Introduction
Liver biopsy has been performed since the end of the 19th century. Paul Ehrlich (Germany) performed liver biopsy for the first time in 1883, and Sheila Sherlock described percutaneous biopsy technique in 1945 (1,2). Menghini performed biopsy with aspiration technique in 1958 (3). The first ultrasound (USG)-guided biopsy was performed in 1972 (4). Today, despite technological advancements in imaging modalities such as USG, computed tomography (CT) and magnetic resonance imaging (MRI), liver biopsy is still recognized as the gold standard method in order to establish the diagnosis, to evaluate the prognosis and to design a treatment plan (5,6).
Major indications for liver biopsy include liver neoplasm, cholestatic liver disease, presence of abnormal hepatic function tests, chronic viral hepatitis, unexplained jaundice, or evaluation of suspicious drug reactions. In addition, liver biopsy is performed to evaluate rejection or to plan treatment in liver transplantation, and to confirm the diagnosis and prognosis in diffuse liver diseases (7,8). Contraindications for liver biopsy are classified into absolute and partial contraindications. Absolute contraindications include non-cooperative patients, severe bleeding disorder (INR >1.6, platelet count <50.000), infection of the hepatic bed, and extrahepatic biliary obstruction, while partial contraindications are abdominal ascites, cyst hydatid, vascular lesions, amyloidosis, and morbid obesity (8,9). The most common complications following liver biopsy are pain and hemorrhage. Pneumothorax, hemothorax, organ perforations, biliary peritonitis, infections, and hemobilia are among the other complications which are rarely seen (8,10).
Liver biopsy is performed using three different methods: percutaneous, transvenous (transjugular, transfemoral) and surgical-laparoscopic biopsy. There are three different methods for percutaneous biopsies as palpation/percussion, radiologic marking, and real time imaging guidance (11,12). Aspiration (Menghini, Jamshidi, Klatskin) needles, manual (Vim-Silverman) or full/semi-automatic Tru-cut needles are used as the biopsy needle (8,11). Technique and needle selection may vary depending on personal experience of the physician, type of approach or biopsy indication.
In this study, we aimed to compare liver biopsy techniques performed in patients with chronic hepatitis B (CHB) and needle selection. Accordingly, we compared USG-guided real time biopsy technique performed with semi-automatic 16 gauge (G) and 18G Tru-cut needles and percutaneous liver biopsy carried out with Menghini (aspiration) needles and investigated the effects of methods used and needle selection on pathologic evaluation.
Materials and Methods
A total of 104 patients diagnosed with CHB and undergone liver biopsy in Erzincan Binali Yıldırım University Medical Faculty between 2013 and 2018 were retrospectively examined and included in the study. This study was approved by Erzincan Binali Yıldırım University Ethics Committee (approval number: 104), and informed consent was obtained from the patients. Coagulation tests were studied in all patients before the biopsy procedure, and biopsy was performed after impaired parameters were improved in patients with a risk for bleeding. The same USG device (GE Logiq P5, Korea, Sangdaewon-don; 1.6-4.5 MHz convex transducer) was used for guidance in all procedures. In biopsies performed with Menghini needle, patients were assessed with USG before the procedure to determine and mark the most appropriate site of biopsy. Similarly, patients were evaluated with USG before the procedure in biopsies performed with Tru-cut needles. The most appropriate position and biopsy site for the patients were determined. None of the patients received sedation. In all patients, the operation site was cleaned with 10% povidone iodine and after waiting for one minute, skin antisepsis was made with 72% alcohol. Local anesthesia (Prilocain, Citanest, AstraZeneca, Germany) was then applied. A small incision was made in the needle entry site. The probe was covered with a sterile sheath in the cases of Tru-cut needles. 18G Menghini (Bard Magnum, Bard Peripheral Vascular Inc. AZ, USA) needles were used in aspiration technique, while 16G 15 cm or 18G 15 cm semi-automatic Tru-cut needles (Geotek Semi-Automatic Biopsy Needle, Ankara, Turkey) were used in the real time application. Biopsy was repeated in the case of a sample length <0.5 cm. The samples were kept in formalin and evaluated by a pathologist experienced in hepatology. ISHAK score, material length, the number of viewed periportal sites, and fibrosis stage were determined for the obtained samples.
