Background: Palliative care addresses a range of needs, from symptom management to providing support to patients with hepatocellular cancer (HCC) and their families throughout the illness. However, research on palliative care in HCC remains limited, particularly during the COVID-19 pandemic. This study investigates the healthcare utilization associated with palliative care referral among patients with HCC. Methods: This is a retrospective cross-sectional analysis conducted using the National Inpatient Sample (NIS) database from 2019 to 2021 among patients with HCC age ≥18 years. Results: Among the 35,220 hospitalizations with HCC as the principal diagnosis, 18.7% received inpatient palliative care referrals. Factors associated with increased palliative care referrals included age ≥65 years, Midwest region, Charlson Comorbidity Index (CCI) score ≥3, and end-of-life care, as reflected by discharge resulting in death. No racial or insurance disparities were observed. Palliative care consultations were associated with lower total hospital costs ($20,573 vs $26,035, <0.0001). A higher prevalence of \"do-not-resuscitate\" status was also found among patients with palliative care referrals. Conclusion: The study provides an understanding of palliative care utilization across pre-pandemic and pandemic periods. Factors such as advanced age, hospital region, and underlying comorbidities influenced the likelihood of referral, with no discernible racial or insurance disparities identified. Palliative care involvement has also been shown to provide cost-effective supportive care with lower hospital costs. These findings provide invaluable guidance for optimizing the integration of palliative care alongside HCC management.

BACKGROUND: Older adults undergoing cancer treatment often experience more treatment-related toxicities and increased risk of mortality compared to younger patients. The role of frailty among older individuals as a predictor of outcomes has gained growing significance. We evaluated the association between frailty and overall survival (OS) in patients with hepatocellular carcinoma (HCC) ≥60 years.
METHODS: Older adults ≥60 years with HCC enrolled in a prospective single-institution registry underwent a patient-reported geriatric assessment (GA) covering multiple health domains related to prior to their initial medical oncology appointment. Frailty was measured using a 44-item deficit accumulation frailty index. We categorized patients as robust, pre-frail, and frail using standard cutpoints. The primary outcome was overall survival (OS). Univariable and multivariable models were built to evaluate the association between frailty and OS after adjusting for potential confounders.
RESULTS: Total of 116 older adults with HCC with a median age of 67 years were enrolled; 82% male, 27% Black, and 78% with stage III/IV disease. Overall, 19 (16.3%) were robust, 39 (33.6%) pre-frail, and 58 (50.1%) frail. There were 76 patients receiving liver directed therapy. Of these, 13 (17%) were robust, 26 (34%) were pre-frail, and 37 (49%) were frail. Over a median follow up of 0.9 years, 53 patients died. After adjusting for age, stage, etiology, and Child-Pugh class, being frail (vs. robust) was associated with worse OS (hazard ratio (HR) 2.6 [95% CI 1.03-6.56]; p = 0.04).
CONCLUSIONS: Half of the participants in this study were frail, which was independently associated with worse survival in adults ≥60 years of age with HCC. Identification of pre-treatment frailty may allow opportunities to guide treatment decisions and prognostication.

OBJECTIVE: Our study aimed to evaluate the impact of concomitant medications on the response and survival of patients with advanced digestive tract cancer receiving an immunotherapy-antiangiogenesis combination.
METHODS: We conducted a three-center observational retrospective study of patients with advanced digestive tract cancer who received programmed death-1 (PD-1) inhibitors plus antiangiogenic agents between March 2019 and July 2022 in China. The patients had one of the three types of primary tumors: hepatocellular carcinoma (HCC), colorectal cancer (CRC), and gastric cancer (GC).
RESULTS: The study included 352 patients. The most frequently prescribed co-medications were nonsteroidal anti-inflammatory drugs (NSAIDs) (46.3%), proton pump inhibitors (PPIs) (38.0%), systemic antibiotics (33.8%), and corticosteroids (30.1%). Probiotics had a direct correlation with a higher objective response rate (ORR) (OR 2.4, 95% CI 1.2 to 4.7, p = 0.013). Patients who received PPIs for gastritis/gastroesophageal reflux disease (GERD) (HR 0.7, 95% CI 0.5 to 1.0, p = 0.045), anticoagulants (HR 0.5, 95% CI 0.3 to 0.9, p = 0.009), and probiotics (HR 0.7, 95% CI 0.5 to 1.0, p = 0.034) had longer progression-free survival (PFS). Patients who received PPIs for gastritis/GERD (HR 0.6, 95% CI 0.4 to 0.9; p = 0.009) had longer overall survival (OS), while patients receiving opioids (HR 1.5, 95% CI 1.1 to 2.0, p = 0.010) had a significantly higher risk of death.
CONCLUSIONS: Patients with advanced digestive tract cancer who were administered PPIs for gastritis/GERD indication, anticoagulants, or probiotics in combination with PD-1 inhibitors and antiangiogenic agents experienced improved clinical outcomes. However, opioid administration was linked to reduced OS in patients receiving combined therapy.

