Postoperative Hepatocellular Carcinoma Research Articles

Pathologic assessment of hepatocellular carcinoma in the era of immunotherapy: a narrative review.

Immune checkpoint inhibitor (ICI)-based therapy has achieved impressive success in various cancer types. Several ICIs have been unprecedentedly approved as the treatment regimens for advanced hepatocellular carcinoma (HCC) in recent decade. Meanwhile, numerous clinical trials are being performed to exploit more ICIs into initially unresectable HCC and postoperative HCC to expectantly induce adequate tumor downstaging for further resection or implement adjuvant treatment for relapse-free survival, respectively. In this review, we aim to summarize some pragmatic histomorphologic, immunohistochemical, and molecular pathologic parameters which promisingly indicate the response of neoadjuvant/conversion ICI-related therapy and predict the efficacy of adjuvant/therapeutic ICI-related therapy for HCC. We searched PubMed using the terms hepatocellular carcinoma, immunotherapy, immune checkpoint inhibitor, immune checkpoint blockade, conversion therapy, neoadjuvant therapy, adjuvant therapy, biomarker, pathologic evaluation, pathologic assessment till February 2023. Although there is no consensus regarding the pathologic evaluation of relevant HCC specimens, it is encouraging that a few of studies have concentrated on this field, and moreover, the methods and parameters noted on other cancer types are also worthy of reference. For the pathologic assessment of HCC specimens underwent immunotherapy, a suitable sampling scheme, identifying immunotherapy-related pathologic response, and quantification of pathologic response rate should be emphasized. For the patients of HCC who are scheduled to receive immunotherapy, tumor-infiltrating lymphocyte, intratumoral tertiary lymphoid structure, programmed cell death ligand 1, Wnt/β-catenin, microsatellite instability and mismatch repair, tumor mutational burden and tumor neoantigen, as well as some other signaling pathways are the potential predictive biomarkers of treatment response of ICI. The management of HCC in the era of immunotherapy arises a brand-new pathological challenge that is to provide an immunotherapy-related diagnostic report. Albeit many related researches are preclinical or insufficient, they may tremendously alter the immunotherapy strategy of HCC in future.

Effect of Sarcopenia on the Prognosis of Clinical Outcomes in Patients With Hepatocellular Carcinoma After Hepatic Resection.

We aimed to study the prognostic impact of sarcopenia on overall survival (OS), disease-free survival (DFS), and postoperative outcomes among patients with Hepatocellular carcinoma (HCC) who underwent curative hepatic resection. Data were collected retrospectively from patients with HCC underwent curative hepatic resection and preoperative abdominal computed tomography (CT) at our institution between January 2010 and December 2020. Sarcopenia was evaluated by the skeletal muscle mass at the inferior direction of the third-lumbar-vertebra (L3) cross-sectional area based on preoperative CT imaging using software analysis. Cutoff values for skeletal muscle index (SMI) were 43.75 and 41.10cm2/m2 for males and females. The patients were classified into sarcopenia and nonsarcopenia groups. The association between preoperative sarcopenia and clinicopathological factors, impact of sarcopenia on survival, and postoperative outcomes were analyzed. Sarcopenia was present in 39 of 83 (47.0%) patients who underwent curative hepatic resection for HCC and was significantly correlated with lower SMI, lower serum albumin levels, higher intraoperative blood loss, higher postoperative complications, and longer hospital stay. The 5-year OS was significantly lower in sarcopenic patients than in nonsarcopenic patients (58.2% vs 83.6%; P = .006), but the 5-year DFS was not significantly different between the 2 groups. Multivariate analysis revealed that sarcopenia was a significant risk factor for poor OS (HR 4.728; 95% CI, 1.458-15.329; P = .010). Sarcopenia was identified as a prognostic factor for poor OS after hepatic resection, and major postoperative complications were more frequent in sarcopenia. Early sarcopenia detection and management may improve OS and clinical outcomes in postoperative HCC.

Novel Preoperative Type IV Collagen to Predict the Risk of Hepatocellular Carcinoma in Patients with Hepatitis B Virus-Related Cirrhotic Portal Hypertension After Laparoscopic Splenectomy and Azygoportal Disconnection.

