Liver stiffness measurement predicts short-term and long-term outcomes in patients with hepatocellular carcinoma after curative liver resection

doi:10.1016/j.surge.2021.01.004

The Surgeon

Volume 20, Issue 2, April 2022, Pages 78-84

https://doi.org/10.1016/j.surge.2021.01.004 Get rights and content

Highlights

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Higher liver stiffness measurement (LSM) is associated with shorter survivals.
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Patients with LSM ≥ 12 kPa had higher complication rate.
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High LSM value is the only predictive factor for late recurrence.

Abstract

Background and aim

Hepatocellular carcinoma is one of the commonest cancer in the world. Despite curative resection, recurrence remains the largest challenge. Many risk factors were identified for predicting recurrence, including liver fibrosis and cirrhosis. Transient elastography (Fibroscan) is an accurate tool in measuring liver fibrosis. This study aimed to evaluate the use of preoperative liver stiffness measurement (LSM), with Fibroscan in predicting long-term recurrence of hepatocellular carcinoma (HCC) after curative resection.

Method

A prospective cohort study was conducted from February 2010 – June 2017 in Prince of Wales hospital. All consecutive patients with HCC undergone hepatectomy were included. Demographic factors, preoperative LSM, tumor characteristics and operative details were assessed. Primary outcome and secondary outcome were overall survival and disease free survival at 1 year, 3 year and 5 year respectively.

Results

A total of 401 cases were included. Patients with LSM ≥12kPa had significantly lower 5-year overall survival rate (75.1% vs 57.3%, p < 0.001) and disease free survival rate (45.8% vs. 26.7%, p < 0.001). On multivariate analysis, pre-operative creatinine and vascular invasion of tumor were significant factors in predicting early recurrence (p = 0.012 and p = 0.004). LSM ≥12kPa were the only significant factor in predicting late recurrence (p = 0.048).

Conclusion

Pre-operative liver stiffness measurement could predict the late recurrence of hepatocellular carcinoma after curative resection.

Introduction

Hepatocellular carcinoma (HCC) is one of the commonest cancers in world-wide. Currently hepatic resection is the mainstay of curative treatment for these patients. However long-term survival remains unsatisfactory due to recurrence. Many studies have been performed to identify the risk factors for recurrence. Except tumour size or number, underlying liver fibrosis and cirrhosis is one of the risk factors for recurrence.¹

The preoperative degree of liver fibrosis predicts prognosis of disease and therefore may change the treatment modality for patients with HCC. Transient elastography (Fibroscan) is a non-invasive tool for liver stiffness measurement (LSM). It is easy to operate, quick, reproducible and accurate. It is also a useful tool for regular measurement of liver stiffness during the treatment of chronic hepatitis and monitor treatment outcome.² The use of LSM in predicting HCC prognosis is still under study. Some studies already showed preoperative LSM with Fibroscan is a predictor for postoperative complication³^,⁴ and early recurrence.5, 6, 7 This study aims to evaluate the use of preoperative LSM by Fibroscan in predicting long-term outcome of HCC.

Section snippets

Study population

A prospective cohort study of all consecutive patients undergoing hepatectomy for HCC from Feb 2010 to Jun 2017 in a tertiary hospital were recruited. All patients received detailed pre-operative assessments including LSM and indocyanine green (ICG) retention rate at 15 min (measured by pulse spectrophotometry, ≤14% as cutoff). Operability depended on preoperative computed tomography and ICG retention rate at 15min (measured by pulse spectrophotometry, ≤14% as cutoff). All patients had

Statistical analysis

All data were measured as mean ± standard deviation (SD) or median (interquartile range). Continuous variables were compared by Student t-test or Mann Whiney U test. Categorical data compared by $x^{2}$ test. Survival were compared with log-rank test and presented as Kaplan–Meier curve. Individual risk factors for recurrence were analyzed by univariate analysis and significant risk factors were included in multivariate analysis. All data were processed using SPSS version 25.

Patient characteristics

A total of 532 patients received pre-hepatectomy LSM assessment during the study period. Among them, 131 patients were excluded due to unsuitable for operation or refused operation. These patients subsequently underwent local ablation (n = 73), transarterial chemoembolization (n = 36) or systemic chemotherapy (n = 8) [Fig. 1]. As a result, a total of 401 patients finally received hepatectomy as a treatment for HCC.

Among these 401 patients, 323 (80.5%) of them were hepatitis B carrier, 29 (7.2%)

Discussion

Our study demonstrated that patients with higher LSM (≥12 kPa) had significantly worse short-term and long-term outcomes with lower 5-year overall survival rate (57.3% vs 75.1%, p < 0.001) and 5-year disease free survival rate (26.7% Vs 45.8%, p < 0.001). Higher LSM is also the only predictive factor for late recurrence (OR 2.04, p = 0.048).

