Most patients receiving atezolizumab-bevacizumab (AB) for hepatocellular carcinoma will eventually experience disease progression. Randomized clinical trials (RCTs) are undergoing to identify second-line treatments. Where RCTs are unavailable or patients are non-eligible, sorafenib is often prescribed based on approval and reimbursement policies. However, evidence supporting this approach is minimal. To assess the efficacy and safety of sorafenib in patients who permanently discontinued AB. The ARTE database prospectively collects patients treated with AB in a real-life setting. We analysed the outcome of patients who received sorafenib as second-line treatment. Amongst 213 patients, 130 (61.0 %) permanently discontinued AB. Of them, 54 received second- line treatments, and sorafenib was prescribed in 40 patients. The disease control rate (DCR) was 10.0 %. The median progression-free (PFS) and overall survival were 3.3 (95 % confidence interval [CI] 2.7-3.9) and 6.9 months (95 % CI 2.7-11.1), respectively. In patients progressing under AB, the efficacy of sorafenib on different outcomes is limited.

Background and aims: Sarcopenia has been associated with poor outcomes in patients with cirrhosis and hepatocellular carcinoma. We investigated the impact of sarcopenia on survival in patients with advanced hepatocellular carcinoma treated with Sorafenib. Methods: A total of 328 patients were retrospectively analyzed. All patients had an abdominal CT scan within 8 weeks prior to the start of treatment. Two cohorts of patients were analyzed: the “Training Group” (215 patients) and the “Validation Group” (113 patients). Sarcopenia was defined by reduced skeletal muscle index, calculated from an L3 section CT image. Results: Sarcopenia was present in 48% of the training group and 50% of the validation group. At multivariate analysis, sarcopenia (HR: 1.47, p = 0.026 in training; HR 1.99, p = 0.033 in validation) and MELD > 9 (HR: 1.37, p = 0.037 in training; HR 1.78, p = 0.035 in validation) emerged as independent prognostic factors in both groups. We assembled a prognostic indicator named “SARCO-MELD” based on the two independent prognostic factors, creating three groups: group 1 (0 prognostic factors), group 2 (1 factor) and group 3 (2 factors), the latter with significantly worse survival and shorter time receiving treatment.

Background: The Barcelona Clinic Liver Cancer staging system considers, among patients with HCC, “ideal candidates” (ICs) for hepatic resection (HR) those with a single lesion, normal bilirubin, and without clinically significant portal hypertension (CSPH). We compared the outcome of HR between ICs and non-ICs. Methods: Retrospective analysis was conducted on Child–Pugh A patients. CSPH was defined by the presence of gastroesophageal varices and/or platelet count <100,000/mm³. Hyperbilirubinemia was accepted up to 2 mg/dL. The selected 1057 patients were distributed in 3 calendar periods (2000–2022). Results: In all calendar periods, non-ICs were more prevalent than ICs. Among non-ICs, the proportion of patients with isolated CSPH did not change over time (from 22.6% to 30.3%; p=0.359), while patients with multinodular HCC (mHCC) increased (from 35.5% to 50.2%; p=0.042). Patients with hyperbilirubinemia decreased (from 20.4% to 10.1%; p=0.036), likewise those with hyperbilirubinemia+CSPH (from 21.5% to 9.4%; p=0.005). Over a median follow-up of 41.0 months, median overall survival was higher in ICs compared to non-ICs (104.9 vs. 75.3 months; p<0.001). However, compared to ICs, median overall survival did not differ in patients with isolated CSPH (93.1 mo; p=0.432) or isolated hyperbilirubinemia (86.0 mo; p=0.356), while it was lower in those with hyperbilirubinemia+CSPH (60.0 mo; p<0.001) or mHCC (61.9 mo; p<0.001). Compared to ICs, only hyperbilirubinemia+CSPH patients showed a higher perioperative mortality. Conclusions: In real-world practice, among resected patients, the proportion of non-ICs has remained constantly higher than that of non-ICs since 2000. HR can be offered to Child–Pugh A patients with CSPH or modest hyperbilirubinemia without compromising its outcome. For patients with 2 of these features or mHCC, which generate a poorer prognosis, studies comparing HR versus non-surgical therapies are warranted.

Background: Transarterial chemoembolisation (TACE) and radioembolisation (TARE) can lead to the deterioration of liver function, especially in cases of a high tumour burden, potentially lessening the benefits of subsequent systemic treatments. We aimed to verify whether a high number of previous transarterial treatments modified the outcomes of patients who received sorafenib as a frontline systemic treatment. Methods: A retrospective analysis of a large multicenter dataset containing prospectively collected data of sorafenib-treated patients was conducted. Results: Data from 696 patients were analysed, with 139 patients having received >two transarterial procedures before starting sorafenib. A propensity score matched 139 identified pairs of patients. Having received >two locoregional treatments was independently associated with a shorter survival (hazard ratio 1.325, 95% confidence interval 1.018–1.725, p = 0.039). This pattern was confirmed amongst responders to sorafenib, but not in progressors. A trend toward a higher rate of the permanent discontinuation of sorafenib due to liver failure (18.7 vs. 10.8%, p = 0.089) and a lower rate of eligibility for second-line treatments (24.5 vs. 17.3%, p = 0.184) was observed in patients who had received >two transarterial procedures. Conclusions: Repeated endovascular treatments negatively impacted the survival of HCC patients, especially sorafenib-responders. An early switch to systemic therapies should be considered in cases that are unlikely to respond.