Jiawu Li

Stiffness Value and Serum Biomarkers in Liver Fibrosis Staging: Study in Large Surgical Specimens in Patients with Chronic Hepatitis B

Purpose To investigate the capabilities of stiffness value and serum biomarkers in the staging of liver fibrosis in patients with chronic hepatitis B (CHB), with pathologic findings in large surgical specimens serving as the reference standard. Materials and Methods This study was approved by the institutional review board, and informed consent was obtained from all patients. Liver stiffness (determined by means of ultrasonography-based elastography point quantification), aspartate aminotransferase-platelet ratio index (APRI), and fibrosis index (based on the four-factor Fibrosis-4 [FIB-4] calculation) were obtained in 386 patients with CHB. With pathologic fibrosis stages in large surgical specimens as the reference standard, capabilities and cutoffs of stiffness and serum biomarkers were first investigated in a cohort of 284 patients and then validated in an independent cohort of 102 patients by means of area under the receiver operating characteristic curve (AUC) analysis. Results Liver stiffness demonstrated significantly stronger correlation with fibrosis stages than did APRI and FIB-4 (r = 0.738 vs r = 0.477 vs r = 0.427, respectively; P < .05 for all). In the development cohort, liver stiffness had significantly higher AUCs in identifying fibrosis of stage 1 or higher, stage 2 or higher, stage 3 or higher, and stage 4 or higher (0.97, 0.96, 0.91, and 0.87, respectively) than APRI (0.89, 0.84, 0.73, and 0.74, respectively) and FIB-4 (0.82, 0.79, 0.70, and 0.72, respectively). In the validation cohort, liver stiffness was validated as showing significantly higher AUCs in identifying fibrosis of stage 1 or higher, stage 2 or higher, stage 3 or higher, and stage 4 or higher (0.99, 0.95, 0.89, and 0.88, respectively) than APRI (0.83, 0.76, 0.78, and 0.68, respectively) and FIB-4 (0.76, 0.69, 0.75, and 0.67, respectively). Conclusion Liver stiffness demonstrated considerable capability in identifying each stage of liver fibrosis in patients with CHB, whereas serum biomarkers showed limited capabilities. (©) RSNA, 2016 Online supplemental material is available for this article.

Hepatocellular Carcinoma: Stiffness Value and Ratio to Discriminate Malignant from Benign Focal Liver Lesions

PURPOSE To investigate the use of stiffness value and stiffness ratio (ratio of lesion to background liver parenchyma values) to discriminate malignant from benign focal liver lesions by using histologic results as the reference standard. MATERIALS AND METHODS This study was approved by the institutional review board, and written informed consent was obtained. Three hundred seventy-three patients with focal liver lesions proven at histologic examination underwent measurement of liver stiffness with elastography point quantification. First, stiffness values in two regions of the background liver parenchyma (at 0.5-2 cm and >2 cm from the lesion periphery) near 163 hepatocellular carcinomas were analyzed to determine a reference background liver for calculating the stiffness ratio. Second, the use of the lesion stiffness value and the stiffness ratio for prediction of liver malignancy was investigated in a cohort of patients with 58 benign and 201 malignant lesions. Results were validated in another independent cohort of patients with 25 benign and 89 malignant lesions by using analysis of the area under the receiver operating characteristic (AUC) curve. RESULTS The coefficient of variation for the background liver at 0.5-2 cm from the lesion was higher (196%) than that at greater than 2 cm from the lesion (66%). In the development phase, diagnostic accuracy with use of the stiffness value was significantly higher than that with use of the stiffness ratio for discrimination of malignant from benign lesions (AUC, 0.86 vs 0.66, respectively; P < .001). Diagnostic performance with the stiffness value was lower than that with the stiffness ratio (AUC, 0.53 vs 0.86, respectively; P < .001) for discrimination of cirrhotic nodules from other benign lesions. Diagnostic performance with the stiffness value was significantly lower than that with the stiffness ratio (AUC, 0.58 vs 0.71 respectively; P = .007) for discrimination of metastasis from primary liver cancers. In the validation phase, similar findings were revealed for the discrimination of malignant from benign lesions (AUC, 0.87 vs 0.67; P < .001) and discrimination between metastasis and primary liver cancers (AUC, 0.49 vs 0.73; P < .001). CONCLUSION Use of stiffness values measured in the liver parenchyma at more than 2 cm from the lesion allowed better diagnostic performance than did values measured in a region closer to the tumor. Stiffness value was more accurate than stiffness ratio for differentiation of malignant from benign focal liver lesions, but the stiffness ratio might be useful for subclassification of benign and malignant lesions. Online supplemental material is available for this article.

