Diagnosis Of Small Hepatocellular Carcinoma Research Articles

Clinical Significance of Liver MR Imaging.

MRI is widely used in clinical practice for detecting liver diseases. Since the introduction of gadoxetic acid, MRI has become the most effective modality for the detection and characterization of focal liver lesions. According to previous meta-analyses, the area under the receiver operating characteristic curve (AUROC) was 0.97-0.99 for the diagnosis of small hepatocellular carcinoma (≥ 2 cm) by gadoxetic-acid-enhanced MRI. Moreover, the AUROC for the diagnosis of colorectal liver metastases was significantly high (0.98). Despite gadoxetic acid's drawbacks, its clinical utility outweighs them, making it the contrast agent of choice in routine liver MRIs. Moreover, clinically, liver MRI has become more prevalent for a quantitative assessment. Liver fibrosis can be evaluated using MR elastography; whereas, hepatic steatosis and iron overload can be evaluated using proton density fat fraction, with high accuracy and reproducibility. This article reviewed the usefulness of liver MRI, which can be a comprehensive imaging modality in clinical practice.

Comparison of the value of conventional two-dimensional ultrasound, contrast-enhanced ultrasound and MSCT in early diagnosis of small hepatocellular carcinoma.

article: Comparison of the value of conventional two-dimensional ultrasound, contrast-enhanced ultrasound and MSCT in early diagnosis of small hepatocellular carcinoma - Minerva Gastroenterology 2022 Sep 23 - Minerva Medica - Journals

Clinical value of contrast-enhanced ultrasound in early diagnosis of small hepatocellular carcinoma (≤ 2 cm).

BACKGROUNDHepatocellular carcinoma (HCC) is the most common type of primary liver malignancy. Contrast-enhanced ultrasound (CEUS) uses contrast microbubbles during ultrasound, allowing the detection and characterization of malignant focal liver lesions with much higher diagnostic accuracy than conventional ultrasound; however, there are few reports focusing on the pattern of enhancement of CEUS for the diagnosis of HCC smaller than 2 cm.AIMTo investigate the clinical value of CEUS in the early detection of small HCC with high risk factors.METHODSA total of 395 patients with 632 nodules at high risk of HCC, who underwent regular follow-up at Xuhui Dahua Hospital from January 2007 to December 2021, were retrospectively examined. Conventional ultrasonography combined with CEUS was adopted to analyze the echo, size, location, and enhancement characteristics of benign and malignant nodules, as well as the enhancement methods for HCC with different diameters. RESULTSThe follow-up rate and duration were 92.15% (364/395) and 51.28 ± 45.09 mo, respectively. Conventional ultrasonography combined with CEUS revealed 65 (11.80%) nodules with a follow-up diagnosis of HCC, 19 (3.45%) dysplastic nodules, and 467 (84.75%) benign cirrhotic hyperplastic nodules. Among 65 cases of confirmed HCC, 40 (61.54%) were transformed from hypoechoic nodules, 9 (13.85%) from hyperechoic nodules, and the remaining 16 (24.62%) from isoechoic nodules. Significant differences in CEUS characteristics were found among cirrhotic nodules, dysplastic nodules, and HCC nodules at each phase. Significant differences in the enhancement mode were observed between nodules ≤ 1 cm and those 1–2 cm. The smaller the HCC nodule, the later the contrast agent began to flush and the longer the duration of contrast enhancement. CONCLUSIONConventional ultrasonography combined with CEUS could identify small HCC and help monitor patients with an early diagnosis of HCC. Significant differences in the enhancement mode are noted between nodules ≤ 1 cm and those 1–2 cm.

CT imaging combined with multimodal magnetic resonance imaging in the diagnosis of small hepatocellular carcinoma in the background of cirrhosis.

article: CT imaging combined with multimodal magnetic resonance imaging in the diagnosis of small hepatocellular carcinoma in the background of cirrhosis - Minerva Surgery 2022 Jan 13 - Minerva Medica - Journals

Study on clinical application of susceptibility weighted imaging ombined with diffusion weighted imaging in patients with Liver Cirrhosis complicated with small Hepatocellular Carcinoma.

