Effect of nucleos(t)ide analogue discontinuation on the prognosis of HBeAg-negative hepatitis B virus-related hepatocellular carcinoma after hepatectomy: A propensity score matching analysis.

BACKGROUND: Although nucleos(t)ide analogues (NAs) are thought to reduce the risk of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), the effect of NA discontinuation on the prognosis of HBV-related HCC after hepatectomy is rarely reported. We aimed to investigate the potential for hepatitis B virus e antigen (HBeAg)-negative HBV-related HCC patients to discontinue NAs based on preoperative hepatitis B virus surface antigen (HBsAg) status. METHODS: This historical cohort study involved 1232 NA-treated HBeAg-negative patients who underwent curative hepatectomy for HBV-related HCC from 2014 to 2019. The recurrence-free survival (RFS) and overall survival (OS) of patients discontinuing NAs before surgery were compared with those continuing NAs. Propensity score matching (PSM) was used to balance baseline characteristics. RESULTS: Of all enrolled patients, 839 (68.1%) patients continued NAs, and 393 (31.9%) patients discontinued NAs. Continuation of NAs was identified as an independent risk factor for RFS (HR 2.047, 95% CI 1.348-3.109, p < 0.001 before PSM and HR 2.756, 95% CI 1.537-4.942, p < 0.001 after PSM) in HBsAg-negative patients. Similarly, subgroup survival analyses showed that NA discontinuation was associated with better RFS (p = 0.029 before PSM and p < 0.001 after PSM) and comparable OS (p = 0.935 before PSM and p = 0.115 after PSM) than NA continuation in HBsAg-negative patients. The interaction between HBsAg status and continuation or discontinuation of NAs was significant (p for interaction <0.001). CONCLUSIONS: These findings demonstrate the potential for HBeAg-negative HBV-related HCC patients who have achieved HBsAg seroclearance to discontinue NAs under strict monitoring.

Tumour burden score combined with albumin-to-alkaline phosphatase ratio predicts prognosis in patients with intrahepatic cholangiocarcinoma.

Tumour morphology (tumour burden score (TBS)) and liver function (albumin-to-alkaline phosphatase ratio (AAPR)) have been shown to correlate with outcomes in intrahepatic cholangiocarcinoma (ICC). This study aimed to evaluate the combined predictive effect of TBS and AAPR on survival outcomes in ICC patients. We conducted a retrospective analysis using a multicentre database of ICC patients who underwent curative surgery from 2011 to 2018. The Kaplan-Meier method was employed to examine the relationship between a new index (combining TBS and AAPR) and long-term outcomes. The predictive efficacy of this index was compared to other conventional indicators. A total of 560 patients were included in the study. Based on TBS and AAPR stratification, patients were classified into three groups. Kaplan-Meier curves demonstrated that 124 patients with low TBS and high AAPR had the best overall survival (OS) and recurrence-free survival (RFS), while 170 patients with high TBS and low AAPR had the worst outcomes (log-rank p < 0.001). Multivariate analyses identified the combined index as an independent predictor of OS and RFS. Furthermore, the index showed superior accuracy in predicting OS and RFS compared to other conventional indicators. Collectively, this study demonstrated that the combination of liver function and tumour morphology provides a synergistic effect in evaluating the prognosis of ICC patients. The novel index combining TBS and AAPR effectively stratified postoperative survival outcomes in ICC patients undergoing curative resection.

The role of cholesterol-modified prognostic nutritional index in nutritional status assessment and predicting survival after liver resection for hepatocellular carcinoma.

Malnutrition, which is often underestimated in patients with hepatocellular carcinoma (HCC), has a proven adverse effect on survival rates. The purpose of this study was to verify the effectiveness of the cholesterol-modified prognostic nutritional index (CPNI) in determining the nutritional status and predicting overall survival (OS) and recurrence-free survival (RFS) in patients with HCC by comparing it with several other nutritional indicators. This retrospective single-center study enrolled 1450 consecutive HCC patients who underwent curative liver resection from January 2015 to November 2019. We evaluated the prognostic significance of several nutritional indicators, including CPNI, the controlling nutritional status (CONUT), the nutritional risk index (NRI), and the prognostic nutritional index (PNI), by applying time-dependent receiver operating characteristic (ROC) curves, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis. Among several objective nutrition evaluations (including CPNI, CONUT, NRI, and PNI), CPNI demonstrated the greatest prognostic predictive power for predicting OS. Meanwhile, CPNI demonstrated marginally higher accuracy in predicting RFS compared to PNI, and significantly outperformed CONUT and NRI. Univariate and multivariate analyses suggested that CPNI was an independent risk factor for the OS and RFS of patients with HCC undergoing curative liver resection. In most subgroups, malnutrition as identified by CPNI demonstrates strong stratification ability in predicting both OS and RFS. CPNI serves as an accurate and stable instrument for evaluating nutritional status and forecasting survival outcomes in HCC patients following liver resection, which has the potential to markedly influence clinical decision-making processes and the management of patient care.

