Diagnostic Performance For Hepatocellular Carcinoma Research Articles

Suboptimal performance of LI-RADS v2018 on gadoxetic acid-enhanced MRI for detecting hepatocellular carcinoma in liver transplant candidates.

To evaluate the diagnostic performance for hepatocellular carcinoma (HCC) detection of the Liver Imaging Reporting and Data System (LI-RADS) version 2018 on gadoxetic acid-enhanced MRI, comparing liver transplant candidates (LT group) with patients who underwent surgical resection (SR group), and to determine significant clinical factors for diagnostic performance of LI-RADS v2018. Patients who underwent gadoxetic acid-enhanced MRI and subsequent SR or LT for HCC were retrospectively included between January 2019 and December 2020. The sensitivity and specificity of LI-RADS LR-5 for HCC were compared between the two groups using generalized estimating equations. The accuracy of patient allocation according to the Milan criteria was calculated for the LT group. Univariable and multivariable logistic regression analyses were performed to determine significant clinical factors associated with the sensitivity of LI-RADS. Of the 281 patients, 237 were assigned to the SR group, and 44 were assigned to the LT group. The LT group showed significantly lower per-patient (48.5% vs. 79.6%, p < .001) and per-lesion sensitivity (31.0% vs. 75.9%, p < .001) than the SR group, whereas no significant difference in both per-patient (100.0% vs. 91.7%, p > .99) and per-lesion specificities (100.0% vs. 94.1%, p > .99). The accuracy of patient allocation was 50.0%. Sensitivity was significantly lower in patients with a smaller lesion size (p < .001), a larger lesion number (p = .002), and a higher Child-Pugh score (p = .009). LI-RADS v2018 on gadoxetic acid-enhanced MRI might be insufficient in liver transplant candidates and other diagnostic imaging tests should be considered in patients with these significant clinical factors. In liver transplant candidates with a smaller lesion size, a larger lesion number, and a higher Child-Pugh score, imaging tests other than gadoxetic acid-enhanced MRI may be clinically useful to determine the transplant eligibility. • The sensitivity of the Liver Imaging Reporting and Data System (LI-RADS) was lower in liver transplant candidates than in those who underwent surgical resection. • With the use of gadoxetic acid-enhanced MRI, the accuracy of patient allocation for liver transplantation on the basis of the Milan criteria was suboptimal. • The sensitivity of LI-RADS v2018 was significantly associated with lesion size, lesion number, and Child-Pugh classification.

SP70 is a novel biomarker of hepatocellular carcinoma.

Tumor-specific protein 70 (SP70) was identified as a new biomarker associated with the proliferation and invasion of cancer cells. This study aimed to investigate the expression of SP70 in hepatocellular carcinoma (HCC) and assess its clinical value in the diagnosis and prediction of early HCC recurrence. A total of 1049 subjects from the First Affiliated Hospital of Nanjing Medical University were recruited in this study. Serum SP70, alpha-fetoprotein (AFP) and prothrombin induced by vitamin K absence II (PIVKA-II) were measured. The diagnostic performance for HCC was obtained using the receiver operating characteristic (ROC) curve, and recurrence-free survival (RFS) was calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify predictive factors of RFS. SP70 was highly expressed in HCC cells and HCC tissue. Serum SP70 levels in the HCC group were significantly higher than in the benign liver diseases group and healthy control group (P<0.001). SP70 combined with AFP showed the best diagnostic performance (AUC=0.909, 95%CI [confidence interval]=0.890-0.929). Kaplan-Meier analysis revealed that patients with high SP70 levels had shorter median RFS than those with low SP70 levels (P=0.003). In addition, high SP70 levels were significantly associated with shorter RFS (P=0.037) in the AFP-negative subgroup. Univariate and multivariate analyses confirmed that preoperative serum SP70 level, serum AFP, tumor diameter and microvascular invasion were independent prognostic factors of RFS. SP70 is a promising biomarker in diagnosing HCC. High preoperative serum SP70 level is associated with an increased risk of early relapse and could be used as a valuable marker to predict early recurrence of HCC after resection.

Performance of free-breathing dynamic T1-weighted sequences in patients at risk of developing motion artifacts undergoing gadoxetic acid-enhanced liver MRI.