Objectives:To evaluate the clinical value of susceptibility weighted imaging (SWI) combined with diffusion weighted imaging (DWI) in patients with liver cirrhosis complicated with small hepatocellular carcinoma (SHCC).Methods:A total of 40 patients with liver cirrhosis and 44 nodules were treated with conventional nuclear magnetic scanning (T1WI, T2WI) and SWI combined with DWI; the results were judged by two senior physicians; the t test, χ2 test, rank sum test, and other methods were used for contrastive analysis of the pathological results of different scanning methods after operation or puncture.Results:Contrast analysis of the different MRI scanning methods and pathological results showed that among the 32 nodules of small hepatocellular carcinoma, 24 cases were diagnosed by conventional MRI, with the coincidence rate being 75%, 30 cases were diagnosed by SWI DWI, with the coincidence rate being 96%; significant difference was found between the two groups (p=0. 04). Significant differences were found in the specificity, sensitivity and accuracy of different scanning methods in the diagnosis of small hepatocellular carcinoma (specificity, accuracy, p=0.04; sensitivity p=0.01). The SWI of small hepatocellular carcinoma nodules showed hyperintensity, and the degree of iron deposition was low. Significant difference was found between small hepatocellular carcinoma nodules and other nodules (comparison of SWI signal degree, p=0.01; comparison of iron deposition degree, p=0.00).Conclusion:The SWI of small hepatocellular carcinoma nodules showed hyperintensity, and the degree of iron deposition was low. The coincidence rate of SWI+DWI scanning is higher than that of conventional scanning methods in the diagnosis of small hepatocellular carcinoma, and the difference in specificity, sensitivity and accuracy has obvious advantages. SWI+DWI scanning can improve the detection rate of liver cirrhosis complicated with small hepatocellular carcinoma.

CT-Value (△HU and CT-Value ratioin) differential diagnosis of small hepatocellular carcinoma from focal nodular hyperplasia

CT-Value (△HU and CT-Value ratioin) differential diagnosis of small hepatocellular carcinoma from focal nodular hyperplasia

CT-Value (△HU and CT-Value ratioin) differential diagnosis of small hepatocellular carcinoma from focal nodular hyperplasia

CT-Value (△HU and CT-Value ratioin) differential diagnosis of small hepatocellular carcinoma from focal nodular hyperplasia

A meta-analysis of the added value of diffusion weighted imaging in combination with contrast-enhanced magnetic resonance imaging for the diagnosis of small hepatocellular carcinoma lesser or equal to 2 cm.

Diffusion weighted imaging (DWI) has been found to increase the sensitivity in the diagnosis of small hepatocellular carcinoma (HCC), although additional studies are required to confirm its value. The aim of the present study was to explore the diagnostic performance of DWI combined with contrast-enhanced magnetic resonance imaging (MRI) for small HCC by performing a meta-analysis. Literature databases (PubMed, Embase, Web of Science and Cochrane Library databases) were searched to identify studies reporting the sensitivity and specificity of MRI with DWI for the diagnosis of small HCCs. Pooled sensitivity and specificity were generated using a bivariate random effect model. Multilevel mixed-effects logistic regression analysis was used to examine the value of DWI combined with conventional MRI. A total of 837 small HCCs and 545 benign liver lesions from 10 studies were included. The overall sensitivity and specificity of DWI combined with contrast-enhanced MRI was 0.88 (95% CI, 0.80–0.93) and 0.90 (95% CI, 0.81–0.95), respectively. Compared with that in contrast-enhanced MRI, DWI with contrast-enhanced MRI had a significantly higher sensitivity for the diagnosis of small HCC (P=0.01) while there was no significant difference in the specificity (P=0.603). The present meta-analysis suggests that DWI combined with contrast-enhanced MRI may increase the sensitivity, whilst maintaining high specificity for the diagnosis of small HCCs with a diameter ≤2 cm.

