Shear wave elastography and fibrosis-4 index for assessing liver fibrosis after hepatectomy in cirrhotic patients

Abstract

BACKGROUND

Noninvasive assessment of residual liver fibrosis after hepatectomy in patients with cirrhosis remains challenging. While shear wave elastography (SWE) and the fibrosis-4 (FIB-4) index can both be used individually for fibrosis assessment, their combined value in predicting post-hepatectomy fibrosis has not been established. We hypothesize that combining preoperative SWE with FIB-4 may more accurately predict significant postoperative liver fibrosis compared to using either method alone.

AIM

To assess whether preoperative SWE plus FIB-4 can predict significant liver fibrosis after hepatectomy in patients with cirrhosis.

METHODS

This retrospective study included 128 patients with cirrhosis who underwent hepatectomy at a tertiary hospital from January 2023 to October 2025. Postoperative histopathology divided patients into two groups: 85 patients with significant postoperative fibrosis (Scheuer ≥ S2) and 43 patients without significant postoperative fibrosis. Preoperative shear wave SWE, FIB-4, and laboratory indicators were collected. Multivariate logistic regression and receiver operating characteristic curve analysis were used, and the area under the curve (AUC) was calculated to assess predictive performance.

RESULTS

Multivariable analysis identified total bilirubin [odds ratio (OR) = 1.543, 95% confidence interval (CI): 1.038-2.294, P = 0.032], FIB-4 (OR = 4.716, 95%CI: 2.026-10.977, P < 0.001), and SWE (OR = 1.659, 95%CI: 1.211-2.273, P = 0.002) as independent predictors. Receiver operating characteristic curve analysis showed that both FIB-4 (AUC = 0.952) and SWE (AUC = 0.870) exhibited good predictive performance. When FIB-4 and SWE were used together, the AUC value reached 0.979, which was better than using either indicator alone.

CONCLUSION

Preoperative SWE combined with FIB-4 index has high predictive accuracy for significant fibrosis after liver resection in patients with cirrhosis, and is helpful for preoperative risk stratification.

Key Words: Shear wave elastography; Fibrosis-4 index; Liver cirrhosis; Hepatectomy; Liver fibrosis; Non-invasive assessment; Preoperative risk stratification

Core Tip: This study demonstrates that combining preoperative shear wave elastography with the fibrosis-4 index significantly improves the predictive accuracy of significant liver fibrosis after hepatectomy in patients with cirrhosis. The combined model achieved an area under the curve of 0.979, superior to either index alone. This non-invasive and easy-to-implement strategy facilitates more accurate preoperative risk stratification and individualized surgical planning, potentially improving patient outcomes.

INTRODUCTION

Cirrhosis is the end stage of many chronic liver diseases. Diffuse liver fibrosis, the development of regenerating nodules, and the breakdown of liver lobule structure are its hallmarks. These conditions may lead to major complications, including portal hypertension, liver decompensation, and even hepatocellular cancer[1,2]. Cirrhosis is becoming more common worldwide due to the ongoing rise in the prevalence of underlying liver illnesses like alcoholic liver disease, non-alcoholic fatty liver disease, and viral hepatitis[3]. For patients with early-stage liver cancer complicated with cirrhosis, hepatectomy is still the main treatment for potential radical cure. The liver reserve function is limited in the context of cirrhosis. While removing the lesion, hepatectomy also causes secondary damage to the remaining liver parenchyma[4]. Therefore, accurate preoperative assessment of liver reserve function and the degree of liver fibrosis is of great significance for individualized surgical decision-making, perioperative management and prognosis.