To evaluate the recall rate and performance of free-breathing T1W dynamic imaging in patients who underwent gadoxetic acid-enhanced liver MRI. We retrospectively reviewed patients who underwent free-breathing dynamic T1WI liver MRI using Cartesian (XD-VIBE) or self-gated radial (SG-GRASP) sequences at two institutions. Four radiologists independently reviewed the overall image quality, streak, and motion artifacts for precontrast, arterial, and portal venous phases on a 4-point scale. Hepatic observations were annotated and assessed according to LI-RADS v2018. In total, 360 patients were included (XD-VIBE [n = 253], SG-GRASP [n = 107]). The overall image quality of free-breathing T1WI was 3.4 ± 0.4, 3.2 ± 0.4, and 3.5 ± 0.4 for precontrast, arterial, and portal venous phases, respectively. The actual recall rate was 0.6% (2/360). The SG-GRASP group showed fewer motion artifacts and more streak artifacts than the XD-VIBE group in all phases (p < 0.001 for all). The overall image quality was not significantly different between the two sequences in arterial (3.2 ± 0.4 in both, p = 0.607) and portal venous phases (3.5 ± 0.4 in XD-VIBE, 3.4 ± 0.4 in SG-GRASP, p = 0.214). Two sequences did not show significant differences in the lesion detection rate (figure of merit, FOM: 0.67 vs. 0.68, p = 0.876) or diagnostic performance for hepatocellular carcinoma (FOM: 0.55 vs. 0.62, p = 0.105). Both XD-VIBE and SG-GRASP provided sufficient image quality for patients at risk of developing motion artifacts, without significant differences in image quality or the lesion detection rate between sequences. • The overall image quality of free-breathing T1-weighted images using Cartesian or radial sequences was 3.4 ± 0.4, 3.2 ± 0.4, and 3.5 ± 0.4 for precontrast, arterial, and portal venous phases, respectively. • Only 0.3% (1/360) had undiagnostic exams and the actual recall rate was 0.6% (2/360) in patients who underwent free-breathing dynamic T1WI. • The overall lesion detection rate was 0.67 without a significant difference between Cartesian and radial sequences (figure of merit: 0.67 vs. 0.68, respectively, p = 0.876).

Using arterial phase hyperenhancement on CT instead of gadoxetic acid arterial phase enhancement may improve the diagnostic performance for hepatocellular carcinoma

The diagnostic performance for hepatocellular carcinoma (HCC) is hampered using gadoxetic acid-enhanced magnetic resonance (MR) imaging due to the high incidence of transient severe motion in arterial phase (AP). Dynamic contrast enhanced computed tomography (CT) imaging yield high detection rate for hepatic nodules in AP, and the combined use of CT arterial phase (CTAP) imaging with gadoxetic acid-enhanced MR imaging may improve the diagnostic performance for HCC. Thus, this study aimed to determine whether the combined use of CTAP and gadoxetic acid-enhanced MR imaging can improve the diagnostic performance for HCC based on various imaging diagnostic criteria. A total of 169 surgically histologically confirmed hepatic nodules (137 HCCs and 32 non-HCC-nodules) were retrospectively enrolled. Two different imaging protocol sets were reviewed: (I) full gadoxetic acid-enhanced magnetic resonance imaging (MRI) sequences; and (II) CTAP imaging combined with the gadoxetic acid-enhanced MRI but excluding the MR imaging AP images. Three independent reviewers followed the 2018 Liver Reporting and Data System (LI-RADS), European Association for the Study of the Liver (EASL), and 2018 Korean guidelines to characterize these heaptic nodules by reviewing the two imaging protocol sets and the diagnostic peformance were compared by using McNemar test. The detection rate of AP hyperenhancement (APHE) was higher in CTAP than in the MR arterial phase (MRAP) for hepatic nodules (87.57% vs. 75.15%) and HCCs (97.08% vs. 82.48%) (all P<0.001). For the LI-RADS criteria, the Protocol-II increased the sensitivity to 75.91% from 70.80% of Protocol-I (P=0.016), with a minimal decrease of the specificity to 71.88% from 75.00% (P=1.000). For the EASL criteria, the numerical increases were found of Protocol-II than Protocol-I in both sensitivity (81.02% vs. 78.10%) and specificity (75.00% vs.71.88%), but with no statistical significance. For the Korean criteria, the Protocol-II increased the sensitivity to 94.89% from 83.21% of Protocol-I (P<0.001). The specificity increased to 65.63% from 62.50%, with no statistical significance (P=1.000). Using CTAP instead of gadoxetic acid-enhanced MRAP can improve the diagnostic sensitivity for HCC and also yields a comparable specificity. Thus, the combined use of CTAP and gadoxetic acid-enhanced MR imaging may improve the diagnostic performance for HCC.