Although laparoscopic splenectomy and azygoportal disconnection (LSD) can significantly decrease portal vein pressure and even the incidence of hepatocellular carcinoma (HCC) in patients with cirrhotic portal hypertension (CPH), postoperative HCC inevitably occurs in certain patients. The purpose of this study was to seek a novel preoperative non-invasive predictive indicator to predict the occurrence of postoperative HCC. From April 2012 to April 2022, we collected clinical data of 178 hepatitis B virus (HBV)-related CPH patients. Based on inverse treatment probability weighting, candidate variables for predicting postoperative HCC were determined by means analysis. Then, a novel preoperative non-invasive prediction indicator (ie, type IV collagen-alpha fetoprotein-fibrosis-4 score [IVAF-FIB-4]) was established based on candidate variables, and its predictive ability was explored. Postoperative HCC occurred in 9 (5.1%) patients. Correlation analyses showed that the IVAF-FIB-4 had a significant positive correlation with HCC (r = 0.835, P < 0.001). IVAF-FIB-4 showed a high accuracy (the area under the receiver operating characteristic curve: 0.939, 95% confidence interval [CI]: 0.818-1.000; sensitivity: 88.9%; specificity: 93.5%). At the end of follow-up, the incidence density of HCC in patients with IVAF-FIB-4 (1) was significant higher than that in patients with IVAF-FIB-4 (0) (138.1/1000 vs 1.1/1000 person-years; rate ratio: 130.475, 95% CI: 16.318-1043.227). In logistic regression, IVAF-FIB-4 was an independent risk factor for HCC (odds ratio: 668.000, 95% CI: 53.895-8279.541; P < 0.001). IVAF-FIB-4 is a novel preoperative noninvasive predictive indicator for predicting postoperative HCC in HBV-related CPH patients after LSD, with satisfactory predictive ability.

In Situ Nanofiber Patch Boosts Postoperative Hepatocellular Carcinoma Immune Activation by Trimodal Combination Therapy.

Poor clinical efficacy associated with postoperative hepatocellular carcinoma (HCC) often results from recurrence and metastasis. Hence, research has focused on establishing an effective multimodal therapy. However, complex combinations of active ingredients require multiple functions in therapeutic systems. Herein, a portable nanofiber patch composing germanium phosphorus (GeP) and anlotinib (AL) was designed to form a versatile platform for molecularly targeted photothermal-immune checkpoint blockade (ICB) trimodal combination therapy. The patches possess hydrophilic, satisfactory mechanical, and excellent photothermal conversion properties. Moreover, they achieve a penetrating and sustained drug release. The near-infrared light-assisted GeP-induced temperature increase regulates AL release, downregulating the expression of vascular-related factor receptors, triggering immunogenic cell death of tumor cells, and inducing dendritic cell maturation. Simultaneously, ICB therapy (programmed cell death ligand 1, PD-L1) was introduced to improve treatment outcomes. Notably, this trimodal combination therapy significantly inhibits vascular hypergrowth, enhances effector T-cell infiltration, and sensitizes the PD-L1 antibody response, boosting immunotherapy to suppress residual HCC recurrence and metastasis. Further validation of the genome sequencing results revealed cell pathways related primarily to regulatory immune effects. This study demonstrates the use of an effective and practical nanofiber patch to improve multimodal therapy of postoperative HCC, with high clinical translation value.

Bifidobacterium longum promotes postoperative liver function recovery in patients with hepatocellular carcinoma

Timely liver function recovery (LFR) is crucial for postoperative hepatocellular carcinoma (HCC) patients. Here, we established the significance of LFR on patient long-term survival through retrospective and prospective cohorts and identified a key gut microbe, Bifidobacterium longum, depleted in patients with delayed recovery. Fecal microbiota transfer from HCC patients with delayed recovery to mice similarly impacted recovery time post hepatectomy. However, oral gavage of B.longum improved liver function and repair in these mice. In a clinical trial of HCC patients, orally administering a probiotic bacteria cocktail containing B.longum reduced the rates of delayed recovery, shortened hospital stays, and improved overall 1-year survival. These benefits, attributed to diminished liver inflammation, reduced liver fibrosis, and hepatocyte proliferation, were associated with changes in key metabolic pathways, including 5-hydroxytryptamine, secondary bile acids, and short-chain fatty acids. Our findings propose that gut microbiota modulation can enhance LFR, thereby improving postoperative outcomes for HCC patients.

