Search

Background: Alterations to DNA methylation have been identified in both hepatocellular carcinoma (HCC) tumor and circulating DNA from affected individuals. These markers have potential utility in HCC screening. Adherence to HCC screening is poor and acceptable HCC screening tests are needed., Methods: A feasibility study was performed on a subset of case patients and control subjects from a prior study of risk factors for HCC. Case patients (n=12) included adults aged 47-85 years with a first diagnosis of HCC between 2011 and 2016 and without viral hepatitis. Control subjects (n=12) were matched on age, sex, and state of residence. Participants provided saliva samples for DNA genotyping. Log fold change in salivary DNA methylation at 1359 CpG sites representing 25 candidate genes previously associated with HCC was compared across case patients and control subjects., Results: The quantity of DNA ranged from 9.65 to 257.79 μg. The purity of DNA isolates was good, with mean OD260/280 ratio of 1.78 (SD: 0.14). Of 25 candidate genes, 16 had at ≥1 CpG site with detectable differences in methylation across HCC case patients and control subjects. Sites differentially methylated in HCC case patients included genes encoding tumor suppressors (PRDM2, RUNX3, p15/16, and RASSF1/5), regulators of cell cycle progression (DAPK1 and TP73), and DNA repair (MGMT and GSTP1). No associations met the significance threshold 3.7 × 10-5 required for multiple comparisons., Conclusions: Salivary DNA may be a feasible alternative to blood samples in the era of novel DNA-based screening tests for HCC. The ease of saliva-based testing supports further investigation of its potential., (© 2024 The Author(s).)

We sought to determine the influence of background liver biopsies on hepatocellular carcinoma (HCC) management. The pathology database at a large university hospital was searched between 2013 and 2018 for all instances of when a separate biopsy of the nontumoral liver was performed within 6 months of an HCC biopsy. Patients were evaluated for baseline demographic and clinical characteristics, treatment proposed prior to biopsy, and impact of biopsy results on management. Among the 104 identified cases of paired liver biopsies, 22% were women; the median age was 64 years; and most were of earlier HCC stages at diagnosis (Barcelona Clinic Liver Cancer stages 0-A: 70%). Four patients among 10 in whom cirrhosis status was clinically unclear were confirmed to have cirrhosis on biopsy, and 4 patients did not have cirrhosis despite clinical suspicion. Treatment was altered by the background parenchymal findings for 5 patients (5%): management was less aggressive for 4 patients and more aggressive for 1 patient. A background liver biopsy can significantly impact the management of a small subset of HCC patients, especially those with early disease, and should be considered concurrently with the biopsy of the mass., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background Patients with intermediate- and advanced-stage hepatocellular carcinoma (HCC) represent a highly heterogeneous patient collective with substantial differences in overall survival. Purpose To evaluate enhancing tumor volume (ETV) and enhancing tumor burden (ETB) as new criteria within the Barcelona Clinic Liver Cancer (BCLC) staging system for optimized allocation of patients with intermediate- and advanced-stage HCC to undergo transarterial chemoembolization (TACE). Materials and Methods In this retrospective study, 682 patients with HCC who underwent conventional TACE or TACE with drug-eluting beads from January 2000 to December 2014 were evaluated. Quantitative three-dimensional analysis of contrast-enhanced MRI was performed to determine thresholds of ETV and ETB (ratio of ETV to normal liver volume). Patients with ETV below 65 cm 3 or ETB below 4% were reassigned to BCLC B n , whereas patients with ETV or ETB above the determined cutoffs were restratified or remained in BCLC C n by means of stepwise verification of the median overall survival (mOS). Results This study included 494 patients (median age, 62 years [IQR, 56-71 years]; 401 men). Originally, 123 patients were classified as BCLC B with mOS of 24.3 months (95% CI: 21.4, 32.9) and 371 patients as BCLC C with mOS of 11.9 months (95% CI: 10.5, 14.8). The mOS of all included patients (including the BCLC B and C groups) was 15 months (95% CI: 12.3, 17.2). A total of 152 patients with BCLC C tumors were restratified into a new BCLC B n class, in which the mOS was then 25.1 months (95% CI: 21.8, 29.7; P < .001). The mOS of the remaining patients (ie, BCLC C n group) ( n = 222; ETV ≥65 cm 3 or ETB ≥4%) was 8.4 months (95% CI: 6.1, 11.2). Conclusion Substratification of patients with intermediate- and advanced-stage hepatocellular carcinoma according to three-dimensional quantitative tumor burden identified patients with a survival benefit from transarterial chemoembolization before therapy. © RSNA, 2022 Online supplemental material is available for this article .