A proposal for a useful algorithm to diagnose small hepatocellular carcinoma on MRI.

To assess MRI features for the diagnosis of small hepatocellular carcinomas (HCCs) and especially for nodules not showing both of the typical hallmarks. Three hundred and sixty-four cirrhotic patients underwent liver MRI for 10-30 mm nodules suggestive of HCC. The diagnostic performances of MRI features [T1, T2; diffusion-weighted (DW) imaging signal, enhancement, capsule, fat content] were tested, both individually and in association with both typical hallmarks and as substitutions for one hallmark. The diagnostic reference was obtained using a multifactorial algorithm ensuring high specificity (Sp). Four hundred and ninety-three nodules were analyzed. No alternative features, associations or substitutions outperformed the typical hallmarks for the diagnosis of HCC. For 10-20 mm nodules not displaying one of the typical hallmarks, hyperintensity on DW images was the most accurate substitutive sign, providing a sensitivity of 71.4% and Sp of 75% for nodules without arterial enhancement and sensitivity = 65.2% and Sp = 66% for nodules without washout on the portal or delayed phases. A new diagnostic algorithm, including typical hallmarks as a first step then the best-performing substitutive signs (capsule presence or DW hyperintensity) in combination with the nonmissing typical hallmark as a second step, enabled the correct classification of 77.7% of all nodules, regardless of size. Using MRI, the typical hallmarks remain the best criteria for the diagnosis of small HCCs. However, by incorporating other MRI features, it is possible to build a simple algorithm enabling the noninvasive diagnosis of HCCs displaying both or only one of the typical hallmarks.

Comparison of extracellular and hepatobiliary MR contrast agents for the diagnosis of small HCCs

The aim of this study was to use a head-to-head nodule comparison to compare the performance of extracellular contrast agent MRI (ECA-MRI) with that of hepatobiliary contrast agent MRI (HBA-MRI) for the non-invasive diagnosis of small hepatocellular carcinomas (HCCs). Between August 2014 and October 2017, 171 patients with cirrhosis, each with 1 to 3 nodules measuring 1-3 cm, were enrolled across 8 centers. All patients underwent both an ECA-MRI and an HBA-MRI within a month. A non-invasive diagnosis of HCC was made when a nodule exhibited arterial phase hyper-enhancement (APHE) with washout at the portal venous phase (PVP) and/or delayed phase (DP) for ECA-MRI, or the PVP and/or HB phase (HBP) for HBA-MRI. The gold standard was defined by using a previously published composite algorithm. A total of 225 nodules, of which 153 were HCCs and 72 were not, were included. The sensitivites of both MRI techniques were similar. Specificity was 83.3% (95% CI 72.7-91.1) for ECA-MRI and 68.1% (95% CI 56.0-78.6) for HBA-MRI. In terms of HCC diagnosis on ECA-MRI, 138 nodules had APHE, 84 had washout at PVP, and 104 at DP; on HBA-MRI, 128 nodules had APHE, 71 had washout at PVP, and 99 at HBP. For nodules 2-3 cm in size, sensitivity and specificity were similar between the 2 approaches. For nodules 1-2 cm in size, specificity dropped to 66.1% (95% CI 52.2-78.2) for HBA-MRI vs. 85.7% (95% CI 73.8-93.6) for ECA-MRI. HBA-MRI specificity is lower than that of ECA-MRI for diagnosing small HCCs in patients with cirrhosis. These results raise the question of the proper use of HBA-MRI in algorithms for the non-invasive diagnosis of small HCCs. There are 2 magnetic resonance imaging (MRI)-based approaches available for the non-invasive diagnosis of hepatocellular carcinoma (HCC), using either extracellular or hepatobiliary contrast agents. The current results showed that the sensitivity of MRI with hepatobiliary contrast agents was similar to that with extracellular contrast agents, but the specificity was lower. Thus, hepatobiliary contrast agent-based MRI, although detailed in international guidelines, should be used with caution for the non-invasive diagnosis of HCC. NCT00848952.

