Liver Nodules In Patients Research Articles

Natural History of Indeterminate Liver Nodules in Patients With Advanced Liver Disease: A Multicenter Retrospective Cohort Study.

Indeterminate liver nodules (ILNs) are frequently encountered on diagnostic imaging after positive hepatocellular carcinoma (HCC) surveillance results, but their natural history remains unclear. We conducted a multicenter retrospective cohort study among patients with ≥1 newly detected LI-RADS 3 (LR-3) lesion ≥1 cm or LI-RADS 4 (LR-4) lesion of any size (per LI-RADS v2018) between January 2018 and December 2019. Patients were followed with repeat imaging at each site per institutional standard of care. Multivariable Fine-Gray models were used to evaluate associations between potential risk factors and patient-level time-to-HCC diagnosis, with death and liver transplantation as competing risks. Of 307 patients with ILNs, 208 had LR-3 lesions, 83 had LR-4 lesions, and 16 had both LR-3 and LR-4 lesions. HCC incidence rates for patients with LR-3 and LR-4 lesions were 110 (95% CI 70-150) and 420 (95% CI 310-560) per 1,000 person-year, respectively. In multivariable analysis, incident HCC among patients with LR-3 lesions was associated with older age, thrombocytopenia (platelet count ≤150 ×10 9 /L), and elevated serum alpha-fetoprotein levels. Among those with LR-4 lesions, incident HCC was associated with a maximum lesion diameter >1 cm. Although most patients had follow-up computed tomography or magnetic resonance imaging, 13.7% had no follow-up imaging and another 14.3% had follow-up ultrasound only. ILNs have a high but variable risk of HCC, with 4-fold higher risk in patients with LR-4 lesions than those with LR-3 lesions, highlighting a need for accurate risk stratification tools and close follow-up in this population.

Compared with SonoVue® LR-5, Sonazoid® modified LR-5 has better diagnostic sensitivity for hepatocellular carcinoma: a systematic review and meta-analysis.

The contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) is a standardized system for reporting liver nodules in patients at risk of developing hepatocellular carcinoma (HCC) and is only recommended for pure blood pool agents such as SonoVue®. A modified LI-RADS was proposed for Sonazoid®, a Kupffer cell-specific contrast agent. This meta-analysis was conducted to compare the diagnostic efficiency of the CEUS LI-RADS for SonoVue® and the modified LI-RADS for Sonazoid®. The PubMed, Medline, Web of Science, Embase, and Cochrane Library databases were systematically searched to retrieve studies on the diagnostic efficiency of the CEUS LI-RADS algorithms in diagnosing HCC using SonoVue® and/or Sonazoid® from January 2016 to June 2023. Histopathology or imaging follow-up served as the reference standards. Only articles published in English on retrospective or prospective studies with full reports were included in the meta-analysis. A bivariate random-effects model was used. Data pooling, meta-regression, and sensitivity analysis were performed for the meta-analysis. Deeks' funnel plot asymmetry test was used to evaluate publication bias, and the QUADAS-2 tool was used to assess the methodological quality of eligible studies. In total, 26 studies comprising 8,495 patients with 9,244 lesions were included in the meta-analysis. The pooled data results for SonoVue® LI-RADS category 5 (LR-5) and Sonazoid® modified LR-5 were as follows: pooled sensitivity: 0.68 [95%confidence interval (CI): 0.64-0.73, I2=89.20%; P<0.01] and 0.82 (95% CI: 0.74-0.87, I2=85.39%; P<0.01) (P<0.05); pooled specificity: 0.93 (95% CI: 0.90-0.96, I2=86.52%; P<0.01) and 0.86 (95% CI: 0.79-0.91, I2=59.91%; P=0.01) (P<0.05); pooled area under the curve (AUC): 0.86 (95% CI: 0.82-0.89) and 0.91 (95% CI: 0.88-0.93) (P<0.05), respectively. The meta-regression analysis revealed that the study design, subject enrollment method, and reference standard contributed to the heterogeneity of SonoVue® LR-5, and the number of lesions was a source of heterogeneity for Sonazoid® modified LR-5. The diagnostic performance of the LI-RADS category M (LR-M) algorithms of SonoVue® and Sonazoid® was comparable. The Sonazoid® modified LR-5 algorithm had a higher diagnostic sensitivity, lower specificity, and higher AUC than SonoVue® LR-5.

