Assessment of disease control rate and safety of sorafenib in targeted therapy for advanced liver cancer.

OBJECTIVE: The clinical efficacy and safety of sorafenib in patients with advanced liver cancer (ALC) were evaluated based on transarterial chemoembolization (TACE). METHODS: 92 patients with ALC admitted to our hospital from May 2020 to August 2022 were randomly rolled into a control (Ctrl) group and an observation (Obs) group, with 46 patients in each. Patients in the Ctrl group received TACE treatment, while those in the Obs group received sorafenib molecular targeted therapy (SMTT) on the basis of the treatment strategy in the Ctrl group (400 mg/dose, twice daily, followed by a 4-week follow-up observation). Clinical efficacy, disease control rate (DCR), survival time (ST), immune indicators (CD3+, CD4+, CD4+/CD8+), and adverse reactions (ARs) (including mild fatigue, liver pain, hand-foot syndrome (HFS), diarrhea, and fever) were compared for patients in different groups after different treatments. RESULTS: the DCR in the Obs group (90%) was greatly higher to that in the Ctrl group (78%), showing an obvious difference (P < 0.05). The median ST in the Obs group was obviously longer and the median disease progression time (DPT) was shorter, exhibiting great differences with those in the Ctrl group (P < 0.05). Moreover, no great difference was observed in laboratory indicators between patients in various groups (P > 0.05). After treatment, the Obs group exhibited better levels in all indicators. Furthermore, the incidence of ARs in the Obs group was lower and exhibited a sharp difference with that in the Ctrl group (P < 0.05). CONCLUSION: SMTT had demonstrated good efficacy in patients with ALC, improving the DCR, enhancing the immune response of the body, and reducing the incidence of ARs, thereby promoting the disease outcome. Therefore, it was a treatment method worthy of promotion and application.

ICG-Fluorescence Imaging for Margin Assessment During Minimally Invasive Colorectal Liver Metastasis Resection.

Importance: Unintended tumor-positive resection margins occur frequently during minimally invasive surgery for colorectal liver metastases and potentially negatively influence oncologic outcomes. Objective: To assess whether indocyanine green (ICG)-fluorescence-guided surgery is associated with achieving a higher radical resection rate in minimally invasive colorectal liver metastasis surgery and to assess the accuracy of ICG fluorescence for predicting the resection margin status. Design, Setting, and Participants: The MIMIC (Minimally Invasive, Indocyanine-Guided Metastasectomy in Patients With Colorectal Liver Metastases) trial was designed as a prospective single-arm multicenter cohort study in 8 Dutch liver surgery centers. Patients were scheduled to undergo minimally invasive (laparoscopic or robot-assisted) resections of colorectal liver metastases between September 1, 2018, and June 30, 2021. Exposures: All patients received a single intravenous bolus of 10 mg of ICG 24 hours prior to surgery. During surgery, ICG-fluorescence imaging was used as an adjunct to ultrasonography and regular laparoscopy to guide and assess the resection margin in real time. The ICG-fluorescence imaging was performed during and after liver parenchymal transection to enable real-time assessment of the tumor margin. Absence of ICG fluorescence was favorable both during transection and in the tumor bed directly after resection. Main Outcomes and Measures: The primary outcome measure was the radical (R0) resection rate, defined by the percentage of colorectal liver metastases resected with at least a 1 mm distance between the tumor and resection plane. Secondary outcomes were the accuracy of ICG fluorescence in detecting margin-positive (R1; <1 mm margin) resections and the change in surgical management. Results: In total, 225 patients were enrolled, of whom 201 (116 [57.7%] male; median age, 65 [IQR, 57-72] years) with 316 histologically proven colorectal liver metastases were included in the final analysis. The overall R0 resection rate was 92.4%. Re-resection of ICG-fluorescent tissue in the resection cavity was associated with a 5.0% increase in the R0 percentage (from 87.4% to 92.4%; P < .001). The sensitivity and specificity for real-time resection margin assessment were 60% and 90%, respectively (area under the receiver operating characteristic curve, 0.751; 95% CI, 0.668-0.833), with a positive predictive value of 54% and a negative predictive value of 92%. After training and proctoring of the first procedures, participating centers that were new to the technique had a comparable false-positive rate for predicting R1 resections during the first 10 procedures (odds ratio, 1.36; 95% CI, 0.44-4.24). The ICG-fluorescence imaging was associated with changes in intraoperative surgical management in 56 (27.9%) of the patients. Conclusions and Relevance: In this multicenter prospective cohort study, ICG-fluorescence imaging was associated with an increased rate of tumor margin-negative resection and changes in surgical management in more than one-quarter of the patients. The absence of ICG fluorescence during liver parenchymal transection predicted an R0 resection with 92% accuracy. These results suggest that use of ICG fluorescence may provide real-time feedback of the tumor margin and a higher rate of complete oncologic resection.

