Multinodular Hepatocellular Carcinoma Research Articles

Liver Resection vs Nonsurgical Treatments for Patients With Early Multinodular Hepatocellular Carcinoma

The 2022 Barcelona Clinic Liver Cancer algorithm currently discourages liver resection (LR) for patients with multinodular hepatocellular carcinoma (HCC) presenting with 2 or 3 nodules that are each 3 cm or smaller. To compare the efficacy of liver resection (LR), percutaneous radiofrequency ablation (PRFA), and transarterial chemoembolization (TACE) in patients with multinodular HCC. This cohort study is a retrospective analysis conducted using data from the HE.RC.O.LE.S register (n = 5331) for LR patients and the ITA.LI.CA database (n = 7056) for PRFA and TACE patients. A matching-adjusted indirect comparison (MAIC) method was applied to balance data and potential confounding factors between the 3 groups. Included were patients from multiple centers from 2008 to 2020; data were analyzed from January to December 2023. LR, PRFA, or TACE. Survival rates at 1, 3, and 5 years were calculated. Cox MAIC-weighted multivariable analysis and competing risk analysis were used to assess outcomes. A total of 720 patients with early multinodular HCC were included, 543 males (75.4%), 177 females (24.6%), and 350 individuals older than 70 years (48.6%). There were 296 patients in the LR group, 240 who underwent PRFA, and 184 who underwent TACE. After MAIC, LR exhibited 1-, 3-, and 5-year survival rates of 89.11%, 70.98%, and 56.44%, respectively. PRFA showed rates of 94.01%, 65.20%, and 39.93%, while TACE displayed rates of 90.88%, 48.95%, and 29.24%. Multivariable Cox survival analysis in the weighted population showed a survival benefit over alternative treatments (PRFA vs LR: hazard ratio [HR], 1.41; 95% CI, 1.07-1.86; P = .01; TACE vs LR: HR, 1.86; 95% CI, 1.29-2.68; P = .001). Competing risk analysis confirmed a lower risk of cancer-related death in LR compared with PRFA and TACE. For patients with early multinodular HCC who are ineligible for transplant, LR should be prioritized as the primary therapeutic option, followed by PRFA and TACE when LR is not feasible. These findings provide valuable insights for clinical decision-making in this patient population.

Long-term Outcomes of Hepatic Resection Combined With Intraoperative Ablation Versus Hepatic Resection Alone for Multinodular Hepatocellular Carcinoma: Insights from a Single-center Study.

The efficacy of combining hepatic resection (HR) with ablation therapy in treating multinodular hepatocellular carcinoma (mHCC) remains uncertain. This study aimed to compare the long-term survival outcomes of patients with mHCC undergoing HR combined with intraoperative ablation (HRA) versus those undergoing HR alone. A retrospective analysis was conducted on 296 patients diagnosed with early-stage [Barcelona Clinic Liver Cancer (BCLC)-A] or intermediate-stage (BCLC-B) mHCC who underwent initial HR. Patients were divided into two groups: those who received HRA (HRA group, n=159) and those who underwent HR alone (HR group, n=137). Propensity score (PS), estimated as the likelihood of undergoing HRA, was applied to adjust for between-group differences in baseline characteristics. Overall survival (OS) and relapse-free survival (RFS) were compared using Cox regression and Kaplan-Meier analyses. There were no significant differences in survival between the HRA and HR groups, with 5-year OS and RFS rates of 47.7% versus 51.9% (p=0.837) and 17.0% versus 25.9% (p=0.094), respectively. After adjusting for PS, the differences remained non-significant (p=0.579 for OS and p=0.410 for RFS). Consistent results were also observed in PS-adjusted subgroup analysis stratified by factors such as BCLC stage, "Up-to-7" criteria, and Child-Pugh class. HRA may offer comparable long-term efficacy to HR alone in mHCC, suggesting broader treatment options that challenge the guideline-based monotherapy.

Outcomes of Liver Resection and Transarterial Chemoembolization in Patients with Multinodular BCLC-A Hepatocellular Carcinoma.