Currently, liver biopsy remains the gold standard for diagnosing liver fibrosis, but it is invasive, has sampling variability and complications, and is difficult to use repeatedly in routine clinical practice[5,6]. In recent years, non-invasive assessment methods have recently become a research focus[7]. Shear wave elastography (SWE) is an emerging ultrasound technique that quantitatively measures liver stiffness by tracking the propagation velocity of mechanically induced shear waves. Unlike transient elastography, SWE can be integrated into conventional B-mode ultrasound, enabling real-time guidance and selective measurement of regions of interest while avoiding large blood vessels and focal lesions. It has advantages such as ease of operation, high repeatability, and real-time imaging[8]. Meanwhile, serological models based on standard laboratory indicators are often used in clinical practice for screening and staging liver fibrosis due to their low cost and ease of access[9,10]. Fibrosis-4 (FIB-4) is calculated from age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count (PLT), and reflects not only liver fibrosis but also systemic inflammation and portal hypertension. However, due to the complex interactions between fibrosis, inflammation, and changes in hemodynamic parameters, the performance of any single method in patients with cirrhosis may be poor.

However, the accuracy of single non-invasive indicators in assessing patients with cirrhosis, especially those scheduled for hepatectomy, remains limited. Theoretically, combining SWE, which reflects liver structural stiffness, with the FIB-4 index, which reflects serological changes in systemic inflammation and fibrosis, holds promise for achieving complementary advantages and constructing a more comprehensive and reliable assessment model. SWE provides direct local tissue biomechanical information, while the FIB-4 index provides indirect evidence from the perspective of systemic metabolism and inflammation. The combination of the two may improve diagnostic accuracy and reduce misjudgments caused by short-term postoperative physiological disturbances[11,12]. To provide a theoretical basis and useful reference for improving preoperative risk assessment systems and patient prognosis, this study aims to explore the clinical value of SWE combined with the FIB-4 index in assessing the status of liver fibrosis after hepatectomy in patients with cirrhosis.

MATERIALS AND METHODS

General information

This retrospective study analyzed clinical data from 128 patients with cirrhosis who underwent hepatectomy at our hospital from January 2023 to October 2025. Baseline data collected from electronic medical records included demographic and anthropometric characteristics (age, sex, height, weight, and body mass index), clinical characteristics (cause of cirrhosis, indications for hepatectomy, extent of resection, and Child-Pugh classification), laboratory parameters [total bilirubin (TBIL), AST, ALT, alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), PLT, and white blood cell count (WBC)] and their derived composite indices [AST/ALT ratio (AAR), AST/platelet ratio index (APRI), and FIB-4], and imaging data (liver stiffness measured by shear wave). Elastography (SWE) and pathological data (postoperative fibrosis staging based on the Scheuer scoring system). Based on the severity of postoperative pathological liver fibrosis, participants were categorized into two groups: Those with significant post-resection fibrosis (n = 85) and those with non-significant post-resection fibrosis (n = 43). This study was approved by the ethics committee of our hospital.

Inclusion criteria: (1) Preoperative clinical diagnosis of cirrhosis; (2) Hepatectomy and complete postoperative pathological data; and (3) Complete preoperative SWE examination and laboratory test data.

Exclusion criteria: (1) Coexistence of other malignancies; (2) Presence of severe dysfunction in the heart, lungs, liver, or kidneys; (3) Diagnosis of systemic infectious conditions; and (4) Insufficient or incomplete clinical documentation.

Liver fibrosis

Histopathological evaluation was performed on liver tissue obtained from the resected surgical specimens. While this approach does not directly sample the remnant liver, growing evidence supports a strong correlation between fibrosis severity in the resected specimen and that in the residual parenchyma, particularly in patients with cirrhosis who have homogeneous fibrosis distribution. Therefore, the fibrosis stage assessed from the surgical specimen was used as a surrogate for the residual liver fibrotic burden.

Two experienced liver pathologists independently assessed the degree of fibrosis using the Scheuer scoring system[13] without knowledge of all clinical and imaging data. The system classifies fibrosis into five grades: S0 (no fibrosis); S1 (mild portal vein dilatation, no septa); S2 (moderate periportal fibrosis, occasional thin septa); S3 (severe fibrosis, with numerous interconnected septa, no regenerating nodules); and S4 (diagnosed cirrhosis, with regenerating nodules).