Diagnosis and management of indeterminate liver nodules in patients with cirrhosis.

Diagnosis and management of indeterminate liver nodules in patients with cirrhosis.

Apparent diffusion coefficient is a good marker in predicting the prognosis in colorectal cancer liver metastases: a diagnostic study.

Colorectal cancer (CRC) is one of the most common malignant tumors. Up to 10% CRC patients can have liver metastases at the first diagnosis. At present, clinical diagnosis of CRC liver metastasis (CRCLM) is mostly based on imaging, and there is a certain false-positive rate and false-negative rate. Improving the diagnostic accuracy of imaging for CRCLM is highly significant. Apparent diffusion coefficients showed high predicting value in other cancers. The aim of the present study was to explore the diagnostic value of apparent diffusion coefficients based on magnetic resonance diffusion weighted imaging for CRCLM. Fifty patients with CRCLM admitted to Hebei Yanda Hospital from January 2018 to December 2018 were retrospectively collected, and the data of 50 patients with benign liver nodules were collected at the same time. The diagnostic value of apparent diffusion coefficients on liver metastatic cancer was analyzed using receiver operating characteristic curve. The correlation between apparent diffusion coefficients and clinical pathological features of patients with CRCLM was also analyzed. The diagnosis of liver metastatic cancer was based on pathological biopsy. Three-year follow up after surgery was conducted in clinic or via phone. Compared with the benign liver nodule group, the apparent diffusion coefficients of patients in the CRCLM group were significantly decreased [(1.14±0.26 vs. 2.06±0.57)×10-3 mm2/s, P<0.001]. The apparent diffusion coefficient was of high value in differentiating between benign liver nodules and liver metastatic cancer. The area under the curve was 0.927 [95% confidence interval (CI): 0.879-0.975, P<0.001]. Compared with patients with highly differentiated tumors, the apparent diffusion coefficients of patients with moderately and poorly differentiated tumors were significantly reduced [(1.08±0.26 vs. 1.29±0.22)×10-3 mm2/s, P=0.010]. Compared with patients who survived 3 years after operation, the apparent diffusion coefficients of patients who died were significantly lower [(1.05±0.26 vs. 1.23±0.23)×10-3 mm2/s, P=0.011]. The apparent diffusion coefficients of liver nodules in patients with CRCLM is a good marker in predicting postoperative 3-year survival, and the area under the curve was 0.728 (95% CI: 0.580-0.876, P=0.006). The apparent diffusion coefficient can sever as a marker in diagnosing CRCLM and predicting prognosis.

The Feasibility of Liver Biopsy for Undefined Nodules in Patients under Surveillance for Hepatocellular Carcinoma: Is Biopsy Really a Useful Tool?

Background: The aim of the present study is to determine the feasibility of biopsy for atypical liver nodules in patients under surveillance for hepatocellular carcinoma (HCC), assessing which factors influence the decision to perform it. Methods: A total of 128 atypical liver nodules in 108 patients under surveillance for HCC, who underwent CT between September 2018 and September 2019, were included. All the images were saved digitally (on CD-ROM) and the two most representative images in the arterial and delayed phases were selected for each lesion and inserted into a digital atlas (on PDF). Two experienced radiologists (Readers 1 and 2) reviewed both the CD-ROM and the PDF to define the feasibility of biopsy in both scenarios, specifying the reasons for the unfeasibility of biopsy. The intra-observer variability and inter-observer variability were assessed. Results: When reviewing the PDF, 76 (59.4%) and 68 (53.1%) nodules were deemed unfeasible for biopsy by the less experienced radiologist (Reader 1) and the more experienced radiologist (Reader 2), respectively (p = 0.604). When reviewing the entire CT study, both percentages decreased slightly (Reader 1 = 70/128 (54.7%); Reader 2 = 61/128 (47.6%); p = 0.591). The intra-reader agreement on the PDF was substantial (k = 0.648 (95% CI = 0.513–0.783)). The inter-reader agreement on the PDF was slight (k = 0.185 (95% CI = 0.021–0.348)) and moderate on the entire CT study (k = 0.424 (95% CI = 0.269–0.579)). When assessing the PDF, the nodule size (10–20 mm) and location in segments six and eight were negatively and positively associated with the feasibility of liver biopsy, respectively. When assessing the CD-ROM, only the nodule dimension was associated with the unfeasibility of liver biopsy. Conclusions: The unfeasibility of liver biopsy is mainly due to the small size of the lesions and their location.

