BACKGROUND:To investigate the outcomes of combined lenvatinib plus immune checkpoint inhibitors (ICIs) in patients with unresectable, recurrent, or metastatic hepatocellular carcinoma (HCC) in a real-world setting. MATERIAL AND METHODS:This retrospective study included patients with unresectable, recurrent, or metastatic HCC who received lenvatinib combined with ICIs at the Fifth Medical Center of the Chinese PLA General Hospital between May 2018 and November 2022. The study outcomes were overall survival (OS), progression-free survival (PFS), and treatment response. RESULTS:This study included 117 patients. The objective response rate (comprising both complete and partial responses) was 53.2%. Among those with first-line lenvatinib plus ICI (n = 109), the disease control rate (complete response, partial response, and stable disease) was 89.9%. In all patients, the median OS and PFS were 26.0 (95% CI, 22.0-30.4) and 15.3 (95% CI, 13.2-17.5) months, respectively. In first-line patients, the median OS and PFS were 27.6 (95% CI, 23.4-34.6) and 15.4 (95% CI, 13.4-18.2) months, respectively. Among the 117 patients, treatment was discontinued in 58 (50%) because of AE (n = 9, 16%), PD (n = 43, 74%), or an unknown reason (n = 6, 10%). Among the 117 patients, treatment was interrupted in 26 (22%), and the dose was adjusted in 24 (21%). CONCLUSION:This real-world study supports the possibility of using lenvatinib combined with ICI for the management of patients with unresectable, recurrent, or metastatic HCC, including first-line treatment. Confirmation through a formal clinical trial would provide firmer conclusions.

BACKGROUND/AIMS:International guidelines recommend initiating transjugular intrahepatic portosystemic shunt (TIPS) placement with an 8-mm stent. However, there is an evident lack of randomized controlled trials evaluating TIPS diameters < 8 mm in cirrhotic patients with a relatively small liver. The aim of this study was to determine whether 7 mm-covered TIPS, compared with 8-mm stents, could achieve comparable shunt function with a lower incidence of hepatic encephalopathy (HE). METHODS:In this multicenter randomized controlled trial, patients with cirrhosis and relatively small liver were randomized 1:1 to receive TIPS with a 7-mm (n = 92) or 8-mm (n = 92) covered stent to prevent variceal rebleeding. The primary endpoint was the incidence of overt HE after randomization. All-cause rebleeding, orthotopic liver transplantation (OLT)-free survival and a composite of these outcomes, were designated as secondary endpoints. RESULTS:Among the 184 enrolled patients, the predominant etiologies of liver cirrhosis were hepatitis B virus infection (56.0%) and alcohol-related liver disease (20.7%). Over a median follow-up of 26.5 months, overt HE occurred in 19 patients (20.7%) in the 7-mm group and 33 patients (35.9%) in the 8-mm group. The 2-year cumulative incidence of overt HE was significantly lower in the 7-mm group than in the 8-mm group (21.4% vs. 37.2%, p = 0.02). Stent diameter, post-TIPS portosystemic pressure gradient, pre-covert HE and MELD-Na score were identified as independent risk factors for overt HE. The rates of shunt dysfunction were statistically similar between groups (8.7% vs. 8.7%, p = 1.0), as were 2-year rebleeding rates (10.9% vs. 9.8%, p = 0.81) and OLT-free survival rates (91.3% vs. 88.0%, p = 0.82). CONCLUSIONS:A 7-mm covered TIPS demonstrated comparable shunt function to an 8-mm covered stents, with a significantly lower risk of overt HE. These findings support consideration of 7-mm TIPS stents for preventing variceal rebleeding in cirrhotic patients with a small liver who are undergoing TIPS. TRAIL REGISTRATION:ClinicalTrials.gov, NCT02541825.

