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Background: Racial and ethnic disparities in diagnosis and overall outcomes for HCC are well known. We present updated real-world data on racial or ethnic differences in LT and post-LT survival among patients with HCC in a large population-based database., Methods: We used the TriNetX database to retrospectively identify patients who had HCC (ICD-10 C22.0, C22.8) and underwent LT (CPT codes 47,135, 47,140, 47,140, 47,141, 47,142) from 2012 to 2022 and compared outcomes across racial and ethnic subgroups., Results: Majority of the patients were Caucasians (2403/2901, 84.8%), followed by African Americans (267/2901, 9.2%) Hispanic/Asian (231/2901, 7.9%). At follow up of 5 years, we noted no significant difference in mortality between AA and Caucasian patients [HR = 1.087 (95% CI 0.76, 1.56, p = 0.59)] as well as Hispanic/Asian and Caucasian patients [HR = 1.14 (95% CI 0.73, 1.78, p = 0.10)]., Conclusions: These results indicate that stringent implementation of policies aimed at ensuring equitable access to LT may contribute to bridging disparities in overall outcomes in HCC., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy about 50% of PDAC are metastatic at presentation. In this study, we evaluated PDAC demographics, annual trend analysis, racial disparities, survival rate, and the role of different treatment modalities in localized and metastatic disease., Methods: A total of 144,824 cases of PDAC were obtained from the SEER database from 2000 to 2018., Results: The median age was 69 years, with a slightly higher incidence in males (52%) and 80% of all cases were white. Among cases with available data, 43% were grade III tumors and 57% were metastatic. The most common site of metastasis was the liver (15.7%). The annual incidence has increased steadily from 2000 to 2018. The overall observed (OS) 5-year survival rate was 4.4% (95% CI 4.3-4.6%), and 5 years cause-specific survival (CSS) was 5% (95% CI 5.1-5.4%). The 5-year survival with multimodal therapy (chemotherapy, surgery, and radiation) was 22% (95% CI 20.5-22.8%). 5-year CSS for the blacks was lower at 4.7% (95% CI 4.2-5.1%) compared to the whites at 5.3% (95% CI 5.1-5.4%). Multivariate analysis found male gender and black race associated with worse prognosis. Kaplan-Meier survival analysis found multimodal therapy to have the best outcomes in all three stages., Conclusion: PDAC is an aggressive malignancy with male gender and black race are associated with a poor prognosis. Surgery with chemoradiation was associated with the best overall survival. With steadily increasing rates of PDAC, improved treatment modalities are paramount to improving survival in these patients., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Background: Liver-directed treatments - ablative therapy (AT), surgical resection (SR), liver transplantation (LT), and transarterial chemoembolization (TACE) - improve the overall survival of patients with early-stage hepatocellular carcinoma (HCC). Although racial and socioeconomic disparities affect access to liver-directed therapies, the temporal trends for the curative-intent treatment of HCC remain to be elucidated., Methods: This study performed chi-square, logistic regression, and temporal trends analyses on data from the Nationwide Inpatient Sample from 2011 to 2019. The outcome of interest was the rate of AT, SR, LT (curative-intent treatments), and TACE utilization, and the primary predictors were racial/ethnic group and socioeconomic status (SES; insurance status)., Results: African American and Hispanic patients had lower odds of receiving AT (African American: odds ratio [OR], 0.78; P < .001; Hispanic: OR, 0.84; P = .005) and SR (African American: OR, 0.71; P < .001; Hispanics: OR, 0.64; P < .001) than White patients. Compared with White patients, the odds of LT was lower in African American patients (OR, 0.76; P < .001) but higher in Hispanic patients (OR, 1.25; P = .001). Low SES was associated with worse odds of AT (OR, 0.79; P = .001), SR (OR, 0.66; P < .001), and LT (OR, 0.84; P = .028) compared with high SES. Although curative-intent treatments showed significant upward temporal trends among White patients (10.6%-13.9%; P < .001) and Asian and Pacific Islander/other patients (14.4%-15.7%; P = .007), there were nonsignificant trends among African American patients (10.9%-10.1%; P = .825) or Hispanic patients (12.2%-13.7%; P = .056)., Conclusion: Our study demonstrated concerning disparities in the utilization of curative-intent treatment for HCC based on race/ethnicity and SES. Moreover, racial/ethnic disparities have widened rather than improved over time., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Background: Orthotopic liver transplantation is the recommended treatment option for patients with early-stage hepatocellular carcinoma and concomitant cirrhosis. Waitlist candidacy can be affected by social determinants of health that vary across races and ethnicities. Our study sought to evaluate whether racial/ethnic disparities exist in access to orthotopic liver transplantation in patients with hepatocellular carcinoma., Methods: The National Cancer Database participant use file was used to analyze data between 2004 and 2020. Patients 18-70 years of age with TNM clinical stage I and II hepatocellular carcinoma who received either orthotopic liver transplantation or liver directed/nonsurgical therapies were included. Baseline demographic variables and treatment modalities were collected. Patients were assigned fixed categories on the basis of race and ethnicity. Descriptive statistics, multivariable logistical regressions, effects modification analysis, and propensity matching were used., Results: There were 23,313 non-Hispanic White, 5,215 non-Hispanic Black, 5,581 Hispanic, and 2,768 other patients included in this analysis. Significant socioeconomic variation was observed across races. Non-Hispanic White patients were more likely to undergo orthotopic liver transplantation than non-Hispanic Black patients. The proportion of patients insured by Medicare was the same between non-Hispanic White and non-Hispanic Black patients. There was a graeter proportion of non-Hispanic Black patients with Medicaid compared with non-Hispanic White patients, whereas a lower proportion of non-Hispanic Black patients were insured via private insurance compared with non-Hispanic White patients. Effect modification analysis showed the non-Hispanic Black patients were less likely to undergo orthotopic liver transplantation for those with private and Medicare coverage compared with non-Hispanic White patients. Propensity matching showed a significantly decreased rate of orthotopic liver transplantation in non-Hispanic Black patients compared with non-Hispanic White patients., Conclusion: Non-Hispanic Black patients were less likely to undergo orthotopic liver transplantation for early-stage hepatocellular carcinoma, despite adjusting for cancer stage and socioeconomic factors, compared with non-Hispanic White patients. Social determinants of health were associated with the probability of undergoing orthotopic liver transplantation. Understanding disparities related to social determinants of health will help guide health policy changes and improved access to care., Competing Interests: Conflicts of Interest/Disclosure The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pediatric Hepatoblastoma is a rare malignancy of the liver. This study used the National Cancer Database (NCDB) to identify 1068 patients diagnosed with hepatoblastoma from 2004 to 2020. χ 2 and Analysis of Variance testing, as well as Kaplan-Meier, Cox Regression, and multinomial logistic regression models were used. Data was analyzed using SPSS version 27, and statistical significance was set at α=0.05. Our results found Black patients experienced a significantly lower median survival rate compared with White patients, a difference which persisted after controlling for covariates. Black patients were also less likely to receive surgery and chemotherapy and more likely to be from low-income households than White patients. White patients had a significantly shorter inpatient hospital stay compared to Black patients and were more likely to receive treatment at more than 1 CoC accredited facility. There was no significant difference in grade, size of tumor, metastasis, or time of diagnosis to surgery. This study showed Black patients experienced inferior overall survival when diagnosed and treated for hepatoblastoma compared to White patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is a highly lethal cancer with few treatment options available to patients. Most HCC cases in Arizona, a state with a high proportion of Hispanic adults, have not been included in recent reports of HCC incidence. This study describes trends in HCC incidence and stage at diagnosis among Arizona residents between 2009-2017 and reports on racial and ethnic disparities for these outcomes., Methods: The Arizona Cancer Registry was used to identify Arizonans aged 19 or older diagnosed with liver cell carcinoma diagnosed between 2009-2017. A total of 5043 cases were examined. Adjusted annual and 3-year HCC incidence rates (per 100,000) were examined for non-Hispanic White (NHW) and Hispanic adults., Results: The total age-adjusted HCC incidence rate increased significantly between 2009-2012 and then declined significantly between 2012-2017. Across nearly all years, age-adjusted HCC incidence in Hispanic adults was twice that of NHW adults. Hispanic adults were more likely to be diagnosed at a later stage across all time periods. The disparity in 3-year age-adjusted HCC incidence rate between NHW and Hispanic adults decreased between 2009-2017., Conclusion: Whe total age-adjusted HCC incidence rate increased significantly between 2009-2012 and then declined significantly between 2012-2017. Across nearly all years, age-adjusted HCC incidence in Hispanic adults was twice that of NHW adults. Hispanic adults were more likely to be diagnosed at a later stage across all time periods. The disparity in 3-year age-adjusted HCC incidence rate between NHW and Hispanic adults decreased between 2009-2017., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Asian, Pacific Islander, African, and Caribbean communities in the U.S. are heavily impacted by chronic hepatitis B (HBV) and hepatocellular carcinoma (HCC). Educating these groups about the link between the two diseases is imperative to improve screening rates and health outcomes. This study aims to identify and incorporate preferred mediated communication methods into community-specific educational campaigns which emphasize the connection between the conditions, to promote uptake of prevention and management behaviors for HBV and HCC. Fifteen focus groups and two key informant interviews were conducted with Micronesian, Chinese, Hmong, Nigerian, Ghanaian, Vietnamese, Korean, Somali, Ethiopian, Filipino, Haitian, and Francophone West African communities. Data were analyzed using thematic coding and analysis. Findings demonstrate that all communities preferred materials be offered in both English and native languages and requested that materials highlight the connection between HBV and HCC. Delivery channel preferences and messaging themes varied by group. This study provides insight into community-specific preferences for learning about HBV and HCC. The findings can be used to design culturally and linguistically tailored, multi-platform, health education campaigns to facilitate improved HBV screening and vaccination rates and increase knowledge about HCC risk among highly impacted communities in the U.S.

