A novel remnant liver-first strategy for liver autotransplantation in patients with end-stage hepatic alveolar echinococcosis: a retrospective case series.

BACKGROUND: Ex vivo liver resection combined with autotransplantation is an effective therapeutic strategy for unresectable end-stage hepatic alveolar echinococcosis (HAE). However, ex vivo liver resection combined with autotransplantation is a technically demanding and time-consuming procedure associated with significant morbidity and mortality. The authors aimed to present our novel remnant liver-first strategy of in vivo liver resection combined with autotransplantation (IRAT) technique for treating patients with end-stage HAE. METHODS: This retrospective study included patients who underwent IRAT between January 2014 and December 2020 at two institutions. Patients with end-stage HAE were carefully assessed for IRAT by a multidisciplinary team. The safety, feasibility, and outcomes of this novel technique were analyzed. RESULTS: IRAT was successfully performed in six patients, with no perioperative deaths. The median operative time was 537.5 min (range, 501.3-580.0), the median anhepatic time was 59.0 min (range, 54.0-65.5), and the median cold ischemia time was 165.0 min (range, 153.8-201.5). The median intraoperative blood loss was 700.0 ml (range, 475.0-950.0). In-hospital complications occurred in two patients. No Clavien-Dindo grade III or higher complications were observed. At a median follow-up of 18.6 months (range, 15.4-76.0) , all patients were alive. No recurrence of HAE was observed. CONCLUSION: The remnant liver-first strategy of IRAT is feasible and safe for selected patients with end-stage HAE. The widespread adoption of this novel technique requires further studies to standardize the operative procedure and identify patients who are most likely to benefit from it.

Overexpression of transcription factor 3 drives hepatocarcinoma development by enhancing cell proliferation via activating Wnt signaling pathway.

BACKGROUND: Transcription factor 3 (TCF3) plays pivotal roles in embryonic development, stem cell maintenance and carcinogenesis. However, its role in hepatocellular carcinoma (HCC) remains largely unknown. This study aimed to analyze the correlation between TCF3 expression and clinicopathological features of HCC, and further explore the underlying mechanism in HCC progression. METHODS: The expression of TCF3 was collected from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) HCC datasets, and further confirmed by immunostaining and Western blotting assays. The correlation between TCF3 expression and the clinicopathological features was evaluated. Bioinformatical analysis and in vitro experiments were conducted to explore the potential role of TCF3 in HCC development. RESULTS: Both the mRNA and protein levels of TCF3 were significantly higher in HCC tumor tissues compared to tumor adjacent tissues (P < 0.001 and P < 0.01). Analysis based on TCGA datasets showed that TCF3 was positively correlated with tumor clinical stage and grade, and patients with high TCF3 expression had shorter overall survival (P = 0.012), disease-specific survival (P = 0.022) and progression-free survival (P = 0.013). Similarly, the immunostaining results revealed that the high expression of TCF3 was closely correlated with tumor size (P = 0.001) and TNM stage (P = 0.002), and TCF3 was an independent risk factor of HCC. In vitro study exhibited that TCF3 knockdown dramatically suppressed cancer cell proliferation, and the underlying mechanism might be that the silencing of TCF3 reduced the expression of critical regulating proteins towards cell cycle and proteins involved in Wnt signaling pathways. CONCLUSIONS: TCF3 expression is significantly elevated in HCC and positively associated with the tumor size and TNM stage, as well as poor prognosis of HCC patients. The mechanism might be that TCF3 promotes cancer cell proliferation via activating Wnt signaling pathway.

Efficacy and safety of sirolimus early conversion protocol in liver transplant patients with hepatocellular carcinoma: A single-arm, multicenter, prospective study.

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data. Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869.

Standard liver weight model in adult deceased donors with fatty liver: A prospective cohort study.

