Locoregional Therapy For Hepatocellular Carcinoma Research Articles

Chronic Liver Disease and COVID-19: Alcohol Use Disorder/Alcohol-Associated Liver Disease, Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis, Autoimmune Liver Disease, and Compensated Cirrhosis.

Chronic Liver Disease and COVID-19: Alcohol Use Disorder/Alcohol-Associated Liver Disease, Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis, Autoimmune Liver Disease, and Compensated Cirrhosis.

Population-based matching comparison between radiofrequency ablation and percutaneous ethanol or acetic acid injection for hepatocellular carcinoma

BackgroundLoco-regional therapies are evolving for hepatocellular carcinoma (HCC) treatment. Radiofrequency ablation (RFA) has changed the landscape in treating HCC; however, percutaneous ethanol or acetic acid injection (PEI/PAI) remains a widely used and easily performed technique by experienced clinicians. Nevertheless, the effectiveness of RFA compared to that of PEI/PAI remains unclear. MethodsRecords of 73,136 patients with newly diagnosed HCC between 2007 and 2013 were drawn from the Taiwan Cancer Registry. The primary outcome measures were the overall survival and local recurrence-free survival. Propensity score matching (PSM) was performed to compare the effectiveness of RFA and PEI. Median follow-up time was 61.6 months (36–120 months). ResultsAfter PSM, 4496 patients diagnosed with stage I-III HCC, who were initially treated with RFA (3372 patients) or PEI/PAI (1124 patients), were assessed. Compared to PEI/PAI, patients treated with RFA had better 5- and 9-year overall survival, cancer-specific survival, disease-free survival, and local recurrence-free survival. Median overall survival and recurrence-free survival of patients treated with RFA vs PEI/PAI were 61.5 vs 41.9 months and 72.1 vs 45.2 months, respectively. Multivariate Cox model analysis revealed that, except for patients with high cell grade or advanced stage, RFA resulted in better overall survival (HR: 0.74, 95% CI 0.68–0.81, P < 0.001) and local recurrence-free survival (HR: 0.69, 95% CI 0.63–0.75, P < 0.001) than PEI/PAI. ConclusionsRFA provides advantages over conventional PEI/PAI for HCC. Considering technological advances in instruments, loco-regional therapies for HCC can be employed in carefully selected patients.

Abstract No. 428 Parthenolide induces thiol oxidation-mediated cytotoxicity in human and rat hepatocellular carcinoma cell lines

Parthenolide (PTL) is a naturally occurring sesquiterpene lactone that has anti-tumor activity. The redox environment of hepatocellular carcinoma (HCC) becomes an important target due to the differences between cancer and normal tissue metabolism. We hypothesize that in vitro PTL will induce HCC cell death through increased thiol oxidation. Half maximal inhibitory concentrations (IC50) response to PTL was determined in human (HepG2, SNU-423) and rat (McARH7777) hepatoma cell lines using MTT assays for 24 h. Cellular respiration response to PTL was measured over 24 h using Seahorse Flux Analyzer. Intracellular glutathione (GSH) and oxidized glutathione (GSSG) levels were measured using spectrophotometry at 2 h, 4 h and 24 h. The overall oxidation status of cell lines was also determined using thiol redox-sensitive ratiometric sensor roGFP. PTL had over 90% cytotoxicity at high concentrations 20 μM for SNU-423, 54 μM for HepG2, and 40 μM for rat HCC after 24 h. IC50 concentrations of 6.6 μM for SNU-423, 18 μM for HepG2 and 13 μM for rat HCC were determined after 24 h. Cytotoxic doses of PTL induced a decline in cellular respiration of the HCC cell lines after 2 h. Furthermore, 2 h PTL treatment at IC50 or high concentration caused cyto-roGFP sensor to be oxidized 2.5- to 4-fold in human and rat HCC. PTL at IC50 doses resulted in increased percent GSSG as early as 2 h in human and rat cells. This increase was compensated by upregulation of total GSH levels to minimize cell toxicity in HepG2 cells, which appeared to be offset at high doses of PTL. In HepG2 cells increased percent GSSG levels also demonstrated a similar trend in both IC50 and high PTL doses. In vitro PTL decreased cellular respiration, increased overall oxidation status and increased glutathione oxidation in HCC as early as 2 h after treatment. In HepG2 cells, IC50 dose caused a compensatory upregulation of GSH levels to ostensibly overcome thiol oxidation induced cytotoxicity. However, higher concentrations of PTL overwhelmed this mechanism and caused significant cytotoxicity in all 3 cells lines suggesting PTL can potentially be delivered at high concentrations as locoregional therapy for HCC in vivo.