Comparison of modified CEUS LI-RADS with sonazoid and CT/MRI LI-RADS for diagnosis of hepatocellular carcinoma.

To compare the diagnostic performance based on the modified CEUS Liver Imaging Reporting and Data System (LI-RADS), which includes Kupffer-phase findings as a major imaging feature, with that of CT and MRI (CT/MRI) LI-RADS for liver nodules in patients at high risk of HCC. A total of 120 patients with 120 nodules were included in this retrospective study. The median size of the lesions was 20.0mm (interquartile range, 14.0-30.8mm). Of these lesions, 90.0% (108 of 120) were confirmed as HCCs, 6.7% (8 of 120) were intrahepatic cholangiocarcinomas, 1.7% (2 of 120) were metastases, and 1.7% (2 of 120) were dysplastic nodules. All nodules were diagnosed histopathologically. Each nodule was categorized according to the modified CEUS LI-RADS and CT/MRI LI-RADS version 2018. The diagnostic performance and inter-modality agreement of each criterion was compared. The inter-modality agreement for the modified CEUS LI-RADS and CT/MRI LI-RADS was slight agreement (kappa=0.139, p=0.015). The diagnostic accuracies of HCCs for the modified CEUS LR-5 and CT/MRI LR-5 were 70.0% (95% confidence interval [CI]: 61.0%, 78.0%) versus 70.8% (95% CI: 61.8%, 78.8%) (p=0.876), respectively. The diagnostic accuracies of non-HCC malignancies for the modified CEUS LR-M and CT/MRI LR-M were 84.2% (95% CI: 76.4%, 90.2%) versus 96.7% (95% CI: 91.7%, 99.1%) (p=0.002), respectively. The diagnostic performance for HCCs on the modified CEUS LR-5 and CT/MRI LR-5 are comparable. In contrast, CT/MRI LR-M has better diagnostic performance for non-HCC malignancy than that of the modified CEUS LR-M.

Benign Hepatic Nodules in Patients With Primary Extrahepatic Portal Vein Obstruction: Clinical and Magnetic Resonance Imaging Features

To retrospectively evaluate the magnetic resonance imaging (MRI) features of benign hepatic nodules in patients with extrahepatic portal vein obstruction (EHPVO) and assess predictable features for their development. This retrospective observational study included 18 diagnosed patients of EHPVO who underwent contrast enhanced abdominal MRI at our Institute between June 2016 and May 2017, and who could be followed up for at least two years. The patients with liver nodules formed the study group (n= 8; 4 males, 4 females; mean age: 26.1±10.9 years) and patients without liver nodules were controls (n= 10; 3 males, 7 females; mean age: 24.2±15.1 years). Liver nodules were confirmed as benign by either biopsy or stability on follow up imaging. MRI features of liver nodules were assessed. Clinical details and imaging data of the study group were compared with controls to assess predictable features. There was no statistically significant difference in age, gender, clinical characteristics and upper gastrointestinal endoscopic findings between the study and control groups. The size of the lienorenal collateral,left renal vein and superior mesenteric vein were significantly larger in the study group (P < 0.05). In the study group, the majority had multiple hepatic nodules with most of them being isointense on T1 (18/35; 51.4%) and T2-weighted images (16/35; 45.7%) and showing restriction of diffusion (21/35; 60%). All (n= 35) lesions showed arterial phase hyperenhancement and none showed washout in the venous phase. The patients in the control group did not develop any liver nodules during the follow-up period. Liver nodules in patients with EHPVO are likely to be benign and have characteristic MRI features. Significantly larger lienorenal collateral,left renal vein and superior mesenteric vein were associated with the development of these nodules.