Background and Objectives: The incidence of metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocellular carcinoma (HCC) is increasing worldwide, alongside the epidemic of obesity and metabolic syndrome. Based on preliminary reports regarding the potential association of HCC and periodontitis, this study aimed to analyze the involvement of periodontal bacteria as well as the oral and intestinal bacterial flora in MASH-related HCC (MASH-HCC). Materials and Methods: Forty-one patients with MASH and nineteen with MASH-HCC participated in the study, completing survey questionnaires, undergoing periodontal examinations, and providing samples of saliva, mouth-rinsed water, feces, and peripheral blood. The oral and fecal microbiome profiles were analyzed by 16S ribosomal RNA sequencing. Bayesian network analysis was used to analyze the causation between various factors, including MASH-HCC, examinations, and bacteria. Results: The genus Fusobacterium had a significantly higher occupancy rate (p = 0.002) in the intestinal microflora of the MASH-HCC group compared to the MASH group. However, Butyricicoccus (p = 0.022) and Roseburia (p < 0.05) had significantly lower occupancy rates. The Bayesian network analysis revealed the absence of periodontal pathogenic bacteria and enteric bacteria affecting HCC. However, HCC directly affected the periodontal bacterial species Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in the saliva, as well as the genera Lactobacillus, Roseburia, Fusobacterium, Prevotella, Clostridium, Ruminococcus, Trabulsiella, and SMB53 in the intestine. Furthermore, P. gingivalis in the oral cavity directly affected the genera Lactobacillus and Streptococcus in the intestine. Conclusions: MASH-HCC directly affects periodontal pathogenic and intestinal bacteria, and P. gingivalis may affect the intestinal bacteria associated with gastrointestinal cancer.

OBJECTIVE: Advances in surgical procedures and immunosuppressive therapies have considerably improved the outcomes of patients who have undergone liver transplantation in the past few decades. In 2020, the Italian Liver Transplant Working Group published practice-oriented algorithms for immunosuppressive therapy (IT) in adult liver transplant (LT) recipients. Due to the rapidly evolving LT field, regular updates to the recommendations are required. This review presents a consensus- and evidence-based update of the 2020 recommendations.
METHODS: The Italian Liver Transplant Working Group set out to address new IT issues, which were discussed based on supporting literature and the specialists\' personal experiences. The panel deliberated on and graded each statement before consensus was reached.
RESULTS: A series of consensus statements were formulated and finalized on: (i) oncologic indications for LT; (ii) management of chronic LT rejection; (iii) combined liver-kidney transplantation; (iv) immunosuppression for transplantation with an organ donated after circulatory death; (v) transplantation in the presence of frailty and sarcopenia; and (vi) ABO blood group incompatibility between donor and recipient. Algorithms were updated in the following LT groups: standard patients, critical patients, oncology patients, patients with specific etiology, and patients at high immunologic risk. A steroid-free approach was generally recommended, except for patients with autoimmune liver disease and those at high immunologic risk.
CONCLUSIONS: The updated consensus- and evidence-based 2024 recommendations for immunosuppression regimens in adult patients with ABO-compatible LT address a range of clinical variables that should be considered to optimize the choice of the immunosuppression treatment in clinical practice in Italy.