Development of a machine learning-based model for predicting risk of early postoperative recurrence of hepatocellular carcinoma

BACKGROUND Surgical resection is the primary treatment for hepatocellular carcinoma (HCC). However, studies indicate that nearly 70% of patients experience HCC recurrence within five years following hepatectomy. The earlier the recurrence, the worse the prognosis. Current studies on postoperative recurrence primarily rely on postoperative pathology and patient clinical data, which are lagging. Hence, developing a new pre-operative prediction model for postoperative recurrence is crucial for guiding individualized treatment of HCC patients and enhancing their prognosis. AIM To identify key variables in pre-operative clinical and imaging data using machine learning algorithms to construct multiple risk prediction models for early postoperative recurrence of HCC. METHODS The demographic and clinical data of 371 HCC patients were collected for this retrospective study. These data were randomly divided into training and test sets at a ratio of 8:2. The training set was analyzed, and key feature variables with predictive value for early HCC recurrence were selected to construct six different machine learning prediction models. Each model was evaluated, and the best-performing model was selected for interpreting the importance of each variable. Finally, an online calculator based on the model was generated for daily clinical practice. RESULTS Following machine learning analysis, eight key feature variables (age, intratumoral arteries, alpha-fetoprotein, pre-operative blood glucose, number of tumors, glucose-to-lymphocyte ratio, liver cirrhosis, and pre-operative platelets) were selected to construct six different prediction models. The XGBoost model outperformed other models, with the area under the receiver operating characteristic curve in the training, validation, and test datasets being 0.993 (95% confidence interval: 0.982-1.000), 0.734 (0.601-0.867), and 0.706 (0.585-0.827), respectively. Calibration curve and decision curve analysis indicated that the XGBoost model also had good predictive performance and clinical application value. CONCLUSION The XGBoost model exhibits superior performance and is a reliable tool for predicting early postoperative HCC recurrence. This model may guide surgical strategies and postoperative individualized medicine.

Prognostic Factors for Patients with Proliferative Hepatocellular Carcinoma After Liver Resection.

There is a scarcity of predictive models currently accessible for prognosticating proliferative hepatocellular carcinoma (HCC), an integrated class of subtype, characterized by a dismal prognosis. Consequently, this study aimed to develop and validate a novel prognostic model capable of accurately predicting the prognosis of proliferative HCC after curative resection. This retrospective multicenter study included patients with solitary HCC who underwent curative liver resection from August 2014 to December 2020 (n = 816). Patients were stratified into either the proliferative HCC cohort (n = 259) or the nonproliferative HCC cohort (n = 557) based on histological criteria. Disease-free survival (DFS) was compared between the two groups before and after one-to-one propensity score matching (PSM). Of all the proliferative HCC patients, 203 patients were assigned to training cohort, and 56 patients were assigned to validation cohort. Univariate and multivariate analyses were performed in training cohort to identify risk factors associated with worse DFS. Thereafter, a predictive model was constructed, subsequently validated in the validation cohort. The DFS of proliferative HCC was significantly worse than nonproliferative HCC before and after PSM. Meanwhile, multivariate regression analysis revealed that liver cirrhosis (P = 0.032) and larger tumor size (P = 0.000) were independent risk factors of worse DFS. Lastly, the discriminative abilities of the predictive model for 1, 3, 5-year DFS rates, as determined by receiver operating characteristic (ROC) curves, were 0.702, 0.720, and 0.809 in the training cohort and 0.752, 0.776, and 0.851 in the validation cohort, respectively. This study developed a predictive model with satisfactory accuracy to predict the worse DFS in proliferative HCCs after liver resection. Moreover, this predictive model may serve as a valuable tool for clinicians to predict postoperative HCC recurrence, thereby enabling them to implement early preventative strategies.

An offline to online cognitive behavioral stress management caring program effectively improves psychological pressure, spiritual well-being, and quality of life in postoperative hepatocellular carcinoma patients.