Comparison of values of CT and MRI imaging in the diagnosis of hepatocellular carcinoma and analysis of prognostic factors.

Value of computed tomography (CT) and magnetic resonance imaging (MRI) in the diagnosis of small hepatocellular carcinoma (HCC), and in analysis of the prognostic factors of primary hepatocellular carcinoma (PHC) were compared. A total of 300 patients with PHC were selected from January 2013 to January 2016. Among them, 170 patients were diagnosed with small HCC. Patients were diagnosed by MRI and CT scans, respectively, and diagnostic efficacy of the methods was compared. A single factor and multivariate analysis of prognostic factors were performed on 300 patients. The sensitivity of MRI screening was 78.82%, specificity was 78.46%, accuracy was 78.67%, positive predictive value was 82.72%, and negative predictive value was 73.91%. CT screening showed a sensitivity of 62.35%, a specificity of 73.85%, an accuracy of 67.33%, a positive predictive value of 75.71%, and a negative predictive value of 60.00%. Differences in sensitivity, accuracy, and negative predictive value between MRI and CT screening were statistically significant (P<0.05). There was no statistically significant difference between two groups in specificity and positive predictive value (P>0.05). Diagnostic efficiency of MRI is better than that of CT diagnosis. Univariate analysis showed that age, hepatitis B cirrhosis background, tumor stage, and portal vein embolization were prognostic factors for PHC. Cox multivariate regression analysis showed that the background of liver cirrhosis, tumor stage, and portal thrombosis were independent risk factors for poor prognosis for PHC patient and the differences were statistically significant (P<0.05). MRI is superior to CT in the sensitivity, specificity and accuracy of the diagnosis of small HCC. Individualized comprehensive treatment plans based on the patient's condition may be effective in prolonging the patient's survival time. Imaging diagnosis can provide survival basis for patients, improve diagnostic accuracy, and help to improve the survival rate.

Assessment of small hepatocellular carcinoma: perfusion quantification and time-concentration curve evaluation using color-coded and quantitative digital subtraction angiography.

To explore the role of quantitative digital subtraction angiography (QDSA) in the diagnosis of small hepatocellular carcinoma (HCC).Between November 2015 and November 2017, all patients who underwent chemoembolization for HCC were retrospectively reviewed. Patients with tumors measuring more than 5 cm or evident post-processing imaging artifacts were excluded. Images were post-processed using the QDSA technique. Regions of interest were manually drawn on proper hepatic artery (as a reference), target HCC and peritumoral liver. Time-concentration curves and flow parameters of the peak ratio, subtracted time-to-peak (TTP), and area under the curve (AUC) ratio was obtained and analyzed.A total of 146 HCCs (mean diameter, 1.6 cm) of 71 cirrhotic patients (54 men, 17 women; mean age, 67.7 years) were enrolled. Compared with liver parenchyma, HCCs showed an increased and more rapid flow (peak ratio, AUC ratio, subtracted TTP, and wash-in slope; all P <.001). Compared with untreated HCCs, chemoembolized HCCs showed a slower flow (subtracted TTP and wash-in slope, P = .004 and .002, respectively). HCCs with a typical enhancement pattern on computed tomography (CT) or magnetic resonance imaging (MRI) had a trend toward Type III (washout pattern) time-concentration curves (P <.001). Chemoembolized HCCs had a trend toward Type II (plateau pattern) time-concentration curves (P = .005).QDSA technology can be used to quantify perfusion measurements of HCC and hepatic parenchyma and to assess perfusion changes after HCC chemoembolization.

Angio-Computed Tomograph-Guided Immediate Lipiodol Computed Tomograph for Diagnosis of Small Hepatocellular Carcinoma Lesions during Transarterial Chemoembolization.

