Hepatocellular Carcinoma Cases Research Articles

Serum microRNA-16 as a potential biomarker for HCV-induced hepato-cellular carcinoma in Egyptian patients

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in the world. Two risk factors that cause 80–90% of HCC cases globally are chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). The diagnostic value of circulating microRNAs (miRNAs) in numerous tumors has been described. Our research assessed microRNA-16 (miR-16) as a novel biomarker in patients with HCV-induced HCC. The study included three groups. Group 1 included 55 individuals with cirrhosis caused by liver HCV infection in addition to HCC. Group 2 included 55 individuals with cirrhosis brought on by HCV infection. Group 3 included 55 normal control individuals. Expression of miR-16 in blood was assessed by real-time polymerase chain reaction (RT-PCR). The mean level of miR-16 was significantly different in the three groups, with group 1 having the greatest value (1.098 ± 0.647), followed by group 2 (1.1035 ± 0.8567) and group 3 (control subjects) having the lowest value (0.3842 ± 0.21485). The receiver operating characteristic (ROC) curve analysis showed that miR-16 had a higher diagnostic value at area under the curve (AUC) of 0.935 than alpha-feto protein (AUC of 0.859) to differentiate between HCC and control subjects. MiR-16 has a sensitivity of 81.82 % and a specificity of 69.09%, to distinguish between patients with liver cirrhosis and HCC patients. Our findings illustrated that circulating miR-16 can be proposed as a marker for detection of patients with HCV-induced HCC.

Efficacy of immune checkpoint inhibitors differs in various status of carcinoma: a study based on 29 cohorts with 3255 participants

BackgroundPre-clinical data have revealed that viral infection, such as Hepatitis B virus (HBV), Hepatitis C virus (HCV), and Human Papilloma virus (HPV), may lead to the development of “hot” or “immune-sensitive” tumors, which may impact the efficacy of immune checkpoint inhibitor (ICIs). Therefore, This study aimed to investigate the impact of viral status on the efficacy of ICIs.MethodsElectronic databases were searched to identify relevant trials. The primary endpoints were overall survival (OS) and progression-free survival (PFS) measured by hazard ratio (HR). Stratified analyses were accomplished based on viral types, treatment regimens, and patient locations.ResultsA total of 3255 participants were recruited, including 252 cases of gastric cancer, 156 cases of nasopharyngeal carcinoma, 1603 cases of hepatocellular carcinoma, and 1244 cases of head and neck squamous cell carcinoma. Pooled results demonstrated a significant association between viral infection and favorable outcomes in patients receiving ICIs, including improved OS [HR = 0.67, 95%CI (0.57–0.79), P < 0.0001], increased ORR [OR = 1.43, 95%CI (1.14–1.80), P = 0.0018], and a trend toward enhanced PFS [HR = 0.75, 95%CI (0.56–1.00), P = 0.05]. In subgroup analyses, patients treated with ICIs who were exposed to HBV/HCV or HPV infection exhibited an evidently superior OS without heterogeneity, compared to those without infection.ConclusionsThis study indicated that the presence of viral infection was evidently associated with improved outcomes in cancer patients undergoing ICIs, particularly in cases of HBV/HCV and HPV infections.

Paraneoplastic Syndromes in Hepatocellular Carcinoma, Epidemiology, and Survival: A Retrospective Seven Years Study.

Background and Objectives: Liver cancer poses a significant global health threat, ranking among the top three causes of cancer-related deaths. Patients with hepatocellular carcinoma (HCC) often present with symptoms associated with neoplasms or unusual clinical features such as paraneoplastic syndromes (PNS), including hypoglycemia, hypercholesterolemia, thrombocytosis, and erythrocytosis. Our study aimed to investigate the prevalence, clinical characteristics, and survival outcomes associated with PNS in HCC patients and assess each PNS's impact on patient survival. Materials and Methods: We conducted a retrospective analysis of PNS clinical features and survival among consecutive HCC patients diagnosed at our department over seven years, comparing them with HCC patients without PNS. The study involved a retrospective data evaluation from 378 patients diagnosed with HCC between January 2016 and October 2023. Results: We obtained a PNS prevalence of 25.7%, with paraneoplastic hypercholesterolemia at 10.9%, hypoglycemia at 6.9%, erythrocytosis at 4.5%, and thrombocytosis at 3.4%. Patients with PNS tended to be younger and predominantly male. Multivariate analysis revealed a strong correlation between PNS and levels of alpha-fetoprotein and tumor size, with diabetes also showing a significant statistical association (p < 0.05). Subgroup analysis based on specific paraneoplastic syndromes demonstrated shorter survival in patients with PNS, albeit without significant statistical differences, except for hypoglycemia (p < 0.0001). Matched analysis indicated a shorter survival rate for patients with PNS, although no significant statistical differences were observed. Conclusions: PNS are frequently observed in HCC cases and are associated with unfavorable prognoses and decreased survival rates due to their correlation with increased tumor burdens. However, they do not independently predict poor survival. The impact of individual PNS on HCC prognosis varies.

