The Different Prognoses of Hepatocellular Carcinoma with Previous Tenofovir versus Entecavir Treatment for Chronic Hepatitis B Virus: Analysis Based on 15 Propensity Score-Matched Studies.

BACKGROUND: Currently, enough studies with aggregated study-level data have demonstrated that there was no clinically meaningful difference in the risk of hepatocellular carcinoma (HCC) between patients who received entecavir and patients who received tenofovir treatment for chronic hepatitis B virus (CHBV). However, many studies found many differences in prognosis of these HCC patients. This meta-analysis of high-quality propensity score-matched (PSM) studies was designed to provide robust estimates for comparative HCC prognosis between groups receiving tenofovir or entecavir. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to July 10, 2022, for relevant studies that compare the different prognoses of HCC between tenofovir and entecavir treatment. The primary outcomes were the difference of overall death or liver transplantation between tenofovir and entecavir treatment. The secondary outcomes included risk factors of overall death or liver transplantation and different treatment responses between tenofovir and entecavir treatment for CHBV. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2. RESULTS: A total of 15 PSM studies were identified, with 24,035 sample sizes in tenofovir group and 61,410 sample sizes in entecavir group, respectively. Pooled data indicated that, compared with entecavir, patients receiving tenofovir experienced significantly lower overall death or liver transplantation, with a pooled OR of 0.55 (95% CI: 0.45-0.68; p < 0.00001). Subgroup analysis by population also found similar results with pooled ORs of 0.52 (95% CI: 0.38-0.70; p < 0.0001) in entire cohort and 0.62 (95% CI: 0.50-0.77; p < 0.0001) in PSM cohort. Similarly, the subgroup analysis also found that HCC patients without cirrhosis receiving tenofovir experienced significantly lower overall death or liver transplantation than entecavir (OR: 0.56; 95% CI: 0.49-0.66), but no significant result was found in HCC patients with cirrhosis. In addition, both univariate (OR: 0.46; 95% CI: 0.31-0.69) and multivariable analyses (OR: 0.86; 95% CI: 0.82-0.91) also indicated significant reduction of overall death or liver transplantation in tenofovir group than entecavir group. CONCLUSION: Our analysis indicated that there was clinically meaningful difference in prognosis of HCC between patients who received entecavir and patients who received tenofovir. Patients who received tenofovir experienced much lower overall death or liver transplantation than patients who received entecavir. Tenofovir treatment may be one of independent favorable factors of prognosis for HCC patients with CHBV.

NFAT2 overexpression suppresses the malignancy of hepatocellular carcinoma through inducing Egr2 expression.

BACKGROUND: Nuclear factor of activated T cells 2 (NFAT2) has been reported to regulate the development and malignancy of few tumors. In this study, we aimed to explore the effect of NFAT2 expression on cell fate of HepG2 cell and its potential mechanisms. METHODS: Firstly, the pcDNA3.1-NFAT2 plasmid was transfected into HepG2 cells to construct NFAT2 overexpressed HepG2 cells. Then, the chemical count kit-8 cell viability assay, Annexin V-FITC apoptosis detection, EdU labeling proliferation detection, transwell and wound healing experiments were performed. The expression of Egr2 and FasL, and the phosphorylation of AKT and ERK, after ionomycin and PMA co-stimulation, was detected, while the Ca2+ mobilization stimulated by K+ solution was determined. At last, the mRNA and protein expression of NFAT2, Egr2, FasL, COX-2 and c-myc in carcinoma and adjacent tissues was investigated. RESULTS: The NFAT2 overexpression suppressed the cell viability, invasion and migration capabilities, and promoted apoptosis of HepG2 cells. NFAT2 overexpression induced the expression of Egr2 and FasL and suppressed the phosphorylation of AKT and ERK. The sensitivity and Ca2+ mobilization of HepG2 cells was also inhibited by NFAT2 overexpression. Compared with adjacent tissues, the carcinoma tissues expressed less NFAT2, Egr2, FasL and more COX-2 and c-myc. CONCLUSION: The current study firstly suggested that NFAT2 suppressed the aggression and malignancy of HepG2 cells through inducing the expression of Egr2. The absence of NFAT2 and Egr2 in carcinoma tissues reminded us that NFAT2 may be a promising therapeutic target for hepatocellular carcinoma treatment.

One-stop-shop preoperative evaluation for living liver donors with gadoxetic acid disodium-enhanced magnetic resonance imaging: efficiency and additional benefit.