Background:The diagnosis and treatment of small hepatocellular carcinoma (HCC) play a vital role in the prognosis of patients with HCC. The purpose of our study was to evaluate angio-computed tomography (angio-CT)-guided immediate lipiodol CT (a CT scan performed immediately after transarterial chemoembolization [TACE]) in the diagnosis of potential HCCs ≤1 cm in diameter.Methods:This study retrospectively analyzed 31 patients diagnosed with HCCs after routine imaging (contrast-enhanced CT or magnetic resonance imaging) or pathologic examinations with undefined or undetermined tumor lesions (diameter ≤1 cm) from February 2016 to September 2016. After TACE guided by digital subtraction angiography of the angio-CT system, potential HCC lesions with a diameter ≤1 cm were diagnosed by immediate lipiodol CT. The number of well-demarcated lesions was recorded to calculate the true positive rate. The correlation between the number of small HCCs detected by immediate lipiodol CT and the size of HCC lesions (diameter >1 cm) diagnosed preoperatively was analyzed 1 month after TACE. A paired t-test was used to analyze differences in liver function. Pearson analysis was used to analyze correlation. Chi-square test was used to compare the rates.Results:Fifty-eight lesions were detected on preoperative routine imaging examinations in 31 patients including 15 lesions with a diameter ≤1 cm. Ninety-one lesions were detected on immediate lipiodol CT, of which 48 had a diameter ≤1 cm. After 1 month, CT showed that 45 lesions had lipiodol deposition and three lesions had lipiodol clearance. Correlation analysis showed that the number of small HCCs detected by lipiodol CT was positively correlated with the size of HCC lesions diagnosed by conventional imaging examination (R2 = 0.54, P < 0.05).Conclusion:Immediate lipiodol CT may be a useful tool in the diagnosis of potential HCC lesions with a diameter of ≤1 cm.

Expansile invasive growth pattern is definite evidence for the diagnosis of small hepatocellular carcinomas: a comparative study of 37 cases

Small HCCs, including seHCC and spHCC, are rarely encountered in daily practice. Definite diagnosis is difficult for general pathologists. In this study, we reviewed 1025 cases of HCC and examined the histologic characteristics of small HCCs to facilitate more accurate diagnosis. Slides of archived HCC cases were reviewed by 2 senior pathologists, and small HCCs were identified according to the canonical criteria. Additional immunohistochemical stains were performed. Thirty-seven cases of small HCC were identified, including 22 cases of seHCC and 15 cases of spHCC. We found 2 types of invasive growth patterns in these lesions. The first is the expansile invasive growth pattern, with monomorphic tumor cells penetrating through the incomplete fibrous capsules and expanding into the adjacent noncancerous liver with a spherical, hemispheric, or mushroom shape. The second is the classic stromal invasion pattern. At least one type of invasive pattern was observed in all of the 37 cases of small HCC, and the seHCCs exhibit the expansile invasive growth pattern more frequently than the classic stromal invasion pattern. On the contrary, stromal invasive pattern was more common in spHCC nodules. In conclusion, with the background of chronic hepatitis and cirrhosis, histologic features including crowdedness of hepatocytic trabeculae and the expansile invasive growth pattern are strong evidence for the diagnoses of small HCC.

Clinical value of contrast-enhanced ultrasound in early diagnosis of liver cirrhosis complicated with small hepatocellular carcinoma

