The clinical management of hepatocellular carcinoma (HCC) is strongly influenced by several prognostic factors, mainly tumor stage, patient's health, liver function and specific characteristics of each intervention. The interplay between these factors should be carefully evaluated by a multidisciplinary tumor board. To support this, the novel "multiparametric therapeutic hierarchy" (MTH) concept has been recently proposed. This review will present the main features of available surgical treatments for HCC (liver transplantation, liver resection, ablation). Strengths and weaknesses are reported in the light of clinical decision making and of treatment allocation, with a special focus on the collocation of each treatment in the MTH framework and on how MTH may be useful in supporting clinical decision. Sequential treatments and their role to allow further surgical treatments will also be analyzed.

Recent advances in the systemic treatment of advanced hepatocellular carcinoma (HCC) with immunotherapy have once again reignited discussion over the role of combined therapy in earlier stages. This year, different international meetings have presented recent results from clinical trials on adjuvant therapy alone (IMBrave-050) and combined with transarterial chemoembolization (EMERALD-1 and LEAP-12). Increased enthusiasm for the use of adjuvant and neoadjuvant therapy for liver transplantation, surgery, and local-regional treatment of HCC has been shown. However, the initial results from these trials should be interpreted cautiously as we wait for final analyses and effects on overall survival. In this position paper from the special interest group from the Latin American Association for the Study of Liver Diseases (ALEH), we underline the caveats of the applicability of these potential treatments in our region, explore points of agreement, and highlight areas of uncertainty. Moreover, we underscore the role of hepatologists in the clinical decision-making process and management of these patients.

Hepatocellular carcinoma (HCC) patients with advanced symptoms or liver failure are often ineligible for transplantation, leading only to symptom control. Additionally, various factors lead to other HCC stage patients remaining in natural history.

To describe the demographic of untreated HCC patients and to analyze survival-influencing factors.

single-center retrospective observational study examining HCC patients diagnosed from 2015 to 2021 who received symptom control as their primary treatment. Baseline characteristics and survival data were collected and analyzed.

Of 685 HCC patients, 26% (n=181) remained in natural history, median age 71 years, 82% male patients, 93% with cirrhosis, 53% with previous decompensation. At a mean follow-up of 9.98 months, the mortality rate was 84%. While 49.8% of patients were BCLC-D stage, other reasons for remaining in natural history included frailty (25.4%) comorbidities (16%), and patient's treatment refusal (8%). Independent survival factors were BCLC stage, previous decompensation and diagnosis within the screening program, with 37% of untreated patients detected through surveillance.

Liver function, BCLC stage and functional status influence survival in natural HCC history. A significant 37% diagnosed through screening indicates inclusion criteria refinement necessity to avoid overdiagnosis and optimize resources.

Preoperative hepatitis B virus (HBV) DNA level has been shown to correlate with the prognosis of patients with HBV-associated hepatocellular carcinoma (HCC) following liver resection, but its dynamic changes have not been reported. The aim of this longitudinal multicenter retrospective observational study was to describe the trajectory of HBV DNA after R0 liver resection in patients receiving antiviral therapy and to investigate its impact on clinical outcomes.

This study included patients with HBV-related HCC from nine hospitals in China who received antiviral therapy and R0 hepatectomy between 2015 and 2016. A latent class growth mixed model (LCGMM) was applied to group the trajectories of HBV DNA changes. The relative importance of each variable to predict survival was evaluated using the χ2.

Six hundred and eighty-four patients with HCC who met the inclusion exclusion criteria were included. Patients were divided into 5 trajectories of HBV DNA changes using LCGMM. By combining subgroups with similar survival characteristics, patients were reclassified into three groups: slow decline, slow zeroing, and fast zeroing group, the 5-year OS rates are 34.5 %, 53.0 %, 70.9 %, respectively. Multifactorial COX regression results showed that ALBI grade, HBV reactivation, cirrhosis, maximum tumor diameter, microvascular invasion, and HBV DNA trajectory groups were independent risk factors for OS.

HBV DNA trajectories were associated with OS for patients with HBV-related HCC after R0 liver resection, and it is necessary to receive antiviral therapy and to monitor HBV status regularly.

Laparoscopic microwave ablation (LMWA) has yet to gain a specific place in treatment guidelines for early hepatocellular carcinoma (HCC). This study compared the outcomes of LMWA and trans-arterial chemoembolization (TACE) for early non-resectable patients with HCC, taking percutaneous radiofrequency ablation (PRFA) as the reference treatment.

A retrospective multicenter observational study was conducted, enrolling non-transplantable, non-resectable patients who had early HCC treated with LMWA (n = 658) from Padua and Milan centers, and with PRFA (n = 844), and TACE (n = 425) from the ITA.LI.CA multicenter database. The matching-adjusted indirect comparison (MAIC) method was used to obtain weighted LMWA and TACE populations similar to the reference PRFA population.

Laparoscopic ablation showed an excellent safety profile, and MAIC-weighted early postoperative deaths were comparable among the groups. The MAIC-weighted overall survival was similar between the LMWA (1-, 3-, and 5 year survival of 91.0 %, 67.9 %, 47.0 %, respectively) and PRFA (1-, 3- and 5 year survivals of 90.0 %, 64.7 %, 46.6 %, respectively) groups (p = 0.678) and significantly better for the LMWA group than for the TACE group (1-, 3- and 5 year survivals of 84.7 %, 48.8 %, 33.6 %, respectively) (p < 0.001). Weighted multivariate overall survival analysis and competing risk/subgroup analyses confirmed the non-inferiority of LMWA to PRFA and its superiority to TACE. The LMWA- and PRFA-treated patients had a significantly lower risk of HCC-related death (p = 0.004) than the TACE-treated patients (p = 0.001). Conversely, the groups did not differ significantly in terms of non-HCC-related deaths.

The non-inferiority of LMWA to PRFA, its superiority to TACE, and its applicability to a wide range of presentations with few contraindications support its inclusion among radical therapies for treating early-HCC patients.

To systematically review the diagnostic efficacy of abbreviated magnetic resonance imaging sequence (AMRI) screening for hepatocellular carcinoma (HCC).