This study aimed to compare the outcomes of liver resection (LR) and transarterial chemoembolization (TACE) in patients with multinodular hepatocellular carcinoma (HCC) within the Milan criteria who were not eligible for liver transplantation. We retrospectively analyzed 483 patients with multinodular HCC within the Milan criteria, who underwent either LR or TACE as an initial therapy between 2013 and 2022. The overall survival (OS) in the entire population and recurrence-free survival (RFS) in patients who underwent LR and TACE and achieved a complete response were analyzed. Propensity score (PS) matching analysis was also used for a fair comparison of outcomes between the two groups. Among the 483 patients, 107 (22.2%) and 376 (77.8%) underwent LR and TACE, respectively. The median size of the largest tumor was 2.0 cm, and 72.3% of the patients had two HCC lesions. The median OS and RFS were significantly longer in the LR group than in the TACE group (p <0.01 for both). In the multivariate analysis, TACE (adjusted hazard ratio [aHR], 1.81 and aHR, 2.41) and large tumor size (aHR, 1.43 and aHR, 1.44) were significantly associated with worse OS and RFS, respectively. The PS-matched analysis also demonstrated that the LR group had significantly longer OS and RFS than the TACE group (PS <0.05). In this study, LR showed better OS and RFS than TACE in patients with multinodular Barcelona Clinic Liver Cancer stage A HCC. Therefore, LR can be considered an effective treatment option for these patients.

Oncological outcomes of liver resection for large and multinodular hepatocellular carcinoma

Oncological outcomes of liver resection for large and multinodular hepatocellular carcinoma

Regional Differences in Clinical Presentation and Prognosis of Patients With Post–Sustained Virologic Response Hepatocellular Carcinoma

Widespread use of direct-acting antivirals for hepatitis C virus infection has been paralleled with increased numbers of patients with hepatocellular carcinoma (HCC) after achieving sustained virologic response (post-SVR HCC) worldwide. Few data compare regional differences in the presentation and prognosis of patients with post-SVR HCC. We identified patients with advanced fibrosis (F3/F4) who developed incident post-SVR HCC between March 2015 and October 2021 from 30 sites in Europe, North America, South America, the Middle East, South Asia, East Asia, and Southeast Asia. We compared patient demographics, liver dysfunction, and tumor burden by region. We compared overall survival by region using Kaplan-Meier analysis and identified factors associated with survival using multivariable Cox regression analysis. Among 8796 patients with advanced fibrosis or cirrhosis who achieved SVR, 583 (6.6%) developed incident HCC. There was marked regional variation in the proportion of patients detected by surveillance (range: 59.5%-100%), median maximum tumor diameter (range, 1.8-5.0 cm), and the proportion with multinodular HCC (range, 15.4%-60.8%). The prognosis of patients highly varied by region (hazard ratio range, 1.82-9.92), with the highest survival rates in East Asia, North America, and South America, and the lowest survival rates in the Middle East and South Asia. After adjusting for geographic region, HCC surveillance was associated with early stage detection (Barcelona Clinic Liver Cancer stage 0/A, 71.0% vs 21.3%; P < .0001) and lower mortality rates (adjusted hazard ratio, 0.29; 95% CI, 0.18-0.46). Clinical characteristics, including early stage detection, and prognosis of post-SVR HCC differed significantly across geographic regions. Surveillance utilization appears to be a high-yield intervention target to improve prognosis among patients with post-SVR HCC globally.

Estimating Microvascular Invasion in Patients with Resectable Multinodular Hepatocellular Carcinoma by Using Preoperative Contrast-Enhanced MRI: Establishment and Validation of a Risk Score.