Advancing Korean nationwide registry for hepatocellular carcinoma: a systematic sampling approach utilizing the Korea Central Cancer Registry database.

Hepatocellular carcinoma (HCC) presents a substantial public health challenge in South Korea as evidenced by 10,565 new cases annually (incidence rate of 30 per 100,000 individuals), in 2020. Cancer registries play a crucial role in gathering data on incidence, disease attributes, etiology, treatment modalities, outcomes, and informing health policies. The effectiveness of a registry depends on the completeness and accuracy of data. Established in 1999 by the Ministry of Health and Welfare, the Korea Central Cancer Registry (KCCR) is a comprehensive, legally mandated, nationwide registry that captures nearly all incidence and survival data for major cancers, including HCC, in Korea. However, detailed information on cancer staging, specific characteristics, and treatments is lacking. To address this gap, the KCCR, in partnership with the Korean Liver Cancer Association (KLCA), has implemented a systematic approach to collect detailed data on HCC since 2010. This involved random sampling of 10-15% of all new HCC cases diagnosed since 2003. The registry process encompassed four stages: random case selection, meticulous data extraction by trained personnel, expert validation, anonymization of personal data, and data dissemination for research purposes. This random sampling strategy mitigates the biases associated with voluntary reporting and aligns with stringent privacy regulations. This innovative approach positions the KCCR and KLCA as foundations for advancing cancer control and shaping health policies in South Korea.

Changing etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide.

Approximately 80% of hepatocellular carcinoma (HCC) cases arise in sub-Saharan Africa and Eastern Asia, following a similarly high prevalence of chronic hepatitis B virus (HBV) carriers in these regions. The etiology and epidemiology of HCC have recently changed worldwide. Although HBV infection is the main contributor to HCC development, a slow but continuous decline in HBV infection rates has been reported since 1990. Owing to the widespread use of direct-acting antivirals, the incidence of hepatitis C virus-related HCC has remarkably decreased in Japan and European countries. In Korea, Taiwan, and Singapore, the incidence of HBV-related HCC has significantly decreased owing to vaccination against HBV. Globally, while HBV accounted for more than half of HCCs in 1990, this had decreased to 42% in 2019. In contrast, the proportion of patients with alcoholic- and nonalcoholic steatohepatitis (NASH) increased from 13% to 18% and from 5% to 6%, respectively. NASH-related HCC has characteristics that differ from those of virus-associated HCC. Compared with other etiologies, patients with NASHassociated HCC are older, have a higher body mass index, and have higher rates of type 2 diabetes mellitus, hypertension, hyperlipidemia, and cardiovascular disease. Nonalcoholic fatty liver disease (NAFLD)-associated HCC is also known to develop in the absence of cirrhosis, unlike alcohol-related and autoimmune liver diseases. Because patients with NAFLD usually have diabetes or obesity, surveying this population is challenging. Optimal selection of the target population and surveillance tools among patients with NAFLD needs to be determined.

Low-Carbohydrate Diet Score and Risk of Hepatocellular Carcinoma: Findings from a Prospective Cohort Study.

In a large cohort study of more than 63,000 Chinese Singaporeans, we found that a diet with lower carbohydrate and higher animal fat and protein was associated with increased risk of HCC, suggesting that dietary modification could be an effective strategy in primary prevention to reduce the HCC burden.

Abstract 4802: Accuracy of the GALAD serologic model in the diagnosis of hepatocellular carcinoma in Ghanaian patients

