Viable Hepatocellular Carcinoma Research Articles

Usefulness of contrast-enhanced ultrasound-guided biopsy for suspected viable hepatocellular carcinoma after treatment: a single-arm prospective study.

The utility of contrast-enhanced ultrasound (CEUS)-guided liver biopsy in patients with treated hepatocellular carcinoma (HCC) was evaluated. This study prospectively enrolled 36 patients (mean age±standard deviation [SD], 65.3±9.2 years; 31 men) who underwent CEUS-guided biopsy for treated HCC between September 2020 and April 2022, constituting the CEUS group. An additional 60 patients (mean age±SD, 60.7±12.3 years; 50 men) who underwent B-mode image-guided biopsy for treated HCC between January 2017 and December 2018 were retrospectively enrolled in the B-mode, or control, group. Biopsy success rates were compared between CEUS and B-mode groups using the chi-square test. The biopsy success rate in the CEUS group was 88.9% (32 of 36 patients), which was significantly higher than the 70.0% (42 of 60 patients) observed in the B-mode group (P=0.044). No significant difference was found between CEUS and B-mode groups in the size of the lesions targeted for biopsy (mean±SD, 3.8±2.3 cm vs. 3.7±3.3 cm, respectively; P=0.332). For both the whole tumor and the viable tumor, conspicuity scores were significantly higher on CEUS than on grayscale ultrasound in the CEUS group (whole tumor: 2.7±0.5 vs. 1.8±0.9, P<0.001; viable tumor: 2.6±0.7 vs. 1.4±0.8, P<0.001). Relative to non-diagnostic results, diagnostic results more frequently exhibited a late mild washout pattern (87.5% [28 of 32] vs. 25.0% [1 of 4], P=0.004). No significant difference in the arterial enhancement pattern was noted between these subgroups (P=0.415). By increasing the viable-tumor conspicuity, CEUS-guided biopsy is useful for confirmative histopathologic diagnosis in patients with treated HCC.

Per-patient Negative Predictive Value of the CT and MRI Liver Imaging Reporting and Data System Version 2018 Treatment Response Algorithm for Hepatocellular Carcinoma.

Background The Liver Imaging Reporting and Data System version 2018 (LI-RADS) treatment response algorithm (TRA) is a high-specificity, lower-sensitivity grading system to diagnose hepatocellular carcinoma (HCC) and recurrence after local-regional therapy. However, the emphasis on specificity can result in disease understaging, potentially leading to poorer posttransplant outcomes. Purpose To determine the negative predictive value (NPV) of pretransplant CT and MRI assessment for viable HCC on a per-patient basis using the LI-RADS TRA, considering explant pathology as the reference standard. Materials and Methods Patient records from 218 consecutive adult patients from a single institution with HCC who underwent liver transplant from January 2011 to November 2017 were retrospectively reviewed. Two readers blinded to the original report reviewed immediate (within 90 days) pretransplant imaging and characterized observations according to the LI-RADS TRA. Based on this, patients with LR-4, LR-5, or LR-TR (treatment response) viable tumors were designated as viable tumor; patients with solely LR-3 or LR-TR equivocal tumors were designated as equivocal; and patients with only LR-TR nonviable lesions were designated as no viable disease. Patients were designated as within or outside the Milan criteria. These per-patient designations were compared with the presence of viable disease at explant pathology. Fisher exact test was used to compare the differences between CT and MRI. Weighted κ values were used to calculate interreader reliability. Results Final study sample consisted of 206 patients (median age, 61 years [IQR, 57-65 years]; 157 male patients and 49 female patients). Per-patient LI-RADS TRA assessment of pretransplant imaging had an NPV of 32% (95% CI: 27, 38) and 26% (95% CI: 20, 33) (readers 1 and 2, respectively) for predicting viable disease. Seventy-five percent (reader 1) and 77% (reader 2) of patients deemed equivocal had residual tumors at explant pathology. Weighted interreader reliability was substantial (κ = 0.62). Conclusion Patient-based stratification of viable, equivocal, and nonviable disease at pretransplant CT or MRI, based on LI-RADS TRA, demonstrated low negative predictive value in excluding HCC at explant pathology. © RSNA, 2023 See also the editorial by Tamir and Tau in this issue.