Medline (via PubMed), EMbase, The Cochrane Library, Web of Science, CNKI, WanFang Data, and VIP databases were electronically searched to collect studies on the diagnostic efficacy of AMRI screening for HCC from inception to August 10th, 2024. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2), then, the meta-analysis with a bivariate mixed-effects regression model was performed by using Stata 14.0 software.

A total of 19 studies involving 3914 participants were included which published from 2013 to 2024. The results of meta-analysis showed that pooled sensitivity and specificity of AMRI for HCC were 0.85 (95% confidence interval (CI) 0.83 to 0.87) and 0.93 (95%CI 0.91 to 0.94). Subgroup analysis showed that the pooled sensitivity and specificity of NC (Non-Contrast) AMRI and HBP (Hepatobiliary Phase Images) AMRI were 0.84 (95%CI 0.80 to 0.87), 0.92 (95%CI 0.89 to 0.94) and 0.88 (95%CI 0.84 to 0.91), 0.93 (95%CI 0.91 to 0.95), respectively. And the T2 (T2 Weighted Imaging)+DWI (Diffusion Weighted Imaging)+HBP protocol in HBP AMRI had the highest diagnostic efficacy, its pooled sensitivity, specificity and the area under the summary receiver operating characteristic (SROC) curve (AUC) were 0.88 (95%CI 0.83 to 0.92), 0.93 (95%CI 0.91 to 0.95), and 0.96 (95%CI 0.94 to 0.98), respectively.

Current evidence suggests that the AMRI protocols demonstrated potential for HCC detection, which employing a limited number of sequences with the aim of achieving a diagnostic performance comparable to conventional complete contrast-enhanced MRI (CE-MRI). Among them, T2+DWI+HBP protocol shows the relatively highest diagnostic efficiency, which is perhaps the most promising application in clinical practice. Nevertheless, the results still should be carefully interpreted in the relevant context of medical history, physical examination, and biochemical indicators.

There is significant variation in HCC management across different centers with poor adherence to evidence-based clinical practice guidelines as assessed in prior studies. In Australia, quality indicators (QIs) have recently been proposed by a multidisciplinary group of experts to help provide a framework to assess and monitor the quality of HCC care. In this review, we discuss the many areas where real-world practice deviates from evidence-based medicine, the role that QI sets play in addressing this gap, and the similarities and differences between Australian QIs and other leading treatment guidelines and QI sets from around the world. We focus on the utility of QI sets to identify opportunities for targeted improvement in the real-world clinical environment. We conclude with a discussion about the formation of a national clinical quality registry as a long-term measure to facilitate continual improvements in patient care within and across sites in order to optimize patient outcomes.

Novel steatotic liver disease (SLD) definitions were introduced in 2023. Accurate and meaningful classifications using clinical data are needed to study interventions and outcomes.

In a national cohort of Veterans with cirrhosis and imaging-confirmed steatosis, 7 algorithms differentially emphasizing cardiometabolic risk factors (CMRFs) and alcohol exposure were developed to define alcohol-associated liver disease (ALD), metabolic dysfunction associated SLD (MASLD), and MASLD with increased alcohol intake (MetALD). The primary outcome was classification of SLD, which was validated using hospitalizations for major acute cardiac events (MACE) and alcohol use disorder (AUD). Secondary outcomes included longitudinal Child-Turcotte-Pugh class, incident hepatocellular carcinoma, and all-cause mortality.

In all, 31,514 patients with cirrhosis (median age 64 years) were included. CMRFs (98.8% ≥ 1) and hazardous alcohol use (65.3%) were highly prevalent. The distributions of MASLD, MetALD, and ALD varied substantially across classification methods with varying CMRF and alcohol criteria. For example, MetALD ranged from 4.7% to 47.2%. Using method 4, incidence rates of MACE hospitalizations in MASLD, MetALD, and ALD were 16.7, 14.5, and 8.4 per 100 person-years, respectively, and incidence rates of AUD hospitalizations were 2.0, 26.1, and 47.6 per 100 person-years, respectively. Hypertriglyceridemia and low high-density lipoprotein were common across SLD subtypes, including ALD (67.3% hypertriglyceridemia; 48.2% low high-density lipoprotein). Patients with ALD (hazard ratio, 1.41; 95% confidence interval, 1.34-1.48) had significantly higher hazards of mortality relative to MASLD.

Classification of SLD is highly sensitive to relative weighting of CMRFs and alcohol use. Clinically relevant definitions should consider data availability on alcohol and the limitations of lipid measurements in distinguishing SLD subtypes.

Hepatobiliary tumors have evolving management guidelines. Patient educational needs and interest in community engagement are unknown. This study serves as a needs assessment.

A prospective, needs assessment, survey study of hepatobiliary patients was performed (2016-2019). Surveys (n = 169) were distributed covering three domains of interest: informational needs, interest in outreach, and engagement preferences.

Seventy patients completed the survey (response rate = 41.4%). Most patients had completed surgical treatment (84.3%). Cancer treatment was ranked as their primary topic of interest (n = 39, 55.7bold%), followed by symptom management, nutrition, and survivorship. Most patients did not participate in screening (n = 57, 81.4%), though were interested in learning more about these programs. Thirty-nine patients (55.7%) stated they would want to receive more education. Only 17 (24.3%) were interested in attending in-person events. Patients preferred online methods for education (n = 49, 70%). While patients were aware of their case presentation at tumor board, only 38 (54.3%) felt well-informed about recommendations.

Multidisciplinary care is complex and difficult for patients to navigate. Most patients have interest in educational resources and prefer online modalities. Patients understand multidisciplinary tumor boards, but communication could be improved.

These data inform a new, innovative, approach to outreach efforts in this population.

We report a case of alveolar rhabdomyosarcoma of the infratemporal region in a female child. An 8year old female was diagnosed with alveolar rhabdomyosarcoma 10 years ago. A computed tomography (CT) scan showed large mass in the right pterygopalatine fossa extending into the buccal, masticator and parapharyngeal spaces with involvement of the pterygoid and masseter muscles. Several multidisciplinary discussions were held concerning the case to determine the best treatment strategy. Child received neoadjuvant chemotherapy followed by radiotherapy. Six months post radiotherapy, CT scan reported a residual lesion for which multiple biopsies showed no residual tumor. Patient is doing well 10 years after treatment with no evidence of recurrence, Notably, this was the first case discussed at the inception of the pediatric multidisciplinary tumor board.

