Search Results (12)

Objective: This study aimed to investigate the prognostic value of preoperative myosteatosis and the albumin–bilirubin (ALBI) grade in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) and develop a robust prognostic score based on these factors. Methods: Patients with HCC who underwent TACE between January 2009 and December 2020 were included. Multivariate Cox regression analysis identified prognostic factors. CT-based body composition parameters were acquired from baseline abdominal CT images at the level of the third lumbar vertebra. A prognostic score (Myo-ALBI) was developed based on the presence of preoperative myosteatosis and the ALBI grade, and its prognostic value was evaluated. Results: Of 446 patients, 63% were male, and the mean age was 62.4 years. Preoperative myosteatosis was present in 41.5% of patients. The BCLC stages were mostly B (67.9%). Multivariate analysis shows that preoperative myosteatosis, ALBI grade 2, and ALBI grade 3 were independent prognostic factors. The Myo-ALBI grade was incorporated into a prognostic model, including alpha-fetoprotein and up-to-seven criteria, to generate a nomogram. The C-index of the nomogram based on the Myo-ALBI grade (0.743) was significantly higher than the non-Myo-ALBI nomogram (0.677), the up-to-seven criteria (0.653), the ALBI grade (0.616), and the Child–Pugh class (0.573) (all p < 0.05). The t-ROC curve for the nomogram was consistently superior to the other models throughout the observation period in all patients and the BCLC-B subgroup. Conclusions: The combination of preoperative CT-derived myosteatosis and ALBI grade enhances prognostication for patients with unresectable HCC undergoing TACE. The Myo-ALBI nomogram constructed in this study could support individualized prognosis prediction, assisting in treatment decision-making for HCC patients. Full article

We aimed to assess changes in the composition of the waiting list for liver transplantation (LT) after expanding from Milan to “up-to-seven” criteria in patients with hepatocellular carcinoma (HCC). A consecutive cohort of 255 LT candidates was stratified in a pre-expansion era (2016–2018; n = 149) and a post-expansion era (2019–2021; n = 106). The most frequent indication for LT was HCC in both groups (47.7% vs. 43.4%; p = 0.5). The proportion of patients exceeding the Milan criteria in the explanted liver was nearly doubled after expansion (12.5% vs. 21.1%; p = 0.25). Expanding criteria had no effect in drop-out (12.3% vs. 20.4%; p = 0.23) or microvascular invasion rates (37.8% vs. 38.7%; p = 0.93). The length on the waiting list did not increase after the expansion (172 days [IQR 74–282] vs. 118 days [IQR 67–251]; p = 0.135) and was even shortened in the post-expansion HCC subcohort (181 days [IQR 125–232] vs. 116 days [IQR 74–224]; p = 0.04). Tumor recurrence rates were reduced in the post-expansion cohort (15.4% vs. 0%; p = 0.012). In conclusion, expanding from Milan to up-to-seven criteria for LT in patients with HCC had no meaningful impact on the waiting list length and composition, thus offering the opportunity for the adoption of more liberal policies in the future. Full article

Despite the promising efficacy of atezolizumab plus bevacizumab (atezo/bev), some patients with unresectable hepatocellular carcinoma (HCC) experience disease progression. This retrospective study, which included 154 patients, aimed to evaluate predictors of treatment efficacy of atezo/bev for unresectable HCC. Factors associated with treatment response were examined, focusing on tumor markers. In the high-alpha-fetoprotein (AFP) group (baseline AFP ≥ 20 ng/mL), a decrease in AFP level > 30% was an independent predictor of objective response (odds ratio, 5.517; p = 0.0032). In the low-AFP group (baseline AFP < 20 ng/mL), baseline des-gamma-carboxy prothrombin (DCP) level < 40 mAU/mL was an independent predictor of objective response (odds ratio, 3.978; p = 0.0206). The independent predictors of early progressive disease were an increase in AFP level ≥ 30% at 3 weeks (odds ratio, 4.077; p = 0.0264) and the presence of extrahepatic spread (odds ratio, 3.682; p = 0.0337) in the high-AFP group and up-to-seven criteria, OUT (odds ratio, 15.756; p = 0.0257) in the low-AFP group. In atezo/bev therapy, focusing on early AFP changes, baseline DCP, and tumor burden of up-to-seven criteria are useful in predicting response to treatment. Full article