e16162 Background: Advanced intrahepatic cholangiocarcinoma (ICC) carries a dismal prognosis, with limited second-line options after failure of gemcitabine-based chemotherapy. Adebrelimab (anti-PD-L1 antibody) plus lenvatinib has shown potential in hepatobiliary cancers. This study evaluated the efficacy and safety of this combination in advanced ICC patients with heavy tumor burden and impaired liver function. Methods: This single-arm, open-label, phase II study enrolled patients with histologically confirmed unresectable or metastatic ICC who progressed on or were intolerant to first-line chemotherapy. Patients received adebrelimab (20 mg/kg IV Q3W) and oral lenvatinib (8 mg/day for weight < 60 kg; 12 mg/day for ≥60 kg). The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety (CTCAE v5.0). Results: As of January 12, 2026, 28 patients were enrolled (median age, 60.0 years). The cohort represented an exceptionally high-risk population: 18 patients (64.3%) had extrahepatic metastases, 13 (46.4%) had vascular invasion, and 20 (71.4%) were Child-Pugh class B. Furthermore, 24 patients (85.7%) met the "up-to-seven" criteria. After a median follow-up of 8.5 months (95% CI, 4.5 to 12.2), the median OS reached 12.2 months (95% CI, 6.3 to not reached), with a 12-month OS rate of 59.5% (95% CI, 40.9% to 86.5%). The median PFS was 6.3 months (95% CI, 4.0 to 12.4). In the ITT population, the ORR was 7.1% (2 of 28) and the DCR was 53.6% (15 of 28); however, response assessment was confounded by early treatment discontinuation or pending evaluations in 12 patients (42.9%). Treatment-related adverse events (TRAEs) of any grade occurred in 27 patients (96.4%). Grade 3-4 TRAEs were reported in 6 patients (21.4%), most commonly hepatic encephalopathy (3 patients, 10.7%), limb/shoulder pain (2 patients, 7.1%), and hyperbilirubinemia (2 patients, 7.1%). No treatment-related deaths were observed. Conclusions: Adebrelimab combined with lenvatinib demonstrated an unprecedented median OS of 12.2 months in second-line advanced ICC. Importantly, this survival benefit was maintained even in a population predominantly comprised of Child-Pugh class B patients with significant tumor burden. This combination represents a potential breakthrough for this difficult-to-treat population and warrants further validation in a randomized controlled trial. Clinical trial information: ChiCTR2300078869.

Aim: To evaluate the efficacy and safety of transarterial chemoembolization (TACE) plus regorafenib and PD-1 inhibitor (T-R-P) versus regorafenib plus PD-1 inhibitor (R-P) as the second-line treatment for unresectable hepatocellular carcinoma (uHCC). Methods: In this retrospective, single-center cohort study, 130 uHCC patients who received second-line therapy between February 2020 and July 2024 were enrolled. Among the 130 enrolled patients, 69 received T-R-P and 61 received R-P. Propensity score matching (PSM) and inverse probability treatment weighting (IPTW) were used to minimize confounding factors. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). Multivariate Cox regression analysis was used to identify prognostic factors. Subgroup analyses were conducted to assess the treatment benefits in specific patient populations. Results: After PSM, the T-R-P regimen showed significantly improved OS (14.3 vs 8.1 months) and PFS (8.4 vs 4.3 months) compared to the R-P regimen (P < 0.001). According to mRECIST, ORR (56.5% vs 15.2%) and DCR (69.6% vs 37.0%) were also significantly higher with the T-R-P regimen. Multivariate Cox regression analysis identified the T-R-P regimen as an independent protective factor for both OS (hazard ratio [HR] = 0.33, P < 0.001) and PFS (HR = 0.39, P < 0.001). These consistent survival benefits in the T-R-P regimen were maintained in both the unmatched cohort and after IPTW. Subgroup analyses further confirmed the consistent survival benefits of the T-R-P regimen across the most predefined patient subgroups. No treatment-related deaths occurred during the study period. Conclusion: After PSM, the T-R-P regimen continued to demonstrate statistically significant and clinically meaningful improvements in both OS and PFS, coupled with a manageable safety profile, compared to the R-P regimen in patients with uHCC. These findings provide a rationale for considering the T-R-P regimen as a potential second-line treatment option.