Comparison of contrast-enhanced ultrasonography and MRI results obtained by expert and novice radiologists indicating short-term response after transarterial chemoembolisation for hepatocellular carcinoma

To evaluate inter-reader agreement between novice and expert radiologists in assessing contrast-enhanced ultrasonography (CEUS) and magnetic resonance imaging (MRI) images for detecting viable tumours with different sizes after conventional transarterial chemoembolisation (cTACE). This prospective study included patients who had less than five hepatomas and who underwent cTACE. Hepatomas with one or two feeding arteries were selected as target lesions. CEUS and MRI were performed within 1 week after cTACE to evaluate viable tumours. The expert group had higher kappa values in evaluating all tumour sizes via CEUS compared with MRI. The novice group had similar kappa values. In patients with tumours measuring ≤3 cm, the expert group had higher kappa values in reading CEUS compared with MRI images; however, in the novice group, the kappa value was lower in evaluating CEUS compared with MRI images. In patients with tumours measuring >3 cm, the expert and novice groups had good to excellent kappa values. The confidence level of the two groups in reading MRI images was high; however, the novice group had a lower confidence level. CEUS is a convenient, cost-effective, and easy to apply imaging tool that can help interventionists perform early detection of viable hepatocellular carcinoma post-TACE. It has a higher inter-rater agreement in interpreting CEUS images compared with MRI images among expert radiologists even when they are extremely familiar with post-cTACE MRI images. In novice radiologists, there may be a learning curve to achieve good consistency in CEUS interpretation.

Soft Reconstruction Kernels Improve HCC Imaging on a Photon-Counting Detector CT

Hepatocellular carcinoma (HCC) is the only tumor entity that allows non-invasive diagnosis based on imaging without further histological proof. Therefore, excellent image quality is of utmost importance for HCC diagnosis. Novel photon-counting detector (PCD) CT improves image quality via noise reduction and higher spatial resolution, inherently providing spectral information. The aim of this study was to investigate these improvements for HCC imaging with triple-phase liver PCD-CT in a phantom and patient population study focusing on identification of the optimal reconstruction kernel. Phantom experiments were performed to analyze objective quality characteristics of the regular body and quantitative reconstruction kernels, each with four sharpness levels (36-40-44-48). For 24 patients with viable HCC lesions on PCD-CT, virtual monoenergetic images at 50keV were reconstructed using these kernels. Quantitative image analysis included contrast-to-noise ratio (CNR) and edge sharpness. Three raters performed qualitative analyses evaluating noise, contrast, lesion conspicuity, and overall image quality. In all contrast phases, the CNR was highest using the kernels with a sharpness level of 36 (all p<0.05), with no significant influence on lesion sharpness. Softer reconstruction kernels were also rated better regarding noise and image quality (all p<0.05). No significant differences were found in image contrast and lesion conspicuity. Comparing body and quantitative kernels with equal sharpness levels, there was no difference in image quality criteria, neither regarding in vitro nor in vivo analysis. Soft reconstruction kernels yield the best overall quality for the evaluation of HCC in PCD-CT. As the image quality of quantitative kernels with potential for spectral post-processing is not restricted compared to regular body kernels, they should be preferred.

Quantitative Prediction of Posttransplant Hepatocellular Carcinoma Prognosis Using ADV Score: Validation with Korea-Nationwide Transplantation Registry Database

ObjectiveThe aim of this study is to validate the prognostic impact of ADV score (α-fetoprotein [AFP]–des-γ-carboxyprothrombin [DCP]–tumor volume [TV] score) for predicting prognosis of hepatocellular carcinoma (HCC) following liver transplantation (LT). BackgroundADV score has been reported as a prognostic surrogate biomarker of HCC following LT and hepatectomy. MethodsThe study patients were 1599 LT recipients selected from the Korean Organ Transplantation Registry database. ResultsDeceased-donor and living-donor LTs were performed in 143 and 1456 cases, respectively. Weak correlation was present among AFP, DCP, and TV. The viable HCC group showed ADV score-dependent disease-free survival (DFS) and overall patient survival (OS) rates from 1log to 10log (p<0.001). Prognosis of complete pathological response group was comparable to that of ADV score <1log (p≥0.099). ADV score cutoff of 5log (ADV-5log) for DFS and OS was obtained through receiver operating characteristic curve analysis with area under the curve ≥0.705. Both ADV-5log and Milan criteria were independent risk factors for DFS and OS, and their prognostic impacts were comparable to each other. Combination of these two factors resulted in further prognostic stratification, showing hazard ratios for DFS and OS as 2.98 and 2.26 respectively for one risk factor and 7.92 and 8.19 respectively for two risk factors (p<0.001). ABO-incompatible recipients with ADV score ≥8log or two risk factors showed higher recurrence rates. ConclusionsThis validation study revealed that ADV score is a reliable surrogate biomarker for posttransplant HCC prognosis, which can be used for selecting LT candidates and guiding risk-based posttransplant follow-up surveillance.

