Prediction of posthepatectomy liver failure in patients with hepatocellular carcinoma through ultrasound elastography

Abstract

In this article, we comment on the article by Cheng et al published in recently. Posthepatectomy liver failure (PHLF) remains a leading cause of hepatectomy-related mortality and can be evaluated according to liver reserve function. Liver stiffness (LS) measured by ultrasonic elastography and spleen area demonstrate a strong correlation with hepatic proliferation, fibrosis, and portal vein congestion, thus indirectly reflecting liver reserve function. This article highlights a meticulous study aimed at investigating the potential of two-dimensional shear wave elastography in assessing LS, as well as its integration with spleen area, surgical factors, and laboratory indicators, for predicting the risk of PHLF in hepatocellular carcinoma patients. In this article, we discussed the non-invasive elastography modality by ultrasound and magnetic resonance imaging to assess LS. Based on literature data, we subsequently suggested that several risk factors may contribute to PHLF, including excessive intrahepatic neutrophil accumulation, the formation of neutrophil extracellular traps, end-stage liver disease scores, and albumin-bilirubin scores. Therefore, a more comprehensive study incorporating detailed information requires further investigation.

Key Words: Posthepatectomy liver failure; Liver stiffness; Hepatocellular carcinoma; Elastography; Ultrasound; Magnetic resonance imaging

Core Tip: Posthepatectomy liver failure (PHLF) is a major cause of mortality following hepatectomy, and its risk can be assessed by liver reserve function, which is indirectly reflected by liver stiffness measured via ultrasonic elastography. A PHLF nomogram based on ultrasonic measured liver stiffness and spleen area helped to predict PHLF risk in patients with hepatocellular carcinoma.

TO THE EDITOR

Hepatocellular carcinoma (HCC) is the most frequently diagnosed liver cancer and ranks as the third-leading cause of cancer-related mortality, with approximately estimated 7.5 million deaths annually, contributing to approximately 7.8% of all cancer globally[1]. Surgical resection remains the preferred and highly effective treatment option for HCC. However, it is noteworthy that between 1% and 32% of patients may experience posthepatectomy liver failure (PHLF) following hepatectomy[2], which constitutes the primary cause of mortality among these patients within the first 30 postoperative days[3]. In this clinical setting, conducting a comprehensive and thorough preoperative assessment of liver reserve function is essential for devising a prudent surgical strategy aimed at minimizing the occurrence of PHLF. In this article, we comment on the article published by Cheng et al[4] in recently. In their study, the authors utilized the two-dimensional (2D) shear wave elastography (SWE) to quantify liver stiffness (LS) and spleen area, thereby facilitating the prediction of PHLF in HCC patients[4]. In this article, we elaborate in depth some additional techniques of ultrasonic elastography to enhance the discourse on this topic. We also endeavor to compare the disparate predictive capabilities of magnetic resonance imaging (MRI) and review the most recent literature pertaining to the assessment of LS as an indirect indicator of liver reserve function.

THE DISCUSSION OF MRI AND ULTRASOUND ELASTOGRAPHY

Elastography utilizing either MRI or ultrasound platforms has emerged as a favored non-invasive imaging modality for clinically assessing liver function, serving as a quantitative surrogate biomarker for evaluating PHLF condition[5]. The current available ultrasonic elastography techniques can be broadly categorized into strain and SWE. However, the assessment using strain elastography is limited in clinical applications due to its inability to measure the tissue stiffness. The 2D-SWE technique was chosen in this article to measure the LS, taking into account its advantages of performing in combination with routine ultrasound examination in real-time, and adjusting the region of interest in size and location by the operator. Furthermore, 2D-SWE has been extensively validated, demonstrating comparable diagnostic performance across various liver diseases, such as portal hypertension in cirrhosis[6], esophageal varices, and others, compared with vibration-controlled transient elastography[7]. In order to improve the accuracy and repeatability of the measurement, the liver parenchyma of 2 cm in diameter located 1-2 cm below liver envelope and at least 2 cm from the margin of liver mass, avoiding the intrahepatic vessels and bile duct, was selected to measure stiffness in kilo-pascals. Moreover, spleen volume was associated with a higher rate of PHLF and worse overall survival[8]. Therefore, the nomogram comprehensively evaluated the impact of relevant factors on the risk of PHLF, and visually displayed their individual contribution in this predictive model. Ultrasound elastography, particularly 2D-SWE, offers a promising non-invasive method for assessing LS and predicting the risk of PHLF in patients with HCC, yet the accuracy and reliability of this technology must be further validated in a wider patient population through additional clinical studies to confirm and optimize our findings.