OBJECTIVE: To explore the efficiency, cost, and time for examination of one-stop-shop gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in preoperative evaluation for parent donors by comparing with multidetector computer tomography combined with conventional MR cholangiopancreatography (MDCT-MRCP). MATERIALS AND METHODS: Forty parent donors were evaluated with MDCT-MRCP, and the other 40 sex-, age-, and weight-matched donors with Gd-EOB-DTPA-enhanced MRI. Anatomical variations and graft volume determined by pre- and intra-operative findings, costs and time for imaging were recorded. Image quality was ranked on a 4-point scale and compared between both groups. RESULTS: Gd-EOB-DTPA-enhanced MRI provided better image quality than MDCT-MRCP for the depiction of portal veins and bile ducts by both reviewers (p < 0.05), hepatic veins by one reviewer (p < 0.05), rather hepatic arteries by both reviewers (p < 0.01). Sixty-nine living donors proceeded to liver donation with all anatomical findings accurately confirmed by intra-operative findings. The "in-room" time of Gd-EOB-DTPA-enhanced MRI was 12 min longer than MDCT-MRCP. Gd-EOB-DTPA-enhanced MRI was cheaper than MDCT-MRCP (US$519.72 vs. US$631.85). CONCLUSION: One-stop-shop Gd-EOB-DTPA-enhanced MRI has similar diagnostic accuracy as MDCT-MRCP and can provide additional benefit in terms of costs and convenience in preoperative evaluation for parent donors.

Inhibition of KIF20A enhances the immunotherapeutic effect of hepatocellular carcinoma by enhancing c-Myc ubiquitination.

Immune therapy has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients, yet its efficacy remains limited, underscoring the urgency to identify new therapeutic targets and biomarkers. Here, we investigated the pathological and physiological roles of KIF20A and assess its potential in enhancing HCC treatment efficacy when combined with PD-1 inhibitors. We initially assess KIF20A's oncogenic function using liver-specific KIF20A knockout (Kif20a CKO) mouse models and orthotopic xenografts. Subsequently, we establish a regulatory axis involving KIF20A, FBXW7, and c-Myc, validated through construction of c-Myc splicing mutants. Large-scale clinical immunohistochemistry (IHC) analyses confirm the pathological relevance of the KIF20A-FBXW7-c-Myc axis in HCC. We demonstrate that KIF20A overexpression correlates with poor prognosis in HCC by competitively inhibiting FBXW7-mediated degradation of c-Myc, thereby promoting glycolysis and enhancing tumor proliferation. Conversely, KIF20A downregulation suppresses these effects, impairing tumor growth through c-Myc downregulation. Notably, KIF20A inhibition attenuates c-Myc-induced MMR expression, associated with improved prognosis in HCC patients receiving PD-1 inhibitor therapy. Furthermore, in Kif20a CKO HCC mouse models, we observe synergistic effects between Kif20a knockout and anti-PD-1 antibodies, significantly enhancing immunotherapeutic efficacy against HCC. Our findings suggest that targeting the KIF20A-c-Myc axis could identify HCC patients likely to benefit from anti-PD-1 therapy. In conclusion, we propose that combining KIF20A inhibitors with anti-PD-1 treatment represents a promising therapeutic strategy for HCC, offering new avenues for clinical development and patient stratification.

Application value of mixed reality in hepatectomy for hepatocellular carcinoma.

BACKGROUND: As a new digital holographic imaging technology, mixed reality (MR) technology has unique advantages in determining the liver anatomy and location of tumor lesions. With the popularization of 5G communication technology, MR shows great potential in preoperative planning and intraoperative navigation, making hepatectomy more accurate and safer. AIM: To evaluate the application value of MR technology in hepatectomy for hepatocellular carcinoma (HCC). METHODS: The clinical data of 95 patients who underwent open hepatectomy surgery for HCC between June 2018 and October 2020 at our hospital were analyzed retrospectively. We selected 95 patients with HCC according to the inclusion criteria and exclusion criteria. In 38 patients, hepatectomy was assisted by MR (Group A), and an additional 57 patients underwent traditional hepatectomy without MR (Group B). The perioperative outcomes of the two groups were collected and compared to evaluate the application value of MR in hepatectomy for patients with HCC. RESULTS: We summarized the technical process of MR-assisted hepatectomy in the treatment of HCC. Compared to traditional hepatectomy in Group B, MR-assisted hepatectomy in Group A yielded a shorter operation time (202.86 ± 46.02 min vs 229.52 ± 57.13 min, P = 0.003), less volume of bleeding (329.29 ± 97.31 mL vs 398.23 ± 159.61 mL, P = 0.028), and shorter obstructive time of the portal vein (17.71 ± 4.16 min vs 21.58 ± 5.24 min, P = 0.019). Group A had lower alanine aminotransferas and higher albumin values on the third day after the operation (119.74 ± 29.08 U/L vs 135.53 ± 36.68 U/L, P = 0.029 and 33.60 ± 3.21 g/L vs 31.80 ± 3.51 g/L, P = 0.014, respectively). The total postoperative complications and hospitalization days in Group A were significantly less than those in Group B [14 (37.84%) vs 35 (60.34%), P = 0.032 and 12.05 ± 4.04 d vs 13.78 ± 4.13 d, P = 0.049, respectively]. CONCLUSION: MR has some application value in three-dimensional visualization of the liver, surgical planning, and intraoperative navigation during hepatectomy, and it significantly improves the perioperative outcomes of hepatectomy for HCC.