Introduction Lenvatinib resistance causes less than 40% of the objective response rate. Therefore, it is urgent to explore new therapeutic targets to reverse the lenvatinib resistance for HCC. HAND2-AS1 is a critical tumor suppressor gene in various cancers.Methods Here, we investigated the role of HAND2-AS1 in the molecular mechanism of lenvatinib resistance in HCC. It was found that HAND2-AS1 was lowly expressed in the HepG2 lenvatinib resistance (HepG2-LR) cells and HCC tissues and associated with progression-free intervals via TCGA. Overexpression of HAND2-AS1 (OE-HAND2-AS1) decreased the IC50 of lenvatinib in HepG2-LR cells to reverse lenvatinib resistance. Moreover, OE-HAND2-AS1 induced intracellular concentrations of malondialdehyde (MDA) and lipid ROS and decreased the ratio of glutathione to glutathione disulfide (GSH/GSSG) to promote ferroptosis.Results A xenograft model in which nude mice were injected with OE-HAND2-AS1 HepG2-LR cells confirmed that OE-HAND2-AS1 could reverse lenvatinib resistance and decrease tumor formation in vivo. HAND2-AS1 promoted the expression of ferroptosis-related genes (TLR4, NOX2, and DUOX2) and promoted ferroptosis to reverse lenvatinib resistance by increasing TLR4/NOX2/DUOX2 via competing endogenous miR-219a-1-3p in HCC cells. Besides, patients with a low HAND2-AS1 level had early recurrence after resection.Conclusion HAND2-AS1 promotes ferroptosis in HCC cells and reverses lenvatinib resistance by regulating TLR4/NOX2/DUOX2 axis. It suggested that HAND2-AS1 may be a potential therapeutic target and an indicator of early recurrence for HCC.

BackgroundChronic hepatitis B and cirrhosis pose significant global health threats. Few studies have explored the disease burden and mortality trend of cirrhosis caused by hepatitis B virus infection among adolescents and young adults (AYAs, aged 15–39 years). This study aimed to assess the disease burden and trends.MethodsPublicly available data were obtained from the 2021 GBD database. The rates of incidence, mortality, and disability-adjusted life years were calculated at the global, regional, and national levels. Temporal trends were assessed using joinpoint regression analysis, while the Bayesian age-period-cohort model was used to predict future trends.ResultsFrom 1990 to 2021, the global incidence rate of hepatitis B-related cirrhosis decreased from 111.33 (95% uncertainty interval: 89.18 to 134.98) to 67.75 (54.06 to 82.71) per 100,000 with an average annual percentage change of −1.58 (95% confidence interval: −1.66 to −1.51, p < 0.001). However, between 1990 and 2021, the incidence numbers in the 30–34 and 35–39 age groups increased by 23.75 and 21.24%, respectively. The number of deaths in low and low-middle Socio-demographic Index (SDI) areas increased by 79.51 and 20.62%, respectively. Moreover, it is predicted that the numbers of incidences and deaths will continue to rise in areas with low SDI. At the regional level, Central Sub-Saharan Africa had the highest incidence and mortality rates. In 2021, Somalia and the Democratic Republic of Congo had the highest incidence rates, whereas Kiribati and Cambodia had the highest mortality rates.ConclusionThe overall burden of hepatitis B-related cirrhosis among AYAs has decreased over the past three decades. Nevertheless, there was a slight increase in the incidence number among individuals aged 30–39 years. The substantial burden and predicted rise in the numbers of incidences and deaths in low SDI areas underscore the need for sustained and targeted public health interventions.

e16215 Background: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy with limited efficacy of second-line treatment following intolerance or failure of first-line therapy. This study aimed to explore the efficacy, safety, and effectiveness-related biological characteristics of adebrelimab combined with lenvatinib as second-line regimen in patients with advanced ICC. Methods: This single-arm, open-label phase II study enrolled patients with unresectable or metastatic ICC who had experienced progression or intolerance to first-line chemotherapy. Adebrelimab was administered via intravenous infusion (20 mg/kg, Q3W), combined with oral lenvatinib (8 mg for body weight < 60 kg or 12 mg for ≥ 60 kg, once daily). The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), time to deterioration(TTD), and disease control rate (DCR), safety and quality of life (QoL). Exploratory endpoints focused on identifying molecular markers in sensitive populations, biomarkers of treatment response, and mechanisms of resistance. Results: As of the data cut-off in January 2025, 10 patients were enrolled, of whom 7 were evaluable. The median age was 53.5 years (IQR, 10.5), and 40.0% had HBV infection history. Most patients (70.0%) were classified as Child-Pugh A and 90.0% met “up to seven” criteria. Two patients (20%) underwent surgery and 80% received transcatheter arterial chemoembolization (TACE) as prior locoregional treatment. Among 7 patients available for imaging evaluation, the ORR was 10.0% (1 partial response (PR), 4 stable disease (SD) , and 2 progressive disease (PD)) and the DCR was 50.0%, based on mRECIST and RECIST 1.1. The most frequently reported treatment-related AEs (any grade) were leukopenia (100.0%), anemia (70.0%), abdominal pain (70.0%), and thrombocytopenia (50.0%). The most common grade 3 or 4 AEs included leukopenia, abdominal pain, thrombocytopenia, vomiting and limb pain, each occurring in 10.0% of patients. Conclusions: Adebrelimab combined with lenvatinib showed promising antitumor activity and manageable safety profile in patients with unresectable or metastatic ICC who had progressed on or were intolerant to first-line chemotherapy. These findings provide a rationale for further investigation of this regimen as a second-line treatment option. Clinical trial information: ChiCTR2300078869 .