This study designed an offline to online cognitive behavioral stress management (OOCBSM) caring program, intending to investigate its effect on mental health and quality of life (QoL) using multiple scales in postoperative hepatocellular carcinoma (HCC) patients. 254 postoperative HCC patients were randomly (1:1) allocated into OOCBSM (included a 10-week offline CBSM and subsequent online CBSM until M6) and normal care (NC) groups (10-week NC). Hospital anxiety-and-depression scale (HADS), Zung's self-reporting anxiety (SAS) and depression scale (SDS), FACIT-SP, European quality-of-life-5 dimensions (EQ-5D), and quality-of-life questionnaire-core30 (QLQ-C30) were assessed over 6 months (M). HADS-defined-anxiety rates at M3 (P=0.036) and M6 (P=0.025), SAS-defined-anxiety rate at M6 (P=0.049), HADS-defined-depression rates at M3 (P=0.026) and M6 (P=0.049), and SDS-defined-depression rates at M3 (P=0.015) and M6 (P=0.043) were all lower in OOCBSM group compared to NC group. Furthermore, FACIT-SP scores at M1 (P=0.004), M3 (P=0.003), and M6 (P<0.001) were higher in OOCBSM group compared with NC group. EQ-5D scores at M1 (P=0.025) and M3 (P=0.030) but not M6 (P=0.128), and QLQ-C30-symptom score at M3 (P=0.014) but not M1 (P=0.198) and M6 (P=0.058) were lower in OOCBSM group versus NC group; QLQ-C30-global-health-status scores at M3 (P=0.027) and M6 (P=0.001) but not M1 (P=0.312), QLQ-C30-function scores at M3 (P=0.005) and M6 (P=0.001) but not M1 (P=0.084) were higher in OOCBSM group versus NC group. Patients with younger ages or higher education benefited more from OOCBSM. OOCBSM improves psychological pressure, spiritual well-being, and QoL in postoperative HCC patients, especially in those with younger ages or higher education.

Radiomics-guided prognostic assessment of early-stage hepatocellular carcinoma recurrence post-radical resection.

The prognosis of early-stage hepatocellular carcinoma (HCC) patients after radical resection has received widespread attention, but reliable prediction methods are lacking. Radiomics derived from enhanced computed tomography (CT) imaging offers a potential avenue for practical prognostication in HCC patients. We recruited early-stage HCC patients undergoing radical resection. Statistical analyses were performed to identify clinicopathological and radiomic features linked to recurrence. Clinical, radiomic, and combined models (incorporating clinicopathological and radiomic features) were built using four algorithms. The performance of these models was scrutinized via fivefold cross-validation, with evaluation metrics including the area under the curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE) being calculated and compared. Ultimately, an integrated nomogram was devised by combining independent clinicopathological predictors with the Radscore. From January 2016 through December 2020, HCC recurrence was observed in 167 cases (64.5%), with a median time to recurrence of 26.7months following initial resection. Combined models outperformed those solely relying on clinicopathological or radiomic features. Notably, among the combined models, those employing support vector machine (SVM) algorithms exhibited the most promising predictive outcomes (AUC: 0.840 (95% Confidence interval (CI): [0.696, 0.984]), ACC: 0.805, SEN: 0.849, SPE: 0.733). Hepatitis B infection, tumour size > 5cm, and alpha-fetoprotein (AFP) > 400ng/mL were identified as independent recurrence predictors and were subsequently amalgamated with the Radscore to create a visually intuitive nomogram, delivering robust and reliable predictive performance. Machine learning models amalgamating clinicopathological and radiomic features provide a valuable tool for clinicians to predict postoperative HCC recurrence, thereby informing early preventative strategies.

Adjuvant immune checkpoint inhibitors and association with recurrence-free survival in postoperative hepatocellular carcinoma (PREVENT): A prospective cohort study.

4119 Background: Adjuvant therapy may improve survival of patients with hepatocellular carcinoma (HCC) after curative resection, yet no such therapy is universally recommended. This study compared safety and efficacy outcomes between patients at high risk of recurrence who received different types of adjuvant therapy or no such therapy after hepatic resection for HCC. Methods: Recurrence-free survival (RFS), overall survival, and adverse events were compared among patients who received adjuvant immune checkpoint inhibitors (ICIs) alone, ICIs with tyrosine kinase inhibitors (TKIs), or no adjuvant therapy at our medical center between 13 March 2019 and 19 March 2022. In some analyses, patients who received adjuvant therapy were matched based on propensity scores to patients who did not, in order to reduce confounding due to baseline differences. This study was registered on ClinicalTrials.gov (NCT05221398). Results: Of the 492 patients in our final analysis, 410 (83.3%) received no adjuvant therapy, 50 (10.2%) received ICIs alone, and 32 (6.5%) received adjuvant ICIs and TKIs. During median follow-up of 23.3 months (IQR 15.6 to 31.1 months), HCC recurred in 221 (53.9%) of patients who received no adjuvant therapy, compared to 22 (44.0%) of patients who received ICIs and 18 (56.3%) of patients who received ICIs and TKIs. RFS was significantly longer among patients who received either type of adjuvant therapy (23.9 months, 95%CI 14.0-33.7) than among those who received none (16.8 months, 95%CI 13.2-20.3), and this difference remained significant after propensity score matching (HR 0.61, 95%CI 0.39-0.94, P = 0.033). However, overall survival was unaffected by either type of adjuvant therapy, even after propensity score matching. The rate of grade 3 or 4 adverse events was similar between the two types of adjuvant therapy. Conclusions: ICIs alone or with TKIs may improve RFS of patients at high risk of recurrence after curative resection. Clinical trial information: NCT05221398 .

