Risk Factors For Hepatocellular Carcinoma Recurrence Research Articles

346.1: Hepatitis B virus Suppression Predicts Better Recurrencefree Survivals in Liver Transplant Patients With Hepatocellular Carcinoma

Introduction: High serum load of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is known to be a strong risk factor of hepatocellular carcinoma (HCC) development. The aim of study was to investigate the predictive role of HBV DNA levels in recurrence of HCC after liver transplantation (LT). Methods: From June 2006 to May 2020, 729 recipients underwent LT for HBV-related HCC in Seoul National University Hospital. The risk factors for HCC recurrence after LT were analyzed including serum HBV DNA load. Results: Recurrence-free survival at 1, 3, 5, and 10 years were 99.6%, 98%, 95.1%, and 87.8%, respectively. Detectable HBV DNA level (higher than 10 IU/mL) before transplant was significant predictors of HCC recurrence in univariate analysis (P=0.027). Further subgroup analysis was performed to demonstrate the significance of HBV DNA level according to the risk of HCC recurrence. Based on the score of the predicted survival after liver transplantation for HCC (SALT), patients were divided in three groups. In high risk group of recurrence with SALT score more than 2.44, detectable HBV DNA level were significantly associated with recurrence free survival (57.9 % vs. 78.7 %, P<0.0001). Conclusion: There is a close relationship between HBV DNA level and HCC recurrence after transplant. High HBV DNA levels before transplant are associated with HCC recurrence after transplant, especially in high recurrence risk group.

The Combination of AFP and "Up-To-Seven" Criteria May Be a Better Strategy for Liver Transplantation in Chinese Cirrhotic HCC Patients.

BackgroundOrthotopic liver transplantation (OLT) is a life-saving option for patients with hepatocellular carcinoma (HCC), but the expanded OLT criteria remain controversial.ObjectiveThe study aimed to explore whether expanded OLT criteria can be applied to Chinese cirrhotic patients with HCC.MethodsThis retrospective study analyzed risk factors for HCC recurrence and death and compared patients’ tumor characteristics and outcomes in groups of Milan, “Up-to-seven,” and Hangzhou criteria, and groups between met and unmet the combinative criteria of “Up-to-seven” and AFP of < 1000 ng/mL.ResultsAmong 153 patients who underwent OLT for HCC from January 2015 to February 2019 in 4 years of follow-up, 20 (13.1%) patients had HCC recurrence, and 11 (7.2%) had HCC-related death. Multivariate Cox regression analysis showed that preoperative alpha-fetoprotein (AFP) of > 1000 ng/mL (hazard ratio [HR]: 10.05, 95% confidence interval [CI]: 2.45–41.13, P = 0.001) was an independent risk factor for HCC recurrence and HCC-related death (HR: 6.63, 95%CI: 1.31–33.52, P = 0.022). Patients who did not meet Milan criteria but satisfied the “Up-to-seven” criteria had no differences in overall survival (OS) (P = 0.69) and disease-free survival (DFS) (P = 0.35) than patients who met the Milan criteria. The combination of “Up-to-seven” criteria and AFP of < 1000 ng/mL differed significantly (HR: 18.9; 95% CI: 4.0–89.2; P < 0.001). Patients with HCC who met the “Up-to-seven” criteria and AFP of < 1000 ng/mL (n = 121) had excellent survival with 4-year OS of 91.6% (P < 0.001) and DFS of 90.8% (P < 0.001), which is significantly better compared to the other group (n = 32) (OS of 67.5% and DFS of 46.5%) and patients who met the Milan criteria (n = 108, OS of 89.8%, DFS of 89.6%), allowing 28.9% (13/45) of patients who did not meet the Milan criteria to benefit from OLT.ConclusionChinese cirrhotic patients with HCC who met the combinative criteria of “Up-to-seven” and AFP of < 1000 ng/mL had better survival than those who met the Milan criteria, and these combinative criteria benefited more patients and may become a better option for OLT.

A Scoring System for Predicting Microvascular Invasion in Hepatocellular Carcinoma Based on Quantitative Functional MRI.

Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is a histopathological marker and risk factor for HCC recurrence. We integrated diffusion-weighted imaging (DWI) and magnetic resonance (MR) image findings of tumors into a scoring system for predicting MVI. In total, 228 HCC patients with pathologically confirmed MVI who underwent surgical resection or liver transplant between November 2012 and March 2021 were enrolled retrospectively. Patients were divided into a right liver lobe group (n = 173, 75.9%) as the model dataset and a left liver lobe group (n = 55, 24.1%) as the model validation dataset. Multivariate logistic regression identified two-segment involved tumor (Score: 1; OR: 3.14; 95% CI: 1.22 to 8.06; p = 0.017); ADCmin ≤ 0.95 × 10−3 mm2/s (Score: 2; OR: 10.88; 95% CI: 4.61 to 25.68; p = 0.000); and largest single tumor diameter ≥ 3 cm (Score: 1; OR: 5.05; 95% CI: 2.25 to 11.30; p = 0.000), as predictive factors for the scoring model. Among all patients, sensitivity was 89.66%, specificity 58.04%, positive predictive value 68.87%, and negative predictive value 84.41%. For validation of left lobe group, sensitivity was 80.64%, specificity 70.83%, positive predictive value 78.12%, and negative predictive value 73.91%. The scoring model using ADCmin, largest tumor diameter, and two-segment involved tumor provides high sensitivity and negative predictive value in MVI prediction for use in routine functional MR.

Direct-acting antivirals for hepatitis C virus-infected patients with hepatocellular carcinoma.

BACKGROUNDHepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients has a high risk of recurrence. Although eradication of HCV is expected to reduce this risk, the risk in patients with a history of HCC may be high after treatment with direct-acting antivirals (DAAs).AIMTo determine the risk factors for HCC recurrence in patients with HCV and a history of HCC.METHODSThe risk of HCC recurrence in patients with a history of HCC and/or of HCC occurrence in patients without a history of HCC after DAA therapy was retrospectively analyzed in 311 HCV patients treated at our institution and several neighboring hospitals. The frequency and predictors of HCC recurrence/ occurrence after DAA treatment were included in these analyses. The clinical course of HCC before and after DAA treatment was also evaluated.RESULTSHCV patients with a history of HCC were older and had greater progression of liver fibrosis and diabetes than patients without a history of HCC. Median recurrence-free survival (RFS) was 1092 d in patients with a history of HCC, and post-DAA HCC recurrence/occurrence was observed in 29 patients (53.7%) with and 5 (1.9%) without a history of HCC over 6 years (P < 0.001). RFS in patients with a history of HCC did not differ significantly before and after DAA treatment. The frequency of HCC recurrence/occurrence in patients with a history of HCC was lower after than before DAA treatment. Multivariate analysis showed that the incidence rate of HCC recurrence/occurrence before DAA treatment was the only independent predictor of HCC recurrence/occurrence after DAA treatment. Liver function was well preserved and clinical course was good in patients with HCC recurrence/occurrence after DAA therapy.CONCLUSIONDAA therapy in patients infected with HCV is also effective in patients with a history of HCC. Curative treatment for HCC is desirable before DAA therapy. The frequency of HCC recurrence/occurrence before DAA therapy was associated with a significantly increased risk of HCC recurrence after DAA therapy. Careful observation after DAA therapy is required in patients with a history of HCC.

Clinical Nursing Paths Benefit Patient Outcomes Undergoing Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma.

Objective The purpose of the study is to investigate patient outcomes of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) under clinical nursing paths (CNP) and whether the application of CNP can be a protective factor against the recurrence of HCC. Methods The study comprised of 48 patients who received TACE for HCC under the CNP (assigned into the CNP group) and 41 who received TACE for HCC under the routine care (assigned into the control group). Their treatment safety, pain, and psychology were compared. The nursing satisfaction and quality of life were investigated when patients were discharged from the hospital. A 6-month follow-up was performed to analyze the related factors affecting disease recurrence. Results In the CNP group, the incidence rate of total adverse reactions, VAS scores, SAS and SDA scores were lower, but conversely, the satisfaction and SF-36 scores were higher than those in the control group (P < 0.05). Logistic regression analysis revealed that advanced TNM stage, larger tumor diameter, greater Child-Pugh classification, and the presence of peripheral blood vessel invasion were independent risk factors of HCC recurrence (P < 0.05). Conclusion The study demonstrated that CNP intervention can improve the safety and quality of life of patients undergoing TACE for HCC and reduce their negative emotions and pain feelings, which is worthy of clinical application.