This study evaluated the prognostic value of metabolic parameters based on the standardized uptake value (SUV) normalized by total body weight (bwSUV) and by lean body mass (SUL) measured on ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for predicting tumor recurrence after primary living donor liver transplantation (LDLT) in patients with hepatocellular carcinoma (HCC) without transplantation locoregional therapy. This retrospective study enrolled 49 patients with HCC. The maximum tumor bwSUV (T-bwSUVmax) and SUL (T-SULmax) were measured on PET. The maximum bwSUV (L-bwSUVmax), mean bwSUV (L-bwSUVmean), maximum SUL (L-SULmax), and mean SUL (L-SULmean) were measured in the liver. All metabolic parameters were evaluated using survival analyses and compared to clinicopathological factors. Tumor recurrence occurred in 16/49 patients. Kaplan–Meier analysis revealed that all metabolic parameters were significant (p < 0.05). Univariate analysis revealed that prothrombin-induced by vitamin K absence or antagonist-II; T-stage; tumor number; tumor size; microvascular invasion; the Milan criteria, University of California, San Francisco (UCSF), and up-to-seven criteria; T-bwSUVmax/L-bwSUVmean; T-SULmax; T-SULmax/L-SULmax; and T-SULmax/L-SULmean were significant predictors. Multivariate analysis revealed that the T-SULmax/L-SULmean (hazard ratio = 115.6; p = 0.001; cut-off, 1.81) and UCSF criteria (hazard ratio = 172.1; p = 0.010) were independent predictors of tumor recurrence. SUL-based metabolic parameters, especially T-SULmax/L-SULmean, were significant, independent predictors of HCC recurrence post-LDLT. Full article

In Europe and the United States, approximately 1100 and 1800 liver transplantations, respectively, are performed every year for hepatocellular carcinoma (HCC), compared with an annual incidence of 65,000 and 39,000 new cases, respectively. Because of organ shortages, proper patient selection is crucial, especially for those exceeding the Milan criteria. Downstaging is the reduction of the HCC burden to meet the eligibility criteria for liver transplantation. Many techniques can be used in downstaging, including ablation, chemoembolisation, radioembolisation and systemic treatments, with a reported success rate of 60–70%. In recent years, an increasing number of patient responders to downstaging procedures has been included in the waitlist, generally with a comparable five-year post-transplant survival but with a higher probability of dropout than HCC patients within the Milan criteria. While the Milan criteria are generally accepted as the endpoint of downstaging, the upper limits of tumour burden for downstaging HCC for liver transplantation are controversial. Very challenging situations involve HCC patients with large nodules, macrovascular invasion or even extrahepatic metastasis at baseline who respond to increasingly more effective downstaging procedures and who aspire to be placed on the waitlist for transplantation. This narrative review analyses the most important evidence available on cohorts subjected to “extended” downstaging, including HCC patients over the up-to-seven criteria and over the University of California San Francisco downstaging criteria. We also address surrogate markers of biological aggressiveness, such as alpha-fetoprotein and the response stability to locoregional treatments, which are very useful in selecting responders to downstaging procedures for waitlisting inclusion. Full article

Mortality and recurrence rates of hepatocellular carcinoma (HCC) are high. Recent studies show that for patients with HCC beyond up-to-seven criteria, treatment with molecular-targeted agents (MTAs) is recommended because the treatment efficiency of transcatheter arterial chemoembolization (TACE) is poor; further, TACE increases decline in liver function. However, the relationship between TACE and liver function decline in patients with HCC within up-to-seven criteria has not been clarified. Hence, we aimed to investigate this relationship. This retrospective observational study included 189 HCC tumors within up-to-seven criteria in 114 Child–Pugh class A patients. Twenty-four (12.7%) tumors were changed from Child–Pugh class A to B after TACE, and 116 (61.4%) tumors exhibited recurrence within 6 months after TACE. Prothrombin time (PT) and albumin–bilirubin (ALBI) score before TACE were significantly associated with liver dysfunction from Child–Pugh class A to B. The combination of PT and ALBI score before TACE had high predictive ability for liver dysfunction from Child–Pugh class A to B after TACE (specificity = 100%, sensitivity = 91.7%). The combined use of pre-TACE PT and ALBI score has a high predictive ability for liver dysfunction after TACE for Child–Pugh class A patients with HCC within up-to-seven criteria. Full article