Assessment of the Clinical Value of Platelet-to-Lymphocyte Ratio in Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is associated with higher mortality as a result of poor prognosis and unavailability of effective treatment options. This study retrospectively analyzed the clinical value of platelet-to-lymphocyte ratio (PLR) to aid in differentiating early hepatocellular carcinoma from liver cirrhosis patients. Three hundred and nine (309) patients including 155 patients with hepatocellular carcinoma (HCC) and 154 patients with liver cirrhosis were enrolled in this study. General clinical characteristics and blood parameters of each patient were collected, calculated, and retrospectively analyzed. Mann-Whitney U test was calculated to compare the two groups. Receiver operating characteristics (ROC) curve was performed to investigate the diagnostic potential of PLR in the prediction of HCC at a cut-off with high accuracy (area under the curve [AUC]) > 0.80. Hemoglobin (HB) concentration, red blood cell (RBC) count, neutrophil (NEU) count, platelet count, platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) were significantly higher in the HCC patients than in the liver cirrhosis patients (p < 0.05). ROC curve analysis showed that the AUC, optimal cut-off value, sensitivity, and specificity of PLR to predict HCC patients were 0.912, 98.7, 81.2%, and 80.6% respectively. The results suggest that PLR is a potential biomarker that can be used to predict early HCC.

Social Inequities in the Survival of Liver Cancer: A Nationwide Cohort Study in Korea, 2007-2017.

BACKGROUND: To analyze the effects of socioeconomic status (type of insurance and income level) and cancer stage on the survival of patients with liver cancer in Korea. METHODS: A retrospective cohort study was constructed using data from the Healthcare Big Data Platform project in Korea between January 1, 2007, and December 31, 2017. A total of 143,511 patients in Korea diagnosed with liver cancer (International Classification of Diseases, 10th Revision [ICD-10] codes C22, C220, and C221) were followed for an average of 11 years. Of these, 110,443 died. The patient's insurance type and income level were used as indicators of socioeconomic status. Unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a Cox proportional hazards regression model to analyze the relationship between the effects of sex, age, and cancer stage at first diagnosis (Surveillance, Epidemiology, and the End Results; SEER), type of insurance, and income level on the survival of patients with liver cancer. The interactive effects of the type of insurance, income level, and cancer stage on liver cancer death were also analyzed. RESULTS: The lowest income group (medical aid) showed a higher risk for mortality (HR (95% CI); 1.37 (1.27-1.47) for all patients, 1.44 (1.32-1.57) for men, and 1.16 (1.01-1.34) for women) compared to the highest income group (1-6) among liver cancer (ICD-10 code C22) patients. The risk of liver cancer death was also higher in the lowest income group with a distant cancer stage (SEER = 7) diagnosis than for any other group. CONCLUSION: Liver cancer patients with lower socioeconomic status and more severe cancer stages were at greater risk of death. Reducing social inequalities is needed to improve mortality rates among patients in lower social class groups who present with advanced cancer.

Medicaid expansion and palliative care for advanced-stage liver cancer.

BACKGROUND: Medicaid expansion (ME) has contributed to transforming the United States healthcare system. However, its effect on palliative care of primary liver cancers remains unknown. This study aimed to evaluate the association between ME and the receipt of palliative treatment in advanced-stage liver cancer. METHODS: Patients diagnosed with stage IV hepatocellular carcinoma or intrahepatic cholangiocarcinoma were identified from the National Cancer Database and divided into pre-expansion (2010-2013) and postexpansion (2015-2019) cohorts. Logistic regression identified predictors of palliative treatment. Difference-in-difference (DID) analysis assessed changes in palliative care use between patients living in ME states and patients living in non-ME states. RESULTS: Among 12,516 patients, 4582 (36.6%) were diagnosed before expansion, and 7934 (63.6%) were diagnosed after expansion. Overall, rates of palliative treatment increased after ME (18.1% [pre-expansion] vs 22.3% [postexpansion]; P < .001) and are more pronounced among ME states. Before expansion, only cancer type and education attainment were associated with the receipt of palliative treatment. Conversely, after expansion, race, insurance, location, cancer type, and ME status (odds ratio [OR], 1.23; 95% CI, 1.06-1.44; P = .018) were all associated with palliative care. Interestingly, the odds were higher if treatment involved receipt of pain management (OR, 2.05; 95% CI, 1.23-2.43; P = .006). Adjusted DID analysis confirmed increased rates of palliative treatment among patients living in ME states relative to non-ME states (DID, 4.4%; 95% CI, 1.2-7.7; P = .008); however, racial disparities persist (White, 5.6; 95% CI, 1.4-9.8; P = .009; minority, 2.6; 95% CI, -2.5 to 7.6; P = .333). CONCLUSION: The implementation of ME contributed to increased rates of palliative treatment for patients residing in ME states after expansion. However, racial disparities persist even after ME, resulting in inequitable access to palliative care.

