Hepatocellular Carcinoma Cases Research Articles

Aldo-keto reductase family 1 member B10 is regulated by nucleos(t)ide analogues for chronic hepatitis B

The number of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients persists even under nucleos(t)ide analogues (NAs) treatment. Aldo-keto reductase family 1 member B10 (AKR1B10) expression has been reported in advanced chronic liver diseases as well as cancer tissues. We observed an association between related to HCC incidence and serum AKR1B10 by analyzing patients under treatment with NAs. Serum AKR1B10 levels measured by ELISA were higher in HCC cases under NA treatment compared with non-HCC cases and were associated with lamivudine- and adefovir pivoxil-, but not entecavir- or tenofovir alafenamide-treated cases. The latter drugs did not increase AKR1B10 values even in HCC cases, suggesting that they influence the reduction of AKR1B10 in any cases. This analysis was supported by in-vitro examination, which showed reduced AKR1B10 expression by entecavir and tenofovir via immunofluorescence staining. In conclusion there was a relationship between HBV-related HCC incidence and AKR1B10 under nucleos(t)ide analogues, especially in the use of lamivudine and adefovir pivoxil, but entecavir and tenofovir had suppressive effects of AKR1B10.

Life span-associated ferroptosis-related genes identification and validation for hepatocellular carcinoma patients as hepatitis B virus carriers.

Hepatitis B virus (HBV)-infected population accounts for approximately 50% of all hepatocellular carcinoma (HCC) cases and has a relatively poor prognosis. Although the significant role of ferroptosis in the development and therapeutic response of various cancers has been validated, the key ferroptosis-related genes (FRGs) on the stratification of HBV-associated HCC are still unclear. Through the random forest, GSVA and Cox regression analyses, we established a comprehensive prognostic system covering multiple FRGs to elevate the predictive accuracy for the survival rate of HBV-related HCC using information obtained from public databases. The association between key FRGs and the immune microenvironment was evaluated, and the molecular mechanism was identified by GSEA and SNV analyses. Finally, the differential expression of key FRGs was validated by immunohistochemistry staining of patient tissue microarrays. Within the top 10 key FRGs, EPAS1 and GABARAPL1 were taken as protective factors, and SQLE, RAD51AP1, RPL8, CAPG, RRM2, SLC1A5, SLC38A1, and SRC were the other eight dangerous markers. Cox regression analysis combined with clinicopathological features indicated the independent prognostic efficacy of GSVA complex score based on these FRGs. In addition, key FRGs were related to immune and metabolic-related functions. Especially, the immunohistochemical analysis of SQLE in 50 clinical samples showed significantly higher expression in HBV+ HCC tissues. These results indicate that 10 FRGs may be potential biomarkers and therapeutic targets for long-term survival in HBV-related HCC.

Comparison of computed tomography and magnetic resonance imaging findings and histopathological features of macrotrabecular-massive hepatocellular carcinoma.

Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is a novel subtype of HCC, one of eight distinct subtypes, that accounts for 5% of all cases of HCC and is associated with a worse prognosis. Preoperative diagnosis of MTM-HCCs using imaging findings can facilitate patient treatment decision-making. The purpose of this study was to describe computed tomography (CT) and magnetic resonance imaging (MRI) findings of MTM-HCCs and compare these findings with histopathological features. This retrospective case-control study was performed at Shenzhen People's Hospital. The cohort included 17 patients with surgically confirmed MTM-HCCs and 232 patients with surgically confirmed non-MTM-HCCs who were enrolled by searching the pathological database from January 2018 to June 2022. CT and MRI findings were retrospectively analyzed and compared with pathological features. Student's t-test or Mann-Whitney U test for continuous variables and χ2 test or Fisher's exact test for categorical variables were implemented to compare imaging manifestations between MTM-HCCs and non-MTM-HCCs, as appropriate. Seventeen tumors with a mean diameter of 8.58±2.83 cm were identified in the 17 patients. In addition to the typical findings of hepatocellular carcinomas (HCCs), such as arterial phase hyperenhancement (APHE), wash out, restricted diffusion, capsule and non-uptake at the hepatobiliary phase (HBP), the most common findings in MTM-HCCs were necrosis in 11 patients (64.7%, 11/17), followed by intratumoral arteries in 6 patients (35.3%, 6/17), peritumoral arterial transitive enhancement in 3 patients (17.6%, 3/17) and peritumoral hypointensive areas at the HBP in 3 of 8 patients (37.5%, 3/8) who received gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) enhancement. The tumor size of non-MTM-HCCs was 5.26±1.94 cm, which was smaller than the 8.58±2.83 cm of MTM-HCCs (P<0.001). The frequency of necrosis and intratumoral arteries was significantly higher in MTM-HCCs than in non-MTM-HCCs (necrosis: 64.7% vs. 34.6%, P=0.012; intratumoral arteries: 47.1% vs. 19.7%, P=0.008). MTM-HCCs tend to be large in size with intratumoral artery and intratumoral necrosis, which are characteristics that may distinguish them from non-MTM-HCCs.