Transarterial chemoembolization (TACE) is the standard of care for intermediate stage hepatocellular carcinoma (HCC). We aimed to identify unsuitable cases who were at risk of ALBI-grade migration by TACE. Consecutive 531 BCLC-B HCC patients undergoing TACE were reviewed, and factors associated with ALBI-grade migration were analyzed. There were 129 (24.3%) patients experienced acute ALBI-grade migration after TACE, and 85 (65.9%) out of the 129 patients had chronic ALBI-grade migration. Incidences of acute ALBI-grade migration were 13.9%, 29.0% for patients within or beyond up-to-7 criteria (p < 0.001) and 20.0%, 36.2% for patients within or beyond up-to-11 criteria (p < 0.001), respectively. HBV infection, tumor size plus tumor number criteria were risk factors associated with acute ALBI-grade migration. Bilobar tumor involvement was the risk factor of chronic ALBI-grade migration in patients with acute ALBI-grade migration. Up-to-eleven (p = 0.007) performed better than up-to-seven (p = 0.146) to differentiate risk of dynamic ALBI score changes. Moreover, ALBI-grade migration to grade 3 has adverse effect on survival. In conclusion, tumor burden beyond up-to-eleven was associated with ALBI-grade migration after TACE, indicating that up-to-eleven can select TACE-unsuitable HCC patients who are at risk of liver function deterioration. Full article

Several models have been developed using conventional regression approaches to extend the criteria for liver transplantation (LT) in hepatocellular carcinoma (HCC) beyond the Milan criteria. We aimed to develop a novel model to predict tumor recurrence after LT by adopting artificial intelligence (MoRAL-AI). This study included 563 patients who underwent LT for HCC at three large LT centers in Korea. Derivation (n = 349) and validation (n = 214) cohorts were independently established. The primary outcome was time-to-recurrence after LT. A MoRAL-AI was derived from the derivation cohort with a residual block-based deep neural network. The median follow-up duration was 74.7 months (interquartile-range, 18.5–107.4); 204 patients (36.2%) had HCC beyond the Milan criteria. The optimal model consisted of seven layers including two residual blocks. In the validation cohort, the MoRAL-AI showed significantly better discrimination function (c-index = 0.75) than the Milan (c-index = 0.64), MoRAL (c-index = 0.69), University of California San Francisco (c-index = 0.62), up-to-seven (c-index = 0.50), and Kyoto (c-index = 0.50) criteria (all p < 0.001). The largest weighted parameter in the MoRAL-AI was tumor diameter, followed by alpha-fetoprotein, age, and protein induced by vitamin K absence-II. The MoRAL-AI had better predictability of tumor recurrence after LT than conventional models. The MoRAL-AI can also evolve with further data. Full article

Since the introduction of Milan Criteria, all scoring models describing the prognosis of hepatocellular cancer (HCC) after liver transplantation (LT) have been exclusively based on characteristics available at surgery, therefore neglecting the intention-to-treat principles. This study aimed at developing an intention-to-treat model through a competing-risk analysis. Using data available at first referral, an upper limit of tumor burden for downstaging was identified beyond which successful LT becomes an unrealistic goal. Twelve centers in Europe, United States, and Asia (Brussels, Sapienza Rome, Padua, Columbia University New York, Innsbruck, Medanta-The Medicity Dehli, Hong Kong, Kyoto, Kaohsiung Taiwan, Mainz, Fukuoka, Shulan Hospital Hangzhou) created a Derivation (n = 2318) and a Validation Set (n = 773) of HCC patients listed for LT between January 2000–March 2017. In the Derivation Set, the competing-risk analysis identified two independent covariables predicting post-transplant HCC-related death: combined HCC number and diameter (SHR = 1.15; p < 0.001) and alpha-fetoprotein (AFP) (SHR = 1.80; p < 0.001). WE-DS Model showed good diagnostic performances at internal and external validation. The identified upper limit of tumor burden for downstaging was AFP ≤ 20 ng/mL and up-to-twelve as sum of HCC number and diameter; AFP = 21–200 and up-to-ten; AFP = 201–500 and up-to-seven; AFP = 501–1000 and up-to-five. The WE-DS Model proposed here, based on morphologic and biologic data obtained at first referral in a large international cohort of HCC patients listed for LT, allowed identifying an upper limit of tumor burden for downstaging beyond which successful LT, following downstaging, results in a futile transplantation. Full article