Chemoembolization combined radiofrequency ablation vs. chemoembolization alone for treatment of beyond the Milan criteria viable hepatocellular carcinoma (CERFA): study protocol for a randomized controlled trial

BackgroundMany previous studies evaluated a combination of transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) for treating early hepatocellular carcinoma (HCC); however, studies evaluating combination therapy for beyond-the-Milan criteria HCC are scarce.MethodsA total of 120 patients with beyond-the-Milan criteria HCC who have viable tumour after first TACE will be enrolled in this multi-institutional, parallel, pragmatic, randomized controlled trial. Patients with metastasis, vascular invasion, or a sum of tumour diameter > 8 cm will be excluded. Eligible patients will be randomly assigned to combination TACE and RFA therapy or TACE monotherapy groups. Patients in the combination therapy group will receive a second TACE and subsequent RFA at the viable tumour. Patients in the TACE monotherapy group will receive only second TACE. Patients in both groups will undergo magnetic resonance imaging 4–6 weeks after second TACE. The primary endpoint is 1-month tumour response, and secondary endpoints are progression-free survival, overall response rate, number of treatments until CR, overall survival, and change in liver function.DiscussionAlthough TACE can be used to treat intermediate-stage HCC, it is difficult to achieve CR by first TACE in most intermediate-stage patients. Recent studies show a survival advantage of combination therapy over monotherapy. However, most studies evaluating combination therapy included patients with a single tumour sized < 5 cm, and no studies included patients with intermediate-stage but more advanced (i.e., beyond-the-Milan criteria) HCC. This study will evaluate the efficacy of combined TACE and RFA therapy for patients with advanced HCC within the intermediate stage.Trial registrationClinical Research Information Service (CRiS) KCT0006483.

Stronger Neo‐Minophagen C (SNMC): A stronger adjuvant for TACE?

Stronger <scp>Neo‐Minophagen</scp> C (<scp>SNMC</scp>): A stronger adjuvant for <scp>TACE</scp>?

Prospective evaluation of Gadoxetate-enhanced magnetic resonance imaging and computed tomography for hepatocellular carcinoma detection and transplant eligibility assessment with explant histopathology correlation

BackgroundWe aimed to prospectively compare the diagnostic performance of gadoxetic acid-enhanced MRI (EOB-MRI) and contrast-enhanced Computed Tomography (CECT) for hepatocellular carcinoma (HCC) detection and liver transplant (LT) eligibility assessment in cirrhotic patients with explant histopathology correlation.MethodsIn this prospective, single-institution ethics-approved study, 101 cirrhotic patients were enrolled consecutively from the pre-LT clinic with written informed consent. Patients underwent CECT and EOB-MRI alternately every 3 months until LT or study exclusion. Two blinded radiologists independently scored hepatic lesions on CECT and EOB-MRI utilizing the liver imaging reporting and data system (LI-RADS) version 2018. Liver explant histopathology was the reference standard. Pre-LT eligibility accuracies with EOB-MRI and CECT as per Milan criteria (MC) were assessed in reference to post-LT explant histopathology. Lesion-level and patient-level statistical analyses were performed.ResultsSixty patients (49 men; age 33–72 years) underwent LT successfully. One hundred four non-treated HCC and 42 viable HCC in previously treated HCC were identified at explant histopathology. For LR-4/5 category lesions, EOB-MRI had a higher pooled sensitivity (86.7% versus 75.3%, p < 0.001) but lower specificity (84.6% versus 100%, p < 0.001) compared to CECT. EOB-MRI had a sensitivity twice that of CECT (65.9% versus 32.2%, p < 0.001) when all HCC identified at explant histopathology were included in the analysis instead of imaging visible lesions only. Disregarding the hepatobiliary phase resulted in a significant drop in EOB-MRI performance (86.7 to 72.8%, p < 0.001). EOB-MRI had significantly lower pooled sensitivity and specificity versus CECT in the LR5 category with lesion size < 2 cm (50% versus 79%, p = 0.002 and 88.9% versus 100%, p = 0.002). EOB-MRI had higher sensitivity (84.8% versus 75%, p < 0.037) compared to CECT for detecting < 2 cm viable HCC in treated lesions. Accuracies of LT eligibility assessment were comparable between EOB-MRI (90–91.7%, p = 0.156) and CECT (90–95%, p = 0.158).ConclusionEOB-MRI had superior sensitivity for HCC detection; however, with lower specificity compared to CECT in LR4/5 category lesions while it was inferior to CECT in the LR5 category under 2 cm. The accuracy for LT eligibility assessment based on MC was not significantly different between EOB-MRI and CECT.Trial registrationClinicalTrials.gov Identifier: NCT03342677, Registered: November 17, 2017.