Cutoff values of protein induced by vitamin K absence or antagonist II for diagnosing hepatocellular carcinoma.

Protein induced by vitamin K absence or antagonist II (PIVKA-II) is a promising serum marker for hepatocellular carcinoma (HCC). There are limited data on its cutoff value in HCC for Taiwanese cirrhosis patients. This study aimed to investigate the diagnostic value of PIVKA-II levels in patients with suspected HCC. In total, 88 patients with chronic hepatitis and suspected HCC by ultrasound, elevated α-fetoprotein (AFP) or PIVKA-II levels were consecutively enrolled. Their baseline characteristics and findings on dynamic phases of computed tomography (CT) or magnetic resonance imaging (MRI) were examined. Sixty participants had cirrhosis and 34 had HCC. The median levels of PIVKA-II in non-cirrhosis and cirrhosis patients without or with HCC were 28.0, 48.0, and 847.0 mAU/mL, respectively. The optimal cutoff value of PIVKA-II in predicting HCC was 78.0 mAU/mL. Combining AFP with PIVKAII mildly increased its diagnostic performance for HCC, yielding higher specificity and positive predictive value. Significant factors predicting HCC in multivariate regression analysis were PIVKA >78.0 mAU/mL and fatty liver. Monitoring PIVKA-II level is suitable for noninvasively assessing HCC in patients with chronic hepatitis, particularly with AFP.

Risk factors and diagnostic biomarkers for nonalcoholic fatty liver disease-associated hepatocellular carcinoma: Current evidence and future perspectives.

High rates of excessive calorie intake diets and sedentary lifestyles have led to a global increase in nonalcoholic fatty liver disease (NAFLD). As a result, this condition has recently become one of the leading causes of hepatocellular carcinoma (HCC). Furthermore, the incidence of NAFLD-associated HCC (NAFLD-HCC) is expected to increase in the near future. Advanced liver fibrosis is the most common risk factor for NAFLD-HCC. However, up to 50% of NAFLD-HCC cases develop without underlying liver cirrhosis. Epidemiological studies have revealed many other risk factors for this condition; including diabetes, other metabolic traits, obesity, old age, male sex, Hispanic ethnicity, mild alcohol intake, and elevated liver enzymes. Specific gene variants, such as single-nucleotide polymorphisms of patatin-like phospholipase domain 3, transmembrane 6 superfamily member 2, and membrane-bound O-acyl-transferase domain-containing 7, are also associated with an increased risk of HCC in patients with NAFLD. This clinical and genetic information should be interpreted together for accurate risk prediction. Alpha-fetoprotein (AFP) is the only biomarker currently recommended for HCC screening. However, it is not sufficiently sensitive in addressing this diagnostic challenge. The GALAD score can be calculated based on sex, age, lectin-bound AFP, AFP, and des-carboxyprothrombin and is reported to show better diagnostic performance for HCC. In addition, emerging studies on genetic and epigenetic biomarkers have also yielded promising diagnostic potential. However, further research is needed to establish an effective surveillance program for the early diagnosis of NAFLD-HCC.

Non-invasive diagnosis strategy of hepatocellular carcinoma in low-risk population