IntroductionDysregulation in lipid metabolism contributes to the occurrence and development of various cancers. The connection between changes in lipid metabolism and the development of intrahepatic cholangiocarcinoma remains uncertain. Our objective was to investigate the significance of blood lipid levels in patients with intrahepatic cholangiocarcinoma who have undergone surgery.MethodsNinety-seven ICC patients who underwent surgery were retrospectively enrolled. After 92.2 months of follow-up, the Kaplan-Meier analysis and Cox proportional hazard model were used to calculate overall survival and recurrence-free survival.ResultsThe median age of this cohort was 56 years, and 79 (81.4%) of them were male. Eighty-eight (90.7%) patients presented with tumor recurrence and 73 (75.3%) died. In multivariate analyses, high-density lipoprotein cholesterol level (< 0.91 vs. ≥ 0.91 mmol/L, hazard ratio [HR] = 2.55; 95% CI: 1.38-4.71), lymph node metastasis (Yes vs. No, HR = 2.58; 95% CI: 1.28-5.19), etiology factor (chronic HBV infection vs. others, HR = 0.5; 95% CI: 0.28-0.88) and multiple tumor lesions (Yes vs. No, HR = 1.85; 95% CI: 1.01-3.39) were independent predictors of overall survival. However, only high-density lipoprotein cholesterol level (HR = 1.86; 95% CI: 1.19-2.92) emerged as the independent factor for recurrence-free survival. High-density lipoprotein cholesterol level (HR = 2.07; 95% CI: 1.26-3.41), etiology factor (HR = 0.49; 95% CI: 0.29-0.84), and multiple tumor lesions (HR = 2.00; 95% CI: 1.14-3.51) were independent predictors of early recurrence. For patients who did not experience the spread of cancer to the lymph nodes, there was a significant correlation between the level of high-density lipoprotein cholesterol and their overall survival, recurrence-free survival, and early recurrence. For patients with low pre-operation high-density lipoprotein cholesterol levels, high post-operation high-density lipoprotein cholesterol levels were associated with better prognosis.ConclusionsLow serum high-density lipoprotein cholesterol level might serve as a sign of poor clinical outcomes (overall survival and recurrence-free survival) and early recurrence among intrahepatic cholangiocarcinoma patients. Strengthening the monitoring and intervention of intrahepatic cholangiocarcinoma patients with poor prognosis might be critical for improving the prognosis.

Background and Aims: The predominantly progressive, indeterminate, and predominantly regressive (P-I-R) classification extends beyond staging and provides information on dynamic changes of liver fibrosis. However, the prognostic implication of P-I-R classification is not elucidated. Therefore, in the present research, we investigated the utility of P-I-R classification in predicting the on-treatment clinical outcomes.Approach and Results: In an extension study on a randomized controlled trial, we originally enrolled 1000 patients with chronic hepatitis B and biopsy-proven histological significant fibrosis, and treated them for more than 7 years with entecavir-based therapy. Among the 727 patients with a second biopsy at treatment week 72, we compared P-I-R classification and Ishak score changes in 646 patients with adequate liver sections for the histological evaluation. Progressive, indeterminate, and regressive cases were observed in 70%, 17%, and 13% of patients before treatments and 20%, 14%, and 64% after 72-week treatment, respectively, which could further differentiate the histological outcomes of patients with stable Ishak scores. The 7-year cumulative incidence of HCC was 1.5% for the regressive cases, 4.3% for the indeterminate cases, and 22.8% for the progressive cases (p<0.001). After adjusting for age, treatment regimen, platelet counts, cirrhosis, Ishak fibrosis score changes, and Laennec staging, the posttreatment progressive had a HR of 17.77 (vs. posttreatment regressive; 95% CI: 5.55-56.88) for the incidence of liver-related events (decompensation, HCC, and death/liver transplantation).Conclusions: The P-I-R classification can be a meaningful complement to the Ishak fibrosis score not only in evaluating the histological changes but also in predicting the clinical outcomes.

