Suboptimal outcomes of sorafenib as a second-line treatment after atezolizumab-bevacizumab for unresectable hepatocellular carcinoma.

Background: 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.

Easy recognition and high autoimmune hepatitis specificity of smooth muscle antibodies giving an actin microfilament immunofluorescent pattern on embryonal vascular smooth muscle cells.

Smooth muscle antibodies (SMA) with anti-microfilament actin (MF-SMA) specificity are regarded as highly specific markers of type 1 autoimmune hepatitis (AIH-1) but their recognition relying on immunofluorescence of vessel, glomeruli, and tubules (SMA-VGT pattern) in rodent kidney tissue, is restricted by operator-dependent interpretation. A gold standard method for their identification is not available. We assessed and compared the diagnostic accuracy for AIH-1 of an embryonal aorta vascular smooth muscle (VSM) cell line-based assay with those of the rodent tissue-based assay for the detection of MF-SMA pattern in AIH-1 patients and controls.

From an understanding of etiopathogenesis to novel therapies-what is new in the treatment of celiac disease?

Celiac disease, a chronic autoimmune disorder caused by genetic factors and exposure to gluten, is increasingly being recognized and diagnosed in both children and adults. Scientists have been searching for a cure for this disease for many years, but despite the impressive development of knowledge in this field, a gluten-free diet remains the only recommended therapy for all patients. At the same time, the increasing diagnosis of celiac disease in adults, which was considered a childhood disease in the 20th century, has opened a discussion on the etiopathology of the disease, which is proven to be very complex and involves genetic, immunological, nutritional, environmental and gut microbiota-related factors.

Prediction of cardiovascular risk in patients with hepatocellular carcinoma receiving anti-angiogenic drugs: lessons from sorafenib.

Antiangiogenics are associated with an increased risk of major adverse cardiac and cerebrovascular events (MACE). The identification of at-risk subjects is relevant in the case of hepatocellular carcinoma (HCC), for which anti-angiogenic TKIs and bevacizumab are used in first and subsequent lines of therapy, to select alternative drugs for patients with excessive risk. We verified the ability to predict MACE in sorafenib-treated patients of the 2022 European Society of Cardiology (ESC-2022) score for anti-angiogenics and the recently proposed CARDIOSOR score.

Impact of Sarcopenia on the Survival of Patients with Hepatocellular Carcinoma Treated with Sorafenib.

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.

Sorafenib and Metronomic Capecitabine in Child-Pugh B patients with advanced HCC: A real-life comparison with best supportive care.

Background And Aims: The efficacy of systemic therapy for unresectable advanced hepatocellular carcinoma (aHCC) has not been proven in patients with Child-Pugh (C-P) B cirrhosis. Nevertheless, in real-world these patients are treated both with tyrosine kinase inhibitors (TKIs) and with metronomic capecitabine (MC). This study aimed to compare sorafenib and MC outcomes versus best supportive care (BSC) in C-P B patients.

Autoimmune Polyendocrine Syndromes in Adult Italian Celiac Disease Patients.

Celiac disease (CD) is frequently associated with other autoimmune disorders. Different studies have explored the association between CD and single autoimmune endocrine disease (AED), especially autoimmune thyroiditis (AIT) and type-1 diabetes mellitus (T1DM). Data about CD as a component of autoimmune polyendocrine syndrome (APS) are scant.

Genetic, Immunological, Dietary, Gut Microbiota, and Environmental Determinants of Osteoporosis in the Course of Celiac Disease: Which Factor Plays the First Violin in This Orchestra?

Celiac disease (CD) is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The worldwide prevalence of CD is estimated to be 0.7-1.

Second-Line Chemotherapy for Intrahepatic Cholangiocarcinomas: What Is the Real Gain?

Background: The presence of actionable alterations in advanced biliary tract cancer patients opened new therapeutic possibilities for second-line treatments. However, for around 60% of the patients, chemotherapy remains the only therapeutic option. The aim of our study was to evaluate outcomes and prognostic parameters in patients with intrahepatic cholangiocarcinomas treated with second-line chemotherapy.

Bone Metastases from Intrahepatic Cholangiocarcinoma Confer Worse Prognosis.

Background: Metastatic intrahepatic cholangiocarcinoma still has a dismal prognosis. The aim of our study was to investigate the prognostic role of bone metastases in patients affected by intrahepatic cholangiocarcinoma.

Methods: A total of 186 metastatic intrahepatic cholangiocarcinoma patients were retrospectively reviewed.

Prognostic Impact of Metastatic Site in Patients Receiving First-Line Sorafenib Therapy for Advanced Hepatocellular Carcinoma.

Extrahepatic spread is a well-known negative prognostic factor in patients with advanced hepatocellular carcinoma (HCC). The prognostic role of different metastatic sites and their response rate to systemic treatment is still being debated. We considered 237 metastatic HCC patients treated with sorafenib as first-line therapy in five different Italian centers from 2010 to 2020.