OBJECTIVE: Our purpose was to assess the impact of muscle quality on overall survival (OS) in patients with advanced HCC.
METHODS: This is a subanalysis of the SORAMIC trial. Overall, 363 patients were included. The SIRT/Sorafenib treatment group comprised 182 patients and the sorafenib group 181 patients. Myosteatosis was defined as skeletal muscle density (SMD) < 41 HU for patients with a body mass index up to 24.9 kg/m2 and <33 HU for patients with a body mass index ≥25 kg/m2. Albumin-gauge score was calculated as follows: serum albumin (g/dL) × SMD (HU). To assess the impact of muscle quality on clinical variables and OS, a Cox regression model was used. Hazard ratios are presented together with 95 % confidence intervals (95 % CI). Kaplan-Meier curves were used for survival analysis.
RESULTS: In the SIRT/sorafenib cohort, low albumin-gauge score was an independent predictor of worse OS, HR = 1.74, CI 95% (1.16-2.62), p = 0.01. In the sorafenib cohort, muscle quality parameters did not predict OS. In alcohol-induced HCC (n = 129), myosteatosis independently predicted OS, HR = 1.85, CI 95% (1.10; 3.12), p = 0.02. In viral-induced HCC (n = 99), parameters of muscle quality did not predict OS. In patients with NASH/Non-alcoholic fatty liver disease (NAFLD) induced HCC, albumin-gauge score was a strong independent predictor of worse OS in the subgroup undergoing combined treatment with SIRT and sorafenib, HR = 9.86, CI 95% (1.12; 86.5), p = 0.04.
CONCLUSIONS: Myosteatosis predicts independently worse OS in patients with alcohol-induced HCC undergoing combined treatment with SIRT and sorafenib. In patients with NASH/NAFLD induced HCC undergoing treatment with SIRT and sorafenib, albumin-gauge score predicts independently worse OS.
UNASSIGNED: Associations between parameters of muscle quality and OS are different in accordance to the treatment strategy and etiology of HCC. These findings highlight the prognostic potential of skeletal muscle quality in patients with advanced HCC.