Intravenous albumin reduces mortality in spontaneous bacterial peritonitis (SBP). We sought to characterize albumin use for SBP over time and investigate patient-level and hospital-level factors associated with use.

A retrospective cohort study in the Veterans Health Administration between 2008 and 2021 evaluated trends and patient-level, practice-level, and facility-level factors associated with use among patients with cirrhosis hospitalized for SBP confirmed with ascitic fluid criteria.

Among 3,871 veterans with SBP, 803 (20.7%) did not receive albumin, 1,119 (28.9%) received albumin but not per guidelines, and 1,949 (50.3%) received albumin per guidelines; use increased from 66% in 2008 to 88% in 2022. Veterans who identified as Black compared with White were less likely to receive guideline-recommended albumin (Odds ratio [OR] 0.76, 95% confidence interval [CI] 0.59-0.98) in all analyses. Guideline-recommended albumin was more likely to be administered to veterans with Child-Turcotte-Pugh class B (OR 1.39, 95% CI 1.17-1.64) and C (OR 2.21, 95% CI 1.61-3.04) compared with Child-Turcotte-Pugh A; and acute kidney injury Stage 1 (OR 1.48, 95% CI 1.22-1.79), Stage 2 (OR 2.17, 95% CI 1.62-2.91), and Stage 3 (OR 1.68, 95% CI 1.18-2.40) compared with no acute kidney injury. gastroenterology/hepatology consultation (OR 1.60, 95% CI 1.29-1.99), nephrology consultation (OR 1.60, 95% CI 1.23-2.07), and having both gastroenterology/hepatology and nephrology consultations (OR 2.17, 95% CI 1.60-2.96) were associated with higher albumin administration. In exploratory analyses accounting for interactions between model for end-stage liver disease sodium and albumin, guideline-recommended albumin was associated with lower in-hospital mortality (HR 0.90, 95% CI 0.85-0.96).

Future studies should investigate optimizing albumin use for SBP to reduce the variability and mitigate healthcare disparities.

Prognosticating survival among patients with HCC and cirrhosis must account for both the tumor burden/stage, as well as the severity of the underlying liver disease. Although there are many staging systems used to guide therapy, they have not been widely adopted to predict patient-level survival after the diagnosis of HCC. We sought to develop a score to predict long-term survival among patients with early- to intermediate-stage HCC using purely objective criteria.

Retrospective cohort study among patients with HCC confined to the liver, without major medical comorbidities within the Veterans Health Administration from 2014 to 2023. Tumor data were manually abstracted and combined with clinical and laboratory data to predict 5-year survival from HCC diagnosis using accelerated failure time models. The data were randomly split using a 75:25 ratio for training and validation. Model discrimination and calibration were assessed and compared to other HCC staging systems.

The cohort included 1325 patients with confirmed HCC. A risk score using baseline clinical, laboratory, and HCC-related survival had excellent discrimination (integrated AUC: 0.71 in the validation set) and calibration (based on calibration plots and Brier scores). Models had superior performance to the BCLC and ALBI scores and similar performance to the combined BCLC-ALBI score.

We developed a risk score using purely objective data to accurately predict long-term survival for patients with HCC. This score, if validated, can be used to prognosticate survival for patients with HCC, and, in the setting of liver transplantation, can be incorporated to consider the net survival benefit of liver transplantation versus other curative options.

In order to identify opportunities to streamline hepatopancreaticobiliary (HPB) multidisciplinary teams (MDT) for cancer care, it is important to first document variability in MDT team practices worldwide. We aimed to develop a comprehensive checklist of parameters to evaluate existing practices and guide the development of MDTs for new cancer services.

Participants were recruited via the International Hepato-Pancreato-Biliary Association (IHPBA) and European-African HPB Association (E-AHPBA) and emailed an anonymised online survey. The survey comprised 29 questions, including a combination of closed-ended and open-ended questions. Responses were analysed using descriptive statistics and inductive content analysis.

Analysing 72 responses from 31 countries, we found substantial variations in HPB MDT practices across regions. Notable variability was found in core team composition, chairing practices, caseload planning, information practices and MDT audit practices. Issues impacting efficiency were common to many MDTs.

MDT care is understood and applied differently across the world. There is a lack of standardisation of practice, and an apparent need for better case preparation, effective specialist contribution, improved audit frequency and metrics to improve performance. It may be valuable to consider human factors while designing MDTs to support team decision processes, minimise errors, and enhance efficiency.

Multidisciplinary team (MDT) meetings have emerged as a promising approach for the treatment of cancer patients. These meetings involve a team of healthcare professionals from different disciplines working together to develop a holistic, patient-centered treatment. Although MDT meetings are well established in oncology, they play a minor role in other diseases. Recent evidence suggests that the implementation of MDT meetings can improve patient outcomes in musculoskeletal infections. The aim of this retrospective, observational study was to present the agenda of our multidisciplinary limb board including live microscopy with a special focus on the pathologist's role. The descriptive analysis of the limb board included 66 cases receiving live microscopy at the meeting and a total of 124 histopathological findings and 181 stainings. We could elucidate that pathologists seem to play an important role especially in clarifying the correct diagnosis. In 80.3 % of the findings, the pathologist specified the clinical diagnosis of the requesting physician leading to a consensus-based treatment plan for each patient. The implementation of MDT meetings including live microscopy in patients with musculoskeletal infections holds potential benefits, such as improved communication, scientific collaboration, and raising clinicians' awareness and understanding of histopathology findings. However, potential challenges, such as organizational effort and technical prerequisites should be considered.