P-L01 Newly detected liver nodules with a history of colorectal cancer: are they metastasis?

Abstract Background The diagnosis of newly detected liver nodules in patients with colorectal cancer (CRC) is crucial for determining prognosis and treatment. Accurate identification of benign nodules can help avoid unnecessary therapy. The aim of our study was to retrospectively review CRC patients who underwent liver resection for newly detected liver nodules in our institution. Methods We went over all patients with a history of CRC, who underwent liver resection from January 2012 to December 2019 in our institution. We specifically focused on nodules pathologically confirmed benign. Clinicopathological characteristics of these patients were collected. Results From 2012 to 2019, a total of 2632 CRC patients received liver resection for liver nodules, among which 2584 cases were proved to be malignant, and 48 cases were benign. Among these 48 cases, 24 were pathologically confirmed as focal nodular hyperplasia (FNH), 10 were inflammatory lesions, 9 were peliosis, and 5 were hemangioma. At least one pre-operative imaging examination (MRI, US, or PET-CT) indicated CRLM, while no one underwent gadoxetic acid-enhanced MRI. The median size of nodule was 2.0 cm (range, 0.4-8.0 cm). For therapy, ten patients received laparoscopic surgery, and 38 patients received open surgery; ten patients received chemotherapy after discovery of liver nodules. Conclusions Newly detected liver nodules with a history of colorectal cancer could be benign. Gadoxetic acid-enhanced MRI should be considered especially for indeterminate liver nodules that would be mimicker of colorectal cancer liver metastasis.

Liver nodules after the Fontan operation: role of the computerised tomography scan.

Currently, there is an increasing prevalence of liver nodules in patients following the Fontan operation. The appropriate non-invasive modalities have been applied to assess a diagnosis of Fontan-associated liver disease. The aims of this study were to determine the prevalence and associated factors for the presence of liver nodules using CT scan. A cross-sectional study of 34 patients older than 15 years of age was recruited. Ultrasound upper abdomen, ultrasound liver elastography, and CT scan of the upper abdomen were performed after the Fontan operation. The median age of patients was 20 years (range 14-36 years). The median age at the Fontan operation was 7 years (range 5-17 years) and the duration after the Fontan operation was 12 years (range 4-22 years). The prevalence of liver nodules was 62% as detected by CT scans. Hepatic vein pressure in patients with liver nodules was significantly higher than in those without liver nodules. Hepatic vein pressure above 13 mmHg was a factor associated with liver nodules. There was little agreement between the ultrasound of the upper abdomen and CT scan of the upper abdomen in the evaluation of liver nodules. Hepatic pressure was the only associated factor for the occurrence of liver nodules in patients following the Fontan operation. The prevalence of liver nodules was very high after the Fontan operation. The upper abdomen CT scan should be performed for the surveillance of liver nodules in every Fontan patient over the age of 15 years.

Newly detected liver nodules with a history of colorectal cancer: are they metastatic? Review of 2,632 cases in a single center.

BackgroundThe diagnosis of newly detected liver nodules in patients with colorectal cancer (CRC) is crucial for determining prognosis and treatment. Accurate identification of benign nodules can help avoid unnecessary therapy. The aim of our study was to retrospectively review patients with CRC who underwent liver resection for benign liver nodules misdiagnosed as CRC metastasis (CRLM) in our institution.MethodsWe reviewed all patients with a history of CRC who underwent liver resection from January 2012 to December 2019 in our institution. We specifically focused on nodules pathologically confirmed as benign. The pathology was rechecked by an independent pathologist. The clinicopathological characteristics of these patients were collected. Preoperative imaging examinations, including ultrasound (US), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT) were reviewed.ResultsFrom 2012 to 2019, a total of 2,632 patients with CRC who were preoperatively diagnosed CRLM received liver resection, among which 2,584 (98.2%) cases were proven to be malignant, and 48 (1.8%) cases were benign. Among these 48 cases, 24 were pathologically confirmed as focal nodular hyperplasia (FNH), 9 were peliosis, 10 were inflammatory lesions, and 5 were hemangioma. At least one preoperative imaging examination indicated CRLM, with a median size of 2.0 cm (range, 0.4–8.0 cm). Before liver resection, ten patients received chemotherapy after the discovery of liver nodules.ConclusionsIt should be noted that newly detected liver nodules in patients with a history of CRC could be benign. Accurate diagnosis of liver nodules in CRC is necessary to avoid overtreatment and to identify cost-effective medication.