UNASSIGNED: Primary liver tumors constitute one of the most common tumors. These are aggressive tumors with poor survival. Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), most commonly used functional imaging, shows limited tracer retention and poor tumor to background ratios (TBR). Novel 68Ga-fibroblast-activation-protein inhibitor (FAPI) PET/CT has shown better tracer uptake and detection efficacy in liver tumors. However, most of the available literature is limited to single center studies with limited number of patients. So, we tried to review and analyze the head-to-head comparison of 18F-FDG PET/CT and 68Ga-FAPI PET/CT in evaluation of liver tumors.
UNASSIGNED: Literature available on head to head comparison of diagnostic accuracy of 18F-FDG PET/CT and 68Ga-FAPI PET/CT was searched in databases like PubMed, SCOPUS, EMBASE and Google Scholar for published original studies till April 2023. The relevant studies were selected and assessed using the Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies-2 checklist. A random-effect model was used for calculating pooled sensitivity and specificity. They were represented with 95% confidence intervals (95% CI) and demonstrated in Forest plots. I-square statistic was used to assess heterogeneity in the studies.
UNASSIGNED: Pooled sensitivity and specificity of FAPI PET/CT and 18F-FDG PET/CT for detection of primary liver tumors was 94.3% (95% CI: 90.6-96.8%); 89.3% (95% CI: 71.8-97.7%) and 56.1% (95% CI: 49.7-62.5%); 96.4% (95% CI: 81.7-99.9%) respectively. Pooled sensitivity for detection of extrahepatic metastatic disease was 92.2% (range: 88.1-100%; 95% CI: 87.8-95.4%) and 72.4% (range: 69.8-76.5; 95% CI: 65.9-78.2%) respectively. Also, the maximum standardized uptake value (SUVmax) and TBR were higher for FAPI PET/CT than 18F-FDG PET/CT in the included studies.
UNASSIGNED: Overall, FAPI PET/CT showed higher sensitivity for detection of liver tumors with better SUVmax and TBR than 18F-FDG PET/CT.
UNASSIGNED: Primer karaciğer tümörleri en sık görülen tümörlerdendir. Bunlar hayatta kalma oranı düşük olan agresif tümörlerdir. En sık kullanılan fonksiyonel görüntüleme olan florodeoksiglukoz (FDG) pozitron emisyon tomografisi/bilgisayarlı tomografi (PET/BT), sınırlı radyofarmasötik tutulumu ve zayıf tümör/arka plan oranları (TBR) gösterir. Yeni 68Ga-fibroblast aktivasyon protein inhibitörü (FAPI) PET/BT, karaciğer tümörlerinde daha iyi radyofarmasötik tutulumu ve tespit etkinliği göstermiştir. Ancak mevcut literatürün çoğu, sınırlı hasta sayısıyla yapılan tek merkezli çalışmalarla sınırlıdır. Bu nedenle, karaciğer tümörlerinin değerlendirilmesinde 18F-FDG PET/BT ve 68Ga-FAPI PET/BT’nin birebir karşılaştırmasını gözden geçirip analiz etmeye çalıştık.
UNASSIGNED: 18F-FDG PET/BT ve 68Ga-FAPI PET/BT’nin tanısal doğruluğunun birebir karşılaştırılması konusunda mevcut literatür, Nisan 2023’e kadar yayınlanmış araştırma makaleleri için PubMed, SCOPUS, EMBASE ve Google Scholar gibi veritabanlarında tarandı. İlgili çalışmalar Tanısal Doğruluk Çalışmalarının Kalite Değerlendirmesi için Gözden Geçirilmiş Araç-2 kontrol listesi kullanılarak seçilmiş ve değerlendirilmiştir. Birleştirilmiş duyarlılığı ve özgüllüğü hesaplamak için rastgele etki modeli kullanıldı. Bunlar %95 güven aralıklarıyla (%95 GA) temsil edildi ve Orman grafiklerinde gösterildi. Çalışmalardaki heterojenliği değerlendirmek için I-kare istatistiği kullanıldı.
UNASSIGNED: Primer karaciğer tümörlerinin tespiti için FAPI PET/BT’nin havuzlanmış duyarlılığı ve özgüllüğü sırasıyla %94,3 (%95 GA: %90,6-96,8) ve %89,3 (%95 GA: %71,8-97,7); 18F-FDG PET/BT’nin havuzlanmış duyarlılığı ve özgüllüğü sırasıyla %56,1 (%95 GA: %49,7-62,5) ve %96,4 (%95 GA: %81,7-99,9) idi. Ekstrahepatik metastatik hastalığın saptanması için havuzlanmış duyarlılık FAPI PET/BT ve 18F-FDG PET/BT için sırasıyla %92,2 (aralık: %88,1-100; %95 GA: %87,8-95,4) ve %72,4 (aralık: 69,8-76,5; %95 GA: %65,9-78,2) idi. Ayrıca, dahil edilen çalışmalarda FAPI PET/BT için maksimum standardize tutulum değeri (SUVmaks) ve TBR, 18F-FDG PET/BT’den daha yüksekti.
UNASSIGNED: Genel olarak, FAPI PET/BT, karaciğer tümörlerinin tespitinde 18F-FDG PET/BT’ye göre daha iyi SUVmaks ve TBR ile daha yüksek duyarlılık gösterdi.