Efficacy and prognostic factors of repeated hepatectomy for postoperative intrahepatic recurrence of hepatocellular carcinoma undergoing initial hepatectomy.

Postoperative recurrence of hepatocellular carcinoma (HCC) is associated with low survival rates. While HCC treatment options have expanded substantially, they are accompanied by several challenges. This study assessed the outcomes of repeated hepatectomy (RH) for postoperative intrahepatic recurrence of HCC among patients undergoing initial hepatectomy (IH) as well as independent risk factors for HCC recurrence among patients undergoing repeated hepatectomy (RH). Clinical data from 84 patients undergoing both IH and RH and 66 recurrent HCC patients who had received radiofrequency ablation (RFA) from July 2011 to September 2017 were retrospectively reviewed. The following groups were compared: (1) RH Group A (n = 84), (2) IH Group (n = 84, same individuals as RH Group A), (3) RH Group B (n = 45/84 from RH Group A), and (4) RFA Group (n = 66). The clinical pathology and operative characteristics of the patients in RH Group A were compared to those in the IH Group. Meanwhile, the clinical pathology and pre- and post-treatment features of the patients in RH Group B were compared to those in the RFA Group. The tumor-free survival time was compared between patients in RH Group A and the IH Group as well as between patients in RH Group B and the RFA Group. The independent risk factors for the 1-year postoperative tumor-free survival of RH Group A patients were investigated using univariate and multivariate analysis. Measures of clinical pathology, including AFP, Child-Pugh score, HBV-DNA, tumor number, liver cirrhosis, tumor differentiation, surgical approach, and TNM stage differed significantly between patients in RH Group A and the IH Group (all P < 0.05), with the exception of tumor number and tumor size (both P > 0.05). No significant differences were found in these measures between the patients in RH Group B and the RFA Group (all P > 0.05). While patients in the RH Group A had a longer operation time than those in the IH Group (4.35 ± 1.25 h vs. 3.55 ± 0.92 h, P < 0.001), the level of intraoperative bleeding was similar (400.00 ± 199.25 ml vs. 359.40 ± 213.37 ml, P = 0.204). RH Group B patients had a longer hospitalization time than those in the RFA Group (6.5 ± 0.8 d vs. 5.5 ± 1.1 d, P < 0.001), however, the difference in hospitalization costs was not statistically significant (29,009 ± 3,806 CNY vs. 29,944 ± 3,752 CNY, P = 0.202). Five-day post-operative serum biomarker levels, including direct bilirubin (DB) and albumin (ALB), were significantly higher in RH Group B than in the RFA Group (all P < 0.05), with the exception of ALT, AST, and total bilirubin (TB) (all P > 0.05). Patients in RH Group A had a lower tumor-free survival time than those in the IH Group (median: 12 vs. 22 months, P < 0.001), and patients in the RH Group B had a significantly higher tumor-free survival time than those in the RFA group (median: 15 months vs. 8 months, P < 0.001). Age ≥50 y, Child-Pugh class A, and negative HBV-DNA were independent risk factors that positively impacted the 1-year postoperative tumor-free survival rate of postoperative intrahepatic recurrent HCC patients undergoing RH (P < 0.001, respectively). Due to the potential of harm related to relapse of recurrent HCC for cancer patients, RH is a superior option. RH could offer better outcomes for recurrent HCC patients undergoing IH. Compared with lesion pathology, the better target organ of the liver will be key to ameliorating tumor-free survival for recurrent HCC patients undergoing RH.

The tumor microenvironment in the postsurgical liver: Mechanisms and potential targets of postoperative recurrence in human hepatocellular carcinoma.

Surgery remains to be the mainstay of treatment for hepatocellular carcinoma (HCC). Nonetheless, its therapeutic efficacy is significantly impaired by postoperative recurrence, which occurs in more than half of cases as a result of intrahepatic metastasis or de novo tumorigenesis. For decades, most therapeutic strategies on inhibiting postoperative HCC recurrence have been focused on the residual tumor cells but satisfying therapeutic outcomes are barely observed in the clinic. In recent years, a better understanding of tumor biology allows us to shift our focus from tumor cells towardthe postoperative tumor microenvironment (TME), which is gradually identified to play a pivotal role in tumor recurrence. In this review, we describe various surgical stress and surgical perturbation on postoperative TME. Besides, we discuss how such alternations in TME give rise to postoperative recurrence of HCC. Based on its clinical significance, we additionally highlight the potential of the postoperative TME as a target for postoperative adjuvant therapeutics.