Background and Aims: Several models have been developed to predict tumor the recurrence of hepatocellular carcinoma (HCC) after liver transplantation besides the conventional Milan criteria (MC), including the MoRAL score. This study aimed to compare the prognostication power of the MoRAL score to most models designed so far in the Eastern and Western countries. Methods: This study included 564 patients who underwent living donor liver transplantation (LDLT) in three large-volume hospitals in Korea. The primary and secondary endpoints were time-to-recurrence, and overall survival (OS), respectively. The performance of the MoRAL score was compared with those of other various Liver transplantation (LT) criteria, including the Milan criteria, University of California San Francisco (UCSF) criteria, up-to-seven criteria, Kyoto criteria, AFP model, total tumor volume/AFP criteria, Metroticket 2.0 model, and Weill Cornell Medical College group model. Results: The median follow-up duration was 78.1 months. Among all models assessed, the MoRAL score showed the best discrimination function for predicting the risk of tumor recurrence after LT, with c-index of 0.78, compared to other models (all p < 0.001). The MoRAL score also represented the best calibration function by Hosmer-Lemeshow test (p = 0.15). Especially in the beyond-MC sub-cohort, the MoRAL score predicted tumor recurrence (c-index, 0.80) and overall survival (OS) (c-index, 0.70) significantly better than any other models (all p < 0.001). When the MoRAL score was low (<314.8), the five-year cumulative risks of tumor recurrence and death were excellent in beyond-MC (27.8%, and 20.5%, respectively) and within-MC (16.3%, and 21.1%, respectively) sub-cohorts. Conclusions: The MoRAL score provides the most refined prognostication for predicting HCC recurrence after LDLT. Full article

Although transcatheter arterial chemoembolization (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma (HCC), this is a largely heterogeneous disease that includes a subgroup of patients who do not benefit from TACE. The treatment strategy for this subgroup of patients currently remains an unmet need in clinical practice. Here, we performed a proof-of-concept study that lenvatinib may be a more favorable treatment option over TACE as an initial treatment in intermediate-stage HCC patients with large or multinodular tumours exceeding the up-to-seven criteria. This proof-of-concept study included 642 consecutive patients with HCC initially treated with lenvatinib or conventional TACE (cTACE) between January 2006 and December 2018. Of these patients, 176 who received lenvatinib or cTACE as an initial treatment and met the eligibility criteria (unresectable, beyond the up-to-seven criteria, no prior TACE/systemic therapy, no vascular invasion, no extrahepatic spread and Child–Pugh A liver function) were selected for the study. Propensity score matching was used to adjust for patient demographics. After propensity-score matching, the outcome of 30 patients prospectively treated with lenvatinib (14 in clinical trials, one in an early access program and 15 in real world settings) and 60 patients treated with cTACE as the initial treatment was compared. The change of albumin-bilirubin (ALBI) score from baseline to the end of treatment were −2.61 to −2.61 for 30 patients in the lenvatinib group (p = 0.254) and −2.66 to −2.09 in the cTACE group (p < 0.01), respectively. The lenvatinib group showed a significantly higher objective response rate (73.3% vs. 33.3%; p < 0.001) and significantly longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; p < 0.001). Overall survival was significantly longer in the lenvatinib group than in the cTACE group (37.9 vs. 21.3 months; hazard ratio: 0.48, p < 0.01). In patients with large or multinodular intermediate-stage HCC exceeding the up-to-seven criteria with Child–Pugh A liver function, who usually do not benefit from TACE, lenvatinib provides a more favorable outcome than TACE. Full article

Transarterial chemoembolization (TACE) is the recommended first-line treatment for intermediate-stage hepatocellular carcinoma (HCC). In patients who became refractory to TACE, a treatment switch to tyrosine kinase inhibitors (TKIs) needs to be considered. However, TACE could worsen liver function, thereby narrowing the time window for a switch to TKIs because TKIs are recommended for patients with Child-Pugh grade A (CP-A). We investigated the factors associated with CP grade deterioration after TACE. Among patients who underwent TACE, 125 patients with CP-A were enrolled. The cumulative CP grade deterioration rates were 20.3%, 27.1%, and 41.4% at six months, one year, and two years, respectively. Multivariate analysis revealed that factors associated with CP grade deterioration included high Mac-2 binding protein glycosylation isomer (M2BPGi) levels (>2.00 cut-off index) and beyond the up-to-seven criteria. The cumulative CP grade deterioration rates of patients with high M2BPGi and beyond the up-to-seven criteria were 50.6% and 59.2% at six months and one year, respectively, which were significantly higher than for those in any other groups. The combination of M2BPGi and up-to-seven criteria could be a surrogate marker for predicting CP grade deterioration after TACE. In patients with intermediate-stage HCC, elevated M2BPGi levels, and beyond the up-to-seven criteria, an early treatment switch to TKIs should be considered to improve their prognosis. Full article