In this study, specimens of grade S2 and above were classified as the postoperative significant fibrosis group (hereinafter referred to as the postoperative significant fibrosis group), while specimens of grades S0-S1 were classified as the postoperative non-significant fibrosis group[14].

Blood and serum biomarker testing

Preoperative laboratory data were systematically collected, covering key hematological and biochemical markers. These included TBIL for assessing hepatic excretory function, liver enzymes (such as AST and ALT) for assessing hepatocyte integrity, and cholestasis markers (such as ALP and GGT). Additionally, PLT and WBC were recorded, reflecting coagulation status and systemic inflammatory response, respectively. Based on the test results, composite indices were calculated[15,16].

SWE inspection

All SWE examinations were performed using a Siemens Acuson S3000 ultrasound system equipped with acoustic-tactile elastography functionality, employing a convex array probe with a frequency range of 3-5 MHz. All examinations were performed by an experienced sonographer with over five years of elastography experience.

Patients were placed in a supine position with their right arm elevated after an overnight fast. A routine B-mode ultrasound was first performed to assess liver morphology and identify a suitable region of interest (ROI) with homogeneous echogenicity, avoiding major blood vessels and bile ducts. The system was then switched to SWE mode. A circular ROI with a diameter of 20 mm was placed approximately 1.5 cm below the liver capsule, maintaining an area between 0.5 and 0.8 cm².

During image acquisition, patients were instructed to hold their breath for 3-5 seconds to reduce motion artifacts. Images were considered acceptable when the elastogram image was stable, the sampling frame was uniformly filled with color and free of significant noise, and the stability index reached ≥ 4 stars. Young’s modulus (kPa) was measured at the center of the ROI on the frozen elastogram image. Five consecutive measurements were taken from the same region, and the median was recorded as the final result. Intra-observer reliability was assessed in a pre-trial sample of 20 cases, and the results showed an intra-group correlation coefficient of 0.92 [95% confidence interval (CI): 0.88-0.95], indicating excellent repeatability.

Statistical analysis

All statistical analyses were performed using IBM SPSS Statistics version 21.0. Continuous variables were presented as mean ± SD and compared using t test. Categorical variables were expressed as n (%) and analyzed using χ² test. Variables with P < 0.05 in univariable analysis were considered for multivariable modeling. Collinearity was assessed using the variance inflation factor (VIF); variables with VIF ≥ 5 were excluded. Independent predictors were identified using backward-stepwise binary logistic regression, with results reported as adjusted odds ratios (OR) and 95%CI. Discriminative performance was evaluated using receiver operating characteristic curves, with the area under the curve (AUC). A two-tailed P < 0.05 was considered statistically significant.

RESULTS

Baseline characteristics overview

Among 128 cirrhotic patients, 85 were classified into the significant post-resection fibrosis group (Scheuer stage ≥ S2) and 43 into the non-significant group (Scheuer stage S0-S1). No significant differences were observed in age, sex, body mass index, cirrhosis etiology, indication for hepatectomy, extent of resection, Child-Pugh class, ALT, or GGT (all P > 0.05), whereas significant differences were found in TBIL, AST, ALP, PLT, WBC, AAR, APRI, FIB-4, and SWE (all P < 0.05). Details are provided in Table 1.

Table 1 Baseline characteristics overview, n (%)/mean ± SD.