Artificial intelligence-based reticulin proportionate area - anovel histological outcome predictor in hepatocellular carcinoma.

Reticulin stain is used routinely in the histological evaluation of hepatocellular carcinoma (HCC). The goal of this study was to assess whether the histological reticulin proportionate area (RPA) in HCCs predicts tumour-related outcomes. We developed and validated a supervised artificial intelligence (AI) model that utilises a cloud-based, deep-learning AI platform (Aiforia Technologies, Helsinki, Finland) to specifically recognise and quantify the reticulin framework in normal livers and HCCs using routine reticulin staining. We applied this reticulin AI model to a cohort of consecutive HCC cases from patients undergoing curative resection between 2005 and 2015. A total of 101 HCC resections were included (median age = 68 years, 64 males, median follow-up time = 49.9 months). AI model RPA reduction of > 50% (compared to normal liver tissue) was predictive of metastasis [hazard ratio (HR) = 3.76, P = 0.004, disease-free survival (DFS, HR = 2.48, P < 0.001) and overall survival (OS), HR = 2.80, P = 0.001]. In a Cox regression model, which included clinical and pathological variables, RPA decrease was an independent predictor of DFS and OS and the only independent predictor of metastasis. Similar results were found in the moderately differentiated HCC subgroup (WHO grade 2), in which reticulin quantitative analysis was an independent predictor of metastasis, DFS and OS. Our data indicate that decreased RPA is a strong predictor of various HCC-related outcomes, including within the moderately differentiated subgroup. Reticulin, therefore, may represent a novel and important prognostic HCC marker, to be further explored and validated.

Aflatoxins in food products consumed in the Kingdom of Saudi Arabia: A preliminary dietary risk assessment.

Aflatoxins (AFs) are hepatotoxic, mutagenic, genotoxic, and immunosuppressive toxins. Several food commodities consumed in the Kingdom of Saudi Arabia (KSA) are susceptible to AF contamination because of improper storage practices and the warm and humid climate of the country. Therefore, the occurrence of AFs in 2388 food samples was measured and the estimated daily intake (EDI) of AFs in Saudi adults was assessed. The risks of AFB1 exposure were characterized using the margin of exposure (MoE) approach and by estimating the number of possible hepatocellular carcinoma (HCC) cases in the KSA. The results revealed that 12.1% of the analyzed samples were contaminated with AFs and the highest concentration of total AFs was observed in the nut and seed group. The mean EDI of AFB1 was estimated to be 0.21 and 0.55 ng/kg body weight (bw)/day for the lower bound (LB) and upper bound (UB) scenarios, respectively. The MoEs were estimated to be 1902.4 and 722.1, while the estimated liver cancer risk ranged from 0.002 to 0.008 cancer cases/year/100,000 persons. Based on the study's findings, contamination with AFs in the KSA is low; however, AFs are considered potent genotoxic contaminants, and therefore, exposure through food should be kept as low as possible.

Association of Statin Use With Risk of Liver Disease, Hepatocellular Carcinoma, and Liver-Related Mortality

