BACKGROUND AND AIMS:The ASAP algorithm incorporating Age, Sex, Alpha-fetoprotein (AFP), and prothrombin induced by vitamin K absence/antagonist II (PIVKA-II) has been shown to predict hepatocellular carcinoma (HCC) development. Our study evaluated the prognostic value of ASAP for early HCC recurrence after complete radiological response (CR) to locoregional therapy. METHODS:This single-center study enrolled patients with newly diagnosed HCC who achieved CR by ablation (MWTA) or chemoembolization (TACE) and available serum samples on the day of treatment. CR was evaluated by CT-scan 1 month after treatment. PIVKA-II and AFP levels were measured using Fujirebio assays. Patients were followed up every three months until recurrence, death, or last follow-up. RESULTS:127 patients with HCC (median age 66 years, 79 % male, 79 % with viral etiology) who achieved CR were enrolled. At time of treatment, median AFP and PIVKA-II levels were 6.6 ng/mL and 144 mAU/mL, respectively, while median ASAP score was 0.60. During follow-up, HCC recurred in 72 (56.7 %) patients (63 within 24 months, early recurrence). ASAP score was the sole independent predictor of early recurrence [HR 2.57 (95 % CI 1.50-4.40), p=0.001] and its new cutoff of 0.797 (AUC 66 %, sensitivity 57 %, specificity 75 %) outperformed other scores and biomarkers. CONCLUSIONS:The ASAP score accurately predicted early HCC recurrence post-CR, warranting further validation.

Background & Aims: In advanced hepatocellular carcinoma (HCC), neoplastic portal vein thrombosis (nPVT) and extrahepatic metastases could represent distinct manifestations of tumour burden. However, under first-line atezolizumab–bevacizumab (A+B), the relative prognostic weight of these features remains insufficiently explored. This study aimed to assess how vascular invasion and metastatic involvement influence clinical outcomes, including early decompensating events (EHD), in patients receiving A+B.Methods: Five hundred and six cirrhotic patients with unresectable HCC treated with first-line A+B within the prospective ARTE dataset were included. Patients were evaluated for the presence of nPVT and extrahepatic metastases. EHD was defined as new-onset ascites, encephalopathy, jaundice, or variceal bleeding within 12 weeks of treatment initiation. Primary endpoints were overall survival (OS), progression-free survival (PFS), and radiological progression.Results: nPVT was present in 331 patients (59.9%) and extrahepatic metastases in 185 (36.5%). EHD occurred in 53 patients (10.5%) and was strongly associated with nPVT (OR 3.13, 95% CI 1.71–6.44), even after adjustments for baseline liver function (Child-Pugh or ALBI grade), whereas metastases showed no association. Patients who developed EHD experienced markedly worse survival (median OS 8.2 vs 19.6 months, p<0.001) and shorter duration of treatment (3.5 months, IQR 1.4–9.8 vs 7.3 months, IQR 3.5–15.2).In time-dependent multivariable Cox analysis for OS, EHD (HR 1.85, 95% CI 1.27–2.70), ALBI grade ≥2 (HR 1.49, 95% CI 1.14–1.95), and AFP ≥400 ng/mL (HR 1.45, 95% CI 1.10–1.94) were independent predictors, whereas neither nPVT nor metastases retained significance after adjusting for liver function and EHD.Conversely, extrahepatic metastases were independently associated with radiological progression (HR 1.47, 95% CI 1.15–1.88) and shorter PFS (HR 1.40, 95% CI 1.05–1.64), while nPVT showed no association with either endpoint.Conclusions: Among patients treated with A+B, nPVT and metastases appear to influence prognosis through different pathways: nPVT primarily by predisposing to early hepatic decompensation, and metastases mainly by accelerating tumour progression. Once EHD occurs, its impact on survival outweighs that of both vascular invasion and metastatic spread, likely due to the shorter treatment duration observed in this group. These findings suggest that assessing early liver deterioration alongside baseline tumour pattern may improve early risk stratification in advanced HCC and help contextualise the prognostic relevance of nPVT and metastases under A+B therapy.

