Hepatocellular carcinoma is one of the leading causes of cancer deaths globally and a key hindrance to extending life expectancy. Celastrol (CEL) demonstrates excellent antitumor activity, but faces challenges like low solubility and a narrow therapeutic window, limiting its clinical application. To address these limitations, drug combinations and nano-delivery systems have emerged as effective solutions. Curcumin (CUR), known for its antitumor and hepatoprotective effects, also exhibits good biocompatibility and the ability to mitigate drug-induced liver injury. Considering the complementary properties of CEL and CUR, including CEL's potent antitumor activity and CUR's hepatoprotective effects, we developed a novel self-assembling nanodrug delivery system (CCPN) for the co-loading of both compounds. CCPN nanoparticles were constructed through non-covalent interactions, including hydrogen bonding, π-π stacking, and electrostatic forces, which confer good stability and significantly enhance the solubility and bioavailability of CEL and CUR. Extensive in vitro and in vivo experiments demonstrated that CCPN effectively reduced CEL-induced hepatotoxicity in zebrafish and mouse models, exhibiting good biosafety. Additionally, CUR's fluorescence provides a unique advantage for real-time monitoring of drug distribution and release, facilitating the tracking of therapeutic progress. Furthermore, CCPN nanoparticles enhanced delivery efficiency in HepG2 cells, exhibiting superior anti-liver tumor outcomes, which are associated with the promotion of apoptosis in tumor cells. This study presents CCPN as a promising therapeutic strategy for hepatocellular carcinoma, integrating reduced hepatotoxicity, self-monitoring capabilities, and superior therapeutic efficacy.

Since 2017, immune checkpoint inhibitors (ICIs) have been available for the treatment of advanced hepatocellular carcinoma (HCC) or unresectable HCC, but their adoption into national medical insurance programs is still limited. Cost-effectiveness evidence can help to inform treatment decisions. This systematic review aimed to provide a critical summary of economic evaluations of ICIs as a treatment for advanced HCC and identify key drivers (PROSPERO 2023: CRD42023417391). The databases used included Scopus, Web of Science, PubMed, Embase, and Cochrane Central. Economic evaluations of ICIs for the treatment of advanced HCC were included. Studies were screened by two people. Of the 898 records identified, 17 articles were included. The current evidence showed that ICIs, including atezolizumab plus bevacizumab, sintilimab plus bevacizumab/bevacizumab biosimilar, nivolumab, camrelizumab plus rivoceranib, pembrolizumab plus lenvatinib, tislelizumab, durvalumab, and cabozantinib plus atezolizumab, are probably not cost-effective in comparison with tyrosine kinase inhibitors or other ICIs. The most influential parameters were price of anticancer drugs, hazard ratios for progression-free survival and overall survival, and utility for health statest. Our review demonstrated that ICIs were not a cost-effective intervention in advanced HCC. Although ICIs can significantly enhance the survival of patients with advanced HCC, decision-makers should consider the findings of economic evaluations and affordability before adoption of new therapies.

Hepatocellular carcinoma (HCC) is a malignant primary liver cancer with poor prognosis. Most previous studies on anti-HCC effects of traditional Chinese medicines (TCM) have focused on the mechanism of direct action and few researchers considered that TCM can inhibit tumor progression and improve prognosis of HCC patients through regulating tumor microenvironment (TME). In this study, network pharmacology combined bioinformatics methods were employed to analysis mechanism of Bombyx batryticatus (B. batryticatus, one of the most frequently used traditional Chinese animal medicines, has been used in some Asian countries for centuries as an anticancer agent, anti-inflammatory agent, and antioxidant.) in regulating TME of HCC. The results showed that 24 core targets and 2 compounds were identified from overlapping between differential expression genes related to HCC in the cancer genome atlas (TCGA) database and targets of B. batryticatus in TCMSP database. For further analyzing the role of TME heterogeneity of HCC on anti-HCC mechanism of B. batryticatus, the correlation of core targets related with overall survival of HCC with TME cells in hepatitis C or hepatitis B virus-associated hepatocellular carcinoma (VIR) and non-hepatitis C or hepatitis B virus-associated hepatocellular carcinoma (NVIR) were calculated, respectively. The results showed that AKR1C3, SPP1 were significantly related with macrophages in VIR and other targets including NR1I2, CYP1A2 and CYP3A4 were significantly associated with macrophages in NVIR; the target protein AKR1C3 was significantly negative correlated with macrophages M1 in VIR (cor=-0.35, P-value0.05). In conclusion, the molecular mechanism of anti-HCC of B. batryticatus can be related to the tumor microenvironment to some extent. B. batryticatus may exert its anti-cancer effects and improve prognosis of patients by regulating macrophages M1 in VIR and NVIR through acting on different targets.

BACKGROUND: Quality indicators are the measurable components of clinical standards. Data are limited the design and impact of interventions to improve quality indicators for patients with chronic liver disease. METHODS: A systematic review of PubMed, Web of Science and conference proceedings was performed to find reports of quality improvement (QI) interventions. Data regarding the several indicators was collected. The search focused on vaccination against hepatitis A or hepatitis B virus, management of spontaneous bacterial peritonitis (SBP), screening for varices, management of acute variceal hemorrhage, hepatocellular carcinoma (HCC) screening and 30-day readmissions. RESULTS: Fifteen studies reported on the results of QI interventions. Nine focused on specific quality indicators (1 specific to vaccination, 2 SBP, 3 gastrointestinal bleeding, and 4 HCC screening); 5 focused on clinical outcomes. Most studies employed a pre-post study design. Interventions included checklists, educational conferences, electronic decision supports, nurse coordinators and systematic changes to facilitate specialist co-management. Successful interventions optimized clinical workflow, closed knowledge gaps among frontline providers, created forced-functions in the electronic ordering system, added dedicated staff to manage specific indicators and provided viable alternatives to hospitalization in order to reduce readmission. Unsuccessful interventions included case-management, phone-calls and home-visits to reduce readmissions, checklists and educational programs. CONCLUSION: Past experience with QI provides generalizable rules for successful future interventions aimed at improve quality indicator adherence and patient outcomes

AIM: To investigate the association between thrombocytopenia and relapse after treatment for hepatocellular carcinoma (HCC). METHODS: We searched the PubMed, EMBASE, and Web of Science databases to obtain eligible studies. The hazard ratios (HRs) values and 95% confidence intervals (CIs) were pooled by random effects model. Subsequently, we estimated the heterogeneity, performed a sensitivity analysis, determined the publication bias, and performed subgroup and meta-regression analyses. Study quality was assessed by using the Oxford Center for Evidence Based Medicine tool. RESULTS: We identified 18 eligible studies by retrieval (published during 2000-2014). Out of the 4163 patients with HCC who were recruited, 2746 (66.0%) experienced recurrence. In general, our meta-analysis suggested that low platelet count (PLT) before therapy significantly increased the probability of postoperative recurrence (HR = 1.53, 95%CI: 1.29-1.81). PLT was also valuable in the prediction of intrahepatic distant recurrence (HR = 1.49, 95%CI: 1.25-1.77). Subgroup and meta-regression analyses identified various therapeutic modalities as the source of a high degree of heterogeneity. The pooled HR values showed no obvious change when a single study was removed, but otherwise, an opposite-effects model was used. In addition, no significant publication bias was detected. CONCLUSION: Thrombocytopenia before treatment might be an inexpensive and useful predictor of postoperative recurrence in patients with HCC