To determine the preoperative clinicoradiological factors to predict microvascular invasion (MVI) in patients with resectable multinodular hepatocellular carcinoma (mHCC), and further to establish and validate a stratified risk scoring system. Two hundred and seventy-three patients with pathologically confirmed mHCC (≥2 lesions) without major vascular invasion and biliary tract tumor thrombosis, who underwent preoperative contrast-enhanced MRI and hepatectomy, were consecutively enrolled (training/validation cohort=193/80). Preoperative clinicoradiological variables were collected and analyzed. The multivariable logistic regression was performed to determine the independent predictors of MVI and create a risk score system. The C-index, calibration curve and decision curve were used to evaluate the performance of the risk score. A risk score-based prognostic stratification system was performed in mHCC patients. The risk score system was further verified in the validation cohort. AFP > 400 ng/mL, presence of satellite nodule, mosaic architecture and increased total tumor diameter were independent predictors of MVI while fat in mass was an independent protective factor of MVI. The risk score yielded satisfactory C-index values (training/validation cohort: 0.777/0.758) and fitted well in calibration curves. Decision curve analysis further confirmed its clinical utility. Based on the risk score, mHCC patients were stratified into high-/low-MVI-risk subgroups with significantly different recurrence-free survival (both P < 0.001). The presented risk score incorporating clinicoradiological parameters could stratify mHCC patients into high-risk and low-risk subgroups and predict prognosis in patients with resectable mHCC.

An MRI-Based Prognostic Stratification System for Medical Decision-Making of Multinodular Hepatocellular Carcinoma Patients Beyond the Milan Criteria.

The suitability of hepatectomy among patients with multinodular hepatocellular carcinoma (MHCC) beyond the Milan criteria remains controversial. There is a need for a reliable risk stratification tool among these patients for the selection of ideal candidates of curative resection. To determine the clinicoradiological prognostic factors for patients with MHCC beyond the Milan criteria to further develop a stratification system. Retrospective. 176 patients with pathologically confirmed MHCC beyond the Milan criteria. The 1.5 T scanner, including T1-, T2-, diffusion-weighted imaging, in/out-phase imaging, and dynamic contrast-enhanced imaging. Conventional MRI features and preoperative laboratory data including aspartate aminotransferase (AST) and α-fetoprotein (AFP) were collected and analyzed. Two nomograms incorporating clinicoradiological variables were independently constructed to predict recurrence-free survival (RFS) and overall survival (OS) with Cox regression analyses and verified with 5-fold cross validation. Based on the nomograms, two prognostic stratification systems for RFS and OS were further developed. The Cohen's kappa/intraclass correlation coefficient, C-index, calibration curve, Kaplan-Meier curve, log-rank test. A P value <0.05 was considered statistically significant. AST > 40 U/L, increased tumor burden score, radiological liver cirrhosis and nonsmooth tumor margin were independent predictors for poor RFS, while AST > 40 U/L, AFP > 400 ng/mL and radiological liver cirrhosis were independent predictors for poor OS. The two nomograms demonstrated good discrimination performance with C-index of 0.653 (95% confidence interval [CI], 0.602-0.794) and 0.685 (95% CI, 0.623-0.747) for RFS and OS, respectively. The 5-fold cross validation further validated the discrimination capability of the nomograms. Based on the nomogram models, MHCC patients beyond the Milan criteria were stratified into low-/medium-/high-risk groups with significantly different RFS and OS. The proposed MRI-based prognostic stratification system facilitates the refinement and further subclassification of patients with MHCC beyond the Milan criteria. 4. 2.

The predictive value of the modified AFP model for liver transplantation outcomes in multinodular hepatocellular carcinoma patients

BackgroundThere is a lack of studies focusing on the benefit of liver transplantation (LT) in hepatocellular carcinoma (HCC) patients with > 3 tumors. This study aims to establish a model to effectively predict overall survival in Chinese HCC patients with multiple tumors (> 3 tumors) who undergo LT.MethodsThis retrospective study included 434 HCC liver transplant recipients from the China Liver Transplant Registry. All HCC patients had more than 3 tumor nodules. Three selection criteria systems (i.e., AFP, Metroticket 2.0, and Up-to-7) were compared regarding the prediction of HCC recurrence. The modified AFP model was established by univariate and multivariate competing risk analyses.ResultsThe AFP score 2 and the AFP score ≥ 3 groups had 5-year recurrence rates of 19.6% and 40.5% in our cohort. The prediction of HCC recurrence based on the AFP model was associated with a c-statistic of 0.606, which was superior to the Up-to-7 and Metroticket 2.0 models. AFP level > 1000 ng/mL, largest tumor size ≥ 8 cm, vascular invasion, and MELD score ≥ 15 were associated with overall survival. The 5-year survival rate in the modified AFP score 0 group was 71.7%.ConclusionsThe AFP model is superior in predicting tumor recurrence in HCC patients with > 3 tumors prior to LT. With the modified AFP model, patients likely to derive sufficient benefit from LT can be identified.

