Hepatocellular Carcinoma Cases Research Articles

Decreasing incidence of hepatocellular carcinoma among most racial groups: SEER-22, 2000-2019.

Hepatocellular carcinoma (HCC) incidence was rising in the United States. Previously, using data collected by the Surveillance, Epidemiology, and End Results (SEER) Program through 2017, we found that overall incidence had begun to decline, although not in Black and American Indian/Alaska Native (AI/AN) populations. Utilizing expanded SEER data encompassing ~50% of the population, we examined secular trends and demographic differences in HCC incidence through 2019. We included cases of HCC diagnosed in adults aged ≥20 years residing in SEER-22 registry areas. We examined case counts, incidence rates (per 100,000 person-years), annual percent changes (APCs), and calendar years when APCs changed significantly. HCC incidence increased from 5.56 in 2000 to 8.89 in 2009 (APC, 5.17%), then rose more slowly during 2009-2015 (APC, 2.28%). After peaking at 10.03 in 2015, incidence fell to 9.20 in 2019 (APC, -2.26%). In Asian/Pacific Islanders (A/PI), the decline began in 2007 and accelerated in 2015 (APCs: 2007-2015, -1.84%; 2015-2019, -5.80%). In 2014, incidence began to fall in the White (APC: 2014-2019, -1.11%) and Hispanic populations (APC: 2014-2019, -1.72%). In 2016, rates began to fall in Black individuals (APC: 2016-2019, -6.05%). In the AI/AN population, incidence was highest in 2017, although the subsequent decline was not statistically significant. In 2019, population-specific rates were: White, 6.94; Black, 10.74; A/PI, 12.11; AI/AN, 14.56; Hispanic, 15.48. HCC incidence is now decreasing in most US racial/ethnic populations, including among Black individuals. The onset of decline differed among racial/ethnic groups and wide disparities in HCC rates remain.

Racial Disparities in the Utilization of Stereotactic Body Radiation Therapy (SBRT) in Patients with Hepatocellular Carcinoma

SBRT has now been demonstrated to improve OS, PFS and TTP in patient with hepatocellular carcinoma (HCC) when compared to systemic therapy alone. Disparities in the availability and utilization of SBRT for minority racial patients may affect oncologic outcomes. This study examines racial and sociodemographic disparities in the utilization of SBRT for HCC patients. In this registry-based cohort study, data from the American College of Surgeons National Cancer Database (NCDB) from 2004 - 2017 was analyzed. Adults with a new diagnosis of localized, non-metastatic, HCC were included in this analysis. Patients were sub-grouped by race and whether they were treated with liver SBRT. In this analysis, SBRT was defined as radiation delivered in 3-5 fractions and in the 30-60Gy range. The primary outcome of this study was the utilization rate of liver SBRT in HCC, depending on race. Survival was also examined in these patients. Statistical analysis was performed using SPSS v28 for univariate and multivariate logistical regression and Kaplan-Meier analysis. From 2004 - 2017, 95132 cases of localized HCC were identified in patients who were white, non-Spanish, non-Hispanic (WNH) and 40964 cases who were black or Hispanic/Spanish (BH). Of all these patients, only 1963 patients, or 1.4%, were treated with liver SBRT. Comparing WNH patients to BH patients, 1423 (1.5%) WNH patients were treated with SBRT and 334 (0.8%) BH patients were treated with SBRT (p<0.001). Looking at the number of patients treated with SBRT each year, there has been a yearly increase in the use of liver SBRT, from 48 patients in 2007 to 340 patients in 2017. The utilization of SBRT in WNH patients has increased at a higher rate than for BH patients over this time period. The median survival for patients with localized HCC was similar for both WNH and BH patients with a median survival of 17 months (p = 0.36). However, patients who were treated with liver SBRT had an improved median survival of 25 months for WNH patients and 34 months for BH patients (p<0.001). Overall, liver SBRT is severely underutilized for patients with localized HCC in the patient population represented in this database, and fewer BH patients are treated with liver SBRT compared with WNH patients. Liver SBRT is associated with improved survival of HCC patients in this study. With the findings of the RTOG 1112 trial, demonstrating improved OS and PFS with the use of SBRT for HCC, it is essential to adopt liver SBRT more broadly and to develop strategies to reduce the racial disparities in utilization.