Characterization of molecular and immune landscape of microvascular invasion in hepatocellular carcinoma and prognostic significance.

e16162 Background: Partial hepatectomy is potentially curative treatment in selected patients (pts) with hepatocellular carcinoma (HCC). Microvascular invasion (MVI) is one of the strongest predictors of prognosis and recurrence of HCC. In this study, we analyzed the gene mutation signature and immune factors associated with MVI, and the prognostic value. Methods: Pts who were diagnosed with HCC between Jan 2018 and Sep 2020 in Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively enrolled in this study. Next-generation sequencing (NGS) was performed on tumor tissues after radical partial hepatectomy. The different immune makers (PD1, PD-L1, CD3, CD8, CD68, and CD163) of tumor-infiltrating lymphocytes (TILs) were identified with immunofluorescence-based microenvironment analysis panel (MAP). Results: In the MVI+ group (n = 39, 59.1 %), there were significantly more pts with larger tumor size, and capsules invasion by tumors. The mutation spectra revealed that 61 (92.4%) pts harbored somatic mutations and the most frequently mutated gene was telomerase reverse transcriptase (TERT), which was present in 31.8% (n = 20) HCC pts. Mutations in the promoter of TERT were found in 95.2% (20/21) pts. 90.0% (18/20) had one hotspot point mutation located 124bp upstream of the translation start site. The mutation frequency in the TERT promoter was significantly higher in the MVI+ group compared with the MVI- group (41.0% vs. 14.8%, p &lt; 0.05). Pts with TERT promoter mutations tend to be MVI+ rather than MVI- and more HCC driver mutations were detected in MVI+ pts with TERT promoter mutations (p &lt; 0.05). Based on MAP, we found MVI+ pts had significantly lower CD3+ TILs (p &lt; 0.05). The multivariable analysis indicated that pts with copy number variations (CNV, hazard ratios [HR] 2.62, 95% confidence interval [CI] 1.07-6.40; p = 0.028), elevated PT/INR (HR 0.29, 95% CI 0.11-0.77; p = 0.008), and lower serum prealbumin concentration (PALB, HR 3.03, 95% CI 1.08-8.51; p = 0.027) had significantly shorter recurrence-free survival (RFS) after surgery. Similar findings were also observed for immune factors within cancer parenchyma, including CD68+ (HR 7.14, 95% CI 0.95-53.55; p = 0.025), CD163+ (HR 3.07, 95% CI 1.10-8.53; p = 0.023), CD68+/CD163- (HR 11.35, 95% CI 1.51-85.05; p = 0.003), CD68+/CD163+ (HR 3.51, 95% CI 1.4-8.79; p = 0.004), which indicated tumor-associated macrophage (TAM) infiltration was independent risk factor for RFS. Conclusions: In this study, we characterized the molecular and immune landscape of MVI in HCC patients. MVI presence highly correlated with adverse biological markers, mutations in the promoter of TERT, and higher CD3+ TILs. Some risk factors of HCC recurrence were identified, including CNV, PT/INR, CA 19-9, PALB, and TAM. Transcriptional alterations and immune tumor microenvironment change may contribute to MVI in HCC.

Impact of Statins on Hepatocellular Carcinoma Recurrence After Living-Donor Liver Transplantation.

BackgroundLiver transplantation (LT) has been validated widely all over the world as the curative treatment for hepatocellular carcinoma (HCC). Statins have been reported to prevent the progression of HCC. There are many factors that affect recurrence of HCC, but the precise role of statins is unknown. Therefore, we examined whether statin therapy is associated with decreased HCC recurrence in patients who underwent living-donor LT (LDLT) for HCC.Material/MethodsWe retrospectively analyzed 844 HCC patients who underwent primary adult-to-adult LDLT in our center between January 2007 and December 2016. Statin therapy was defined as administration of statins for more than 30 cumulative defined daily doses (cDDDs) after LT. We compared HCC recurrence and patient survival between non-statin (n=334) and statin (n=52) groups.ResultsThe recurrence rate was higher in the non-statin group; however, time-dependent multivariate analysis with Kaplan-Meier curves showed that statin users did not significantly benefit in terms of HCC recurrence-related survival or overall survival. Further, risk factor analysis of HCC recurrence and patient survival confirmed multiple regional treatments (≥3 times), high alpha fetoprotein level (≥100 ng/mL), large tumor size (≥3 cm), and microvascular invasion as risk factors for HCC recurrence, but statin treatment was not associated with a significantly lower recurrence rate of HCC or reduced mortality after adjusting for other risk factors.ConclusionsStatin use might be associated with prevention of HCC progression, but no significant decrease in HCC recurrence rates in LDLT patients was recorded in this study.