Postoperative outcomes and recurrence patterns of intermediate-stage hepatocellular carcinoma dictated by the sum of tumor size and number

The selection criteria for Barcelona Clinic Liver Cancer (BCLC) intermediate-stage hepatocellular carcinoma (HCC) patients who would truly benefit from liver resection (LR) remain undefined. To identify BCLC-B HCC patients more suitable for LR. We included patients undergoing curative LR for BCLC stage A or B multi-nodular HCC (MNHCC) and stratified BCLC-B patients by the sum of tumor size and number (N + S). Overall survival (OS), recurrence-free survival (RFS), recur-rence-to-death survival (RTDS), recurrence patterns, and treatments after recurrence in BCLC-B patients in each subgroup were compared with those in BCLC-A patients. In total, 143 patients who underwent curative LR for MNHCC with BCLC-A (n = 25) or BCLC-B (n = 118) were retrospectively analyzed. According to the N + S, patients with BCLC-B HCC were divided into two subgroups: BCLC-B1 (N + S ≤ 10, n = 83) and BCLC-B2 (N + S > 10, n = 35). Compared with BCLC-B2 patients, those with BCLC-B1 had a better OS (5-year OS rate: 67.4% vs 33.6%; P < 0.001), which was comparable to that in BCLC-A patients (5-year OS rate: 67.4% vs 74.1%; P = 0.250), and a better RFS (median RFS: 19 mo vs 7 mo; P < 0.001), which was worse than that in BCLC-A patients (median RFS: 19 mo vs 48 mo; P = 0.022). Further analysis of patients who developed recurrence showed that both BCLC-B1 and BCLC-A patients had better RTDS (median RTDS: Not reached vs 49 mo; P = 0.599), while the RTDS in BCLC-B2 patients was worse (median RTDS: 16 mo vs not reached, P < 0.001; 16 mo vs 49 mo, P = 0.042). The recurrence patterns were similar between BCLC-B1 and BCLC-A patients, but BCLC-B2 patients had a shorter recurrence time and a higher proportion of patients had recurrence with macrovascular invasion and/or extrahepatic metastasis, both of which were independent risk factors for RTDS. BCLC-B HCC patients undergoing hepatectomy with N + S ≤ 10 had mild recurrence patterns and excellent OS similar to those in BCLC-A MNHCC patients, and LR should be considered in these patients.

Comparison of the long-term outcomes of patients with hepatocellular carcinoma within the Milan criteria treated by ablation, resection, or transplantation.

Liver transplantation (LT), resection (LR), and ablation (LA) are three curative-intent treatment options for patients with early hepatocellular carcinoma (HCC). We aimed to develop a prognostic calculator to compare the long-term outcomes following each of these therapies. A total of 976 patients with HCC within the Milan criteria who underwent LT, LR, and LA between 2009 and 2019 from four institutions were evaluated. Multistate competing risks prediction models for recurrence-free survival (RFS), recurrence within the Milan criteria (RWM), and HCC-specific survival (HSS) were derived to develop a prognostic calculator. During a median follow-up of 51 months, 420 (43%) patients developed recurrence. In the multivariate analysis, larger tumor size, multinodularity, older age, male, higher alpha-fetoprotein (AFP), higher albumin-bilirubin (ALBI) grade, and the presence of portal hypertension were significantly associated with higher recurrence and decreased survival rates. The RFS and HSS were both significantly higher among patients treated by LT than by LR or LA and significantly higher between patients treated by LR than by LA (all p< 0.001). For multinodular HCC ≤3cm, although LT had better RFS and HSS than LR or LA, LA was noninferior to LR. An online prognostic calculator was then developed based on the preoperative clinical factors that were independently associated with outcomes to evaluate RFS, RWM, and HSS at different time intervals for all three treatment options. Although LT resulted in the best recurrence and survival outcomes, LR and LA also offered durable long-term alternatives. This prognostic calculator is a useful tool for clinicians to guide an informed and personalized discussion with patients based on their tumor biology and liver function.