Challenges and Solutions in the Management of Hepatocellular Carcinoma Associated with Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) has gained attention in the last few years due to its increasing prevalence worldwide becoming a global epidemic. The increasing incidence of NAFLD and the concurrent increase in the number of hepatocellular carcinoma (HCC) cases at a global level is a matter of concern. HCC has several risk factors, of which NAFLD and its associated metabolic disturbances-type 2 diabetes mellitus, obesity, and dyslipidemia-are of great interest due to their accelerating rise in incidence worldwide. There is a high amount of data derived from basic and clinical studies that reveal the molecular pathways that drive NAFLD-associated HCC. Based on these findings, new prevention, surveillance, and treatment strategies are emerging. However, current data on treatment modalities in NAFLD-associated HCC are still scarce, though the results from non-NAFLD HCC studies are promising and could provide a basis for a future research agenda to address NAFLD/NASH patients. Clinicians should carefully assess all the clinical and radiological parameters and establish a prognosis based on the Barcelona Clinic Liver Cancer classification and discuss in a multidisciplinary team the treatment strategy. The specific factors associated with NAFLD-associated HCC which can have a negative impact on survival even in patients with early HCC, such as cardiovascular disease, type 2 diabetes, and obesity, should be taken into consideration. This review aims to discuss the latest recommendations regarding the diagnosis and treatment of NAFLD-associated HCC and the remaining challenges.

Outcome of Proton Beam Therapy for Primary Hepatocellular Carcinoma with “Unfavorable” Macroscopic Classification

Transcatheter arterial chemoembolization (TACE) is the standard treatment for early to intermediate-stage hepatocellular carcinoma (HCC) unfit for hepatectomy or radiofrequency/microwave ablation (RFA/MWA). Putting aside its hepatic toxicity, local control of TACE is far from satisfactory, especially with non- "simple nodular type" appearances, to an extent where systemic therapy is suggested to be more beneficial. We here analyzed the outcome of proton beam therapy (PBT) for primary HCC by macroscopic classification. Primary HCC treated with PBT between 2010 and 2018 were extracted from an all-in treatment database. The macroscopic classification was defined by CT or MRI prior to PBT. Local recurrence was defined as tumor re-enlargement or the appearance of arterial phase hyperenhancement. Adverse events were evaluated by CTCAE v5.0. Overall survival, local control, intrahepatic recurrence-free survival, and extrahepatic recurrence-free survival were determined by the Kaplan-Meier method, and the association with treatment factors was analyzed by log-rank and cox regression model. A total of 202 primary HCC cases were extracted, all not a candidate for hepatectomy nor RFA/MWA. Out of them, 75 cases were simple nodular type, 79 were simple nodular type with extranodular growth, 38 were confluent multinodular type, and 10 were infiltrative type. 26 cases were HBV positive, and 84 cases were HCV positive. 35 cases had macroscopic vascular invasion (MVI). With a median follow-up period of 3.72 years (IQR: 1.79-5.85years), the 3-year overall survival rate was 68.1% (95% CI 61.0 - 74.3%), the 3-year local control rate was 89.6% (95% CI 83.4-93.5), the 3-year intrahepatic recurrence-free survival rate was 53.7% (95% CI 45.9-60.8%), and the 3-year extrahepatic recurrence-free survival rate was 87.4% (95% CI: 81.5-91.6%). Simple nodular type had better overall survival (73.2% vs 65.2% p = 0.012) and extrahepatic recurrence free survival (96.9% vs 81.9% p<0.01), but there was no statistically significant difference in local control (92.7% vs 87.6% p = 0.06) and intrahepatic recurrence-free survival (62.0% vs 48.5% p = 0.114). Multivariate analysis of risk factors against OS, including age, sex, AFP, MVI, and macroscopic classification, revealed age and macroscopic classification as independent risk factors. Adverse events of grade 3 included 2 cases of gastrointestinal bleeding, 7 cases of liver function disorder, 1 cases of biliary hemorrhage, and 1 case of pleural effusion. Other than one case of early death (2 weeks after treatment) with an unknown causal relationship, there were no adverse events of grade 4 or severe. PBT for non- "simple nodular type" primary HCC appears to be safe and effective, whilst suppression of out-of-field recurrence is needed for further survival prolongment.