AimsWith prevalence of hepatocellular carcinoma (HCC) in low-risk population (LRP), establishing a non-invasive diagnostic strategy becomes increasingly urgent to spare unnecessary biopsies in this population. The purposes of this study were to find characterisics of HCC and to establish a proper non-invasive method to diagnose HCC in LRP.MethodsA total of 681 patients in LRP (defined as the population without cirrhosis, chronic HBV infection or HCC history) were collected from 2 institutions. The images of computed tomography (CT) and magnetic resonance imaging (MRI) were manually analysed. We divided the patients into the training cohort (n = 324) and the internal validating cohort (n = 139) by admission time in the first institution. The cohort in the second institution was viewed as the external validation (n = 218). A multivariate logistic regression model incorporating both imaging and clinical independent risk predictors was developed. C-statistics was used to evaluate the diagnostic performance.ResultsBesides the major imaging features of HCC (non-rim enhancement, washout and enhancing capsule), tumor necrosis or severe ischemia (TNSI) on imaging and two clinical characteristics (gender and alpha fetoprotein) were also independently associated with HCC diagnosis (all P < 0.01). A clinical model (including 3 major features, TNSI, gender and AFP) was built to diagnose HCC and achieved good diagnostic performance (area under curve values were 0.954 in the training cohort, 0.931 in the internal validation cohort and 0.902 in the external cohort).ConclusionsThe clinical model in this study developed a satisfied non-invasive diagnostic performance for HCC in LRP.

New Liver MR Imaging Hallmarks for Small Hepatocellular Carcinoma Screening and Diagnosing in High-Risk Patients.

ObjectiveEarly detection and diagnosis of hepatocellular carcinoma (HCC) is essential for prognosis; however, the imaging hallmarks for tumor detection and diagnosis has remained the same for years despite the use of many new immerging imaging methods. This study aimed to evaluate the detection performance of hepatic nodules in high risk patients using either hepatobiliary specific contrast (HBSC) agent or extracellular contrast agent (ECA), and further to compare the diagnostic performances for hepatocellular carcinoma (HCC) using different diagnostic criteria with the histopathological results as reference standard.MethodsThis prospective study included 247 nodules in 222 patients (mean age, 53.32 ± 10.84 years; range, 22–79 years). The detection performance and imaging features of each nodule were evaluated in all MR sequences by three experienced abdominal radiologists. The detection performance of each nodule on all MR sequences were compared and further the diagnostic performance of various diagnostic criteria were evaluated.ResultsFor those patients who underwent ECA-MRI, the conventional imaging hallmark of “AP + PVP and/or DP” was recommended, as 60.19% diagnostic sensitivity, 80.95% specificity and 100% lesion detection rate. Additionally, for those patients who underwent HBSC-MRI, the diagnostic criteria of “DWI + HBP” was recommended. This diagnostic criteria demonstrated, both in all tumor size and for nodules ≤2 cm, higher sensitivity (93.07 and 90.16%, all p <0.05, respectively) and slightly lower specificity (64.71 and 87.50%, all p >0.05, respectively) than that of the European Association for the Study of the Liver (EASL) criteria.ConclusionsDifferent abbreviated MR protocols were recommended for patients using either ECA or HBSC. These provided imaging settings demonstrated high lesion detection rate and diagnostic performance for HCC.

LI-RADS Major Features on MRI for Diagnosing Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

The reported diagnostic performance for hepatocellular carcinoma (HCC) of each major imaging feature on MRI using standardized definitions of the Liver Imaging Reporting and Data System (LI-RADS) is variable. It is important to know the actual performance of each LI-RADS major imaging feature for imaging diagnosis of HCC and determine the sources of heterogeneity between the reported results. To systematically determine the performance of each major imaging feature of LI-RADS for diagnosing HCC using either extracellular contrast agent-enhanced MRI (ECA-MRI) or gadoxetate disodium-enhanced MRI (EOB-MRI). Systematic review and meta-analysis. Sixteen original articles with 3542 lesions. A 1.5 T and 3.0 T. Data extraction was independently performed by two reviewers who identified and reviewed original articles reporting the diagnostic performance of each LI-RADS major imaging feature-arterial phase hyperenhancement (APHE), observation size, washout appearance, enhancing "capsule," and threshold growth-using MRI. Study characteristics, study population characteristics, MRI characteristics, contrast agent, LI-RADS version, reference standards, and study outcomes were extracted from included studies. Risk of bias and concerns regarding applicability were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Bivariate random-effects models were used to obtain summary estimates of the diagnostic performance of each LI-RADS major imaging feature. Hierarchical summary receiver operating characteristic curves were plotted. Meta-regression analyses were performed to explore potential sources of heterogeneity. The pooled per-observation sensitivities and specificities for diagnosing HCC were 85% (95% confidence interval [CI]=78%-89%) and 57% (95% CI=44%-70%) for arterial phase hyperenhancement (APHE), 77% (95% CI=72%-82%), and 74% (95% CI=63%-83%) for washout appearance, and 52% (95% CI=41%-64%) and 90% (95% CI=85%-94%) for enhancing "capsule," respectively. Among the LI-RADS major features, the sensitivity was the highest for APHE and the specificity was the highest for enhancing "capsule" in the diagnosis of HCC. 3 TECHNICAL EFFICACY: Stage 2.