Background: Understanding how specific populations are affected by liver cancer is important for identifying priorities, policies, and interventions to mitigate health risks and reduce disparities. This study aims to provide comprehensive analysis of rates and trends in liver cancer mortality for different racial and ethnic populations in the USA nationally and at the county level from 2000 to 2019., Methods: We applied small-area estimation methods to death registration data from the US National Vital Statistics System and population data from the US National Center for Health Statistics to estimate liver cancer mortality rates by county, racial and ethnic population, and year (2000-19) in the USA. Race and ethnicity were categorised as non-Latino and non-Hispanic American Indian or Alaska Native (AIAN), non-Latino and non-Hispanic Asian or Pacific Islander (Asian), non-Latino and non-Hispanic Black (Black), Latino or Hispanic (Latino), and non-Latino and non-Hispanic White (White). Estimates were adjusted using published misclassification ratios to correct for inaccuracies in race or ethnicity as recorded on death certificates, and then age-standardised. Mortality rate estimates are presented for all county and racial and ethnic population combinations with a mean annual population greater than 1000., Findings: Nationally, the age-standardised liver cancer mortality rate increased between the years 2000 (4·2 deaths per 100 000 population [95% uncertainty interval 4·1-4·3]) and 2016 (6·0 per 100 000 [5·9-6·1]), followed by a stabilisation in rates from 2016 to 2019 (6·1 per 100 000 [6·0-6·2]). Similar trends were observed across the AIAN, Black, Latino, and White populations, whereas the Asian population showed an overall decrease across the 20-year study period. Qualitatively similar trends were observed in most counties; however, the mortality rate and the rate of change varied substantially across counties, both within and across racial and ethnic populations. For the 2016-19 period, mortality continued to increase at a substantial rate in some counties even while it stabilised nationally. Nationally, the White population had the lowest mortality rate in all years, while the racial and ethnic population with the highest rate changed from the Asian population in 2000 to the AIAN population in 2019. Racial and ethnic disparities were substantial: in 2019, mortality was highest in the AIAN population (10·5 deaths per 100 000 [9·1-12·0]), notably lower for the Asian (7·5 per 100 000 [7·1-7·9]), Black (7·6 per 100 000 [7·3-7·8]), and Latino (7·7 per 100 000 [7·5-8·0]) populations, and lowest for the White population (5·5 [5·4-5·6]). These racial and ethnic disparities in mortality were prevalent throughout the country: in 2019, mortality was higher in minoritised racial and ethnic populations than in the White population living in the same county in 408 (87·7%) of 465 counties with unmasked estimates for the AIAN population, 604 (90·6%) of 667 counties for the Asian population, 1207 (81·2%) of 1486 counties for the Black population, and 1073 (73·0%) of 1469 counties for the Latino population., Interpretation: Although the plateau in liver cancer mortality rates in recent years is encouraging, mortality remains too high in many locations throughout the USA, particularly for minoritised racial and ethnic populations. Addressing population-specific risk factors and differences in access to quality health care is essential for decreasing the burden and disparities in liver cancer mortality across racial and ethnic populations and locations., Funding: US National Institutes of Health (Intramural Research Program, National Institute on Minority Health and Health Disparities; National Heart, Lung, and Blood Institute; Intramural Research Program, National Cancer Institute; National Institute on Aging; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Office of Disease Prevention; and Office of Behavioral and Social Sciences Research)., Competing Interests: Declaration of interests L M Force reports funding (grants or contracts) from the Bill & Melinda Gates Foundation, Conquer Cancer Foundation, St Jude Children's Research Hospital, St Baldrick's Foundation, and the National Institutes of Health Loan Repayment Program., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Importance: Accurate representation of racial and ethnic population subgroups in clinical trials is fundamental to ensure universal effectiveness of new therapies as well as to decrease disparities in oncology care., Objective: To determine whether Hispanic people are underrepresented in Phase I and II clinical trials for liver cancer in the United States., Participants: A database search was performed in clinicaltrials.gov for interventional liver cancer studies based only in the US with reported results from September 1, 2002, to February 1, 2023. A total of 37 trials with 963 total patients met inclusion criteria and were included for further analysis. Proportion of total patients by race/ethnicity was calculated for non-Hispanic white, non-Hispanic black, Asian, Hispanic, and American Indian/Alaska Native subpopulations. The age-adjusted incidence rates of liver and intrahepatic bile duct were acquired from the National Cancer Institute, Surveillance, Epidemiology, and End Results Program., Results: Liver cancer incidence rates (per 100,000 people) were highest in Indians/Alaska Native people (18.8 cases) followed by Hispanic people (15.1 cases), then Asian people (12.5 cases), then non-Hispanic black people (11 cases), and non-Hispanic white people (7.5 cases). From a total of 91 phase I or II clinical trials for liver cancer in the US, 41% reported race/ethnicity enrollment data; among these, 62.8% of patients were non-Hispanic White, 15.9% were non-Hispanic black, 8.8% were Hispanic, 12.7% Asian, and 0.5% American Indian/Alaska Native., Conclusions and Relevance: Less than half of phase I or II clinical trials for liver cancer in the US in the last 20 years reported race/ethnicity data to clinicaltrials.gov. Compared to the relative incidence rate of liver cancer, non-Hispanic black people and Hispanic people are underrepresented in these clinical trials., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA. Cancer Medicine published by John Wiley & Sons Ltd.)

Hepatocellular carcinoma (HCC) is highly prevalent in Asians and Pacific Islanders (API) but this heterogenous group is often aggregated into a single category, despite vast differences in culture, socioeconomic status, education, and access to care among subgroups. There remains a significant knowledge gap in HCC outcomes among different subgroups of API. The Surveillance, Epidemiology, and End Results (SEER) database was accessed, and site/ICD codes were used to identify HCC patients during 2010-2019 who were API ethnicity. Data collected: demographics, socioeconomic status, tumor characteristics, treatment, and survival. Subgroup analyses were performed among different Asian ethnicities in a secondary analysis. 8,249 patients were identified/subdivided into subgroups of Asian ethnicities and Other Pacific Islanders (NHOPI) groups. The median age was 65 years for Asians and 62 years for NHOPI (p < 0.01), and significant differences were found in income (p < 0.01). A higher proportion of NHOPI lived in rural areas compared to Asians (8.1 vs. 1.1%, p < 0.01). There were no statistically significant differences in tumor size, stage, pre-treatment AFP level, or surgical treatments between the two groups. However, Asians had higher overall median survival than NHOPI (20 months v 12 months, p < 0.01). Secondary analyses among different subgroups of Asian ethnicities revealed significant differences in tumor size and staging, surgical resection, transplant rates, and median survival. While API had similar tumor characteristics and treatment, Asians had much higher survival than NHOPI. Socioeconomic differences and access to care may contribute to these differences. This study also found significant survival disparities within API ethnicities., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Among patients with cirrhosis, it remains unclear whether there are racial/ethnic differences in cirrhosis complications and mortality. We examined the associations between race/ethnicity and risk for hepatocellular carcinoma (HCC), cirrhosis decompensation, and all-cause mortality overall and by cirrhosis etiology., Methods: US Veterans diagnosed with cirrhosis from 2001 to 2014 (n = 120,992), due to hepatitis C virus (HCV; n = 55,814), alcohol-associated liver disease (ALD; n = 36,323), hepatitis B virus (HBV; n = 1,972), nonalcoholic fatty liver disease (NAFLD; n = 17,789), or other (n = 9,094), were followed through 2020 for incident HCC (n = 10,242), cirrhosis decompensation (n = 27,887), and mortality (n = 81,441). Multivariable Cox proportional hazards regression was used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI)., Results: Compared with non-Hispanic White patients, Hispanic patients had higher risk for HCC overall (aHR, 1.32; 95% CI, 1.24-1.41) and by cirrhosis etiology, particularly for ALD- (aHR, 1.63; 95% CI, 1.42-1.87) and NAFLD-cirrhosis (aHR, 1.76; 95% CI, 1.41-2.20), whereas non-Hispanic Black patients had lower HCC risk in ALD- (aHR, 0.79; 95% CI, 0.63-0.98) and NAFLD-cirrhosis (aHR, 0.54; 95% CI, 0.33-0.89). Asian patients had higher HCC risk (aHR, 1.70; 95% CI, 1.29-2.23), driven by HCV- and HBV-cirrhosis. Non-Hispanic Black patients had lower risk for cirrhosis decompensation overall (aHR, 0.71; 95% CI, 0.68-0.74) and by cirrhosis etiology. There was lower risk for mortality among all other racial/ethnic groups compared with non-Hispanic White patients., Conclusions: Race/ethnicity is an important predictor for risk of developing HCC, decompensation, and mortality., Impact: Future research should examine factors underlying these racial/ethnic differences to inform prevention, screening, and treatment for patients with cirrhosis., (©2023 The Authors; Published by the American Association for Cancer Research.)