Tislelizumab versus sorafenib as first-line treatment for advanced hepatocellular carcinoma in China: a cost-effectiveness analysis.

Objective: The goal of this study is to compare the cost-effectiveness of tislelizumab and sorafenib as first-line treatment for advanced hepatocellular carcinoma in China. Methods: A comprehensive cost-effectiveness analysis was undertaken within the framework of a partitioned survival model to accurately gage the incremental cost-effectiveness ratio (ICER) of tislelizumab compared to sorafenib. The model incorporated relevant clinical data and all survival rates were from RATIONALE-301 trials. The stability of the partitioned survival model was assessed by performing one-way and two-way sensitivity analyses. Results: The total cost incurred for the tislelizumab treatment was $16181.24, whereas the sorafenib was $14306.87. The tislelizumab regimen resulted in a significant increase of 0.18 quality-adjusted life years (QALYs) and an extra cost of $1874.37 as compared to chemotherapy. The ICER was $10413.17 per QALY, which was found to be below the willingness-to-pay (WTP) threshold of $37304.34/QALY. The results of the sensitivity analysis found that no fluctuations in any of the factors affected our results, even when these parameters fluctuated. Conclusion: Tislelizumab appears to be a cost-effective first-line treatment for advanced hepatocellular carcinoma when compared to sorafenib in China. These findings can inform decision-making processes regarding the selection of the most cost-effective treatment option for advanced hepatocellular carcinoma.

Predicting the Risk of Morbidity by GLIM-Based Nutritional Assessment and Body Composition Analysis in Oncologic Abdominal Surgery in the Context of Enhanced Recovery Programs : The PHase Angle Value in Abdominal Surgery (PHAVAS) Study.

BACKGROUND: Preoperative nutritional status and body structure affect short-term prognosis in patients undergoing major oncologic surgery. Bioimpedance vectorial analysis (BIVA) is a reliable tool to assess body composition. Low BIVA-derived phase angle (PA) indicates a decline of cell membrane integrity and function. The aim was to study the association between perioperative PA variations and postoperative morbidity following major oncologic upper-GI surgery. PATIENTS AND METHODS: Between 2019 and 2022 we prospectively performed BIVA in patients undergoing surgical resection for pancreatic, hepatic, and gastric malignancies on the day before surgery and on postoperative day (POD) 1. Malnutrition was defined as per the Global Leadership Initiative on Malnutrition criteria. The PA variation (ΔPA) between POD1 and preoperatively was considered as a marker for morbidity. Uni and multivariable logistic regression models were applied. RESULTS: Overall, 542 patients with a mean age of 64.6 years were analyzed, 279 (51.5%) underwent pancreatic, 201 (37.1%) underwent hepatobiliary, and 62 (11.4%) underwent gastric resections. The prevalence of preoperative malnutrition was 16.6%. The overall morbidity rate was 53.3%, 59% in those with ΔPA < -0.5 versus 46% when ΔPA ≥ -0.5. Age [odds ratio (OR) 1.11; 95% confidence interval (CI) (1.00; 1.22)], pancreatic resections [OR 2.27; 95% CI (1.24; 4.18)], estimated blood loss (OR 1.20; 95% CI (1.03; 1.39)], malnutrition [OR 1.77; 95% CI (1.27; 2.45)], and ΔPA [OR 1.59; 95% CI (1.54; 1.65)] were independently associated with postoperative complications in the multivariate analysis. CONCLUSIONS: Patients with preoperative malnutrition were significantly more likely to develop postoperative morbidity. Moreover, a decrease in PA on POD1 was independently associated with a 13% increase in the absolute risk of complications. Whether proactive interventions may reduce the downward shift of PA and the complication rate need further investigation.

Cost-utility analysis of atezolizumab combined with bevacizumab for unresectable hepatocellular carcinoma in Thailand.