Should Threshold Growth Be Considered a Major Feature in the Diagnosis of Hepatocellular Carcinoma Using LI-RADS?

ObjectiveBased on the Liver Imaging Reporting and Data System version 2018 (LI-RADS, v2018), this study aimed to analyze LR-5 diagnostic performance for hepatocellular carcinoma (HCC) when threshold growth as a major feature is replaced by a more HCC-specific ancillary feature, as well as the frequency of threshold growth in HCC and non-HCC malignancies and its association with tumor size.Materials and MethodsThis retrospective study included treatment-naive patients who underwent gadoxetate disodium-enhanced MRIs for focal hepatic lesions and surgery between January 2009 and December 2016. The frequency of major and ancillary features was evaluated for HCC and non-HCC malignancies, and the LR-category was assessed. Ancillary features that were significantly more prevalent in HCC were then used to either replace threshold growth or were added as additional major features, and the diagnostic performance of the readjusted LR category was compared to the LI-RADS v2018.ResultsA total of 1013 observations were analyzed. Unlike arterial phase hyperenhancement, washout, or enhancing capsule which were more prevalent in HCCs than in non-HCC malignancies (521/616 vs. 18/58, 489/616 vs. 19/58, and 181/616 vs. 5/58, respectively; p < 0.001), threshold growth was more prevalent in non-HCC malignancies than in HCCs (11/23 vs. 17/119; p < 0.001). The mean size of non-HCC malignancies showing threshold growth was significantly smaller than that of non-HCC malignancies without threshold growth (22.2 mm vs. 42.9 mm, p = 0.040). Similar results were found for HCCs; however, the difference was not significant (26.8 mm vs. 33.1 mm, p = 0.184). Additionally, Fat-in-nodule was more frequent in HCCs than in non-HCC malignancies (99/616 vs. 2/58, p = 0.010). When threshold growth and fat-in-nodule were considered as ancillary and major features, respectively, LR-5 sensitivity (73.2% vs. 73.9%, p = 0.289) and specificity (98.2% vs. 98.5%, p > 0.999) were comparable to the LI-RADS v2018.ConclusionThreshold growth is not a significant diagnostic indicator of HCC and is more common in non-HCC malignancies. The diagnostic performance of LR-5 was comparable when threshold growth was recategorized as an ancillary feature and replaced by a more HCC-specific ancillary feature.

Extended application of subtraction arterial phase imaging in LI-RADS version 2018: a strategy to improve the diagnostic performance for hepatocellular carcinoma on gadoxetate disodium-enhanced MRI.

This study aimed to assess the detection of hepatocellular carcinoma (HCC) utilizing subtraction AP (arterial phase) imaging only for T1 hyperintense observations compared with the detection of HCC on subtraction AP imaging that included T1 hyper-, iso-, and hypointense lesions on gadoxetate disodium-enhanced MRI. This retrospective study included 234 patients (311 observations including 239 HCCs) at high risk for HCC who underwent gadoxetate disodium-enhanced MRI with subtraction AP imaging between 2015 and 2017. Arterial phase hyperenhancement (APHE) was divided into two subtypes: conventional APHE, where subtraction AP imaging is used to detect APHE only for T1 hyperintense observations; and modified APHE, where subtraction AP imaging is applied to T1 hyper-, iso-, and hypointense lesions. Two readers independently reviewed all observations and the per-observation diagnostic performances were compared using McNemar's test. Modified nonrim APHE showed significantly higher sensitivity than conventional nonrim APHE (90.0% vs 82.8%; p < 0.001) for diagnosing HCC, without a significant difference in specificity (66.7% vs 68.1%; p > 0.999). The LR-5 category with modified nonrim APHE provided better sensitivity than the LR-5 with conventional nonrim APHE (70.3% vs 63.2%; p < 0.001), without a significant decrease in specificity (94.4% vs 95.8%; p > 0.999). Extended application of subtraction AP imaging for T1 hypo- or isointense observations on gadoxetate disodium-enhanced MRI can improve sensitivity in the diagnosis of HCC without a significant difference in specificity. • Modified nonrim arterial phase hyperenhancement (APHE), extended application of subtraction arterial phase imaging for T1 hypo- or isointense observation, outperforms conventional nonrim APHE. • The LR-5 category with modified nonrim APHE provided better sensitivity in diagnosing HCC than the LR-5 with conventional APHE, without a significant decrease in specificity.