Multiple Pretransplant Treatments for Patients Without Pathological Complete Response may Worsen Posttransplant Outcomes in Patients with Hepatocellular Carcinoma.

Liver transplant (LT) candidates with hepatocellular carcinoma (HCC) often receive cancer treatment before transplant. We investigated the impact of pre-transplant treatment for HCC on the risk of posttransplant recurrence. Adult HCC patients with LT at our institution between 2013 and 2020 were included. The impact of pre-LT cancer treatments on the cumulative recurrence was evaluated, using the Gray and Fine-Gray methods adjusted for confounding factors. Outcomes were considered in two ways: 1) by pathologically complete response (pCR) status within patients received pre-LT treatment; and 2) within patients without pCR, grouped by pre-LT treatment as A) none; B) one treatment; C) multiple treatments. The sample included 179 patients, of whom 151 (84%) received pretreatment and 42 (28% of treated) demonstrated pCR. Overall, 22 (12%) patients experienced recurrence. The 5-year cumulative post-LT recurrence rate was significantly lower in patients with pCR than those without pCR (4.8% vs. 19.2%, P = 0.03). In bivariable analyses, pCR significantly decreased risk of recurrence. Among the 137 patients without pCR (viable HCC in the explant), 28 (20%) had no pretreatment (A), 70 (52%) had one treatment (B), and 39 (20%) had multiple treatments (C). Patients in Group C had higher 5-year recurrence rates than those in A or B (39.6% vs. 8.2%, 6.5%, P = 0.004 and P < 0.001, respectively). In bivariable analyses, multiple treatments was significantly associated with recurrence. pCR is a favorable prognostic factor after LT. When pCR was not achieved by pre-LT treatment, the number of treatments might be associated with post-LT oncological prognosis.

Clinical outcomes of antithrombinIII-based therapy for patients with portal vein thrombosis: A retrospective, multicenter study.

The association between thrombolytic therapy and the outcome in patients with portal vein thrombosis (PVT) remains controversial. This study aimed to evaluate the outcome in patients with PVT who received antithrombinIII-based therapy. This study was a retrospective, multicenter study to investigate the liver-related events and the survival rates in 240 patients with PVT who received the therapy. The patients comprised 151 men and 89 women, with a median age of 69years. The rate of favorable response, defined as maximum area of PVT changed to ≤75%, was 67.5% (162/240). The cumulative rates of liver-related events at 1, 2, and 3years were 38.2%, 53.9%, and 68.5%, respectively. The multivariate analysis showed that viable hepatocellular carcinoma, absence of maintenance therapy, non-responder, and PVT progression were significantly associated with liver-related events. The PVT progression was observed in 23.3% (56/240). The multivariate analysis identified older age, absence of maintenance therapy, and non-responder as independent factors associated with PVT progression. The multivariate analysis revealed that younger age, no hepatocellular carcinoma, presence of maintenance therapy, and lower Model for End-stage Liver Disease-Sodium score significantly contributed to 3-year survival. Of the 240 patients, 13 (8.9%) prematurely discontinued treatment due to any adverse events. This study suggests that maintenance therapy, favorable response, and absence of PVT progression may suppress or control liver-related events in antithrombinIII-based therapy for patients with PVT. Specifically, maintenance therapy could suppress not only liver-related events, but also PVT progression and improve the prognosis.

S1349 Utility of LAD Score for Treatment Response Assessment and Recurrence Monitoring in Patients With Hepatocellular Carcinoma

