A preliminary study of optimal treatment response rates in patients undergoing hepatic arterial infusion chemotherapy combined with molecular targeting and immunotherapy.

Objectives: This study aimed to examine the effectiveness of the best response rate (BRR) as a surrogate for overall survival (OS), using the modified Response Evaluation Criteria in Solid Tumors (mRECIST), in patients with unresectable hepatocellular carcinoma (HCC) undergoing hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) combined with molecular targeting and immunotherapy. Methods: This study enrolled 111 consecutive patients who had complete imaging data. The median age of patients was 58 years (IQR 50.5-65.0). Among the patients, those with Barcelona Clinic Liver Cancer (BCLC) stage A, BCLC stage B, and BCLC stage C comprised 6.4%, 19.1%, and 73.6%, respectively. The optimal threshold of BRR can be determined using restricted cubic splines (RCS) and the rank sum statistics of maximum selection. Survival curves of patients in the high rating and low rating groups were plotted. We then used the change-in-estimate (CIE) method to filter out confounders and the inverse probability of treatment weighting (IPTW) to balance confounders between the two groups to assess the robustness of the results. Results: The median frequency of the combination treatment regimens administered in the overall population was 3 times (IQR 2.0-3.0). The optimal BRR truncation value calculated was -0.2. Based on this value, 77 patients were categorized as the low rating group and 34 as the high rating group. The differences in the OS between the high and low rating groups were statistically significant (7 months [95%CI 6.0-14.0] vs. 30 months [95%CI 30.0-]; p< 0.001). Using the absolute 10% cut-off value, the CIE method was used to screen out the following confounding factors affecting prognosis: successful conversion surgery, baseline tumor size, BCLC stage, serum total bilirubin level, number of interventional treatments, alpha-fetoprotein level, presence of inferior vena cava tumor thrombus, and partial thrombin activation time. The survival curve was then plotted again using IPTW for confounding factors, and it was found that the low rating group continued to have better OS than the high rating group. Finally, the relationship between BRR and baseline factors was analyzed, and inferior vena cava tumor thrombus and baseline tumor size correlated significantly with BRR. Conclusions: BRR can be used as a surrogate endpoint for OS in unresectable HCC patients undergoing FOLFOX-HAIC in combination with molecular targeting and immunotherapy. Thus, by calculating the BRR, the prognosis of HCC patients after combination therapy can be predicted. Inferior vena cava tumor thrombus and baseline tumor size were closely associated with the BRR.

Prognostic value of CD8+T cells related genes and exhaustion regulation of Notch signaling pathway in hepatocellular carcinoma.

Immunotherapy has emerged as the primary treatment modality for patients with advanced Hepatocellular carcinoma (HCC). However, its clinical efficacy remains limited, benefiting only a subset of patients, while most exhibit immune tolerance and face a grim prognosis. The infiltration of immune cells plays a pivotal role in tumor initiation and progression. In this study, we conducted an analysis of immune cell infiltration patterns in HCC patients and observed a substantial proportion of CD8+T cells. Leveraging the weighted gene co-expression network analysis (WGCNA), we identified 235 genes associated with CD8+T cell and constructed a risk prediction model. In this model, HCC patients were stratified into a high-risk and low-risk group. Patients in the high-risk group exhibited a lower survival rate, predominantly presented with intermediate to advanced stages of cancer, displayed compromised immune function, showed limited responsiveness to immunotherapy, and demonstrated elevated expression levels of the Notch signaling pathway. Further examination of clinical samples demonstrated an upregulation of the Notch1+CD8+T cell exhaustion phenotype accompanied by impaired cytotoxicity and cytokine secretion functions that worsened with increasing Notch activation levels. Our study not only presents a prognostic model but also highlights the crucial involvement of the Notch pathway in CD8+T cell exhaustion-a potential target for future immunotherapeutic interventions.

A prognostic signature established based on genes related to tumor microenvironment for patients with hepatocellular carcinoma.