BACKGROUND: Standard liver weight (SLW) is frequently used in deceased donor liver transplantation to avoid size mismatches with the recipient. However, some deceased donors (DDs) have fatty liver (FL). A few studies have reported that FL could impact liver size. To the best of our knowledge, there are no relevant SLW models for predicting liver size. AIM: To demonstrate the relationship between FL and total liver weight (TLW) in detail and present a related SLW formula. METHODS: We prospectively enrolled 212 adult DDs from West China Hospital of Sichuan University from June 2019 to February 2021, recorded their basic information, such as sex, age, body height (BH) and body weight (BW), and performed abdominal ultrasound (US) and pathological biopsy (PB). The chi-square test and kappa consistency score were used to assess the consistency in terms of FL diagnosed by US relative to PB. Simple linear regression analysis was used to explore the variables related to TLW. Multiple linear regression analysis was used to formulate SLW models, and the root mean standard error and interclass correlation coefficient were used to test the fitting efficiency and accuracy of the model, respectively. Furthermore, the optimal formula was compared with previous formulas. RESULTS: Approximately 28.8% of DDs had FL. US had a high diagnostic ability (sensitivity and specificity were 86.2% and 92.9%, respectively; kappa value was 0.70, P < 0.001) for livers with more than a 5% fatty change. Simple linear regression analysis showed that sex (R2, 0.226; P < 0.001), BH (R2, 0.241; P < 0.001), BW (R2, 0.441; P < 0.001), BMI (R2, 0.224; P < 0.001), BSA (R2, 0.454; P < 0.001) and FL (R2, 0.130; P < 0.001) significantly impacted TLW. In addition, multiple linear regression analysis showed that there was no significant difference in liver weight between the DDs with no steatosis and those with steatosis within 5%. Furthermore, in the context of hepatic steatosis, TLW increased positively (non-linear); compared with the TLW of the non-FL group, the TLW of the groups with hepatic steatosis within 5%, between 5% and 20% and more than 20% increased by 0 g, 90 g, and 340 g, respectively. A novel formula, namely, -348.6 + (110.7 x Sex [0 = Female, 1 = Male]) + 958.0 x BSA + (179.8 x FLUS [0 = No, 1 = Yes]), where FL was diagnosed by US, was more convenient and accurate than any other formula for predicting SLW. CONCLUSION: FL is positively correlated with TLW. The novel formula deduced using sex, BSA and FLUS is the optimal formula for predicting SLW in adult DDs.

Histidine-tryptophan-ketoglutarate solution versus University of Wisconsin solution in adult-to-adult living donor liver transplantation: A propensity score matching analysis from mainland China.

ABSTRACT: To compare the difference between University of Wisconsin (UW) solution and histidine-tryptophan-ketoglutarate (HTK) solution in adult living donor liver transplantation (LDLT).This study included LDLT patients at the Liver Transplantation Center of West China Hospital of Sichuan University from November 2001 to June 2018. These patients were classified into 2 groups depending on the use of the different preservation solutions, and the confounding factors between the 2 groups were eliminated by propensity score matching. Finally, the incidence of complications; serum examination at postoperative days 1, 3, 5, 7, 14, 21, and 30; and the overall survival rate of the 2 groups were compared to observe whether there were any differences between the 2 preservation solutions.Of the 298 patients we screened, 170 were treated with UW solution and 128 with HTK solution. After propensity score matching, 106 pairs of patients were selected. In the comparison of the 2 groups, the length of intensive care unit stay in the UW group was significantly longer than that in the HTK group (P = .022), but there was no difference in the total length of hospital stay between the 2 groups (P = .277). No statistically significant difference was observed in the 2 groups in terms of the incidence of complications or postoperative examinations. However, the incidence of early allograft dysfunction in the HTK group was slightly lower than that in the UW group (HTK: UW = 14.1%: 20.7%), although the difference was not statistically significant. In terms of the overall survival rate, the 1, 3, and 5-year survival rates of the HTK group were 85.5%, 70.2%, and 65.1%, respectively, while the 1, 3, and 5-year survival rates of the UW group were 83.1%, 67.2%, and 59.8%, respectively, and there was no significant difference between the 2 groups.In conclusion, our study shows that UW solution and HTK solution are equivalent in perioperative safety, the recovery of transplanted liver function, the occurrence of postoperative complications and overall survival and can be safely and effectively applied in adult LDLT. If economic factors are taken into account, HTK can save costs to a certain extent.

Liver fibrosis is a major risk factor for liver regeneration: A comparison between healthy and fibrotic liver.

BACKGROUND: Blood flow factors, such as congestion or ischemia after hepatectomy, have a significant impact on liver regeneration, but with the popularization of precise hepatectomy technology, segmental hepatectomy without congestion or ischemia has become the preferred treatment. Our aim is to investigate the factors affecting liver regeneration after hepatectomy without blood flow changes, and to provide clinical evidence for surgeons on the timing of second hepatectomy for cirrhosis patients with hepatocellular carcinoma (HCC). METHODS: This study retrospectively analyzed data from patients who underwent right hepatectomy without middle hepatic vein (MHV) in West China Hospital between January 2016 and January 2018. Eighteen living-donors without MHV as normal group and 45 HCC patients, further classified into 3 subgroups based on the severity of fibrosis using the Scheure system. Demographic data, pre- and postoperative liver function indexes, and remnant liver volume (RLV) were retrospectively compared. We also analyzed the remnant liver regeneration rate (RLRR) post-operatively in each group. The significant indexes in univariate analysis were further analyzed using both receiver operating characteristic (ROC) analysis and multivariate regression analysis. RESULTS: Liver regeneration occurred in both living-donor and HCC groups after hepatectomy; the RLRRs at 1 month were 59.46 ±â€Š10.39% and 57.27 ±â€Š4.77% (P = .509), respectively. Regeneration in the cirrhosis group occurred more slowly and less completely compared with that in other groups. The regeneration rate in the first 6 months showed rapid increase and the RLRR reached above 70% in cirrhosis group. Multivariate and ROC analyses revealed that Alb and the hepatic fibrosis grade in the early postoperative period were significant predictors of remnant liver regeneration. CONCLUSION: The liver regenerated in all HCC patients; however, regeneration was significantly slower and less complete compared with the normal liver, especially in the patients with cirrhosis. Therefore, it can be concluded that the degree of liver fibrosis is a major predictor of liver regeneration. Furthermore, the optimal time for second resection in recurrent HCC patients with cirrhosis was 6 months after the first operation.