Preferred Treatment with Curative Intent for Left Lateral Segment Early Hepatocellular Carcinoma under the Era of Minimal Invasive Surgery.

Background: Hepatocellular carcinoma (HCC) occurring at the left lateral segment (LLS) is relatively susceptible to treatment with curative intent in terms of tumor location. However, outcomes might vary depending on the selection of treatment modalities. This study aimed to analyze patients who had undergone curative treatment for early HCC at LLS. Methods: A retrospective analysis of 179 patients who underwent curative treatment for early HCC at LLS was performed. Patients were grouped based on treatment modalities, including radiofrequency ablation (RFA) and liver resection (LR). The long-term outcomes of the two groups were compared. Additionally, the impact of the LR approach on patient outcomes was analyzed. Results: Among these patients, 60 received RFA and 119 underwent LR as primary treatment with curative intent. During follow-up, a significantly higher incidence of HCC recurrence was observed in the RFA group (37/60, 61.7%) than in the LR group (45/119, 37.8%) (p = 0.0025). The median time of HCC recurrence was 10.8 (range: 1.1–60.9 months) and 17.6 (range: 2.4–94.8 months) months in the RFA and LR groups, respectively. In addition, multivariate analysis showed that liver cirrhosis, multiple tumors, and RFA treatment were significant risk factors for HCC recurrence. The 1-, 2-, and 5-year overall survival rates in the RFA and LR groups were 96.4%, 92.2%, and 71.5% versus 97.3%, 93.6%, and 87.7%, respectively. (p = 0.047). Moreover, outcomes related to LR were comparable between laparoscopic and conventional open methods. The 1-, 2-, and 5-year recurrence free survival rates in the laparoscopic (n = 37) and conventional open (n = 82) LR groups were 94.1%, 82.0%, and 66.9% versus 86.1%, 74.6%, and 53.1%, respectively. (p = 0.506) Conclusion: Early HCC at LLS had satisfactory outcomes after curative treatment, in which LR seems to have a superior outcome, as compared to RFA treatment. Moreover, laparoscopic LR could be considered a preferential option in the era of minimally invasive surgery.

Concurrent Cholecystectomy Is Associated with a Lower Risk of Recurrence after Curative Resection in Early-Stage Hepatocellular Carcinoma: A 10 Year Observational Single-Center Study.

Background: Cholecystectomy has been reported to be associated with increased risk of developing hepatocellular carcinoma (HCC). However, there is little information about the impact of cholecystectomy on the outcome of HCC. Aims: To evaluate the long-term effect of concurrent cholecystectomy on recurrence and overall survival in HCC after curative hepatectomy. Patients and Methods: We retrospectively enrolled 857 patients with BCLC stage 0 or A HCC who underwent primary resection from January 2001 to June 2016. The impact of concurrent cholecystectomy on overall survival (OS) and recurrence-free survival (RFS) were analyzed by Cox’s proportional hazards models after one-to-one propensity score matching (PSM). Results: Of the 857 patients, 539 (62.9%) received concurrent cholecystectomy (cholecystectomy group) and 318 (37.1%) did not (non-cholecystectomy group). During the mean follow-up period of 75.0 months, 471 (55.0%) patients experienced recurrence, and 321 (37.5%) died. RFS and OS were not significantly different between the groups. After PSM, a total of 298 patients were enrolled in each group. RFS was significantly higher in the cholecystectomy than non-cholecystectomy group (p = 0.044). In multivariate analysis, age (p = 0.022), serum AFP (p = 0.008), liver cirrhosis (p < 0.001), diabetes (p = 0.004), tumor number (p = 0.005), tumor size (p = 0.002), histological grade (p = 0.001), microvascular invasion (p < 0.001) and cholecystectomy (p = 0.021) were independent risk factors for HCC recurrence. However, there were no significant differences in OS between the cholecystectomy and non-cholecystectomy groups. Conclusions: Concurrent cholecystectomy may reduce recurrence in early-stage HCC after curative resection. Further studies are needed to validate our results.

Circulating Cancer Stem Cells Expressing EpCAM/CD90 in Hepatocellular Carcinoma: A Pilot Study for Predicting Tumor Recurrence after Living Donor Liver Transplantation.