Abstract Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. In sub-Saharan Africa, HCC is the second most common cancer in men and the sixth in women. African patients present with HCC at a young age and at advanced stage of disease. Improved surveillance can increase early HCC detection. The GALAD score has good sensitivity in the diagnosis of HCC in Asia, Europe and North America, however, it has not been validated in an African cohort. The aim of this study was to assess the performance of the GALAD score in the diagnosis of HCC in Ghanaian patients. Methods: Clinical data from patients with cirrhosis (n=93) or HCC (n=78) from out-patient hepatology clinics at 3 teaching hospitals in Ghana were abstracted, and serum samples analyzed. A logistic regression model predicting HCC status based on GALAD score was constructed to obtain the Receiver Operating Characteristics (ROC) curve for GALAD. The area under the curve (AUC) with 95% confidence interval was calculated and used to assess the performance of the GALAD score in surveillance for HCC. Results: The median AFP (5010.2 vs. 3.4), L3% (28.3 vs. 0.3) and DCP (507.6 vs. 0.2) levels were all significantly higher among HCC cases than the controls (p&amp;lt;0.0001). The median GALAD score was also higher among HCC patients (8.0 vs. -4.1, p&amp;lt;0.0001). The AUC of the GALAD score in the diagnosis of HCC was 0.86 (95% CI 0.79 - 0.92). At a cut-off value of -0.37, the GALAD score had a sensitivity of 0.81 and a specificity of 0.86. In a re-fit of the logistic regression model, the most significant factors in the GALAD model in our cohort were AFP-L3% and log(DCP). The AUC of the new GALAD model after model selection was 0.89. Conclusion: The GALAD score can be used to detect HCC in Ghana and has the potential to improve HCC surveillance in low-resource settings in sub-Saharan Africa. Citation Format: Yvonne Ayerki Nartey, Ju Dong Yang, Tyler Zemla, Joshua Ayawin, Shadrack Osei Asibey, Mohamed El-Kassas, Sally Afua Bampoh, Amoako Duah, Adwoa Agyei-Nkansah, Yaw Asante Awuku, Mary Yeboah Afihene, Hiroyuki Yamada, Jun Yin, Amelie Plymoth, Lewis Rowland Roberts. Accuracy of the GALAD serologic model in the diagnosis of hepatocellular carcinoma in Ghanaian patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4802.

Abstract 822: A retrospective study on the disparities of hepatocellular carcinoma

Abstract Background: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and the third leading cause of cancer-related deaths worldwide. Studies report that the incidence of, and mortality from HCC vary significantly by age, sex, and race/ethnicity; however, disparities in the expression level of tumor biomarkers, liver functions, lipid profiles, and comorbidities have not been thoroughly investigated among subpopulations of patient with HCC. Methods: A retrospective study was conducted to review 247 serial HCC cases enrolled in the University of Mississippi Medical Center during June 2000 to May 2023. The entire HCC population was stratified into subpopulations by race, gender, age and BMI. Then comparisons were performed between two corresponding subpopulations in the expression level of HCC-related biomarkers including Alpha-FP, liver functions including albumin, ALT, AST, and ALP, plasma lipid profiles including cholesterol, and comorbidity conditions including cirrhosis in benign liver tissues, smoking, alcohol using, and illness with viral hepatitis. Two-tailed Student’s T-test was used to calculate the difference in mean values, and Chi-Square Test was used to compare the difference in rates or percentages. The significant p value was set at p&amp;lt;0.05. Results: In total 247 HCC cases, males were 178 (72.1%) and females were 69 (27.9%) with a male to female ratio of 2.6:1; black patients were 108 (43.7%), white patients were 127 (51.4%), and others were 4.9%. The mean age was 59.6 years and mean BMI was 27.04. AFP was the only one of detected tumor biomarkers showing disparities: it was significantly higher in patients of male (p=0.026), younger age (p&amp;lt;0.0001), lower BMI (p=0.039), smokers (p=0.0325) and illness with viral hepatitis (p=0.0007). Disparities in liver functions included: 1) AST was significantly higher in Black HCC patients (p=0.027); 2) no statistical difference of liver functions in gender; 3) younger HCC patients had significantly lower level of Albumin (p=0.006), and higher levels of ALT (p=0.014) and AST (p=0.0032); 4) HCC patients with lower BMI also had lower level of Albumin (p=0.015), and higher levels of AST (p=0.0480 and ALP (p=0.0057). There was no statistical difference of plasma lipid profiles between subpopulations, Black HCC patients except that Black HCC patients had significantly higher levels of cholesterol (p=0.0006) and HDL (p=0.048). In comorbidity, Black HCC patients had higher rates of alcohol using and existence of cirrhosis; and male HCC patients had higher rates of smoking, alcohol usage and viral hepatitis. Conclusions: HCC patients are greatly disparate in the expression level of tumor biomarkers, liver functions, plasma lipid profiles and comorbidity conditions between subpopulations stratified by race, gender, age and BMI. These results could provide useful information for clinical management and prognosis of patients with HCC. Citation Format: Xinchun Zhou, Barrett Aldridge, Nazar Rahmanov, Zhirong Liu, Jinghe Mao, Neha Varshney. A retrospective study on the disparities of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 822.