BACKGROUND: Hepatocellular cancer (HCC) is one of the most harmful tumors to human health. Currently, there is still a lack of highly sensitive and specific HCC biomarkers in clinical practice. In this study, we aimed to explore the diagnostic performance of prostaglandin A2 (PGA2) for the early detection of HCC.
METHODS: Untargeted metabolomic analyses on normal control (NC) and HCC participants in the discovery cohort were performed, and PGA2 was identified to be dysregulated in HCC. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for detecting serum PGA2 was established and applied to validate the dysregulation of PGA2 in another independent validation cohort. Receiver operating characteristic (ROC), decision curve analysis (DCA) and some other statistical analyses were performed to evaluate the diagnostic performance of PGA2 for HCC.
RESULTS: At first, PGA2 was found to be dysregulated in HCC in untargeted metabolomic analyses. Then a precise quantitative LC-MS/MS method for PGA2 has been established and has passed rigorous method validation. Targeted PGA2 analyses confirmed that serum PGA2 was decreased in HCC compared to normal-risk NC and high-risk cirrhosis group. Subsequently, PGA2 was identified as a novel biomarker for the diagnosis of HCC, with an area under the ROC curve (AUC) of 0.911 for differentiating HCC from the combined NC + cirrhosis groups. In addition, PGA2 exhibited high performance for differentiating small-size (AUC = 0.924), early-stage (AUC = 0.917) and AFP (-) HCC (AUC = 0.909) from the control groups. The combination of PGA2 and AFP might be useful in the surveillance of risk population for HCC and early diagnosis of HCC.
CONCLUSIONS: This study establishes that PGA2 might be a novel diagnostic biomarker for HCC.

BACKGROUND: Increased level of serum cholic acid (CA) is often accompanied with decreased CYP2E1 expression in hepatocellular carcinoma (HCC) patients. However, the roles of CA and CYP2E1 in hepatocarcinogenesis have not been elucidated. This study aimed to investigate the roles and the underlying mechanisms of CYP2E1 and CA in HCC cell growth.
METHODS: The proteomic analysis of liver tumors from DEN-induced male SD rats with CA administration was used to reveal the changes of protein expression in the CA treated group. The growth of CA-treated HCC cells was examined by colony formation assays. Autophagic flux was assessed with immunofluorescence and confocal microscopy. Western blot analysis was used to examine the expression of CYP2E1, mTOR, AKT, p62, and LC3II/I. A xenograft tumor model in nude mice was used to examine the role of CYP2E1 in CA-induced hepatocellular carcinogenesis. The samples from HCC patients were used to evaluate the clinical value of CYP2E1 expression.
RESULTS: CA treatment significantly increased the growth of HCC cells and promoted xenograft tumors accompanied by a decrease of CYP2E1 expression. Further studies revealed that both in vitro and in vivo, upregulated CYP2E1 expression inhibited the growth of HCC cells, blocked autophagic flux, decreased AKT phosphorylation, and increased mTOR phosphorylation. CYP2E1 was involved in CA-activated autophagy through the AKT/mTOR signaling. Finally, decreased CYP2E1 expression was observed in the tumor tissues of HCC patients and its expression level in tumors was negatively correlated with the serum level of total bile acids (TBA) and gamma-glutamyltransferase (GGT).
CONCLUSIONS: CYP2E1 downregulation contributes to CA-induced HCC development presumably through autophagy regulation. Thus, CYP2E1 may serve as a potential target for HCC drug development.

UNASSIGNED: The five-year recurrence rate of hepatocellular carcinoma (HCC) remains as high as 70%. A complete clinical response has not been observed without surgical resection. Here, we report a rare case of clinical complete response and long-term survival in a patient with massive HCC receiving treatment with immunotherapy, anti-angiogenic therapy, and radiotherapy.
UNASSIGNED: A 38-year-old woman presented to our hospital for abdominal pain that persisted for 3 months. She was diagnosed as Barcelona Clinic Liver Cancer(BCLC) stage A, with a Cancer of the Liver Italian Program (CLIP) score of 3, American Joint Committee on Cancer (AJCC) Tumor-Node-Metastasis (TNM) staging systems stage IB. She refused surgical resection and trans-arterial chemoembolization and accepted a non-invasive systematic treatment strategy involving immunotherapy, anti-angiogenic therapy, and radiotherapy. Her tumor burden decreased, and she experienced partial response before radiotherapy. Following radiotherapy, she experienced a complete clinical response and has been alive for more than 36 months after her initial presentation. She is currently alive.
UNASSIGNED: A non-invasive systematic treatment strategy is a potential radical treatment option for patients with massive HCC.