BACKGROUND: Clinical trials have proven the efficacy and safety of atezolizumab combined with bevacizumab (A+B) in treating unresectable hepatocellular carcinoma (uHCC). This study aimed to assess the cost-utility of A+B compared to best supportive care (BSC) among uHCC patients in Thailand. METHODS: We conducted a cost-utility analysis from a societal perspective. We used a three-state Markov model to estimate relevant costs and health outcomes over the lifetime horizon. Local cost and utility data from Thai patients were applied. All costs were adjusted to 2023 values using the consumer price index. We reported results as incremental cost-effectiveness ratios (ICERs) in United States dollars ($) per quality-adjusted life year (QALY) gained. We discounted future costs and outcomes at 3% per annum. We then performed one-way sensitivity analysis and probabilistic sensitivity analysis to assess parameter uncertainty. The budget impact was conducted to estimate the financial burden from the governmental perspective over a five-year period. RESULTS: Compared to BSC, A+B provided a better health benefit with 0.8309 QALY gained at an incremental lifetime cost of $45,357. The ICER was $54,589 per QALY gained. The result was sensitive to the hazard ratios for the overall survival and progression-free survival of A+B. At the current Thai willingness-to-pay (WTP) threshold of $4,678 per QALY gained, the ICER of A+B remained above the threshold. The projected budgetary requirements for implementing A+B in the respective first and fifth years would range from 8.2 to 27.9 million USD. CONCLUSION: Although A+B yielded the highest clinical benefit compared with BSC for the treatment of uHCC patients, A+B is not cost-effective in Thailand at the current price and poses budgetary challenges.

Determination and risk assessment of aflatoxin B1 in the kernel of imported raw hazelnuts from Eastern Azerbaijan Province of Iran.

Aflatoxin B1 (AFB1) is widespread and seriously threatens public health worldwide. This study aimed to investigate AFB1 in imported hazelnut samples in northwest of Iran (Eastern Azerbaijan Province) using High-Performance Liquid Chromatography with a Fluorescent Detector (HPLC-FLD). In all tested samples AFB1 was detected. The mean concentration of AFB1 was 4.20 µg/kg and ranged from 3.145 to 8.13 µg/kg. All samples contained AFB1 levels within the maximum acceptable limit except for one sample. Furthermore, the human health risk assessment of AFB1 from consuming imported hazelnuts by Iranian children and adults was evaluated based on the margin of exposure (MoE) and quantitative liver cancer risk approaches. The MoE mean for children was 2529.76, while for adults, it was 8854.16, indicating a public health concern. The present study found that the risk of developing liver cancer among Iranian children was 0.11100736 per 100,000 people, and in the Iranian adult population was 0.0314496 cancers per 100,000 people. Since environmental conditions potentially affect aflatoxin levels in nuts, countries are advised to monitor aflatoxin contents in imported nuts, especially from countries with a conducive climate for mold growth.

Comparison of the LiMAx test vs. the APRI+ALBI score for clinical utility in preoperative risk assessment in patients undergoing liver surgery - A European multicenter study.

INTRODUCTION: Posthepatectomy liver failure (PHLF) remains the main reason for short-term mortality after liver surgery. APRI+ALBI, aspartate aminotransferase to platelet ratio (APRI) combined with albumin-bilirubin grade (ALBI), score and the liver function maximum capacity test (LiMAx) are both established preoperative (preop) liver function tests. The aim of this study was to compare both tests for their predictive potential for clinically significant PHLF grade B and C (B+C). MATERIALS AND METHODS: 352 patients were included from 4 European centers. Patients had available preop APRI+ALBI scores and LiMAx results. Predictive potential for PHLF, PHLF B+C and 90-day mortality was compared using receiver operating characteristic (ROC) curve analysis and calculation of the area under the curve (AUC). Published cutoffs of ≥ -2.46 for APRI+ALBI and of <315 for LiMAx were assessed using chi-squared test. RESULTS: APRI+ALBI showed superior predictive potential for PHLF B+C (N = 34; AUC = 0.766), PHLF grade C (N = 20; AUC = 0.782) and 90-day mortality (N = 15; AUC = 0.750). When comparing the established cutoffs of both tests, APRI+ALBI outperformed LiMAx in prediction of PHLF B+C (APRI+ALBI ≥2.46: Positive predictive value (PPV) = 19%, negative predictive value (NPV) = 97%; LiMAx <315: PPV = 3%, NPV = 90%) and 90-day mortality (APRI+ALBI ≥2.46: PPV = 12%, NPV = 99%; LiMAx <315: PPV = 0%, NPV = 94%) CONCLUSION: In our analysis, APRI+ALBI outperformed LiMAx measurement in the preop prediction of PHLF B+C and postoperative mortality, at a fraction of the costs, manual labor and invasiveness.