Given the burden of chronic liver disease on the health care system, more information on the hepatoprotective association of statins in the general population is needed. To examine whether regular statin use is associated with a reduction in liver disease, particularly hepatocellular carcinoma (HCC) and liver-related deaths, in the general population. This cohort study used data from the UK Biobank (UKB) (individuals aged 37-73 years) collected from baseline (2006-2010) to the end of follow-up in May 2021, from the TriNetX cohort (individuals aged 18-90 years) enrolled from baseline (2011-2020) until end of follow-up in September 2022, and from the Penn Medicine Biobank (PMBB) (individuals aged 18-102 years) with ongoing enrollment starting in 2013 to the end of follow-up in December 2020. Individuals were matched using propensity score matching according to the following criteria: age, sex, body mass index, ethnicity, diabetes with or without insulin or biguanide use, hypertension, ischemic heart disease, dyslipidemia, aspirin use, and number of medications taken (UKB only). Data analysis was performed from April 2021 to April 2023. Regular statin use. Primary outcomes were liver disease and HCC development as well as liver-associated death. A total of 1 785 491 individuals were evaluated after matching (aged 55 to 61 years on average, up to 56% men, and up to 49% women). A total of 581 cases of liver-associated death, 472 cases of incident HCC, and 98 497 new liver diseases were registered during the follow-up period. Individuals were aged 55-61 years on average, with a slightly higher proportion of men (up to 56%). In UKB individuals (n = 205 057) without previously diagnosed liver disease, statin users (n = 56 109) had a 15% lower hazard ratio (HR) for the association of developing a new liver disease (HR, 0.85; 95% CI, 0.78-0.92; P < .001). In addition, statin users demonstrated a 28% lower HR for the association with liver-related death (HR, 0.72; 95% CI, 0.59-0.88; P = .001) and a 42% lower HR for the development of HCC (HR, 0.58; 95% CI, 0.35-0.96; P = .04). In TriNetX individuals (n = 1 568 794), the HR for the association of HCC was reduced even further for statin users (HR, 0.26; 95% CI, 0.22-0.31; P = .003). The hepatoprotective association of statins was time and dose dependent, with a significant association in PMBB individuals (n = 11 640) for incident liver diseases after 1 year of statin use (HR, 0.76; 95% CI, 0.59-0.98; P = .03). Taking statins was particularly beneficial in men, individuals with diabetes, and individuals with a high Fibrosis-4 index at baseline. Carriers of the heterozygous minor allele of PNPLA3 rs738409 benefited from statin use and had a 69% lower HR for the association with HCC (UKB HR, 0.31; 95% CI, 0.11-0.85; P = .02). This cohort study indicates substantial preventive associations of statins against liver disease, with an association with duration and dose of intake.

Cytomorphology of paediatric hepatocellular carcinoma: A useful diagnostic adjunct.

Hepatocellular carcinoma (HCC) is a common primary malignancy of the liver but is rare in the paediatric age group; thus, it may be misdiagnosed as the more common tumour, hepatoblastoma. Management varies in both these tumours, and pathological diagnosis thus plays an important role for definitive therapy. Only a few case reports available in the literature have described the cytological characteristics of paediatric HCC. The present study was thus planned to evaluate the cytomorphological features of paediatric HCC. Cases diagnosed with HCC on ultrasound-guided fine needle aspiration cytology over a period of 14 years were retrieved. The cases were evaluated for detailed cytological features including cellularity, architecture, sinusoidal wrapping, trabecular thickness, necrosis, anisonucleosis, chromatin, nucleoli, nuclear contours, bi- or multinucleation, intranuclear and intracytoplasmic inclusions, naked nuclei, extra-medullary haematopoiesis, monomorphism, and nuclear overlapping. Twelve cases of HCC were included in the study. The median age at diagnosis was 10 years. Serum alpha-fetoprotein level was raised in most of them. Five of the 12 cases were characterised as moderately differentiated, three as poorly differentiated, two as well differentiated, and two as the fibrolamellar type of HCC. Cytohistological correlation was performed in seven cases. Ultrasound-guided fine needle aspiration serves as a useful tool to diagnose paediatric HCC and differentiate it from other primary hepatic malignancies, especially hepatoblastoma which closely mimics HCC in this age group, as serum alpha protein levels and imaging findings are unable to distinguish these two tumours.

Daytime napping, nighttime sleeping duration, and risk of hepatocellular carcinoma and liver disease-related mortality