54 Background: Hepatocellular carcinoma (HCC) is characterized by hypovascularity, the efficacy of transcatheter arterial chemoembolization (TACE) has been suboptimal. This study sought to evaluate and compare the efficacy and safety profiles of cryoablation (CRYO) plus lenvatinib (LEN) against TACE plus LEN for unresectable hepatocellular carcinoma (u-HCC) patients within a real-world clinical practice. Methods: A prospective study was conducted involving 234 patients with u-HCC who underwent treatment with LEN plus either CRYO or TACE at the Fifth Medical Center of the Chinese PLA General Hospital from October 2018 to May 2023. Treatment selection was determined through multidisciplinary discussions among a liver cancer board, weighing the pros and cons. The final decision was made by the patients and clinicians based on consensus. Clinical characteristics were balanced using propensity score matching (PSM). The primary endpoint was overall survival (OS), while secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Tumor response was based on RECIST v1.1 and mRECIST by blinded independent imaging review, AEs by CTCAE v5.0. Results: In this study, 212 (90.6%) were male, with an average age of 56 years. 206 (88%) patients were infected with hepatitis B virus (HBV), and 178 (76.1%) and 77 (32.9%) patients were classified as Child-Pugh A and BCLC B. After PSM, the clinical characteristics were comparable between the CRYO plus LEN and the TACE plus LEN group. Over a median follow-up of 31.8 months, 124 patients (53%) died. The CRYO plus LEN group demonstrated similar OS (24.2 vs. 22.0 months, P = 0.64), PFS (8.7 vs. 11.9 months, P = 0.48), ORR (53.1% vs. 53.1%, P = 1.00), and DCR (86.5% vs. 78.1%, P = 0.19) compared to the TACE plus LEN group after PSM, with consistent results observed before PSM. The two groups exhibited comparable AEs. In addition to similar LEN-related AEs, the most common CRYO-related AEs included 50% elevated ALT, 50% elevated AST, and 38.5% fever, which were consistent with the TACE related AEs. Notably, the incidence of abdominal pain was higher in the TACE plus LEN group compared to the CRYO plus LEN group (7.5% vs. 0.8%, P = 0.021), while pleural effusion was more prevalent in the CRYO plus LEN group than that in the TACE plus LEN group (6.2% vs. 0, P = 0.038). Conclusions: The CRYO plus LEN group exhibited comparable efficacy and well-tolerated safety with TACE plus LEN for u-HCC patients within a real-world clinical setting. It offers a viable alternative for HCC characterized by hypovascularity, presenting a promising therapeutic approach in the clinical management of u-HCC. Clinical trial information: ChiCTR2200058643 .

Objective To investigate the role of P-I-R classification and Laennec grading in evaluating histological changes in patients with hepatitis B cirrhosis after receiving antiviral therapy, as well as the association of these two evaluation systems with clinical prognosis. Methods A total of 218 patients from 14 centers were consecutively screened from October 2013 to October 2014, and these patients were diagnosed with liver cirrhosis based on pathology（Ishak score ≥5）, received antiviral therapy for 72 weeks, completed two liver biopsies, and met the P-I-R classification criteria. The 218 patients were divided into non-hepatocellular carcinoma（HCC） group with 186 patients and HCC group with 32 patients. The chi-square test and the Fisher’s exact test were used for comparison of categorical data between groups. For the comparison of HCC after antiviral therapy, the non-parametric Mann-Whitney U test was used for continuous variables, and for the comparison of P-I-R classification and Laennec grading, the non-parametric Kruskal-Wallis H test was used for continuous variables. Univariate and multivariate Cox regression analyses were used to calculate hazard ratio（HR） and 95% confidence interval（CI）, and the Kaplan-Meier method was used to calculate the cumulative incidence rate of HCC. Results After 72 weeks of antiviral therapy, there was a significant difference in P-I-R classification between the non-HCC group and the HCC group（P＜0.001）. There were significant differences in the distribution of Laennec grading and P-I-R classification before and after antiviral therapy（P＜0.001）. After antiviral therapy, the 218 patients were divided into 4A group with 33 patients, 4B group with 71 patients, and 4C group with 114 patients according to Laennec grading, and there were significant differences between these three groups in platelet count（PLT）（H=36.429, P＜0.001）, liver stiffness measurement（LSM）（H=13.983, P=0.004）, Ishak score（χ~2=23.060, P＜0.001）, and HAI score（P＜0.001）. After antiviral therapy, the 218 patients were divided into R group with 70 patients, I group with 52 patients, and P group with 96 patients according to P-I-R classification, and there were significant differences between these three groups in PLT（H=7.193, P=0.028）, LSM（H=6.238, P=0.045）, Ishak score（χ~2=7.986, P＜0.001）, HAI score（P=0.002）, and HCC（P＜0.001）. There was a significant difference in the incidence rate of HCC between the P and R groups based on P-I-R classification（HR=24.21, 95%CI: 0.46-177.99, P=0.002）. After adjustment for other confounding factors, P-I-R classification was an independent predictive factor for HCC（HR=12.69, 95%CI: 4.63-34.80, P=0.002）. Conclusion Both P-I-R classification and Laennec grading can reflect the features and changes of fibrosis before and after antiviral therapy, and P-I-R classification is more sensitive to fibrosis changes after antiviral therapy. P-I-R classification（after treatment） can be used to assess the risk of HCC in patients after antiviral therapy.