Purpose: To assess the Liver Imaging Reporting and Data System (LI-RADS) and radiomic features in pretreatment magnetic resonance (MR) imaging for predicting progression-free survival (PFS) in patients with nodular hepatocellular carcinoma (HCC) treated with radiofrequency (RF) ablation., Material and Methods: Sixty-five therapy-naïve patients with 85 nodular HCC tumors <5 cm in size were included in this Health Insurance Portability and Accountability Act-compliant, institutional review board-approved, retrospective study. All patients underwent RF ablation as first-line treatment and demonstrated complete response on the first follow-up imaging. Gadolinium-enhanced MR imaging biomarkers were analyzed for LI-RADS features by 2 board-certified radiologists or by analysis of nodular and perinodular radiomic features from 3-dimensional segmentations. A radiomic signature was calculated with the most informative features of a least absolute shrinkage and selection operator Cox regression model using leave-one-out cross-validation. The association between both LI-RADS features and radiomic signatures with PFS was assessed via the Kaplan-Meier analysis and a weighted log-rank test., Results: The median PFS was 19 months (95% confidence interval, 16.1-19.4) for a follow-up period of 24 months. Multifocality (P = .033); the appearance of capsular continuity, compared with an absent or discontinuous capsule (P = .012); and a higher radiomic signature based on nodular and perinodular features (P = .030) were associated with poorer PFS in early-stage HCC. The observation size, presence of arterial hyperenhancement, nonperipheral washout, and appearance of an enhancing "capsule" were not associated with PFS (P > .05)., Conclusions: Although multifocal HCC clearly indicates a more aggressive phenotype even in early-stage disease, the continuity of an enhancing capsule and a higher radiomic signature may add value as MR imaging biomarkers for poor PFS in HCC treated with RF ablation., (Copyright © 2022 SIR. Published by Elsevier Inc. All rights reserved.)

The burden of HCC is substantial. To address gaps in HCC care, the American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) aimed to develop a standard set of process-based measures and patient-reported outcomes (PROs) along the HCC care continuum. We identified candidate process and outcomes measures for HCC care based on structured literature review. A 13-member panel with content expertise across the HCC care continuum evaluated candidate measures on importance and performance gap using a modified Delphi approach (two rounds of rating) to define the final set of measures. Candidate PROs based on a structured scoping review were ranked by 74 patients with HCC across 7 diverse institutions. Out of 135 measures, 29 measures made the final set. These covered surveillance (6 measures), diagnosis (6 measures), staging (2 measures), treatment (10 measures), and outcomes (5 measures). Examples included the use of ultrasound (± alpha-fetoprotein [AFP]) every 6 months, need for surveillance in high-risk populations, diagnostic testing for patients with a new AFP elevation, multidisciplinary liver tumor board (MLTB) review of Liver Imaging-Reporting and Data System 4 lesions, standard evaluation at diagnosis, treatment recommendations based on Barcelona Clinic Liver Cancer staging, MLTB discussion of treatment options, appropriate referral for evaluation of liver transplantation candidacy, and role of palliative therapy. PROs include those related to pain, anxiety, fear of treatment, and uncertainty about the best individual treatment and the future. The AASLD PMC has developed a set of explicit quality measures in HCC care to help bridge the gap between guideline recommendations and measurable processes and outcomes. Measurement and subsequent implementation of these metrics could be a central step in the improvement of patient care and outcomes in this high-risk population., (© 2021 American Association for the Study of Liver Diseases.)