Hypoxia is a hallmark of solid tumors. Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment, and CAF-derived exosomes are involved in cancer genesis and progression. Here, this work investigated the role and mechanism of exosomal circHIF1A derived from hypoxia-induced CAFs in hepatocellular carcinoma (HCC) tumorigenesis. CAFs isolated from fresh HCC tissues were incubated in normoxia or hypoxia condition (N/CAFs or H/CAFs), and then the exosomes from N/CAFs or H/CAFs were isolated for functional analysis. Cell proliferation, migration and invasion were analyzed by cell counting kit-8, colony formation, and transwell assays. Immune evasion was evaluated by measuring the cytotoxicity and viability of CD8+T cells. qRT-PCR and western blotting analyses were used for the level measurement of genes and proteins. The binding between Hu antigen R (HuR) and circHIF1A or Programmed death ligand 1 (PD-L1) was analyzed by RNA immunoprecipitation assay. Functionally, we found that CAFs, especially CAFs under hypoxic stress (H/CAFs), promoted the proliferation, migration, invasion and EMT progression in HCC cells, as well as induced immune escape by suppressing CD8+T cell cytotoxicity and activity in an exosome-dependent manner. H/CAFs-derived exosomes showed highly expressed circHIF1A, and could secrete circHIF1A into HCC cells via exosomes. The oncogenic effects of H/CAFs-secreted exosomes were abolished by circHIF1A knockdown. Mechanistically, circHIF1A interacted with HuR to stabilize PD-L1 expression in HCC cells. Meanwhile, circHIF1A silencing suppressed HCC cell proliferation, mobility and immune escape by regulating PD-L1 expression. In all, exosomal circHIF1A derived from hypoxic-induced CAFs promoted the proliferation, migration, invasion, EMT progression and immune escape in HCC cells by up-regulating PD-L1 expression in a HuR-dependent manner.

Increased prevalence of hepatocellular carcinoma (HCC) remains a global health challenge. HCC chemoresistance is a clinical obstacle for its management. Aberrant miRNA expression is a hallmark for both cancer progression and drug resistance. However, it is unclear which miRNAs are involved in HCC chemoresistance.

MicroRNA microarray analysis revealed a differential expression profile of microRNAs between the hepatocellular carcinoma HA22T cell line and the HDACi-R cell line, which was validated by quantitative real-time PCR (qRT-PCR). To determine the biological function of miR-342-5p and the mechanism of the microRNA-342-5p/CFL1 axis in hepatocellular carcinoma HDACi resistance, loss- and gain-of-function studies were conducted in vitro.

Here we demonstrated the molecular mechanism of histone deacetylase inhibitor (HDACi) resistance in HCC. Differential miRNA expression analysis showed significant down regulation of miR-342-5p in HDACi-R cells than in parental HA22T cells. Mimics of miR-342-5p enhanced apoptosis through upregulation of Bax, cyto-C, cleaved-caspase-3 expressions with concomitant decline in anti-apoptotic protein (Bcl-2) in HDACi-R cells. Although HDACi did not increase cell viability of HDACi-R, overexpression of miR-342-5p decreased cofilin-1 expression, upregulated reactive oxygen species (ROS) mediated apoptosis, and sensitized HDACi-R to HDACi in a dose-dependent manner.

Our findings demonstrated the critical role of miR-342-5p in HDACi resistance of HCC and that this mechanism might be attributed to miR-342-5p/cofilin-1 regulation.

Studies have shown that the abnormal expression of circular RNA (circRNA) is inextricably linked to hepatocellular carcinoma (HCC). Recently, hsa_circ_0000518 (circ_0000518) was discovered in many cancer progressions. However, its function in HCC is still unclear. Through GEO database analysis combined with gene expression detection of HCC related clinical samples and cell lines, we identified that circ_0000518 was abnormally overexpressed in HCC. Cell and animal model experiments jointly indicated that circ_0000518 can stimulate HCC cell proliferation, migration, invasion and suppress apoptosis. Furthermore, we also found that knocking down the circ_0000518 could inhibit the Warburg effect in HCC cells. Mechanistically, circ_0000518 was found to be primarily localized in the cytoplasm, and sponge hsa-miR-326 (miR-326) promoted integrin alpha 5 (ITGA5) expression. In addition, circ_0000518 could enhance the stability of HuR-mediated ITGA5 mRNA, thereby activating the Warburg effect. In conclusion, this study elucidated that circ_0000518 was a cancer-promoting circRNA, which could enhance ITGA5 expression through competing endogenous RNAs (ceRNA) and RNA Binding Protein (RBP) mechanisms, thus facilitating the development of HCC. It provides a meaningful diagnostic and therapeutic target for HCC.

The 2022 Barcelona Clinic Liver Cancer algorithm currently discourages liver resection (LR) for patients with multinodular hepatocellular carcinoma (HCC) presenting with 2 or 3 nodules that are each 3 cm or smaller.

To compare the efficacy of liver resection (LR), percutaneous radiofrequency ablation (PRFA), and transarterial chemoembolization (TACE) in patients with multinodular HCC.

This cohort study is a retrospective analysis conducted using data from the HE.RC.O.LE.S register (n = 5331) for LR patients and the ITA.LI.CA database (n = 7056) for PRFA and TACE patients. A matching-adjusted indirect comparison (MAIC) method was applied to balance data and potential confounding factors between the 3 groups. Included were patients from multiple centers from 2008 to 2020; data were analyzed from January to December 2023.

LR, PRFA, or TACE.

Survival rates at 1, 3, and 5 years were calculated. Cox MAIC-weighted multivariable analysis and competing risk analysis were used to assess outcomes.

A total of 720 patients with early multinodular HCC were included, 543 males (75.4%), 177 females (24.6%), and 350 individuals older than 70 years (48.6%). There were 296 patients in the LR group, 240 who underwent PRFA, and 184 who underwent TACE. After MAIC, LR exhibited 1-, 3-, and 5-year survival rates of 89.11%, 70.98%, and 56.44%, respectively. PRFA showed rates of 94.01%, 65.20%, and 39.93%, while TACE displayed rates of 90.88%, 48.95%, and 29.24%. Multivariable Cox survival analysis in the weighted population showed a survival benefit over alternative treatments (PRFA vs LR: hazard ratio [HR], 1.41; 95% CI, 1.07-1.86; P = .01; TACE vs LR: HR, 1.86; 95% CI, 1.29-2.68; P = .001). Competing risk analysis confirmed a lower risk of cancer-related death in LR compared with PRFA and TACE.

For patients with early multinodular HCC who are ineligible for transplant, LR should be prioritized as the primary therapeutic option, followed by PRFA and TACE when LR is not feasible. These findings provide valuable insights for clinical decision-making in this patient population.