Background/AimsCirculating tumor cells (CTCs) with cancer stemness have been demonstrated to be a direct cause of tumor recurrence, and only few studies have reported the role of CTCs in liver transplantation (LT) for hepatocellular carcinoma (HCC).MethodsEpithelial cell adhesion molecule+ (EpCAM+), cluster of differentiation 90+ (CD90+) and EpCAM+/CD90+ CTCs were sorted via fluorescence-activated cell sorting, and transcripts level of EpCAM, K19 and CD90 in the peripheral blood were analyzed via real-time polymerase chain reaction preoperatively and on postoperative days 1 and 7 in 25 patients who underwent living donor liver transplantation (LDLT) for HCC. EpCAM protein was assessed in HCC tissue using immunohistochemical staining. The median follow-up duration was 40 months.ResultsHCC after LDLT recurred in four out of 25 patients. Detection of EpCAM+ or CD90+ CTCs correlated well with their messenger RNA levels (p<0.05). EpCAM+ CTCs were readily detected in HCC tissue expressing EpCAM protein. The detection of EpCAM+ CTCs or EpCAM+/CD90+ CTCs before surgery and on postoperative day 1 was significantly associated with HCC recurrence after LT (all p<0.05). Pretransplant serum PIVKA-II >100 mAU/mL and postoperative day 1 EpCAM+/CD90+ CTCs were independent risk factors for HCC recurrence (hazard ratio, 14.64; 95% confidence interval, 1.08 to 198.20; p=0.043 and hazard ratio, 26.88; 95% confidence interval, 1.86 to 387.51; p=0.016, respectively).ConclusionsEpCAM+/CD90+ CTCs can be used preoperatively and 1 day after LDLT as key biological markers in LT candidate selection and post-LDLT management.

Application of contrast-enhanced ultrasound in the pathological grading and prognosis prediction of hepatocellular carcinoma.

BackgroundTo explore the clinical application value of contrast-enhanced ultrasound (CEUS) in the pathological grading and prognosis prediction of hepatocellular carcinoma (HCC).MethodsA retrospective analysis was performed of 128 patients with primary HCC who underwent CEUS examination in our hospital from January 2017 to June 2020. Patients were divided into three groups: highly-differentiated group, moderately-differentiated group, and poorly-differentiated group. Quantitative analysis of the relationships between the rise time (RT), time to peak (TTP), mean transit time (mTT), intensity maximum (Imax), enhancement rate, and pathological grade of CEUS was performed. In addition, the follow-up patients were divided into a recurrence group and non-recurrence group, and the relationships between RT, TTP, mTT, Imax, and enhancement rate of CEUS were analyzed.ResultsAmong the 128 patients, 23 were highly-differentiated, 63 were moderately-differentiated, and 42 were poorly-differentiated. In addition, there were 31 patients in the recurrence group and 97 patients in the non-recurrence group. RT, TTP, and enhancement rate had significant differences in the highly-differentiated, moderately-differentiated, and poorly-differentiated groups. At the same time, RT and TTP were positively correlated with the differentiation degree, while the enhancement rate was negatively correlated with the differentiation degree. Furthermore, RT, TTP, and enhancement rate were statistically significant for the diagnosis of HCC with high, moderate, and poor differentiation, among which RT had the highest diagnostic accuracy. In the recurrence group, RT, TTP, and Imax were lower than those in the non-recurrence group, and the enhancement rate was greater than that in the non-recurrence group. Moreover, low levels of RT, TTP, and Imax along with positive microvascular invasion (MVI) and poor differentiation were risk factors for HCC recurrence, and there was no significant relationship between the average tumor diameter and HCC recurrence.ConclusionsCEUS can significantly show the differences between the RT, TTP, and enhancement rate of HCC across different levels of differentiation. It can also predict whether the disease will relapse. Moreover, low levels of RT, TTP, and Imax as well as positive MVI and poor differentiation can cause the recurrence of HCC.

Advanced donor age does not increase risk of hepatocellular carcinoma recurrence after liver transplantation: a retrospective two-centre analysis using competing risk analysis.