Grouping	Significant post-resection fibrosis group (n = 85)	Non-significant post-resection fibrosis group (n = 43)	t/χ2	P value
Age (years)	54.42 ± 7.24	54.30 ± 6.73	0.092	0.927
Gender			1.006	0.316
male	58 (68.24)	33 (76.74)
female	27 (31.76)	10 (23.26)
BMI (kg/m2)	23.87 ± 3.76	25.09 ± 4.23	1.662	0.099
Cirrhosis etiology			1.298	0.730
Viral hepatitis	58 (68.24)	27 (62.79)
Alcohol-related	12 (14.12)	7 (16.28)
MASLD	7 (8.23)	6 (13.95)
Other/mixed	8 (9.41)	3 (6.98)
Indication for hepatectomy			0.307	0.858
Hepatocellular carcinoma	70 (82.35)	34 (79.07)
Benign lesions	9 (10.59)	6 (13.95)
Other malignancies	6 (7.06)	3 (6.98)
Extent of resection			1.493	0.222
Major hepatectomy (≥ 3 segments)	33 (38.82)	12 (27.91)
Minor hepatectomy (< 3 segments)	52 (61.18)	31 (72.09)
Child-Pugh class			2.102	0.147
A	59 (69.41)	35 (81.40)
B	26 (30.59)	8 (18.60)
TBIL (μmol/L)	18.75 ± 2.13	17.09 ± 1.91	4.304	< 0.001
AST (U/L)	137.21 ± 38.84	92.30 ± 35.96	6.331	< 0.001
ALT (U/L)	105.07 ± 25.58	96.32 ± 25.41	1.831	0.069
ALP (U/L)	112.11 ± 20.43	102.50 ± 16.80	2.660	0.009
GGT (U/L)	57.96 ± 14.21	58.10 ± 10.10	0.064	0.949
PLT (× 109/L)	325.87 ± 35.66	339.51 ± 30.20	2.148	0.034
WBC (× 109/L)	7.95 ± 2.42	6.90 ± 1.80	2.515	0.013
AAR	1.29 ± 0.68	0.94 ± 0.18	12.316	< 0.001
APRI	1.03 ± 0.19	0.66 ± 0.21	10.084	< 0.001
FIB-4	2.20 ± 0.35	1.44 ± 0.32	12.030	< 0.001
SWE (KPa)	11.50 ± 3.10	6.80 ± 2.80	8.356	< 0.001

BMI: Body mass index; MASLD: Metabolic dysfunction-associated steatotic liver disease; TBIL: Total bilirubin; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transferase; PLT: Platelet count; WBC: White blood cell count; AAR: Aspartate aminotransferase to alanine aminotransferase ratio; APRI: Aspartate aminotransferase to platelet ratio index; FIB-4: Fibrosis-4 index; SWE: Shear wave elastography.

VIF collinearity screening

Multicollinearity analysis was performed on nine variables that had statistical significance in the univariate analysis. Based on the VIF screening results, the VIF values for AST, PLT, AAR, and APRI were all > 5, indicating strong multicollinearity. According to statistical principles, when high collinearity exists among variables, it is necessary to screen for indicators that have a more critical impact on the dependent variable. Therefore, TBIL, ALP, WBC, FIB-4, and SWE were ultimately included.

Logistic regression analysis

The importance of hepatic fibrosis following hepatectomy in patients with cirrhosis was the dependent variable in a logistic regression analysis of the aforementioned five variables. After controlling for confounding factors (ALP and WBC), the independent risk factors for significant post-resection fibrosis after hepatectomy in patients with cirrhosis were found to be elevated levels of TBIL (OR = 1.543, 95%CI: 1.038-2.294, P = 0.032), FIB-4 (OR = 4.716, 95%CI: 2.026-10.977, P < 0.001), and SWE (OR = 1.659, 95%CI: 1.211-2.273, P = 0.002). Details are provided in Tables 2 and 3.

Table 2 Univariate logistic regression results.

Variable	β	SE	Wald	OR (95%CI)	P value
TBIL	0.440	0.205	4.622	1.553 (1.040-2.321)	0.032
ALP	-0.006	0.021	0.084	0.994 (0.955-1.035)	0.771
WBC	0.039	0.221	0.030	1.039 (0.674-1.604)	0.861
FIB-4	1.594	0.452	12.437	4.923 (2.030-11.940)	< 0.001
SWE	0.510	0.165	9.590	1.664 (1.206-2.298)	0.002
Constant	-16.936	3.914	18.723	< 0.001	< 0.001

OR: Odds ratio; CI: Confidence interval; TBIL: Total bilirubin; ALP: Alkaline phosphatase; WBC: White blood cell count; FIB-4: Fibrosis-4 index; SWE: Shear wave elastography.