Retrospective analysis of the immunogenic effects of intra-arterial locoregional therapies in hepatocellular carcinoma: a rationale for combining selective internal radiation therapy (SIRT) and immunotherapy

BackgroundImmunotherapy represents a promising option for treatment of hepatocellular carcinoma (HCC) in cirrhotic patients but its efficacy is currently inconsistent and unpredictable. Locoregional therapies inducing immunogenic cell death, such as transarterial chemoembolization (TACE) or selective internal radiation therapy (SIRT), have the potential to act synergistically with immunotherapy. For the development of new approaches combining locoregional treatments with immunotherapy, a better understanding of the respective effects of TACE and SIRT on recruitment and activation of immune cells in HCC is needed. To address this question, we compared intra-tumor immune infiltrates in resected HCC after preoperative treatment with TACE or SIRT.MethodsData fromr patients undergoing partial hepatectomy for HCC, without preoperative treatment (SURG, n = 32), after preoperative TACE (TACE, n = 16), or preoperative SIRT (n = 12) were analyzed. Clinicopathological factors, tumor-infiltrating lymphocytes (TILs), CD4+ and CD8+ T cells, and granzyme B (GZB) expression in resected HCC, and postoperative overall and progression-free survival were compared between the three groups.ResultsClinicopathological and surgical characteristics were similar in the three groups. A significant increase in TILs, CD4+ and CD8+ T cells, and GZB expression was observed in resected HCC in SIRT as compared to TACE and SURG groups. No difference in immune infiltrates was observed between TACE and SURG patients. Within the SIRT group, the dose of irradiation affected the type of immune infiltrate. A significantly higher ratio of CD3+ cells was observed in the peri-tumoral area in patients receiving < 100 Gy, whereas a higher ratio of intra-tumoral CD4+ cells was observed in patients receiving > 100 Gy. Postoperative outcomes were similar in all groups. Irrespective of the preoperative treatment, the type and extent of immune infiltrates did not influence postoperative survival.ConclusionsSIRT significantly promotes recruitment/activation of intra-tumor effector-type immune cells compared to TACE or no preoperative treatment. These results suggest that SIRT is a better candidate than TACE to be combined with immunotherapy for treatment of HCC. Evaluation of the optimal doses for SIRT for producing an immunogenic effect and the type of immunotherapy to be used require further evaluation in prospective studies.

Survival analysis of 230 patients with unresectable hepatocellular carcinoma treated with bland transarterial embolization.

Locoregional therapies for hepatocellular carcinoma (HCC) include endovascular treatments such as chemoembolization (TACE) and bland embolization (TAE). TACE is the most adopted technique, despite a lack of definitive evidence of superiority over TAE, which is less costly and better tolerated due to the absence of chemotherapy. However, few studies have reported data on TAE monotherapy for unresectable HCC. We report our results in a cohort of 230 patients with unresectable HCC treated with TAE (TAE with 40-100micron microparticles, TAE with microparticles plus n-butyl-2-cyanoacrylate, TAE with Lipiodol) over the course of seven years. Thirty-seven patients (14%) were down-staged during observation and also received a percutaneous ablation. We observed 1-, 2-, 3-, 4- and 5-year rates of 84,8%, 58,7%, 38,3%, 28,3%, and 18,7%. Patients who also received percutaneous treatment performed best. Our results broaden the body of evidence for the use of TAE in advanced HCC.