Cirrhosis is a well-known strong predisposing factor for development of HCC. The degree of fibrosis is useful in predicting prognosis.⁸ Until today, liver

Declaration of competing interest

Grace LH Wong has served as a speaker for Echosens.

Vincent WS Wong has served as an advisory board member for AbbVie, Gilead and Janssen; a consultant for Merck and NovoMedica; and a speaker for AbbVie, Echosens, Gilead and Roche.

Henry LY Chan has served as a consultant and speaker for Abbvie, Bristol-Myers Squibb, F Hoffmann La Roche, Novartis Pharmaceutical, Gilead; a consultant for Janssen, a speaker for Echosens, and have received unrestricted grant for research from Roche. For the

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Cited by (8)

Value of Multimodal Data From Clinical and Sonographic Parameters in Predicting Recurrence of Hepatocellular Carcinoma After Curative Treatment
2023, Ultrasound in Medicine and Biology
The objective of the work described here was to assess the value of the combination of pre-operative multimodal data—including clinical data, contrast-enhanced ultrasound (CEUS) information and liver stiffness measurement (LSM) based on 2-D shear wave elastography (SWE)—in predicting early (within 1 y) and late (after 1 y) recurrence of hepatocellular carcinoma (HCC) after curative treatment.
We retrospectively included 101 patients with HCC who met the Milan criteria and received curative treatment. The multimodel data from clinical parameters, LSM by 2-D SWE and CEUS enhancement patterns were collected. The association between different variables in HCC recurrence was accessed using a Cox proportional hazard model. On the basis of the independent factors of early recurrence, models with different source variables were established (Clinical Model, CEUS–Clinical Model, SWE–Clinical Model, CEUS–SWE–Clinical Model). The goodness-of-fit of models was evaluated and the performance trends of different models were calculated by time-dependent area under the curve (AUC).
Two-dimensional SWE, CEUS enhancement patterns and clinical parameters (spleen length, multiple tumors, α-fetoprotein, albumin and prothrombin time) were independently associated with early recurrence (all p values <0.05). Multiple tumors and a decrease in albumin independently contributed to the late recurrence. The model fit of CEUS–SWE–Clinical Model was superior to other models in predicting early recurrence (all p values <0.05). The AUCs of the CEUS–Clinical Model were higher from 2 mo to 7 mo, while the SWE–Clinical Model had higher AUCs from 9 mo to 12 mo.
CEUS enhancement patterns and 2-D SWE were independent predictors of HCC early recurrence as the two factors contributed to the predictive performance at different times. The multimodal model, which included diverse data in predicting early HCC recurrence, had the best goodness-of-fit.
Resectable and transplantable hepatocellular carcinoma: Integration of liver stiffness assessment in the decision-making algorithm
2022, Surgery (United States)
Citation Excerpt :
Meanwhile, in the context of HCC surgery, researchers have recently shown that liver stiffness is a risk factor for hepatic decompensation after LR for HCC, with cutoff values ranging from 12 to 22 kPa.26–29 Thus, building on reports of preoperative liver stiffness measurement (LSM) as a predictor of HCC recurrence after LR30–36 and our years of experience with systematic LSM evaluation, this study was undertaken to determine the extent to which LSM could help to select candidates for LR versus LT by predicting their risk of early post-LR recurrence based on strictly preoperative and noninvasive criteria. The research ultimately aimed to propose a simple score anticipating post-LR HCC recurrence risk.
Liver resection is a curative treatment for hepatocellular carcinoma (HCC) and an alternative to liver transplantation (LT). However, post–liver resection recurrence rates remain high. This study aimed to determine whether liver stiffness measurement (LSM) correlated with recurrence and to propose a method for predicting HCC recurrence exclusively using pre–liver resection criteria.
This retrospective monocentric study included patients who had undergone LR liver resection for HCC between 2015 and 2018 and who had (1) preoperative alpha-fetoprotein scores indicating initial transplant viability and (2) available preoperative LSM data. We developed a predictive score for recurrence over time using Cox univariate regression and multivariate analysis with a combination plot before selecting the optimal thresholds (receiver operating characteristic curves + Youden test).
Sixty-six patients were included. After an average follow-up of 40 months, the recurrence rate was 45% (n = 30). Three-year overall survival was 88%. Four preoperative variables significantly impacted the time to recurrence: age ≥70 years, LSM ≥11 kPa, international normalized ratio (INR) ≥1.2, and maximum HCC diameter ≥3 cm. By assigning 1 point per positive item, patients with a score <2 (n = 22) demonstrated greater mean overall survival (69.7 vs 54.8 months, P = .02) and disease-free survival (52.2 vs 34.7 months, P = .02) than those with a score ≥2. Patients experiencing early recurrence (<1 year) presented a significantly higher preoperative LSM (P = .06).