Contrast-enhanced ultrasound LI-RADS 2017: comparison with CT/MRI LI-RADS.

To compare the classification based on contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) with that of contrast-enhanced CT and MRI (CECT/MRI) LI-RADS for liver nodules in patients at high risk of hepatocellular carcinoma. Two hundred thirty-nine patients with 273 nodules were enrolled in this retrospective study. Each nodule was categorized according to the CEUS LI-RADS version 2017 and CECT/MRI LI-RADS version 2017. The diagnostic performance of CEUS and CECT/MRI was compared. The reference standard was histopathology diagnosis. Inter-modality agreement was assessed with Cohen's kappa. The inter-modality agreement for CEUS LI-RADS and CECT/MRI LI-RADS was fair with a kappa value of 0.319 (p < 0.001). The positive predictive values (PPVs) of hepatocellular carcinoma (HCC) in LR-5, LR-4, and LR-3 were 98.3%, 60.0%, and 25.0% in CEUS, and 95.9%, 65.7%, and 48.1% in CECT/MRI, respectively. The sensitivities and specificities of LR-5 for diagnosing HCC were 75.6% and 93.8% in CEUS, and 83.6% and 83.3% in CECT/MRI, respectively. The positive predictive values of non-HCC malignancy in CEUS LR-M and CECT/MRI LR-M were 33.9% and 93.3%, respectively. The sensitivity, specificity, and accuracy for diagnosing non-HCC malignancy were 90.9%, 84.5%, and 85.0% in CEUS LR-M and 63.6%, 99.6%, and 96.7% in CECT/MRI LR-M, respectively. The inter-modality agreement of the LI-RADS category between CEUS and CECT/MRI is fair. The positive predictive values of HCCs in LR-5 of the CEUS and CECT/MRI LI-RADS are comparable. CECT/MRI LR-M has better diagnostic performance for non-HCC malignancy than CEUS LR-M. • The inter-modality agreement for the final LI-RADS category between CEUS and CECT/MRI is fair. • The LR-5 of CEUS and CECT/MRI LI-RADS corresponds to comparable positive predictive values (PPVs) of HCC. For LR-3 and LR-4 nodules categorized by CECT/MRI, CEUS examination should be performed, at least if they can be detected on plain ultrasound. • CECT/MRI LR-M has better diagnostic performance for non-HCC malignancy than CEUS LR-M. For LR-M nodules categorized by CEUS, re-evaluation by CECT/MRI is necessary.

LI-RADS to categorize liver nodules in patients at risk of HCC: tool or a gadget in daily practice?

To determine the effectiveness of liver reporting and data system (LI-RADS) to diagnose hepatocellular carcinoma (HCC) and to retrospectively evaluate its impact on the adopted therapeutic strategy. Preoperative imaging of 40 of 350 patients (median age 66, 31M/9 F) submitted to liver resection for suspected HCC, between January 2008 and August 2019, has been retrospectively analyzed by two radiologists with different expertise, according to CT/MRI LI-RADS®v2018, both blinded to clinical and pathological results and untrained to using aforementioned scoring system. The perfect agreement between the readers was about 62.5% (25/40) (Cohen k: 0.41), better for LR-5 category (16/25) and higher in magnetic resonance imaging (MRI) investigations (68%; 13/19), which has been demonstrated the modality of choice for diagnosis of high probable and certain HCC, with arterial phase hyperenhancement as the most sensitive and accurate major feature. Compared to final histology, LR4 and LR5 scores assigned by senior radiologist reached sensitivity, specificity, positive and negative predictive values (PPV, PNV) and diagnostic accuracy of 90,9%, 29,0%, 93,8%, 62,5% and 87,5%, respectively, slightly higher than junior's ones. Misdiagnosis of HCC was done by both radiologists in the same two patients: 1 primary hepatic lymphoma (PHL) and 1 regenerative liver nodule (RLN). If LI-RADS would have been applied at the time of pre-surgical imaging, treatment planning would be modified in 10% of patients (4/40); the patient scheduled as LR-3 and finally resulted a focal nodular hyperplasia would have avoided liver resection. Application of LI-RADS, especially on MRI, may provide a more accurate evaluation of suspected HCC. PHL and RLN are the Achille's heels according to our experience.