Increased plasma levels of monocyte chemoattractant protein-1 in patients with hepatitis B virus pre-S2 gene deletion mutation predict a higher risk of hepatocellular carcinoma recurrence after curative surgical resection.

Despite resection surgery as a curative therapy for hepatocellular carcinoma (HCC), the high rate of postoperative HCC recurrence remains a big challenge for patient survival. Chronic hepatitis B virus (HBV) infection is the most important risk factor for HCC. Deletion mutation in the HBV pre-S2 gene leads to expression of an essential viral oncoprotein called pre-S2 mutant and represents an independent prognostic biomarker for HCC recurrence after curative surgical resection. Additionally, cytokines are multifunctional secreted proteins and implicated in all stages of HBV-related HCC tumorigenesis. This study aimed to identify the cytokines whose plasma levels were associated with pre-S2 gene deletion mutation and HCC recurrence and evaluate their potential to be combined with pre-S2 gene deletion mutation in predicting HCC recurrence. Among a panel of 27 cytokines examined, plasma levels of monocyte chemoattractant protein-1 (MCP-1) were significantly upregulated in patients with pre-S2 gene deletion mutation or HCC recurrence. MCP-1 was validated as an independent prognostic biomarker for HCC recurrence. Moreover, patients with both the presence of pre-S2 gene deletion mutation and high levels of MCP-1 displayed a higher risk of HCC recurrence than patients with either one or none of these two biomarkers. The combination of pre-S2 gene deletion mutation and MCP-1 levels exhibited a better prognostic performance for HCC recurrence than each biomarker alone. This study discovered that MCP-1 levels had a significance to be as a combination biomarker with pre-S2 gene deletion mutation providing an improved performance in predicting HCC recurrence after curative surgical resection.

Deep Learning Model Based on Contrast-Enhanced Computed Tomography Imaging to Predict Postoperative Early Recurrence after the Curative Resection of a Solitary Hepatocellular Carcinoma

We aimed to develop the deep learning (DL) predictive model for postoperative early recurrence (within 2 years) of hepatocellular carcinoma (HCC) based on contrast-enhanced computed tomography (CECT) imaging. This study included 543 patients who underwent initial hepatectomy for HCC and were randomly classified into training, validation, and test datasets at a ratio of 8:1:1. Several clinical variables and arterial CECT images were used to create predictive models for early recurrence. Artificial intelligence models were implemented using convolutional neural networks and multilayer perceptron as a classifier. Furthermore, the Youden index was used to discriminate between high- and low-risk groups. The importance values of each explanatory variable for early recurrence were calculated using permutation importance. The DL predictive model for postoperative early recurrence was developed with the area under the curve values of 0.71 (test datasets) and 0.73 (validation datasets). Postoperative early recurrence incidences in the high- and low-risk groups were 73% and 30%, respectively (p = 0.0057). Permutation importance demonstrated that among the explanatory variables, the variable with the highest importance value was CECT imaging analysis. We developed a DL model to predict postoperative early HCC recurrence. DL-based analysis is effective for determining the treatment strategies in patients with HCC.

Different power modes of microwave ablation for hepatocellular carcinoma: Evaluation of recurrence rate and factors related to recurrence