Effects of Vascularity and Differentiation of Hepatocellular Carcinoma on Tumor and Liver Stiffness: In Vivo and in Vitro Studies

Tissue stiffness has been found to be a useful predictor of malignancy in various cancers. However, data on the stiffness of hepatocellular carcinomas (HCCs) and their background livers are contradictory. The aim of this study was to investigate the effects of vascularity and histologic differentiation on HCC stiffness. Elastography point quantification (ElastPQ), a new shear wave-based elastography method, was used to measure liver stiffness in vivo in 99 patients with pathology-proven HCC. Lesion vascularity was assessed using contrast-enhanced ultrasound, computed tomography and/or magnetic resonance imaging. The association of HCC vascularity and differentiation with liver stiffness was determined. In addition, in vitro stiffness of 20 of the 99 surgical HCC specimens was mechanically measured and compared with in vivo measurements. We found that in vivo stiffness was significantly higher than in vitro stiffness in both HCCs and their background livers (p < 0.0001). Moreover, significantly higher stiffness was observed in hyper-vascular and poorly differentiated lesions than in hypo-vascular (p = 0.0352) and moderately to well-differentiated lesions (p = 0.0139). These in vivo and in vitro studies reveal that shear wave-based ultrasound elasticity quantification can effectively measure in vivo liver stiffness.

The preliminary application of liver imaging reporting and data system (LI-RADS) with contrast-enhanced ultrasound (CEUS) on small hepatic nodules (≤ 2cm)

To evaluate the diagnostic accuracy of liver imaging reporting and data system (LI-RADS) with contrast-enhanced ultrasound (CEUS) for patients at risk for hepatocellular carcinoma with hepatic nodules (≤2cm). We retrospectively evaluated 56 CEUS exam records of hepatic nodules (≤2cm) performed between January 2015 and July 2016 at West China hospital. Each nodule was classified into a LI-RADS-CEUS category by two radiologists according to imaging features. The ultimate CEUS categories were then compared with pathological reports and their correlation was then calculated. Inter-observer agreement for LI-RADS between reader A and B was κ, 0.690, illustrating good consistency. The diagnostic accuracy of LR-5 on hepatocellular carcinoma (HCC) was 86.49% but 11.11% for LR-M. LI-RADS-CEUS is a potential standardized categorization system for high-risk HCC patients but might also increase the false-negative diagnosis of nodules of less than 2cm.

Hepatic Venous Outflow Stenosis After Auxiliary Left Hemiliver Transplantation Diagnosed by Ultrasonic Shear Wave Elastography Combined With Doppler Ultrasonography

Abstract Hepatic vein stenosis after liver transplantation is a relatively rare complication that could even result in graft loss. However, it is difficult to arrive at a definite diagnosis at the early stage of postoperation, and there are few researches on ultrasonic shear wave elastography in the diagnosis of hepatic vein stenosis. We report the case of an 11-year-old male patient with cirrhosis due to hepatolenticular degeneration who received an auxiliary left hemiliver graft from his uncle. Massive ascites developed in 4 days after the operation. Stenosis was suspected at the site of anastomosis by Doppler ultrasonography when elevating the velocity of the left hepatic vein. Meanwhile, increased stiffness of the graft was revealed by ultrasonic shear wave elastography. The stenosis was confirmed by subsequent digital subtraction angiography. Ascites decreased gradually after the stent implantation. Our case indicates that ultrasonic shear wave elastography combined with Doppler ultrasonography is a promising method for noninvasive diagnosis of hepatic venous outflow stenosis following liver transplantation.