Background and Aims: Hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) remains a major determinant of post-transplant mortality, affecting up to 20% of recipients despite selection within the Milan criteria. The Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score, developed by Mehta et al. (UCSF, USA), integrates three post-transplant prognostic variables: (1) alpha-fetoprotein (AFP) at LT (<20 ng/mL = 0, 20–99 = 1, 100–999 = 2, ≥1000 = 3 points), (2) presence of microvascular invasion (MVI, 2 points if present), and (3) the sum of the largest viable tumor diameter (cm) plus number of viable tumors (0 = no viable tumor, 1 = 1–4.9, 2 = 5–9.9, 3 = ≥10). The score has shown excellent predictive performance in international and recent prospective validations but has never been evaluated in Italian transplant centers. This study aimed to validate the RETREAT score in an Italian multicenter cohort and assess its clinical applicability.Methods: We retrospectively analyzed 262 adults transplanted for HCC between 2010–2020 at two Italian centers (Verona and Milan). All patients met Milan criteria at listing. Predictors of recurrence and survival were analyzed using Cox and logistic regression. RETREAT discrimination was assessed using ROC analysis, Harrell’s C-index, calibration, and decision curve analysis (DCA).Results: Over a median follow-up of 83.2 months, 32 patients (12.2%) developed recurrence and 63 (24.0%) died (overall). Median survival after recurrence diagnosis was 23.5 months (IQR: 6.2-43.5). Pre-transplant locoregional therapy was performed in 80.5% of cases: 24 (9.2%) underwent downstaging, 102 (38.9%) bridge, and 85 (32.4%) had previous treatments in the past. Most of them were TACE (37.7%) and RFA (26.5%). Microvascula invasion (MVI) was the strongest recurrence predictor (OR 5.93, 95% CI 2.73–12.87, p<0.001). RETREAT ≥3 was associated with a 6.7-fold higher recurrence risk (OR 6.72, 95% CI 2.88–15.68, p<0.001) and remained independently associated in multivariable analysis (OR 3.97, 95% CI 1.23–12.27, p=0.016). Exceeding Milan criteria on explant histology was not significant (p=0.239). The score demonstrated excellent discrimination (AUC 0.774, C-index 0.77), good calibration, and positive net benefit on DCA across thresholds of 5–15%. Kaplan-Meier analyses highlighted: (Fig. 1) the strong impact of recurrence on overall survival (p<0.0001); (Fig. 2) significantly worse RFS for high-risk patients (RETREAT ≥3) compared with low-risk (RETREAT ≤2) (p=0.012).Conclusions:This first Italian validation confirms the excellent prognostic accuracy and generalizability of the RETREAT score. RETREAT-based stratification allows effective identification of high-risk patients and supports personalized surveillance strategies across Italian transplant centers.

Background and Aims: The management of comorbidities has gained relevance in hepatocellular carcinoma (HCC) due to improved long-term survival. Bevacizumab, an anti-VEGF drug, increases the risk of major adverse cardiac events (MACE). Identifying at-risk patients is crucial since anti-VEGF-free therapeutic alternatives are now available. This study aimed to assess whether the European Society of Cardiology (ESC) antiangiogenic risk score and the CARDIOSOR score (Carballo-Folgoso, 2021) predict MACE in patients with HCC treated with atezolizumab/bevacizumab (AB).Methods: We retrospectively analyzed prospectively collected data from the multicentric Italian ARTE dataset, including patients treated with AB for unresectable HCC between June 2022 and July 2025. MACE occurrence was evaluated using a competing risk regression, considering non-cardiovascular death as a competing event.Results: Among 538 patients (median age 69.8 years), the prevalence of arterial hypertension and obesity was 56.3% and 18.4%, respectively. Moreover 7.6% had chronic coronary artery disease. Median follow-up was 22.4 months (95% CI 21.0-24.2 months) and median overall survival 19.7 months (95% CI 17.1-22.3). Twenty MACE (3.7%) occurred: 8 cerebrovascular accidents, 7 acute coronary syndromes, 3 strokes, and 2 heart failures. The cumulative incidence of MACE was 10.6%, 3.7%, 2.6%, and 0.7% in very high, high, medium and low risk groups according to the ESC score (sHR 3.80, 95% CI 1.52–9.45, p=0.004). Patients with a high-risk CARDIOSOR score also had an increased risk of MACE (sHR 2.70, 95% CI 1.08–6.74, p=0.03). The two scores performed similarly when we analyzed the goodness of fit achieving an Akaike and Bayesian information criteria of 235 and 239 and 241 and 245.Conclusion: These findings suggest that the ESC and CARDIOSOR scores could be used to stratify the risk of MACE in patients receiving AB. These tools might inform clinicians and provide relevant information when evaluating the choice of the first line regimen.