Clinical Outcomes of Carbon-Ion Radiotherapy for Large-Sized (≥4cm) Hepatocellular Carcinoma

Radical treatment options for bulky unresectable locally advanced hepatocellular carcinoma (HCC) are limited. The purpose of this study is to evaluate the safety and efficacy of carbon-ion radiotherapy (C-ion RT) for bulky (≥4cm) locally advanced HCC. We performed a retrospective cohort study of patients with bulky (≥4cm) locally advanced HCC treated by C-ion RT between April 2000 and March 2020 in our institution. The eligibility criteria for this study were: (1) the treatment protocols of 45.0-48.0 Gy/2 fractions or 52.8-60.0 Gy/4 fractions, which proven the safety and efficacy in the past clinical trials; (2) Tumors within 3 intrahepatic lesions and with a maximum tumor diameter of 4 cm or greater; (3) N0M0 status; (4) an Eastern Cooperative Oncology Group performance status of 0 to 2; (5) controllable ascites; (6) Child-Pugh grade was A or B. Overall survival (OS), progression-free survival (PFS), and local control rate (LC) were calculated by the Kaplan-Meier method, and Cox regression analysis was used for multivariate analysis. Adverse events were evaluated by CTCAE ver. 5.0. JMP® 12 (SAS Institute Inc., Cary, NC, USA) was used for all analyses. We defined p < 0.05 as statistically significant. A total of 187 patients met the criteria and were evaluated. The median patient age was 73 years (range, 37-90), and 139 of 187 patients were male. Child-Pugh grade was A in 163 patients and B in 24. Modified albumin-bilirubin (mALBI) grade was 1 in 96 patients, 2a in 50, and 2b in 41. The number of HCV-related HCC cases was in 80, HBV in 32 and non-B and non-C in 75. In 51 patients, identification of vascular invasion to the first-order branch of the portal vein and/or major hepatic vein was confirmed. The median maximum tumor diameter was 5.1 cm (4.0-13.5 cm). In 76 patients, C-ion RT were treated for recurrence. With a median follow-up period of 25.9 months (range, 1.1-215.1), 2-year overall survival, progression-free survival and local control rates were 68.3% (95% confidence interval [CI], 64.7-72.0%), 39.0% (95% CI, 35.2 - 42.8%) and 86.7% (95% CI, 84.7 - 89.7%), respectively. Late adverse events were observed in 3 patients (1.6%) with Grade 3 liver dysfunction and in 3 patients (1.6%) with Grade 3 skin disorders, but there were no cases of Grade 4 or higher. Multivariate analysis of prognostic factors for overall survival revealed that mALBI grade in 2b(HR:3.13, 1.97-4.78, p<0.0001), tumor status in recurrent treatment (HR:1.50, 1.02-2.21, p = 0.039), the number of tumors in 2 or more (HR:2.16, 1.01-2.17, p = 0.045), and maximum tumor diameter in larger than 6 cm (HR:2.34, 1.50-3.61, p = 0.0001) were the predominant prognostic factors, while age, presence of vascular invasion, AFP and DCP were not. The safety and efficacy of C-ion RT for bulky (≥4cm) locally advanced HCC was demonstrated. These results suggested that C-ion RT may be a new treatment option for locally advanced bulky HCC with no curative treatment options.

Tips for Preparing and Practicing Thermal Ablation Therapy of Hepatocellular Carcinoma.

Thermal ablation therapy, including radiofrequency ablation (RFA) and microwave ablation (MWA), is considered the optimal locoregional treatment for unresectable early-stage hepatocellular carcinomas (HCCs). Percutaneous image-guided ablation is a minimally invasive treatment that is being increasingly performed because it achieves good clinical outcomes with a lower risk of complications. However, the physics and principles of RFA and MWA markedly differ. Although percutaneous thermal ablation under image guidance may be challenging in HCC cases with limited access or a risk of thermal injury, a number of ablative techniques, each of which may be advantageous and disadvantageous for individual cases, are available. Furthermore, even when a HCC is eligible for ablation based on tumor selection and technical factors, additional patient factors may have an impact on whether it is the appropriate treatment choice. Therefore, a basic understanding of the advantages and limitations of each ablation device and imaging guidance technique, respectively, is important. We herein provide an overview of the basic principles of tissue heating in thermal ablation, clinical and laboratory parameters for ablation therapy, preprocedural management, imaging assessments of responses, and early adverse events. We also discuss associated challenges and how they may be overcome using optimized imaging techniques.