Background & AimsSleep duration has been linked to metabolic dysfunction and chronic inflammation, which may contribute to the development of liver cancer and chronic liver disease (CLD). However, little is known about the relationship between sleep or napping duration and hepatocellular carcinoma (HCC) risk and CLD mortality. MethodsWe followed 295,837 individuals in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study. We examined the associations of nighttime sleep duration and daytime napping duration with risk of HCC incidence and CLD mortality. Cox proportional hazards regression was used to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs). ResultsA total of 357 incident HCC cases and 578 CLD deaths were identified after a median follow-up time of 15.5 years. After adjusting for confounder factors, we found U-shaped associations of nighttime sleep duration with the incidence of HCC (HR<5 vs. 7–8 h = 2.00, 95% CI: 1.22–3.26 and HR≥9 vs. 7–8 h = 1.63, 95% CI: 1.04–2.65) and CLD mortality (HR<5 vs. 7–8 h = 1.78, 95% CI: 1.18–2.69 and HR≥9 vs. 7–8 h = 1.91, 95% CI: 1.35–2.70). Daytime napping was associated with higher risk of HCC (HR≥1 vs. non-nappers = 1.46, 95% CI: 1.04–2.06) and higher CLD mortality (HR≥1 h vs. non-nappers = 1.54, 95% CI: 1.18–2.01) compared with no napping. ConclusionsWe observed U-shaped associations for nighttime sleeping and risk of HCC and CLD mortality. Additionally, longer daytime napping duration was associated with higher risk of HCC and CLD death. Our study suggests that clinical follow up of individuals at risk for liver cancer or living with a liver disease should include information on nighttime and daytime sleep. Impact and implicationsSleep or napping duration may play a role in the development of liver cancer and chronic liver disease, but little is known about the relationship between them. In addition, abnormal sleep patterns in patients with chronic liver disease may further promote the development of liver disease, creating a vicious cycle. Our study suggests that clinical follow up of individuals at risk for liver cancer or living with a liver disease should include information on nighttime and daytime sleep, as they can be potentially important factors in the development and progression of liver disease.

Hepatocellular carcinoma complicated by spontaneous rupture

The paper presents a clinical case of hepatocellular carcinoma complicated by rupture. The underlying disease was asymptomatic prior to the development of complications. Despite blood loss of about 30-35% of circulating blood volume, hemorrhagic shock dominated the clinical picture of the acute condition. Neoplasm of the left hepatic lobe with necrosis and rupture was diagnosed by means of videolaparoscopy. Final hemostasis was impossible without liver resection. The tumor was excised within healthy tissues (R0). The authors performed a literature review and analysis. The value of the clinical case is determined by its rare complication.

MHC class I loss is associated with biliary/progenitor cell features and "cold" tumor-immune microenvironment in hepatocellular carcinoma.

Hepatocellular carcinomas (HCCs) with biliary/progenitor cell features frequently show increased programmed death-ligand 1 (PD-L1) expression, but their response to immunotherapy is not high. One possible explanation for this phenomenon could be the loss of major histocompatibility complex (MHC) class I expression on tumor cells, which impairs the presentation of tumor antigens to cytotoxic T cells. However, the potential correlation between MHC class I loss, biliary/progenitor cell features, and the tumor-immune microenvironment remains largely unexplored. Herein, we hypothesized that MHC class I loss could be associated with biliary/progenitor cell features and potentially impact the tumor-immune microenvironment. To evaluate this hypothesis and gain insight into the characteristics of tumor cells and the tumor-immune microenvironment in HCCs with MHC class I loss, we examined a consecutive series of 397 HCC cases. MHC class I loss was observed in 32 HCCs (8.1%). Lipid-less cytologic morphology was significantly associated with MHC class I loss (P = 0.02). CK19 expression and decreased ARG1 expression, both known as biliary/progenitor cell features, were significantly associated with MHC class I loss (P < 0.05). PD-L1 expression was irrelevant to the MHC class I status. HCCs with MHC class I loss exhibited significantly lower infiltration of CD8+, CD4+, CD20+, and FOXP3+ cells than those with intact MHC class I (all Ps < 0.01). Our study reveals an association between MHC class I loss, biliary/progenitor cell features, and a "cold" tumor-immune microenvironment in HCCs. These insights highlight the potential impact of MHC class I loss on tumor cells and the tumor-immune microenvironment.

BCL11B expression in hepatocellular carcinoma relates to chemosensitivity and clinical prognosis.

B-cell lymphoma/leukemia 11B (BCL11B) is a subunit of SWI/SNF chromatin remodeling complexes and functions in cell cycle regulation and apoptosis upon DNA replication stress and damages via transcription. Many malignancies were reported to exhibit changes in BCL11B gene expression; however, no study has focused on the relationship between BCL11B and hepatocellular carcinoma, which potentially exhibits DNA replication stress and damages upon its oncogenesis. Thus, in this study, we examined the molecular characterization of BCL11B expression in hepatocellular carcinoma. The cumulative progression-free survival and overall survival were significantly longer in the clinical cases of BCL11B-negative hepatocellular carcinoma than BCL11B-positve cases. Microarray and real-time PCR analyses in hepatocellular carcinoma cell lines indicated a correlation between BCL11B and GATA6, a gene reported to be correlated with oncogenic activities and resistance to anthracycline, which is often used for hepatocellular carcinoma chemotherapy. Consequently, BCL11B-overexpressing cell lines exhibited resistance to anthracycline in cell growth assays and the resistance has been evidenced by the increased expression of BCL-xL in cell lines. The results were supported by the analyses of human HCC samples showing the correlation between BCL11B and GATA6 expressions. Our results indicated that overexpression of BCL11B amplifies GATA6 expression in hepatocellular carcinoma in vitro and in vivo that leads to anti-apoptotic signal activation, and induces resistance to chemotherapy, which influenced the postoperative prognosis.