Improved survival of viral hepatocellular carcinoma but not non-viral hepatocellular carcinoma from 2000 to 2020: A multi-centre cohort study of 6007 patients from high-volume academic centres in Japan.

While surveillance improves the early detection of hepatocellular carcinoma (HCC), it is unclear whether this has improved prognosis in clinical practice. To investigate the characteristics and prognoses of patients with viral versus non-viral HCC over the previous two decades in Japan, while HCC surveillance has been active. This multi-centre study enrolled 6007 patients initially diagnosed with HCC between 2000 and 2020 at seven high-volume academic centres. Patients were categorised based on dates of diagnosis: 2000-2006, 2007-2013 and 2014-2020. HCC characteristics and post-diagnosis survival rates were compared between periods in patients with viral and non-viral HCC. The percentage of patients with non-viral HCC increased during the study period. The maximal tumour size and percentage of patients with multinodular HCC decreased significantly over time in the viral HCC group but remained unchanged in the non-viral HCC group. Liver function at diagnosis improved over time in both groups, but to a greater extent in the viral HCC group. Survival rates increased significantly with time in the viral HCC group, but not in the non-viral HCC group. The prevalence of non-viral HCC is increasing. Although the survival of patients with viral HCC improved significantly over the past two decades, there was no improvement in patients with non-viral HCC. This was presumably due mainly to lower surveillance among patients with non-viral HCC and failure to diagnose early-stage HCC.

Correlation Between Serum Alpha-Fetoprotein and Tumour Size in Patients With Hepatocellular Carcinoma Treated With Direct-Acting Antivirals.

Objectives: Since its first description, alpha-fetoprotein has become the most widely used marker for diagnosing and monitoring patients with hepatocellular carcinoma (HCC). This study aims to assess the correlation between serum levels of alpha-fetoprotein and tumour dimensions in patients diagnosed with HCC, that were previously treated with direct-acting antivirals for hepatitis C viral infection.Materials and methods: We conducted a retrospective cohort study on 47 patients with a personal history of hepatitis C virus infection, who were diagnosed with different forms of HCC more than one year after achieving sustained virologic response after 12 weeks post-treatment. Patients were monitored by liver function tests, tumoral markers, blood cell count and coagulation profile and underwent imagistic explorations such as abdominal ultrasonography and, in selected cases, computerised tomography/magnetic resonance imaging. Tumour burden was assessed by both tumour burden score and seven-eleven criteria.Results: The study mostly included cirrhotic patients, multinodular HCC being the predominant pattern. All patients had alpha-fetoprotein levels over 100 ng/ml, with values largely varying, in accordance with the tumour dimensions. Most patients had medium-range Tumour Burden Score, a variable that also correlated with nodule size.Conclusions: The study found a significant correlation between serum alpha-fetoprotein and tumour size in patients with HCC. Alpha-fetoprotein also correlated well with Tumour Burden Score and remains a very important diagnostic and prognostic tool for patients with HCC.