Combined FOLFOX4 with all-trans retinoic acid versus FOLFOX4 with placebo in treatment of advanced hepatocellular carcinoma with extrahepatic metastasis: a randomized, double-blind comparative study

The majority of hepatocellular carcinoma (HCC) cases are diagnosed at an advanced stage. Currently, there are only a few therapeutic methods available for patients with advanced HCC and extrahepatic metastasis (EHM). Systemic chemotherapy, such as FOLFOX4 (infusions of fluorouracil, leucovorin, and oxaliplatin), has been reported for treating advanced HCC with EHM, but its effectiveness is very poor. In this randomized, double-blind, placebo-controlled study, we aimed to assess the efficacy and safety of FOLFOX4 with all-trans-retinoic acid (ATRA) as a palliative treatment for HCC patients with EHM, compared to FOLFOX4 with a placebo. The primary endpoint was overall survival (OS), and subsequently, an exploratory model was developed based on bioinformatics to predict the efficacy of FOLFOX4-ATRA treatment. A total of 108 patients were randomly assigned in a 1:1 ratio to receive either FOLFOX4-ATRA or FOLFOX4-placebo. The intention-to-treat (ITT) population showed a median OS of 16.2 months for the FOLFOX4-ATRA group, compared with 10.7 months for the FOLFOX4-placebo group (HR 0.56, 95% CI 0.33–0.93; p = 0.025). The median progression-free survival (PFS) was 7.1 months for the FOLFOX4-ATRA group and 4.2 months for the FOLFOX4-placebo group (HR 0.62, 95% CI 0.41–0.94; p = 0.024). A panel of proteins with unique upregulation during complete response (CR) (SOD3, TTR, SSC5D, GP5, IGKV1D-33) and partial response (PR) (TGFB1, GSS, IGHV5-10-1) effectively predicted CR and PR in patients treated with FOLFOX4-ATRA, as compared to FOLFOX4-placebo. The results suggest that FOLFOX4-ATRA is a safe and effective treatment for patients with advanced HCC and EHM in eastern China.

Construction of a diagnostic model for hepatitis B-related hepatocellular carcinoma using machine learning and artificial neural networks and revealing the correlation by immunoassay

HBV infection profoundly escalates hepatocellular carcinoma (HCC) susceptibility, responsible for a majority of HCC cases. HBV-driven immune-mediated hepatocyte impairment significantly fuels HCC progression. Regrettably, inconspicuous early HCC symptoms often culminate in belated diagnoses. Nevertheless, surgically treated early-stage HCC patients relish augmented five-year survival rates. In contrast, advanced HCC exhibits feeble responses to conventional interventions like radiotherapy, chemotherapy, and surgery, leading to diminished survival rates. This investigation endeavors to unearth diagnostic hallmark genes for HBV-HCC leveraging a bioinformatics framework, thus refining early HBV-HCC detection. Candidate genes were sieved via differential analysis and Weighted Gene Co-Expression Network Analysis (WGCNA). Employing three distinct machine learning algorithms unearthed three feature genes (HHIP, CXCL14, and CDHR2). Melding these genes yielded an innovative Artificial Neural Network (ANN) diagnostic blueprint, portending to alleviate patient encumbrance and elevate life quality. Immunoassay scrutiny unveiled accentuated immune damage in HBV-HCC patients relative to solitary HCC. Through consensus clustering, HBV-HCC was stratified into two subtypes (C1 and C2), the latter potentially indicating milder immune impairment. The diagnostic model grounded in these feature genes showcased robust and transferrable prognostic potentialities, introducing a novel outlook for early HBV-HCC diagnosis. This exhaustive immunological odyssey stands poised to expedite immunotherapeutic curatives' emergence for HBV-HCC.

Liquid biopsy for early detection of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly prevalent and lethal cancer globally. Over 90% of HCC cases arise in the context of liver cirrhosis, and the severity of the underlying liver disease or advanced tumor stage at diagnosis significantly limits treatment options. Early diagnosis is crucial, and all guidelines stress the importance of screening protocols for HCC early detection as a public health objective. As serum biomarkers are not optimal for early diagnosis, liquid biopsy has emerged as a promising tool for diagnosis, prognostication, and patients' stratification for personalized therapy in various solid tumors, including HCC. While circulating tumor cells (CTCs) are better suited for personalized therapy and prognosis, cell-free DNA (cfDNA) and extracellular vesicle-based technologies show potential for early diagnosis, HCC screening, and surveillance protocols. Evaluating the added value of liquid biopsy genetic and epigenetic biomarkers for HCC screening is a key goal in translational research. Somatic mutations commonly found in HCC can be investigated in cfDNA and plasma exosomes as genetic biomarkers. Unique methylation patterns in cfDNA or cfDNA fragmentome features have been suggested as innovative tools for early HCC detection. Likewise, extracellular vesicle cargo biomarkers such as miRNAs and long non-coding RNAs may serve as potential biomarkers for early HCC detection. This review will explore recent findings on the utility of liquid biopsy for early HCC diagnosis. Combining liquid biopsy methods with traditional serological biomarkers could improve the overall diagnostic accuracy for early HCC detection.

