needle passes in ultrasound-guided liver biopsies, although not associated with major complications (not observed in this 228 patients cohort), were correlated with minor bleeding, identified on the postbiopsy ultrasound evaluation—other factors associated to minor bleeding were younger age (<3 years), low bodyweight (<16 kg), low platelet count (<70 G/L), and elevated international normalized ratio (>1.25). In another recently published pediatric study, the rate hemoglobin drop > 2 g/dL was similar to what we reported—6% (12), and although in their cohort there was no need for blood transfusion, it is important to observe that the median age of that group of patients (8.5 years) was significantly higher than our cohort of patients' median age (3.3 years), and the same is true in regards to Bilreiro et al. (11) cohort (median age 9.25) in which no major complications where reported.
Our study limitations include the well-known weaknesses of retrospective studies. As we do not perform routine imaging after procedure, minor bleeding incidents were possibly overlooked. In this study, the choice of who would perform the biopsy was at the discretion of the staff physician, so even in situations when a trainee was available for the procedure, the staff performed biopsies that s/he would judge as a high-risk intervention—although potentially a limitation, this fact actually reflects the reality of physicians in training.
In conclusion, PLB is a safe procedure in children—the incidence of major bleeding in this population is similar to that reported in adults, and, in this study, revealed a rate of major bleeding lower than what it was previously reported in pediatric literature (2) and found no significant differences in the outcomes of biopsies performed by first-year gastroenterology fellows and experienced staff physicians in a tertiary center in Brazil. A prospective and multicenter registry would provide further elements to evaluate outcomes in regards to physician experience for this procedure and potentially to help risk-stratify specific scenarios when a trainee should not perform such an intervention.
CONFLICTS OF INTEREST
Guarantor of the article: Natascha S. Sandy, MD.
Specific author contributions: N.S.S. conceptualized the article, obtained REB approval, collected the data, drafted the initial manuscript, reviewed and revised the manuscript, approved the final draft as submitted, and reviewed the final manuscript for resubmission. G.H. and M.A.B.-B. supervised Natascha throughout all the different phases of this study, analyzed the data, reviewed and revised the manuscript, approved the final draft as submitted, and reviewed the final manuscript as resubmitted.
Financial support: None to report.
Potential competing interests: None to report.
1. Padia SA, Baker ME, Schaeffer CJ, et al. Safety and efficacy of sonographic-guided random real-time core needle biopsy of the liver. J Clin Ultrasound 2009;37(3):138–43.
2. Short SS, Papillon S, Hunter CJ, et al. Percutaneous liver biopsy: Pathologic diagnosis and complications in children. J Pediatr Gastroenterol Nutr 2013;57(5):644–8.
3. Azzam RK, Alonso KM, Emerick KM, et al. Safety of percutaneous liver biopsy in infants less than three months old. J Pediatr Gastroenterol Nutr 2005;41(5):639–43.
4. Angel W, Hawkins CM, Wang JM, et al. Percutaneous hepatic and renal biopsy procedures: An 18-year analysis of changing utilization, specialty roles, and sites of service. J Vasc Interv Radiol 2015;26(5):680–5.
5. Manolakopoulos S, Triantos C, Bethanis S, et al. Ultrasound-guided liver biopsy in real life: Comparison of same-day prebiopsy versus real-time ultrasound approach. J Gastroenterol Hepatol 2007;22(9):1490–3.
6. Honar N, Jooya P, Haghighat M, et al. Complications of blind versus ultrasound-guided percutaneous liver biopsy in children. Arab J Gastroenterol 2015;16(3-4):90–3.
7. Filingeri V, Francioso S, Sforza D, et al. A retrospective analysis of 1.011 percutaneous liver biopsies performed in patients with liver transplantation or liver disease: Ultrasonography can reduce complications? Eur Rev Med Pharmacol Sci 2016;20(17):3609–17.
8. Ghent CN. Who should be performing liver biopsies? Can J Gastroenterol 2009;23(6):437–8.
9. Sporea I, Popescu A, Sirli R. Why, who and how should perform liver biopsy in chronic liver diseases. World J Gastroenterol 2008;14(21):3396–402.
10. Chi H, Hansen BE, Tang WY, et al. Multiple biopsy passes and the risk of complications of percutaneous liver biopsy. Eur J Gastroenterol Hepatol 2017;29(1):36–41.
11. Bilreiro C, Noruegas MJ, Gonçalves I, et al. Ultrasound-guided liver biopsies in children: A single-center experience and risk factors for minor bleeding. J Pediatr Gastroenterol Nutr 2017;65(2):137–40.
12. Almeida P, Schreiber RA, Liang J, et al. Clinical characteristics and complications of pediatric liver biopsy: A single centre experience. Ann Hepatol 2017;16(5):797–801.