Loss of SFXN1 mitigates lipotoxicity and predicts poor outcome in non-viral hepatocellular carcinoma

Hepatocellular carcinoma (HCC) imposes a huge global burden, arising from various etiological factors such as hepatitis virus infection and metabolic syndrome. While prophylactic vaccination and antiviral treatment have decreased the incidence of viral HCC, the growing prevalence of metabolic syndrome has led to an increase in non-viral HCC. To identify genes downregulated and specifically associated with unfavorable outcome in non-viral HCC cases, screening analysis was conducted using publically available transcriptome data. Among top 500 genes meeting the criteria, which were involved in lipid metabolism and mitochondrial function, a serine transporter located on inner mitochondrial membrane SFXN1 was highlighted. SFXN1 protein expression was significantly reduced in 33 of 105 HCC tissue samples, and correlated to recurrence-free and overall survival only in non-viral HCC. Human HCC cells with SFXN1 knockout (KO) displayed higher cell viability, lower fat intake and diminished reactive oxygen species (ROS) production in response to palmitate administration. In a subcutaneous transplantation mouse model, high-fat diet feeding attenuated tumorigenic potential in the control cells, but not in the SFXN1-KO cells. In summary, loss of SFXN1 expression suppresses lipid accumulation and ROS generation, preventing toxic effects from fat overload in non-viral HCC, and predicts clinical outcome of non-viral HCC patients.

Tumor cuproptosis and immune infiltration improve survival of patients with hepatocellular carcinoma with a high expression of ferredoxin 1

BackgroundCuproptosis is a novel cell death pathway dependent on cellular copper ions and ferredoxin 1 (FDX1). Hepatocellular carcinoma (HCC) is derived from healthy liver as a central organ for copper metabolism. It remains no conclusive evidence whether cuproptosis is involved in survival improvement of patients with HCC.MethodA 365–liver hepatocellular carcinoma (LIHC) cohort with RNA sequencing data and paired clinical and survival information was obtained from the The Cancer Genome Atlas (TCGA) dataset. A retrospective cohort of 57 patients with HCC with stages I/II/III was collected by Zhuhai People’s Hospital from August 2016 to January 2022. Low- or high-FDX1 groups were divided according to the median value of FDX1 expression. Cibersort, single-sample gene set enrichment analysis, and multiplex immunohistochemistry analyzed immune infiltration in LIHC and HCC cohorts. Cell proliferation and migration of HCC tissues and hepatic cancer cell lines were evaluated using the Cell Counting Kit-8. Quantitative real-time PCR and RNA interference measured and downregulated FDX1 expression. Statistical analysis was conducted by R and GraphPad Prism software.ResultsHigh FDX1 expression significantly enhanced survival of patients with LIHC from the TCGA dataset, which was also demonstrated through a retrospective cohort with 57 HCC cases. Immune infiltration was different between the low– and high–FDX1 expression groups. Natural killer cells, macrophages, and B cells were significantly enhanced, and PD-1 expression was low in the high-FDX1 tumor tissues. Meanwhile, we found that a high expression of FDX1 decreased cell viability in HCC samples. HepG2 cells with FDX1 expression are sensitive to Cu2+, and interference of FDX1 promoted proliferation and migration of tumor cells. The consistent results were also demonstrated in Hep3B cells.ConclusionThis study reveals that cuproptosis and tumor immune microenvironment were together involved in improvement of survival in patients with HCC with a high expression of FDX1.