Abstract 845: Population attributable fraction of cancer incidence due to infectious agents in 2020 in the Republic of Korea

Abstract Purpose: Earlier in 2009, National Cancer Center Korea estimated population attributable fraction (PAF) of cancer incidence due to infectious agents as 24.5% in men and 15.4% in women. This study aimed to investigate the proportion of cancer incidence attributable to infectious agents in the Korean population as of 2020. Materials and Methods: We organized the Consensus Committee to establish strategy and methodology of PAF estimation. Based on the consensus, infectious agents and cancer sites for PAF estimation were selected according to the IARC List of classification with sufficient evidence in human. As a result, infectious agents included hepatitis B and C virus (HBV and HCV), Helicobacter pylori (H. pylori), human papilloma virus (HPV), Clonorchis sinensis (C.sinensis), Epstein Barr virus, and human immunodeficiency virus, and cancer sites included hepatocellular carcinoma (HCC), cholangiocarcinoma (CCC), gastric cancer, pancreatic cancer, cervical cancer, and non-Hodgkin lymphoma. The PAF was calculated by using Levin’s formula including exposure prevalence and relative risks (RRs). Exposure prevalence data were collected from literature review of studies in Korean population in 2005 or earlier, assuming at least 15 years of latent period from risk exposure to cancer development. We performed systematic review for cohort studies and case-control studies which investigated RRs or ORs of cancer due to infectious agents in Korean population. Pooled RRs were estimated by meta-analysis of RRs or ORs by using random-effects model. Results: The fractions of all cancer incidence attributable to infectious agents were estimated to be 13.5% and 7.1% in men and women, respectively. The reduction in PAFs of cancer incidence due to infection in 2020 compared to 2009 is considered due to decrease in exposure prevalence. The major findings regarding infectious agents with large PAFs are as the following. We found that the fractions of HCC cases attributable to HBV infection were 47.7% and 38.4% for cancer incidence in men and women, respectively. The estimated PAFs of gastric cancer due to H. pylori were 40.4% in men and 38.2% in women. C. sinensis was related to 9.8% of CCC cases in men and 5.2% in women. A total of 77.7% of cervical cancer incidence was attributed to HPV infection. Conclusion: Although the total PAF due to infection has decreased over the last decade, infection still contributes a substantial fraction to cancer incidence in Korea. These recent estimates of cancer burden due to infection are important for planning and evaluating the national cancer prevention programs. Citation Format: Kyung-Shin Lee, Hwa Jin Lee, Yoon-Jung Choi, Moran Ki, Aesun Shin, Jong-Hun Kim, Sue-Kyung Park, So-Seul Sung, Sung Ji Moon, Hong Gwan Seo, Jin-Kyoung Oh, Jeong-Soo Im. Population attributable fraction of cancer incidence due to infectious agents in 2020 in the Republic of Korea [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 845.

Abstract 4865: Income dynamics and the risk of hepatocellular carcinoma in individuals with type 2 diabetes: A nationwide population-based cohort study

Abstract Introduction: Type 2 diabetes (T2D) is associated with over 2 times increased risk of hepatocellular carcinoma (HCC). Low-income status is associated with a higher risk of developing HCC, more advanced stage, and mortality. Evidence is limited on whether income dynamics are associated with the risk of developing HCC in individuals with T2D who are susceptible to income changes. We examined whether income levels and income changes are associated with HCC risk. Methods: Using representative data from the Korean National Health Insurance Service (NHIS), 2,227,893 adults with T2D (aged ≥ 20 years) without a cancer history were included between 2015-2016. Income levels were measured based on health insurance premiums and categorized into 4 levels (quartiles [Q], 1 [low income], to 4 [high income]). These quartiles excluded the very low-income individuals who qualified as Medical Aids beneficiaries (MAB), which comprised a 5th income category. To identify income change, income levels were collected annually from the baseline year backward 4 years. The incident HCC, defined based on ICD-10 codes and special reimbursement codes, was identified until December 2020. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated to assess the association between income parameters and HCC after adjusting for sociodemographic factors, comorbidities, and diabetes duration and treatment. Income parameters included 1) the baseline income status, 2) the cumulative number of years being in each income level, and 3) changes in income level between the two time points (4 years ago vs. baseline). Results: During follow-up (median, 3.9 years), 9,887 HCC cases developed. Individuals who had experienced at least one episode of MAB during the five years showed a significantly higher HCC risk than those who had never qualified as MAB (HRs ranging from 1.52 to 2.01). In contrast, individuals who had experienced high-income status (Q4) during the five years had a lower HCC risk than those who had never experienced (HRs ranging from 0.79 to 0.92; HRn=5 years vs. n=0 years 0.79, 95% CI 0.75-0.83; P for trend &amp;lt;0.05). Individuals in the low-income status (MAB-Q1) at the first assessment (4 years ago) but experienced increased income had a reduced risk of HCC, which linearly declined with increasing income rise. Also, those who experienced a substantial increase in income up to the top quartile (Q4) had the lowest HCC risk (HR 0.73, 95% CI 0.60-0.88; P for trend&amp;lt;0.05) than those who maintained the low-income status. Conclusions: Experiencing any very low- or high-income state was independently associated with increased or decreased HCC risk. Improved income levels among those in the low-income status had an inverse linear association with reduced HCC risk. Our findings underline the need for increased public policy awareness of the impact of income dynamics on HCC risk in adults with T2D. Citation Format: Jongha Baek, Benjamin C. Amick III, Clare C. Brown, Mario Schootman, Marie-Rachelle Narcisse, Seung-Hyun Ko, Pearl A. McElfish, Michael R. Thomsen, Seong-Su Lee, Kyungdo Han, Yong-Moon Mark Park. Income dynamics and the risk of hepatocellular carcinoma in individuals with type 2 diabetes: A nationwide population-based cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4865.