Comprehensive assessment of regulatory T-cells-related scoring system for predicting the prognosis, immune microenvironment and therapeutic response in hepatocellular carcinoma.

INTRODUCTION: Regulatory T cells (Tregs) play important roles in tumor immunosuppression and immune escape. The aim of the present study was to construct a novel Tregs-associated biomarker for the prediction of tumour immune microenvironment (TIME), clinical outcomes, and individualised treatment in hepatocellular carcinoma (HCC). METHODS: Single-cell sequencing data were obtained from the three independent cohorts. Cox and LASSO regression were utilised to develop the Tregs Related Scoring System (TRSSys). GSE140520, ICGC-LIRI and CHCC cohorts were used for the validation of TRSSys. Kaplan-Meier, ROC, and Cox regression were utilised for the evaluation of TRSSys. The ESTIMATE, TIMER 2.0, and ssGSEA algorithm were utilised to determine the value of TRSSys in predicting the TIME. GSVA, GO, KEGG, and TMB analyses were used for mechanistic exploration. Finally, the value of TRSSys in predicting drug sensitivity was evaluated based on the oncoPredict algorithm. RESULTS: Comprehensive validation showed that TRSSys had good prognostic predictive efficacy and applicability. Additionally, ssGSEA, TIMER and ESTIMATE algorithm suggested that TRSSys could help to distinguish different TIME subtypes and determine the beneficiary population of immunotherapy. Finally, the oncoPredict algorithm suggests that TRSSys provides a basis for individualised treatment. CONCLUSIONS: TRSSys constructed in the current study is a novel HCC prognostic prediction biomarker with good predictive efficacy and stability. Additionally, risk stratification based on TRSSys can help to identify the TIME landscape subtypes and provide a basis for individualized treatment options.

Assessment of the mode of action of perchloroethylene-induced mouse liver tumors.

Perchloroethylene (PCE) is used as a solvent and chemical intermediate. Following chronic inhalation exposure, PCE selectively induced liver tumors in mice. Understanding the mode of action (MOA) for PCE carcinogenesis in mice is important in defining its possible human cancer risk. The proposed MOA is based on the extensive examination of the peer-reviewed studies that have assessed the mouse liver effects of PCE and its major oxidative metabolite trichloroacetic acid (TCA). Similar to PCE, TCA has also been demonstrated to liver tumors selectively in mice following chronic exposure. The Key Events (KE) of the proposed PCE MOA involve oxidative metabolism of PCE to TCA [KE 1]; activation of the peroxisome proliferator-activated receptor alpha (PPARα) [KE 2]; alteration in hepatic gene expression including cell growth pathways [KE 3]; increase in cell proliferation [KE 4]; selective clonal expansion of hepatic preneoplastic foci [KE 5]; and formation of hepatic neoplasms [KE 6]. The scientific evidence supporting the PPARα MOA for PCE is strong and satisfies the requirements for a MOA analysis. The PPARα liver tumor MOA in rodents has been demonstrated not to occur in humans; thus, human liver cancer risk to PCE is not likely.

Incidence and Costs of Clinically Significant Events with Systemic Therapy in Patients with Unresectable Hepatocellular Carcinoma: A Retrospective Cohort Study.

INTRODUCTION: Systemic therapies have been associated with clinically significant events (CSEs) in patients with unresectable hepatocellular carcinoma (uHCC). We evaluated the incidence of CSEs (bleeding, clotting, encephalopathy, and portal hypertension), and their impact on healthcare resource utilization (HCRU) and costs, in patients with uHCC treated with first-line (1L) atezolizumab plus bevacizumab (A + B), lenvatinib (LEN), or sorafenib (SOR) in the USA. METHODS: A retrospective cohort study was performed using medical/pharmacy claims from Optum® Clinformatics® Data Mart. Patients diagnosed with HCC who initiated 1L A + B between June 01, 2020 and December 31, 2020 or LEN/SOR between January 01, 2016 and May 31, 2020 were included. Outcomes included incidence rates of CSEs, HCRU, and costs. Subgroup analysis was performed in patients with no CSEs or ≥ 1 CSE. RESULTS: In total, 1379 patients were selected (A + B, n = 271; LEN, n = 217; SOR, n = 891). Clotting (incidence rate per 100 patient-years [PY] 94.9) and bleeding (88.1 per 100 PY) were the most common CSEs in the A + B cohort. The most common CSEs in the LEN cohort were clotting (78.6 per 100 PY) and encephalopathy (66.3 per 100 PY). Encephalopathy (73.0 per 100 PY) and portal hypertension (72.3 per 100 PY) were the most common CSEs in the SOR cohort. Mean total all-cause healthcare costs per patient per month (PPPM) were $32,742, $35,623, and $29,173 in the A + B, LEN, and SOR cohorts, respectively. Mean total all-cause healthcare costs PPPM were higher in patients who had ≥ 1 CSE versus those who did not (A + B $34,304 versus $30,889; LEN $39,591 versus $30,621; SOR $31,022 versus $27,003). CONCLUSION: Despite improved efficacy of 1L systemic therapies, CSEs remain a concern for patients with uHCC, as well as an economic burden to the healthcare system. Newer treatments that reduce the risk of CSEs, while improving long-term survival in patients with uHCC, are warranted.