Association of circulating levels of soluble PD-1, PD-1 gene polymorphisms with HBV infection and HBV infection-associated hepatocellular carcinoma

Objective: To investigate the association of circulating sPD-1 level and PD-1 gene polymorphisms with HBV infection and HBV infection-associated hepatocellular carcinoma. Methods: A case-control study was conducted. A total of 237 chronic HBV infection cases and 138 HBV infection-associated hepatocellular carcinoma in the Department of Infectious Diseases of the First Hospital of Shanxi Medical University from 2018 to 2021 were selected as the case group. About 250 individuals who visited a hospital physical examination center for routine physical examination during the same period were selected as the control group. Plasma sPD-1 levels were measured by using an ELISA kit and genotyping was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The association of sPD-1 levels and PD-1 polymorphisms with HBV infection as well as HBV infection-associated hepatocellular carcinoma was analyzed by using logistic regression models after adjusting for age, sex, alcohol consumption, smoking, ALT and AST levels. The sPD-1 level and PD-1 polymorphisms were independent variables, and HBV infection was the dependent variable. Results: The age of 237 chronic HBV infections, 138 HBV infection-related liver cancer case subjects and 250 control subjects in the study was (49.1±10.8), (51.9±12.7) and (50.7±11.9) years, respectively. Multivariate logistic regression model analysis showed that with a 1 pg/ml increase in sPD-1 level, the OR (95%CI) values for the risk of incident HBV infection cases and HBV hepatocellular carcinoma cases were 1.92 (1.68-2.19) and 2.02 (1.69-2.40). For rs2227981, compared with the CC genotype, the TT genotype had a lower risk of HBV infection and liver cancer associated with HBV infection, with OR (95%CI) values of 0.45 (0.22-0.91) and 0.35 (0.14-0.91). For rs2227982, compared with the CC genotype, the CT and TT genotypes also had a lower risk of HBV infection [OR (95%CI) values of 0.72 (0.53-0.97) and 0.57 (0.35-0.93)] and HBV infection-related liver cancer [OR (95%CI) values of 0.64 (0.45-0.92) and 0.52 (0.29-0.93)]. Conclusions: Plasma sPD-1 levels and PD-1 gene polymorphisms are associated with HBV infection and HBV infection-associated hepatocellular carcinoma.

The current and future burden of hepatitis B in Switzerland: a modelling study.

Chronic hepatitis B infection (defined as sustained detection of hepatitis B virus [HBV] surface antigen [HBsAg] protein in serum) is a leading cause of cirrhosis, hepatocellular carcinoma and liver-related deaths. A situation analysis carried out by the Swiss Federal Office of Public Health estimated the HBsAg prevalence in Switzerland to be 0.53% (95% CI: 0.32-0.89%) in 2015 (~44,000 cases). A lower prevalence of chronic HBV in the younger generation and the adoption of universal coverage in the first year of life are expected to decrease the burden of HBV; however, a number of people in key populations (including migrants) remain undiagnosed and untreated, and infected individuals remain at risk of progressing to cirrhosis, hepatocellular carcinoma and death. Our primary objective was to examine the current and estimate the future disease burden of HBV in Switzerland and the impact of migration. The secondary objective was to estimate the impact of changing future treatment numbers. A modelling study was performed using an existing, validated model (PRoGReSs Model) applied to the Swiss context. Model inputs were selected through a literature search and expert consensus. Population data from the Federal Statistical Office were used alongside prevalence data from the Polaris Observatory to estimate the number of HBV infections among people born abroad. The PRoGReSs Model was populated with and calibrated to the available data and what-if scenarios were developed to explore the impact of intervention on the future burden of disease. A Monte Carlo simulation was used to estimate 95% uncertainty intervals (95% UIs). In 2020, there were an estimated 50,100 (95% UI: 47,500-55,000) HBsAg+ cases among people born abroad. Among people born in Switzerland, there were approximately 62,700 (UI: 58,900-68,400) total HBV infections (0.72% [UI: 0.68-0.79%] prevalence). Prevalence among infants and children under the age of 5 were both <0.1%. By 2030, prevalence of HBV is expected to decrease, although morbidity and mortality will increase. Increasing diagnosis (90%) and treatment (80% of those eligible) to meet the global health sector strategy on viral hepatitis programme targets could prevent 120 cases of hepatocellular carcinoma and 120 liver-related deaths. Thanks to the historical vaccination programmes and the continued rollout of universal 3-dose coverage in the first year of life, Switzerland is expected to exceed the global health sector strategy targets for the reduction of incidence. While overall prevalence is decreasing, the current diagnosis and treatment levels remain below global health sector strategy targets.

Accurate SARC-F Score in Patients with Liver Disease.