Introduction: Immigrants comprise a considerable proportion of those diagnosed with hepatocellular carcinoma (HCC) in the United States. Nativity or birthplace affects incidence and risk factors for HCC, but little is known about its influence on survival after diagnosis., Methods: We identified 51 533 adults with HCC with available birthplace in the California Cancer Registry between 1988 and 2017. HCC cases were categorized as foreign born or US born and stratified by mutually exclusive race and ethnicity groups. Primary outcome was all-cause mortality. Race and ethnicity-specific Cox regression propensity score-weighted models evaluated the relationship between nativity and death as well as region of birth among foreign-born patients., Results: A total of 40% of all HCC cases were foreign born, and 92.2%, 45.2%, 9.1%, and 5.8% of Asian/Pacific Islander (API), Hispanic, White, and Black patients were foreign born, respectively. Five-year survival rates were higher in foreign-born patients compared with US-born patients: 12.9% vs 9.6% for White patients, 11.7% vs 9.8% for Hispanic patients, 12.8% vs 8.1% for Black patients, and 16.4% vs 12.4% for API patients. Nativity was associated with survival, with better survival in foreign-born patients: White patients: hazard ratio (HR) = 0.86 (95% confidence interval [CI] = 0.81 to 0.90), Hispanic patients: HR = 0.90 (95% CI = 0.86 to 0.93), Black patients: HR = 0.89 (95% CI = 0.76 to 1.05), and API patients: HR = 0.94 (95% CI = 0.88 to 1.00). Among foreign-born patients, lower mortality was observed in those from Central and South America compared with Mexico for Hispanic patients, East Asia compared with Southeast Asia for API patients, and East Europe and Greater Middle East compared with West/South/North Europe for White patients., Conclusion: Foreign-born patients with HCC have better survival than US-born patients. Further investigation into the mechanisms of this survival disparity by nativity is needed., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Both inflammatory bowel disease (IBD) and hepato-pancreato-biliary cancers (HPBC) have been established to cause a huge socioeconomic burden. Epidemiological studies have revealed a close association between IBD and HPBC., Methods: Herein, we utilized inverse-variance weighting to conduct a two-sample Mendelian randomization analysis. We sought to investigate the link between various subtypes of IBD and HPBC. To ensure the accuracy and consistency of our findings, we conducted heterogeneity tests, gene pleiotropy tests, and sensitivity analyses., Results: Compared to the general population, IBD patients in Europe exhibited a 1.22-fold increased incidence of pancreatic cancer (PC) with a 95% confidence interval (CI) of 1.0022-1.4888 (p = 0.0475). We also found a 1.14-fold increased incidence of PC in Crohn's disease (CD) patients with (95% CI: 1.0017-1.3073, p = 0.0472). In the East Asian population, the incidence of hepatocellular carcinoma (HCC) was 1.28-fold higher (95% CI = 1.0709-1.5244, p = 0.0065) in IBD patients than in the general population. Additionally, ulcerative colitis (UC) patients displayed 1.12-fold (95% CI: 1.1466-1.3334, p < 0.0001) and 1.31-fold (95% CI: 1.0983-1.5641, p = 0.0027) increased incidences of HCC and cholangiocarcinoma (CCA), respectively. Finally, the incidence of PC was 1.19-fold higher in CD patients than in the general population (95% CI = 1.0741-1.3132, p = 0.0008)., Conclusion: Our study validated that IBD is a risk factor for HPBC. This causal relationship exhibited significant heterogeneity in different European and East Asian populations., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background and Aims: HCC is characterized by racial/ethnic disparities in rates. Recent USA reports suggest that incidence has begun to decline, but it is not clear whether the declines have occurred among all groups, nor whether mortality has declined. Thus, the current study examined USA incidence and mortality between 1992 and 2018., Approach & Results: HCC incidence and incidence-based mortality data from the Surveillance, Epidemiology, and End Results program were used to calculate age-standardized rates by race/ethnicity, sex, and age. Trends were analyzed using joinpoint regression to estimate annual percent change (APC). Age-period-cohort models assessed the effects on trends of age, calendar period, and birth cohort. Overall, HCC incidence significantly declined between 2015 and 2018 (APC, -5.6%). Whereas most groups experienced incidence declines, the trends were most evident among Asians/Pacific Islanders, women, and persons <50 years old. Exceptions were the rates among non-Hispanic Black persons, which did not significantly decline (APC, -0.7), and among American Indians/Alaska Natives, which significantly increased (APC, +4.3%). Age-period-cohort modeling found that birth cohort had a greater effect on rates than calendar period. Among the baby boom cohorts, the 1950-1954 cohort had the highest rates. Similar to the overall incidence decline, HCC mortality rates declined between 2013 and 2018 (APC, -2.2%)., Conclusions: HCC incidence and mortality rates began to decline for most groups in 2015, but persistent differences in rates continued to exist. Rates among non-Hispanic Black persons did not decline significantly, and rates among American Indians/Alaska Natives significantly increased, suggesting that greater effort is needed to reduce the HCC burden among these vulnerable groups., (© 2022 American Association for the Study of Liver Diseases. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Recent data suggest that non-alcoholic fatty liver disease (NAFLD) has become a major public health problem in Asia, with an updated population prevalence of 34%. In parallel, NAFLD-associated hepatocellular carcinoma (HCC) is also on the rise. In this review, we describe the changing epidemiology of HCC in Asia over the past 30 years. While traditional risk factors for HCC (older age, male sex and metabolic factors) are also important in Asia, the PNPLA3 gene polymorphism is particularly prevalent in East Asia and may increase the risk of HCC. NAFLD among non-obese individuals is also commonly described in Asia. Because NAFLD is often undiagnosed, few patients receive HCC surveillance, and the target surveillance population beyond patients with cirrhosis remains poorly defined. As a result, NAFLD-associated HCC is often diagnosed at an advanced stage, rendering curative treatment impossible. Finally, despite around 20-30 years of universal vaccination, chronic HBV infection remains prevalent in Asia, and emerging evidence highlights the importance of metabolic factors and concomitant hepatic steatosis on HCC development in infected patients. Future studies should explore the role of metabolic treatments in HCC prevention among patients with hepatic steatosis and concomitant liver diseases., Competing Interests: Conflicts of interests Grace Wong has served as an advisory committee member for Gilead Sciences and Janssen, and as a speaker for Abbott, Abbvie, Bristol-Myers Squibb, Echosens, Gilead Sciences, Janssen and Roche. Vincent Wong has served as a consultant or advisory board member for 3V-BIO, AbbVie, Allergan, Boehringer Ingelheim, Echosens, Gilead Sciences, Inventiva, Merck, Novartis, Novo Nordisk, Pfizer, ProSciento, Sagimet Biosciences, TARGET PharmaSolutions, and Terns; and a speaker for Abbott, AbbVie, Echosens, Gilead Sciences, and Novo Nordisk. He has received a grant from Gilead Sciences for fatty liver research. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Apoptosis, also called programmed cell death, is a genetically controlled process against hyperproliferation and malignancy. The Fas-Fas ligand (FasL) system is considered a major pathway for apoptosis in cells and tissues. Thus, this study aimed to investigate whether single nucleotide polymorphisms (SNPs) in Fas and FasL gene may have effects on the recurrence and survival of patients with hepatocellular carcinoma (HCC) after curative hepatectomy., Methods: We investigated the relationship between Fas rs1800682, rs2234767 and FasL rs763110 polymorphisms and recurrence-free survival (RFS) as well as overall survival (OS) in 117 Chinese Han patients with HCC who underwent hepatectomy., Results: In Kaplan-Meier survival analysis, only Fas rs1800682 (-670 A/G) was associated with RFS and OS. Compared with AA genotype, the AG/GG genotype was significantly associated with better RFS (P = 0.008) and OS (P = 0.020). Moreover, multivariate Cox regression analysis showed that Fas rs1800682 remained as a significant independent predictor of RFS for HCC patients with hepatectomy [AG/GG vs. AA: adjusted hazard ratio = 0.464, 95% confidence interval: 0.275-0.782, P = 0.004], but was not an independent predictor of OS (P = 0.395)., Conclusions: This study demonstrated that Fas -670 G allele may play a protective role in the recurrence and survival of HCC patients with hepatectomy. Furthermore, Fas rs1800682 polymorphism might be a promising biomarker for HCC patients after hepatectomy., (Copyright © 2021. Published by Elsevier B.V.)