Transarterial chemoembolization of hepatocellular carcinoma

Transarterial chemoembolization (TACE) is used as palliative and neoadjuvant treatment for patients with hepatocellular carcinoma (HCC). TACE should be offered as palliative treatment to patients with intermediate stage large or multinodular HCC if no curative treatment option is available by resection or thermoablation and if extrahepatic metastases and tumor infiltration of main portal and systemic veins has been excluded. TACE is possible only in patients with preserved liver function (Child-PughA-B, best up to 7points) and with good performance status (ECOG0). TACE can be used for bridging and for downstaging prior to liver transplantation with the intention to maintain or reach limited intrahepatic tumor load defined by Milan criteria. TACE should be adapted to the vascularization pattern of the HCC nodules and performed as selective as possible and repetetively if necessary with the goal of complete devascularization of the tumor tissue. Conventional TACE (cytotoxic drugs, iodized oil and embolic particles) and drug-eluting TACE (anthracycline preloaded in microspheres) can be used in acomparable way. During drug-eluting TACE, peripheral concentration of cytotoxic drugs is lower. Using conventional TACE in apalliative setting, survival benefit for patients was 8-11months compared to best supportive care; however, this requires that all known contraindications and other criteria in terms of tumor and liver disease, respectively, associated with negative prognosis be taken into consideration. Better local response is achieved by drug-eluting TACE; however, no related survival benefit was shown compared to conventional TACE so far. Response to neoadjuvant local treatment is associated with improved prognosis after liver transplantation.

Prospect of lenvatinib for unresectable hepatocellular carcinoma in the new era of systemic chemotherapy.

The phase III clinical trial of the novel molecular targeted agent (MTA) lenvatinib for patients with advanced hepatocellular carcinoma (HCC) (REFLECT trial) found that lenvatinib was non-inferior to sorafenib in overall survival. Recently, the efficacy of multiple MTAs, including lenvatinib, in practice has been reported, and therapeutic strategies for Barcelona Clinic Liver Cancer (BCLC) intermediate stage HCC are undergoing major changes. Based on these results, lenvatinib could be recommended for patients with transcatheter arterial chemoembolization (TACE)-refractory, ALBI grade 1, within the up-to-seven criteria in the BCLC intermediate stage. Lenvatinib provides a more favorable outcome than TACE, even in cases with large or multinodular HCC beyond the up-to-seven criteria with Child-Pugh grade A. When patients meet the definitions of TACE-refractory or TACE-unsuitable, switching to systemic chemotherapy, including lenvatinib, is for favorable for preserving liver function. If initial treatment, including MTA, has a significant therapeutic effect and downstaging of HCC is obtained, additional TACE or surgical resection should be considered. Lenvatinib also has a therapeutic effect for poorly differentiated type and non-simple nodular type HCC thanks to the survival-prolonging effect of this drug. Furthermore, a significant therapeutic effect is expected in tumors with more than 50% liver involvement or main portal vein invasion, which have traditionally been considered to have a poor prognosis in patients. This suggests that at the start of lenvatinib treatment, HCC patients with ALBI grade 1 may be able to maintain liver functional reserve.

Photodynamic and Photothermal Therapy of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver tumor. It is ranked the sixth most common neoplasm and the third most common cause of cancer mortality. At present, the most common treatment for HCC is surgery, but the 5-year recurrence rates are still high. Patients with early stage HCC with few nodules can be treated with resection or radiofrequency ablation (RFA); while for multinodular HCC, transarterial chemoembolization (TACE) has been the first-line treatment. In recent years, based on medical engineering cooperation, nanotechnology has been increasingly applied to the treatment of cancer. Photodynamic therapy and photothermal therapy are effective for cancer. This paper summarizes the latest progress of photodynamic therapy and photothermal therapy for HCC, with the aim of providing new ideas for the treatment of HCC.

Characteristics of De novo Hepatocellular carcinoma (HCC) in Chronic HCV Egyptian patients received Direct Acting Antivirals (DAAs) therapy: A pilot study