Certain treatments for liver cancer can cause serious side effects, including bleeding, blood clots, brain injury (encephalopathy), or increased blood flow to the liver (portal hypertension). We used an insurance database to find out how often these events, known as clinically significant events, occurred in people with liver cancer who were given treatments that target the immune system (immunotherapy) or specific proteins involved in cancer growth and survival (targeted therapy). The study included 1379 patients treated with atezolizumab (immunotherapy) plus bevacizumab (targeted therapy), or lenvatinib or sorafenib alone (both targeted therapies), as their first treatment. Clotting and bleeding were the most common clinically significant events in patients treated with atezolizumab plus bevacizumab, whereas clotting and encephalopathy were the most common clinically significant events with lenvatinib, and encephalopathy and portal hypertension were the most common clinically significant events with sorafenib. On average, for every 100 patients treated for 1 year, there were more than 50 of each of these events. Average healthcare costs per patient per month ranged from around $29,000 to around $36,000 in the three different treatment groups, and were higher in people who had at least one clinically significant event. These results suggest that clinically significant events are common in people with liver cancer who are given various types of treatment. As well as raising concerns for patient safety, these events result in higher costs to healthcare systems. Therefore, newer treatments that are less likely to cause clinically significant events, while improving survival in patients with liver cancer, are needed.

Occurrence of mycotoxins in meat alternatives: Dietary exposure, potential health risks, and burden of disease.

This study aimed to present the occurrence of sixteen mycotoxins in 105 meat alternatives based on wheat, legumes, and vegetables from Italy. The targeted mycotoxins were aflatoxins (AFB1, AFB2, AFG1, AFG2), fumonisins B1 and B2 (FB1, FB2), alternariol (AOH), alternariol monomethyl ether (AME), tentoxin (TEN), ochratoxin A (OTA), zearalenone (ZEN), T-2/HT-2 toxin, deoxynivalenol (DON), enniatin B (ENNB), and beauvericin (BEA). The occurrence of mycotoxins was between 0% (AFB2) - 97.4% (ENNB). Mycotoxin co-occurrence varied from binary combinations up to mixtures of twelve. To assess the dietary exposure and potential health risks we simulated the replacement of meat consumption for Italian consumers with meat alternatives. The cumulative exposure to Alternaria mycotoxins and trichothecenes indicated a potential health risk while the exposure to aflatoxins and ochratoxin A indicated a potential health concern related to liver and renal cancer in the model scenario. Moreover, we estimated the risk of liver cancer from exposure to AFB1 and quantified the potential burden using Disability-Adjusted Life Years (DALYs). Luckily, the potential risk of liver cancer was low between 0 and 0.05/100,000 individuals with an associated burden of disease of 0.83 DALYs/100,000 individuals. Taking into consideration the presence of meat alternatives on the food market and the ongoing shift towards plant-based diets there is a need for continuous monitoring to keep the occurrence at safe levels. More attention is needed from the regulatory side for policymakers to consider the legislations of mycotoxins in meat alternatives.

Novel high-resolution contrast agent ultrasound techniques HiFR CEUS and SR CEUS in combination with shear wave elastography, fat assessment and viscosity of liver parenchymal changes and tumors.