Forecasting the long-term impact of COVID-19 on hepatitis C elimination plans in Italy: A mathematical modelling approach.

Italy has a high HCV prevalence, and despite the approval of a dedicated fund for 'Experimental screening' for 2 years, screening has not been fully implemented. We aimed to evaluate the long-term impact of the persisting delay in HCV elimination after the Coronavirus disease 2019 (COVID-19) pandemic in Italy. We used a mathematical, probabilistic modelling approach evaluating three hypothetical 'Inefficient', 'Efficient experimental' and 'WHO Target' screening scenarios differing by treatment rates over time. A Markov chain for liver disease progression evaluated the number of active infections, decompensated cirrhosis (DC), hepatocellular carcinoma (HCC) and HCV liver-related deaths up to the years 2030 and 2050. The 'WHO Target' scenario estimated 3900 patients with DC and 600 with HCC versus 4400 and 600 cases, respectively, similar for both 'Inefficient' and 'Efficient experimental' screening up to 2030. A sharp (10-fold) decrease in DC and HCC was estimated by the 'WHO Target' scenario compared with the other two scenarios in 2050; the forecasted number of DC was 420 cases versus 4200 and 3800 and of HCC <10 versus 600 and 400 HCC cases by 'WHO Target,' 'Inefficient' and 'Efficient experimental' scenarios, respectively. A significant decrease of the cumulative estimated number of liver-related deaths was observed up to 2050 by the 'WHO Target' scenario (52000) versus 'Inefficient' or 'Efficient experimental' scenarios (79 000 and 74 000 liver-related deaths, respectively). Our estimates highlight the need to extensively and efficiently address HCV screening and cure of HCV infection in order to avoid the forecasted long-term HCV adverse outcomes in Italy.

Fibrolamellar hepatocellular carcinoma: a case report and gene analysis

BackgroundFibrolamellar hepatocellular carcinoma (HCC) (FL-HCC) is rare in Japan. FL-HCC develops in young patients with no history of cirrhosis and tends to manifest lymphatic metastasis with clinical features similar to those of HCC. We present a case of FL-HCC in a young male patient.Case presentationA 14-year-old male patient underwent abdominal computed tomography (CT) to diagnose appendicitis, wherein a hepatic tumor was detected. Dynamic enhanced CT revealed a 35-mm solid tumor, which contrasted at the early phase of dynamic enhanced study of the right hepatic segments, with occlusion of the right portal vein. We performed right hepatectomy for these lesions. The patient experienced a single lymphatic recurrence on the hepatoduodenal ligament 12 months after the initial surgery. We performed lymphadenectomy for the recurrent tumor. We performed RNA sequencing (RNA-seq) and targeted DNA sequencing of the resected specimens (primary tumor, lymphatic metastasis, and normal liver). RNA-seq detected DNAJB1-PRKACA in both primary and metastatic lesions as previously reported. Furthermore, The Cancer Genome Atlas (TCGA) database was used to compare other gene expressions in this case with those of previously reported cases of FL-HCC and HCC in young patients. Principal component analysis of differentially expressed genes in the top 10% revealed that the gene expression in our case was similar to that of previous FL-HCC cases but was a different cluster from that in HCC cases in young patients. Mutational analysis did not detect any somatic mutations associated with carcinogenesis, including previously reported mutations (Kastenhuber et al. in Proc Natl Acad Sci USA 114: 13076–84, 2017).ConclusionWe encountered a case of FL-HCC, a rare hepatic tumor in an adolescent patient, and evaluated the genetic background. Our findings could contribute to the elucidation of the mechanisms underlying carcinogenesis and progression in patients with FL-HCC and thereby contribute to the development of new therapeutic strategies in the future that may improve patient prognosis.

Spatial proximity of tumor-immune interactions predicts patient outcome in hepatocellular carcinoma.