Impact of tumor size and cirrhotic background for differentiating HCC and ICC with CEUS: does it matter for patients undergoing hepatectomy?

Objectives The aim of this study was to investigate the role of contrast-enhanced ultrasound (CEUS) in differentiating hepatocellular carcinoma (HCC) vs. intrahepatic cholangiocarcinoma (ICC) and primary liver cancer vs. benign liver lesions for surgical decision making. Methods Data from 328 patients (296 primary liver cancer patients: 232 HCC and 64 ICC patients and 32 benign hepatic lesion patients) who underwent hepatectomy at our center were retrospectively collected from 2010 to 2015. Conventional ultrasound (US) and CEUS were performed for all patients before hepatectomy. Enhancement patterns in CEUS were classified and compared for HCC vs. ICC and for primary liver cancer vs. benign lesions. Results Primary liver cancer and hepatic benign lesions could be distinguished by CEUS in different phases. The most obvious differences were in the portal and delayed phases, in which benign lesions could still show hyperenhancement (46.9% vs. 0.0% and p < 0.001 in the portal phase; 43.7% vs. 0.0% and p < 0.001 in the delayed phase). For differentiating HCC and ICC, our results revealed that HCC and ICC displayed different enhancement patterns in the arterial phase (p < 0.001) and the portal phase (p < 0.001). In the subgroup analyses, both HCC and ICC showed a high rate of homogeneous hyperenhancement during the arterial phase when tumors were ≤5 cm (87.2% vs. 64.0% and p = 0.008) or the Ishak score was ≥5 (75.8% vs. 42.9% and p = 0.023), although there was statistical difference. However, during the portal phase, ICC > 5 cm showed significantly more frequent hypoenhancement (92.3% vs. 54.5% and p < 0.001) and less isoenhancement (7.7% vs. 45.5% and p < 0.001) than HCC; additionally, during the portal phase, there was no statistical difference in the enhancement patterns of ICC with different hepatic backgrounds. Conclusions Tumor size and hepatic background should be taken into consideration when distinguishing HCC and ICC before surgery. However, CEUS is a helpful tool for differentiating malignant and benign hepatic lesions. For patients who require surgical treatment, CEUS may help with surgical decision making.

Can ultrasound elastography identify mass-like focal fatty change (FFC) from liver mass?

Abstract Focal fatty change (FFC) may mimic liver mass on conventional B-mode ultrasound. Clinical differentiation of mass-like FFC and liver mass is important due to different clinical interventions. Contrast-enhanced imaging (CEI) or biopsy is reliable for this differentiation, but is expensive and invasive. This study aimed to explore utilities of ultrasound elastography for this differentiation. This study enrolled 79 patients with focal liver lesions (FLLs), of which 26 were mass-like FFC confirmed by at least 2 CEI modalities. The other 53 were liver masses, confirmed by pathology (n = 28) or at least 2 CEI modalities (n = 25). Lesion stiffness value (SV), absolute stiffness difference (ASD), and stiffness ratio (SR) of lesion to background were obtained using point shear-wave elastography (pSWE) and compared between FFC group and liver mass group. The performance of SV, ASD, and SR for identifying FFC from liver mass was evaluated. SV was 5.6 ± 2.4 versus 16 ± 12 kPa, ASD was 2.0 ± 1.9 versus 11 ± 12 kPa, and SR was 1.4 ± 0.6 versus 3.0 ± 1.9 for FFC and liver mass group, respectively (P < .0001). The area under the receiver operating characteristic curve of SV, ASD, and SR for discriminating mass-like FFC and liver mass was 0.840, 0.842, and 0.791, respectively (P < .05). Particularly, with cut-off ASD < 1.0 kPa, positive predictive value was 100%, specificity was 100%, and accuracy was 82% for diagnosing FFC. pSWE may be a potential useful modality for identifying mass-like FFC from liver mass, which might help reduce the necessity for further CEI or biopsy for diagnosing mass-like FFC.

