Neutralizing GDF-15 can overcome anti-PD-1 and anti-PD-L1 resistance in solid tumours.

Cancer immunotherapies with antibodies blocking immune checkpoint molecules are clinically active across multiple cancer entities and have markedly improved cancer treatment. Yet, response rates are still limited, and tumour progression commonly occurs. Soluble and cell-bound factors in the tumour microenvironment negatively affect cancer immunity.

Challenges in Liver Transplantation for Hepatocellular Carcinoma: A Review of Current Controversies.

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.

Histological predictors of aggressive recurrence of hepatocellular carcinoma after liver resection.

Background & Aims: Assessment of recurrence risk after liver resection (LR) is critical in hepatocellular carcinoma (HCC), particularly with the advent of effective adjuvant therapy. The aim of this study was to analyze the clinical and pathological factors associated with recurrence, aggressive recurrence, and survival after LR.

Method: We performed a retrospective study in which all single HCC (BCLC-0/A) patients treated with LR between February 2000 and November 2020 were included.

Evaluation of Overall Survival by Restricted Mean Survival Time of Advanced Biliary Tract Cancer treated with Immunotherapy: A Systematic Review and Meta-Analysis.

Background: For biliary tract cancer (BTC), the addition of immunotherapy (durvalumab or pembrolizumab) to gemcitabine and cisplatin (GemCis) significantly improved overall survival (OS) in phase 3 clinical trials (RCTs). However, the interpretation and magnitude of the treatment effect is challenging because OS Kaplan-Meier curves violate the proportional hazards (PH) assumption. Analysis using restricted mean survival time (RMST) allows quantification of the benefits in the absence of PH.

Induction of the Inflammasome Pathway by Tyrosine Kinase Inhibitors Provides an Actionable Therapeutic Target for Hepatocellular Carcinoma.

During the last decade, tyrosine kinase inhibitors (TKIs) sorafenib and regorafenib have been standard systemic treatments for advanced hepatocellular carcinoma (HCC). Previous data associated sorafenib with inflammasome activation. However, the role of the inflammasome in sorafenib and regorafenib signaling has not been described in liver cancer patients.

Systemic therapies in hepatocellular carcinoma: A revolution?

The evolution in systemic therapies in hepatocellular carcinoma (HCC) signifies a strategy of high-cost, high-gain innovation that originated with sorafenib, despite its limited impact on tumor response. This strategic approach paved the way for the emergence of a second wave of the short-lived competitive advantage, exemplified by the incorporation of atezolizumab plus bevacizumab and tremelimumab plus durvalumab. In the context of safety concerns within the liver cancer domain, the IMBRAVE150 and HIMALAYA trials boldly incorporated bevacizumab and tremelimumab, respectively, demonstrating the continuation of the high-risk, high-reward innovation paradigm.

Risk of Treatment Failure and Death after Ablation in Hepatocellular Carcinoma Patients-A Multiparametric Prediction.

Background: Ablation is a first-line treatment for Barcelona Clinic Liver Cancer (BCLC)-0/A hepatocellular carcinoma (HCC). However, there are scarce data about patients' outcomes after recurrence. The present study evaluates the impact of patient and tumor characteristics at baseline and at recurrence on the Clinical Decision-Making process.

International Liver Cancer Association (ILCA) white paper on hepatocellular carcinoma risk stratification and surveillance.

Major research efforts in liver cancer have been devoted to increasing the efficacy and effectiveness of surveillance for hepatocellular carcinoma (HCC). As with other cancers, surveillance programmes aim to detect tumours at an early stage, facilitate curative-intent treatment, and reduce cancer-related mortality. HCC surveillance is supported by a large randomised-controlled trial in patients with chronic HBV infection and several cohort studies in cirrhosis; however, effectiveness in clinical practice is limited by several barriers, including inadequate risk stratification, underuse of surveillance, and suboptimal accuracy of screening tests.

Outcome of patients with HCC and liver dysfunction under immunotherapy: a systematic review and meta-analysis.

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.

Polymorphism AGT2 (rs4762) is involved in the development of dermatologic events: Proof-of-concept in hepatocellular carcinoma patients treated with sorafenib.

Background: Dermatologic adverse events (DAEs) are associated with a better outcome in patients with hepatocellular carcinoma (HCC) irrespective of the therapeutic agent received. The exact mechanisms associated with the development of DAEs are unknown although several studies point to direct toxicity of tyrosine kinase inhibitors (TKIs) to the skin or an immune-mediated reaction triggered by the oncologic treatment. As is the case in other conditions, individual genetic variants may partially explain a higher risk of DAEs.

Outcome of liver cancer patients with SARS-CoV-2 infection: An International, Multicentre, Cohort Study.

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.

Polyethylene Glycol Drug-Eluting Embolic Microspheres Loaded with Doxorubicin for the Treatment of Hepatocellular Carcinoma: Feasibility, Safety, and Pharmacokinetic Study.