Objectives: The pathologic differences between hepatocellular carcinoma (HCC) arising in noncirrhotic and cirrhotic livers have not been well studied., Methods: We performed a retrospective analysis of 378 HCC cases (95 in noncirrhotic, 283 in cirrhotic livers) from pathology archives (2010-2017)., Results: Patients without cirrhosis were more likely to have hepatitis B (13.68% vs 2.83%, P < .001) or no known liver disease (30.53% vs 4.24%, P < .001), while hepatitis C was more common in patients with cirrhosis (65.72% vs 30.53%, P < .001). HCCs in noncirrhotic livers were larger in size (P < .001); were more likely to have a macrotrabecular histologic pattern (13.68% vs 4.95%, P < .01); were more likely to have fibrolamellar (3.16% vs 0%, P = .02), macrotrabecular-massive (13.68% vs 6.01%, P = .03), and clear cell (16.84% vs 6.71%, P < .01) subtypes; have a higher histologic grade (P < .01); be anaplastic tumor cells (P < .001); have a higher rate of vascular invasion (P < .01); and have a higher tumor stage (P = .04)., Conclusions: The findings indicate that HCCs in noncirrhotic livers demonstrate a larger tumor size; have a more macrotrabecular histologic pattern; have fibrolamellar, macrotrabecular-massive, and clear cell subtypes; have a higher tumor grade and stage; have a higher rate of vascular invasion; and have more anaplastic tumor cells compared with cirrhotic livers. Further studies to explore different pathways that promote oncogenesis in noncirrhotic livers are needed to better understand the pathogenesis of HCC., (© American Society for Clinical Pathology, 2021. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Context.—: Intrahepatic cholangiocarcinoma (iCCA) needs to be distinguished from hepatocellular carcinoma (HCC) and metastasis, and in the absence of any specific biliary markers, is often a diagnosis of exclusion. Hepatocyte nuclear factor (HNF)-1β is a transcription factor that plays a critical role in bile duct system morphogenesis., Objective.—: To investigate the diagnostic value of HNF-1β to differentiate iCCA from HCC by immunohistochemistry and compare HNF-1β with C-reactive protein (CRP), a previously identified marker for iCCA., Design.—: Cases of iCCA (n = 75), combined hepatocellular-cholangiocarcinoma (cHCC-CCA) (n = 13) and HCC (n = 65) were included in the study., Results.—: All cases of iCCA (74 of 74, 100%) expressed HNF-1β compared with CRP expressed in 72.60% (53 of 73). The sensitivity and specificity of HNF-1β to differentiate iCCA from HCC was 100% and 92.31%, whereas the sensitivity and specificity for CRP was 75.58% and 7.79%. The expression of HNF-1β was greater in iCCA and the CCA component of cHCC-CCA compared with CRP (87 of 87, 100% versus 65 of 86, 75.58%; P < .001). On the contrary, CRP was more frequently expressed compared with HNF-1β in HCC and HCC component of cHCC-CCA (71 of 77, 92.21% versus 6 of 78, 7.69%; P < .001)., Conclusions.—: Our data indicate that HNF-1β is a more sensitive and specific marker than CRP for the diagnosis of iCCA and to identify the CCA component in cHCC-CCA. Lack of HNF-1β expression may be used to exclude iCCA from consideration in cases of adenocarcinomas of unknown primary.

Aims: To establish and define a new, not previously reported hepatocellular carcinoma (HCC) variant, termed fibronodular HCC (FN-HCC)., Methods: We retrospectively reviewed 290 HCC cases and identified 29 FN-HCC and 24 scirrhous HCC (SCHCC). Clinical, pathological and radiological features of FN-HCC were reviewed and compared with 30 conventional HCCs (CV-HCC) and SC-HCC., Results: FN-HCCs were more likely to arise in non-advanced fibrotic livers with lower advanced Barcelona Clinic Liver Cancer (BCLC) stage, had lower rates of progression and longer time to progression and were more likely to be surgically resected compared with CV-HCCs and SC-HCCs. Imaging analysis of FN-HCCs demonstrated higher rates of non-peripheral washout and a new distinct pattern of enhancement which is characterised by the presence of multiple rounded nodules within a lesion embedded in fibrotic-appearing parenchyma., Conclusions: FN-HCC may represent a specific variant of HCC with distinct pathological, radiological and clinical features with potential ramifications for outcome., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: HCC incidence has been continuously rising in the US for the past 30 years. To understand the increase in HCC risk, we conducted a case-control study in Connecticut, New Jersey and part of New York City., Methods: Through rapid case ascertainment and random digit dialing, we recruited 673 incident HCC patients and 1,166 controls. Information on demographic and anthropometric characteristics, lifestyle factors, medical and family cancer histories, were ascertained through telephone interviews using a structured questionnaire. Saliva specimens were collected for testing hepatitis C virus (HCV) antibodies. Unconditional logistic regression models were utilized to calculate odds ratio (OR) and 95% confidence interval (CI) to determine HCC associations with risk factors., Results: The study confirmed that HCV infection and obesity were important risk factors for HCC, ORs 110 (95% CI 59.2-204) and 2.13 (95% CI 1.52-3.00), respectively. High BMI and HCV infection had synergy in association with elevated HCC risk. Patients both obese and infected with HCV had HCC detected on average nearly 10 years earlier than those with neither factor. Diabetes, cigarette smoking and heavy alcohol intake were all associated with increased risk of HCC, whereas aspirin and other NSAID use were associated with reduced risk. HCC cases tended to attain less education, with lower household incomes, unmarried, and to have had more sexual partners than the controls., Conclusions: Individuals at risk of HCC in the US comprise a unique population with low socioeconomic status and unhealthy lifestyle choices. Given the multifactorial nature, a comprehensive approach is needed in HCC prevention.