Table 3 Multivariate logistic regression results.

Variable	β	SE	Wald	OR (95%CI)	P value
TBIL	0.434	0.202	4.598	1.543 (1.038-2.294)	0.032
FIB-4	1.551	0.431	12.950	4.716 (2.026-10.977)	< 0.001
SWE	0.506	0.161	9.929	1.659 (1.211-2.273)	0.002
Constant	-17.070	3.934	18.828	< 0.001	< 0.001

OR: Odds ratio; CI: Confidence interval; TBIL: Total bilirubin; FIB-4: Fibrosis-4 index; SWE: Shear wave elastography.

Results of the receiver operating characteristic curve

Receiver operating characteristic curve results showed the efficacy of each indicator and the combined model in assessing significant post-resection fibrosis after hepatectomy with cirrhosis. FIB-4 showed the best assessment efficacy (AUC = 0.952), followed by SWE (AUC = 0.870), while TBIL was the weakest (AUC = 0.718). The AUC of FIB-4 combined with SWE (model 1) was 0.979, and the AUC of all three combined (model 2) was 0.985. The combined model’s predictive efficacy was significantly better than that of a single indicator. Details are provided in Table 4 and Figure 1.

Figure 1 The results of the receiver operating characteristic curve. AUC: Area under the curve.

Table 4 Results of the receiver operating characteristic curve.

Variable	AUC	Youden index	Optimal cutoff value	Sensitivity (%)	Specificity (%)	95%CI	P value
TBIL	0.718	0.379	18.37	56.47	81.40	0.631-0.794	< 0.001
FIB-4	0.952	0.789	1.86	85.88	93.02	0.899-0.982	< 0.001
SWE	0.870	0.601	10.38	67.06	93.02	0.799-0.923	< 0.001
Model 1	0.979	0.836	0.842	85.88	97.67	0.937-0.996	< 0.001
Model 2	0.985	0.882	0.847	88.24	99.40	0.946-0.998	< 0.001

AUC: Area under the curve; CI: Confidence interval; TBIL: Total bilirubin; FIB-4: Fibrosis-4 index; SWE: Shear wave elastography.

DISCUSSION

This retrospective study included 128 cirrhotic patients who underwent hepatectomy to explore the predictive value of preoperative liver stiffness (SWE) and the serum-based FIB-4 index for significant post-resection fibrosis. TBIL, FIB-4, and SWE were independent predictors of significant post-resection fibrosis. The FIB-4 index demonstrated excellent predictive power (AUC = 0.952), and SWE also showed good predictive power (AUC = 0.870). More importantly, the combined model of FIB-4 and SWE (model 1, AUC = 0.979) and the combined model including TBIL (model 2, AUC = 0.985) showed significantly better predictive ability than any single indicator, confirming the superiority of multi-indicator combined assessment strategies in preoperative risk assessment of hepatectomy in patients with cirrhosis.

Univariate analysis in this study revealed significant inter-group differences in multiple parameters. Notably, patients with significant postoperative fibrosis exhibited higher levels of TBIL, AST, ALP, and APRI, as well as lower levels of PLT and WBC. These findings are biologically plausible: Elevated TBIL reflects impaired hepatic excretion secondary to late-stage fibrosis; decreased PLT is a recognized surrogate marker of portal hypertension and splenic retention; and elevated APRI and FIB-4 integrate hepatocellular damage and impaired platelet synthesis into a comprehensive score associated with fibrosis burden. The higher SWE values in the group with significant postoperative fibrosis further confirm the direct relationship between tissue stiffness and the degree of extracellular matrix deposition. In conclusion, these univariate differences highlight the multifaceted nature of fibrosis assessment, encompassing biochemical, hematological, and biomechanical aspects.