Purpose: Polyethylene glycol drug-eluting microspheres (PEG-DEMs) can be loaded to elute doxorubicin. The current study evaluated the pharmacokinetic profile and safety of PEG-DEMs in the treatment of patients with hepatocellular carcinoma (HCC).

Materials And Methods: The current prospective, multicenter, dose-escalation study enrolled 25 patients (68% men) with early or intermediate stage HCC and a performance status of 0.

Beneficial Effects of Silybin Treatment After Viral Eradication in Patients With HCV-Related Advanced Chronic Liver Disease: A Pilot Study.

HCV eradication by direct-acting antivirals (DAAs) improves liver outcomes and reduces overall liver mortality. However, patients with advanced chronic liver disease (ACLD) may experience a progression of liver disease despite viral clearance. Silybin has shown hepatoprotective effects in experimental models, but clinical data are limited.

Liver cancer risk after HCV cure in patients with advanced liver disease without non-characterized nodules.

Background & Aims: Recognition of non-characterized liver nodules (NCLN) prior to direct-acting antivirals (DAAs) is associated with increased hepatocellular carcinoma (HCC) risk in patients with HCV. The risk of HCC has not been defined in F3/F4 patients in whom NCLN have been ruled-out before starting DAAs and at sustained virological response (SVR). This study aimed to estimate HCC incidence in this population.

Current pharmacological treatment of hepatocellular carcinoma.

The landscape of hepatocellular carcinoma (HCC) has changed since the incorporation of sorafenib in 2007 as the first pharmacological treatment for HCC. The combination of atezolizumab plus bevacizumab is currently the first-line treatment for HCC patients, and there are several second-line options approved for patients who had received sorafenib as the first-line treatment. The advantage of having multiple options of pharmacological treatment for HCC patients is associated to the need to redefine the clinical decision-making approach and considering new endpoints for the clinical trials design.

Regorafenib Efficacy After Sorafenib in Patients With Recurrent Hepatocellular Carcinoma After Liver Transplantation: A Retrospective Study.

Safety of regorafenib in hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) has been recently demonstrated. We aimed to assess the survival benefit of regorafenib compared with best supportive care (BSC) in LT patients after sorafenib discontinuation. This observational multicenter retrospective study included LT patients with HCC recurrence who discontinued first-line sorafenib.

Early diarrhoea under sorafenib as a marker to consider the early migration to second-line drugs.

Background: Despite atezolizumab and bevacizumab (A + B) is currently the first-line treatment for hepatocellular carcinoma (HCC) patients, some patients will not be adequate for this combination. In the setting of sorafenib some adverse events have been proposed as prognostic factors.

Objective: To characterize the early diarrhoea development as prognostic factor in 344 HCC patients.

Incidence of Hepatocellular Carcinoma in Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review, Meta-analysis, and Meta-regression.

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) may be a risk factor for hepatocellular carcinoma (HCC), but the extent of this association still needs to be addressed. Pooled incidence rates of HCC across the disease spectrum of NAFLD have never been estimated by meta-analysis.

Methods: In this systematic review, we searched Web of Science, Embase, PubMed, and the Cochrane Library from January 1, 1950 through July 30, 2020.

Mutational profile of skin lesions in hepatocellular carcinoma patients under tyrosine kinase inhibition: a repercussion of a wide-spectrum activity.

Background/aim: Dermatological adverse events (DAE) in hepatocellular carcinoma (HCC) patients treated with sorafenib predicts better outcome. Some turn into skin lesions (SL) requiring pathology examination. We describe incidence, characteristics and molecular profile of SL in HCC patients treated with sorafenib.

Assessing the impact of COVID-19 on liver cancer management (CERO-19).

Background & Aims: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic.

Methods: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project.

Activated Lymphocytes and Increased Risk of Dermatologic Adverse Events during Sorafenib Therapy for Hepatocellular Carcinoma.

Advanced hepatocellular carcinoma patients treated with sorafenib who develop early dermatologic adverse events (eDAEs) have a better prognosis. This may be linked to immune mechanisms, and thus, it is relevant to assess the association between peripheral immunity and the probability of developing eDAEs. Peripheral blood mononuclear cells of 52 HCC patients treated with sorafenib were analyzed at baseline and throughout the first eight weeks of therapy.

Pharmacokinetics and pharmacogenetics of sorafenib in patients with hepatocellular carcinoma: Implications for combination trials.

Background & Aims: Sorafenib and lenvatinib are the first-line treatments approved in hepatocellular carcinoma (HCC), but information is lacking about the relationships between their pharmacokinetics, patients pharmacogenetic profiles, adverse events (AE) and overall survival. We aimed to elucidate these relationships of tyrosine Kinase Inhibitors, such as sorafenib, in order to improve the design of trials testing it in combination with checkpoint inhibitors.

Methods: We assessed the pharmacokinetics of sorafenib and its N-oxide metabolite at day-0, day-7, day-30, day-60, day-90, day-120, day-150 and day-180 and nine single-nucleotide polymorphisms (SNP) in five genes related to sorafenib metabolism/transport to identify the best point for starting the combination between tyrosine kinases and checkpoint inhibitors.