CT scan is more accurate in predicting viable disease after microwave ablation then tace in patients undergoing locoregional treatment in hepatocellular carcinoma

Presenter: Maria Baimas-George MD, MPH | Carolinas HealthCare System Background: The use of locoregional therapies such as laparoscopic tumor ablation or intra-arterial chemotherapy in hepatocellular carcinoma (HCC) to achieve local control, reduce transplant list dropout, downstage, or reduce recurrence is common practice. Assessing tumor response after treatment, however, remains difficult and unreliable without an explant specimen. We sought to determine the accuracy of imaging in treatment success after locoregional therapy in HCC. Methods: Patients with HCC who underwent either microwave ablation (MWA) and/or transarterial chemoembolization (TACE) prior to hepatectomy or transplantation were retrospectively identified from 2008 to 2018. Computed tomography (CT) scans after treatment and prior to resection were evaluated for characteristics consistent with viable tumor. The explant specimen was identified, and tumor response was assessed through pathologic evaluation. The accuracy of the pre-operative CT scan readings was compared with the pathologic findings of the explant specimen. Results: Ninety-one patients were identified who underwent locoregional treatment prior to resection or transplant. Of these, 14 patients underwent laparoscopic MWA, 46 underwent TACE, and 31 underwent both treatments in a neoadjuvant fashion. The ability of CT imaging to predict tumor viability was assessed by treatment modality. For MWA, CT scans demonstrated a 75% positive predictive value (PPV) and a 67% negative predictive value (NPV). This correlated with a 50% sensitivity and 86% specificity. For TACE, CT scans demonstrated an 87% positive predictive value (PPV) and a 25% negative predictive value (NPV). This correlated with an 82% sensitivity and 33% specificity. For MWA-TACE, CT scans demonstrated an 80% positive predictive value (PPV) and a 39% negative predictive value (NPV). This correlated with a 42% sensitivity and 78% specificity. Conclusion: Imaging to guide response to locoregional therapies in HCC has variable accuracy. There is a high probability of finding tumor given a positive CT scan after all three treatment modalities, whereas a negative CT scan is unreliable. Specifically, CT imaging after MWA demonstrates a high specificity and will likely rule out any residual tumor and CT imaging after TACE is highly sensitive and will likely find residual tumor.

Evaluation of treatment response in hepatocellular carcinoma in the explanted liver with Liver Imaging Reporting and Data System version 2017.

To investigate the performance of Liver Imaging Reporting and Data System (LI-RADS) v2017 treatment response algorithm for predicting hepatocellular carcinoma (HCC) viability after locoregional therapy (LRT) using the liver explant as reference. One hundred fourteen patients with 206 HCCs who underwent liver transplantation (LT) after LRT for HCCs were included in this retrospective study. Two radiologists independently evaluated tumor viability using the LI-RADS and modified RECIST (mRECIST) with CT and MRI, respectively. The sensitivity and specificity of arterial phase hyperenhancement (APHE) and LR-TR viable criteria (any of three findings: APHE, washout, and enhancement pattern similar to pretreatment imaging) were compared using logistic regression. Receiver operating characteristics (ROC) analysis was used to compare the diagnostic performance between LI-RADS and mRECIST and between CT and MRI. The sensitivity and specificity for diagnosing viable tumor were not significantly different between APHE alone and LR-TR viable criteria on CT (p = 0.054 and p = 0.317) and MRI (p = 0.093 and p = 0.603). On CT, the area under the ROC curve (AUC) of LI-RADS was significantly higher than that of mRECIST (0.733 vs. 0.657, p < 0.001). On MRI, there was no significant difference in AUCs between LI-RADS and mRECIST (0.802 vs. 0.791, p = 0.500). Intra-individual comparison of CT and MRI showed comparable AUCs using LI-RADS (0.783 vs. 0.795, p = 0.776). LI-RADS v2017 treatment response algorithm showed better diagnostic performance than mRECIST on CT. With LI-RADS, CT and MRI were comparable to diagnose tumor viability of HCC after LRT. • Using Liver Imaging Reporting and Data System (LI-RADS) v2017 treatment response algorithm, the viability of hepatocellular carcinoma (HCC) after locoregional therapy (LRT) can be accurately diagnosed. • LI-RADS v2017 treatment response algorithm is superior to modified Response Evaluation Criteria in Solid Tumors for evaluating HCC viability using CT. • Either CT or MRI can be performed to assess tumor viability after LRT using LI-RADS v2017 treatment response algorithm.