BACKGROUND: Complex cellular signaling network in the tumor microenvironment (TME) could serve as an indicator for the prognostic classification of hepatocellular carcinoma (HCC) patients. METHODS: Univariate Cox regression analysis was performed to screen prognosis-related TME-related genes (TRGs), based on which HCC samples were clustered by running non-negative matrix factorization (NMF) algorithm. Furthermore, the correlation between different molecular HCC subtypes and immune cell infiltration level was analyzed. Finally, a risk score (RS) model was established by LASSO and Cox regression analyses (CRA) using these TRGs. Functional enrichment analysis was performed using gene set enrichment analysis (GSEA). RESULTS: HCC patients were divided into three molecular subtypes (C1, C2, and C3) based on 704 prognosis-related TRGs. HCC subtype C1 had significantly better OS than C2 and C3. We selected 13 TRGs to construct the RS model. Univariate and multivariate CRA showed that the RS could independently predict patients' prognosis. A nomogram integrating the RS and clinicopathologic features of the patients was further created. We also validated the reliability of the model according to the area under the receiver operating characteristic (ROC) curve value, concordance index (C-index), and decision curve analysis. The current findings demonstrated that the RS was significantly correlated with CD8+ T cells, monocytic lineage, and myeloid dendritic cells. CONCLUSION: This study provided TRGs to help classify patients with HCC and predict their prognoses, contributing to personalized treatments for patients with HCC.

Burden of liver cancer mortality by county, race, and ethnicity in the USA, 2000-19: a systematic analysis of health disparities.

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).

Influence of sex on outcomes of liver transplantation for hepatocellular carcinoma: a multicenter cohort study in China.

OBJECTIVE: Sex-specific differences are observed in various liver diseases, but the influence of sex on the outcomes of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains to be determined. This study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with HCC. METHODS: Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were analyzed. The associations between donor, recipient, or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching (PSM). The survival associated with different sex-based donor-recipient transplant patterns was further studied. RESULTS: Among 3,769 patients enrolled in this study, the 1-, 3-, and 5-year overall survival (OS) rates of patients with HCC after LT were 96.1%, 86.4%, and 78.5%, respectively, in female recipients, and 95.8%, 79.0%, and 70.7%, respectively, in male recipients after PSM (P = 0.009). However, the OS was comparable between recipients with female donors and male donors. Multivariate analysis indicated that male recipient sex was a risk factor for post-LT survival (HR = 1.381, P = 0.046). Among the donor-recipient transplant patterns, the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival (P < 0.05). CONCLUSIONS: Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients, and the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival. Livers from male donors may provide the most benefit to female recipients. Our results indicate that sex should be considered as a critical factor in organ allocation.

Role of CCR1/5/7 in hepatocellular carcinoma: a study on prognostic evaluation, molecular subtyping, and association with immune infiltration.

This study aims to assess the prognostic value of the C-C motif chemokine receptor (CCR) gene family in hepatocellular carcinoma (HCC) and its relationship with immune infiltration and molecular subtypes of HCC. The evaluation of the GSE14520 dataset and TCGA database confirmed the prognostic significance of CCR. Building upon the correlation between CCR1, CCR5, and CCR7 and favorable prognosis, we further validated the prognostic importance of CCR1, CCR5, and CCR7 in ICGC database and an independent cohort from Guangxi autonomous region. Then, we constructed a risk prognosis model. Additionally, we observed significant positive correlations between CCR1, CCR5, and CCR7 and the infiltration of B cells, T cells, and macrophages in HCC. Subsequently, we conducted CCK assays, Transwell assays, and colony formation assays to evaluate the molecular biological functions of CCR1, CCR5, and CCR7. These experiments further confirmed that upregulation of CCR1, CCR5, and CCR7 can individually inhibit the proliferation, migration, and stemness of HCC cells. By analyzing the relationship between expression levels and tumor mutation frequency, we discovered that patients with high CCR1 expression were more likely to be classified as non-proliferative HCC. Similar conclusions were observed for CCR5 and CCR7. The association of CCR1, CCR5, and CCR7 with the molecular subtypes of HCC suggests that they may serve as intermediary molecules linking immune status and molecular subtypes in HCC. In summary, CCR1, CCR5, and CCR7 have the potential to serve as prognostic biomarkers for HCC and regulate HCC progression by influencing immune cell infiltration.