Role of Kupffer phase image using sonazoid on CEUS LI-RADS® and diagnostic performance for hepatocellular carcinoma

Role of Kupffer phase image using sonazoid on CEUS LI-RADS® and diagnostic performance for hepatocellular carcinoma

The Diagnostic Performance of lncRNAs from Blood Specimens in Patients with Hepatocellular Carcinoma: A Meta-Analysis.

Long noncoding RNAs (lncRNAs) are widely involved in the carcinogenesis and development of cancers. We conducted a meta-analysis to evaluate the diagnostic performance of lncRNAs in hepatocellular carcinoma (HCC). After the inclusion and exclusion process, relevant information was extracted. Heterogeneity between studies was evaluated, and data synthesis was conducted by employing a bivariate random-effects model. In total, 20 eligible studies were enrolled. The pooled sensitivity and specificity were 0.86 (95% confidence interval [CI], 0.80-0.90) and 0.88 (95% CI, 0.82-0.92), respectively. The pooled positive likelihood ratio, pooled negative likelihood ratio, and pooled diagnostic odds ratio were 7.1 (95% CI, 4.9-10.2), 0.16 (95% CI, 0.11-0.23), and 44 (95% CI, 25-79), respectively. The results of the linear regression method and visual inspection of the Deeks funnel plot did not indicate significant publication bias. Our meta-analysis suggested that lncRNAs have high diagnostic performance for HCC and have the potential for clinical application.

A New Diagnostic Criterion with Gadoxetic Acid-Enhanced MRI May Improve the Diagnostic Performance for Hepatocellular Carcinoma

Background: To prospectively establish and validate new diagnostic criterion (DC) for liver-specific contrast agents and further compared the diagnostic sensitivity and specificity with conventional DC. Methods: Institutional Review Board approved and written informed consent were obtained for this prospective study. Two board-certified reviewers established the reference standard as hepatocellular carcinoma (HCC), non-HCC lesions by using marks on all cross-sectional MR images. Another 2 abdominal radiologists independently performed the marked lesion observations using 5 different DCs, including DC-1: arterial phase hyperenhancement (APHE) and portal venous phase washout; DC-2: APHE and hepatobiliary phase (HBP) hypointensity; DC-3: APHE and diffusion-weighted imaging (DWI) hyperintensity; DC-4: HBP hypointensity and DWI hyperintensity; DC-5: HBP hypointensity, DWI hyperintensity and excluded these markedly T2 hyperintensity. Diagnostic performance of sensitivity, specificity, and accuracy for each imaging DC was calculated, per-lesion diagnostic sensitivity and specificity of imaging criteria were compared by using McNemars test. Results: A total of 215 patients were included (mean age 53.82 ± 11.24 years; range 24–82 years) with 265 hepatic nodules (175 HCCs and 90 non-HCCs). The DC-4 (93.71%; 164/175) and DC-5 (92.57%; 162/175) yielded the highest diagnostic sensitivity and was better than DC-1 (72.57%; 127/175), DC-2 (82.86%; 145/175), and DC-3 (82.29%; 144/175) (all p < 0.001). The specificity of DC-1 (94.44%; 85/90) was significantly higher than that with DC-2 (83.33%; 75/90), DC-3 (84.44%; 76/90), DC-4 (74.44%; 67/90), and DC-5 (82.22%; 74/90) (all p < 0.05). Additionally, the DC-4 and DC-5 achieved the highest area under curve value of 0.841 (95% CI 0.783–0.899) and 0.874 (95% CI 0.822–0.925). Conclusions: The combined use of HBP hypointensity and DWI hyperintensity as a new DC for HCC enables a high diagnostic sensitivity and comparable specificity.