BACKGROUND & AIMS:Hepatocellular Carcinoma (HCC) is a leading cause of death and the large majority of HCC occurs in the setting of cirrhosis. Nevertheless, its impact on the development of decompensation in these patients has not been investigated, yet. Our aim was to investigate the role of HCC in the development of decompensating events in patients with cirrhosis. METHODS:Clinical data of outpatients with cirrhosis from two Italian tertiary centers (Padua and Milan) were collected and followed prospectively from January 2000 to December 2021, until the end of the study, death, or liver transplantation. Demographic, clinical, and laboratory data were collected. The primary outcome was the development of decompensating events after the diagnosis of HCC. HCC and effective etiological treatment were considered as a time-varying covariate for the statistical analysis. RESULTS:Overall, 1,176 patients with cirrhosis of any etiology were enrolled (Padua 876, Milan 300), and 358 (30.4%) developed HCC. In the study cohort (Padua cohort), patients who developed HCC on compensated cirrhosis had a higher risk of developing the first decompensation event (hazard ratio [HR] = 4.05; p <0.001), primarily occurring as ascites (HR = 4.79; p <0.001), hepatic encephalopathy (HR = 3.68; p <0.001), and gastrointestinal bleeding (HR = 2.98; p = 0.004). All these findings were confirmed in the extended cohort (Milan cohort). HCC remained an independent predictor of first decompensation even considering the study period in two eras (2000-2013 and 2014-2021) (HR 3.64, 95% CI 2.10-6.31, 2000-2013; HR 4.95, 95% CI 1.62-15.1, 2014-2021). CONCLUSIONS:The occurrence of HCC is associated with a high risk of first decompensation. Further prospective studies are needed to confirm these results. IMPACT AND IMPLICATIONS:HCC frequently arises in patients with cirrhosis and is associated with poor clinical outcomes, particularly in the presence of decompensating events. Although cirrhosis progresses from a compensated to a decompensated stage characterized by severe complications, the contribution of HCC to this transition remains inadequately understood and underinvestigated. This multicenter study demonstrates that the occurrence of HCC in compensated patients with cirrhosis significantly increases the risk of first decompensation. These results highlight the importance for hepatologists and researchers to include HCC in algorithms aiming to stratify the risk of decompensation in patients with HCC and cirrhosis, thereby enhancing patient management strategies.

Background and aims: Liver transplantation is effective against hepatocellular carcinoma (HCC), but recurrence remains a challenge. Traditional criteria based on tumor size, nodule number, and AFP levels have had limited success in predicting aggressiveness. [18F]FDG PET/CT has shown promise in identifying high-risk tumor features, including microvascular invasion (MVI), which is a key predictor of recurrence. Methods: In this retrospective, single-center study, all consecutive patients who underwent LT for HCC between 2010 and 2019 were included. Prior to listing, the patients underwent [18F]FDG PET/CT, and explant pathology was analyzed for MVI and other histological features. The primary objective was to identify the predictors of early HCC recurrence (within 24 months after LT). Secondary objectives included identifying predictors of high-risk histological features of the explant, describing recurrence patterns, and assessing post-recurrence survival. Results: The study included 143 patients (median age 59 years [IQR 54-64], 85% males, median MELD 10 [IQR 8-14], median AFP value 8.5 [IQR 4-39] ng/mL) and 40 (28%) with intra-hepatic [18F]FDG PET/CT positivity. HCC recurred post-LT in 25 patients (17%) (median post-LT follow-up 49 months [IQR 28.5-77]) and within 24 months in 12 patients (48%). MVI at the explant stage was independently associated with early recurrence (HR: 7.20, 95% CI 1.82-28.45, p = 0.005), while intra-hepatic [18F]FDG PET/CT positivity before LT independently predicted MVI in explants (OR 3.90, 95% CI 1.30-11.71, p = 0.01). Conclusions: [18F]FDG PET/CT may offer a valuable tool for pre-transplant risk assessment by identifying MVI, which is an independent predictor of early cancer recurrence. Its incorporation into the selection criteria for LT may enhance patient stratification and post-transplant outcomes.