Prognosis of hepatocellular carcinoma (HCC) could be affected by lack of or delayed therapy. We aimed to characterize the prevalence, correlates, and clinical impact of therapeutic underuse and delay in patients with HCC. Patients with HCC diagnosed between 2010 and 2017 were analyzed from the United States National Cancer Database. Logistic regression analysis identified factors associated with no and delayed (>90 days after diagnosis) HCC treatment. Cox proportional hazards regression with landmark analysis assessed the association between therapeutic delay and overall survival (OS), accounting for immortal time bias. Of 116,299 patients with HCC, 24.2% received no treatment and 18.4% of treated patients had delayed treatment. Older age, Black, Hispanic, lower socioeconomic status, earlier year of diagnosis, treatment at nonacademic centers, Northeast region, increased medical comorbidity, worse liver dysfunction, and higher tumor burden were associated with no treatment. Among treated patients, younger age, Hispanic, Black, treatment at academic centers, West region, earlier tumor stage, and receipt of noncurative treatment were associated with treatment delays. In multivariable Cox regression with a landmark of 150 days, patients with and without treatment delays had similar OS (adjusted hazard ratio [aHR], 1.01; 95% confidence interval [CI], 0.98-1.04) with a median survival of 33.7 vs. 32.1 months, respectively. However, therapeutic delay was associated with worse OS in patients who had tumor, nodes, and metastases (TNM) stage 1 (aHR, 1.06; 95% CI, 1.01-1.11) or received curative treatment (aHR, 1.12; 95% CI, 1.05-1.18). Conclusion: One-fourth of patients with HCC receive no therapy and one-fifth of treated patients experience treatment delays. Both were associated with demographic, socioeconomic, and clinical characteristics of patients as well as facility type and region. The association between therapeutic delay and survival was stage and treatment dependent., (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

The etiology of hepatoblastoma is largely unknown due to the rarity of this disease. Nucleotide excision repair (NER), a versatile system in repairing DNA damage, is highly implicated in carcinogenesis. However, it remains unclear whether single nucleotide polymorphisms (SNPs) of genes in the NER pathway are related to hepatoblastoma risk. A total of 313 Chinese children diagnosed with hepatoblastoma and 1446 controls were recruited from seven hospitals across China. TaqMan assay was adopted to genotype 19 SNPs in NER pathway genes including ERCC1, XPA, XPC, XPD, XPF and XPG. Of them, only two SNPs in XPC gene predisposed to hepatoblastoma risk. The XPC rs2607775 polymorphism significantly contributed to hepatoblastoma risk (dominant model: adjusted OR = 1.44, 95% CI = 1.01-2.05, P = .046). However, XPC rs1870134 conferred a significantly decreased risk of hepatoblastoma in recessive model (adjusted OR = 0.50, 95% CI = 0.26-0.98, P = .042). Stratified analysis revealed that rs2607775 CG/GG genotype, rs1870134 CC genotype and four to five risk genotypes were associated with the risk of hepatoblastoma under certain subgroups. The significant relationships were confirmed by haplotype analyses and false-positive report probability analyses. In addition, expression quantitative trait locus analysis suggested that rs2607775 G increased expression of XPC mRNA. Collectively, our discover a promising candidate XPC gene as a biomarker for the risk of hepatoblastoma., (© 2021 UICC.)

Background and Aims: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, with a disproportionate impact on racial/ethnic minority groups. However, state-level variation in racial/ethnic disparities and temporal trends of HCC incidence remain unknown. Therefore, we aimed to characterize (1) state-level racial/ethnic disparity in HCC incidence, (2) state-level temporal changes in HCC incidence, and (3) the ecological correlation between HCC incidence and obesity/physical activity levels in the USA., Approach and Results: Trends in HCC incidence between 2001 and 2017 were calculated using data from the Centers for Disease Control and Prevention's National Program of Cancer Registries and the National Cancer Institute's Surveillance, Epidemiology and End Results, and annual percent change in rates were calculated. State-level percent of obesity and level of physical activity were obtained from the Centers for Disease Control and Prevention, and the correlation among obesity, physical activity, and state-specific average annual percent change was tested by Pearson correlation coefficient. There were striking state-level racial/ethnic disparities in HCC incidence; incidence rate ratios ranged between 6.3 and 0.9 in Blacks, 6.1 and 1.7 in Asians/Pacific Islanders, 3.8 and 0.9 in Hispanics, and 6.0 and 0.9 in American Indians/Alaska Natives (compared with Whites as reference). Despite overall decreasing HCC incidence rates after 2015, HCC incidence continued increasing in 26 states over recent years. HCC incidence trends had a moderate correlation with state-level obesity (r = 0.45, P < 0.001) and a moderate inverse correlation with state-level physical activity (r = -0.40, P = 0.004)., Conclusions: There is wide state-level variation in racial/ethnic disparity of HCC incidence. There are also disparate incidence trends across states, with HCC incidence continuing to increase in over half of the states. Regional obesity and lack of physical activity have moderate correlations with HCC incidence trends, suggesting that interventions targeting these factors may help curb rising HCC incidence., (© 2021 by the American Association for the Study of Liver Diseases.)

Background: This study aims to investigate the temporal trend as well as the burden of primary liver cancer among Mongol and non-Mongol in China., Materials and Methods: The registered data from up to 20 monitoring points in the periods of 2008 to 2015 in Inner Mongolia were used to calculate and model the trend of liver cancer among Mongol and non-Mongol using log-linear regression. Logistic regression was used to characterise the risk of liver cancer by using hospitalization records from 2008 to 2017., Results: Over the study period, significant reduction of liver cancer mortality was found among non-Mongol population (4.8/100,000 from 23.7/100,000 to 18.9/100,000, p=0.04), while the increase of liver cancer mortality was observed among the Mongolian population (8.4/100,000 from 10.7/100,000 to 19.1/100,000, p=0.02), particularly the Mongol from East (25.5/100,000 from 11.2/100,000 to 36.7/100,000, p=0.005). Comparing to the non-Mongol patients with primary liver cancer, the Mongolian patients were more likely to be from East Inner Mongolia (aOR=3.65, 95% CI:2.75-4.87) and those residing in urban area (aOR=2.11, 95%CI: 1.55-2.91). In 2015, a total of 3056 primary liver cancer deaths could be converted if the four known risk factors (HBV, Hepatitis C Virus, alcohol consumption and smoking) could be prevented. HBV remained to be the leading risk factor of liver cancer (PAF=56%, contributing to 2616 deaths) with the highest among the Mongol from East (PAF=65.1%, contributing to 763 deaths)., Conclusion: The continuing increase of primary liver cancer among Mongol suggested further interventions were needed to combat its burden.

Background: Hepatocellular carcinoma (HCC) is a common fatal malignant tumor worldwide. Signal transducer and activator of transcription 4 (STAT4) is HCC susceptibility gene identified by genome-wide association study. The purpose of the present study was to determine the association between four candidate single nucleotide polymorphisms (SNPs) in STAT4 genes and HCC risk in Chinese Han population., Methods: A case-control study was conducted to assess the association between STAT4 SNPs and HCC risk in 1011 Chinese Han population. Agena MassARRAY was used to genotype SNPs. The association between SNPs and HCC susceptibility under different genetic models was evaluated by logistic regression analysis. Multifactorial dimension reduction (MDR) analyzed the interaction of 'SNP-SNP' in HCC risk. The difference of clinical characteristics between different genotypes was completed by ANOVA., Results: The results showed that STAT4 rs11889341 was significantly associated with HCC risk under multiple genetic models (homozygote: odds ratio (OR) = 0.60, P=0.033; recessive: OR = 0.63, P=0.028; log-additive: OR = 0.83, P=0.032). The results of subgroup analysis showed that STAT4 rs11889341 is significantly associated with HCC risk with participants who were >55 years, male or smoking. Both STAT4 rs7574865 and rs10174238 were significantly associated with HCC risk among participants who were >55 years, smoking or drinking. STAT4 haplotype (Trs11889341Trs7574865) could reduce the risk of HCC. In addition, rs11889341 and rs7574865 were significantly associated with the level of serum ferritin (SF)., Conclusion: STAT4 rs11889341, rs7574865 or rs10174238 is potentially associated with HCC risk in Chinese Han population. In particular, rs11889341 showed outstanding association with HCC risk., (© 2021 The Author(s).)

