Our analyses of this prospective multicenter randomized controlled study showed that CEUS-guided puncture biopsy in patients with hepatitis can significantly improve diagnostic accuracy, but for nonhepatitis patients, US-guided puncture biopsy has a higher diagnostic accuracy.
Damage to liver cells in patients with hepatitis from various causes including viral and alcoholic leads to cirrhosis. Cirrhosis promotes the occurrence of hepatocellular carcinoma(20). Liver nodules on hepatitis usually undergo a process from benign hyperplastic nodules, atypical hyperplastic nodules and finally hepatocellular liver cancer(21). Due to the intricate liver texture, uneven echogenicity, and significant overlap in the ultrasound appearance of benign and malignant lesions, it is challenging to distinguish liver lesions within a cirrhotic background by conventional US(22). On CEUS, it is easier to identify the cancerous component(23), and the success rate of CEUS-guided biopsy is higher.
A prospective randomized clinical trial(24) showed the consistent conclusion of a contrast-enhanced-guided liver biopsy diagnosis of focal liver lesions developed on a background of advanced chronic liver disease. Then, in patients with a nonhepatitis liver, metastases are more common than primary liver malignant tumors, and conventional US is occasionally helpful in detecting the malignant nature of focal liver lesions by demonstrating a hypoechoic halo and infiltration of intrahepatic vessels. In addition, metastatic lesions are usually different from liver cells. Thus, a diagnosis can often be reached more easily in these cases than in patients with primary tumors, where cells more closely resemble normal liver texture.
The liver is a common site of metastasis. The most common primary lesions in patients with liver metastasis were pancreatic carcinoma (19.1%), lung carcinoma (15.8%), breast cancer (13.4%) and colorectal cancers (13.0%). All patients with liver metastases from breast cancer were accurately diagnosed by biopsy. This finding is consistent with a large-scale nationwide analysis of pathology reports(17, 25).
In this study, conventional US-guided biopsy also had a high diagnostic accuracy (92.5%), especially for nonhepatitis patients, with an accuracy rate of 97%. This may be related to multiple aspects. First, the operator has extensive operational experience in taking an optimal sample by selecting the margins of lesions to avoid necrotic areas and by recognizing the adequacy of the sampled tissue to repeat biopsy immediately if necessary. Second, lesions in a nonhepatitis background were easily identified in conventional US and easily differentiated pathologically.
Acquiring sufficient liver tissue is important for the pathologist to make firm conclusions. Guidelines on the use of liver biopsy in clinical practice(5) recommended the biopsy of focal liver nodules using an 18G needle to obtain a sample of at least 20 mm to facilitate pathological diagnosis.
In this study, 90% of patients underwent a puncture biopsy with an 18G needle. We found that the number of biopsy passes was an independent predictor of an accurate diagnosis. Higher diagnostic accuracy was obtained with 2–3 passes than with a single pass (95.1% vs. 87.3%, P < 0.001), and a continued increase in the number of punctures did not significantly improve the diagnostic accuracy (95.1% vs. 93.2%, P = 0.408). Appelbaum L et al.(26) reported the consistent conclusion that three passes would be diagnostic in almost 90% of all cases. Therefore, 2–3 passes avoid the possibility of unsatisfactory sampling with a single puncture and reduce the risk of bleeding and pain in patients with more than 3 punctures(27).
In our study, size was not found to be a significant independent prognostic factor influencing the accurate diagnostic rate. Appelbaum, Lita et al(26) reported a similar conclusion. Small hepatic lesions are more challenging to target but may have a more uniform distribution of cancerous tissue without hemorrhage, necrosis, or sclerotic changes(28). Biopsy specimens have more tissue cells for pathological diagnosis. In large lesions, US has been able to more clearly show areas of necrosis in larger lesions, obtaining satisfactory sampling.
There were several limitations to our study. First, the final inclusion of US-guided biopsy was visible lesions in conventional ultrasound; therefore, this conclusion applies to patients without hepatitis with visible lesions, and US-guided biopsy has a high diagnostic accuracy. In addition, in this study, a physician with extensive puncture experience performed the puncture and obtained a higher diagnostic accuracy of the puncture, so the influence of the operator's experience on the puncture results needs to be further investigated.