PurposeTo evaluate the safety and efficacy of different power modes(constant power and variable power) percutaneous microwave ablation (MWA) for treating hepatocellular carcinoma (HCC) and to predict the risk factors of recurrence after MWA. Materials and methodsIn this retrospective study, a total of 112 patients with solitary HCC were included from January 2015 to January 2021. All patients received MWA through a percutaneous approach that was guided by ultrasound, 45 patients received variable power MWA, and the remaining 67 were treated with constant power MWA. The complete ablation rates, local recurrence rates, complications, and short-term survival were analyzed. Possible risk factors for tumor recurrence were analyzed. ResultsThe complete ablation rates were 95.9% for the first ablation and 100% for the second ablation for ≤3 cm lesions. The complete ablation rates were 84.2%(95.9% versus 84.2%, p = 0.039) for the first ablation and 94.7% (100% versus 94.7%, p = 0.113) for the second ablation for 3–5 cm lesions. Local and distant recurrence rates were 18.7%(21/112) and 14.3%(16/112). The 1-, 2-year survival rates were 86.3 and 66.3%, respectively. Subgroup analysis showed that 1-, 2-year survival rates were 91.1% and 78.5% in ≤3 cm group, and were 74.4% and 40.9% in 3–5 cm group, respectively. Univariate analysis revealed that a positive correlation existed between the HBV DNA replication(p = 0.007), AFP level of pre-MWA(p = 0.001) and post-MWA(p<0.001), tumor diameter(p<0.001), irregular shape(p = 0.014), proximity to the risk location(p = 0.008), poor differentiation(p = 0.003), constant power(p = 0.028), length(p<0.001) and width of ablation zone(p = 0.001), and present complication(p<0.001), and early recurrence. Multivariate analysis identified HBV DNA replication(OR = 0.266, p = 0.036), AFP level of pre-MWA (OR = 4.001, p = 0.036), tumor diameter (OR = 2.153, p = 0.042), tumor location (OR = 0.910, p = 0.046), and width of ablation zone(OR = 2.530, p = 0.044) were independent prognosis factors causing postoperative HCC recurrence. ConclusionVariable power MWA of HCC appears to be a safe and effective treatment. HBV DNA, AFP level of pre-MWA, tumor diameter, tumor location, and width of ablation range appear to be independent predictors of tumor recurrence.

Pre-operative MRI features predict early post-operative recurrence of hepatocellular carcinoma with different degrees of pathological differentiation

PurposeTo investigate the value of pre-operative gadoxetate disodium (Gd-EOB-DTPA) enhanced MRI predicting early post-operative recurrence (< 2 years) of hepatocellular carcinoma (HCC) with different degrees of pathological differentiation.MethodsRetrospective analysis of pre-operative MR imaging features of 177 patients diagnosed as suffering from HCC and that underwent radical resection. Multivariate logistic regression assessment was adopted to assess predictors for HCC recurrence with different degrees of pathological differentiation. The area under the curve (AUC) of receiver operating characteristics (ROC) was utilized to assess the diagnostic efficacy of the predictors.ResultsAmong the 177 patients, 155 (87.5%) were males, 22 (12.5%) were females; the mean age was 49.97 ± 10.71 years. Among the predictors of early post-operative recurrence of highly-differentiated HCC were an unsmooth tumor margin and an incomplete/without tumor capsule (p = 0.037 and 0.033, respectively) whereas those of early post-operative recurrence of moderately-differentiated HCC were incomplete/without tumor capsule, peritumoral enhancement along with peritumoral hypointensity (p = 0.006, 0.046 and 0.004, respectively). The predictors of early post-operative recurrence of poorly-differentiated HCC were peritumoral enhancement, peritumoral hypointensity, and tumor thrombosis (p = 0.033, 0.006 and 0.021, respectively). The AUCs of the multi-predictor diagnosis of early post-operative recurrence of highly-, moderately-, and poorly-differentiated HCC were 0.841, 0.873, and 0.875, respectively. The AUCs of the multi-predictor diagnosis were each higher than for those predicted separately.ConclusionsThe imaging parameters for predicting early post-operative recurrence of HCC with different degrees of pathological differentiation were different and combining these predictors can improve the diagnostic efficacy of early post-operative HCC recurrence.

Silencing of OGDHL promotes liver cancer metastasis by enhancing hypoxia inducible factor 1 α protein stability.

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases associated with a high rate of mortality. Frequent intrahepatic spread, extrahepatic metastasis, and tumor invasiveness are the main factors responsible for the poor prognosis of patients with HCC. Hypoxia-inducible factor 1 (HIF-1) has been verified to play a critical role in the metastasis of HCC. HIFs are also known to be modulated by small molecular metabolites, thus highlighting the need to understand the complexity of their cellular regulation in tumor metastasis. In this study, lower expression levels of oxoglutarate dehydrogenase-like (OGDHL) were strongly correlated with aggressive clinicopathologic characteristics, such as metastasis and invasion in three independent cohorts featuring a total of 281 postoperative HCC patients. The aberrant expression of OGDHL reduced cell invasiveness and migration in vitro and HCC metastasis in vivo, whereas the silencing of OGDHL promoted these processes in HCC cells. The pro-metastatic role of OGDHL downregulation is most likely attributed to its upregulation of HIF-1α transactivation activity and the protein stabilization by promoting the accumulation of L-2-HG to prevent the activity of HIF-1α prolyl hydroxylases, which subsequently causes an epithelial-mesenchymal transition process in HCC cells. These results demonstrate that OGDHL is a dominant factor that modulates the metastasis of HCC.