The impact of donor age on the recurrence of hepatocellular carcinoma (HCC) after liver transplantation is still debated. Between 2002 and 2014, all patients transplanted for HCC in 2 European liver transplantation tertiary centres were retrospectively reviewed. Risk factors for HCC recurrence were assessed using competing risk analysis, and the impact of donor age < or ≥65years and < or ≥80years was specifically evaluated after propensity score matching. 728 patients transplanted with a median follow-up of 86months were analysed. The 1-, 3- and 5-year recurrence rates were 4.9%, 10.7% and 13.9%, respectively. In multivariable analysis, recipient age (sHR: 0.96 [0.93; 0.98], P<0.01), number of lesions (sHR: 1.05 [1.04; 1.06], P<0.001), maximum size of the lesions (sHR: 1.37 [1.27; 1.48], P<0.01), presence of a hepatocholangiocarcinoma (sHR: 6.47 [2.91; 14.38], P<0.01) and microvascular invasion (sHR: 3.48 [2.42; 5.02], P<0.01) were significantly associated with HCC recurrence. After propensity score matching, neither donor age ≥65 (P=0.29) nor donor age ≥80 (P=0.84) years increased the risk of HCC recurrence. In conclusion, donor age was not found to be a risk factor for HCC recurrence. Patients listed for HCC can receive a graft from an elderly donor without compromising the outcome.

Glutathione S-transferase A2 promotes hepatocellular carcinoma recurrence after liver transplantation through modulating reactive oxygen species metabolism

Hepatocellular carcinoma (HCC) recurrence after liver transplantation remains a significant clinical problem. Ischemia-reperfusion injury (IRI) occurred inevitably at the early phase after liver transplantation (LT) spawns a significant risk of HCC recurrence. However, their linkage and IRI-derived risk factors for HCC recurrence remain exclusive. Understanding the mechanism of post-transplantation hepatic injury could provide new strategies to prevent the later event of HCC recurrence. We demonstrated that glutathione S-transferase A2 (GSTA2) expression was significantly associated with early phase hepatic and systemic injury and ROS level after liver transplantation. Early phase circulating GSTA2 (EPCGSTA2) protein was a significant predictor of HCC recurrence and survival. Heterogeneous single nucleotide polymorphism at G335C of GSTA2 was significantly associated with poor survival of HCC recipients. Enhancement of GSTA2 could protect HCC cells against H2O2-induced cell death by compensating for the elevated ROS stress. We also demonstrated that GSTA2 played crucial roles in regulating the ROS-associated JNK and AKT signaling pathways and ROS metabolism in HCCs in responding to a dynamic ROS environment. Functionally, endogenous or exogenous upregulation of GSTA2 could promote HCC growth and invasion through activating the epithelial–mesenchymal-transition process. Targeted inhibition of GSTA2 could suppress HCC growth and metastasis. In conclusion, GSTA2 could be a novel prognostic and therapeutic target to combat HCC recurrence after liver transplantation.

Impact of MAFLD on HBV-Related Stage 0/A Hepatocellular Carcinoma after Curative Resection.

Backgrounds and Aim: Metabolic-associated fatty liver dis-ease (MAFLD) is a novel term proposed in 2020 to avoid the exclusion of certain subpopulations, though the application of this term in the real world is very limited. Here, we aimed to evaluate the impact of MAFLD on hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative resection. Methods: Patients with chronic hepatitis B (CHB)-related HCC who received hepatectomy between January 2010 and December 2019 were consecutively selected. The association between histologically proven concurrent MAFLD and clinical outcomes were retrospectively analyzed. Results: Among the 812 eligible patients with CHB-related HCC, 369 (45.4%) were diagnosed with concurrent MAFLD. After a mean follow-up of 65 months, 303 patients (37.3%) developed HCC recurrence, 111 (13.7%) died, and 12 (1.5%) received liver transplantation. Although no differences in the incidences of HCC recurrence (HR: 0.902, 95% CI: 0.719–1.131, p = 0.370) and death or liver transplantation (HR: 0.743, 95% CI: 0.518–1.006, p = 0.107) were observed between patients with and without MAFLD in multivariate analysis, the patients with MAFLD tended to achieve better recurrent-free survival compared to patients without MAFLD. Notably, lean MAFLD (BMI < 23 kg/m2) was a relative risk factor for tumor recurrence (HR: 2.030, 95% CI: 1.117–3.690, p = 0.020) among patients with MAFLD. Conclusions: The overall prognosis in HBV-related early-stage HCC, in terms of HCC recurrence and death or liver transplantation, was not significantly different between patients with and without MAFLD. Among patients with MALFD, lean-MAFLD was a risk factor for HCC recurrence. Further studies are warranted to validate these results.

Preoperative Prediction of Cytokeratin 19 Expression for Hepatocellular Carcinoma with Deep Learning Radiomics Based on Gadoxetic Acid-Enhanced Magnetic Resonance Imaging.