We compared and evaluated adequacy of biopsy material for histopathologic evaluation, number of pieces, rate of diagnosis, length of the obtained material, number of portal sites, and rate of complications between the methods and needle types used.
Statistical Analysis
Results of continuous variables were expressed as mean ± standard deviation, and median (minimum-maximum), while categorical variables were given as “n” and percentage (%). Pearson’s chi-square and Fisher Exact tests were used for the analysis of categorical variables. Normality of the variables was tested when statistically significant difference between the groups was analyzed. The independent samples t-test was used in comparisons of two independent groups. One way variance analysis was used to compare more than two groups. Bonferroni test was used for post hoc evaluation. A p value of less than 0.05 was considered statistically significant. Data were analyzed using IBM SPSS v.19 (IBM Corp. Released 2010. IBM SPSS Statistics for Windows version 19.0 Armong, NY, IBM Corp.) package software.
Results
In our study, 104 patients, who were diagnosed with CHB and underwent liver biopsy, were evaluated. Biopsies performed using the Menghini technique (n=26) by marking with USG and those performed with USG guidance using 16G (n=54) and 18G (n=24) semi-automatic Tru-cut needles were compared. The mean age was 40.16±14.95 (range: 17-78) years. Of all patients, 66 were male and 38 female (Table 1). No statistically significant difference was found between the groups in terms of age and gender (p>0.05).
Biopsy procedure was repeated due to the biopsy material length <5 mm in biopsies performed with 16G (n=1) and 18G (n=1). The mean material length in both methods and procedures performed with three needles was found to be 23.03 mm±8.91 with Menghini needles, 10.15 mm±3.57 with 16G Tru-cut needle, and 12.00 mm±3.35 with 18G Tri-cut needle (Figure 1). There was a statistically significant difference between the biopsies performed with Menghini method and Tru-cut method with 16G (p<0.0001) and 18G (p<0.0001) in terms of material length. No statistically significant difference was found between 16G and 18G needles in biopsies performed with Tru-cut method in terms of material length (p>0.05).
When the number of material pieces was examined; the mean piece number was found to be 1.08±0.27 with Menghini needle, 1.09±0.29 with 16G Tru-cut needle and 1.17±0.38 with 18G Tru-cut needle. No significant difference was found in number of pieces between the methods (p>0.05).
When the number of portal sites of the material taken in the biopsies performed with both methods and three needles were compared; the number of portal sites was found to be ≥6 in all biopsies with Menghini needle, 5.80±0.92 with 16G Tru-cut needle and 5.92±0.88 with 18G Tru-cut needle (Table 2). There was no significant difference in number of portal sites between the methods and needle types (p>0.05).
Fibrosis score (100%) was determined in the histopathologic examination of all biopsy materials obtained with the Menghini method. Fibrosis score could not be determined in 5 (9.3%) patients biopsied with 16G Tru-cut needle and 3 (12.5%) patients biopsied with 18G Tru-cut needle (Table 3). No statistically significant difference was found between the groups in terms of the determination of fibrosis score (p>0.05).
ISHAK score (100%) was determined in the histopathologic examination of all biopsy materials obtained with the Menghini method. Fibrosis score could not be determined in 3 (5.6%) patients biopsied with 16G Tru-cut needle and 1 (4.2%) patient biopsied with 18G Tru-cut needle. No statistically significant difference was found between the groups in terms of the determination of ISHAK score (p>0.05).
Material sufficient for histopathologic evaluation could be obtained in all patients biopsied with the Menghini technique, with a diagnosis rate of 100%. Whereas, biopsy material was not sufficient for histopathologic evaluation in 7 (8.97%) biopsies performed with 16G and 18G Tru-cut needles and diagnosis could not be established. The rate of diagnosis was found to be 90.7% and 83.3% in liver biopsies performed with semi-automatic 16G and 18G Tru-cut needles, respectively. No statistically significant difference was found between the methods and needles in terms of the rate of diagnosis in histopathologic evaluation with the obtained material (p>0.05).