Background: Hepatic decompensation is a major complication in patients with advanced hepatocellular carcinoma (aHCC) undergoing Atezolizumab+Bevacizumab (AB). Early identification of high-risk patients is essential to guide management. We aimed to develop a simple score to predict decompensation.Methods: For this study we enrolled 453 consecutive patients with aHCC treated with immunotherapy from 2020 to 2024, derived from the ARTE database. Inclusion criteria were: AB therapy as 1st line; Child-Pugh <A6 cirrhosis without baseline features of decompensation (Baveno-VII). The occurrence of decompensation was recorded, and univariate and multivariate Cox regression analyses were performed to identify predictors. Variables significant in multivariate analysis were used to construct a weighted score based on respective beta coefficient, which was then converted into a simple point-based bedside algorithm. Patients were stratified into low, intermediate, and high-risk groups.Results: In the ARTE database, 74 (16.3%) patients developed hepatic decompensation. Median follow-up was 14 months (IQR 7–22). Neoplastic portal vein thrombosis (HR 1.97, 95% CI 1.20–3.23, p=0.007), elevated bilirubin (HR 2.61, 95% CI 1.52–4.47, p<0.001), and low platelets (HR 1.82, 95% CI 1.07–3.10, p=0.026) were identified as independent predictors of decompensation. These variables were incorporated into the ARTE-score depending on their weighted beta coefficient value. Patients were categorized as low (0–1 points, n=360), intermediate (2 points, n=49), or high risk (3-4 points, n=44). Compared with the low-risk group, intermediate-risk patients had a 1.96-fold higher hazard of decompensation (HR 1.96, 95% CI 1.04–3.71, p = 0.038), while high-risk patients had a 4.28-fold higher hazard (HR 4.28, 95% CI 2.41–7.57, p < 0.001). Kaplan–Meier analysis demonstrated significant separation of decompensation-free survival across risk groups (p<0.001). The ARTE-score showed good discrimination for decompensation (Harrell’s C = 0.7022, Somers’ D = 0.4045). Decompensation-free survival at 12 and 24 months was 87% and 83% for low-risk, 79% and 64% for intermediate-risk, and 57% and 56% for high-risk.Conclusions: The ARTE score is a simple and effective tool to predict hepatic decompensation in aHCC in AB, improving risk stratification and guide clinical decision-making.

BACKGROUND AND AIMS:Unlike other immune-based combinations for hepatocellular carcinoma (HCC), long-term data for atezolizumab-bevacizumab (AB) are lacking, as the IMbrave150 trial closed after a median follow-up of 15.6 months. Consequently, reports of long-term outcomes for AB rely mainly on real-world evidence. We evaluated long-term effectiveness, safety, and clinically relevant on-treatment events in a large prospective real-world cohort of patients treated with AB. APPROACH AND RESULTS:We analyzed 538 patients prospectively enrolled in the Italian ARTE database. Outcomes included overall survival (OS), safety, liver decompensation, rate of patients achieving drug-free disease-free status. On-treatment events were modelled as time-dependent covariates in Cox regression models. After a median follow-up of 24.2 months, median OS was 19.7 months (95% CI 17.2-22.2), with a 36-month survival rate of 30.0%. Independent factors influencing OS included ECOG-PS >0, ALBI grade >1, AFP >400 ng/mL, multinodularity, macrovascular invasion, and on-treatment events (objective response, progression, or liver decompensation). Grade ≥3 AEs occurred in 36.8% of patients; 5 late-onset severe toxicities arose beyond 24 months. Liver decompensation unrelated to tumor progression occurred in 14.1% patients. Eighty patients (14.9%) underwent surgical or locoregional procedures after the initiation of AB; 24 (4.4%) achieved a drug-free disease-free status. CONCLUSIONS:Our data confirmed the sustained effectiveness of AB without new safety concerns. Surgical/locoregional treatments after the start of AB and liver decompensation were common, highlighting the need for a multidisciplinary and integrated approach in advanced HCC.