Abstract 6982: The roles of NDRG1 in HCC progression and its clinical significance

Abstract Background: Hepatocellular carcinoma (HCC) is prevalent globally and the third leading cause of cancer-related mortality. N-myc downstream regulated 1 (NDRG1) was found to be tumor promoting in some cancers while suppressive in others. The expression of NDRG1 is induced by stress signals such as DNA damage and hypoxia. In HCC, it has been found to promote proliferation and metastasis. Contradictory results, however, were also suggested on the functions of NDRG1. Methods: Our own HCC cohort and multiple publicly available databases were examined for NDRG1 expression and clinicopathologic correlation. NDRG1 expression under hypoxic conditions was investigated. Various functional assays were performed for NDRG1-knockdown HCC cell lines Huh-7 and PLC/PRF/5. Results: With RT-qPCR analysis on our 102 pairs of patients’ HCC tumor and corresponding non-tumorous liver samples, we found NDRG1 to be upregulated in HCC tumors. Similarly, RNA-sequencing analysis comparing 41 pairs of samples confirmed NDRG1 enrichment in HCC tumors. The upregulation was significantly and positively correlated with the absence of tumor encapsulation and cellular differentiation. These were further supported by TCGA and ICGC databases, in which upregulation of NDRG1 was significantly correlated with poor HCC patient overall survival. Interestingly, in the TCGA database, only 17% of the HCC cases were inferred to have copy number amplification of NDRG1 gene while NDRG1 mutations were rarely found. As hypoxia is a major tumor microenvironmental factor in HCC, we investigated NDRG1’s expression level in HCC cells under hypoxic or normoxic conditions and found significant increase in NDRG1 expression under hypoxic environment. We further found that NDRG1 knockdown inhibited cell proliferation, self-renewal ability, and migration. RT-qPCR analysis found lower LGR5 and SOX2 expression upon NDRG1 knockdown. This is in line with the positive correlation between NDRG1 and various cancer stemness-related gene expression, including LGR5, CD24, MYC, SOX2, and NOTCH1, in TCGA database. Lastly, in the resected HCC tumors on which spatial transcriptomics using Visium 10X and single-cell RNA-sequencing using Chromium 10X were performed, we found NDRG1 enrichment in both tumors cells and cancer associated fibroblasts (CAFs). Conclusion: NDRG1 was found to be significantly upregulated in HCC cells in our in-house cohort and publicly available databases. NDRG1 consistently promotes various oncogenic features of HCC cells, including proliferation, self-renewal ability, and migration. In addition, NDRG1 was found to be enriched in both the HCC cells and CAFs. Citation Format: Jingyi Lu, Lu Tian, Yu-Man Tsui, Xia Wong, Qingyang Zhang, Daniel Wai-Hung Ho, Irene Oi-Lin Ng. The roles of NDRG1 in HCC progression and its clinical significance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6982.

Optimizing LI-RADS: ancillary features screened from LR-3/4 categories can improve the diagnosis of HCC on MRI