BackgroundHepatocellular carcinoma (HCC) is the major cause of malignancy-related deaths worldwide, and its incidence is likely to increase in the future as life expectancy increases. Therefore, the management of elderly patients with HCC has become a global issue. Aim of this study was to assess whether elderly patients with small HCC could obtain survival benefit from cryoablation (CRYO) in a real-world.Materials and methodsFrom July 2007 to June 2013, 185 patients with small HCC who underwent curative-intent percutaneous CRYO. All patients were divided into three groups according to age distribution. Overall survival (OS) and tumor-free survival (TFS) were compared between among of groups before and after the 1:1 propensity score matching, respectively. Univariate and multivariate Cox analyses were performed to determine the potential relationships between variables and prognostic outcomes.ResultsOne hundred and eighty-five patients (144 men, 41 women) received CRYO for small HCC, including 59 patients with age <50 years, 105 patients with age between 50 and 65 years, and 21 patients with age >65 years. The three age groups showed significant differences in the terms of underlying chronic liver disease and the number of patients with minor postoperative complications. After propensity score matching, the younger and elderly groups showed significant differences in mean OS (P=0.008) and tumor progression (P=0.050). However, no significant differences were shown in mean progression-free survival (PFS) (P=0.303). The Cox multivariate analysis showed that the Child-Pugh grade (HR=3.1, P<0.001), albumin (HR=0.85, P=0.004) and total of bilirubin (HR=1, P=0.024) were the independent prognostic factor for mean OS.ConclusionOur propensity-score-matched study suggested that elderly patients with small HCC can achieve acceptable prognostic outcomes with PFS similar to those of younger patients with small HCC after treatment with CRYO, while Child-Pugh grade, bilirubin and serum albumin levels were associated with the prognosis of small HCCs.

患者,女性,48岁,因"发现肝内占位8个月"于2022年4月入院.患者既往无吸烟和饮酒史,无慢性肝病史,2021年8月体检发现肝内占位,伴有颈部、腹膜后、肝门部淋巴结转移,于2021年9月肝占位穿刺病理:胆管细胞癌.2021年10月首次应用FOLFOX化疗方案(奥沙利铂200 mg+氟尿嘧啶4000 mg+亚叶酸钙0 .7 g )治疗,以后每21天一个周期.前3个周期的治疗,患者化疗后出现不良反应:恶心,呕吐2级,白细胞下降2级,无发热等不适,第4～6周期,患者化疗后出现发热38～39℃,对症处理后体温恢复正常,第7周期化疗,在输第一组奥沙利铂过程中出现高热(41℃)、寒战、面部潮红、面部水肿,无咳嗽、呼吸困难、皮疹,实验室检查血象明显增高(白细胞10 .73 × 109/L ,中性粒细胞百分比96 .4％) ,肝功能异常(总胆红素35 .4 μmol/L ,丙氨酸氨基转移酶370 U/L ,天冬氨酸氨基转移酶810 U/L ) ,降钙素原43 .2 ng/m L;肺C T:双肺未见异常(图1a) ,没有其他器官衰竭的迹象.考虑存在化疗引起的继发感染,予以泰能+替考拉宁抗感染治疗10天,患者体温恢复正常,白细胞和降钙素原恢复正常.