Introduction: The GALAD score, which incorporates the biomarkers AFP, AFP-L3% and DCP, has excellent performance for detection of hepatocellular carcinoma (HCC). However, its accuracy in treatment response assessment and recurrence prediction are unknown. We aimed to evaluate the accuracy of these biomarkers in predicting the presence of post-treatment viable tumor and HCC recurrence. Methods: We identified patients with cirrhosis or chronic hepatitis B infection who underwent curative surgical or locoregional treatment (Y-90, TACE, ablation) for HCC between May 2019 to May 2022, with GALAD labs obtained greater than 1 month post-treatment. Because the study cohort already has known HCC, we removed the demographic factors to calculate a score based solely on the biomarkers (the “LAD” score). The LAD score is calculated from the following formula: .04×(AFP-L3) +2.34×log(AFP)+1.33×log(DCP). Evidence of viable tumor was determined by imaging, biopsy, or liver explant pathology after transplant. Patients with non-viable tumor on initial post-treatment imaging were further analyzed for tumor recurrence. The sensitivity and specificity of the LAD score in predicting tumor viability were calculated. The optimal receiver operating characteristic (ROC) curve was used to calculate the cutoff for the LAD score. Results: A total of 78 patients (97 treatments) with surveillance imaging and biomarkers were analyzed. The number of treatments per patient ranged between 1 and 3 (mean 1.2). Mean age at time of HCC detection was 67 years, and a third of patients were female. The most common treatment modality was TACE (48.6%), followed by Y-90 (29.9%), ablation (16.5%), and resection (7.2%). About a third of cases (34.0%) had a viable tumor on initial post treatment images. The optimal LAD cutoff was calculated at 2.23, yielding a sensitivity and specificity of 87.4% and 60.9% for detection of viable tumors, respectively. After median follow up of 21.3 months, 11 cases (17.2%) developed recurrent HCC (mean time to recurrence 3.5 months) among cases with post-treatment non-viable tumor. A total of 7 recurrence cases (64%) had a positive LAD score at negative post-treatment surveillance images. Positive LAD score had a borderline association with recurrence (HR 3.17; 95%CI [0.92, 10.92], p = 0.067). Conclusion: LAD score is increased in most HCC patients with post-treatment viable tumors, suggesting its utility for post treatment response assessment. It might provide risk stratification for HCC recurrence.Figure 1.: Incidence of HCC Recurrence in LAD Positive vs Negative Cases

Liver imaging reporting and data system (LI-RADS) v2018: Reliability and agreement for assessing hepatocellular carcinoma locoregional treatment response

PurposeThe purpose of this study was to determine the reliability and interobserver agreement of the liver imaging reporting and data system (LI-RADS) treatment response algorithm (LR-TR) v2018 using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and the added value of diffusion-weighted imaging (DWI). Materials and methodsA total of 54 patients who underwent DCE-MRI and DWI after locoregional treatment of 81 hepatocellular carcinoma (HCC) lesions from September 2020 to July 2021 were included. There were 47 men and 7 women, with a mean age of 63.9 ± 9.2 (SD) years (age range: 23–77 years). Locoregional treatments included transarterial chemoembolization (TACE) (53/81; 65.4%), radiofrequency ablation (RFA) (25/81; 30.9%) and microwave ablation (MWA) (3/81; 3.7%). Two independent radiologists retrospectively evaluated DCE-MRI examinations obtained after locoregional treatment using LR-TR, and then three months later both radiologists reevaluated DCE-MRI examinations with DWI. Interobserver agreement was assessed using intraclass correlation coefficient (ICC) and Kappa test. Diagnostic performances were evaluated in term of sensitivity, specificity, and area under ROC curve (AUC) using a composite standard of reference that included results of histopathological examinations and follow-up findings. ResultsUsing DCE-MRI alone, observer 1 had 83.9% sensitivity (26/31; 95% confidence interval [CI]: 66–95%), 88% specificity (44/50; 95% CI: 76–95%) and 86.4% accuracy (70/81; 95%CI: 77–93%), and observer 2 had 71% sensitivity (22/31; 95% CI: 52–86%), 92% specificity (46/50; 95% CI: 81–98%) and 83.9% accuracy (68/81; 95% CI: 74–91%). For the diagnosis of viable tumors using DCE-MRI with DWI, observer 1 and observer 2 had 87.1% (27/31; 95% CI: 70–96%) and 74.2% (23/31; 95% CI: 55–88%) sensitivity, respectively. The diagnostic performance of DCE-MRI with DWI yielded an AUC (0.875; 95% CI: 0.789–0.962) not different from that of DCE-MRI without DWI (0.859; 95% CI: 0.768–0.951) (P = 0.317). Interobserver agreement for arterial phase hyperenhancement, washout, enhancement similar to pretreatment and DWI findings in all treated HCCs was almost perfect (kappa = 0.815, 0.837, 0.826 and 0.81 respectively). Agreement between observers for LR-TR category was substantial (kappa = 0.795; 95% CI: 0.665–0.924). Interobserver agreement for size of viable HCC was excellent (ICC = 0.938; 95% CI: 0.904–0.960). ConclusionLR-TR using DCE-MRI alone or DCE-MRI with DWI are both accurate for detecting viable HCC lesions after locoregional treatment, with no differences in diagnostic performance and excellent interobserver agreement.