Multidisciplinary clinics (MDCs) are gaining momentum throughout the medical field, having initially been pioneered in oncology clinics due to their inherent ability to streamline complex care and improve both patient outcomes and the patient care experience. Liver transplant and hepatobiliary tumor clinics are examples of established MDCs in hepatology. With the changing landscape of liver disease in regard to etiology and patient complexity and acuity, there is a clear need for efficient, highly coordinated care. These changes highlight opportunities for hepatology MDCs in alcohol-associated liver disease, metabolic dysfunction-associated steatotic liver disease, and palliative care. This review provides practical advice in navigating the complex logistics of establishing and maintaining a hepatology MDC while also reviewing the emerging evidence on clinical outcomes for patients seen in these MDCs. As hepatology looks to the future, establishment of MDCs in key clinical areas will be the cornerstone of patient care.

The risk of hepatocellular carcinoma (HCC) declines over time after hepatitis C virus (HCV) cure by direct-acting antiviral (DAA) therapies. Liver society guidelines recommend continuing HCC screening for these patients, but data on screening outcomes are lacking.

To evaluate the association of HCC screening after HCV cure with overall survival.

This cohort study evaluated patients with HCV cirrhosis who achieved DAA-induced HCV cure in the Veterans Affairs health care system between January 2014 and December 2022. Data analysis occurred from October 2023 to January 2024.

The percentage of time spent up to date with recommended HCC screening was calculated by year of follow-up and during the 4 years preceding HCC diagnosis (the detectable asymptomatic phase).

The primary outcome was overall survival after HCC diagnosis and was compared by percentage of time spent up to date with screening using Kaplan-Meier analyses and Cox proportional hazards regression. Early-stage HCC at diagnosis and curative treatment were secondary outcomes assessed using logistic regression.

A total of 16 902 individuals were included (median [IQR] age, 64.0 [60.5-67.4] years; 16 426 male [97.2%]), of whom 1622 developed HCC. The cumulative incidence of HCC declined from 2.4% (409 of 16 902 individuals) to 1.0% (27 of 2833 individuals) from year 1 to year 7 of follow-up. Being up to date with screening for at least 50% of time during the 4 years preceding HCC diagnosis was associated with improved overall survival (log-rank test of equality over strata P = .002). In multivariate analysis, each 10% increase in follow-up spent up to date with screening was associated with a 3.2% decrease in the hazard of death (hazard ratio, 0.97; 95% CI, 0.95-0.99). There was a statistically significant interaction between time since HCV cure and screening, with no association observed among those who received a diagnosis of HCC more than 5 years after HCV cure. Each 10% of time spent up to date with screening was associated with a 10.1% increased likelihood of diagnosis with early-stage HCC (95% CI, 6.3%-14.0%) and a 6.8% increased likelihood of curative treatment (95% CI, 2.8%-11.0%).

In this cohort study of persons with HCV-related cirrhosis who achieved HCV cure and subsequently developed HCC, remaining up to date with screening was associated with improved overall survival, supporting the screening of eligible individuals.

Individuals with cirrhosis experience higher morbidity and mortality rates than the general population, irrespective of the type or scope of surgery. This increased risk is attributed to adverse effects of liver disease, encompassing coagulation dysfunction, altered metabolism of anesthesia and sedatives, immunologic dysfunction, hemorrhage related to varices, malnutrition and frailty, impaired wound healing, as well as diminished portal blood flow, overall hepatic circulation, and hepatic oxygen supply during surgical procedures. Therefore, a frequent clinical dilemma is whether surgical interventions should be pursued in patients with cirrhosis. Several risk scores are widely used to aid in the decision-making process, each with specific advantages and limitations. This review aims to discuss the preoperative risk factors in patients with cirrhosis, describe and compare surgical risk assessment models used in everyday practice, provide insights into the surgical risk according to the type of surgery and present recommendations for optimizing those with cirrhosis for surgical procedures. As the primary focus is on currently available risk models, the review describes the predictive value of each model, highlighting its specific advantages and limitations. Furthermore, for models that do not account for the type of surgical procedure to be performed, the review suggests incorporating both patient-related and surgery-related risks into the decision-making process. Finally, we provide an algorithm for the preoperative assessment of patients with cirrhosis before elective surgery as well as guidance perioperative management.

Cancer-related fatigue (CRF) is a common and debilitating symptom experienced by patients with advanced-stage cancer, especially those undergoing antitumor therapy. This study aimed to evaluate the efficacy and safety of Renshenguben (RSGB) oral solution, a ginseng-based traditional Chinese medicine, in alleviating CRF in patients with advanced hepatocellular carcinoma (HCC) receiving antitumor treatment.

In this prospective, open-label, controlled, multicenter study, patients with advanced HCC at BCLC stage C and a brief fatigue inventory (BFI) score of ≥ 4 were enrolled. Participants were assigned to the RSGB group (RSGB, 10 mL twice daily) or the control group (with supportive care). Primary and secondary endpoints were the change in multidimensional fatigue inventory (MFI) score, and BFI and functional assessment of cancer therapy-hepatobiliary (FACT-Hep) scores at weeks 4 and 8 after enrollment. Adverse events (AEs) and toxicities were assessed.

A total of 409 participants were enrolled, with 206 assigned to the RSGB group. At week 4, there was a trend towards improvement, but the differences were not statistically significant. At week 8, the RSGB group exhibited a significantly lower MFI score (P < 0.05) compared to the control group, indicating improved fatigue levels. Additionally, the RSGB group showed significantly greater decrease in BFI and FACT-Hep scores at week 8 (P < 0.05). Subgroup analyses among patients receiving various antitumor treatments showed similar results. Multivariate linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI, BFI, and FACT-Hep scores at week 8. No serious drug-related AEs or toxicities were observed.

RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period, with no discernible toxicities. These findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.

The role of circRNAs in hepatocellular carcinoma (HCC) progression remains unclear. CircPIAS1 (circBase ID: hsa_circ_0007088) was identified as overexpressed in HCC cases through bioinformatics analysis. This study aimed to investigate the oncogenic properties and mechanisms of circPIAS1 in HCC development.

Functional analyses were conducted to assess circPIAS1's impact on HCC cell proliferation, migration, and ferroptosis. Xenograft mouse models were employed to evaluate circPIAS1's effects on tumor growth and pulmonary metastasis in vivo. Bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays were utilized to elucidate the molecular pathways influenced by circPIAS1. Additional techniques, including RNA pulldown, fluorescence in situ hybridization (FISH), chromatin immunoprecipitation (ChIP), qPCR, and western blotting, were used to further explore the underlying mechanisms.