Spectrum of Imaging Findings by Dynamic MRI Post Hepatic Intervention by Loco-Regional Therapies for Hepatocellular Carcinoma

Abstract Background: Liver cirrhosis and Hepatocellular Carcinoma (HCC) constitute one of the major causes of morbidity, mortality, and high health care costs worldwide. Multiple treatment options are available for HCC depending on the clinical status of the patient, size and location of the tumor, and available techniques and expertise. Locoregional treatment options are multiple. The most challenging part is how to assess the treatment response by different imaging modalities, but our scope will be assessing the response to locoregional therapy for HCC by MRI. Aim of Study: To study the role of dynamic contrast enhanced MRI in follow-up of after treatment by different loco regional procedures and review the spectrum of imaging findings. Subject and Methods: This study was conducted on 45 patients with different age group 30 to 73 years with the mean age of 58 years having different site, size and shape of hepato-cellular carcinoma (proved mainly by combination of elevated alpha-fetoprotein, typically neoplastic enhancement by spiral CT or dynamic MRI and having hepatitis C or/& B viruses). Results: MRI was found to be of great value in the follow-up of cases of HCC that underwent locoregional therapy specially in diagnosing residual or recurrent tumor tissue in the embolized lesions and in detecting new developed lesions. This technique can be implemented simply and reliably. The study found that almost all of the embolized lesions in the unresolved group of patients (residual/recurrence) showed enhancing areas within in the arterial phase, the study also found that 68.9% of the embolized lesions in the resolved group of patients (complete tumor ablation) were not enhanced at all while 24.4% of them showed delayed marginal enhance-ment. Conclusion: MRI is a powerful tool in detection of tumor viability and complications after locoregional treatment of hepatocellular carcinoma.

Tumor necrosis factor-alpha and alpha-fetoprotein as biomarkers for diagnosis and follow-up of hepatocellular carcinoma before and after interventional therapy

IntroductionUp to 90% of the hepatocellular carcinoma (HCC) cases in Egypt were attributable to hepatitis C virus (HCV) infection. The absolute positive and negative markers for HCC are still deficient. Alpha-fetoprotein (AFP), the most widely used biomarker for early detection and clinical follow-up of patients with HCC, has a sensitivity and a specificity of 41–65% and 80–94%, respectively, even with low cutoff value at 20 ng/ ml. High plasma levels of tumor necrosis factor-alpha (TNF-α) are associated with some cancers, and it has an important central role in hepatocarcinogenesis and involved in cancer invasion with or without metastasis.AimTo evaluate the diagnostic accuracy of TNF-α versus AFP as biomarkers for detection of HCC on top of HCV-related cirrhosis and to assess treatment response by using TNF-α and AFP after locoregional intervention of HCC.Patients and methodsA total of 27 normal control, 51 cirrhotic patients, and 69 cirrhotic patients with HCC were studied in two phases. Radiofrequency ablation and transarterial chemoembolization were done, and patients were followed up for response and tumor marker values.ResultsTNF-α in the diagnosis of Egyptian patients with HCC related to HCV cirrhosis had a sensitivity of 100% and a specificity of 94.1% at a cutoff value of more than or equal to 30 pg/ml. Moreover, more than or equal to 15.2% decrement is a good predictor of complete ablation versus partially or failed ablation with a sensitivity of 78.6%, a specificity of 83.3%, and overall accuracy of 80.77%.ConclusionCombined use of TNF-α in addition to AFP increases sensitivity and specificity for early diagnosis of HCC rather than the use of each tumor marker alone. Moreover, TNF-α could be a better noninvasive tumor marker than AFP for assessment of response after locoregional therapy of HCC.

Contemporary Systematic Review of Health-Related Quality of Life Outcomes in Locoregional Therapies for Hepatocellular Carcinoma.

Health-related quality of life has become an important aspect in oncologic decision making. Recent data suggest that Health-Related Quality of Life (HRQoL) measurements can play an important prognostic role in patients with hepatocellular carcinoma (HCC). Locoregional therapies (LRTs) such as radiofrequency ablation, transarterial chemoembolization, and radioembolization (TARE) are important parts of HCC management. Results demonstrated that radiofrequency ablation treatment results in improving HRQoL compared to surgery for up to 3 years after treatment. Between TARE and transarterial chemoembolization, TARE provides the most benefit in terms of HRQoL. This systematic review investigated contemporary data surrounding HRQoL in patients undergoing LRTs and its impact on clinical decision making.