Objective To investigate the clinical value of contrast-enhanced ultrasonography in early diagnosis of liver cirrhosis and small hepatocellular carcinoma. Methods 60 patients with cirrhosis and small hepatocellular carcinoma were diagnosed by pathological examination.The number of lesions in the liver, the mode of enhanced expression were recorded, and all lesions were evaluated as benign and malignant before and after contrast-enhanced ultrasound. Results A total of 60 patients with 70 lesions were detected, all of which were less than 3cm.50 low differentiated carcinoma lesions, accounted for 71.42%, the contrast mode performance for arterial phase rapid enhancement, parenchymal lesion signal was lower than that of normal liver parenchyma, fast forward and fast.14 well differentiated carcinoma lesions, accounted for 20.00%, contrast mode performance for the arterial phase rapid enhancement, parenchymal lesion signal higher than that of normal liver parenchyma, namely fast and slow.Compared with before the contrast, the malignant grade of the lesion was significantly increased (χ2=4.525, P<0.05). Conclusion Ultrasound contrast in the early detection of liver cirrhosis with small liver cancer has high sensitivity, it is helpful to find lesions, evaluate the benign and malignant lesion, it can be used as a imaging method in diagnosis of small hepatocellular carcinoma. Key words: Ultrasonography; Liver Cirrhosis; Liver neoplasms; Early diagnosis

Study on the diagnosis of small hepatocellular carcinoma caused by hepatitis B cirrhosis via multi-slice spiral CT and MRI.

The present study compared the diagnostic accuracy of multi-slice spiral computed tomography (CT) and magnetic resonance imaging (MRI) on small hepatocellular carcinoma (SHCC) caused by hepatitis B cirrhosis. A total of 160 patients with hepatitis B cirrhosis were selected between January 2012 and April 2016, and 183 SHCC lesions were included in the present retrospective study. Patients were divided into the SHCC group (T stage) and the micro hepatocellular carcinoma (MHCC) group (T1 stage). There were a total of 129 SHCC lesions and 54 MHCC lesions identified. All patients underwent multiphasic CT and MRI imaging. The liver acquisition with volume acquisition (LAVA) technique was utilized for MRI. Furthermore, SPSS 20.0 was used for statistical analyses. LAVA in the arterial phase and CT in the arterial phase revealed significantly higher diagnostic rates for the diagnoses of 183 lesions. In addition, standard CT scan exhibited significantly reduced diagnostic rates in SHCC lesions. Results indicated that LAVA in the equilibrium phase had the lowest diagnostic rate in MHCC lesions, which was statistically significant (P<0.05). Overall, the diagnostic rate of CT (79.63%) for MHCC was significantly lower than that of MRI (96.29%) (P<0.05). However, the diagnostic rate of CT for SHCC (96.12%) was significantly higher than that for MHCC (79.63%) (P<0.05). MRI-LAVA in the arterial phase has the highest diagnostic rate for SHCC and MHCC. However, the diagnostic capability of MRI for MHCC lesions is superior to that of CT.

Molecular markers for the monitoring of malignant transformation of hepatocytes and early diagnosis of liver cancer

The monitoring of malignant transformation of hepatocytes or early diagnosis of primary hepatocellular carcinoma (PHC) remains a challenge in the medical world. Routine examinations including serum alpha-fetoprotein level and ultrasound examination have a limited value in the diagnosis of small hepatocellular carcinoma; however, the effective treatment of PHC depends on its early diagnosis. In recent years, molecular markers including important signaling molecules in PHC-related pathways, carcinoembryonic proteins, and non-coding RNA help with the monitoring of malignant transformation of hepatocytes or early diagnosis of liver cancer. This article reviews the valuable molecular markers in the monitoring of malignant transformation of hepatocytes or early diagnosis of liver cancer.

Comparison between Computer Tomography and Magnetic Resonance Imaging in the Diagnosis of Small Hepatocellular Carcinoma