Liver Stiffness and Serum Alpha-Fetoprotein in Discriminating Small Hepatocellular Carcinoma from Cirrhotic Nodule.

Aim This study aimed to investigate the clinical significance of liver stiffness and serum alpha-fetoprotein (AFP) in differentiating small hepatocellular carcinoma (HCC) from cirrhotic nodule. Methods A total of 95 chronic hepatitis B patients who were diagnosed with small HCC (n = 53) or cirrhotic nodule (n = 42) underwent ultrasound elastography point quantification (ElastPQ) examinations on lesion and background liver. Three stiffness parameters, lesion stiffness value (SV), absolute stiffness difference (ASD) of lesion and background liver, stiffness ratio (lesion/background liver) (SR), and serum AFP were retrospectively analyzed. Then, the capabilities of lesion SV, ASD, SR, AFP, and the combination of each individual stiffness parameter with AFP were evaluated in differentiating small HCC from cirrhotic nodule. Results Significantly higher lesion SV, ASD, SR, and serum AFP were observed in small HCC compared with cirrhotic nodule patients (all P ⩽ 0.0001). By comparing the stiffness parameters on the patients with AFP greater than 20 ng/mL and AFP of 20 ng/mL or smaller, a higher lesion SV and comparable ASD and SR were found in the small HCC patients. The diagnostic accuracy of lesion SV, ASD, SR, and AFP in the discrimination of small HCC and cirrhotic nodule was 0.731, 0.825, 0.820, and 0.789, respectively. Moreover, the improved sensitivity was observed in the combination of liver stiffness with AFP (83%, 100%, and 92% for lesion SV/AFP, ASD/AFP, and SR/AFP, respectively). Conclusions This study illustrated that the combination of liver stiffness and serum AFP has considerable clinical value in detecting suspicious small HCC from cirrhotic nodule.

Establishment of a novel rat model of different degrees of portal vein stenosis following 70% partial hepatectomy

Liver transplantation may fail due to complications of insufficient portal vein (PV) flow such as portal vein stenosis (PVS). Therefore, establishing a model to explore the effect of PV flow on liver regeneration is crucial and essential. Rats were randomly divided into 6 groups: sham operation rats group; 70% partial hepatectomy (PH) group (group A); PVS groups with mild, moderate, or severe stenosis (group B–D) and portal vein ligation (PVL) group. PVS was produced by ligating PV with parallelly placed needles of different gauges. Ultrasound was performed to validate the stenosis ratio (SR) and velocity ratio (VR) at the prestenotic and stenotic site. Rats were sacrificed on day 1,3,7, and 14 after surgery, and liver regeneration rate (LRR) was calculated. We successfully established rat models of different degrees of PVS following 70%PH in 72 rats. The SRs of each PVS group were 44.8 ± 5.23%, 59.3 ± 4.07% and 69.5 ± 2.17%, which showed no statistical differences compared with those measured by stenosis ratio measured by ultrasound. The survival rate in groups A-D were 100%, 83.3%, 66.7% and 50% respectively. Differences were demonstrated between groups A and C, as well as groups A and D (both P<0.05). Moreover, LRR negatively correlated with SRu and VR, and the correlation coefficients were −0.534 and −0.522, respectively. The rat model we established has the potential to be applied in most conditions of liver regeneration with reduced PV inflow, and it provides a foundation for further exploring the relationship between PV hemodynamic changes and liver regeneration.