End-hole Versus Microvalve Infusion Catheters in Patients Undergoing Drug-Eluting Microspheres-TACE for Solitary Hepatocellular Carcinoma Tumors: A Retrospective Analysis

IntroductionPre-transplant locoregional therapy for hepatocellular carcinoma (HCC) during bridge-to-transplant impacts recurrence and survival rates following liver transplantation. Optimizing the effectiveness of transarterial chemoembolization (TACE) in this population is imperative, and microvalve infusion catheters offer a means of such improvement.MethodsAll treatment-naive patients with solitary HCC tumors < 6.5 cm who underwent drug-eluting microspheres (DEM) TACE between 04/2015 and 08/2017 were retrospectively reviewed. Eighty-eight included patients underwent DEM-TACE with either standard end-hole catheters (EH) or microvalve infusion catheters (MVI). The EH (n = 70) and MVI (n = 18) cohorts had similar baseline tumor size, laboratory values, and tumor etiologies.ResultsInitial objective response rates were significantly higher in MVI vs. EH (100% vs. 76.5%, p = 0.019). There was no difference in adverse events between groups (p = 0.265). MVI patients exhibited lower AST (p = 0.003) and ALT (p = 0.044) at 6 months. Blinded pathological analysis of explanted livers showed greater concentrations of microspheres within the tumor relative to the surrounding tissue in MVI explants (88.7 ± 10.6%) versus the EH explants (55.3 ± 32.7%) (p = 0.002). There was significantly higher percentage tumor necrosis in the MVI group (89.0 ± 2.2%) compared with the EH group (56.1 ± 44.5%) (p = 0.006).ConclusionIn this retrospective study of a single-center cohort, DEM-TACE procedures with MVI were associated with improved tumor response, increased deposition of microspheres within tumor tissue, and higher percentage tumor necrosis at explant relative to those performed using EH catheters.

Microbubble-enhanced ultrasound for the antivascular treatment and monitoring of hepatocellular carcinoma.

Background and Objective: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, and its current management relies heavily on locoregional therapy for curative therapy, bridge to transplant, and palliative therapy. Locoregional therapies include ablation and hepatic artery therapies such as embolization and radioembolization. In this study we evaluate the feasibility of using novel antivascular ultrasound (AVUS) as a noninvasive locoregional therapy to reduce perfusion in HCC lesions in a rat model and, monitor the effect with contrast-enhanced ultrasound imaging.Methods: HCC was induced in 36 Wistar rats by the ingestion of 0.01% diethylnitrosamine (DEN) for 12 weeks. Two therapy regimens of AVUS were evaluated. A primary regimen (n = 19) utilized 2-W/cm2, 3-MHz ultrasound (US) for 6 minutes insonation with 0.7 ml of microbubbles administered as an intravenous bolus. An alternate dose at half the primary intensity, sonication time, and contrast concentration was evaluated in 11 rats to assess the efficacy of a reduced dose. A control group (n = 6) received a sham therapy. Tumor perfusion was measured before and after AVUS with nonlinear contrast ultrasound (NLC) and power Doppler (PD). The quantitative perfusion measures included perfusion index (PI), peak enhancement (PE), time to peak (TTP), and perfusion area from NLC and PD scans. Total tumor area perfused during the scan was measured by a postprocessing algorithm called delta projection. Tumor histology was evaluated for signs of tissue injury and for vascular changes using CD31 immunohistochemistry.Results: DEN exposure induced autochthonous hepatocellular carcinoma lesions in all rats. Across all groups prior to therapy, there were no significant differences in the nonlinear contrast observations of peak enhancement and perfusion index. In the control group, there were no significant differences in any of the parameters after sham treatment. After the primary AVUS regimen, there were significant changes in all parameters (p ≤ 0.05) indicating substantial decreases in tumor perfusion. Peak enhancement in nonlinear contrast scans showed a 37.9% ± 10.1% decrease in tumor perfusion. Following reduced-dose AVUS, there were no significant changes in perfusion parameters, although there was a trend for the nonlinear contrast observations of peak enhancement and perfusion index to increase.Conclusion: This study translated low-intensity AVUS therapy into a realistic in vivo model of HCC and evaluated its effects on the tumor vasculature. The primary dose of AVUS tested resulted in significant vascular disruption and a corresponding reduction in tumor perfusion. A reduced dose of AVUS, on the other hand, was ineffective at disrupting perfusion but demonstrated the potential for enhancing tumor blood flow. Theranostic ultrasound, where acoustic energy and microbubbles are used to monitor the tumor neovasculature as well as disrupt the vasculature and treat lesions, could serve as a potent tool for delivering noninvasive, locoregional therapy for hepatocellular carcinoma.