MiniPDX-guided postoperative anticancer treatment can effectively prolong the survival of patients with hepatocellular carcinoma.

BACKGROUND: The recurrence rate of hepatocellular carcinoma (HCC) after partial hepatectomy is still high. How to choose the most appropriate anti-tumor drug in the early postoperative period is crucial to improve the prognosis of patients. Recently, MiniPDX has been widely used as a new and reliable preclinical research model capable of predicting the sensitivities of anti-tumor drugs. METHODS: Twenty-eight patients with HCC were selected to use the MiniPDX model to screen the most sensitive anti-tumor drugs from five groups of drug regimens for preventive treatment after partial hepatectomy, and another 42 patients with HCC were selected to be treated with Sorafenib during the same period as the control group. The tumor-free survival rate and overall survival rate were analyzed and compared between these two groups. The relationship between drug sensitivity and biomarkers related to HCC was also analyzed. RESULTS: Kaplan-Meier survival curve analysis showed that the tumor-free survival (DFS) of patients in the MiniPDX group was significantly longer than that in the control group (median DFS: 25.8 months vs. 18.2 months, P = 0.022, HR 2.19, 95% CI 1.17-4.12). The overall survival (OS) of the patients in the MiniPDX group was also longer than that in the control group (median OS: 29.4 months vs. 23.8 months, P = 0.039, HR 2.37, 95% CI 1.12-5.00). The longest follow-up period was 36 months. The relationship analyzed between the efficacy of the five drugs (Regorafenib, Regorafenib, Lenvatinib, Gemcitabine, 5-FU + Oxaliplatin) and AFP, Ki-67, VEGFR, FGFR, P53, and Nrf2 showed different correlations. CONCLUSION: The use of the MiniPDX model to select drugs to guide anti-tumor treatment after partial hepatectomy could effectively prolong the survival of patients with HCC.

[Middle hepatic treatment algorithm in right lobe living donor liver transplantation for donor recipient safety].

OBJECTIVE: The treatment algorithm of donor middle hepatic vein (MHV) was made depending on the remnant liver volume of the total donor liver volume as calculated by computer tomography, estimated graft-to-recipient weight ratio and also anatomy. The present study was to analyze the influence of this algorithm upon the safety of donors and recipients in right lobe living donor liver transplantation (LDLT) and to provide references for our future clinical practices. METHODS: Data of 73 consecutive LDLT cases, operated and managed by the same surgical team according to the pre-operation MHV treatment algorithm, were analyzed. MHV was harvested in 28 cases and not in 45 cases. Donor and recipient gender, age, weight, operation time, blood loss volume, graft weight, non-hepatic phase, graft cold preservation time, perioperative survival rate and the incidence of small-for-size syndrome were compared, and also the peak post-operative values of ALT, AST, T-bilirubin and D-bilirubin. RESULTS: No donor needed blood transfusion and suffered small-for-size syndrome. One recipient recovered from small-for-size syndrome successfully by medical interventions. One recipient had acute hepatic necrosis at Day 6 post-operation and was converted into cadaveric liver transplantation. At Day 30 post-operation, one recipient died from disseminated infections and respiratory failure, but his liver function was normal. There was significant difference in donor and recipient age, actual GRWR, graft cold preservation time and recipient's ALT peak value between the MHV harvest group and the MHV non-harvest group. CONCLUSION: The MHV treatment algorithm is safe to both donors and recipients.

[Clinical analysis of donor hepatectomy in living donor liver transplantation: report of 74 cases].