Hispanics are disproportionally affected by liver fibrosis and hepatocellular carcinoma (HCC). Advanced liver fibrosis is a major risk factor for HCC development. We aimed at identifying somatic mutations in plasma cell-free DNA (cfDNA) of Hispanics with HCC and Hispanics with advanced liver fibrosis but no HCC. Targeted sequencing of over 262 cancer-associated genes identified nonsynonymous mutations in 22 of the 27 HCC patients. Mutations were detected in known HCC-associated genes (e.g., CTNNB1, TP53, NFE2L2, and ARID1A). No difference in cfDNA concentrations was observed between patients with mutations and those without detectable mutations. HCC patients with higher cfDNA concentrations or higher number of mutations had a shorter overall survival ( p < 0.001 and p = 0.045). Nonsynonymous mutations were also identified in 17 of the 51 subjects with advanced liver fibrosis. KMT2C was the most commonly mutated gene. Nine genes were mutated in both subjects with advanced fibrosis and HCC patients. Again, no significant difference in cfDNA concentrations was observed between subjects with mutations and those without detectable mutations. Furthermore, higher cfDNA concentrations and higher number of mutations correlated with a death outcome in subjects with advanced fibrosis. In conclusion, cfDNA features are promising non-invasive markers for HCC risk prediction and overall survival.

Background: This study analyzes the pattern of use of single agent anticancer therapy (SAACT) in the treatment and survival of advanced hepatocellular carcinoma (aHCC) before and after sorafenib was FDA approved in 2007., Methods: Adult patients diagnosed with HCC and treated with only ACT from 2004 - 2014 were identified in NCDB database. Patients were analyzed during three time frames: 2004-2006 (pre-sorafenib (PS)), 2007-2010 (early sorafenib (ES)) and 2011-2014 (late sorafenib (LS)). Cox proportional hazards models and Kaplan-Meier method were used for analyses., Results: The NCDB contained 31,107 patients with HCC diagnosed from 2004-2014 and treated with ACT alone. Patients were generally men (78.0%), >50 years of age (92.5%). A significant increase in the rate of adaption of SAACT was observed over time: 6.2% PS, 15.2% ES, and 22.2% LS (p < 0.0001). During this later period, the highest proportion of SAACT is among academic and integrated network facilities (23.3%) as compared to community facilities (17.0%, p < 0.0001). The median overall survival of patients with aHCC treated only with SAACT improved significantly over time from 8.0 months (m) (95% CI: 7.4-8.8) to 10.7 m (10.4-11.2) to 15.6 m (15.2-16.0, p < 0.001). Multivariate analysis indicates worse outcomes for patients treated at community cancer programs (HR 1.28, (5% CI: 1.23-1.32), patients without insurance (HR 1.11, 1.06-1.16) and estimated household income of <$63,000 (HR 1.09, 1.05-1.13)., Conclusion: aHCC patients treated only with ACT have experienced an overall improvement in survival, but significant differences exist between facility type, insurance status, and income., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths both globally and in Australia. Surveillance for HCC in at-risk populations allows diagnosis at an early stage, when potentially curable. However, most Australians diagnosed with HCC die of the cancer or of liver disease. In the changing landscape of HCC management, unique challenges may lead to clinical practice variation. As a result, there is a need to identify best practice management of HCC in an Australian context. This consensus statement has been developed for health professionals involved in the care of adult patients with HCC in Australia. It is applicable to specialists, general medical practitioners, nurses, health coordinators and hospital administrators., Methods and Recommendations: This statement has been developed by specialists in hepatology, radiology, surgery, oncology, palliative care, and primary care, including medical practitioners and nurses. The statement addresses four main areas relevant to HCC management: epidemiology and incidence, diagnosis, treatment, and patient management. A modified Delphi process was used to reach consensus on 31 recommendations. Principal recommendations include the adoption of surveillance strategies, use of multidisciplinary meetings, diagnosis, treatment options and patient management., Changes in Management as a Result of This Statement: This consensus statement will simplify HCC patient management and reduce clinical variation. Ultimately, this should result in better outcomes for patients with HCC., (© 2020 AMPCo Pty Ltd.)

Background: In the United States, mortality after a diagnosis of hepatocellular carcinoma (HCC) is higher in patients who are Black than in patients of other racial groups. The objective of this study was to clarify factors contributing to this disparity by analyzing liver and tumor characteristics in patients with HCC who have a history of hepatitis C virus (HCV) infection., Methods: Records of patients with HCV and HCC at the authors' institution from 2003 to 2018 were retrospectively reviewed. Race and ethnicity were self-identified. Imaging, laboratory, and pathologic features were compared between Black and non-Black cohorts., Results: Among 1195 individuals with HCC, 390 identified as Black. At the time of HCC diagnosis, Black patients had better liver function, as measured by Child-Pugh score, Model of End-Stage Liver Disease score, histology of nontumor tissue, and fibrosis-4 (FIB-4) score (all P < .05). FIB-4 scores were <3.25 in 31% of Black patients. In addition, Black patients had less early stage HCC (20.2% vs 32.3%; P < .05), larger tumors (median [interquartile range]: 3.5 cm [2.2-6.2 cm] vs 3.1 cm [2.1-5.1 cm]; P < .01), more multiple tumors (median, [interquartile range]: 1 tumor [1-3 tumors] vs 1 tumor [1-2 tumors]; P = .03), more poorly differentiated tumors (30.3% vs 20.5%; P < .05), and more microvascular invasion (67.2% vs 56.5%; P < .05)., Conclusions: Black patients with HCV exposure develop HCC at earlier stages of liver disease than members of other racial groups. Nearly one-third would not qualify for HCC screening using the common FIB-4 cirrhosis threshold. Practice guidelines that stress HCC surveillance for cirrhotic patients with HCV may need to be revised to be more inclusive for Black patients. In addition, tumors in Black patients carry worse prognostic features, and molecular studies are needed to characterize their biologic properties., (© 2021 American Cancer Society.)

Hepatocellular carcinoma (HCC) is the sixth most common cancer and fourth leading cause of cancer-related death worldwide. The number of HCC cases continues to rise despite advances in screening and therapeutic inventions. More importantly, HCC poses two major health disparity issues. First, HCC occurs more commonly in men than women. Second, with the global increase in non-alcoholic fatty liver diseases (NAFLD), it has also become evident that HCC is more prevalent in some races and/or ethnic groups compared to others, depending on its predisposing etiology. Most studies on HCC in the past have been focused on genetic factors as the driving force for HCC development, and the results revealed that genetic mutations associated with HCC are often heterogeneous and involve multiple pathogenic pathways. An emerging new research field is epigenetics, in which gene expression is modified without altering DNA sequences. In this article, we focus on reviewing current knowledge on HCC-related DNA methylation changes that show disparities among different sexes or different racial/ethnic groups, in an effort to establish a point of departure for resolving the broader issue of health disparities in gastrointestinal malignancies using cutting-edge epigenetic approaches.

Background: Texas is the second largest state by area and population in the USA and is reported to have high incidence and mortality rates for hepatocellular carcinoma (HCC). The reasons for the increasingly high burden of HCC in Texas are not clear., Aims: We explored trends and demographic and regional variations in HCC incidence to better understand reasons for the high burden in Texas., Methods: We analyzed Texas Cancer Registry incidence data from 2001 to 2015 and compared results to the U.S. National Program of Cancer Registries and SEER for the same period. Rates were stratified by sex, race/ethnicity, and age at diagnosis. Rates were also compared between the US/Mexico border region of Texas and the rest of Texas., Results: Texas had the highest HCC age-adjusted incidence rate of all states, 13.2/100,000, which was 45% higher than the national average. In Texas and nationally, rates increased by 4% per year between 2001 and 2015. Rates in Texas were 26-37% greater than national rates for Hispanics, African-Americans, and non-Hispanic whites. Among Hispanics in states with the largest percentage of Hispanics, Texas-based Hispanics had the highest HCC incidence rate in 2015 (21.2/100,000) compared with Hispanics in New Mexico, California, Arizona, Nevada, and Florida. Incidence rates were highest in South Texas and US/Mexico border regions., Conclusions: Increasing rates in the large Hispanic population may explain why Texas now has the highest HCC incidence rate in the USA.

Purpose: Gastrointestinal cancers (GICs) account for about a quarter of cancers. Lately, the circulating microRNAs as a non-invasive biomarker for identifying and monitoring diseases have been recognized. Several studies have examined the role of miR-21 in digestive system carcinoma. We conducted a meta-analysis to assess the diagnostic role of miR-21 in GICs. Methods: Seventeen studies involving 1700 individuals were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, DOR, AUC, SROC, and Q* index were calculated based on true-positive, true-negative, false-negative, and false-positive. Moreover, the subgroup analyses have been performed for miR-21 based on sample types (serum/plasma), normalized genes (U6, miR-16, and miR-39), and ethnicity. Results: The pooled sensitivity 0.722 (95% CI: 0.70-0.74), specificity 0.820 (95% CI: 0.801-0.838), PLR 4.375 (95% CI: 3.226-5.933), NLR 0.308 (95% CI: 0.239-0.398), DOR 16.06 (95% CI: 9.732-26.53) as well as AUC 0.86, and Q* index 0.79 represented the high-grade diagnostic precision of miR-21 in identifying GICs (ESCC, GC, CRC, HCC, and PC). Conclusion: This meta-analysis demonstrated that circulating miR-21 levels can be used to monitor the digestive system carcinomas. Therefore, miR-21 can be a useful biomarker of progression and fair diagnosis in GICs patients.