BACKGROUND: The continuous development of ultrasound techniques increasingly enables better description and visualization of unclear lesions. New ultrasound systems must be evaluated with regard to all these diagnostic possibilities. METHODS: A multifrequency C1-7 convex probe (SC7-1M) with the new high-end system Resona A20 Series was used. Modern technologies, including HiFR CEUS, SR CEUS and multimodal tissue imaging with shear wave elastography (SWE), fat evaluation and viscosity measurements (M-Ref) were applied. RESULTS: Of n = 70 (mean value 48,3 years±20,3 years, range 18-84 years) cases examined, a definitive diagnosis could be made in n = 67 cases, confirmed by reference imaging and/or follow-up. Of these, n = 22 cases were malignant changes (HCC (hepatocellular carcinoma) n = 9, CCC (cholangiocellular carcinoma) n = 3, metastases of colorectal carcinomas or recurrences of HCC n = 10). In all 12 cases of HCC or CCC, the elastography measurements using the shear wave technique (with values >2 m/s to 3.7 m/s) showed mean values of 2.3±0.31 m/s and a degree of fibrosis of F2 to F4. In n = 14 cases, changes in the fat measurement (range 0.51 to 0.72 dB/cm/MHz, mean values 0.58±0.12 dB/cm/MHz) in the sense of proportional fatty changes in the liver were detected. In the 4 cases of localized fat distribution disorders, the values were >0.7 dB/cm/MHz in the sense of significant fatty deposits in the remaining liver tissue. Relevant changes in the viscosity measurements with values >1.8 kPa were found in n = 31 cases, in n = 5 cases of cystic lesions with partially sclerosing cholangitis, in n = 13 cases of malignant lesions and in n = 9 cases post-interventionally, but also in n = 4 cases of benign foci with additional systemic inflammation. CONCLUSIONS: The results are promising and show a new quality of ultrasound-based liver diagnostics. However, there is a need for further investigations with regard to the individual aspects, preferably on a multi-center basis.

Cost-effectiveness analysis of Tislelizumab vs Sorafenib as the first-line treatment of unresectable hepatocellular carcinoma.

BACKGROUND: To evaluate the cost-effectiveness of Tislelizumab vs Sorafenib as the first-line treatment of unresectable hepatocellular carcinoma (HCC) from the perspective of the Chinese health service system. METHODS: A lifetime partitioned survival model (PSM) was developed to cost-effectively analyze Tislelizumab vs Sorafenib as the first-line treatment of unresectable HCC. The clinical and safety data were derived from a recently randomized clinical trial (RATIONALE-301). Utilities were collected from the published literature. Costs were obtained from an open-access database (http://www.yaozh.com) and previous studies. The model cycle was 21 days, according to the RATIONALE-301 study, and the simulation period was patients' lifetime. Long-term direct medical costs and quality-adjusted life-years (QALYs) were determined. The incremental cost-effectiveness ratio (ICER) was used as the evaluation index. one-way sensitivity analysis (OSWA) and probabilistic sensitivity analysis (PSA) were used to analyze the uncertainty of parameters and to adjust and verify the stability of the baseline results. RESULTS: The Tislelizumab group generated a cost of $39,746.34 and brought health benefits to 2.146 QALYs, while the cost and utility of the Sorafenib group were $26750.95 and 1.578 QALYs, respectively. The Tislelizumab group increased QALYs by 0.568, the incremental cost was $12995.39, and the ICER was $22869.64/QALY, lower than the willingness to pay threshold (WTP). OSWA results showed that the utility of progressed disease (PD), cost of Camrelizumab, and cost of Tislelizumab were the main factors affecting the ICER. PSA results showed that, within 1000 times the Monte Carlo simulation, the cost of the Tislelizumab group was lower than three times the per capita gross domestic product (GDP) of China ($37653/QALY). The cost-effectiveness acceptability curves (CEAC) revealed that when WTP was no less than $12251.00, the Tislelizumab group was the dominant scheme, and the economic advantage grew with an increasing WTP. When WTP ≥ $19000.00, the Tislelizumab group became the absolute economic advantage. CONCLUSION: Under the current economic conditions in China, the Tislelizumab therapeutic scheme is more cost-effective than the Sorafenib therapeutic scheme for treating patients with unresectable HCC.

Magnetic resonance elastography as a preoperative assessment for predicting intrahepatic recurrence in patients with hepatocellular carcinoma.