ObjectiveTo determine the high-efficiency ancillary features (AFs) screened from LR-3/4 lesions and the HCC/non-HCC group and the diagnostic performance of LR3/4 observations.Materials and methodsWe retrospectively analyzed a total of 460 patients (with 473 nodules) classified into LR-3-LR-5 categories, including 311 cases of hepatocellular carcinoma (HCC), 6 cases of non-HCC malignant tumors, and 156 cases of benign lesions. Two faculty abdominal radiologists with experience in hepatic imaging reviewed and recorded the major features (MFs) and AFs of the Liver Imaging Reporting and Data System (LI-RADS). The frequency of the features and diagnostic performance were calculated with a logistic regression model. After applying the above AFs to LR-3/LR-4 observations, the sensitivity and specificity for HCC were compared.ResultsThe average age of all patients was 54.24 ± 11.32 years, and the biochemical indicators ALT (P = 0.044), TBIL (P = 0.000), PLT (P = 0.004), AFP (P = 0.000) and Child‒Pugh class were significantly higher in the HCC group. MFs, mild-moderate T2 hyperintensity, restricted diffusion and AFs favoring HCC in addition to nodule-in-nodule appearance were common in the HCC group and LR-5 category. AFs screened from the HCC/non-HCC group (AF-HCC) were mild–moderate T2 hyperintensity, restricted diffusion, TP hypointensity, marked T2 hyperintensity and HBP isointensity (P = 0.005, < 0.001, = 0. 032, p < 0.001, = 0.013), and the AFs screened from LR-3/4 lesions (AF-LR) were restricted diffusion, mosaic architecture, fat in mass, marked T2 hyperintensity and HBP isointensity (P < 0.001, = 0.020, = 0.036, < 0.001, = 0.016), which were not exactly the same. After applying AF-HCC and AF-LR to LR-3 and LR-4 observations in HCC group and Non-HCC group, After the above grades changed, the diagnostic sensitivity for HCC were 84.96% using AF-HCC and 85.71% using AF-LR, the specificity were 89.26% using AF-HCC and 90.60% using AF-LR, which made a significant difference (P = 0.000). And the kappa value for the two methods of AF-HCC and AF–LR were 0.695, reaching a substantial agreement.ConclusionWhen adjusting for LR-3/LR-4 lesions, the screened AFs with high diagnostic ability can be used to optimize LI-RADS v2018; among them, AF-LR is recommended for better diagnostic capabilities.

Detection of hepatocellular carcinoma methylation markers in salivary DNA.

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

Spinal Cord Infarction Following Transarterial Chemoembolization of Hepatocellular Carcinoma with Chest Wall Metastasis: A Case Report and Review of the Literature

Spinal cord infarction (SCI) is a rare but detrimental complication following transarterial chemoembolization (TACE). The case report presented a case of hepatocellular carcinoma (HCC) involving the lateral chest wall for which the patient underwent TACE, targeted at the right ninth intercostal artery. After the intervention, the patient fully developed complete spinal cord syndrome immediately after TACE. Magnetic resonance images of the spinal cord showed abnormal hyperintense lesions on T2-weighted images involving the anterior and central part of the 9th to 11th thoracic spinal cord, compatible with SCI. Although corticosteroids were not administered, the patient’s condition subsequently improved, being capable of walking with a gait aid. SCI after TACE is a possible disabling adverse event. To prevent this complication, the collateral vessels of the spinal arteries, such as the intercostal arteries, should be avoided. Furthermore, monitoring for the symptoms of SCI, especially in the first 24 hours after the intervention, should also be done in all TACE cases. Keywords: Spinal cord injury; Spinal cord infarction; Transarterial chemoembolization; Hepatocellular carcinoma; Case report

Meta-analysis: Incidence of cirrhosis and hepatocellular carcinoma in patients with Fontan palliation.

The Fontan palliation is the final stage of surgery for many children born with univentricular physiology. Almost all Fontan patients develop liver fibrosis which may eventually lead to cirrhosis and hepatocellular carcinoma (HCC). These are important causes of morbidity and mortality in these patients. We performed a systematic review and meta-analysis to assess the incidence of cirrhosis and HCC in Fontan patients and stratify it based on time since surgery. A literature search of seven databases identified 1158 records. Studies reporting the number of cirrhosis and HCC cases in Fontan patients and time since Fontan surgery were included. In the cirrhosis cohort, we included only those studies where all patients underwent liver biopsy. A total of 23 studies were included: 12 and 13 studies in the cirrhosis and HCC cohorts, respectively, with two studies included in both cohorts. The incidence of cirrhosis was 0.97 per 100 patient-years (95% CI 0.57-1.63), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 1.61 per 100 patient-years (95% CI 1.24-2.08) and 32.2% (95% CI 25.8%-39.4%), respectively. The incidence of HCC was 0.12 per 100 patient-years (95% CI 0.07-0.21), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 0.20 per 100 patient-years (95% CI 0.12-0.35) and 3.9% (95% CI 2.2%-6.8%), respectively. Only about 70% of patients with HCC (20/28) had underlying cirrhosis. The incidence of cirrhosis and HCC increases over time, especially at ≥20 years post Fontan surgery. Studies are needed to further identify at-risk patients in order to streamline surveillance for these highly morbid conditions.

Clinical significance of small nuclear ribonucleoprotein U1 subunit 70 in patients with hepatocellular carcinoma.