Distinct Gene Expression Profiles in Viable Hepatocellular Carcinoma Treated With Liver-Directed Therapy

BackgroundHepatocellular carcinoma is a heterogeneous tumor that accumulates a mutational burden and dysregulated signaling pathways that differ from early to advanced stages. Liver transplant candidates with early-stage hepatocellular carcinoma (HCC) undergo liver-directed therapy (LDT) to delay disease progression and serve as a bridge to liver transplantation (LT). Unfortunately, >80% of LDT-treated patients have viable HCC in the explant liver, dramatically increasing recurrence risk. Understanding the effect of LDT on early-stage HCC could help identify therapeutic targets to promote complete pathologic necrosis and improve recurrence-free survival. In this study, transcriptomic data from viable HCC in LDT-treated bridged to transplant patients were investigated to understand how treatment may affect tumor signaling pathways.MethodsMultiplex transcriptomic gene analysis was performed with mRNA extracted from viable tumors of HCC patients bridged to transplant using LDT. The NanoString nCounter® Tumor Signaling 360 panel was used that contained 780 genes from 48 pathways involved in tumor biology within the microenvironment as well as antitumoral immune responses.ResultsHierarchical clustering separated tumors into three subtypes (HCC-1, HCC-2, and HCC-3) each with distinct differences in anti-tumoral signaling and immune infiltration within the tumor microenvironment. Immune infiltration (neutrophils, T cells, and macrophages) were all lowest in subtype HCC-3. The tumor inflammatory signature consisting of 18 genes associated with PD-1/PD-L1 inhibition, antigen presentation, chemokine secretion, and adaptive immune responses was highest in subtype HCC-1 and lowest in HCC-3. History of decompensation and etiology were associated with HCC subtype favoring downregulations in inflammation and immune infiltration with upregulation of lipid metabolism. Gene expression among intrahepatic lesions was remarkably similar with >85% of genes expressed in both lesions. Genes differentially expressed (<8 genes per patient) in multifocal disease were all upregulated in LDT-treated tumors from pathways involving epithelial mesenchymal transition, extracellular matrix remodeling, and/or inflammation potentially implicating intrahepatic metastases.ConclusionIncomplete response to LDT may drive expression patterns that inhibit an effective anti-tumoral response through immune exclusion and induce intrahepatic spread.

Repeated loco-regional therapies for hepatocellular carcinoma is associated with inferior outcome after living donor liver transplantation in cirrhotic patients.

Liver transplantation is the definitive treatment for defined stage hepatocellular carcinoma (HCC) in cirrhotic patients. Loco-regional therapy (LRT) may be considered before transplantation to prevent the disease progression and the patient from dropping out of the waiting list. This study aims to evaluate the impact of repeated pretransplant LRTs on the long-term outcomes in HCC liver transplant recipients. Between 2004 and 2019, living donor liver transplantation (LDLT) recipients with viable HCC on the explant livers were enrolled. Uni- and multivariate analysis was performed with the Cox regression model to stratify the risk factors associated with HCC recurrence and patent survival after LDLT. A total of 124 patients were enrolled, in which 65.3% (n = 81) were Barcelona Clinic Liver Cancer classification stage B or D and 89% (n = 110) had advanced fibrosis or cirrhosis on the explanted livers. After a median follow-up of 41 months (IQR: 24-86.5), there were 18 cases (13.7%) of HCC recurrence. Univariate analysis showed that the model of end-stage liver disease and Child-Turcotte-Pugh score, pretransplant alpha-fetoprotein value (>500 ng/ml), repeated pretransplant LRTs (N > 4), increased tumor numbers and maximal size, presence of microvascular invasion, and the histological grading of the tumors are risk factors of inferior outcomes. In multivariate analysis, only repeated pretransplant LRTs (N > 4) had a significant impact on both the overall- and recurrence-free survival. The impact of pretransplant LRT was consistently significant among subgroups based on their LRT episodes (N = 0, 1-4, >4 respectively). Repeated LRT for HCC can be associated with the risk of tumor recurrence and inferior patient survival after LDLT in cirrhotic patients. Early referral of those eligible for transplantation may improve the treatment outcomes in these patients.

Stereotactic body radiation therapy as a salvage treatment for single viable hepatocellular carcinoma at the site of incomplete transarterial chemoembolization: a retrospective analysis of 302 patients