OBJECTIVE: To evaluate the living donor selection, donor hepatectomy technique, and surgical complication in living donor liver transplantation. METHODS: From June 2007 to July 2008, 74 consecutive cases living donor hepatectomy were performed by the same surgical team. Seventy-four donors (64 males and 10 females) with a mean age of 29.2 years old passed the donor liver assessment and evaluation program successfully. The hepatectomy procedure types contained right liver resection (n = 72), of which 27 cases harvested the middle hepatic vein and 45 cases not, left liver resection contain middle hepatic vein (n = 1) and left lateral resection (n = 1). RESULTS: Of all the donors, operation time was (6.5 +/- 6.2) hours, the mean blood loss was 300 ml (100 - 500 ml) and didn't accept foreign blood transfusion. The maximum alanine aminotransferase (ALT) level was (229.5 +/- 108.6) U/L, the ALT returned to normal time was (12.7 +/- 4.8) d, the maximum total bilirubin (TB) level was (78.7 +/- 44.3) micromol/L, the TB returned to normal time was (8.8 +/- 2.7) d, and the mean hospital stay time was 14 days (7 - 28 d). The complications included bile leak (n = 1), cut surface hemorrhage (n = 1) and anaphylactoid purpura (n = 1). All the donors returned to normal work and life finally. CONCLUSIONS: Precisely evaluating donor blood vascular and biliary anatomy before operation, keeping the blood vascular and bile duct integrity during operation and monitoring complication to solve it immediately after operation is crucial to ensure donor safety and recovering successfully.

Health economic assessment of Gd-EOB-DTPA MRI versus ECCM-MRI and multi-detector CT for diagnosis of hepatocellular carcinoma in China.

Limited data exists in China on the comparative cost of gadolinium ethoxybenzyl diethylenetriamine magnetic resonance imaging (Gd-EOB-DTPA-MRI) with other imaging techniques. This study compared the total cost of Gd-EOB-DTPA-MRI with multidetector computed tomography (MDCT) and extracellular contrast media-enhanced MRI (ECCM-MRI) as initial imaging procedures in patients with suspected hepatocellular carcinoma (HCC). We developed a decision-tree model on the basis of the Chinese clinical guidelines for HCC, which was validated by clinical experts from China. The model compared the diagnostic accuracy and costs of alternative initial imaging procedures. Compared with MDCT and ECCM-MRI, Gd-EOB-DTPA-MRI imaging was associated with higher rates of diagnostic accuracy, i.e. higher proportions of true positives (TP) and true negatives (TN) with lower false positives (FP). Total diagnosis and treatment cost per patient after the initial Gd-EOB-DTPA-MRI evaluation was similar to MDCT (¥30,360 vs. ¥30,803) and lower than that reported with ECCM-MRI (¥30,360 vs. ¥31,465). Lower treatment cost after initial Gd-EOB-DTPA-MRI was driven by reduced utilization of confirmatory diagnostic procedures and unnecessary treatments. The findings reported that Gd-EOB-DTPA-MRI offered higher diagnostic accuracy compared with MDCT and ECCM-MRI at a comparable cost, which indicates Gd-EOB-DTPA-MRI could be the preferred initial imaging procedure for the diagnosis of HCC in China.

Liver tumor boundaries identified intraoperatively using real-time indocyanine green fluorescence imaging.

PURPOSE: Clear delineation between tumors and normal tissues is ideal for real-time surgical navigation imaging. We investigated applying indocyanine green (ICG) fluorescence imaging navigation using an intraoperative administration method in liver resection. METHODS: Fifty patients who underwent liver resection were divided into two groups based on clinical situation and operative purpose. In group I, sizes of superficial liver tumors were determined; tiny tumors were identified. In group II, the liver resection margin was determined; real-time navigation was performed. ICG was injected intravenously at the beginning of the operation; the liver surface was observed with a photodynamic eye (PDE). RESULTS: Liver resection margins were determined using PDE. Fluorescence contrast between normal liver and tumor tissues was obvious in 32 of 35 patients. A boundary for half the liver or specific liver segments was determined in nine patients by examining the portal vein anatomy after ICG injection. Eight small tumors not observed preoperatively were detected; the smallest was 2 mm. CONCLUSIONS: ICG fluorescence imaging navigation is a promising, simple, and safe tool for routine real-time intraoperative imaging during hepatic resection and clinical exploration in hepatocellular carcinoma, enabling high sensibility for identifying liver resection margins and detecting tiny superficial tumors.