e16151 Background: Targeted therapy is the most effective therapeutic approach for middle and late-stage hepatocellular carcinoma (HCC). Regorafenib or PD-1 as a second-line treatment of patients with advanced HCC has achieved good results. Argon-helium cryoablation is one commonly used method for local ablation of liver cancer. Whether systemic therapy combined with local therapy can benefit patients with advanced liver cancer is a hot topic. This study is aimed to investigate the efficacy and safety of regorafenib and PD-1 combined with cryoablation in the treatment of patients with advanced HCC after the failure of second-line targeted treatment. Methods: In this retrospective study, unresectable HCC patients received regorafenib and PD-1combined with cryoablation after the failure of second-line targeted treatment from January 2019 to December 2021 were enrolled. Depending on whether combining local therapy, patients were grouped as RP (regorafenib and PD-1), or RPC groups (regorafenib and PD-1 combined with cryoablation). Objective response rate (ORR), disease control regorafenib rate (DCR), progression free survival (PFS), and safety were recorded. The PFS was defined as the time from the first dose of RP, or from the time of using RPC until disease progression or death. Results: A total of 50 patients were reviewed, including 21 patients in RP group and 29 patients in RCP group. One patient was classified as Barcelona Clinic Liver Cancer (BCLC) stage B and 20 patients were at BCLC stage C in RP group, while one patient was at BCLC stage B and 28 patients were at BCLC stage C in RPC group. The ORR and DCR were 4.8% and 23.8% in PR group respectively, and 31.0% and 69.0% in RPC group respectively. The 6-month PFS rate of RP group and RPC group was 14.3% and 53.6% respectively. Thirteen (61.9%) and eighteen (62.1%) patients experienced adverse events (AEs) in two groups respectively. Two (9.5%) and three (10.7%) patients experienced grade 3 AEs that occurred in RP group and RPC group respectively. The most frequency AE was hand-foot-skin reaction in both groups (58.0% and 50.0%, respectively). No patient discontinued regorafenib and PD-1 due to AE in these two groups. Conclusions: Regorafenib and PD-1 combined with cryoablation showed potential anti-tumor effect and tolerance on unresectable HCC after the failure of second-line targeted treatment. [Table: see text]

Objective We aim to explore the immunomodulatory effect of inactivated bacteroides fragilis（IBF） in delayed-type hypersensitivity（DTH）. Methods Wild-type BALB/c mice were randomly divided into control group, model group, low（1×10~6 CFU）, medium（1×10~8 CFU）, high(1×10 10 CFU) dose of IBF group and levamisole group, 10 mice for each group respectively. After immunosuppression with cyclophosphamide（Cy）, the DTH model induced by 2,4-dinitrofluorobenzene（DNFB） was used to study whether IBF has immunomodulatory ability. The degree of ear swelling, thymus index and spleen index were the main observation indicators. Various blood cells of mice were counted at the same time. Results The medium and high dose of IBF could significantly increase the ear swelling of mice inhibited by cyclophosphamide, and regulate the number of white blood cells, monocytes, neutrophils, basophils and eosinophils. Each dose of IBF has no significant improvement on thymus index, but can significantly increase spleen index. Conclusion IBF can recover the DTH caused by exogenous allergens in mice, and can resist the spleen atrophy caused by Cy.

Background: We explore the dose-efficacy relationship of lenvatinib plus anti-PD-1 in patients with unresectable hepatocellular carcinoma (u-HCC) infected with hepatitis B virus (HBV) in real-world practice. Furthermore, we identify the population sensitive to lenvatinib plus anti-PD-1 treatments. Methods: This retrospective study included 70 patients treated with lenvatinib plus at least 3 cycles of anti-PD-1 and 140 with lenvatinib alone. Stabilized inverse probability of treatment weighting (SIPTW) was used to balance clinical features between the two groups. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were analyzed. Subpopulation treatment effect pattern plot (STEPP) estimated treatment-effect differences between the two groups. Results: The median age was 54 years, and 189 (90%) cases were male. A total of 180 (85%) patients were infected with HBV. A slowly increasing 12-month survival rate was with the cycles of anti-PD-1, and 5 cycles and more of anti-PD-1 appeared the most beneficial and stable survival rate. The lenvatinib plus at least 3 cycles anti-PD-1 group had better OS (21.4 vs 14 months, p = 0.041), PFS (8.0 vs 6.3 months, p = 0.015) than the lenvatinib alone group in unadjusted cohorts, and the SIPTW adjusted cohorts had confirmed it. For patients with portal vein trunk invasion (PVTI) or extrahepatic spread (EHS) combined with Child-Pugh class B (CPB), lenvatinib plus anti-PD-1 made the 12-month survival rate increase by 38%, while, in the other population, it did only 18%. The two groups had similar AEs (p >= 0.05). Conclusion: The lenvatinib combined with at least 3 cycles of anti-PD-1 was efficacy and safe for u-HCC patients infected with HBV. Especially, patients with PVTI or EHS combined with CPB may benefit most from the combination therapy.