Background:Hepatocellular carcinomas (HCCs) less than 2 cm in diameter generally demonstrate a good outcome after curative therapy. However, the diagnosis of small HCC can be problematic and requires one or more dynamic imaging modalities. This study aimed to compare the sensitivity and agreement between CT and MRI for the diagnosis of small HCCs.Methods:CT and/or MRI scans of HCCs (1-2 cm) diagnosed by histopathology or typical vascular pattern according to the 2005 AASLD criteria were blindly reviewed by an abdominal radiologist. The reports were defined as conclusive/typical when arterial enhancement and washout during the portal/delayed phases were observed and as inconclusive when typical vascular patterns were not observed. The sensitivity and Cohen’s kappa (k) for agreement were calculated.Results:In 27 patients, 27 HCC nodules (1-2 cm) were included. Diagnosis with a single-imaging modality (CT or MRI) was 81 % versus 48 % (p = 0.01). The CT sensitivity was significantly higher than MRI (78 % versus 52 %, p = 0.04). Among 27 nodules that underwent both CT and MRI, a discordance in typical enhancement patterns was found (k = 0.319, p = 0.05). In cases with inconclusive CT results, MRI gave only an additional 3.7 % sensitivity to reach a diagnosis. In contrast, further CT imaging following inconclusive MRI results gave an additional 29.6 % sensitivity.Conclusions:A single typical imaging modality is sufficient to diagnose small HCCs. Compared with MRI, multiphasic CT has a higher sensitivity. The limitations of MRI could be explained by the greater need for patient cooperation and the types of MRI contrast agent.

A meta-analysis of contrast-enhanced ultrasound for small hepatocellular carcinoma diagnosis.

To discuss the efficacy of contrast-enhanced ultrasound (CEUS) for diagnosis of small hepatocellular carcinoma (HCC) by pooling the open published data. A comprehensive publication electronic search was performed by reviewers in the databases of PubMed, Embase, Web of Science, and China National Knowledge Infrastructure. The open published studies about CEUS for small HCC diagnosis were collected. The sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), and diagnostic odds ratio (DOR) were pooled by stata 12.0 software. A total of 16 studies were included in the present study. The sensitivity, specificity, +LR, and -LR were aggregated by random effects model because of significant heterogeneity (I2 >50.0%). However, DOR was pooled by fixed effects model without significant heterogeneity (I2 <50.0%). The aggregate sensitivity was 0.86 (95% confidence interval [CI]: 0.79-0.91); the aggregate specificity was 0.87 (95% CI: 0.75-0.94); the aggregate +LR and -LR were 7.06 (95% CI: 1.64-30.36) and 0.20 (95% CI: 1.64-30.36), respectively. The DOR was 33.71 (95% CI: 20.34-55.88); the area under the receiver operating characteristic was 0.93 (95% CI: 0.90-0.95). There was significant publication bias tested by funnel plot and line regression test (t = 2.29, P < 0.05). With the present evidence, CEUS is useful for diagnosis of small HCC with relatively high sensitivity and specificity.

Metabolomics Identifies Biomarker Pattern for Early Diagnosis of Hepatocellular Carcinoma: from Diethylnitrosamine Treated Rats to Patients.

Early diagnosis of hepatocellular carcinoma (HCC) remains challenging to date. Characteristic metabolic deregulations of HCC may enable novel biomarkers discovery for early diagnosis. A capillary electrophoresis-time of flight mass spectrometry (CE-TOF/MS)-based metabolomics approach was performed to discover and validate potential biomarkers for HCC from the diethylnitrosamine-induced rat hepatocarcinogenesis model to human subjects. Time series sera from the animal model were evaluated using multivariate and univariate analyses to reveal dynamic metabolic changes. Two independent human cohorts (populations I and II) containing 122 human serum specimens were enrolled for validations. A novel biomarker pattern of ratio creatine/betaine which reflects the balance of methylation was identified. This biomarker pattern achieved effective classification of pre-HCC and HCC stages in animal model. It was still effective in the diagnosis of HCC from high-risk patients with cirrhotic nodules, achieving AUC values of 0.865 and 0.905 for two validation cohorts, respectively. The diagnosis of small HCC from cirrhosis with an AUC of 0.928 highlighted the potential for early diagnosis. This ratio biomarker can also improve the diagnostic performance of α-fetoprotein (AFP). This study demonstrates the efficacy of present strategy for biomarker discovery, and the potential of metabolomics approach to provide novel insights for disease study.