Liver resection is superior to tumor ablation in patients with multifocal hepatocellular carcinoma.

INTRODUCTION: The management of T2 multifocal hepatocellular carcinoma (MHCC) is controversial, and the comparative impact of liver resection (LR) versus tumor ablation (TA) on survival continues to be debated. The aim of our study was to examine short- and long-term survival for LR and TA in a nationally representative cohort. We hypothesized that patients who underwent LR would have improved survival. METHODS: We utilized the National Cancer Database (2004-2015) to identify patients diagnosed with non-metastatic T2 MHCC. Kaplan-Meier survival curves were generated to compare 10-year overall survival (OS) between LR and TA patients. Kaplan-Meier analysis with stratification was also performed based on lymphovascular invasion, resection margin status, and Charlson-Deyo score. Cox proportional hazard models were used in multivariable analyses. RESULTS: A total of 1225 patients met the inclusion criteria. 991 patients received LR, and 234 received TA. The majority of patients were male, White, and older than ≥60 years old. Clinicodemographic characteristics were generally similar between LR and TA patients. Among patients who underwent LR, 84% had negative margins, and 17% had lymphovascular invasion. Mortality at 30 days was significantly higher among LR patients compared to TA patients (5.4% vs 0.0%, p < 0.001), with those having a Charlson-Deyo score ≥2 facing the highest risk at 7.3%. Nevertheless, 10-year OS for the LR cohort was 27.5% (95% confidence interval [CI]: 24.4%-30.8%) versus 14.7% (95% CI: 9.8%-20.7%, p < 0.001) for TA patients. In stratified analysis, survival benefit was statistically significant only among those with negative resection margin, no lymphovascular invasion, and Charlson-Deyo score ≤1. In multivariable Cox analysis, LR was independently associated with improved survival compared to TA (hazard ratio: 0.80; 95% CI = 0.67-0.95). CONCLUSION: LR poses a higher long-term survival benefit than TA. Prospective studies are warranted to confirm these findings. Although our study patients are a highly selected group of multifocal T2 patients, it gives us a good insight into the fact that LR provides better outcomes if a transplant option is unavailable.

Prognostic Nutritional Index as a Prognostic Factor for Very Early-Stage Hepatocellular Carcinoma.

INTRODUCTION: Field factors play more important roles in predicting the outcomes of patients compared with tumor factors in early-stage hepatocellular carcinoma (HCC). However, the prognostic ability of noninvasive serum marker scores for hepatic fibrosis and liver functional reserve on very early-stage HCC is still not yet determined. We aimed to investigate the performance of these serum marker scores in predicting the prognoses of patients with very early-stage HCC. METHODS: A total of 446 patients with very early-stage HCC from 2012 to 2022 were retrospectively enrolled. Serum biomarkers and prognostic scores determining overall survival (OS) were analyzed by Cox proportional hazards model. We compared the Akaike information criterion among the prognostic nutritional index (PNI), aspartate aminotransferase-to-platelet ratio index, albumin-bilirubin (ALBI) score, EZ (easy)-ALBI score, modified ALBI score, fibrosis-4 score, and lymphocyte-to-monocyte ratio to determine the predictability on the OS. RESULTS: After a median follow-up of 41.0 months (interquartile range 36.9-45.1 months), 81 patients died, with a 5-year OS rate of 71.0%. Among the noninvasive serum marker scores, PNI had the best performance in predicting the OS with the lowest Akaike information criterion (846.407) compared with other scores. Moreover, we stratified the patients into high-risk (PNI <45) and low-risk (PNI ≥45) groups. It showed that the 5-year OS rates were 83.4% and 60.8% in the low-risk and high-risk PNI groups, respectively ( P < 0.001). DISCUSSION: PNI had the best performance in predicting the OS for patients with very early-stage HCC.