Progressive hepatic fibrosis leads to hepatocellular carcinoma (HCC) and decompensated cirrhosis. The aim of this study was to identify the high-risk population for progressive hepatic fibrosis and the incidence of HCC and decompensated cirrhosis in chronic hepatitis B (CHB) patients with antiviral therapy. The data came from a multicenter, center-randomized, double-blind clinical trial that analyzed only patients in the ETV-treated arm. There was 156 hepatitis B e antigen (HBeAg)-positive and 135 HBeAg-negative patients in 14 institutions. The primary endpoint was fibrosis reversal on 72-week Entecavir (ETV) treatment. The 7-year cumulative incidence of HCC and decompensated cirrhosis were analyzed. Multivariate logistic and LASSO regression analyses were used to screen variables associated with fibrosis reversal. 86/156 (55

Abstract Background Hepatocellular carcinoma (HCC) poses significant challenges to prognosis prediction due to its heterogeneity and high recurrence rate. Disulfidoptosis, a unique form of cell death dependent on disulfide aggregation in cells overexpressing SLC7A11 under glucose starvation, distinguishes itself from known programmed cell death. However, the prognostic implications of disulfidoptosis-related genes in HCC require further elucidation. Methods From public databases, we gathered mRNA expression profiles and corresponding clinical data on HCC patients. Utilizing the least absolute shrinkage and selection operator (LASSO) Cox regression model, a four-gene signature was constructed in the TCGA cohort. Validation was performed from the ICGC and GSE14520 cohorts. According to the risk score, TIMER algorithm was used to analyze the infiltration of immune cells in the microenvironment of HCC. Predicted the sorafenib-therapeutic response was conducted based on the Genomics of Drug Sensitivity in Cancer (GDSC). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses was performed to gain insights into the biological functions of the disulfidptosis model-associated genes. Results Seven known disulfidoptosis-related genes significantly correlated with overall survival (OS) according to univariate Cox regression analysis (P adj. < 0.05). High-risk patients demonstrated a significantly lower OS than low-risk patients (P = 0.002 in the TCGA and P = 0.004 in the ICGC cohort). The risk scores served as independent predictors of OS in both TCGA and ICGC cohorts, according to multivariate Cox regressions (HR > 1, P < 0.001). Gene signature prediction was further validated by receiver operating characteristic (ROC) analysis. Notably, immune cell infiltration and the sorafenib treatment response differed between the two groups. Functional analysis revealed enrichment of mitosis-related pathways. Conclusion our study proposes a novel disulfidoptosis-related gene signature with potential clinical utility for prognostic prediction in HCC. For HCC, targeting disulfidoptosis may be a promising therapeutic option.

Hepatocellular carcinoma (HCC) poses a significant global burden, with most patients being diagnosed at an advanced stage, leading to poor prognosis due to the lack of systemic treatment. The approval of oral tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors, and anti-angiogenic agents has rapidly expanded the treatment prospects for HCC. However, the use of these drugs has also increased the incidence of portal hypertension (PHT) and upper gastrointestinal variceal bleeding in HCC patients. The diagnosis, screening, emergency treatment, and secondary prevention of upper gastrointestinal variceal rebleeding in advanced HCC patients undergoing oral TKIs therapy have become clinically urgent and critical issues. This review provides an overview of the existing understanding regarding the uses and limitations of transjugular intrahepatic portosystemic shunt (TIPS) insertion for managing HCC in cirrhosis patients with PHT and variceal hemorrhage. Additionally, it explores the potential of TIPS in managing acute upper gastrointestinal bleeding and preventing rebleeding in advanced HCC patients undergoing TKIs therapy. The placement of TIPS within the treatment hierarchy is determined by the specific clinical environment and the individual attributes of the patient.