SARC-F is a well-accepted screening tool for sarcopenia. A SARC-F value of 1 point is reported to be more discriminating in identifying sarcopenia than 4 points (recommended cutoff point). The prognostic impact of the SARC-F score was investigated in patients with liver disease (LD, n = 269, median age = 71 years, 96 hepatocellular carcinoma (HCC) cases). Factors associated with SARC-F ≥ 4 points and SARC-F ≥ 1 point were also examined. In the multivariate analysis, age (p = 0.048), and Geriatric Nutritional Risk Index (GNRI) score (p = 0.0365) were significant factors linked to SARC-F ≥ 1 point. In our patients with LD, the SARC-F score is well correlated with the GNRI score. The 1-year cumulative overall survival ratio in patients with SARC-F ≥ 1 (n = 159) and SARC-F 0 (n = 110) was 78.3% and 90.1% (p = 0.0181). After excluding 96 HCC cases, similar tendencies were found (p = 0.0289). In the receiver operating curve (ROC) analysis based on the prognosis for the SARC-F score, the area under the ROC was 0.60. The sensitivity was 0.57, the specificity was 0.62, and the optimal cutoff point of the SARC-F score was 1. In conclusion, sarcopenia in LDs can be affected by nutritional conditions. A SARC-F score of ≥1 is more useful than a score of 4 in predicting the prognosis of patients with LD.

Two cases of unresectable hepatocellular carcinoma treated via atezolizumab and bevacizumab combination therapy

BackgroundTreatment of hepatocellular carcinoma (HCC) varies widely depending on the patient's condition. In recent years, combination therapy with immune checkpoint inhibitors has emerged as the treatment of choice due to its superior antitumor effects for unresectable HCC (uHCC). Conversion surgery (CS) after systemic chemotherapy is expected to be an effective treatment strategy for uHCC. Here, we report two cases of uHCC with bilateral porta hepatis invasion, in which atezolizumab plus bevacizumab therapy regressed the tumor invasion of the porta hepatis, followed by CS with R0 resection.Case presentationThe first patient—a 71-year-old man with S4 HCC—developed porta hepatis, and the tumor compressed the right portal vein and bile duct. R0 resection with left trihepatectomy was impossible because of insufficient liver function, and combination therapy using atezolizumab and bevacizumab was initiated. After ten courses of treatment, the tumor shrunk with regression of the porta hepatis contact, and segmentectomy of S4 was performed with a sufficient surgical margin. Histopathological findings showed that the primary tumor was mostly necrotic with no residual viable tumor cells. The second patient was a 72-year-old man with an S4 HCC extending to the porta hepatis. The patient’s condition was almost similar to that in the first case and required left tri-segmentectomy with R0 resection; however, insufficient liver function made liver resection impossible. An atezolizumab plus bevacizumab regimen was administered, and after seven courses of treatment, porta hepatis compression regressed, following which left lobectomy was performed with adequate surgical margins. The pathological diagnosis was moderately differentiated HCC, most of which was necrotic, and R0 resection was confirmed.ConclusionsAtezolizumab plus bevacizumab therapy has the potential to facilitate radical resection in patients with uHCC.

A resected case of giant pseudoglandular hepatocellular carcinoma that was challenging to distinguish from hepatic angiosarcoma, suspected to relate with exposure to vinyl chloride monomer

症例は80歳代男性．20歳頃から15年間，溶接業に従事した．PTP誤飲で当院救急外来受診された際に腹部単純CT検査で肝S2に8 cm大の巨大腫瘍を認めた．肝血管腫と診断したが，巨大であるために厳重経過観察とした．1カ月後に施行した腹部EOB-MRI検査では，同腫瘍は9.8 cm大に増大傾向で肝内にも多発する小病変が認められ，肝血管肉腫の可能性が疑われるも肝細胞癌の可能性も十分に考えられた．診断的意義も考えて肝左葉切除術を施行した．肉眼的には腫瘍内部は凝血塊で充満し一部隔壁を伴う腫瘍で，肝血管肉腫の可能性も十分に考えられた．病理組織学的には偽腺管構造を呈する中分化型肝細胞癌と診断した．偽腺管型の肝細胞癌は肝血管腫に非常に類似した画像所見を呈するために，特に塩化ビニルモノマー曝露歴を有する場合，肝血管腫と診断されている症例でも増大傾向を示すような症例では特に注意が必要であると思われた．

Risk factors, clinical characteristics, and treatment outcomes for hepatocellular carcinoma in Rwanda.