Small nuclear ribonucleoprotein U1 subunit 70 (SNRNP70) as one of the components of the U1 small nuclear ribonucleoprotein (snRNP) is rarely reported in cancers. This study aims to estimate the application potential of SNRNP70 in hepatocellular carcinoma (HCC) clinical practice. Based on the TCGA database and cohort of HCC patients, we investigated the expression patterns and prognostic value of SNRNP70 in HCC. Then, the combination of SNRNP70 and alpha-fetoprotein (AFP) in 278 HCC cases was analyzed. Next, western blotting and immunohistochemistry were used to detect the expression of SNRNP70 in nucleus and cytoplasm. Finally, Cell Counting Kit-8 (CCK-8) and scratch wound healing assays were used to detect the effect of SNRNP70 on the proliferation and migration of HCC cells. SNRNP70 was highly expressed in HCC. Its expression was increasingly high during the progression of HCC and was positively related to immune infiltration cells. Higher SNRNP70 expression indicated a poor outcome of HCC patients. In addition, nuclear SNRNP70/AFP combination could be a prognostic biomarker for overall survival and recurrence. Cell experiments confirmed that knockdown of SNRNP70 inhibited the proliferation and migration of HCC cells. SNRNP70 may be a new biomarker for HCC progression and HCC diagnosis as well as prognosis. SNRNP70 combined with serum AFP may indicate the prognosis and recurrence status of HCC patients after operation.

Hepatitis C Elimination in Rwanda: Progress, Feasibility, and Economic Evaluation

ObjectivesIn 2018, Rwanda launched a national program to eliminate the hepatitis C virus (HCV). We aim to assess the impact of the program to date and identify strategies to achieve the World Health Organization’s HCV elimination goals by 2030. MethodsWe developed a microsimulation model to simulate Rwanda’s HCV epidemic from 2015 through 2050 and evaluated temporal trends in HCV infection, prevalence, mortality, and the total cost of care for scenarios that could achieve HCV elimination by 2030. ResultsBetween 2018 and 2022, over 7 million people were screened for HCV, and 60 000 were treated. The study projected that Rwanda could achieve HCV elimination as early as 2027. A feasible strategy of an annual screening rate of 15% and a treatment rate of 100% would achieve all World Health Organization elimination goals by 2028, requiring screening an additional 4 million people and treating 23 900 patients by 2030. The elimination strategy costs $25 million for screening and diagnosis and $21 million for treatment from 2015 to 2050. The national program would avert 4900 hepatocellular carcinoma cases and 6700 HCV-related deaths and save the health system $25.33 million from 2015 to 2050. ConclusionsRwanda is poised to become one of the first countries in the world to eliminate HCV. Rwanda’s program serves as a blueprint for other countries in the African region. By rapid screening and treatment scale-up (eg, by leveraging HIV platforms) and by drug price negotiations, HCV elimination is not only feasible but can be cost-saving in low-income settings.

Laparoscopic liver resection is superior to radiofrequency ablation for small hepatocellular carcinoma: a systematic review and meta-analysis of propensity score-matched studies.

The approach in small hepatocellular carcinoma (HCC) is controversial, no prospective randomized trials to compare ablative or surgical approaches. We compared the surgical and oncological outcomes after laparoscopic hepatectomy (LH) and radiofrequency ablation (RFA) in small HCC patients based on matched cohort studies that performed propensity score matching (PSM). We systemically searched the PubMed, Cochrane Library, Embase, Web of Science, and the Chinese BioMedical Literature (CBM) databases. All published propensity score-matched studies that compared LH and RFA for small HCC were included in this study. Eight studies with a total of 1273 small HCC cases were included. The results of the meta-analysis revealed that there was no significant difference in the 1- year overall survival (OS) rate between the two groups, whereas the LH group had significantly higher 3- year overall survival rate (RR = 1.14, 95% CI 1.08-1.20, p < 0.00001) as well as 1- and 3-year disease-free survival (DFS) rates (RR = 1.31, 95% CI 1.22-1.42, p < 0.00001; RR = 1.66, 95% CI 1.46-1.90, p < 0.00001) than the RFA group. Meanwhile, the local recurrence rate and intrahepatic distant recurrence rate were significantly lower in the LH group than in the RFA group (RR = 0.29, 95% CI 0.20-0.42, p < 0.00001; RR = 0.67, 95% CI 0.49-0.92, p = 0.01). In comparison with the LH group, the RFA group had a lower incidence of overall and major postoperative complications (RR = 1.81, 95% CI 1.47-2.24, p < 0.00001; RR = 2.76, 95% CI 1.48-5.12, p = 0.001), but there was no significant difference in postoperative mortality between the two groups. In addition, further comparison of single postoperative complications showed that the incidence of ascites was lower in the RFA group than in the LH group (RR = 3.62, 95% CI 1.64-7.96, p = 0.001), whereas there was no significant difference in the incidence of postoperative bleeding, abdominal infection and bile leakage between the two groups (RR = 3.50, 95% CI 0.74-16.61, p = 0.11; RR = 5.00, 95% CI 0.59-42.23, p = 0.14; RR = 4.00, 95% CI 0.45-35.23, p = 0.21). Besides, the hospital stay was shorter in the RFA group than in the LH group (MD = 4.29, 95% CI 2.06-6.53, p = 0.0002). Our meta-analysis demonstrated that in comparison with RFA in the treatment of small HCC, LH provided superior long-term OS and DFS together with lower rates of local and intrahepatic distant recurrence after surgery. However, RFA was associated with better short-term outcomes.