Remnant vital tissue following locoregional therapy for hepatocellular carcinoma: another player in the game.

The applicability of liver transplantation (LT) as a curative option for patients with hepatocellular carcinoma (HCC) is limited by organ shortage. In addition to tumor size and number, other variables, particularly those that are surrogates of tumor biology should be incorporated into the allocation policies to improve the estimation of post-LT benefit. In this issue of Transplant International, Manzia etal. analyze the role of remnant vital tissue (RVT) of the target lesion after locoregional therapies (LRT) in predicting post-LT HCC recurrence This article is protected by copyright. All rights reserved.

Efficacy of contrast-enhanced FDG PET/CT in patients awaiting liver transplantation with rising alpha-fetoprotein after bridge therapy of hepatocellular carcinoma.

To assess the diagnostic accuracy and illustrate positive findings of contrast-enhanced fluorine-18 fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) image in patients awaiting liver transplantation (LT) with rising alpha-fetoprotein (AFP) after bridge therapy of hepatocellular carcinoma (HCC). This prospective study included 100 patients who were waiting for LT and who previously underwent locoregional therapy (LRT) of HCC. These patients had rising AFP levels on a routine follow-up examination awaiting LT. All patients underwent a contrast-enhanced 18F-FDG PET/CT examination. We calculated for each patient the maximum standardised uptake value (SUVmax) of the tumour and the ratio of the tumoral SUVmax to the normal-liver SUVmax. The diagnostic accuracy and positive contrast-enhanced findings of 18F-FDG PET/CT were established by histopathology and clinical and imaging follow-up as the reference standards. Contrast-enhanced 18F-FDG PET/CT detected tumour relapse in 78 patients (13 patients had intrahepatic lesions, 10 patients had extrahepatic metastases and 55 patients with combined lesions). The sensitivity, specificity and accuracy values of contrast-enhanced 18F-FDG PET/CT examination in the detection of HCC recurrence were 92.8%, 94.1% and 93%, respectively. A significant correlation was found between the AFP level and SUVmax ratio (r = 0.2283; p = 0.0224). The best threshold for 18F-FDG PET positivity was >1.21. Contrast-enhanced 18F-FDG PET/CT is a valuable tool for the detection of intrahepatic HCC recurrence or extrahepatic metastasis following rising AFP levels after LRT of HCC, and should be incorporated during routine workup awaiting LT. • 18F-FDG PET/CT is a valuable tool for the detection of HCC recurrence • 18 F-FDG PET/CT should be incorporated during routine workup awaiting liver transplantation • Significant correlation was found between AFP level and SUVmax ratio • The best threshold for 18 F-FDG PET positivity was >1.21 • The ideal cut-off value for AFP was >202.

THU-175 - Outcomes of single or sequential dual modality loco-regional therapies in Hepatocellular carcinoma

THU-175 - Outcomes of single or sequential dual modality loco-regional therapies in Hepatocellular carcinoma

Abstract No. 530 Association of radiological complete response following locoregional therapy prior to liver transplantation with long-term outcomes of hepatocellular carcinoma patients