However, it is widely accepted that magnetic resonance (MR) elastography is the most accurate non-invasive imaging method for detecting and quantifying LS[9], with high intra- and inter-observer agreement[10]. Equipped with requisite hardware and software, the prevalent MR elastography pulse of 2D gradient echo sequence, can be integrated into both existing clinical MR scanners and current abdominal protocols. The passive driver, positioned on the lower chest wall and right upper abdomen overlying the liver, received continuous acoustic vibrations at 60 Hz generated by the active driver and transmitted through a tube. A systematic analysis of 9 studies involving 232 patients revealed that MR elastography exhibited a consistently high area under the receiver operating characteristic curve in each stage of fibrosis, independent of body mass index and degree of inflammation[11]. For preoperative assessment of most HCC patients, the incorporation of both ultrasound and MRI examination, with particular consideration to the benefits of MR elastography, is paramount to ensure no diagnostic information is neglected. However, MRI and ultrasonic elastography each possess their distinct advantages and limitations, fueling an ongoing discussion about which modality prevails as the optimal approach. There are no studies on a comprehensive prediction model incorporating MR elastography, ultrasonic elastography, surgical factors, and clinical information to evaluate the risk of PHLF in HCC patients.

PREOPERATIVE RISK FACTORS FOR PHLF

The assessment of PHLF mainly depends on liver reserve function, which can be estimated by a diverse array of parameters, including routine blood biochemistry tests, clinical scoring systems, dynamic liver function evaluations, markers of LS and fibrosis, as well as imaging modalities[4]. In order to achieve a comprehensive assessment of PHLF occurrence in patients with HCC, this article developed a prediction nomogram that integrated various factors, including the LS data by 2D-SWE, spleen size, surgical factors of blood loss and liver resection range, and laboratory indices of alanine transaminase, prothrombin time, international normalized ratio and total bilirubin. This integrated approach indeed has the potential to provide significant predictive value for assessing risk and evaluating treatment effects, which could greatly benefit patients and their healthcare providers. The clinical reference value of such a model is undeniable, and it is imperative to validate its effectiveness in larger clinical settings. This will not only confirm its utility but also help refine the model further, potentially incorporating additional factors that could enhance its predictive accuracy.

In addition, human data together with the findings of rodent experiments emphasized the significance of excessive intrahepatic neutrophil accumulation and the formation of neutrophil extracellular traps in association with PHLF, as circulating markers of neutrophil activation correlate with indicators of intrahepatic injury[12]. Hence, more relative factors should be encompassed in the predictive model for enhanced accuracy. In the article, the correlation between the PHLF model and previous reported models of end-stage liver disease (MELD) and albumin-bilirubin (ALBI) was analyzed. Perhaps it would be even more accurate if we combined MELD and ALBI scores, blood biochemical tests, liver function examinations, and imaging data to predict the risk of PHLF in HCC patients.

CONCLUSION

In summary, this multi-center prospective study by Cheng et al[4] revolutionized clinical decision-making and patient outcomes by pioneering a novel risk prediction nomogram based on the potential of 2D-SWE techniques and comprehensive surgical-clinical data integration. This PHLF nomogram, predominantly relying on LS measured by 2D-SWE and spleen area, emerged as a superior predictor of PHLF in HCC patients, outperforming the MELD scores and ALBI scores in its predictive accuracy.

ACKNOWLEDGEMENTS

Thanks Yan-Qing Ma for his valuable contributions throughout the writing and submission process of the article.