CircPIAS1 expression was elevated in HCC tissues and cells. Silencing circPIAS1 suppressed HCC cell proliferation and migration both in vitro and in vivo. Mechanically, circPIAS1 overexpression inhibited ferroptosis by competitively binding to miR-455-3p, leading to upregulation of Nuclear Protein 1 (NUPR1). Furthermore, NUPR1 promoted FTH1 transcription, enhancing iron storage in HCC cells and conferring resistance to ferroptosis. Treatment with ZZW-115, an NUPR1 inhibitor, reversed the tumor-promoting effects of circPIAS1 and sensitized HCC cells to lenvatinib.

This study highlights the critical role of circPIAS1 in HCC progression through modulation of ferroptosis. Targeting the circPIAS1/miR-455-3p/NUPR1/FTH1 regulatory axis may represent a promising therapeutic strategy for HCC.

Management of hepatocellular carcinoma (HCC) is challenging due to the complex relationship between underlying liver disease, tumor burden, and liver function. HCC is also notorious for its high recurrence rate even after curative treatment for early-stage tumor. Liver transplantation can substantially alter patient prognosis, but donor availability varies by each patient which further complicates treatment decision. Recent advancements in HCC treatments have introduced numerous potentially efficacious treatment modalities. However, high level evidence comparing the risks and benefits of these options is limited. In this complex situation, multidisciplinary approach or multidisciplinary team care has been suggested as a valuable strategy to help cope with escalating complexity in HCC management. Multidisciplinary approach involves collaboration among medical and health care professionals from various academic disciplines to provide comprehensive care. Although evidence suggests that multidisciplinary care can enhance outcomes of HCC patients, robust data from randomized controlled trials are currently lacking. Moreover, the implementation of a multidisciplinary approach necessitates increased medical resources compared to conventional cancer care. This review summarizes the current evidence on the role of multidisciplinary approach in HCC management and explores potential future directions.

This review explores the evolution of cancer staging, focusing on intermediate hepatocellular carcinoma (HCC), and the challenges faced by physicians. The Barcelona Clinic Liver Cancer (BCLC) staging system, introduced in 1999, was designed to address the limitations associated with providing accurate prognostic information for HCC and allocating specific treatments, to avoid overtreatment. However, criticism has emerged, particularly regarding the intermediate stage of HCC (BCLC-B) and its heterogeneous patient population. To overcome this limitation, various subclassification systems, such as the Bolondi and Kinki criteria, have been proposed. These systems are aimed at refining categorizations within the intermediate stage and have demonstrated varying degrees of success in predicting outcomes through external validation. This study discusses the shift in treatment paradigms, emphasizing the need for a more personalized approach rather than strictly adhering to cancer stages, without dismissing the relevance of staging systems. It assesses the available treatment options for intermediate-stage HCC, highlighting the importance of considering surgical and nonsurgical options alongside transarterial chemoembolization for optimal outcomes. In conclusion, the text advocates for a paradigm shift in staging systems prioritizing treatment suitability over cancer stage. This reflects the evolving landscape of HCC management, where a multidisciplinary approach is crucial for tailoring treatments to individual patients, ultimately aiming to improve overall survival.

Hepatocellular carcinoma (HCC) accounts for 75% of primary liver tumors. Controlling risk factors associated with its development and implementing screenings in risk populations does not seem sufficient to improve the prognosis of these patients at diagnosis. The development of a predictive prognostic model for mortality at the diagnosis of HCC is proposed.

In this retrospective multicenter study, the analysis of data from 191 HCC patients was conducted using machine learning (ML) techniques to analyze the prognostic factors of mortality that are significant at the time of diagnosis. Clinical and analytical data of interest in patients with HCC were gathered.

Meeting Milan criteria, Barcelona Clinic Liver Cancer (BCLC) classification and albumin levels were the variables with the greatest impact on the prognosis of HCC patients. The ML algorithm that achieved the best results was random forest (RF).

The development of a predictive prognostic model at the diagnosis is a valuable tool for patients with HCC and for application in clinical practice. RF is useful and reliable in the analysis of prognostic factors in the diagnosis of HCC. The search for new prognostic factors is still necessary in patients with HCC.

Liver cancer is the third most common cause of cancer-related deaths worldwide, and hepatocellular carcinoma (HCC) makes up the majority of liver cancer cases. Despite the stabilization of incidence rates in recent years due to effective viral hepatitis treatments, as well as improved outcomes from early detection and treatment advances, the burden of HCC is anticipated to rise again due to increasing rates of metabolic dysfunction-associated steatotic liver disease and alcohol-related liver disease. The treatment landscape is evolving and requires a multidisciplinary approach, often involving multi-modal treatments that include surgical resection, transplantation, local regional therapies, and systemic treatments. The optimal approach to the care of the HCC patient requires a multidisciplinary team involving hepatology, medical oncology, diagnostic and interventional radiology, radiation oncology, and surgery. In order to determine which approach is best, an individualized treatment plan should consider the patient's liver function, functional status, comorbidities, cancer stage, and preferences. In this review, we provide an overview of the current treatment options and key trials that have revolutionized the management of HCC. We also discuss evolving treatment paradigms for the future.

There is growing acceptance that principles of palliative care should be integrated into the management of serious illnesses affecting the liver, such as acute-on-chronic liver failure (ACLF). However, rates, patterns, and predictors of specialty palliative care consultation among patients with ACLF have not been well-described.

We performed a retrospective cohort study of patients hospitalized with ACLF between 1/1/2008 and 12/31/2018 using the VOCAL cohort. Patients were followed until 6/2021. We used mixed-effects regression analyses to identify significant patient and facility factors associated with palliative care consultation. We examined timing of consultation, the influence of ACLF characteristics, and facility-level variation on receipt of palliative care consultation.