The fitness and viability of a tumor ecosystem are influenced by the spatial organization of its cells. We aimed to study the structure, architecture, and cell-cell dynamics of the heterogeneous liver cancer tumor microenvironment using spatially resolved multiplexed imaging. We performed co-detection by indexing multiplexed immunofluorescence imaging on 68 HCC biopsies from Thai patients [(Thailand Initiative in Genomics and Expression Research for Liver Cancer (TIGER-LC)] as a discovery cohort, and then validated the results in an additional 190 HCC biopsies from Chinese patients [Liver Cancer Institute (LCI)]. We segmented and annotated 117,270 and 465,632 cells from the TIGER-LC and LCI cohorts, respectively. We observed 4 patient groups of TIGER-LC (IC1, IC2, IC3, and IC4) with distinct tumor-immune cellular interaction patterns. In addition, patients from IC2 and IC4 had much better overall survival than those from IC1 and IC3. Noticeably, tumor and CD8 + T-cell interactions were strongly enriched in IC2, the group with the best patient outcomes. The close proximity between the tumor and CD8 + T cells was a strong predictor of patient outcome in both the TIGER-LC and the LCI cohorts. Bulk transcriptomic data from 51 of the 68 HCC cases were used to determine tumor-specific gene expression features of our classified subtypes. Moreover, we observed that the presence of immune spatial neighborhoods in HCC as a measure of overall immune infiltration is linked to better patient prognosis. Highly multiplexed imaging analysis of liver cancer reveals tumor-immune cellular heterogeneity within spatial contexts, such as tumor and CD8 + T-cell interactions, which may predict patient survival.

Laparoscopic right posterior sectionectomy for a large hepatocellular carcinoma close to inferior vena cava.

Approximately 20% of hepatocellular carcinomas (HCC) occur in noncirrhotic livers. Resection may be considered for patients with HCC, provided sufficient future liver remnant is available, regardless of the tumor size. Tumors located posteriorly near the right hepatic vein (RHV), or inferior vena cava can be managed through anterior or caudal approaches. RHV is typically conserved during right posterior sectionectomy. When a large posteriorly placed tumor causes chronic compression on RHV, the right anterior section drainage is redirected preferentially to the middle hepatic vein. The division of RHV in such instances does not cause congestion of segments 8 and 5. The technical complexity of laparoscopic right posterior sectionectomy arises from the large transection surface, positioned horizontally. We describe in this multimedia article, a case of large HCC in segments 6 and 7, which was successfully treated using laparoscopic anatomic right posterior sectionectomy.

The Current Status of the Liver Liquid Biopsy in MASH Related HCC: Overview and Future Directions.

Metabolic dysfunction-associated steatohepatitis (MASH) is one of the major risk factors for chronic liver disease and hepatocellular carcinoma (HCC). The incidence of MASH in Western countries continues to rise, driving HCC as the third cause of cancer-related death worldwide. HCC has become a major global health challenge, partly from the obesity epidemic promoting metabolic cellular disturbances but also from the paucity of biomarkers for its early detection. Over 50% of HCC cases are clinically present at a late stage, where curative measures are no longer beneficial. Currently, there is a paucity of both specific and sensitive biological markers for the early-stage detection of HCC. The search for biological markers in the diagnosis of early HCC in high-risk populations is intense. We described the potential role of surrogates for a liver biopsy in the screening and monitoring of patients at risk for nesting HCC.

MBOAT7 rs641738 Variant Is Not Associated with an Increased Risk of Hepatocellular Carcinoma in a Latin American Cohort

BackgroundThe rs641738 C > T single-nucleotide polymorphism of MBOAT7 has been associated with hepatocellular carcinoma (HCC) and nonalcoholic fatty liver disease (NAFLD). Latin Americans have high rates of HCC and NAFLD, but no assessment between MBOAT7 and HCC has been performed in this population.AimsWe provide the first assessment of the impact of MBOAT7 on HCC risk in Latin Americans.MethodsPatients were prospectively recruited into the ESCALON network, designed to collect samples from Latin American patients with HCC in 6 South American countries (Argentina, Ecuador, Brazil, Chile, Peru, and Colombia). A European cohort and the general Hispanic population of gnomAD database were included for comparison. Associations between HCC and MBOAT7 were evaluated using logistic regression.ResultsIn total, 310 cases of HCC and 493 cases of cirrhosis without HCC were assessed. The MBOAT7 TT genotype was not predictive of HCC in Latin Americans (TT vs CC OR adjusted = 1.15, 95% CI 0.66–2.01, p = 0.610) or Europeans (TT vs CC OR adjusted = 1.20, 95% CI 0.59–2.43, p = 0.621). No significant association was noted on subgroup analysis for NAFLD, viral hepatitis, or alcohol-related liver disease. The TT genotype was increased in the NAFLD-cirrhosis cohort of Latin Americans compared to a non-cirrhotic NAFLD cohort (TT vs CC + CT OR = 2.75, 95% CI 1.10–6.87, p = 0.031).ConclusionThe rs631738 C > T allele of MBOAT7 was not associated with increased risk of HCC in Latin Americans or Europeans. An increase in the risk of cirrhosis was noted with the TT genotype in Latin Americans with NAFLD.Graphical