Risk and prognostic factors in patients with colon cancer with liver metastasis.

OBJECTIVE: The most common site of metastasis in patients with colon cancer is the liver. This study aimed to identify patients with colon cancer at high risk of developing liver metastasis and to explore their prognosis. METHODS: The clinical characteristics, treatment methods and survival outcomes of patients diagnosed with colon cancer from 2010 to 2015 were identified from the Surveillance, Epidemiology and End Results (SEER) database. Patients were divided into two groups according to the presence of liver metastasis, and multivariate logistic and Cox regression models were used to identify risk and prognostic factors. RESULTS: A total of 60,018 patients with colon cancer were selected from the SEER database. The incidence of liver metastasis was 9.2%. African American ethnicity, poor differentiation, higher tumor stage, higher lymph node ratio, and lung metastases were common factors associated with both liver metastasis risk and prognosis. CONCLUSIONS: Metastasectomy might improve survival among patients with colon cancer with resectable liver metastasis lesions and no other organ involvement.

Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Liver Cancer and Chronic Liver Disease Mortality.

Importance: Approximately 65% of adults in the US consume sugar-sweetened beverages daily. Objective: To study the associations between intake of sugar-sweetened beverages, artificially sweetened beverages, and incidence of liver cancer and chronic liver disease mortality. Design, Setting, and Participants: A prospective cohort with 98 786 postmenopausal women aged 50 to 79 years enrolled in the Women's Health Initiative from 1993 to 1998 at 40 clinical centers in the US and were followed up to March 1, 2020. Exposures: Sugar-sweetened beverage intake was assessed based on a food frequency questionnaire administered at baseline and defined as the sum of regular soft drinks and fruit drinks (not including fruit juice); artificially sweetened beverage intake was measured at 3-year follow-up. Main Outcomes and Measures: The primary outcomes were (1) liver cancer incidence, and (2) mortality due to chronic liver disease, defined as death from nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, alcoholic liver diseases, and chronic hepatitis. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs) and 95% CIs for liver cancer incidence and for chronic liver disease mortality, adjusting for potential confounders including demographics and lifestyle factors. Results: During a median follow-up of 20.9 years, 207 women developed liver cancer and 148 died from chronic liver disease. At baseline, 6.8% of women consumed 1 or more sugar-sweetened beverage servings per day, and 13.1% consumed 1 or more artificially sweetened beverage servings per day at 3-year follow-up. Compared with intake of 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more servings per day had a significantly higher risk of liver cancer (18.0 vs 10.3 per 100 000 person-years [P value for trend = .02]; adjusted HR, 1.85 [95% CI, 1.16-2.96]; P = .01) and chronic liver disease mortality (17.7 vs 7.1 per 100 000 person-years [P value for trend <.001]; adjusted HR, 1.68 [95% CI, 1.03-2.75]; P = .04). Compared with intake of 3 or fewer artificially sweetened beverages per month, individuals who consumed 1 or more artificially sweetened beverages per day did not have significantly increased incidence of liver cancer (11.8 vs 10.2 per 100 000 person-years [P value for trend = .70]; adjusted HR, 1.17 [95% CI, 0.70-1.94]; P = .55) or chronic liver disease mortality (7.1 vs 5.3 per 100 000 person-years [P value for trend = .32]; adjusted HR, 0.95 [95% CI, 0.49-1.84]; P = .88). Conclusions and Relevance: In postmenopausal women, compared with consuming 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more sugar-sweetened beverages per day had a higher incidence of liver cancer and death from chronic liver disease. Future studies should confirm these findings and identify the biological pathways of these associations.

Association of nativity with survival among adults with hepatocellular carcinoma.

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.