Detection of Dysplastic Liver Nodules in Patients with Cirrhosis Using the Multi-Arterial CAIPIRINHA-Dixon-TWIST-Volume-Interpolated Breath-Hold Examination (MA-CDT-VIBE) Technique in Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

BackgroundThe multi-arterial CAIPIRINHA-Dixon-TWIST-volume-interpolated breath-hold examination (MA-CDT-VIBE) sequence has the advantage of detecting hypervascular lesions during the arterial phase of magnetic resonance imaging (MRI) of the liver. Liver cirrhosis may be associated with dysplastic nodules. This study aimed to compare the use of routine liver MRI sequences with the MA-CDT-VIBE sequence to identify dysplastic liver nodules in patients with liver cirrhosis.Material/MethodsBetween February 2016 and March 2017, there were 21 patients with liver cirrhosis who had 33 dysplastic liver nodules, which were detected by comprehensive multisequence MRI as the reference standard for nodule imaging. Liver MRI using edge sharpness assessment by parametric (ESAP) modeling was compared with five dynamic arterial subphases that were included in the MA-CDT-VIBE sequence with a temporal resolution of 2.8 s and an acquisition time of 20 s during one breath-hold.ResultsIn the 21 patients included in the study, the MA-CDT-VIBE technique (30/33 for the first reading and 33/33 for the second reading) showed an improved lesion detection rate compared with the ESAP technique (27/33 for the first reading and 29/33 for the second reading), and for 73% of the patients, MA-CDT-VIBE imaging showed improved arterial parenchyma contrast. There was a high degree of interobserver agreement between the two reads (κ: 0.68–0.91; P<0.001).ConclusionsThe MA-CDT-VIBE sequence of MRI liver imaging improved the detection of dysplastic nodules in cirrhosis of the liver compared with routine liver MRI sequences.

Diagnostic Accuracy of CEUS LI-RADS for the Characterization of Liver Nodules 20 mm or Smaller in Patients at Risk for Hepatocellular Carcinoma.

Background American College of Radiology contrast agent-enhanced US Liver Imaging Reporting and Data System (CEUS LI-RADS) was developed to improve the accuracy of hepatocellular carcinoma (HCC) diagnosis at contrast agent-enhanced US. However, to the knowledge of the authors, the diagnostic accuracy of the system in characterization of liver nodules 20 mm or smaller has not been fully evaluated. Purpose To evaluate the diagnostic accuracy of CEUS LI-RADS in diagnosing HCC in liver nodules 20 mm or smaller in patients at risk for HCC. Materials and Methods Between January 2015 and February 2018, consecutive patients at risk for HCC presenting with untreated liver nodules 20 mm or less were enrolled in this retrospective double-reader study. Each nodule was categorized according to the CEUS LI-RADS and World Federation for Ultrasound in Medicine and Biology (WFUMB)-European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) criteria. Diagnostic performance of CEUS LI-RADS and WFUMB-EFSUMB characterization was evaluated by using tissue histologic analysis, multiphase contrast-enhanced CT and MRI, and imaging follow-up as reference standard and compared by using McNemar test. Results The study included 175 nodules (mean diameter, 16.1 mm ± 3.4) in 172 patients (mean age, 51.8 years ± 10.6; 136 men). The sensitivity of CEUS LR-5 versus WFUMB-EFSUMB criteria in diagnosing HCC was 73.3% (95% confidence interval [CI]: 63.8%, 81.5%) versus 88.6% (95% CI: 80.9%, 94%), respectively (P < .001). The specificity of CEUS LR-5 versus WFUMB-EFSUMB criteria was 97.1% (95% CI: 90.1%, 99.7%) versus 87.1% (95% CI: 77%, 94%), respectively (P = .02). No malignant lesions were found in CEUS LR-1 and LR-2 categories. Only two nodules (of 41; 5%, both HCC) were malignant in CEUS LR-3 category. The incidences of HCC in CEUS LR-4, LR-5, and LR-M were 48% (11 of 23), 98% (77 of 79), and 75% (15 of 20), respectively. Two of 175 (1.1%) histologic analysis-confirmed intrahepatic cholangiocarcinomas were categorized as CEUS LR-M by CEUS LI-RADS and misdiagnosed as HCC by WFUMB-EFSUMB criteria. Conclusion The contrast-enhanced US Liver Imaging Reporting and Data System (CEUS LI-RADS) algorithm was an effective tool for characterization of small (≤20 mm) liver nodules in patients at risk for hepatocellular carcinoma (HCC). Compared with World Federation for Ultrasound in Medicine and Biology-European Federation of Societies for Ultrasound in Medicine and Biology criteria, CEUS LR-5 demonstrated higher specificity for diagnosing small HCCs with lower sensitivity. Published under a CC BY 4.0 license. See also the editorial by Crocetti in this issue.