Incidence of Etiology-specific Hepatocellular Carcinoma: Diverging Trends and Significant Heterogeneity by Race and Ethnicity

The main causes of hepatocellular carcinoma (HCC) include chronic hepatitis C and B viral infections (HCV, HBV), nonalcoholic fatty liver disease (NAFLD), and alcohol-related disease (ALD). Etiology-specific HCC incidence rates and temporal trends on a population-basis are needed to improve HCC control and prevention. All 14,420 HCC cases from the Florida statewide cancer registry were individually linked to data from the hospital discharge agency and the viral hepatitis department to determine the predominant etiology of each case diagnosed during 2010 to 2018. Age-adjusted incidence rates (AAIRs) were used to assess the intersection between etiology and detailed race-ethnicity. Etiology-specific temporal trends based on diagnosis year were assessed using Joinpoint regression. HCV remains the leading cause of HCC among men, but since 2017 NAFLD-HCC is the leading cause among women. HCV-HCC AAIRs are particularly high among U.S.-born minority men, including Puerto Rican (10.9 per 100,000), African American (8.0 per 100,000), and U.S.-born Mexican American men (7.6 per 100,000). NAFLD is more common among all Hispanics and Filipinos and HBV-HCC among Asian and Haitian black men. HCV-HCC surpasses HBV-HCC in Asian women. ALD-HCC is high among specific Hispanic male groups. Population-based HCV-HCC rates experienced a rapid decline since 2015 (-9.6% annually), whereas ALD-HCC (+6.0%) and NAFLD-HCC (+4.3%) are rising (P < .05). New direct acting anti-viral drugs have impacted rates of HCV-HCC, offsetting important increases in both ALD- and NAFLD-HCC. Hispanics may be a group of concern because of higher rates for ALD- and NAFLD-HCC. HCC etiology varies remarkably and may warrant specific interventions by detailed race-ethnicity.

Circular SERPINA3 and its target microRNA-944 as potential biomarkers in hepatitis C virus-induced hepatocellular carcinoma in Egyptian population.

The most prevalent cancer in Egypt is hepatocellular carcinoma (HCC) mainly due to the infection with the hepatitis C virus. So it is critical to find sensitive biomarkers for early diagnosis of HCC and avoid post-operation tumor recurrence. Therefore, this research was designed to demonstrate the circSERPINA3 role in the regulation of microRNA-944 gene expression in HCV-related HCC cases and compare these results with circSERPINA3 and microRNA-944 gene expression levels in HCV-infected patients. Study participants were divided into three groups: healthy controls, HCV- infected, and HCV-induced HCC patients. The gene expression levels of circSERPINA3 and microRNA-944 were evaluated using Real-Time qPCR. Then the immunoblotting procedure was applied to measure the serum levels of MDM2 and E-cadherin besides, the serum concentration levels of glypican-3 and alpha-fetoprotein were measured by sandwich ELISA. The gene expression level of circSERPINA3 was significantly upregulated in both HCV-infected and HCC patients causing suppression of the antitumor effect of miR-944 and showing a lower 1-year survival rate than the participants who had low circSERPINA3 gene expression levels. Subsequently, the miR-944 downstream protein, MDM2 was remarkably upregulated, exaggerating the metastasis and oxidative stress in HCC cases. Additionally, the results confirmed the downregulation of microRNA-944 improved the progression of viral hepatitis C cases to hepatocarcinogenesis through the significantly increased serum level of the metastatic marker, E-cadherin. Although alpha-fetoprotein is a common diagnostic marker used in the diagnosis of HCC, our results showed that glypican-3 had greater sensitivity and specificity and positively correlated to the IGF-1 signaling pathway of HCC cases. Moreover, the gene expression levels of circSERPINA3 and E-cadherin in both the HCV and HCV-induced HCC were significantly positively correlated. circSERPINA3 and miR-944 were sensitive molecular markers for early diagnosis of HCC and could be prospective treatment targets for HCV-infected patients to avoid tumor recurrence in HCC cases.

Interpretation of Farnesoid X Receptor Immunohistochemical Expression in Discriminating Hepatocellular Carcinoma from Its Non-Neoplastic Mimics as an Adjunct to Glypican 3.