We identified a simple preoperative score predictive of early hepatocellular carcinoma recurrence after liver resection, highlighting the role of liver stiffness. This score could help physicians select patients and make decisions concerning perioperative medical treatment.
MR elastography as a biomarker for prediction of early and late recurrence in HBV-related hepatocellular carcinoma patients before hepatectomy
2022, European Journal of Radiology
Citation Excerpt :
The potential possible reasons for explanation of this discrepancy may include: (1) LS was assessed by TE, and the majority (85.2%) of the LR patients had cirrhosis; however, TE may be inferior to MRE for assessing liver fibrosis due to its intrinsic limitations (i.e., cannot evaluate the whole liver) and the significant heterogeneity of the liver in patients with cirrhosis [34]; and (2) the majority of patients had hepatitis B virus (HBV)-related liver disease rather than hepatitis C virus (HCV)-related liver disease in our study. However, our results showed that peritumoral liver cirrhosis in pathologic results was not a significant and independent factor for LR (p = 0.321), which was consistent with other studies [32,33]. Due to the heterogeneous deposition of matrix in the liver during the fibrosis process, the degree of liver fibrosis assessed by the peritumoral tissue may not represent that of the whole liver [35].
To investigate the diagnostic performance of preoperative MR elastography (MRE) in predicting early recurrence (ER) and late recurrence (LR) of HCC after hepatectomy.
In total, 180 patients (median age, 52 years; interquartile range, 41–50 years; 161 men) who underwent conventional MRI and MRE before hepatectomy between December 2014 and April 2020 were retrospectively recruited. A preoperative clinic-radiologic model and a combined postoperative clinic-pathologic and radiologic model were built using quantitatively MRE-derived stiffnesses, and image features to predict tumor ER and LR after hepatectomy. The Cox proportional hazards model and ROC analyses were used to identify the value of parameters to predict ER and LR.
Seventy-three (40.5%) and 16 (8.9%) developed ER and LR after hepatectomy, respectively. For prediction of ER, the preoperative model integrated higher tumor stiffness (TS) (hazard ratio [HR],1.142; p < 0.001) with AFP ≥ 400 ng/mL (HR,1.761; p = 0.022), multifocal tumors (HR,3.229; p < 0.001) and lower ADC (HR,0.998; p = 0.017) variables; and the postoperative model incorporated higher TS, microvascular invasion, multifocal tumors, Child-Pugh class and ADC predictors. The two models provided comparable predictive performance (pre- 0.812 vs. post- 0.834, p = 0.283). Moreover, TS alone had a high sensitivity (90.4%) for predicting ER. Liver stiffness (LS) (HR, 1.757; p < 0.001) was the only independent predictor for LR in multivariate analysis in both the pre- and postoperative models with high specificity (90.0%), and its AUC with an optimal cut-off of 3.62 kPa was 0.860.
Quantitative MRE-based stiffness is a useful biomarker for preoperative prediction of ER and LR of HCC.
Research progress on the diagnosis, treatment evaluation and prognostic prediction of hepatocellular carcinoma using ultrasound elastography
2024, Chinese Journal of Hepatobiliary Surgery
Elastic modulus-reflected liver lesion stiffness relates to worse prognosis in pancreatic cancer patients with liver metastasis
2023, World Journal of Surgical Oncology
Tumor matrix stiffness provides fertile soil for cancer stem cells
2023, Cancer Cell International

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View full text

Liver stiffness measurement predicts short-term and long-term outcomes in patients with hepatocellular carcinoma after curative liver resection

Highlights

Abstract

Background and aim

Method

Results

Conclusion

Introduction

Section snippets

Study population

Statistical analysis

Patient characteristics

Discussion

Declaration of competing interest

Surgery

Ultrasound Med Biol

Prognostic factors for hepatocellular carcinoma recurrence

World J Gastroenterol

On-treatment monitoring of liver fibrosis with transient elastography in chronic hepatitis B patients

Antivir Ther

Liver stiffness measurement by transient elastography as a predictor on posthepatectomy outcomes

Ann Surg

Liver stiffness measurement predicts high-grade post-hepatectomy liver failure: a prospective cohort study

J Gastroenterol Hepatol

Prediction of recurrence after curative resection of hepatocellular carcinoma using liver stiffness measurement (FibroScan(R))

Ann Surg Oncol

Clinical significance of preoperative liver stiffness measurements in primary HBV-positive hepatocellular carcinoma

Future Oncol