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Objective: We performed an updated meta-analysis to determine the diagnostic performance of Liver Imaging Reporting and Data System (LI-RADS, LR) 5 category for hepatocellular carcinoma (HCC) using LI-RADS version 2018 (v2018), and to evaluate differences by imaging modalities and type of MRI contrast material. Methods: The MEDLINE and Embase databases were searched for studies reporting the performance of LR-5 using v2018 for diagnosing HCC. A bivariate random-effects model was used to calculate the pooled per-observation sensitivity and specificity. Subgroup analysis was performed based on imaging modalities and type of MRI contrast material. Results: Forty-eight studies qualified for the meta-analysis, comprising 9031 patients, 10,547 observations, and 7216 HCCs. The pooled per-observation sensitivity and specificity of LR-5 for diagnosing HCC were 66% (95% CI, 61–70%) and 91% (95% CI, 89–93%), respectively. In the subgroup analysis, MRI with extracellular agent (ECA-MRI) showed significantly higher pooled sensitivity (77% [95% CI, 70–82%]) than CT (66% [95% CI, 58–73%]; p = 0.023) or MRI with gadoxetate (Gx-MRI) (65% [95% CI, 60–70%]; p = 0.001), but there was no significant difference between ECA-MRI and MRI with gadobenate (gadobenate-MRI) (73% [95% CI, 61–82%]; p = 0.495). Pooled specificities were 88% (95% CI, 80–93%) for CT, 92% (95% CI, 86–95%) for ECA-MRI, 93% (95% CI, 91–95%) for Gx-MRI, and 91% (95% CI, 84–95%) for gadobenate-MRI without significant differences (p = 0.084–0.803). Conclusions: LI-RADS v2018 LR-5 provides high specificity for HCC diagnosis regardless of modality or contrast material, while ECA-MRI showed higher sensitivity than CT or Gx-MRI. Clinical relevance statement: Refinement of the criteria for improving sensitivity while maintaining high specificity of LR-5 for HCC diagnosis may be an essential future direction. Key Points: • The pooled per-observation sensitivity and specificity of LR-5 for diagnosing HCC using LI-RADSv2018 were 66% and 91%, respectively. • ECA-MRI showed higher sensitivity than CT (77% vs 66%, p = 0.023) or Gx-MRI (77% vs 65%, p = 0.001). • LI-RADS v2018 LR-5 provides high specificity (88–93%) for HCC diagnosis regardless of modality or contrast material type. [ABSTRACT FROM AUTHOR]

Objectives: The current LR-5 criteria of Liver Imaging Reporting and Data System (LI-RADS) determined by only major features provide high specificity, but unsatisfactorily low sensitivity for the noninvasive diagnosis of hepatocellular carcinoma (HCC). This study aimed to identify significant ancillary features (AFs) in LI-RADS version 2018 and develop the upgraded LR-5 criteria to improve diagnostic performance on gadoxetic acid–enhanced magnetic resonance imaging (MRI). Methods: This retrospective study included 280 patients (366 observations including 281 HCCs) at high-risk for HCC who underwent gadoxetic acid–enhanced MRI between 2015 and 2017. Two readers evaluated major features and AFs for each observation and assigned a LI-RADS category. Independently significant AFs were identified through logistic regression analysis. Upgraded LR-5 criteria were developed by combining independently significant AFs with LR-4 assigned by major features alone. Sensitivities and specificities of the diagnostic criteria were compared using McNemar's test. Results: Two of the AFs favoring malignancy in general (mild-moderate T2 hyperintensity and hepatobiliary phase hypointensity) and two of the AFs favoring HCC in particular (nonenhancing "capsule" and mosaic architecture) were independently significant features for diagnosing HCC. By using the upgraded LR-5 criteria (LR-4 by major features alone + each aforementioned AF), sensitivities were significantly increased (69.4–76.9%) compared with the standard LR-5 (66.2%; all, p ≤ 0.004), whereas specificities (95.3–96.5%) were not significantly different (96.5%; all, p > 0.999). Conclusions: Independently significant AFs may be used to upgrade from LR-4 to LR-5 to improve sensitivity without impairing specificity on gadoxetic acid–enhanced MRI. Key Points: • Independently significant AFs for HCC on gadoxetic acid–enhanced MRI were mild-moderate T2 hyperintensity, hepatobiliary phase hypointensity, nonenhancing "capsule," and mosaic architecture. • When LR-4 criteria by major features alone in combination with significant AFs were upgraded to LR-5, sensitivities were higher than the standard LR-5, without impairing specificity. • Independently significant ancillary features in Liver Imaging Reporting and Data System version 2018 may be used to upgrade from LR-4 to LR-5 to improve sensitivity without impairing specificity on gadoxetic acid–enhanced MRI. [ABSTRACT FROM AUTHOR]