Recent Mortality Patterns and Time Trends for the Major Cancers in 47 Countries Worldwide.

BACKGROUND: Most prior studies have reported cancer mortality trends across countries for specific cancer types. Herein, we examine recent patterns and trends in cancer mortality rates for the eight common forms of cancer in 47 countries across five continents (except Africa) based on the World Health Organization mortality database. METHODS: Rates were age-standardized to the 1966 Segi-Doll world population, and trends in the age-standardized rates for the most recent 10 years of data were examined using Joinpoint regression. RESULTS: Cancer-specific mortality rates vary substantially across countries, with rates of infection-related (cervix and stomach) and tobacco-related cancers (lung and esophagus) varying by 10-fold. Recent mortality rates for all major cancers decreased in most of the studied countries except lung cancer in females and liver cancer in males, where increasing rates were observed in most countries. Rates decreased or stabilized in all countries for lung cancer in men and stomach cancer in both sexes. CONCLUSIONS: The findings reinforce the importance of implementing and strengthening resource-stratified and targeted cancer prevention and control programs in all parts of the world to further reduce or halt the rising cancer burden. IMPACT: The results may inform cancer prevention and treatment strategies and in so doing, reduce the marked global cancer disparities observed today.

Associations of Race and Ethnicity with Hepatocellular Carcinoma, Decompensation, and Mortality in US Veterans with Cirrhosis.

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.

Disparities in Hepatocellular Carcinoma Outcomes Among Subgroups of Asians and Pacific Islanders: A SEER Database Study.

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.

Impact of skeletal muscle volume on patients with BCLC stage-B hepatocellular carcinoma undergoing sorafenib therapy.

AIM: Skeletal muscle volume has been reported to be an important factor that determines overall survival (OS) and post-progression survival (PPS) in patients with hepatocellular carcinoma (HCC). However, the impact of skeletal muscle volume on HCC with Barcelona Clinic Liver Cancer (BCLC) stage B (BCLC-B) remains unclear. We conducted sub-analyses of a previous study on BCLC-B and compared our findings with data on HCC with BCLC stage C (BCLC-C). METHODS: We retrospectively enrolled 356 patients with HCC (BCLC-B, n = 78; and BCLC-C, n = 278) undergoing sorafenib therapy. Prognostic factors were analyzed using various parameters, including skeletal muscle volume. Muscle volume (MV) depletion was designated as less than the median value of the skeletal muscle index for each gender (cutoff value: 45.0 cm2 /m2 for male and 38.0 cm2 /m2 for female participants). RESULTS: Both OS and PPS showed no significant differences in patients with non-MV depletion and those with MV depletion in the BCLC-B group (Median OS [MST] 19.3 vs. 13.5 months [p = 0.348]; median PPS 9.7 vs. 10.8 months [p = 0.578]). In the BCLC-C group, patients with non-MV depletion had a significantly longer OS and PPS compared to patients with MV depletion (MST 12.4 vs. 9.0 months [p = 0.001] and median PPS 7.9 vs. 5.4 months [p = 0.002]). Multivariate analysis revealed that MV depletion was an independent prognostic factor of OS and PPS in the BCLC-C group but not in the BCLC-B group. CONCLUSIONS: Skeletal muscle volume showed little impact on the clinical outcomes of patients with BCLC-B undergoing sorafenib therapy.

Isolated Hepatitis B Core Antibody Positivity and Long-Term Liver-Related Mortality in Korea: A Cohort Study.