PurposeCytokeratin 19 (CK19) expression is a proven independent prognostic predictor of hepatocellular carcinoma (HCC). This study aimed to develop and validate the performance of a deep learning radiomics (DLR) model for CK19 identification in HCC based on preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI).Patients and MethodsA total of 141 surgically confirmed HCCs with preoperative gadoxetic acid-enhanced MRI from two institutions were included. Prediction models were established based on hepatobiliary phase (HBP) images using a training set (n=102) and validated using time-independent (n=19) and external (n=20) test sets. A receiver operating characteristic curve was used to evaluate the performance for CK19 prediction. Recurrence-free survival (RFS) was also analyzed by incorporating the CK19 expression and other factors.ResultsFor predicting CK19 expression, the area under the curve (AUC) of the DLR model was 0.820 (95% confidence interval [CI]: 0.732–0.907, P<0.001) with sensitivity, specificity, accuracy of 0.800, 0.766, and 0.775, respectively, and reached 0.781 in the external test set. Combined with alpha fetoprotein, the AUC increased to 0.833 (95% CI: 0.753–0.912, P<0.001) and the sensitivity was 0.960. Intratumoral hemorrhage and peritumoral hypointensity on HBP were independent risk factors for HCC recurrence by multivariate analysis. Based on predicted CK19 expression and the independent risk factors, a nomogram was developed to predict RFS and achieved C-index of 0.707.ConclusionThis study successfully established and verified an optimal DLR model for preoperative prediction of CK19-positive HCCs based on gadoxetic acid-enhanced MRI. The prediction of CK19 expression in HCC using a non-invasive method can help inform preoperative planning.

Liver transplantation for hepatocellular carcinoma using grafts from uncontrolled circulatory death donation

Controversy exists regarding whether the rate of hepatocellular carcinoma (HCC) recurrence after orthotopic liver transplantation (OLT) differs when using livers from donation after controlled circulatory death (DCD) versus livers from donation after brain death (DBD). The aim of this cohort study was to analyze rates of HCC recurrence, patient survival, and graft survival after OLT for HCC, comparing recipients of DBD livers (n = 103) with recipients of uncontrolled DCD livers (uDCD; n = 41). No significant differences in tumor size, tumor number, serum alpha-fetoprotein, proportion of patients within Milan criteria, or pre-OLT bridging therapies were identified between groups, although the waitlist period was significantly shorter in the uDCD group (p = 0.040). HCC recurrence was similar between groups. Patient survival was similar between groups, but graft survival was lower in the uDCD group. Multivariate analysis identified recipient age (p = 0.031), pre-OLT bridging therapy (p = 0.024), and HCC recurrence (p = 0.048) as independent risk factors for patient survival and pre-OLT transarterial chemoembolization (p = 0.045) as the single risk factor for HCC recurrence. In conclusion, similar patient survival and lower graft survival were observed in the uDCD group. However, the use of uDCD livers appears to be justified due to a shorter waitlist time, and lower waitlist dropout and HCC recurrence rates.

Recipient C7 rs9292795 genotype and the risk of hepatocellular carcinoma recurrence after orthotopic liver transplantation in a Han Chinese population

BackgroundComplement component(C7) gene has been shown to influence the prognosis in Hepatocellular carcinoma (HCC) patients. The association between C7 and HCC recurrence after orthotopic liver transplantation (OLT), however, is still unknown. The purpose of this study was to evaluate whether the donor and recipient C7 gene polymorphisms are related to HCC recurrence after OLT in the Han Chinese population.MethodsA total of 73 consecutive patients with HCC who had undergone OLT, both donors and recipients, were involved in this research. A single nucleotide polymorphism of C7, rs9292795, was genotyped using Sequenom MassARRAY in the cohort. The expression of C7 and the association between C7 gene polymorphisms and HCC recurrence following OLT were analyzed by bioinformatics and statistical analysis, respectively.ResultsAs shown in database, the expression of C7 was higher in HCC tissues than that in normal tissues, and represented a worse prognosis. We also found that recipient C7 rs9292795 polymorphism, rather than the donor, was significantly associated with HCC recurrence after OLT. Multivariate logistic regression analysis confirmed that TNM stage (P = 0.001), Milan criteria (P = 0.000) and recipient rs9292795 genotype (TT vs AA/AT, P = 0.008) were independent risk factors for HCC recurrence. Furthermore, the recipient carrying AA/AT showed higher recurrence-free survival (RFS) and overall survival (OS) than that carrying TT (P < 0.05). In Cox proportional hazards model, TNM stage, recipient rs9292795 genotype, and Milan criteria were identified as independent factors for RFS and OS (P < 0.05) as well as pre-OLT serum alpha fetoprotein (AFP) level was associated with OS (P < 0.05).ConclusionsRecipient C7 rs9292795 gene polymorphism is related to the recurrence of HCC after OLT, which may be a helpful prognostic marker for HCC patients who receive OLT.