Discussion
ercutaneous biopsy is a widely used interventional procedure for tissue sampling. Imaging methods are a safe tool in access of the needle to the target (13,14,15). The first preferred method is USG-guided liver biopsy because of its advantages such as evaluation of the parenchyma, imaging of the gallbladder, ability to distinguish intrahepatic main vascular structures with Doppler, not exposing patients to radiation, and being inexpensive, easy to use and portable. In addition, real time imaging is another advantage of USG-guided biopsy (15,16). Percutaneous biopsies using imaging methods have largely prevented complications of blind biopsy and unnecessary operations (10,13). The rate of complications associated with percutaneous liver biopsy is 1%-5% and the rate of mortality is 0.01%-0.009% (17). There are studies reporting that the Menghini and Tru-cut biopsy techniques have no superiority on each other in terms of complications, although there are publications reporting more pain with the Menghini method (18,19,20). Negative pressure created by the nature of the technique in blind biopsies performed with the Menghini method is thought to cause more pain at follow-up after biopsy (21). In our study, none of the patients developed major complication. This was thought to be resulted from small number of our patients and experience of the practitioner. Comparison of complications among the three groups was not included in the study as the number of complications was low.
There are many studies in the literature evaluating liver biopsy-related complications and sufficiency of establishing diagnosis with different techniques and needles of different thickness. However, we could not find a study comparing diagnostic material sufficiency specifically between Menghini and Tru-cut biopsy needle in patients with CHB (6,22,23,24,25).
Quality of liver biopsy is usually determined with length, width, fragmentation, and total number of portal triads and portal routes (26). Quality of a liver biopsy sample plays an important role in evaluation of grade and stage of liver disease in patients with CHB. Length of the material obtained with biopsy is thought to be one of the most important factors in establishing a correct diagnosis (11,23,27). Today, the number of portal triads is thought to be important for a reliable grading and staging. In general, it is accepted that the most appropriate liver biopsy sample must be 20-25 mm in length and must have more than 11 portal triads (28,29). Whereas some studies have reported that materials of 15 mm in length with at least 6-8 portal sites were sufficient for the evaluation (30). In the present study, we considered 6 and more portal triads as sufficient for evaluation.
In our study, material length was statistically significantly longer in the biopsies performed using the Menghini technique compared to those performed with Tru-cut method. However, no significant difference was found in comparisons made for determination of portal sizes, ISHAK scoring or fibrosis.
Although there are studies stating that it is possible to grade CH with 19G and thinner needles, the use of thick cutting needles is recommended in diffuse liver diseases (24,31). Since we considered that the risk of obtaining insufficient tissue with thin needles in biopsies, we preferred 16-18G. In our study, the rates of diagnosis with 16G and 18G needles were 90.7% and 83.3%, respectively, and no statistically significant difference was found between the needles in terms of establishing the diagnosis. However, our rate of diagnosis was lower compared to that in studies in the literature (25,32).
Percutaneous biopsies have become safer and more efficient with innovations in needle designs and technological advancements in imaging modalities (15).
Persons without experience on liver aspiration biopsy are more likely to obtain high-quality samples with fully automatic Tru-cut biopsy needles (15,33,34). Higher-quality tissue samples are obtained with automatic biopsy needles compared to aspiration needles in patients with advanced fibrosis or cirrhosis. Therefore, it has been stated that automatic needles should be preferred in patients with suspected advanced fibrosis or cirrhosis (35).
Study Limitation
Data about biopsy complications were insufficient because of the retrospective design of the study, and relatively lower number of patients compared to the similar studies.
Conclusion
In our study the rates of diagnosis in liver biopsies performed with 16G and 18G Tru-cut biopsies was partially lower compared to the literature. Much more portal sites could be evaluated with Menghini technique compared to the other method since longer tissue pieces were obtained with this technique. Therefore, there was no insufficient sample in biopsies performed with this technique. However, no statistically significant difference was found between this method and the other two methods in terms of pathologic evaluation. Given safety and comfort of the patient, we recommend using USG-guided Tru-cut biopsy rather than the Menghini technique, which causes more trauma.
Ethics
Ethics Committee Approval: This study was approved by Erzincan Binali Yildirim University Ethics Committee (approval number: 104).
Informed Consent: Informed consent was obtained from the patients.
Peer-review: Externally peer-reviewed.
Authorship Contributions
Surgical and Medical Practices: E.K., Concept: E.K., Design: E.K., Data Collection or Processing: E.K., F.K., M.G.B., Analysis or Interpretation: E.K., Literature Search: E.K., Writing: E.K., F.K.
Conflict of Interest: The authors declare no conflict of interest.
Financial Disclosure: The authors declare that this study has not received any financial support.