Abstract Background Direct-acting antiviral agents for chronic hepatitis C have initiated a revolution in the management and control of this important liver disease with cure rates over 90%. However, it has been suggested that HCC may occur or recur in patients with chronic HCV infection who received DAAs therapy. Aim To compare characteristics and behavior of de novo Hepatocellular carcinoma (HCC) in chronic HCV patients who received direct acting antiviral treatment with those who didn't receive DAAs . Patients and methods The current study was conducted on patients with de novo HCC presented at HCC clinic, Tropical medicine department Ain Shams University Hospitals between December 2017 and December 2018, aged (18-70 years old) . Total number of HCC cases visited the clinic during the study period was 416 patients. 160 patients with de novo HCC were enrolled in the study fullfiling the inclusion criteria and divided to two groups, 80 patients with HCC who received Direct antiviral treatment, the other 80 patients who didn't receive Direct antiviral treatment. Results Unlike some previous concerns about increased biologic aggressiveness of HCC after DAA treatment, resulting in infiltrative pattern and multinodular HCC outside Milan criteria, our results on de novo HCC after DAAs were mostly single, small, and diagnosed in early stages, resulting in BCLC stage 0-B in the majority of patients. There were no statistical differences regarding total size of tumor,or vascular invasion or AFP, but there’s a statistical difference in largest size of HFLs that was more significant in group (A) P = 0.04 The mean Child score was 5.75 in group A, with 61 patients (76.3%) were Child class A,19 patients (23.8%) were Child class B and 0 patients were child C. For the patients in group (B) the mean Child score was 6.15, with 50 patients (62.5%) were Child class A, 26 patients (32.5%) were Child class B and 4 patients (5%) were child C. Conclusion The current study shows no differences between the 2 studied groups as regard tumor aggressiveness, but data on risk of HCC and behaviour after DAAs is still conflicting and further studies are needed

Whole-liver transcatheter arterial chemoinfusion and bland embolization with fine-powder cisplatin and trisacryl gelatin microspheres for treating unresectable multiple hepatocellular carcinoma

PurposeTo evaluate the safety and effectiveness of whole-liver transcatheter arterial chemoinfusion and bland embolization (TACBE) with fine-powder cisplatin and trisacryl gelatin microspheres for the treating unresectable multinodular hepatocellular carcinoma (HCC).Materials and methodsThe medical records of all patients who underwent TACBE sessions were retrospectively reviewed. 15 patients (11 men, 4 women; mean age, 72.5 years) and 22 procedures (BCLC B;17 C;5) were included in the analysis. The cisplatin resulting solution and microspheres were infused through a microcatheter placed nonselectively. Overall survival (OS) was defined as the time from commencement of initial TACBE until any cause of death. Toxicity was assessed by the CTCAE version 5.0, and the tumor response was evaluated by the mRECIST. Liver function was assessed by the albumin–bilirubin (ALBI) score.ResultsThe 1-year OS rate was 64.6% (95% CI 0.438–0.955). Severe adverse effects were not observed except for grade 3 increase in the ALT, ALT, vasovagal episode. The objective response and disease control rare were 54.5% and 68.2%, respectively. The ALBI scores from pre-treatment to the follow-up ranged from − 2.39 to − 2.26 (p = 0.38).ConclusionWhole-liver TABCE with fine-powder cisplatin and trisacryl gelatin microspheres was well tolerated and effective in patients with multinodular HCC.

Conditional disease-free survival after liver resection for HCC

Background: A high recurrence rate after resection of hepatocellular carcinoma (HCC) is one of the most debated issues in literature.Conditional survival is defined as the probability of surviving for another “Y” years, given that the person has already survived “X” years and is derived from the concept of conditional probability in biostatistics. The literature about conditional disease-free survival (CDFS) in patients with HCC after curative resection is very limited.The study aim was to investigate the long-term change in tumor recurrence risk in disease-free patients (DFS) after hepatic resection for HCC. Recurrence probability over time was estimated by CDFS analysis. Methods: 477 consecutive patients that underwent liver resection surgery with curative intent for HCC at the General and Hepatobiliary Surgery Department of the University of Verona from May 1989 to December 2020 were retrospectively analyzed.Long-term endpoints were the DFS, i.e., the time elapsed between the intervention and the first relapse (or the last follow up in case of no relapse) and calculation of the conditional disease-free survival (CDFS) specified as the 1, 2 and 3-year CDFS, which represents the probability of remaining disease-free for an additional 1, 2 and 3 years. Besides, prognostic factors associated with disease-free survival were identified and the change in their impact over time was analyzed. Results: Disease-free survival was 68.2%, 53.6%, 41.6% at 1, 2 and 3 years. Conditional disease-free survival rates of the entire study population based on the time already lived after surgical resection have been evaluated.There were significant differences between DFS and CDFS. The disease-free survival at 5 years was 27.0%, but patients who had already 3 years of disease-free after surgery, had a 64.9% chance of having a further 2 years of disease-free survival. Prognostic factors for DFS and their changes over time have been evaluated. We found that multinodular HCC, HCV, macrovascular invasion and high AFP were significantly related to DFS in baseline analysis, but these factors were no longer related with DFS after X months. Cirrhosis remains the only risk factor for recurrence with statistical significance over the 3 years of DFS. Conclusions: Conditional disease-free survival analysis shows that the prognosis varies over time and is an important tool that can provide more accurate and dynamic prognostic information useful to guide follow-up strategies.

Methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF) polymorphisms in Brazilian patients with Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)

OBJECTIVE:The folate pathway is involved in hepatic carcinogenesis and angiogenesis. Polymorphisms in genes related to such processes, including methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF)] may play an important role in the development of hepatocellular carcinoma (HCC). The objective of this study was to evaluate MTHFR and VEGF polymorphisms in Brazilian patients with hepatitis C virus (HCV)-related HCC.METHODS:A total of 119 patients diagnosed with confirmed HCC and HCV were included in the study. SNP genotyping assays were performed using real-time PCR. VEGFA (rs2010963, rs3025039, and rs833061) and MTHFRC677T (rs1801133, rs1801131) polymorphisms were evaluated.RESULTS:The C alleles of MTHFR (rs1801131) and VEGF (rs2010963) were associated with protection against the development of multinodular HCC, while the T allele of MTHFR (rs1801133) was associated with a higher risk of multinodular presentation [p=0.04 OR 1.835 CI (1.022-3.297)]. Multivariate analysis revealed that the GG/GC genotypes of VEGF rs2010963 were independently associated with multinodular tumors at diagnosis (p=0.013; OR 4.78 CI (1.38-16.67)].CONCLUSION:Our results suggest that these polymorphisms may increase the risk of rapid tumor progression in patients with HCV infection. This subgroup of patients with HCC and who present polymorphism is more likely to be diagnosed with multinodular disease and not be amenable to receiving curative treatments. These data must be validated in larger cohorts, and the screening intervals can be customized based on genetic history.

Predictive factors for long-term survival in patients with advanced hepatocellular carcinoma treated with sorafenib.

Sorafenib, used for advanced-stage hepatocellular carcinoma (HCC), has an overall survival (OS) of 10 months. However, some patients have better response and long-term survival (LTS). Aims to assess predictive factors for LTS. Retrospectively reviewed 77 advanced HCC patients, starting sorafenib treatment between 2007 and 2016, with LTS (OS ≥24 months) as primary endpoint. Univariate and multivariable analysis of clinical variables were performed in order to identify predictive factors for LTS. Patients: seventy (90.9%) males; median age: 65 years (39-82). All had cirrhosis mostly HCV infection (n = 32, 41.6%). Majority were Child-Pugh class A (n = 50, 64.9%); median MELD-Na: 11 (6-30). Multinodular HCC: 74% (n = 57); portal vein invasion (PVI): 50.6% (n = 39); extrahepatic spread: 18.2% (n = 14). Median time between HCC diagnosis and sorafenib start: 3.3 months (0-37.6). Median OS: 13 months [95% confidence interval (CI) 8.2-17.8]. Twenty-five (32.5%) patients were considered LTS, with amedian OS: 52.3 months (95% CI 17.1-87.4). Multivariable analysis identified Child-Pugh class A [odds ratio (OR) 11.1, 95% CI 1.78-69.54] and absence of PVI (OR 7.88, 95% CI 1.56-39.8) as independent predictors of LTS. Sub-analysis of Child-Pugh class A: absence of PVI (OR 7.13, 95% CI 1.69-30.2) and alpha-fetoprotein <400 ng/ml (OR 5.82, 95% CI 1.18-28.75) independently related to LTS. Despite global short median OS, sorafenib treatment is associated with longer than 2-year survival in a sub-group, more likely in compensated liver disease and absence of PVI.