Although liver biopsy is still the gold standard for staging hepatic fibrosis, its use in regular preoperative assessment is limited due to its inherent invasiveness, potential risk of complications, and sample inaccuracy[17,18]. Therefore, developing accurate and non-invasive evaluation instruments remains a focus of medical studies[19]. Serological models such as FIB-4 and APRI are widely used due to their simplicity and cost-effectiveness[20]. This study confirms the fact that FIB-4 index has an excellent accuracy for significant post-resection fibrosis in patients undergoing liver resection for cirrhosis, which is consistent with previous studies showing that FIB-4 has high diagnostic efficacy for terminal inflammation and cirrhosis in individuals who have chronic liver disease[21,22]. Age, AST, ALT, and PLT are all integrated by FIB-4, which indirectly represents liver inflammatory activity, synthetic function, possible fibrotic process, and portal hypertension[23,24]. Meanwhile, imaging elastography techniques, such as SWE, provide structural mechanics basis for assessing liver fibrosis by directly and quantitatively measuring liver stiffness[25,26]. Preoperative liver stiffness is closely linked to the fibrotic load of the postoperative residual liver, according to this study, where SWE values were significantly higher in the significant post-resection fibrosis group than in the non-significant group and were an independent risk factor. The advantages of SWE are that it can provide focal, real-time tissue stiffness information, and it is simple to operate, highly repeatable, fast in imaging, and has a high success rate in quantitative measurement[27].

However, single indicators inevitably have limitations. Serological indicators are easily affected by general condition and non-hepatic factors; while SWE may be affected by factors such as operator experience, measurement location, hepatic steatosis or congestion[28,29]. This study found strong collinearity among indicators such as AST, PLT, AAR, and APRI through VIF analysis, which suggests that variables should be carefully selected to avoid redundancy when constructing multivariate models. The variables ultimately included in the multivariate model were TBIL, FIB-4, and SWE, providing information from three different dimensions of liver function (bile excretion), serological composite index, and tissue mechanics, respectively, achieving complementary advantages. The combined model (models 1 and 2) has an AUC close to 0.99, showing excellent discrimination ability, and its sensitivity and specificity are also improved simultaneously. This provides clinicians with a powerful tool to more accurately identify high-risk patients preoperatively who are likely to develop significant post-hepatectomy fibrosis (i.e., poor residual liver reserve).

The clinical significance of this study lies in providing an efficient, non-invasive, quantitative method for preoperative assessment of hepatectomy in patients with cirrhosis. By combining readily available blood parameters with rapid ultrasound elastography, a more comprehensive non-surgical assessment of liver injury can be performed preoperatively. This helps surgeons better balance tumor resection with preservation of adequate liver parenchyma in surgical decisions, optimize surgical planning, predict postoperative liver function compensation, and develop individualized perioperative management strategies, potentially improving patient outcomes.

This study has several limitations. First, the single-center retrospective design and relatively small sample size may introduce selection bias, and the lack of internal validation (e.g., bootstrapping) suggests that the reported AUC values require external validation. Second, the study population was limited to cirrhotic patients who underwent hepatectomy, limiting the applicability of the results to non-surgical patients or other chronic liver disease populations. Third, the relatively high PLTs observed may reflect selection bias, as patients with severe thrombocytopenia may have been excluded due to surgical risks. Fourth, fibrosis staging was assessed based on the resected specimen rather than the residual liver, although a strong correlation existed between the two in patients with homogeneous fibrosis distribution. Fifth, this study did not quantitatively analyze inter-observer variability. The lack of clarity regarding measurement variability among different operators may limit the application and wider adoption of SWE in broader clinical settings. Future multicenter prospective studies are needed to validate the applicability of our findings across different etiologies and populations.

CONCLUSION

Preoperative SWE combined with the FIB-4 index has high clinical value in predicting significant liver fibrosis after hepatectomy in patients with cirrhosis. This combined strategy is non-invasive, convenient, and economical, and is expected to become a powerful auxiliary tool for preoperative risk assessment of hepatectomy in patients with cirrhosis, providing an important reference for achieving more precise individualized treatment management in clinical practice.