We identified 21,987 patients hospitalized with ACLF, of whom 30.5% received specialty palliative care consultation. Higher ACLF grade (ACLF-2 [odds ratio (OR) 1.82, 95% CI 1.67-1.99], ACLF-3 [OR 3.06, 95% CI 2.76-3.40]), prior specialty palliative care consultation (OR 2.62, 95% CI 2.36-2.91), and hepatocellular carcinoma (OR 2.10, 95% CI 1.89-2.33) were associated with consultation. Consultation occurred latest and closest to the time of death for patients with ACLF-3 compared to ACLF-1 and ACLF-2. Significant facility-level variation in consultation persisted among patients with ACLF-3, despite adjusting for multiple patient and facility factors.

In this large cohort of hospitalized patients with ACLF, specialty palliative care consultation was rare, more common in patients with higher grade ACLF, and tended to occur closer to the time of death for the sickest patients. Greater attention should be placed on earlier integration of palliative care during acute hospitalizations in patients with ACLF.

Though palliative care consultation is recommended for patients with acute-on-chronic liver failure, there is no data demonstrating how often this occurs during hospitalizations, on a population level. We found that consultation occurs in only 30.5% of patients and occurs later for patients with grade 3 acute-on-chronic liver failure. Our data should provoke clinicians to urgently consider quality improvement efforts to integrate palliative care into the management of these seriously ill patients.

Worldwide, hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. The remarkable improvements in treating HCC achieved in the last years have increased the complexity of HCC management. Following the need to have updated guidelines on the multidisciplinary treatment management of HCC, the Italian Scientific Societies involved in the management of this cancer have promoted the drafting of a new dedicated document. This document was drawn up according to the GRADE methodology needed to produce guidelines based on evidence. Here is presented the first part of guidelines, focused on the multidisciplinary tumor board of experts and surgical treatments of HCC.

The ubiquitin-proteasome system is a vital protein degradation system that is involved in various cellular processes, such as cell cycle progression, apoptosis, and differentiation. Dysregulation of this system has been implicated in numerous diseases, including cancer, vascular disease, and neurodegenerative disorders. Induction of cellular senescence in hepatocellular carcinoma (HCC) is a potential anticancer strategy, but the precise role of the ubiquitin-proteasome system in cellular senescence remains unclear. In this study, we show that the E3 ubiquitin ligase, TRIM22, plays a critical role in the cellular senescence of HCC cells. TRIM22 expression is transcriptionally upregulated by p53 in HCC cells experiencing ionizing radiation (IR)-induced senescence. Overexpression of TRIM22 triggers cellular senescence by targeting the AKT phosphatase, PHLPP2. Mechanistically, the SPRY domain of TRIM22 directly associates with the C-terminal domain of PHLPP2, which contains phosphorylation sites that are subject to IKKβ-mediated phosphorylation. The TRIM22-mediated PHLPP2 degradation leads to activation of AKT-p53-p21 signaling, ultimately resulting in cellular senescence. In both human HCC databases and patient specimens, the levels of TRIM22 and PHLPP2 show inverse correlations at the mRNA and protein levels. Collectively, our findings reveal that TRIM22 regulates cancer cell senescence by modulating the proteasomal degradation of PHLPP2 in HCC cells, suggesting that TRIM22 could potentially serve as a therapeutic target for treating cancer.

The 2022 Barcelona Clinic Liver Cancer (BCLC) algorithm does not recommend liver resection (LR) in BCLC A patients with oligo-nodular (two or three nodules ≤3 cm) hepatocellular carcinoma (HCC). This sharply contrasts with the therapeutic hierarchy concept, implying a precise treatment order exists within each BCLC stage. This study aimed to compare the outcomes of LR versus radiofrequency ablation (RFA) or trans-arterial chemoembolization (TACE) in BCLC A patients.

A meta-analysis adhering to PRISMA guidelines and the Cochrane Handbook was performed. All RCT, cohort and case-control studies that compared LR versus RFA or TACE in oligo-nodular BCLC A HCC published between January 2000 and October 2023 were comprehensively searched on PubMed, Embase, the Cochrane Library and China Biology Medicine databases. Primary outcomes were overall survival (OS) and disease-free survival (DFS) at 3 and 5 years. Risk ratio (RR) was computed as a measure of treatment effect (OS and DFS benefit) to calculate common and random effects estimates for meta-analyses with binary outcome data.

2601 patients from 14 included studies were analysed (LR = 1227, RFA = 686, TACE = 688). There was a significant 3- and 5-year OS benefit of LR over TACE (RR = 0.55, 95% c.i. 0.44 to 0.69, P < 0.001 and RR 0.57, 95% c.i. 0.36 to 0.90, P = 0.030, respectively), while there was no significant 3- and 5-year OS benefit of LR over RFA (RR = 0.78, 95% c.i. 0.37 to 1.62, P = 0.452 and RR 0.74, 95% c.i. 0.50 to 1.09, P = 0.103, respectively). However, a significant 3- and 5-year DFS benefit of LR over RFA was found (RR = 0.70, 95% c.i. 0.54 to 0.93, P = 0.020 and RR 0.82, 95% c.i. 0.72 to 0.95, P = 0.015, respectively). A single study comparing LR and TACE regarding DFS showed a significant superiority of LR. The Newcastle-Ottawa Scale quality of studies was high in eight (57%) and moderate in six (43%).

In BCLC A oligo-nodular HCC patients, LR should be preferred to RFA or TACE (therapeutic hierarchy concept). Additional comparative cohort studies are urgently needed to increase the certainty of this evidence.

Hepatocellular carcinoma (HCC) presents significant treatment challenges despite considerable advancements in its management. The Indian National Association for the Study of the Liver (INASL) first published its guidelines to aid healthcare professionals in the diagnosis and treatment of HCC in 2014. These guidelines were subsequently updated in 2019. However, INASL has recognized the need to revise its guidelines in 2023 due to recent rapid advancements in the diagnosis and management of HCC, particularly for intermediate and advanced stages. The aim is to provide healthcare professionals with evidence-based recommendations tailored to the Indian context. To accomplish this, a task force was formed, and a two-day round table discussion was held in Puri, Odisha. During this event, experts in their respective fields deliberated and finalized consensus statements to develop these updated guidelines. The 2023 INASL guidelines offer a comprehensive framework for the diagnosis, staging, and management of intermediate and advanced HCC in India. They represent a significant step forward in standardizing clinical practices nationwide, with the primary objective of ensuring that patients with HCC receive the best possible care based on the latest evidence. The guidelines cover various topics related to intermediate and advanced HCC, including biomarkers of aggressive behavior, staging, treatment options, and follow-up care.