PURPOSE: Magnetic resonance elastography (MRE) is a noninvasive tool for diagnosing hepatic fibrosis with high accuracy. We investigated the preoperative clinical and imaging predictors of intrahepatic recurrence after curative resection of hepatocellular carcinoma (HCC), and evaluated MRE as a predictor of intrahepatic recurrence. METHODS: We retrospectively evaluated 80 patients who underwent preoperative contrast-enhanced magnetic resonance imaging (MRI) with two-dimensional MRE and curative resection for treatment-naïve HCC between May 2019 and December 2021. Liver stiffness (LS) was measured on the elastograms, and the optimal cutoff of LS for predicting intrahepatic recurrence was obtained using receiver operating characteristic (ROC) analysis. An LS above this cutoff was defined as MRE-recurrence. Preoperative imaging features of the tumor were assessed on MRI, including features in the Liver Imaging Reporting and Data System and microvascular invasion (MVI). Recurrence-free survival (RFS) rates were estimated using the Kaplan-Meier method, and differences were compared using the log-rank test. Using a Cox proportional hazards model, we conducted a multivariable analysis to investigate the factors affecting recurrence-free survival. RESULTS: During a median follow-up period of 32 months (range, 4-52 months), thirteen patients (16.3%) developed intrahepatic recurrence. ROC analysis determined an LS cutoff of ≥4.35 kPa to define MRE-recurrence. The 4-year RFS rate was significantly higher in patients without MRE-recurrence than in those with MRE-recurrence (93.4% vs. 48.9%; p = 0.001). In multivariable analysis, MRE-recurrence (Hazard ratio [HR], 5.9; 95% confidence interval [CI], 1.5-23.1) and MVI (HR, 3.4; 95% CI, 1.0-11.3) were independent predictors of intrahepatic recurrence. CONCLUSIONS: Patients without MRE-recurrence had significantly higher RFS rates than those with MRE-recurrence. MRE-recurrence and MVI were independent predictors of intrahepatic recurrence in patients after curative resection for HCC.

Disparities in Access to Liver Transplant Referral and Evaluation among Patients with Hepatocellular Carcinoma in Georgia.

Liver transplantation offers the best survival for patients with early-stage hepatocellular carcinoma (HCC). Prior studies have demonstrated disparities in transplant access; none have examined the early steps of the transplant process. We identified determinants of access to transplant referral and evaluation among patients with HCC with a single tumor either within Milan or meeting downstaging criteria in Georgia.Population-based cancer registry data from 2010 to 2019 were linked to liver transplant centers in Georgia. Primary cohort: adult patients with HCC with a single tumor ≤8 cm in diameter, no extrahepatic involvement, and no vascular involvement. Secondary cohort: primary cohort plus patients with multiple tumors confined to one lobe. We estimated time to transplant referral, evaluation initiation, and evaluation completion, accounting for the competing risk of death. In sensitivity analyses, we also accounted for non-transplant cancer treatment.Among 1,379 patients with early-stage HCC in Georgia, 26% were referred to liver transplant. Private insurance and younger age were associated with increased likelihood of referral, while requiring downstaging was associated with lower likelihood of referral. Patients living in census tracts with ≥20% of residents in poverty were less likely to initiate evaluation among those referred [cause-specific hazard ratio (csHR): 0.62, 95% confidence interval (CI): 0.42-0.94]. Medicaid patients were less likely to complete the evaluation once initiated (csHR: 0.53, 95% CI: 0.32-0.89).Different sociodemographic factors were associated with each stage of the transplant process among patients with early-stage HCC in Georgia, emphasizing unique barriers to access and the need for targeted interventions at each step. SIGNIFICANCE: Among patients with early-stage HCC in Georgia, age and insurance type were associated with referral to liver transplant, race, and poverty with evaluation initiation, and insurance type with evaluation completion. Opportunities to improve transplant access include informing referring providers about insurance requirements, addressing barriers to evaluation initiation, and streamlining the evaluation process.

Cost-effectiveness of switching from tenofovir disoproxil fumarate to tenofovir alafenamide versus entecavir for chronic hepatitis B patients in Greece.

Aim: This study assessed the clinical impact and cost-effectiveness of switching from tenofovir disoproxil fumarate (TDF) to either tenofovir alafenamide (TAF) or entecavir (ETV) in a Greek chronic hepatitis B (CHB) population. Patients & methods: A Markov model from the perspective of a third-party payer in Greece quantified the health and economic benefits of switching from TDF to either TAF or ETV over a lifetime horizon. Results: Over a lifetime, patients who switch from TDF to TAF versus patients who switch from TDF to ETV had an overall lower incidence of compensated cirrhosis (0.4% lower), decompensated cirrhosis (0.04% lower) and hepatocellular carcinoma (0.25% lower). Chronic kidney disease and end-stage renal disease were also lower in patients who switch to TAF; major osteoporotic fractures were similar for both groups. While total costs were higher for switching from TDF to TAF versus TDF to ETV due to the higher cost of TAF, switching from TDF to TAF versus ETV was cost effective with an incremental cost-effectiveness ratio of €17,113 per quality-adjusted life year. Conclusion: Switching from TDF to TAF in patients living with CHB is a cost effective strategy to reduce adverse liver disease outcomes, while improving bone- and renal-related safety outcomes.