Background: At present, the diagnostic accuracy of alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) surveillance is insufficient. It remains controversial whether prothrombin induced by vitamin K absence II (PIVKA-II) has a better diagnostic value than AFP for HCC patients., Objective: To investigate the diagnostic role of PIVKA-II alone or in combination with AFP in Chinese HCC patients., Methods: Serum AFP and PIVKA-II levels were detected and analyzed in 308 HCC afflicted patients and 120 unafflicted controls. The receiver operator curve (ROC) and area under the curve (AUC) were conducted to evaluate the clinical value of AFP and PIVKA-II for diagnosing HCC and early HCC., Results: In the whole HCC cohort, the diagnostic values of PIVKA-II were better than that of AFP. The AUC of PIVKA-II and AFP was 0.90 (95% CI 0.87-0.94) and 0.79 (95% CI 0.74-0.84), respectively. "AFP + PIVKA-II" yielded a high sensitivity of 95.1% and a specificity of 83.3%, with the AUC 0.89 (95% CI 0.85-0.93). In the early stage HCC group, the diagnostic accuracy of PIVKA-II was also better than that of AFP. The AUC of PIVKA-II and AFP was 0.83 (95% CI 0.77-0.89) and 0.75 (95% CI 0.68-0.81), respectively. "AFP + PIVKA-II" achieved the sensitivity of 83.3% and specificity of 89.1%, with an AUC of 0.86 (95% CI 0.81-0.91). Moreover, for AFP-negative HCC patients, serum PIVKA-II showed good diagnostic performance, with an AUC of 0.804 (95% CI 0.720-0.887). Besides, elevated PIVKA-II level was a strong independent risk factor for HCC patients with portal vein tumor thrombus (PVTT) (OR = 4.890, P = 0.020)., Conclusion: PIVKA-II is superior to AFP in HCC screening, and AFP in combination with PIVKA-II significantly improves the diagnostic value for Chinese HCC patients. PIVKA-II could effectively indicate HCC accompanied by PVTT and help to optimize the therapeutic strategy., Competing Interests: No conflicting relationship exists for any authors., (Copyright © 2021 Fei Xu et al.)

Background: This study was aimed to evaluate the association between interleukin-6 (IL-6) gene polymorphisms and the risk of hepatocellular carcinoma (HCC) in a meta-analysis., Methods: A literature search was performed for case-control studies published during May, 1993 to May, 2020 focusing on IL-6 gene polymorphisms (-174G > C, -572G > C, and -597G > A) and HCC susceptibility by using PubMed, Cochrane Database, EMBASE, Web of science, and China National Knowledge Infrastructure. From 128 full-text articles, 11 were included in this meta-analysis. I index was used to assess heterogeneity and Newcastle-Ottawa Scale was utilized for quality assessment., Results: For IL-6 -174G > C polymorphism, in codominant (GG vs CC: odds ratios [OR] = 2.78, 95% confidence intervals [CI] = 1.25-6.19, P = .01, I = 16%) and recessive (GG+GC vs CC: OR = 2.76, 95% CI = 1.29-5.90, P = .009, I = 3%) models, IL-6 -174G>C polymorphism was significantly associated with the risk of HCC. In dominant (GG vs CC+GC: OR = 1.80, 95% CI = 0.92-3.54, P = .09, I = 86%) and allele (G vs C: OR = 1.49, 95% CI = 0.95-2.32, P = .08, I = 68%) models, IL-6 -174G>C polymorphism had no impact on the risk of HCC. However, in non-Italian Caucasian population, IL-6 -174G>C polymorphism was significantly related to the occurrence of HCC in both dominant (GG vs CC+GC: OR = 3.26, 95% CI = 2.29-4.65, P < .00001, I = 0%) and allele (G vs C: OR = 2.48, 95% CI = 1.48-4.15, P = .0006) models. Such correlations also could be observed when healthy individuals were selected as controls. For IL-6 -572G>C and -597G>A polymorphisms, no significant association was observed in all models, regardless of the source of control and population subgroups. No publication bias could be calculated when Begg and Egger tests were employed., Conclusion: This meta-analysis indicated that IL-6 -174G>C polymorphism was significantly related with the risk for HCC, especially in non-Italian Caucasian population. No significant association was observed for the correlation between IL-6 -572G>C and -597G>A polymorphisms and HCC susceptibility.

Recently, four single nucleotide polymorphisms (rs2585428, rs4809960, rs6022999 and rs6068816) in CYP24A1 gene were extensively studied for their associations with cancer risk. However, these studies included only a few types of cancer, which calls for further investigations. In view of this, we here conducted a case-control study to explore the associations between these four CYP24A1 gene polymorphisms and risk of liver, lung and gastric cancer in a Chinese population. A total of 480 liver cancer patients, 550 lung cancer patients, 460 gastric cancer patients and 800 normal controls were recruited in this study. The genotyping of CYP24A1 gene polymorphisms was applied with Sanger sequencing assay. Single-locus analysis demonstrated that rs6022999 was significantly associated with risk of liver and lung cancer, while rs6068816 was significantly associated with the risk of gastric cancer. Haplotype analysis revealed that haplotype GTAT was associated with an increased risk of liver cancer and a decreased risk of lung cancer, and haplotype ATGC was associated with a decreased risk of lung cancer. The further meta-analysis of rs6068816 and lung cancer risk showed that rs6068816 was not associated with lung cancer risk in Chinese population, which confirmed our present finding. Conclusively, rs6022999 may be a genetic biomarker for liver and lung cancer susceptibility in Chinese population, and rs6068816 may be used to predict gastric cancer risk in Chinese population., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Purpose: Hepatitis B (HBV), the leading cause of hepatocellular carcinoma (HCC), disproportionately affects minorities. Compared to other races, Blacks more often present with advanced HCC and have decreased survival. We observed higher HBV-associated HCC rates among Blacks than reported nationally. In our center, Haitian Blacks had the highest rates of HBV-associated HCC and shorter survival compared to other Blacks. We investigated knowledge and perceptions regarding HBV and HCC among Blacks born in the United States or Haiti., Methods: Using community partnerships, participants were recruited via word of mouth, email, social media or from Hepatology clinic. Focus groups were conducted in Haitian Creole or English and stratified by birthplace, gender and infection status. Discussions were audio-recorded and transcribed verbatim. A constant comparative method was used for data analysis; themes are based on conversational details., Results: There were 55 participants; 49% were male and 27% had chronic HBV. Only 42% of Haitian Blacks knew about HBV prior to participation vs. 78% of African Americans, p 0.03. Both groups expressed that fear, mistrust of the medical establishment, denial and stigma might compel persons to avoid seeking care. Both groups attributed higher rates of late stage HCC diagnosis in Blacks to inadequate financial resources and education. Those with HBV reported confusion regarding their infection and suboptimal communication with healthcare providers., Conclusions: In two communities disproportionately affected by HBV, misconceptions about disease transmission, stigma, low health literacy and decreased access to care may limit detection for HBV. Culturally relevant community-based interventions are needed to increase HBV detection.