5-Methylcytosine (m5C) is one of the most ubiquitous modifications of mRNA and contributes to cancer pathogenesis. Aly/REF export factor (ALYREF), an m5C reader, is associated with the prognosis of liver hepatocellular carcinoma (LIHC). However, the effects of ALYREF on the progression of LIHC and the underlying molecular mechanisms remains elusive. Through an analysis of an online database and 3 independent LIHC cohorts, we found that ALYREF was markedly elevated in human liver cancer tissues and was significantly correlated with LIHC clinicopathological parameters, including Ki67+ cell rate, high-grade TNM stage, and poor prognosis. Several experiments were conducted to investigate the molecular basis and functional role of ALYREF-related progression in this study. ALYREF could enhance LIHC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro and tumor formation in vivo. Mechanistically, ALYREF promoted the progression of human LIHC through EGFR pathways. Furthermore, ALYREF could directly bind to the m5C modification site of EGFR 3' untranslated region (3' UTR) to stabilize EGFR mRNA. Collectively, ALYREF played a crucial oncogenic role in LIHC via the stabilization of EGFR mRNA and subsequent activation of the STAT3 signaling pathway. Our results may help to elucidate the potential mechanisms of ALYREF-induced m5C modification in the progression of human LIHC.

To study the experiences of patients with hepatocellular carcinoma (HCC) contributing to treatment discrepancy in the United States.

Using Surveillance, Epidemiology, and End Results data from National Cancer Institute (NCI), Medicare (2002-2015) beneficiaries with HCC who completed a Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey were included. Six CAHPS items (3 global scores: global care rating [GCR], primary doctor rating [PDR], and specialist rating [SR]; 3 composite scores: getting needed care [GNC], getting care quickly [GCQ], and doctor communication [DC]) assessed patient experience. Covariates assessed between treated and nontreated groups included patient, disease, hospital, and CAHPS items.

Among 548 patients with HCC, 211 (39%) received treatment and 337 (61%) did not receive treatment. Forty-two percent (GCR), 29% (PDR), 30% (SR), 36% (GNC), 78% (GCQ), and 35% (DC) of patients reported less-than-excellent experiences on the respective CAHPS items. Chronic liver disease (CLD) was present in 52% and liver decompensation (LD) in 60%. A minority of the hospitals were NCI-designated cancer centers (47%), transplant centers (27%), and referral centers (9%). On univariable analysis, patients with at least a high school degree (odds ratio [OR], 1.9), admittance to a ≥400-bed hospital (OR, 2.7), CLD (OR, 3.0), or LD (OR, 1.7) were more likely to receive treatment, whereas older patients (≥75 years) (OR, 0.5) were less likely to receive treatment. On multivariable, patients with CLD (OR, 6.8) and an excellent experience in GNC with a specialist (OR, 10.6) were more likely to receive treatment.

HCC treatment discrepancy may be associated with patient-related factors, such as lack of specialist care (GNC), and disease-related factors, such as absence of underlying CLD.

Multidisciplinary team care coordinates with medical teams to improve the quality of cancer care. This study explored multidisciplinary team care in hepatitis B or hepatitis C virus-related hepatocellular carcinoma patients from the time of diagnosis to the first-time treatment interval and investigated treatment outcomes and prognosis.

This retrospective cohort study included data from a nationwide population from 2007 to 2016. Data were collected from the Taiwan Cancer Registry Database, linked to the Taiwan National Health Insurance Research Database. Propensity score matching was applied at a ratio of 1:2 to reduce the selection bias. A multiple regression model with generalized estimating equations was used to analyze whether multidisciplinary team care affected the diagnosis-to-treatment interval. The stratified Cox proportional hazards model examined whether involvement in multidisciplinary team care influenced survival status.

A total of 10,928 and 21,856 patients with hepatocellular carcinoma received multidisciplinary and non-multidisciplinary care, respectively. Participants with multidisciplinary care had a longer diagnosis-to-treatment interval but a lower risk of cumulative cancer death (HR=0.88, 95% CI:0.84-0.92). In patients with intermediate- to advanced-stage hepatocellular carcinoma, multidisciplinary team care has obvious benefits for improving survival.

Patients with hepatocellular carcinoma who participated in multidisciplinary team care had a longer diagnosis-to-treatment interval but a lower risk of cancer death. Patients with intermediate- to advanced-stage hepatocellular carcinoma who received multidisciplinary team care significantly benefited from this outcome. Hospitals should provide HCC patients with multidisciplinary team care to improve cancer care.

Diabetes is associated with HCC; however, the impact of longitudinal blood glucose (BG) control on HCC risk in cirrhosis is not well known. We investigated this knowledge gap in a cohort of United States Veterans with cirrhosis from 2015 to 2021.

We used repeated hemoglobin A1c measurements to categorize follow-up time according to BG control (defined as hemoglobin A1c < 7%) state over time: uncontrolled, nonsustained control (≤2 y), or sustained control (>2 y). We performed a sensitivity analysis using hemoglobin A1c < 8% to define BG control. We used Fine and Gray Cox proportional hazards regression with death and transplant as competing events to compare rates of incident HCC.

Our study included 81,907 individuals, 56.2% of whom had diabetes at baseline. There were 8,002 incident HCCs. The rate of HCC was 18% higher in diabetes (95% CI: 13% - 24%), and the relative increase in the rate of HCC varied by etiology of cirrhosis from nonsignificant (HCV) to an increase of 120% (HBV). Uncontrolled and nonsustained BG control was associated with 1.80 (95% CI: 1.70-1.91) and 2.34 (95% CI: 2.21-2.48) times the rate of HCC compared to sustained BG control, respectively. Using Hgb A1c < 8% to define BG control, HCC rates in uncontrolled and nonsustained BG control were 2.43 (2.28-2.58) and 2.23 (2.11-2.36) times that observed in sustained BG control.

Associations between diabetes and HCC in cirrhosis vary according to the longitudinal BG control state. Inadequate BG control is consistently associated with a higher risk of HCC, and long-term BG control should be considered in comprehensive cirrhosis care.