Background & Aims: The liver Imaging Reporting and Data System (LI‐RADS) is a comprehensive system for standardizing liver imaging in patients at high risk for hepatocellular carcinoma (HCC). We performed a meta‐analysis to determine the diagnostic performance of the LR‐5 category for HCC and the pooled proportions of HCCs in each LI‐RADS category using CT/MRI LI‐RADS v2017. Methods: We searched multiple databases for original studies reporting on the diagnostic accuracy of CT/MRI LI‐RADS v2017. Random‐effects models were used to determine the summary estimates of the diagnostic performance of the LR‐5 category and the pooled proportions of HCCs for each LI‐RADS category. Risk of bias and concerns regarding applicability were evaluated with the Quality Assessment of Diagnostic Accuracy Studies‐2 tool. Results: Fourteen studies (3 prospective studies and 11 retrospective studies) were included in the final analysis, consisting of 2056 patients, 2589 observations, and 1693 HCCs. The pooled per‐observation sensitivity was 67% (95% confidence interval [CI], 62%‐72%) with specificity of 92% (95% CI, 88%‐95%) in the LR‐5 category of CT/MRI LI‐RADS v2017 for diagnosing HCC. The pooled proportions of HCCs were 0% (95% CI, 0%‐0%) for LR‐1, 4% (95% CI, 0%‐8%) for LR‐2, 34% (95% CI, 23%‐44%) for LR‐3, 67% (95% CI, 53%‐81%) for LR‐4, and 92% (95% CI, 87%‐96%) for LR‐5. The proportions of HCCs were significantly different among LI‐RADS categories 1‐5 (P =.034). Conclusions: The LR‐5 category of CT/MRI LI‐RADS v2017 shows moderate sensitivity and high specificity for diagnosing HCC. Higher LI‐RADS categories contained higher proportions of HCCs. [ABSTRACT FROM AUTHOR]

Background & Aims The therapeutic outcomes of surgical resection (SR) or radiofrequency ablation (RFA) for perivascular hepatocellular carcinoma (HCC) have not been compared. The aim of this study was to compare SR with RFA as first-line treatment in patients with perivascular HCC and to evaluate the long-term outcomes of both therapies. Methods This retrospective study was approved by the institutional review board. The requirement for informed consent was waived. Between January 2006 and December 2010, a total of 283 consecutive patients with small perivascular HCCs (≤3 cm, Barcelona Clinic Liver Cancer stage 0 or A) underwent SR (n = 182) or RFA (n = 101) as a first-line treatment. The progression-free survival (PFS) and overall survival (OS) rates were compared by propensity score matching. Subgroup analysis of these outcomes was conducted according to the type of hepatic vessels. Results The median follow-up was 7.8 years. Matching yielded 62 pairs of patients. In the two matched groups, the PFS rates at 5 and 10 years were 58.0% and 17.8%, respectively, in the SR group, and 25.4% and 14.1%, respectively, in the RFA group ( p  <0.001). The corresponding OS rates at 5 and 10 years were 93.5% and 91.9% in the SR group and 82.3% and 74.1% in the RFA group, respectively ( p  <0.001). In contrast to those in patients with perivenous HCCs, subgroup analysis indicated that extrahepatic recurrence and OS were significantly different according to the treatment modality in patients with periportal HCCs ( p  = 0.004 and p  <0.001, respectively). Conclusions In patients with small perivascular HCCs, SR provided better long-term tumor control and OS than RFA, particularly for periportal tumors. Lay summary Surgical resection and radiofrequency ablation are both treatment options for perivascular hepatocellular carcinoma. We compared outcomes in patients treated with either method. Surgical resection provided better long-term tumor control and overall survival than radiofrequency ablation for patients with a small perivascular hepatocellular carcinoma (≤3 cm) as a first-line treatment, particularly for periportal tumors. The location of the tumor and the type of peritumoral hepatic vessels need to be considered when choosing between surgical resection and radiofrequency ablation for small HCCs. [ABSTRACT FROM AUTHOR]

To gain insight into liver and pancreas development, we investigated the target of 2F11, a monoclonal antibody of unknown antigen, widely used in zebrafish studies for labeling hepatopancreatic ducts. Utilizing mass spectrometry and in vivo assays, we determined the molecular target of 2F11 to be Annexin A4 (Anxa4), a calcium binding protein. We further found that in both zebrafish and mouse endoderm, Anxa4 is broadly expressed in the developing liver and pancreas, and later becomes more restricted to the hepatopancreatic ducts and pancreatic islets, including the insulin producing ß-cells. Although Anxa4 is a known target of several monogenic diabetes genes and its elevated expression is associated with chemoresistance in malignancy, its in vivo role is largely unexplored. Knockdown of Anxa4 in zebrafish leads to elevated expression of caspase 8 and Δ113p53 , and liver bud specific activation of Caspase 3 and apoptosis. Mosaic knockdown reveal that Anxa4 is required cell-autonomously in the liver bud for cell survival. This finding is further corroborated with mosaic anxa4 knockout studies using the CRISPR/Cas9 system. Collectively, we identify Anxa4 as a new, evolutionarily conserved hepatopancreatic factor that is required in zebrafish for liver progenitor viability, through inhibition of the extrinsic apoptotic pathway. A role for Anxa4 in cell survival may have implications for the mechanism of diabetic ß-cell apoptosis and cancer cell chemoresistance. [ABSTRACT FROM AUTHOR]