Development and validation of a 14-gene signature for prognosis prediction in hepatocellular carcinoma.

Worldwide, hepatocellular carcinoma (HCC) remains a crucial medical problem. Precise and concise prognostic models are urgently needed because of the intricate gene variations among liver cancer cells. We conducted this study to identify a prognostic gene signature with biological significance. We applied two algorithms to generate differentially expressed genes (DEGs) between HCC and normal specimens in The Cancer Genome Atlas cohort (training set included) and performed enrichment analyses to expound on their biological significance. A protein-protein interactions network was established based on the STRING online tool. We then used Cytoscape to screen hub genes in crucial modules. A multigene signature was constructed by Cox regression analysis of hub genes to stratify the prognoses of HCC patients in the training set. The prognostic value of the multigene signature was externally validated in two other sets from Gene Expression Omnibus (GSE14520 and GSE76427), and its role in recurrence prediction was also investigated. A total of 2000 DEGs were obtained, including 1542 upregulated genes and 458 downregulated genes. Subsequently, we constructed a 14-gene signature on the basis of 56 hub genes, which was a good predictor of overall survival. The prognostic signature could be replicated in GSE14520 and GSE76427. Moreover, the 14-gene signature could be applied for recurrence prediction in the training set and GSE14520. In summary, the 14-gene signature extracted from hub genes was involved in some of the HCC-related signalling pathways; it not only served as a predictive signature for HCC outcome but could also be used to predict HCC recurrence.

Gamma-glutamyl transpeptidase-to-platelet ratio and the fibrosis-4 index in predicting hepatitis B virus-related hepatocellular carcinoma development in elderly chronic hepatitis B patients in China: A single-center retrospective study.

Gamma-glutamyl transpeptidase-to-platelet ratio (GPR) and fibrosis-4 (FIB-4) index have been reported to be useful predictors in predicting hepatocellular carcinoma (HCC) development in chronic hepatitis B (CHB) patients. However, their predictive performances on HCC development have not been validated in elderly patients. Thus, the aim of this study was to evaluate the predictive values of the GPR and FIB-4 index on HCC in elderly CHB patients with in China.Between January 2007 and December 2016, 1011 CHB patients older than 60 years were enrolled in the study, and their data were retrospectively analyzed. Receiver-operating characteristic (ROC) curve analysis was used to determine the optimal cutoff points of GPR and the FIB-4 index. Cumulative HCC incidence rates were calculated by the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate analyses were performed to detect risk factors for HCC development. The prediction performances of GPR and FIB-4 index were compared based on time-dependent ROC analyses.After a median follow-up of 6.8 (interquartile range 3.9-8.4) years, 39 (3.9%) patients developed HCC. The ROC analysis of GPR and the FIB-4 index at the 5-year time point revealed that the optimal cutoff point was 0.23 for GPR and 4.15 for the FIB-4 index. When stratified by low and high GPR values and FIB-4 indices, the patients' subgroups showed significantly different cumulative incidences of HCC. The multivariate analysis revealed that high GPR (hazard ratio [HR] 4.224; 95% confidence interval [CI] 1.891-9.434, P < .001) was an independent risk factor for HCC development, whereas a high FIB-4 index was not (HR 0.470; 95% CI 0.212-1.043; P = .063). In the time-dependent ROC analysis, GPR showed higher area under curve (AUC) values than the FIB-4 index did at all time points and reached statistical significance at the 5-, 7-, and 10-year time points (GPR vs FIB-4 index, AUC 0.725 vs 0.549 at 5 years, P = .005; GPR vs FIB-4 index, AUC 0.733 vs 0.578 at 7 years, P = .001; GPR vs FIB-4 index, AUC 0.837 vs 0.475 at 10 years, P < .001).In conclusion, our study suggests GPR is superior to the FIB-4 index in predicting HCC development in elderly CHB patients in China.