Differentiating hepatocellular carcinoma (HCC) and non-neoplastic lesions may be challenging. Immunohistochemistry (IHC) can help in the comparative morphologic evaluation of HCC and its mimics. Farnesoid X receptor (FXR) is a nuclear metabolic receptor essential for bile salts homeostasis and other biological functions of liver cells. Preliminary studies have shown that FXR can be useful for diagnosing HCC. This study aimed to assess the role of Farnesoid X receptor (FXR) combined with Glypican 3 (GPC3) in differentiation between HCC and non-neoplastic hepatic lesions. Immunohistochemistry of GPC3 and FXR was performed in 38 cases of primary hepatic lesions using an automated immunohistochemical stainer. The study included 17 primary HCC cases and 21 non-neoplastic hepatic lesions (5 cases were focal nodular hyperplasia, 7 were regenerative nodules and 9 were dysplastic nodules). The percentage of positive GPC3 and low or negative FXR expression was significantly higher in HCC cases than non-neoplastic hepatic lesions (P value <0.001). The sensitivity and specificity of GPC3 in differentiating HCC from non-neoplastic hepatic lesions were 70.6% and 85.7%, respectively, while the sensitivity and specificity of FXR were 58.8% and 100%, respectively. The present work revealed that FXR could be combined with GPC3 in distinguishing between HCC and non-neoplastic hepatic lesions with improved specificity rather than using an individual marker.

The application of 18F-FDG PET/CT imaging for human hepatocellular carcinoma: a narrative review.

Primary hepatocellular carcinoma (HCC) poses a significant threat to human health. The mean overall survival (OS) of HCC is approximately 15.8 months whereas the 6-month and 1-year OS rates are only 71.6% and 49.7%, respectively. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has been widely used for the management of several solid cancers; however, HCC frequently displays low 18F-FDG uptake; approximately 50% of HCC cases do not take up 18F-FDG. Therefore, 18F-FDG PET is not considered very useful for the visualization of HCC and is not currently a recommended standard imaging modality for HCC. Conversely, 18F-FDG PET/CT has been reported to be clinically important in the management, staging, and prognosis of HCC patients. Currently, reports relating to 18F-FDG uptake in HCC are unclear and controversial. There is an urgent need to clarify the efficacy of 18F-FDG PET for the management of HCC. The PubMed database was searched for all articles on the application of 18F-FDG PET/CT imaging for human HCC up to December 2021. The following search terms were used: 'Hepatocellular carcinoma', '[18F]FDG PET/CT', 'Hypoxia', '[11C]Choline'. In this review, we re-evaluate the potential hypoxia-dependent uptake mechanism of 18F-FDG in HCC and review the usefulness of 18F-FDG PET/CT for identifying, managing, and investigating the biological properties of HCC. 18F-FDG PET/CT is very useful for HCC visualization, management, and the evaluation of biological properties. A negative test for 18F-FDG uptake is not meaningless and may reflect a relatively better outcome. 18F-FDG-positive lesions indicate a significantly less favorable prognosis.

Fibrolamellar Hepatocellular Carcinoma in Young Adult: A Case Report and Literature Review

Fibrolamellar carcinoma (FLC), a truly unique and uncommon variation of hepatocellular carcinoma (HCC), accounting for barely 1%–9% of all HCC cases. Fibrolamellar carcinoma, an unclear malignancy, appears to be more commonly observed in youthful individuals without any preexisting liver conditions. The nomenclature "fibrolamellar" originates from the presence of dense fibrous collagen bands enveloping the neoplastic cells. Contrary to hepatocellular carcinoma (HCC), cirrhosis and viral hepatitis infection do not serve as predisposing factors for fibrolamellar carcinoma (FLC). Additionally, FLC is not typically associated with increased levels of serum alpha-fetoprotein. Patients with FLC frequently manifest with nonspecific abdominal discomfort, queasiness, general discomfort, and decreased in body mass. Surgical intervention, specifically resection or liver transplantation, serves as the cornerstone of treatment and represents the sole potentially curative avenue. FLCs, or fibrolamellar carcinomas, have historically exhibited lower responsiveness to chemotherapy compared to conventional hepatocellular carcinomas (HCC). Nevertheless, it is important to note that in cases of advanced FLCs, the utilization of multi-modality treatments has shown promising effectiveness. The purpose of this review is to explain the clinical characteristics, diagnostic techniques, and therapeutic approaches for this uncommon tumor in order to enhance the knowledge of healthcare professionals.