Evaluation of Contrast-enhanced US LI-RADS version 2017: Application on 2020 Liver Nodules in Patients with Hepatitis B Infection.

Background Use of contrast material-enhanced (CE) US Liver Imaging Reporting and Data System (LI-RADS) version 2017 has not been validated in large populations where hepatitis B virus (HBV) is endemic. Purpose To evaluate the diagnostic performance of CE US LI-RADS version 2017 in a population with a high prevalence of HBV infection. Materials and Methods In this retrospective study, liver nodules in patients with HBV who were evaluated from January 2004 to December 2016 were categorized as CE US LR-1 to LR-5 through LR-M. A subgroup of LR-M nodules was reclassified as LR-5, and additional analysis was performed. The reference standard consisted of histologic evaluation or composite imaging and clinical follow-up findings. Diagnostic performance was assessed with sensitivity, specificity, positive predictive value (PPV), and negative predictive value. Results A total of 2020 nodules in 1826 patients (median age, 54 years ± 12 [standard deviation]; 1642 men) were included. Of the 1159 LR-5 lesions, 1141 were hepatocellular carcinoma (HCC); three, intrahepatic cholangiocarcinomas; six, other malignancies; six, atypical hyperplasia; and three, benign lesions. The PPV of LR-5 for HCC was 98% (95% confidence interval [CI]: 98%, 99%). In LR-M nodules, 153 showed arterial phase hyperenhancement, early washout, and absence of punched-out appearance within 5 minutes, and 142 of 153 (93%; 95% CI: 89%, 97%) were HCC. If these nodules were reclassified as LR-5, LR-M specificity and PPV as a predictor of non-HCC malignancy increased from 88% (95% CI: 87%, 89%) and 36% (95% CI: 31%, 41%) to 96% (95% CI: 95%, 97%) and 58% (95% CI: 51%, 65%), respectively (P < .001). Despite reclassification, LR-5 specificity and PPV remained high (94% [95% CI: 92%, 96%] and 98% [95% CI: 97%, 99%], respectively). Conclusion The contrast-enhanced US Liver Imaging Reporting and Data System version 2017 category LR-5 is effectively predictive of the presence of hepatocellular carcinoma. In patients with hepatitis B virus infection, performance may be further improved by reclassification of category LR-M nodules with arterial phase hyperenhancement, early washout, and no punched-out appearance to LR-5. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Sidhu in this issue.