Background & Aims: HDV infection causes severe chronic liver disease in individuals infected with HBV. However, the factors associated with poor prognosis are largely unknown. Thus, we aimed to identify prognostic factors in patients with HDV infection., Methods: The French National Reference Centre for HDV performed a nationwide retrospective study on 1,112 HDV-infected patients, collecting epidemiological, clinical, virological and histological data from the initial referral to the last recorded follow-up., Results: The median age of our cohort was 36.5 (29.9-43.2) years and 68.6% of our cohort were male. Most patients whose birthplace was known were immigrants from sub-Saharan Africa (52.5%), southern and eastern Europe (21.3%), northern Africa and the Middle East (6.2%), Asia (5.9%) and South America (0.3%). Only 150 patients (13.8%) were French native. HDV load was positive in 659 of 748 tested patients (88.1%). HDV-1 was predominant (75.9%), followed by sub-Saharan genotypes: HDV-5 (17.6%), HDV-7 (2.9%), HDV-6 (1.8%) and HDV-8 (1.6%). At referral, 312 patients (28.2%) had cirrhosis, half having experienced at least 1 episode of hepatic decompensation. Cirrhosis was significantly less frequent in African than in European patients regardless of HDV genotype. At the end of follow-up (median 3.0 [0.8-7.2] years), 48.8% of the patients had developed cirrhosis, 24.2% had ≥1 episode(s) of decompensation and 9.2% had hepatocellular carcinoma. European HDV-1 and African HDV-5 patients were more at risk of developing cirrhosis. Persistent replicative HDV infection was associated with decompensation, hepatocellular carcinoma and death. African patients displayed better response to interferon therapy than non-African patients (46.4% vs. 29.1%, p <0.001). HDV viral load at baseline was significantly lower in responders than in non-responders., Conclusion: Place of birth, HDV genotype and persistent viremia constitute the main determinants of liver involvement and response to treatment in chronic HDV-infected patients., Lay Summary: Chronic liver infection by hepatitis delta virus (HDV) is the most severe form of chronic viral hepatitis. Despite the fact that at least 15-20 million people are chronically infected by HDV worldwide, factors determining the severity of liver involvement are largely unknown. By investigating a large cohort of 1,112 HDV-infected patients followed-up in France, but coming from different areas of the world, we were able to determine that HDV genotype, place of birth (reflecting both viral and host-related factors) and persistent viremia constitute the main determinants of liver involvement and response to treatment., Competing Interests: Conflict of interest Dr. Nahon received honoraria from Astra-Zeneca, Abbvie, Bayer, Bristol-Myers Squibb, Gilead and Ipsen. He consults for Abbvie and Bristol-Myers Squibb. Dr Roudot-Thoraval received honoraria from Gilead and AbbVie. Dr Roulot received honoraria from Gilead. All other authors report no conflict of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Purpose: We investigated the effect of race and age on the distribution of prostate cancer metastases., Materials and Methods: Records for patients with metastatic prostate cancer were abstracted from the National Inpatient Sample database (2008-2015)., Results: Of 6,963 patients with metastatic prostate cancer 3,881 (72.2%) were Caucasian and 1,494 (27.8%) were African American. Bone metastases were the most common site of metastases in Caucasian and African American patients (83.9% and 87.0%, respectively), followed by distant lymph node metastases in Caucasian (13.9% of Caucasian vs 13.2% of African American), liver metastases in African American (13.8% of African American vs 13.3% of Caucasian) and lung metastases in Caucasian and African American patients (9.3% and 13.1%, respectively). No clinically meaningful differences were recorded in age and race analyses, except for lymph node metastases (61.1% to 23.4% in Caucasian vs 39.0% to 25.1% in African American patients), which decreased with age. Specific single organ metastatic sites, outside of bone and lymph nodes, were low in both racial groups (2.1% or less). The rate of brain metastases was also rare in both racial groups at 1.4% or less, regardless of other metastatic locations. Thoracic metastases, in the absence of bone and abdominal metastases, were present in 1.9% of Caucasian and African American patients., Conclusions: The most important finding according to age and race resided in rates of lymph node metastases. Conversely, all other racial and age related differences were subtle. Nonetheless, they are important in the context of planning and/or design of clinical trials. Finally, brain (1.4%) and thoracic (1.9%) metastases affect few patients and routine brain and chest imaging may not be warranted.

MicroRNAs (miRNAs) play important roles in the regulation of gene expression at the posttranscriptional level and are involved in human carcinogenesis. The aim of the current study was to investigate the associations between miR-182 single nucleotide polymorphisms and HCC risk in a southern Chinese population. In this case-control study of 863 HCC patients and 908 cancer-free controls, we performed genotyping of miR-182 rs4541843 and assessed its association with HCC risk. We found that individuals carrying the AG/AA genotypes of miR-182 rs4541843 were significantly associated with an increased risk of HCC compared with those carrying the GG genotype (adjusted odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.07-2.76, P = 0.026). In the stratified analysis, this increased risk was more pronounced in the subgroups of older individuals (adjusted OR = 1.98, 95% CI = 1.04-3.76, P = 0.037), males (adjusted OR = 1.81, 95% CI = 1.09-2.99, P = 0.021), and never drinkers (adjusted OR = 1.84, 95% CI = 1.03-3.30, P = 0.041). Our results suggested that miR-182 polymorphism rs4541843 may contribute to the susceptibility to HCC. Our findings require validation in further studies with larger sample sizes.

Background: The ability of the pretreatment lymphocyte to monocyte ratio (LMR) to predict outcomes of patients with hepatocellular carcinoma (HCC) receiving sorafenib is not conclusively determined., Methods: We retrospectively studied patients treated with sorafenib for HCC in two tertiary referral centres in Asia and North America. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Predictive factors for the outcomes were determined by Cox proportional hazards models. A risk assessment tool was developed., Results: Compared to the North America cohort, the Asia cohort was more heavily pretreated (72.1% vs. 35.2%; p < 0.001), had higher hepatitis B virus infection (87.6% vs. 5.6%; p < 0.001), and more distant metastases (83.2% vs. 25.4%; p < 0.001). Lower monocyte count in the Asia cohort (median 462.7 vs. 600.0/μL; p = 0.023) resulted in a higher LMR (median 2.6 vs. 1.8; p < 0.001). High LMR was associated with a significantly higher OS [hazard ratio (HR) 0.88; 95% confidence interval (CI) 0.81‒0.97; p = 0.007]. This was confirmed in a sensitivity analysis including patients treated in Asia only (HR 0.89; 95% CI 0.81‒0.97; p = 0.010). An OS nomogram was constructed with the following variables selected in the multivariate Cox model: LMR, treatment location, previous treatment, performance status, alpha-fetoprotein, lymph node metastasis, and Child‒Pugh score. The concordance score was 0.71 (95% CI, 0.67‒0.75). LMR did not predict PFS., Conclusion: LMR measured before sorafenib administration predicts OS in advanced HCC patients. Our OS nomogram, incorporating LMR, can be offered to clinicians to improve their ability to assess prognosis, strengthen the prognosis-based decision-making, and inform patients in the clinic.

Purpose: Surveillance, treatment, and outcomes for African-American (AA) populations with hepatocellular carcinoma (HCC) remain under evaluated. This study evaluated demographics, surveillance, therapy, and outcomes for a predominately AA population., Methods: The electronic medical records of a large health-care provider were used to identify 274 patients with visits for HCC between 2010 and 2017. Tumor size at diagnosis was defined by imaging with ≤ 5 cm being defined as "small." Surveillance for HCC was defined based on ultrasound (US) assessments., Results: Patients were primarily AA (78%) and male (76%) with an average age at diagnosis of 62 years. Hepatitis C virus (HCV) was more likely to be a risk factor for the development of HCC in AA as compared to non-AA (92% vs 67%; p < 0.005). Surveillance rates were low (16% for AA vs 7% for non-AA). An aspartate aminotransferase platelet ratio index (APRI) value > 0.7 within 2 years of tumor diagnosis was a strong predictor for the risk of the development of HCC (86% AA vs 79 % non-AA). In this study, race was not a factor in treatment or outcomes, and most patients received tumor ablative treatment., Conclusion: Given the low surveillance rates and the demonstrated increased survival for patients with small tumors, ways to increase surveillance must be initiated. The results of this study demonstrate the need for physician/patient education on the importance of surveillance US. Further, this study supports routine assessment of APRI in AA patients in an effort to identify patients in whom intensive surveillance will significantly improve earlier detection of tumors.

Background: Hepatitis B (HBV), the leading cause of hepatocellular carcinoma (HCC) worldwide, disproportionately affects minorities in the USA. Undiagnosed HBV precludes HCC screening and contributes to late-stage cancer presentation and decreased survival. Barriers to HBV and HCC screening include lack of insurance and limited diffusion of guidelines. We aimed to assess knowledge about HBV and HCC screening indications and explore barriers to screening., Methods: We surveyed trainees from the University of Miami/Jackson Memorial Hospitals, Palmetto General Hospital, and Mount Sinai Medical Center. We assessed knowledge using clinical vignettes. We performed bivariate and Chi-squared analyses., Results: There were 183 respondents; median age was 31 and 52% were male. The sample was 35% Hispanic, 29% White, 18% Asian, and 9% Black. Training department was Internal Medicine, 71%; Family Medicine, 11%; Infectious Diseases, 6%; or Gastroenterology, 7%. Only 59% correctly estimated national HBV prevalence; 25% correctly estimated global prevalence. In vignettes with behavioral risk factors, trainees correctly advised screening, 63-96%. However, when the risk factor was the birthplace, correct responses ranged from 33 to 53%. Overall, 45% chose an incorrect combination of HBV screening tests. Perceived barriers to screening included limited expertise in screening of immigrants and limited patient education. Respondents were more likely to recommend HCC screening in cirrhotic patients versus non-cirrhotic HBV patients. Key barriers to HCC screening included uncertainty about HCC guidelines and patient financial barriers., Conclusions: Knowledge of HBV and HCC screening recommendations is suboptimal among trainees. Efforts to broadly disseminate HBV and HCC guidelines through targeted educational interventions are needed.