To evaluate the long-term outcomes of patients with hepatocellular carcinoma (HCC) who achieve complete vs. incomplete imaging response on pretransplant imaging studies following locoregional therapy (LRT) prior to orthotopic liver transplantation (OLT). Institutional database was reviewed to identify the patients listed for OLT with HCC (Mar1998-Dec2010). Patient and baseline tumor characteristics as well as type of LRT and post-transplant outcomes were recorded. Imaging response to LRT was evaluated on pretransplant contrast-enhanced CT or MRI based on mRECIST criteria. Survival analysis was performed using Kaplan-Meier estimation and log-rank test. 155 HCC patients were identified who received OLT following LRT for HCC. Posttreatment imaging was available in 109 (70%) patients while 46 patients (30%) were transplanted after LRT prior to any imaging study. Complete response was achieved in 65 patients (60%) versus incomplete response in 44 (40%). The table lists the baseline demographic, clinical and tumor characteristics of the study population at the time of diagnosis. Type of LRT was TACE in 55, RFA in 9, and sequential TACE and RFA in 1 patient for the complete response group compared to TACE in 34, RFA in 4, sequential TACE and RFA in 5 and radioembolization in 1 for the incomplete response group (p-value = 0.1). Mean progression-free survival from the time of listing was significantly better for HCC patients who achieved complete response after LRT (mean survival of 144 ± 8.4 vs. 131 ± 13.9 months, p-value = 0.04). 3, 5 and 7-year recurrence free survival after OLT was 81%, 74% and 65% for patients in the complete response group compared to 68%, 59% and 47% for patients with incomplete response (p value = 0.04). Achieving an imaging complete response following LRT prior to OLT for HCC is associated with better progression-free survival after being listed and improved recurrence free survival after liver transplant.Tabled 1Age at DiagnosisGender (Female)MELD ScoreDays on WaitlistMean Longest Diameter of Largest HCC at Diagnosis (mm)Mean Number of TumorsBCLC 0BCLC ABCLC BComplete response (n = 65)55.5 ± 1.110 (15%)10.3 ± 0.5242.4 ± 39.928.5 ± 1.31.5 ± 0.15 (8%)39 (60%)21 (32%)Incomplete response (n = 44)57.5 ± 1.18 (18%)10.1 ± 0.4227.2 ± 40.030.1 ± 1.71.7 ± 0.14 (9%)23 (52%)17 (39%)P Value0.20.70.80.80.40.060.7 Open table in a new tab

Deterioration of hepatic function after locoregional therapy (LRT) for hepatocellular carcinoma (HCC) measured by hepatic cholate clearance: A pilot study.

468 Background: LRT is used in treating HCC, but is associated with a risk of hepatotoxicity, which is not accurately predicted by traditional measures of liver function. In this pilot study, we evaluated the change in liver function after LRT as measured by a test using dual, oral and IV, cholate clearances (HepQuantSHUNT). Our hypothesis is that LRT would impose a significant reduction in the disease severity index (DSI) measured in the HepQuant SHUNT test, as an indicator of reduced liver function. Methods: We conducted a prospective cohort study of 11 subjects undergoing LRT for HCC. HepQuantSHUNT was performed at baseline (T0) and 4-10 weeks after LRT (T1). Clinical assessment was performed at T0 and T1, and at 12-18 weeks after LRT (T2). Decompensation was defined as either a new complication of cirrhosis or an increase in Child-Pugh (CP) score by ≥2 points. Results: Median age was 61 years, 73% were men, 55% had hepatitis C. Median CP score was 7[5-8], including 36%CP A and 64%CP B. Subjects had a BCLC stage A(64%) or BCLC stage B(36%) HCC. LRT modalities were TACE (45%) or SBRT (55%). From T0 to T1, there was a reduction in oral cholate clearance(422[235-768] vs 339[208-362], p = 0.03) and in IV cholate clearance(210[150-300] vs 191[144-203],p = 0.04) as well as a trend towards a worsening disease severity index (DSI) (32.0[19.5-37.8] vs 33.0[29.7-38.0],p = 0.10); however, there was no significant change in MELD(12[9-13]vs 11[10-12],p = 0.72) or CP score(7[5-8] vs 7[6-8],p = 0.15). 89% of the subjects had a reduction in oral and IV cholate clearance, and 78% had a worsening DSI; while 44% subjects had increase in CP score, and 56% had an increase in MELD. Decompensation was observed in 43% of CP B patients and none of CP A patients; and in 60% patients with a DSI &gt; 35, and none of the patients with DSI &lt; 35. Conclusions: The dual cholate clearance assay HepQuant-SHUNT detects a deterioration in liver function after LRT for HCC more frequently than clinical measures of liver function. DSI 35 might be a cutoff for risk of clinical decompensation after LRT for HCC. Additional research is needed to evaluate the role of the HepQuant SHUNT test in improving the selection of Child B patients for LRT.

Locoregional therapies for hepatocellular carcinoma and the new LI-RADS treatment response algorithm.