Recent progress in molecular mechanisms of postoperative recurrence and metastasis of hepatocellular carcinoma.

Hepatectomy is currently considered the most effective option for treating patients with early and intermediate hepatocellular carcinoma (HCC). Unfortunately, the postoperative prognosis of patients with HCC remains unsatisfactory, predominantly because of high postoperative metastasis and recurrence rates. Therefore, research on the molecular mechanisms of postoperative HCC metastasis and recurrence will help develop effective intervention measures to prevent or delay HCC metastasis and recurrence and to improve the long-term survival of HCC patients. Herein, we review the latest research progress on the molecular mechanisms underlying postoperative HCC metastasis and recurrence to lay a foundation for improving the understanding of HCC metastasis and recurrence and for developing more precise prevention and intervention strategies.

Post-operative recurrence of liver cancer according to antiviral therapy for detectable hepatitis B viremia: A nationwide study

BackgroundHigh postoperative recurrence of hepatitis B virus (HBV)-infected hepatocellular carcinoma (HCC) remains a significant challenge. Here, we aimed to compare the postoperative HCC recurrence between patients with AVT for detectable serum HBV-DNA vs. those without. MethodsData of patients undergoing curative resection of HBV-infected HCC as an initial therapy from 2015 to 2017 were obtained from the National Health Insurance Service database in South Korea. AVT was initiated when serum HBV-DNA was detectable. The primary outcome was HCC recurrence. The cumulative risk of HCC recurrence between AVT users and non-users was estimated using the Kaplan–Meier method. ResultsDuring follow-up (median 2.7 years) with 3034 patients, 25.7% and 23.6% of AVT users and non-users experienced HCC recurrence, respectively. The 1-, 2-, and 3-year cumulative recurrence rates were similar (p = 0.57): 15.6%, 23.3%, and 26.4% in AVT users versus 15.3%, 22.0%, and 24.9% in non-users, respectively. After adjusting for covariates, multivariable Cox regression analysis showed comparable outcomes between the two groups with adjusted hazard ratios (aHR 1.08, 95% confidence interval [CI] 0.89–1.31; p = 0.439). Similar outcomes between the two groups were reproduced after stratification of liver cirrhosis. Inverse probability treatment weighting analysis also showed comparable outcomes between the two groups in the subgroups with liver cirrhosis (aHR 1.01, 95% CI 0.80–1.29; p = 0.92) and non-cirrhosis (aHR 1.08, 95% CI 0.87–1.34; p = 0.472). ConclusionsInitiating AVT based on detectable serum HBV-DNA provided the similar risk of postoperative HCC recurrence in HBV-infected HCC patients with and without detectable serum HBV-DNA.

Prognostic Impact of MAFLD Following Surgical Resection of Hepatitis B Virus-Related Hepatocellular Carcinoma: A Nationwide Cohort Study.

Simple SummaryWe examined the relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and the recurrence of hepatocellular carcinoma in patients treated by surgical resection of a primary hepatitis B virus-related HCC. MAFLD was significantly associated with 22% and 44% increased risk of HCC recurrence and all-cause mortality, respectively. This study was undertaken to underline the need for developing effective preventive strategies through the management of metabolic health to reduce the incidence of MAFLD in the population.The association between the metabolic effects of hepatic steatosis as a part of postoperative outcomes of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) has rarely been studied. This study aimed to assess the relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and patients’ prognoses following curative resection of HBV-related HCC. Patients who underwent surgical resection for HBV-related HCC between 2009 and 2015 were recruited. The study endpoints were postoperative hepatocellular carcinoma (HCC) recurrence and all-cause mortality. Adjusted hazard ratios (aHRs) for the outcomes were estimated using multivariate Cox regression models. The mean age of the 2032 enrolled patients was 55.0 years, and 77.9% were men. During follow-up (median 5.3 years), HCC recurrence and all-cause mortality occurred in 954 (47.0%) and 422 (20.8%) patients, respectively. HCC recurrence and all-cause mortality were significantly associated with MAFLD, with aHRs of 1.22 (p = 0.003) and 1.44 (p < 0.001), respectively. Propensity score matching and inverse probability treatment weighting analyses confirmed similar results (p < 0.05). MAFLD was associated with significantly poor prognoses in terms of HCC recurrence and all-cause mortality following surgical resection of HBV-related HCC. Further studies are needed to develop an effective preventive strategy through the management of metabolic health.