BACKGROUND AND AIM:Dual immune checkpoint blockade with tremelimumab plus durvalumab (STRIDE) is an established first-line therapy for unresectable hepatocellular carcinoma (uHCC); however, real-world evidence on its safety, toxicity kinetics and liver function dynamics remains limited. We aimed to evaluate the tolerability and on-treatment changes in hepatic function and effectiveness in a multicentre cohort of patients treated with STRIDE in routine practice. METHODS:We conducted a retrospective analysis of prospectively collected data from 115 consecutive patients with uHCC treated with STRIDE across 12 centres in Lombardy, Italy. Clinical, biochemical and radiological variables were recorded at baseline and throughout the therapy. Adverse events were graded per CTCAE v5.0, and Child-Pugh was used to assess hepatic functional evolution. The temporal toxicity patterns were evaluated using smoothed hazard functions. Progression-free survival (PFS), overall survival (OS) and competing-risk cumulative incidences of progression and death were examined. RESULTS:The median follow-up was 8.9 months. More than 80% of the adverse events occurred within the first 2 months, and severe toxicities were infrequent. Child-Pugh deterioration from class A to B occurred in 7.8% of patients from baseline to day 28, increasing to 12.1% by day 56. PFS was 5.7 months; the median OS was not reached, with OS rates of 78.2% at 6 months and 53.3% at 18 months. Progression was the predominant early event, with a cumulative incidence of 49.2% at 6 months. CONCLUSIONS:In routine clinical practice, STRIDE shows reproducible effectiveness and a manageable safety profile, with an early and stabilising incidence of adverse events. Dynamic assessment of liver function shows that hepatic function declines modestly but is still clinically meaningful in affected patients.

Background and aims: Hepatocellular carcinoma (HCC) patients frequently present with comorbidities that limit therapeutic options and increase mortality. This study evaluated the performance of the Charlson Comorbidity Index (CCI) and a modified CCI (mCCI) in stratifying patients with HCC to predict treatment allocation and survival. Methods: A retrospective single-center cohort study analyzed 401 patients with de novo HCC (74% male, median age 68 years, 80% Child-Pugh-Turcotte (CPT) A, 65% viral etiology, 70% Barcelona Clinic Liver Cancer stage (BCLC) 0/A). CCI and mCCI (with points related to HCC and chronic liver disease excluded), were calculated at diagnosis for each patient. The primary endpoint was overall survival (OS) estimated by Kaplan-Meier method and compared across mCCI classes; Cox uni/multivariable models were applied to identify predictors of mortality. The secondary aim was evaluating the association between mCCI and treatment allocation. Results: While CCI classified 94% of patients as "high-risk", mCCI reclassified patients into "high-risk" (21%), "intermediate-risk" (48%), and "low-risk" (31%), demonstrating better stratification whilst maintaining a strong correlation with CCI (Kendall's tau-b = 0.57, p < 0.001). BCLC B patients with "high-risk" mCCI exhibited significantly lower access to first-line curative treatment (14% vs. 47%, p = 0.03). Moreover, "high" or "intermediate-risk" patients according to mCCI experienced significantly shorter OS compared to "low-risk" (median OS 36 vs. 49 vs. 74 months, p < 0.001). "High-risk" and "intermediate-risk" mCCI classes were independent predictors of mortality, alongside alpha-fetoprotein, CPT and BCLC stage. Considering the items composing mCCI, age and cardiovascular diseases were independent predictors of mortality. Conclusions: mCCI provides a more accurate assessment of comorbidities than the standard CCI and is associated with survival, hence it can contribute to designing patient-tailored therapeutic strategies.