Characterizing Computed Tomography-Detected Arterial Hyperenhancing-Only Lesions in Patients at Risk of Hepatocellular Carcinoma: Can Non-Contrast Magnetic Resonance Imaging Be Used for Sequential Imaging?

ObjectiveTo test the feasibility of non-contrast magnetic resonance imaging (MRI) in a sequential imaging study for characterizing computed tomography (CT)-detected arterial-enhancing nodules that do not washout in patients at risk of hepatocellular carcinoma (HCC).Materials and MethodsIn this retrospective study, 134 patients (mean age ± standard deviation, 56.8 ± 10.0 years) with 151 arterial enhancing-only nodules measuring up to 2 cm during multiphasic CT that were subsequently evaluated using gadoxetic acid-enhanced MRI in treatment-naïve at-risk patients from three tertiary referral centers were included. Tentative diagnostic criteria for HCC and hepatic malignancy were defined as the presence of one of eight MRI features favoring HCC in combinations of the following sequences: T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), T1-weighted dual gradient-echo in-phase and out-of-phase imaging (Dual-GRE), and hepatobiliary phase imaging (HBP). Typical hemangiomas and arterioportal shunts were excluded from the analysis. Diagnostic performance for HCC and hepatic malignancy was calculated and compared between the abbreviated MRI and full-sequence gadoxetic acid-enhanced MRI.ResultsOf 151 nodules (mean size, 1.2 cm) 68 HCCs and 83 non-HCC benignities and malignancies were included. The combination of T2WI, DWI, and Dual-GRE showed per-lesion sensitivity, specificity, and accuracy of 88.2%, 90.4%, and 89.4%, respectively, comparable to those of full-sequence MRI. Applying the same sequence combination to diagnose hepatic malignancy had per-lesion sensitivity, specificity, and accuracy of 86.8%, 97.3%, and 92.1%. In nodules < 1 cm, adding HBP increased sensitivity by up to 13% without compromising the specificity or accuracy.ConclusionThe non-contrast MRI protocol comprising T2WI, DWI, and Dual-GRE showed reasonable and comparable performance to full-sequence MRI for discriminating HCC and primary liver malignancies in CT-detected indeterminate arterial enhancing-only nodules in at-risk patients, and can be potentially used for sequential imaging in place of a full-sequence MRI. In nodules < 1 cm, HBP may still be needed to preserve sensitivity.

A New Diagnostic Criterion with Gadoxetic Acid-Enhanced MR Imaging May Improve the Diagnostic Performance for Hepatocellular Carcinoma

Background: To prospectively establish and validate new DCs for liver-specific contrast agents and further compared the diagnostic sensitivity and specificity with conventional DC. Methods: Institutional review board approved and written informed consent were obtained for this prospective study. Two board-certified reviewers established the reference standard as HCC, non-HCC lesions by using marks on all cross-sectional MR images. Another two abdominal radiologists independently performed the marked lesion observations using five different diagnostic criterions, including DC-1: arterial phase hyperenhancement (APHE) and portal venous phase (PVP) washout; DC-2: APHE and hepatobiliary phase (HBP) hypointensity; DC-3: APHE and diffusion weighted imaging (DWI) hyperintensity; DC-4: HBP hypointensity and DWI hyperintensity; DC-5: HBP hypointensity, DWI hyperintensity and excluded these markedly T2 hyperintensity. Diagnostic performance of sensitivity, specificity and accuracy for each imaging DC was calculated, per-lesion diagnostic sensitivity and specificity of imaging criteria was compared by using McNemars test. Findings: A total of 173 patients were included (mean age, 53.82 ±11.04 years; range, 24-82 years) with 211hepatic nodules (145 HCCs and 66 non-HCCs). The DC-4 and DC-5 yielded the highest diagnostic sensitivity of 95.17% (138/145) and was better than DC-1 (69.66%, 101/145), DC-2 (80.69%, 117/145) and DC-3 (82.07%, 119/145) (all p<0.001). The specificity of DC-1 was significantly higher than that with DC-2 (78.79%, 52/66), DC-3 (80.30%, 53/66) and DC-4 (80.30%, 53/66) (all p<0.05), but no significant difference was obtained from DC-5 (84.85%, 56/66) (p=0.109). Interpretation: The combined use of HBP hypointensity and DWI hyperintensity as s new DC for HCC enables a high diagnostic sensitivity and comparable specificity. Funding: This work was supported by National Nature Science Foundation of China (Grant number 81771797), Science and Technology Support Program of Sichuan Province (Grant number 2017SZ0003). Declaration of Interest: The authors declare no potential conflicts of interests. Ethical Approval: Institutional review board approved and written informed consent were obtained for this prospective study.