e16339 Background: Hepatocellular carcinoma (HCC) is increasing worldwide with limited treatment options, a poor prognosis, and survival rates of less than 5 years. In Sub-Saharan Africa, over 46,000 new cases are reported every year, and HCC is commonly associated with alcohol consumption, viral hepatitis, especially Hepatitis B (HBV) and C (HCV), aflatoxin exposure, obesity, type II diabetes, and HIV infection. In Rwanda, often young people are diagnosed with HCC in the late stages of the disease, and treatment options are limited. Rwanda has made great achievements in the prevention and treatment of HBV and HCV. However, there is a lack of data on HCC in Rwanda and its associated risk factors. In this study, we report the prevalence of common risk factors, available treatment options, and treatment outcomes among patients with HCC in Rwanda. Methods: This was a retrospective study of patients aged 18 years of age and above diagnosed with HCC from 2016 to 2021 in three tertiary hospitals: University Teaching Hospital of Kigali, King Faisal Hospital, and Rwanda Military Hospitals. Data were abstracted from patients’ paper charts and electronic medical records and recorded in REDCap and analyzed in STATA. Results: Overall, 219 individuals were included in the study. 32.9% were female, the median age was 32 (26–54) years, and 48.4% came from the capital city of Kigali. Only 13.3% of patients had histo-pathological confirmation of HCC, while 86.7 % were diagnosed clinically with radiological images, alpha-fetoprotein, and other clinical findings. The most common risk factors were HCV and HBV infection with a prevalence of 27.4% and 20.1%, respectively. HIV infection and diabetes mellitus were present in 6.9% and 6.2% of patients, respectively. More than 80% of patients had had clinical or ultrasound evidence of cirrhosis, including ascites or hepatic encephalopathy and only 8.9% of patients received Sorafenib, and no patient had surgical resection, ablation, or liver transplant. Only 15.1% of patients received palliative care with opiate therapy. Among all patient diagnosed with HCC, 36% died within 3 months of diagnosis. Conclusions: In this retrospective study of the three largest treatment centers in Rwanda, the majority of HCC cases occurred at a young age with a high rate of mortality. HBV and HCV were the most frequent risk factors, and the majority of patients had clinical characteristics of decompensated liver failure. There is a clear lack of diagnostic tools, most glaringly pathologic diagnosis, and an extreme lack of treatment options. Increased awareness for HBV and HCV prevention and screening as well as further studies on etiology of HCC cases and management are needed.

Clinicopathological Features of Hepatocellular Carcinoma with Metabolic Risk Factors.

This study aims to explore the pathological characteristics of metabolic-related hepatocellular carcinoma (HCC) and its correlation with metabolic factors. Fifty-one patients with liver cancer of unknown causes were enrolled. Biopsy of the liver and staining of the liver tissues with hematoxylin-eosin as well as special and immunohistochemical stains were performed. The histological subtypes of HCC were diagnosed based on the WHO Classification of Malignant Hepatocellular Tumors. The NAFLD activity score system was adopted for assessing the surrounding non-neoplastic liver tissues. Of the total, 42 (82.4%) patients were diagnosed with HCC, 32 had metabolic risk factors, 20 patients met the diagnostic criteria of the metabolic-associated fatty liver disease (MAFLD)-related HCC, and 40.6% (13/32) had liver cirrhosis. The incidence of cirrhosis (p = 0.033) and diabetes mellitus type 2 (p = 0.036) in patients with MAFLD-related HCC was notably higher than that in HCC patients with only metabolic risk factors. Among the 32 HCC cases with metabolic risk factors, trabecular type was the most prevalent, followed by steatohepatitis type, scirrhous type, solid type, pseudoglandular type, clear-cell type, and macrotrabecular type. The degree of tumor cells' swelling and ballooning was found to be positively related to the degree of fibrosis in the surrounding liver tissues (p = 0.011) as well as the proportion of cirrhosis (p = 0.004). Moreover, the degree of fibrosis in the surrounding liver tissues showed a negative correlation with the levels of serum cholesterol (p = 0.002), low-density lipoprotein (p = 0.002), ApoA1 (p = 0.009), ApoB (p = 0.022), total protein (p = 0.015), WBC count (p = 0.006), and PLT count (p = 0.015). Pathological characteristics of the tumor and adjacent non-neoplastic liver tissues of HCC with metabolic risk factors were found to be correlated with metabolic abnormalities.