Radiologists play a central role in the assessment of patient response to locoregional therapies for hepatocellular carcinoma (HCC). The identification of viable tumor following treatment guides further management and potentially affects transplantation eligibility. Liver Imaging Reporting and Data Systems (LI-RADS) first introduced the concept of LR-treated in 2014, and a new treatment response algorithm is included in the 2017 update to assist radiologists in image interpretation of HCC after locoregional therapy. In addition to offering imaging criteria for viable and nonviable HCC, new concepts of nonevaluable tumors as well as tumors with equivocal viability are introduced. Existing guidelines provided by response evaluation criteria in solid tumors (RECIST) and modified RECIST address patient-level assessments and are routinely used in clinical trials but do not address the variable appearances following different locoregional therapies. The new LI-RADS treatment response algorithm addresses this gap and offers a comprehensive approach to assess treatment response for individual lesions after a variety of locoregional therapies, using either contrast-enhanced CT or MRI.

Average treatment effect of hepatic resection versus locoregional therapies for hepatocellular carcinoma.

When comparing the efficacy of surgical and non-surgical therapies for hepatocellular carcinoma (HCC), a major limitation is the causal inference problem. This concerns the impossibility of seeing both outcomes of two different treatments for the same individual at the same time because one is inevitably missing. This aspect can be addressed methodologically by estimating the so-called average treatment effect (ATE). To estimate the ATE of hepatic resection over locoregional therapies for HCC, data from patients treated in two tertiary care settings between August 2000 and December 2014 were used to obtain counterfactual outcomes using an inverse probability weight survival adjustment. A total of 1585 patients were enrolled: 815 underwent hepatic resection, 337 radiofrequency ablation (RFA) and 433 transarterial chemoembolization (TACE). The option of operating on all patients who had tumour ablation returned an ATE of +9·8 months for resection (effect size 0·111; adjusted P = 0·064). The option of operating on all patients who had TACE returned an ATE of +27·9 months (effect size 0·383; adjusted P < 0·001). The ATE of surgery was negligible in patients undergoing ablation for very early HCCs (effect size 0·027; adjusted P = 0·627), independently of albumin-bilirubin (ALBI) grade; or in patients with ALBI liver function grade 2 (effect size 0·083; adjusted P = 0·213), independently of tumour stage. In all other instances, the ATE of surgery was notably greater. Operating on patients who had TACE with multinodular HCC beyond the Milan criteria resulted in a mild ATE (effect size 0·140; adjusted P = 0·037). ATE estimation suggests that hepatic resection is a better treatment option than ablation and TACE in patients with HCC.

Management of Hepatocellular Carcinoma: Prevention, Surveillance, Diagnosis, and Staging.

More than 600 000 people die from hepatocellular carcinoma each year. Worldwide, research on the disease needs to be intensified in both the medical and pharmaceutical fields, with a focus on providing help to geographic areas where resources are limited. Treatment approaches depend on the stage of the disease at diagnosis and on access to complex treatment regimens. However, advanced disease is not curable, and treating these patients is expensive and only marginally effective for increasing quality-adjusted life-years. Although the Milan criteria are often used to determine which patients will benefit from liver transplantation, many centers have their own criteria for patient selection. According to criteria developed by Başkent University in Ankara, Turkey, patients with hepatocellular carcinoma and a cirrhotic liver but without extrahepatic disease should be candidates for liver transplant when possible, and living-donor liver transplant should be considered as an alternative rescue therapy for many of these patients. Tumor size and number should not be the sole criteria for excluding liver transplant. Although significant vascular invasion and extrahepatic dissemination definitely indicate major tumor dissemination, until sensitive tests for measuring circulating tumor cells are developed, we continue to recommend liver transplant regardless of tumor size and number. Various locoregional therapies for hepatocellular carcinoma are used before transplant to prevent tumor progression and to decrease the risk of recurrence after transplant. In turn, response to locoregional therapy to decrease tumor stage in hepatocellular carcinoma may be an indicator of tumor behavior and may determine a patient's selection for liver transplant. The delivery of healthcare services for hepatocellular carcinoma could be improved by developing centers of excellence. Concentrating medical care in this way can lead to an increased level of expertise so that resections are performed by surgeons who understand liver disease and the limitations of these and other procedures.