Extracellular contrast agent-enhanced MRI: 15-min delayed phase may improve the diagnostic performance for hepatocellular carcinoma in patients with chronic liver disease.

To determine the value of a 15-min delayed phase in extracellular contrast agent (ECA)-enhanced magnetic resonance imaging (MRI) for evaluation of hepatocellular carcinoma (HCC) in patients with chronic liver disease. Between 2014 and 2015, 103 patients with chronic liver disease underwent ECA-enhanced MRI; 133 lesions consisting of 107 HCCs, 23 benign lesions and three non-HCC malignancies were identified with pathological or clinical diagnosis. MRI images were reviewed by two abdominal radiologists independently using the European Association for the Study of the Liver (EASL) and Liver Imaging Reporting and Data System (LI-RADS) criteria. Imaging features observed in the 15-min delayed phase were recorded. Of 107 HCCs, three or four additional HCCs were diagnosed according to the EASL criteria by adding the 15-min delayed phase, increasing sensitivity (Reviewer 1, from 69.2-72.0 % [P = 0.072]; Reviewer 2, from 75.7-79.4 % [P = 0.041]). Reviewers 1 and 2 upgraded one and four HCCs from LR-4 to LR-5 based on the LI-RADS, respectively. Among 23 benign lesions, no additional findings were observed in the 15-min delayed phase. Including the 15-min delayed phase in ECA-enhanced MRI may improve the diagnostic performance for HCC in patients with chronic liver disease. • Additional acquisition of 15-min delayed phase (FDP) requires approximately 20 s. • About 5 % of HCCs show washout or capsule appearance only in FDP. • Including FDP improves the sensitivity of extracellular contrast agent-enhanced MRI for HCC. • These results are applicable only to patients with chronic liver disease.

Diagnostic criteria for hepatocellular carcinoma ⩽3 cm with hepatocyte-specific contrast-enhanced magnetic resonance imaging

Current diagnostic imaging criteria for hepatocellular carcinoma (HCC) are dedicated to imaging with nonspecific extracellular contrast agents. This study aimed to evaluate diagnostic criteria for HCC ⩽3 cm on magnetic resonance imaging (MRI) with a hepatocyte-specific contrast agent through an inception cohort study. Of 291 patients with chronic liver disease and new nodules of 1-3 cm in diameter at surveillance ultrasonography, 295 solid nodules (194 HCCs, 98 benign nodules, and three other malignancies) in 198 patients with a confirmed final diagnosis or ⩾24 months follow-up were evaluated on gadoxetic acid-enhanced MRI. Through univariate and multivariate logistic regression analyses, various diagnostic criteria were developed by combining significant MRI findings for diagnosing HCC. The diagnostic performance of each criterion was compared with that of the European Association for the Study of the Liver (EASL) criteria. Four MRI findings (arterial-phase hyperintensity, transitional-phase hypointensity, hepatobiliary-phase hypointensity, and rim enhancement) were independently significant for diagnosis of HCC ⩽3 cm. For whole nodules, EASL criteria showed the best performance for diagnosing HCC (sensitivity, 83.5%; specificity, 81.2%). For nodules ⩽2 cm in diameter, a new criterion (arterial-phase hyperintensity and hepatobiliary-phase hypointensity) showed a significantly higher sensitivity than that of the EASL criteria (83.0% vs. 74.5%, p=0.008), without a significantly different specificity (76.7% vs. 81.1%, p=0.125). EASL criteria exhibit the best diagnostic performance for HCC ⩽3 cm on hepatocyte-specific contrast-enhanced MRI. A newly identified criterion (arterial-phase hyperintensity and hepatobiliary-phase hypointensity) may increase the diagnostic sensitivity of small (⩽2 cm) HCC.