INTRODUCTION: Whether isolated hepatitis B core antibody (anti-HBc) positivity is a risk factor for long-term liver-related outcomes in hepatitis B virus (HBV)-endemic areas remains unclear. We aimed to investigate liver-related and liver cancer mortality of isolated anti-HBc positivity in Korean adults. METHODS: A cohort study comprised 609,299 Korean adults who underwent hepatitis B serologic markers, as a part of health examination. Liver-related and liver cancer mortality were determined using the National Death Records. RESULTS: During a median follow-up of 9.0 years (interquartile range, 5.5-13.7 years), 554 liver-related deaths were identified (liver-related mortality, 9.6 cases per 10 5 person-years). The prevalence of isolated anti-HBc positivity was 3.8% (n = 23,399) and was age-dependent. After adjustment for age, sex, and other confounders, hazard ratios (95% confidence interval) for liver-related mortality in isolated anti-HBc-positive and hepatitis B surface antigen-positive subjects compared with HBV-unexposed subjects were 1.69 (1.22-2.33) and 27.02 (21.45-34.04), respectively. These associations were pronounced in the analyses using liver cancer mortality as an outcome. Among isolated anti-HBc-positive patients, the risks of liver-related and liver cancer mortality were significantly higher in those with high fibrosis-4 scores compared with patients unexposed to HBV with the multivariable-adjusted hazard ratios (95% confidence interval) of 15.59 (9.21-26.37) and 72.66 (36.96-142.86), respectively. DISCUSSION: In this cohort of Korean adults, isolated anti-HBc positivity was associated with an increased risk of liver-related and liver cancer mortality, especially when accompanied by a high fibrosis score. Isolated anti-HBc positivity may be an independent risk factor for liver-related outcomes, especially in high-endemic areas.

New Pyroptosis -Associated Gene Signature for Overall Survival Forecast among Patients Suffering from Hepatocellular Carcinoma.

Due to the heterogeneity of tumors, we do not understand the given effect of pyroptosis on hepatocellular carcinoma (HCC) fully, particularly its influences on prognosis. The paper aims at exploring the prognostic value of pyroptosis-associated genes and its role in immune status in HCC. A multigene prognostic signature is set up by utilizing the least absolute shrinkage and choosing operator Cox exploration. The comparison of survival between different risk groups is made with the Kaplan-Meier exploration and Cox regression. LASSO Cox regression analysis is adopted to set up a pyroptosis-associated gene signature (CEP55 and MMP1). By comparing with the group at low risks, the high-risk group displayed greatly decreased OS. The fatidic ability of the prognostic gene signature is confirmed by the receiver-running feature curve analysis. According to multivariate Cox exploration, the risk mark is an independent predicting agent for OS. A new signature established with two pyroptosis-associated genes can be adopted for prognostic forecast and influence the immune situation in HCC.

Transarterial chemoembolization combined with camrelizumab for recurrent hepatocellular carcinoma.

PURPOSE: To evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with camrelizumab (hereafter, TACE-camrelizumab) in the treatment of patients with recurrent hepatocellular carcinoma (R-HCC) after curative resection. PATIENTS AND METHODS: R-HCC patients who underwent TACE plus camrelizumab or TACE-alone from January 2016 to August 2021 were retrospectively evaluated. Patients were assessed for tumor response, progression-free survival, survival rates and adverse events. RESULTS: Seventy-one patients were included in this study, including 20 patients in the TACE- camrelizumab group and 51 patients in the TACE-alone group. The objective response rate was 56.9% in the TACE-alone group and 40% in the TACE-camrelizumab group at 3 months (P = 0.201). The disease control rates were 84.3% in TACE-alone group and 80% in TACE-camrelizumab group at 3 months (P = 0.663). The progression-free survival (PFS) of the TACE-alone group was slightly longer than those of the TACE- camrelizumab group (9 months vs. 6 months). However, there were no statistically significant differences in the median PFS (P = 0.586). Similarly, there were no significant differences in the half-year and one-year survival rates (P = 0.304, P = 0.430). Multivariate analysis revealed that Neutrophil-to-lymphocyte ratio (NLR) was associated with PFS significantly. 75% patients developed at least one type of AEs related to camrelizumab in TACE-camrelizumab group, and no patients developed severe AEs. CONCLUSION: Comparing with TACE-Alone, the efficacy of TACE-camrelizumab for patients with R-HCC was similar. Meanwhile, the results of this study also indicated that TACE is still a better choice for patients with R-HCC.