Prevalence, features and predictive factors of liver nodules in Fontan surgery patients: The VALDIG Fonliver prospective cohort

Fontan surgery is used to treat a variety of congenital heart malformations, and may lead to advanced chronic liver disease in the long-term. This study examines the prevalence, characteristics and predictors of liver nodules in patients following Fontan surgery. This was a prospective, cross-sectional, observational study conducted at 8 European centres. Consecutive patients who had undergone Fontan surgery underwent blood tests, abdominal ultrasonography (US), transient elastography (Fibroscan®), echocardiography, haemodynamic assessments, and abdominal MRI/CT scan. The primary outcome measure was liver nodules detected in the MRI/CT scan. Predictors of liver nodules were identified by multivariate logistic regression. One hundred and fifty-two patients were enrolled (mean age 27.3 years). The mean time elapsed from surgery to inclusion was 18.3 years. Liver nodule prevalences were 29.6% (95% CI 23-37%) on US and 47.7% (95% CI 39-56%) on MRI/CT. Nodules were usually hyperechoic (76.5%), round-shaped (>80%), hyperenhancing in the arterial phase (92%) and located in the liver periphery (75%). The sensitivity and specificity of US were 50% (95% CI 38-62%) and 85.3% (95% CI 75-92%), respectively. Inter-imaging test agreement was low (adjusted kappa: 0.34). In the multivariate analysis, time since surgery >10 years was the single independent predictor of liver nodules (odds ratio 4.18; p= 0.040). Hepatocellular carcinoma was histologically diagnosed in 2 of the 8 patients with hypervascular liver nodules displaying washout. While liver nodules are frequent in Fontan patients, they may go unnoticed in US. Liver nodules are usually hyperechoic, hypervascular and predominantly peripheral. This population is at risk of hepatocellular carcinoma, the diagnosis of which requires confirmatory biopsy. Fontan surgery is the standard of care for many patients with univentricular congenital cardiopathies. Recent advances have improved the survival of Fontan patients, and nowadays most of them reach adulthood. In this setting, Fontan-associated liver disease (FALD) is increasingly recognised, and has become a significant prognostic factor. Liver nodules are considered a component of FALD yet their prevalence, imaging features and predictors have hardly been evaluated. In this study, we observed that liver nodules are frequent, typically hyperechoic, hypervascular and predominantly peripheral in patients with FALD. This population is at risk of hepatocellular carcinoma, the diagnosis of which must be confirmed by biopsy.

Imaging for the diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis.

CT, extracellular contrast-enhanced MRI, or gadoxetate-enhanced MRI could not be definitively preferred for HCC diagnosis in patients with cirrhosis; in patients with cirrhosis and an indeterminate mass, there were insufficient data comparing biopsy to repeat cross-sectional imaging or alternative imaging. (Hepatology 2018;67:401-421).

Management of Solitary 1 cm to 2 cm Liver Nodules in Patients with Compensated Cirrhosis: A Decision Analysis

Current guidelines, based on expert opinion, recommend that suspected 1 cm to 2 cm hepatocellular carcinoma (HCC) detected on screening be biopsied and, if positive, treated (eg, resection or transplantation). Alternative strategies are immediate treatment or observation until disease progression occurs. A Markov decision model was developed that compared three management strategies - immediate resection, biopsy and resection if positive, and ultrasound surveillance every three months until disease progression - for a single 1 cm to 2 cm liver nodule suspicious for HCC following ultrasound screening and computed tomography confirmation. The cohort included 55-year-old patients with compensated cirrhosis and no significant comorbidities. The model used in the present study incorporated the probabilities of false-positive and false-negative results, needle-track seeding, HCC recurrence, cirrhosis progression and death. The quality-adjusted life expectancy (LE) and the unadjusted LE were evaluated and the model's strength was assessed with sensitivity analyses. In the base case analysis, biopsy, resection and surveillance yielded an unadjusted LE of 60.5, 59.7 and 56.6 months, respectively, and a quality-adjusted LE of 46.6, 45.6 and 43.8 months, respectively. In probabilistic sensitivity analyses, biopsy was the preferred strategy 69.5% of the time, resection 30.5% of the time and surveillance never. Resection was the optimal decision if the sensitivity of biopsy was very low (less than 0.45) or if the accuracy of the imaging tests resulted in a high percentage of HCC-positive patients (greater than 76%) in the screened cohort, as with expert interpretation of triphasic computed tomography. The present model suggests that biopsy is the preferred management strategy for these patients. When postimaging probability of HCC is high or pathology expertise is lacking, resection is the best alternative. Surveillance is never the optimal strategy.