Background and aims: Patients with hepatocellular carcinoma (HCC) have a risk of malnutrition and sarcopenia of 65-90% and 39%, both associated with worse survival in early stages. The prevalence and impact of these conditions in patients with unresectable HCC (uHCC) candidates to immune-based therapy (IO) have not been investigated. We aimed to study nutritional status and muscular reserve in uHCC patients starting IO and their impact on overall survival (OS).Methods: Monocentric retrospective study of 106 consecutive patients treated with IO for uHCC. Nutritional scores (Prognostic Nutritional Index-PNI; Systemic Immune-inflammation Index-SII) and sarcopenia were evaluated on blood samples and CT within 1 month prior to IO.Sarcopenia was defined according to EASL-AASLD cut-off (EA cut-off) for Smooth Muscle Index (SMI) at L3 on CT. By ROC analysis and Youden’s Index, a new cut-off was determined for OS prediction.OS according to malnutrition and sarcopenia was assessed by Kaplan-Meier analysis, while predictors of OS by Cox models.Results: Patients were predominantly males (80%), with median age 69 years and BMI 25.3 kg/m2. Most patients had cirrhosis (92%) with preserved liver function (95% ALBI 1-2), varices in 33%. BCLC C HCC in 78%; 79% treated with atezolizumab-bevacizumab and 21% with durvalumab-tremelimumab.Patients “high risk” for malnutrition were 18% according to SII>752 × 10⁹ and 74% to PNI<50.Median SMI was 46.0 (IQR 32.8-54.0) for women, 47.5 (IQR 42.4-55.5) cm/m2 for men. Prevalence of sarcopenia was 63.4% according to EA cut-off and 59% to new cut-off (38.6 for women, 48.8 cm/m2 for men).A lower OS was observed in “high-risk” patients according to SII (6 (IQR 4-15) vs 20 (IQR 10-30) months; p<0.001; Fig.1) and PNI (15 (IQR 6-24) vs 29 (IQR 20-31) months; p=0.01). However, only SII >752 × 10⁹ independently predicted mortality (HR 2.94 (95%CI 1.62-5.37), p<0.001) at multivariable Cox analysis.A trend toward shorter OS was observed in sarcopenic patients, but the difference was not significant [EA cut-off: 14(6–30) vs 21(9–36) months, p=0.52; new cut-off: 14(6–27) vs 21(7–27) months, p=0.09](Fig.2). Notably, survival curves according to new cut-off diverged after 4 months, with no proportional hazards assumption violation (p=0.97), so we performed an exploratory multivariable analysis including sarcopenia (new cut-off) with liver function, sex and BCLC stage. LASSO-selected models with bootstrap validation confirmed stability of the identified predictors, suggesting sarcopenia as an independent predictor of mortality (HR 2.24 (IQR 1.21-4.14), p=0.01), potentially exerting a delayed effect, with male sex and bilirubin.Conclusion: Malnutrition estimated by SII is a predictor of mortality in patients undergoing IO for uHCC. Sarcopenia by our new cut-off shows a potential delayed effect on survival in exploratory analyses.

Background: The incidence of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) is approximately 17%. We aimed to retrospectively compare the outcomes of patients who received systemic treatment with different tyrosine kinase inhibitors (TKIs) for recurrent HCC post-LT.Methods: Patients with recurrent HCC post-LT between 2002 and 2025 were included in a multicenter study involving three liver transplant centers in Northern Italy. The impact of first line sorafenib or lenvatinib treatment for recurrent HCC was evaluated in terms of safety (adverse events, AEs) and effectiveness, using survival analysis and stratifying patients according to significantly different baseline variables.Results: Ninety-seven patients developed HCC recurrence post-LT and received TKIs: sorafenib (SOR-group, n=50) or lenvatinib (LEN-group, n=47). At recurrence, patients treated with sorafenib were younger (median age 56 vs. 65 years, p=0.001). In both groups patients were mainly males (80% vs. 89%, p=0.20) and recurrence was mostly intra- and extra-hepatic (52% vs. 53% p=0.51), with AFP values similar between the two groups (median value 11 µg/L in SOR-group vs. 7 µg/L in LEN-group, p=0.94). No significant differences were observed between groups in terms of proportion of patients receiving surgery or locoregional treatment before TKI (50% vs. 68%; p=0.07) as well as the time between LT and TKI start (median time 23 vs. 29 months p=0.56). During a median follow-up of 13 months of TKI therapy, 69 (71%) patients died [43 (86%) SOR-group and 26 (55%) LEN-group]. Median treatment duration was similar in the two groups (6.5 months in SOR-group vs. 5 months in LEN-group, p=0.45). The most frequently reported grade > 3 AEs in the SOR-treated group were hand-foot syndrome [18 (36%) patients vs. 1 (2%) patient in the LEN group], fatigue [15 (30%) patients vs. 5 (10%) patients], and diarrhea [13 (26%) patients vs. 1 (2%) patient]. In the LEN-treated group, the main grade > 3 AE was proteinuria [6 (12%) patients, vs 0 in the SOR-group]. Overall, patients experiencing at least one grade ≥3 AEs were more frequent in SOR-group compared to LEN-group [31 (62%) vs. 13 (28%), p=0.001)]. Only one patient treated with sorafenib died due to grade-5 AE (GI bleeding). Response to treatment was similar in the two groups, with an overall response rate of 15% in sorafenib and 18% (p=0.67) and a disease control rate of 59% and 57%, (p=0.79) and a similar median overall survival: 17 months [95% confidence interval (CI), 6-32] in SOR-group vs. 18 months (95% CI 11-34) in LEN-group, p=0.71.Conclusions: Our findings suggest that lenvatinib is a safer option as compared to sorafenib for patients with HCC recurrence after LT, granting a comparable survival with a lower risk of severe adverse events.