Cost-Effectiveness of Strategies for Treatment Timing for Perinatally Acquired Hepatitis C Virus

Prevalence of chronic hepatitis C virus (HCV) infection among pregnant people is increasing in the US. HCV is transmitted vertically in 7% to 8% of births. Direct-acting antiviral (DAA) therapy was recently approved for children with HCV who are 3 years or older. The clinical and economic impacts of early DAA therapy for young children with HCV, compared with treating at older ages, are unknown. To develop a state-transition model to project clinical and economic outcomes for children with perinatally acquired HCV to investigate the cost-effectiveness of treating at various ages. The study team modeled the natural history of perinatally acquired HCV to simulate disease progression and costs of a simulated a cohort of 1000 US children with HCV from 3 years old through death. Added data were analyzed January 5, 2021, through July 1, 2022. The study compared strategies offering 8 weeks of DAA therapy at 3, 6, 12, or 18 years old, as well as a comparator of never treating HCV. Outcomes of interest include life expectancy from 3 years and average lifetime per-person health care costs. Other clinical outcomes include cases of cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma (HCC). The study team projected that treating HCV at 3 years old was associated with lower mean lifetime per-person health care costs ($148 162) than deferring treatment until 6 years old ($164 292), 12 years old ($171 909), or 18 years old ($195 374). Projected life expectancy was longest when treating at 3 years old (78.36 life years [LYs]) and decreased with treatment deferral until 6 years old (76.10 LYs), 12 years old (75.99 LYs), and 18 years old (75.46 LYs). In a cohort of 1000 children with perinatally acquired HCV, treating at 3 years old prevented 89 projected cases of cirrhosis, 27 cases of HCC, and 74 liver-related deaths compared with deferring treatment until 6 years old. In sensitivity analyses, increasing loss to follow-up led to even greater clinical benefits and cost savings with earlier treatment. These study results showed that DAA therapy for 3-year-old children was projected to reduce health care costs and increase survival compared with deferral until age 6 years or older. Measures to increase DAA access for young children will be important to realizing these benefits.

Chemoembolization as first-line treatment for hepatocellular carcinoma invading segmental portal vein with tumour burden limited to a monosegmental level.

To evaluate the safety and effectiveness of chemoembolization for hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT) confined to a monosegment of the liver. A total of 192 treatment-naive patients who received chemoembolization between March 2008 and January 2023 as a first-line treatment for locally advanced HCC with PVTT limited to a monosegment were retrospectively analysed. Overall survival (OS) and the identification of pretreatment risk factors related to OS were investigated using Cox regression analysis. Complications, radiologic tumour response, and progression-free survival (PFS) following chemoembolization were investigated. After chemoembolization, the 1-, 3-, and 5-year OS rates were 86%, 48%, and 39%, respectively, and the median OS was 33 months. Multivariable analyses revealed four significant pretreatment risk factors: infiltrative HCC (P = .02; HR, 1.60), beyond the up-to-11 criteria (P = .002; HR, 2.26), Child-Pugh class B (P = .01; HR, 2.35), and serum AFP ≥400 ng/mL (P = .01; HR, 1.69). The major complication rate was 5%. Of the 192 patients, 1 month after chemoembolization, 35% achieved a complete response, 47% achieved a partial response, 11% had stable disease, and 7% showed progressive disease. The median PFS after chemoembolization was 12 months. Chemoembolization shows high safety and efficiency, and contributes to improved survival in patients with HCC with PVTT confined to a monosegment. Four risk factors were found to be significantly associated with improved survival rates after chemoembolization in patients with HCC with PVTT confined to a monosegment. (1) Although systemic therapy with a combination of atezolizumab and bevacizumab (Atezo-Bev) is recommended as the first-line treatment when HCC invades the portal vein, chemoembolization is not infrequently performed in HCC cases in which tumour burden is limited. (2) Our study cohort (n=192) had a median OS of 33 months and a 5% major complication rate following chemoembolization, findings in the range of candidates typically accepted as ideal for chemoembolization. Thus, patients with HCC with PVTT confined to a monosegment may be good candidates for first-line chemoembolization.