Background: To investigate the impact of insurance status on outcomes in patients with hepatocellular carcinoma (HCC)., Methods: Patients diagnosed with HCC in the cancer registry from 2005 to 2016 were retrospectively stratified by insurance group. Overall survival was assessed via Kaplan-Meier curves and Cox proportional hazard models including potential confounders in multivariable analyses., Results: Seven hundred and sixty-nine patients met inclusion criteria (median age 63 years, 78.8% male, 65.9% Caucasian). 44.5% had private insurance (n = 342), 29.1% had Medicare (n = 224), and 26.4% had Medicaid (n = 203). At diagnosis, Medicaid patients had higher rates of Child-Pugh B (32.0%) and C disease (23.6%) vs Medicare (28.6% and 9.8%) and private insurance (26.9% and 6.7%, P < 0.0001) and higher MELD scores (median 11.0) vs Medicare (9.0) and private insurance (9.0, P = 0.0266). Across insurance groups, patients had similar distribution of American Joint Committee on Cancer stage, tumor size, and multifocal tumor burden. Patients with private insurance had the highest survival (median OS 21.9 months) vs Medicare (17.7 months) and Medicaid (13.0 months, overall P = 0.0061). On univariate analysis, Medicaid patients demonstrated decreased survival vs private insurance (HR 1.40, 95% CI: 1.146-1.715, P = 0.0011). After adjustment for liver disease factors, this survival difference lost statistical significance (Medicaid vs private insurance, HR 1.02, 95% CI: 0.819-1.266, P = 0.8596)., Conclusion: Medicaid was associated with advanced liver disease at HCC diagnosis; however, insurance status is not an independent predictor of HCC survival., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The macrotrabecular (MT) pattern of hepatocellular carcinoma (HCC) has been suggested to represent a distinct HCC subtype. We retrospectively reviewed 231 HCC cases. Detailed pathologic evaluation for histologic patterns, including MT-pattern, was performed for each case and recorded as percentage involved at 10% intervals. MT-pattern was defined as having trabeculae >6 cells thick. After excluding all recognized HCC subtypes, remaining cases were deemed conventional HCC (CV-HCC) and served as controls. HCCs with a component of ≥10%, ≥30% and ≥50% MT-pattern were identified in 41 (17.7%), 24 (10.4%) and 4 (1.7%) cases, respectively. The clinicopathologic features of HCCs with 10% to 29% MT-pattern (n=17, 7.4%) were largely similar to CV-HCC. No significant difference was observed between the 30% and 49% (n=20) and ≥50% (n=4) MT groups, hence these were combined for further analysis as MT-HCC. MT-HCCs (≥30% MT-pattern) were larger tumors (5.5 vs. 3.1 cm), were less likely to be associated with cirrhosis (54% vs. 79%), were more likely to have hepatitis B (21% vs. 5%) and less likely hepatitis C infection (33% vs. 58%) compared with CV-HCC. MT-HCC was associated with the presence of anaplastic tumor cells (42% vs. 14%), higher alpha-fetoprotein level, higher AJCC stage, and higher histologic grade. Compared with patients with CV-HCC, patients with MT-HCC had poorer overall survival. Patients with MT-HCC who underwent primary resection or transplantation had a higher recurrence rate and worse recurrence-free survival. Our findings suggest that ≥30% MT-pattern could be used as the more appropriate cut-off for defining MT-HCC, which represents a unique and aggressive HCC histologic subtype.