BackgroundTo evaluate the clinical outcomes of patients who received stereotactic body radiation therapy (SBRT) for single viable hepatocellular carcinoma (HCC) at the site of incomplete transarterial chemoembolization (TACE).MethodsPatients treated with SBRT for single viable HCC after incomplete TACE between 2012 and 2017 at Asan Medical Center (Seoul, South Korea) were included. Incomplete TACE was defined as (1) evidence of viable HCC at the site of TACE on follow-up dynamic computed tomography (CT) or magnetic resonance imaging following one or more consecutive TACEs, (2) no definite tumor staining on superselective hepatic angiogram, or (3) no definite iodized oil uptake on post-embolization angiogram or CT. Doses of 10–15 Gy per fraction were given over 3–4 consecutive days. The primary outcome was local control rate at 3 years and secondary outcome included tumor response, overall survival rate, out-of-field intrahepatic recurrence-free survival, distant metastasis-free survival and treatment-related toxicities. Treatment-related adverse events were evaluated according to the common terminology criteria for adverse events, version 4.03.ResultsA total of 302 patients were analyzed. The median follow-up duration was 32.9 months (interquartile range [IQR], 23.6–41.7) and the median tumor size was 2.0 cm (range, 0.7–6.9). The local control (LC) and overall survival rates at 3 years were 91.2 and 72.7%, respectively. 95.4% of the tumors reached complete response (CR) during the entire follow-up period (anyCR). The median interval from SBRT to anyCR was 3.4 months (IQR, 1.9–4.7), and 39.9 and 83.3% of the lesions reached CR at 3- and 6-months after SBRT, respectively. Radiation-induced liver disease was observed in 8 (2.6%) patients. No patients experienced gastroduodenal bleeding within the radiation field.ConclusionSBRT could be considered a feasible salvage treatment option for HCC after incomplete TACE.

LI-RADS Treatment Response versus Modified RECIST for Diagnosing Viable Hepatocellular Carcinoma after Locoregional Therapy: A Systematic Review and Meta-Analysis of Comparative Studies.

PurposeTo systematically compare the performance of liver imaging reporting and data system treatment response (LR-TR) with the modified Response Evaluation Criteria in Solid Tumors (mRECIST) for diagnosing viable hepatocellular carcinoma (HCC) treated with locoregional therapy (LRT).Materials and MethodsOriginal studies of intra-individual comparisons between the diagnostic performance of LR-TR and mRECIST using dynamic contrast-enhanced CT or MRI were searched in MEDLINE and EMBASE, up to August 25, 2021. The reference standard for tumor viability was surgical pathology. The meta-analytic pooled sensitivity and specificity of the viable category using each criterion were calculated using a bivariate random-effects model and compared using bivariate meta-regression.ResultsFor five eligible studies (430 patients with 631 treated observations), the pooled per-lesion sensitivities and specificities were 58% (95% confidence interval [CI], 45%–70%) and 93% (95% CI, 88%–96%) for the LR-TR viable category and 56% (95% CI, 42%–69%) and 86% (95% CI, 72%–94%) for the mRECIST viable category, respectively. The LR-TR viable category provided significantly higher pooled specificity (p < 0.01) than the mRECIST but comparable pooled sensitivity (p = 0.53).ConclusionThe LR-TR algorithm demonstrated better specificity than mRECIST, without a significant difference in sensitivity for the diagnosis of pathologically viable HCC after LRT.

Role of DWI in evaluation of HCC after radiofrequency ablation compared to dynamic MRI using MRI (3\xa0T)

BackgroundThe purpose of this study was to investigate the diagnostic performance of diffusion weight imaging (DWI), apparent diffusion coefficient (ADC) map, normalized ADC liver, and normalized ADC spleen compared to the dynamic contrast-enhanced MRI (DCE-MRI) in the evaluation of residual hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) using 3 T (T) magnetic resonance imaging (MRI).ResultsA prospective study was performed on 40 patients with radiofrequency-ablated HCC, and 15 (37.5%) patients had viable lesion post-RFA, while 25 (62.5%) had non-viable lesions. DCE-MRI had a sensitivity, specificity, and accuracy of 100%, 100%, and 100%, respectively, compared to DWI which had a sensitivity, specificity, and accuracy of 80%, 88%, and 85%, respectively, for identifying post-RFA viable HCC. The sensitivity, specificity, and accuracy of ADC at a cutoff value of 1.01 × 10−3 mm2/s were 80%, 100%, and 97.1%, respectively. The optimal cutoff value of normalized ADC liver was 0.81 with a sensitivity of 73.3%, specificity of 96%, and accuracy of 92.8%. The sensitivity, specificity, and accuracy of normalized ADC spleen at a cutoff value of 1.22 were 80%, 92%, and 91.1%, respectively.ConclusionsDWI-MRI is a reliable technique for assessing HCC after radiofrequency ablation. DWI-MRI with ADC may be used as an alternate sequence for assessing radiofrequency-ablated lesions in individuals who have a contraindication to the contrast media, and the normalized ADC value may be of additional benefit.