Reconstruction of Inferior Vena Cava by Autologous Great Saphenous Vein Grafts in Liver Surgery.

BACKGROUND: To secure surgical margin for hepatic lesion with involvement of the inferior vena cava (IVC), combined radical liver resection and IVC replacement are required. A novel method of replacing IVC by newly customized autologous great saphenous vein (GSV) grafts was introduced by this study. This study aimed at reporting the feasibility and outcome of this novel technique. METHODS: From January 2014 to January 2021, all consecutive patients who underwent concomitant hepatectomy and IVC replacement by autogenous GSV graft were enrolled in this study. Technical insights, intraoperative details, demographic data, postoperative complication, graft patency and survival data were collected and analyzed. RESULTS: Concomitant hepatectomy/autotransplantation (ERAT) with IVC replacement by autogenous GSV graft was successful in 47 patients and there was no 30-day mortality. There were 8 out of the 47 patients whose retrohepatic venae cavae were completely invaded by the lesion and their reconstructed IVCs were totally made from GSV grafts. The other 39 patients whose IVCs were partially invaded had their IVCs reconstructed by both the unaffected part of the IVC wall and newly customized GSV graft. Postoperative complications classified as Clavien-Dindo grade II, III A and III B were observed in 10, 7 and 3 patients, respectively. The median follow-up months were 35 months (29-80 months). No patient developed thrombosis of the graft and 100% patency of the IVC was observed throughout the study. CONCLUSION: In selected patients, hepatectomy/ERAT with IVC replacement by autogenous GSV graft is safe and feasible. The newly customized autologous GVS graft was ideal for reconstruction of the IVC in liver surgery.

The Pyroptosis-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Immunotherapeutic Efficiency in Hepatocellular Carcinoma.

Pyroptosis was recently demonstrated to be an inflammatory form of gasdermin-regulated programmed cell death characterized by cellular lysis and the release of several proinflammatory factors and participates in tumorigenesis. However, the effects of pyroptosis-related long noncoding RNAs (lncRNAs) on hepatocellular carcinoma (HCC) have not yet been completely elucidated. Based on the regression coefficients of ZFPM2-AS1, KDM4A-AS1, LUCAT1, NRAV, CRYZL2P-SEC16B, AL031985.3, SNHG4, AL049840.5, AC008549.1, MKLN1-AS, AC099850.3, and LINC01224, HCC patients were classified into a low- or high-risk group. The high-risk score according to pyroptosis-related lncRNA signature was significantly associated with poor overall survival even after adjusting for age and clinical stage. Receiver operating characteristic curves and principal component analysis further supported the accuracy of the model. Our study revealed that a higher pyroptosis-related lncRNA risk score was significantly associated with tumor staging, pathological grade, and tumor-node-metastasis stages. The nomogram incorporating the pyroptosis-related lncRNA risk score and clinicopathological factors demonstrated good accuracy. Furthermore, we observed distinct tumor microenvironment cell infiltration characteristics between high- and low-risk tumors. Notably, based on the risk model, we found that the risk score is closely related to the expression of immune checkpoint genes, immune subtypes of tumors, and the sensitivity of HCC to chemotherapy drugs and immunotherapy. In conclusion, our novel risk score of pyroptosis-related lncRNA can serve as a promising prognostic biomarker for HCC patients and provide help for HCC patients to guide precision drug treatment and immunotherapy.

Tumor Burden Score Stratifies Prognosis of Patients With Intrahepatic Cholangiocarcinoma After Hepatic Resection: A Retrospective, Multi-Institutional Study.