Development of nomogram models of inflammatory markers based on clinical database to predict prognosis for hepatocellular carcinoma after surgical resection.

BACKGROUND: Inflammation plays a significant role in tumour development, progression, and metastasis. In this study, we focused on comparing the predictive potential of inflammatory markers for overall survival (OS), recurrence-free survival (RFS), and 1- and 2-year RFS in hepatocellular carcinoma (HCC) patients. METHODS: A total of 360 HCC patients were included in this study. A LASSO regression analysis model was used for data dimensionality reduction and element selection. Univariate and multivariate Cox regression analyses were performed to identify the independent risk factors for HCC prognosis. Nomogram prediction models were established and decision curve analysis (DCA) was conducted to determine the clinical utility of the nomogram model. RESULTS: Multivariate Cox regression analysis indicated that the prognostic nutritional index (PNI) and neutrophil-to-lymphocyte ratio (NLR) were independent prognostic factors of OS, and aspartate aminotransferase-to-platelet ratio (APRI) was a common independent prognostic factor among RFS, 1-year RFS, and 2-year RFS. The systemic inflammation response index (SIRI) was an independent prognostic factor for 1-year RFS in HCC patients after curative resection. Nomograms established and achieved a better concordance index of 0.772(95% CI: 0.730-0.814), 0.774(95% CI: 0.734-0.815), 0.809(95% CI: 0.766-0.852), and 0.756(95% CI: 0.696-0.816) in predicting OS, RFS, 1-year RFS, and 2-year RFS respectively. The risk scores calculated by nomogram models divided HCC patients into high-, moderate- and low-risk groups (P < 0.05). DCA analysis revealed that the nomogram models could augment net benefits and exhibited a wider range of threshold probabilities in the prediction of HCC prognosis. CONCLUSIONS: The nomograms showed high predictive accuracy for OS, RFS, 1-year RFS, and 2-year RFS in HCC patients after surgical resection. The nomograms could be useful clinical tools to guide a rational and personalized treatment approach and prognosis judgement.

ANP32 Family as Diagnostic, Prognostic, and Therapeutic Biomarker Related to Immune Infiltrates in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide, with high incidence and mortality rate. There is an urgent need to identify effective diagnostic and prognostic biomarkers for HCC. Members of the acidic leucine-rich nucleophosphoprotein 32 (ANP32) family, which mainly includes ANP32A, ANP32B, and ANP32E, are abnormally expressed and have prognostic value in certain cancers. However, the diagnostic, prognostic, and therapeutic value of ANP32 family members in HCC has not yet been fully studied. In this study, we identified the diagnostic and prognostic value of ANP32 family members in HCC. Transcriptome data from public databases, such as the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, suggested that ANP32A, ANP32B, and ANP32E were upregulated in HCC tissues, and high expression of ANP32 family members was associated with advanced pathologic stage and histologic grade. Our immunohistochemistry and western blot results further verified the differential expression of ANP32 family members. ANP32A, ANP32B, and ANP32E had an outstanding diagnostic potential. Survival analysis of HCC patients in TCGA databases demonstrated that ANP32A, ANP32B, and ANP32E were associated with poor overall survival (OS) and disease-specific survival (DSS). Univariate and multivariate Cox analyses suggested the capability of ANP32B and ANP32E to independently predict the OS and DSS of HCC patients. Gene set enrichment analysis (GSEA) showed that ANP32 family members were associated with immune response, epidermal cell differentiation, and stem cell proliferation. Expression of ANP32 family members was associated with immune cell infiltration and immune status in the tumor microenvironment of HCC, and patients with high ANP32 family expression had poor sensitivity to immunotherapy. Finally, we identified potential chemotherapy drugs for HCC patients with high ANP32 family expression by CellMiner database. This study suggested the diagnostic, prognostic, and therapeutic roles of the ANP32 family in HCC patients, providing potential therapeutic targets for HCC.