Expression of ATP-binding cassette B5 (ABCB5) has been demonstrated to confer chemoresistance, enhance cancer stem cell properties and associate with poor prognosis in hepatocellular carcinoma (HCC). The aim of this study was to evaluate the genetic variations of ABCB5 in HCC patients with reference to healthy individuals and the clinicopathological significance. A pilot study has examined 20 out of 300 pairs HCC and paralleled blood samples using conventional sequencing method to cover all exons and exon/intron regions to investigate whether there will be novel variant sequence and mutation event. A total of 300 HCC and 300 healthy blood DNA samples were then examined by Sequenom MassARRAY genotyping and pyrosequencing for 38 SNP and 1 INDEL in ABCB5. Five novel SNPs were identified in ABCB5. Comparison of DNA from blood samples of HCC and healthy demonstrated that ABCB5 SNPs rs75494098, rs4721940 and rs10254317 were associated with HCC risk. Specific ABCB5 variants were associated with aggressive HCC features. SNP rs17143212 was significantly associated with ABCB5 expression level. Nonetheless, the paralleled blood and tumour DNA sequences from HCC patients indicated that ABCB5 mutation in tumours was not common and corroborated the TCGA data sets. In conclusion, ABCB5 genetic variants had significant association with HCC risk and aggressive tumour properties., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Numerous evidence has revealed that single-nucleotide polymorphisms (SNPs) are associated with liver cancer risk. To assess whether the MIR17HG polymorphisms are associated with the liver cancer risk in the Chinese Han population, we performed a case-control (432 liver cancer patients and 430 healthy controls) study. Genotyping of four variants of MIR17HG was performed with the Agena MassARRAY platform. We used χ2 test to compare the distribution of SNPs allele and genotypes frequencies of cases and controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression analysis to evaluate the association under genetic models. The results indicated that the rs7318578 was significantly associated with increased the risk of liver cancer in the allele (OR = 1.45, 95% CI: 1.18-1.77, P=3.04E-04), recessive (OR = 3.69, 95% CI: 2.45-5.56, P=4.52E-10) and additive model (OR = 1.35, 95% CI: 1.13-1.62, P=0.001). Moreover, we found that individuals with the genotype CC of rs7318578 presented with an increased risk of liver cancer (OR = 3.03, 95% CI: 1.98-4.65, P=3.83E-07); however, the CA genotype of rs7318578 significantly decreased the risk of liver cancer (OR = 0.61, 95% CI: 0.45-0.83, P=0.001, compared with those with the AA genotype. Our findings indicated that MIR17HG polymorphism (rs7318578) contributes to liver cancer susceptibility to the Chinese Han population. Further studies with larger samples are required to confirm the results, as well as functional studies to determine the role of this SNP in miRNA expression or molecular pathways., (© 2020 The Author(s).)

Based on accumulating evidence, long noncoding RNAs (lncRNAs) are potential biomarkers and therapeutic targets for many diseases, including tumors. In this study, we consulted The Cancer Genome Atlas (TCGA) database to explore the functions and modulatory mechanisms of lncRNAs as competing endogenous RNAs (ceRNAs) in hepatocellular carcinoma (HCC) in Asian patients and constructed a risk scoring system composed of four lncRNAs (SNHG1, STEAP3-AS1, RUSC1-AS1, and SNHG3) to predict the outcomes of Asian patients with HCC. The prognostic value of this risk model was validated in the internal validation cohort (n = 157). The stratified survival analysis revealed good performance for the risk model in stratifying clinical features. According to the Cox proportional hazard regression analysis, the four-lncRNA risk model is an independent prognostic model for Asian patients with HCC. Finally, we developed a nomogram that integrates prognostic signals and other clinical information to predict 1-, 3-, and 5-year overall survival rates. In conclusion, the prognostic lncRNAs identified in our study exerted potential biological effects on the development of HCC. The risk scoring model based on four lncRNAs may be an effective classification tool for assessing the prognosis of Asian patients with HCC., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Racial/ethnic disparities in prognosis have been reported in patients with hepatocellular carcinoma (HCC); however, few studies have evaluated racial/ethnic disparities in the context of insurance status., Aims: Characterize racial/ethnic and insurance status in early tumor detection, receipt of curative therapy and overall survival in a multicenter diverse cohort of HCC patients from the USA., Study: We included patients with HCC diagnosed between June 2012 and May 2013 at four centers in the USA. Generalized linear mixed effects models were used to compare early tumor detection (defined using Milan Criteria) and curative treatment receipt (liver transplantation, surgical resection, or local ablation) as a function of patient race/ethnicity and insurance status. A multivariable frailty survival model was used to compare risk of death between patient groups., Results: Of 379 HCC patients (52.8% non-Hispanic White, 19.5% Hispanic White, 19.8% Black), 46.4% and 48.0% were found at an early stage and underwent curative therapy, respectively, and median overall survival of the cohort was 25.7 months. Early detection of HCC was associated with gastroenterology subspecialty care and receipt of HCC surveillance but not race/ethnicity or insurance status in adjusted models. However, commercial insurance was significantly associated with higher odds of curative treatment receipt, which in turn was the strongest correlate for overall survival. After adjusting for health system and insurance status, race/ethnicity was not associated with curative treatment receipt or overall survival., Conclusions: Insurance status and access to gastroenterology subspecialty care may be important drivers of racial/ethnic disparities in prognosis among HCC patients.

Cancer is still a major health problem in China although numerous efforts have been made for its prevention and control. Findings from this study showed that lung cancer remains the most common type of cancer diagnosed, and was attributed to nearly 30% of all cancer-related deaths. The incidence of the five most common cancers, in China, in 2015, including cancers of the lungs, stomach, colorectum, liver and breast, accounted for almost 60% of all cancers diagnosed. The high cancer burden in China highlights the need for further improvement in health education, professional training and the building up an anti-cancer network for introducing and implementing sustainable actions for cancer control., (© 2020 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)

Background: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) account for an increasing proportion of liver disease in the Asia-Pacific region. Many areas in the region are experiencing epidemics of metabolic syndrome among rapidly ageing populations., Aims: To estimate using modelling the growth in NAFLD populations, including cases with significant fibrosis that are most likely to experience advanced liver disease and related mortality., Methods: A disease progression model was used to summarise and project fibrosis progression among the NAFLD populations of Hong Kong, Singapore, South Korea and Taiwan. For each area, changes in the adult prevalence of obesity was used to extrapolate long-term trends in NAFLD incidence., Results: In the areas studied, prevalent NAFLD cases were projected to increase 6%-20% during 2019-2030, while prevalent NASH cases increase 20%-35%. Incident cases of hepatocellular carcinoma are projected to increase by 65%-85%, while incident decompensated cirrhosis cases increase 65%-100% by 2030. Likewise, NAFLD-related mortality is projected to increase between 65% and 100% from 2019 to 2030. NAFLD disease burden is expected to increase alongside rising trends in metabolic syndrome and obesity among populations in the region. This leads to more cases of advanced liver disease and associated mortality., Conclusions: Preventing the growth of diabetic and obese populations will be a key factor in reducing ongoing increases in NAFLD-related disease burden in the Asia-Pacific region., (© 2020 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

C677T (Ala>Val, rs1801133 C>T), a non-synonymous variant of methylenetetrahydrofolate reductase (MTHFR) gene, has been found to be associated with an impair enzyme activity of MTHFR. The relationship of MTHFR rs1801133 with hepatocellular carcinoma (HCC) has been extensively investigated. However, the findings were conflicting. Recently, more investigations have been conducted on the relationship of MTHFR rs1801133 with HCC. To obtain a more precise assessment on the effect of this non-synonymous variant to the development of HCC, a pooled-analysis was performed. This meta-analysis consisted of 19 independent case-control studies. By using the odds ratio (OR) combined with 95% confidence interval (CI), the relationship of MTHFR rs1801133 with HCC risk was determined. A total of 19 independent case-control studies were included. Finally, 6,102 HCC cases and 6,526 controls were recruited to examine the relationship of MTHFR rs1801133 with HCC risk. In recessive model (TT vs. CC/CT), the findings reached statistical significance (OR, 0.90; 95%CI, 0.82-0.98; P = 0.016). Subgroup analysis also found an association between MTHFR rs1801133 polymorphism and the decreased risk of HCC in hepatitis/virus related patients (recessive model: OR, 0.85; 95%CI, 0.72-0.99; P = 0.035, and allele model: OR, 0.90; 95%CI, 0.81-0.99; P = 0.028). Subgroup analyses indicated that extreme heterogeneity existed in Asian population, larger sample size investigation, hospital-based study and normal/healthy control subgroups. The shape of Begger's seemed symmetrical. Egger's linear regression test also confirmed these evaluations. Sensitivity analyses suggested that our findings were stable. In summary, our results highlight that MTHFR rs1801133 polymorphism decreases HCC susceptibility. The relationship warrants a further assessment., (© 2020 The Author(s).)