The role of functional imaging; DWI, ADC and 18F-FDG PET/CT in the evaluation of HCC treatment response after transarterial chemoembolization

BackgroundThe transcatheter arterial chemoembolization (TACE) is one of the treatment lines for patients with hepatocellular carcinoma (HCC), this study was conducted to assess the role of functional imaging including the DWI, ADC and 18F-2-fluoro-2-deoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) for detection of residual HCC after TACE as compared to the structural liver imaging reporting and data system (LI-RADS).ResultsThe optimal cut off value of standardized uptake value ratio (SUVmax/liver SUVmean ratio) for detection of residual viable HCC after TACE was 1.09 with 88.9%, 87.5% and 88.6% sensitivity, specificity, and accuracy respectively, a lower diagnostic value was noted in the qualitative visual FDG PET/CT assessment with sensitivity, specificity, and accuracy of 81.5%, 75% and 80% respectively. The sensitivity, specificity, and accuracy of DWI for identification of post-TACE viable HCC were 77.8%, 75%, and 77.1% respectively. The optimal cut off value of ADC for the diagnosis of variable HCC was 1.32 × 10−3 mm2/s with sensitivity, specificity, and accuracy of 81.5%, 75%, and 80% respectively.ConclusionsDWI, ADC and FDG PET/CT are effective functional imaging modalities for the evaluation of viable residual HCC post-TACE with comparable findings for the dynamic cross-section imaging.

Low serum magnesium concentration is associated with the presence of viable hepatocellular carcinoma tissue in cirrhotic patients

This study aimed to ascertain, for the first time, whether serum magnesium (Mg) concentration is affected by the presence of hepatocellular carcinoma (HCC). We retrospectively enrolled consecutive cirrhotic patients with a diagnosis of HCC (n = 130) or without subsequent evidence of HCC during surveillance (n = 161). Serum levels of Mg were significantly (P < 0.001) lower in patients with HCC than in those without (median [interquartile range]: 1.80 [1.62–1.90] mg/dl vs. 1.90 [1.72–2.08] mg/dl). On multivariate logistic regression, low serum Mg was associated with the presence of HCC (OR 0.047, 95% CI 0.015–0.164; P < 0.0001), independently from factors that can influence magnesaemia and HCC development. In a subset of 94 patients with HCC, a linear mixed effects model adjusted for confounders showed that serum Mg at diagnosis of HCC was lower than before diagnosis of the tumor (β = 0.117, 95% CI 0.039–0.194, P = 0.0035) and compared to after locoregional treatment of HCC (β = 0.079, 95% CI 0.010–0.149, P = 0.0259), with two thirds of patients experiencing these changes of serum Mg over time. We hypothesize that most HCCs, like other cancers, may be avid for Mg and behave like a Mg trap, disturbing the body’s Mg balance and resulting in lowering of serum Mg levels.

Evaluation of the LI-RADS treatment response algorithm in hepatocellular carcinoma after trans-arterial chemoembolization

PurposeTo evaluate the diagnostic performance of LI-RADS treatment response algorithm (LR-TRA) and modified RECIST (mRECIST) for the detection of viable hepatocellular carcinoma (HCC) on MRI after trans-arterial chemoembolization (TACE). Materials and methodsThis retrospective study includes cirrhotic patients that underwent trans-arterial chemoembolization prior to liver transplantation from 2013 to 2017 with a pre- and post-treatment MRI available. Three blinded readers assigned a LR-TRA and mRECIST category to each lesion. Lesions on MRI and explant pathology were matched and characterized as complete (100% necrosis) or incomplete necrosis (≤99% necrosis). Diagnostic performance of LR-TRA and mRECIST were calculated with a generalized estimating equation. ResultsA total of 52 patients with 71 lesions were included, 47 with incomplete and 24 with complete necrosis. In consensus, 45 lesions were categorized as LR-TR Nonviable, of which 62.2% (28/45) had incomplete and 37.8% (17/45) had complete necrosis. Six lesions were categorized as LR-TR Equivocal, of which 33.3% (2/6) had incomplete and 66.7% (4/6) had complete necrosis. Twenty lesions were categorized as LR-TR Viable of which 85.0% (17/20) had incomplete and 15.0% (3/20) had complete necrosis. The sensitivity of LR-TR Viable for detecting incompletely necrotic tumor when LR-TR Equivocal was considered as viable, in consensus was 40.4%; specificity 70.8%; accuracy 50.7%. The sensitivity of mRECIST for detecting incompletely necrotic tumor was 37.0%; specificity 79.2%; accuracy 51.4%. There was no significant difference in diagnostic performance between mRECIST and LR-TRA (p = 0.14–0.33). Agreement for LR-TRA category was moderate (k = 0.53 [95% CI: 0.45, 0.67]). ConclusionLI-RADS treatment response algorithm demonstrates high specificity and low to moderate sensitivity for the detection of viable HCC after TACE in a North American cirrhotic cohort, without significant difference in diagnostic performance between LR-TRA and mRECIST.