Absence of differences in the recurrence rates of hepatitis C virus‑associated hepatocellular carcinoma between direct‑acting antivirals and interferon‑based treatments: A multicenter study

Direct‑acting antivirals (DAAs) have a high rate of achieving a sustained virological response (SVR) to hepatitis C virus (HCV). However, there is a possibility that the rapid elimination of HCV by DAAs can decrease internal interferon (IFN) secretion, resulting in an increased rate of hepatocellular carcinoma (HCC) recurrence than that observed with the current IFN‑based treatment. The present study aimed to retrospectively confirm the absence of differences in the recurrence rates of HCC between patients receiving DAAs and IFN‑based treatment, and to investigate the possible risk factors for recurrence. The HCC recurrence rate following treatment was compared between patients who underwent DAA therapy (DAA group, n=257) and those who received an IFN‑based regimen (IFN group, n=47). Kaplan‑Meier analysis and the log‑rank test were used to compare the groups, and baseline confounds were adjusted by Cox proportional methods. Further comparison of the HCC recurrence rate between the DAA and IFN groups was performed after adjusting these potential confounding variables using propensity score matching. Kaplan‑Meier analysis revealed no significant differences in the HCC recurrence rate between the two groups, as well as no significant difference following the adjustment of the confounding variables. In addition, significant independent risk factors were identified for recurrence in the DAA group, including proteins induced by vitamin K absence or antagonist‑II, the number of previous HCC treatments and the Forns index. Following the adjustment for risk factors for HCC recurrence among the patients in the DAA group, no significant differences in the rate were observed between the DAA and IFN groups. On the whole, these results suggested that HCC recurrence following curative treatment was equivalent in patients treated with DAAs and those treated with IFN. The Forns index was identified as a novel risk factor for HCC recurrence following DAA treatment.

Increased Visceral Adipose Tissue and Hyperinsulinemia Raise the Risk for Recurrence of Non-B Non-C Hepatocellular Carcinoma after Curative Treatment.

Simple SummaryWith the increasing prevalence of obesity and diabetes in most countries, the increase in hepatocellular carcinoma (HCC) associated with these factors has recently become a serious healthcare problem. HCC can often emerge in the non-cirrhotic liver among obese patients, and it might suggest that the conventional surveillance strategies for HCC, which is mainly targeted at cirrhotic patients with hepatitis B or C virus, might be insufficient in the overnutrition era. We tried to extract factors that affect recurrence-free survival in patients with non-viral HCC, among obesity and diabetes factors, together with the established recurrence risk factors, using a decision-tree analysis.We investigated the factors affecting recurrence-free survival in patients with non-B non-C hepatocellular carcinoma (HCC) who received curative treatment. Decision-tree analysis was performed in 72 curative cases of non-B non-C HCC to extract the risk factors for recurrence. The reliability of the extracted risk factors was evaluated using the Kaplan–Meier method and the Cox proportional hazards model. The decision-tree analysis extracted three factors—visceral adipose tissue (VAT) index (VATI; <71 and ≥71 cm2/m2), which was the cross-sectional areas of VAT on the computed tomographic image at the umbilical level, normalized by the square of the height, fasting immunoreactive insulin (FIRI; <5.5 and ≥5.5 µU/mL), and alpha-fetoprotein (AFP; <11 and ≥11 ng/mL). The Cox proportional hazards model showed that VATI (hazard ratio (HR): 2.556, 95% confidence interval (CI): 1.191–5.486, p = 0.016), FIRI (HR: 3.149, 95% CI: 1.156–8.575, p = 0.025), and AFP (HR: 3.362, 95% CI: 1.550–7.288, p = 0.002) were all independent risk factors for HCC recurrence. Non-B non-C HCC patients with a higher VATI (≥71 cm2/m2) or higher FIRI (≥5.5 µU/mL) and AFP (≥11 ng/mL) if VATI was <71 cm2/m2 are prone to recurrence after curative treatment.

Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: an individual patient data meta-analysis

ObjectiveThe benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration.DesignWe...