Background: The prognostic significance of tumor burden score (TBS) on patients who underwent curative-intent resection of intrahepatic cholangiocarcinoma (ICC) has not been evaluated. The present study aimed to investigate the impact of TBS and its synergistic effect with CA19-9 (combination of TBS and CA19-9, CTC grade) on long-term outcomes. Methods: Patients who underwent radical resection of ICC between 2009 and 2017 were retrospectively identified from a multi-center database. The overall survival (OS) and recurrence-free survival (RFS) were examined in relation to TBS, serum preoperative CA19-9, and CTC grade. Results: A total of 650 patients were included in our study (509 in the derivation cohort and 141 in the validation cohort). Kaplan-Meier curves showed that both TBS and CA19-9 levels were strong predictors of survival outcomes. Patients with elevated TBS grade or elevated CA19-9 were associated with worse OS and RFS (both p < 0.001). As expected, CTC grade also performed well in predicting long-term outcomes. Patients with low TBS/low CA19-9 (CTC grade 1) were associated with the best OS as well as RFS, while high TBS/high CA19-9 (CTC grade 3) correlated to the worst outcomes. In the validation cohort, TBS grade, preoperative CA19-9, and CTC grade also stratified prognosis among patients (p < 0.001 for each). Conclusions: Both tumor morphology (tumor burden) and tumor-specific biomarker (serum CA19-9) were important when evaluating prognosis of patients with resectable ICC. Serum CA19-9 and TBS showed a synergistic effect on prognostic evaluation. CTC grade was a promising tool in stratifying prognosis of ICC patients after curative resection.

Prognostic Value of Combined CA19-9 with Aspartate Aminotransferase to Lymphocyte Ratio in Patients with Intrahepatic Cholangiocarcinoma After Hepatectomy.

PURPOSE: The prognosis of intrahepatic cholangiocarcinoma (ICC) patients after surgical resection remains poor. Effective prognostic biomarkers are expected to stratify ICC patients and optimize their treatment strategies. To investigate the prognostic value of carbohydrate antigen 19-9 (CA19-9), aspartate aminotransferase to lymphocyte ratio index (ALRI), and their combination (CAC) in predicting long-term outcomes in ICC patients after hepatectomy. PATIENTS AND METHODS: ICC patients underwent initial hepatectomy for curative purpose from January 2009 to September 2017 were reviewed retrospectively. Area under the receiver operating characteristics curve (AUC) was used to distinguish the identification effectiveness of three different measures. Kaplan-Meier curves and Cox proportional hazards regression were used to assess the value of preoperative CAC grade in predicting overall survival (OS) and disease-free survival (DFS). RESULTS: A total of 530 patients were included and randomly divided into two groups (derivation cohort and validation cohort). During a median follow-up of 18 months (1-115.4 months), 317 patients (59.8%) died and 381 patients (71.9%) developed tumor recurrence. Lower ALRI, decreased serum CA19-9 level and CAC grade were found to be associated with better OS and DFS (both P<0.001). Importantly, the AUC for CAC grade was significantly greater than ALRI and CA19-9. In addition, results from Cox proportional hazards regression from both cohorts suggest that tumor number, node invasion, and CAC grade as independent prognostic factors for both OS and DFS. CONCLUSION: This study demonstrated that CAC grade is a valuable biomarker for the prognosis of ICC patients. Specifically, patients with elevated CAC grades were correlated to worse long-term outcome after the hepatectomy. Our data suggest that increased CAC grades can be used to stratify patients and help to decide their treatment strategies.

Integrated nomograms to predict overall survival and recurrence-free survival in patients with combined hepatocellular cholangiocarcinoma (cHCC) after liver resection.

The current clinical classification of primary liver cancer is unable to efficiently predict the prognosis of combined hepatocellular cholangiocarcinoma (cHCC). Accurate satellite nodules (SAT) and microvascular invasion (MVI) prediction in cHCC patients is very important for treatment decision making and prognostic evaluation. The aim of this work was to explore important factors affecting the prognosis of cHCC patients after liver resection and to develop preoperative nomograms to predict SAT and MVI in cHCC patients. The nomogram was developed using the data from 148 patients who underwent liver resection for cHCC patients at our hospital between January 2006 and December 2014. Based on the results of the multivariate analysis, a nomogram integrating all significant independent factors affecting overall survival and recurrence-free survival was constructed to predict the prognosis of cHCC. Next, risk factors for SAT and MVI were evaluated with logistic regression. Blood signatures were established using the LASSO regression, and then, we combined the clinical risk factors and blood signatures of the patients to establish predictive models for SAT and MVI. The C-index of the nomogram for predicting survival was 0.685 (95% CI, 0.638 to 0.732), which was significantly higher than the C-index for other liver cancer classification systems.