Summary: Background: The positive results of the REFLECT trial in terms of survival (sorafenib vs lenvatinib) offer a new first‐line option for hepatocellular carcinoma. Additionally, the expected results of immunotherapy could change the first‐line treatment in hepatocellular carcinoma or the clinical trial design in first and second‐line.Aims: To evaluate the impact of dermatologic adverse events under sorafenib in hepatocellular carcinoma patients as a clinical marker to predict prognosis and critically evaluate outcomes within trials.Methods: A systematic search of original articles published until October 2018 was performed using PubMed/MEDLINE and a meta‐analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement.Results: A total of 393 studies were identified and 13 articles with 2035 patients (79.5% Child‐Pugh‐A, 73.2% BCLC‐C) were selected for qualitative and quantitative analysis. The main type of dermatologic adverse events was hand‐foot skin reaction (47.7%) but other dermatologic adverse events were reported in 31.7% of the cases. Presence of dermatologic adverse events was associated with a lower mortality when compared with those patients without them (pooled Hazard Ratio for the univariate analysis 0.45 (95% CI: 0.38‐0.53) and there was no heterogeneity for the analysis (P = 0.511; I² = 0.0%). Refuting this association would require the future report of 1370 negative studies.Conclusions: This meta‐analysis shows a clinically meaningful association between dermatologic adverse events and a higher probability of longer survival. These data support the use of dermatologic adverse events in the clinical decision‐making when informing the prognosis and when systemic treatment is decided.

Background and Aims: Immunotherapy-based regimes have changed the management of HCC. However, evidence of efficacy in patients with impaired liver function is unknown. This systematic review and meta-analysis assesses survival of HCC patients and liver dysfunction treated with immunotherapy-based regimens. Methods: Systematic review and meta-analysis of original articles or abstracts reporting survival of HCC patients treated with immunotherapy according to liver function between 2017 and 2022. Overal survival (OS) according to restricted mean survival time (RMST) and median OS, and hazard ratio (HR) of Child-Pugh B or B/C versus Child-Pugh A were assessed while considering the line of treatment. Results: Of the 2218 articles considered, 15 articles recruiting 2311 patients were included. Of these, 639 (27.7%) were Child-Pugh B and 34 (1.5%) C. RMST was 8.36 (95% CI, 6.15–10.57; I ²=93%) months, estimated from 8 studies. The HR was reported in 8 studies for survival between Child-Pugh B versus Child-Pugh A and metanalysis disclosed a 1.65 HR (95% CI,1.45–1.84; I ²=0% heterogeneity; p = 0.45). Treatment line data were available for 47% of the patients and 3 studies included patients treated with atezolizumab-bevacizumab in the first line. Conclusions: The high heterogeneity across studies reflects the incapacity of the current evidence to support the indication of immunotherapy in HCC patients with relevant liver dysfunction. It is mandatory to report complementary information to Child-Pugh classification such as prior liver decompensation, use of concomitant medication to control ascites, or signs of clinically significant portal hypertension to allow better patient stratification in future studies.

Liver transplantation (LT) remains one of the most effective treatments for hepatocellular carcinoma (HCC) and significantly enhances patient survival. However, the application of LT for HCC faces challenges owing to advancements in cancer-specific treatment modalities and the increased burden of patients’ comorbidities. This narrative review explores current controversies and advancements in LT for HCC. Key areas of focus include the management of comorbidities and patient education by advanced practice nurses, impacts of frailty on waitlists and post-LT outcomes, selection criteria for LT in the era of new downstaging tools, role of radiology in patient selection, and implications of potential immunotherapy use both before and after LT. Additionally, the importance of immunosuppression management with strategies aimed at minimizing rejection while considering the risk of HCC recurrence and the role of surveillance for HCC recurrence is highlighted. This review also underscores the importance of a multidisciplinary approach for optimizing outcomes in patients with HCC undergoing LT.

Background & Aims: Information about the impact of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in patients with liver cancer is lacking. This study characterizes the outcomes and mortality risk in this population. Methods: Multicentre retrospective, cross‐sectional, international study of liver cancer patients with SARS‐CoV‐2 infection registered between February and December 2020. Clinical data at SARS‐CoV‐2 diagnosis and outcomes were registered. Results: Two hundred fifty patients from 38 centres were included, 218 with hepatocellular carcinoma (HCC) and 32 with intrahepatic cholangiocarcinoma (iCCA). The median age was 66.5 and 64.5 years, and 84.9% and 21.9% had cirrhosis in the HCC and iCCA cohorts respectively. Patients had advanced cancer stage at SARS‐CoV‐2 diagnosis in 39.0% of the HCC and 71.9% of the iCCA patients. After a median follow‐up of 7.20 (IQR: 1.84–11.24) months, 100 (40%) patients have died, 48% of the deaths were SARS‐CoV‐2‐related. Forty (18.4%) HCC patients died within 30‐days. The death rate increase was significantly different according to the BCLC stage (6.10% [95% CI 2.24–12.74], 11.76% [95% CI 4.73–22.30], 20.69% [95% CI 11.35–31.96] and 34.52% [95% CI 17.03–52.78] for BCLC 0/A, B, C and D, respectively; p = .0017). The hazard ratio was 1.45 (95% CI 0.49–4.31; p = .5032) in BCLC‐B versus 0/A, and 3.13 (95% CI 1.29–7.62; p = .0118) in BCLC‐C versus 0/A in the competing risk Cox regression model. Nineteen out of 32 iCCA (59.4%) died, and 12 deaths were related to SARS‐CoV‐2 infection. Conclusions: This is the largest cohort of liver cancer patients infected with SARS‐CoV‐2. It characterizes the 30‐day mortality risk of SARS‐CoV‐2 infected patients with HCC during this period.