TKIs in combination with immunotherapy for hepatocellular carcinoma.

Introduction: The treatment landscape of hepatocellular carcinoma (HCC) has significantly changed over the last 5 years with multiple options in the frontline, second line, and beyond. Tyrosine kinase inhibitors (TKIs) were the first approved systemic treatments for the advanced stage of HCC; however, thanks to the increasing knowledge and characterization of the immunological features of the tumor microenvironment, the systemic treatment of HCC has been further expanded with the immune checkpoint inhibitor (ICI) approach and the following evidence of the higher efficacy obtained with combined treatment with atezolizumab plus bevacizumab over sorafenib.

Areas Covered: In this review, we look at rationale, efficacy, and safety profiles of current and emerging ICI/TKI combination treatments and discuss the available results from other clinical trials using similar combinatorial therapeutic approaches.

COVID-19: Has the Liver Been Spared?

The liver is a secondary and often collateral target of COVID-19 disease but can lead to important consequences. COVID-19 might directly cause a high number of complications in patients with pre-existing chronic liver disease, increasing their risk of hepatic decompensation. Moreover, it also determines indirect consequences in the management of patients with liver disease, especially in those suffering from decompensated cirrhosis and HCC, as well as in the execution of their follow-up and the availability of all therapeutic possibilities.

Role of Etiology in Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Counterfactual Event-Based Mediation Analysis.

Background: Whether the etiology of underlying liver disease represents a prognostic factor in patients with hepatocellular carcinoma (HCC) treated with lenvatinib is still a matter of debate. This study investigates whether the viral etiology of HCC plays a prognostic role in overall survival (OS). Methods: Data derived from a multicenter series of 313 HCC patients treated with lenvatinib between 2019 and 2022 were analyzed.

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.

Outcomes of Sorafenib for Recurrent Hepatocellular Carcinoma After Liver Transplantation in the Era of Combined and Sequential Treatments.

Background: Sorafenib and other tyrosine kinase inhibitors are the current standard of care for hepatocellular carcinoma (HCC) recurring after liver transplantation (LT). Sorafenib is sometimes regarded as a scarcely effective treatment in this setting because of some studies showing a short overall survival (OS) indirectly compared with historical series of nontransplanted patients. Additional data from multicenter prospective studies are needed before drawing definite conclusions.

The Feasibility of Liver Biopsy for Undefined Nodules in Patients under Surveillance for Hepatocellular Carcinoma: Is Biopsy Really a Useful Tool?

: The aim of the present study is to determine the feasibility of biopsy for atypical liver nodules in patients under surveillance for hepatocellular carcinoma (HCC), assessing which factors influence the decision to perform it. : A total of 128 atypical liver nodules in 108 patients under surveillance for HCC, who underwent CT between September 2018 and September 2019, were included. All the images were saved digitally (on CD-ROM) and the two most representative images in the arterial and delayed phases were selected for each lesion and inserted into a digital atlas (on PDF).

Potential feasibility of atezolizumab-bevacizumab therapy in patients with hepatocellular carcinoma treated with tyrosine-kinase inhibitors.

Background: The combination of atezolizumab-bevacizumab has been proven to be superior to sorafenib for the treatment of unresectable hepatocellular carcinoma not amenable to locoregional treatments, becoming the standard of care of systemic therapy.

Aim: This study aimed at assessing real-world feasibility of atezolizumab-bevacizumab in patients treated with tyrosine-kinase inhibitors.

Methods: Among 1447 patients treated with tyrosine-kinase inhibitors from January 2010 to December 2020, we assessed the percentage of those potentially eligible to atezolizumab-bevacizumab (according to IMbrave-150 trial criteria), and the overall survival of eligible and non-eligible patients.

Hepatic Steatosis in Patients with Celiac Disease: The Role of Packaged Gluten-Free Foods.

Background: An increased risk of nonalcoholic fatty liver disease (NAFLD) in patients with celiac disease (CD) adhering to a gluten-free diet (GFD) was recently reported. The nutritional composition of packaged gluten-free foods (PGFF) has been proposed as a possible cause. This hypothesis has not been investigated further, since a systematic structural nutritional interview for all patients would be problematic in clinical practice.

Very Low Alcohol Consumption Is Associated with Lower Prevalence of Cirrhosis and Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease.

The role of moderate alcohol consumption in the evolution of NAFLD is still debated. The aim of this study is to evaluate the impact of current and lifelong alcohol consumption in patients with NAFLD. From 2015 to 2020, we enrolled 276 consecutive patients fulfilling criteria of NAFLD (alcohol consumption up to 140 g/week for women and 210 g/week for men).

Segmental Distribution of Hepatocellular Carcinoma in Cirrhotic Livers.

Background: To evaluate the segmental distribution of hepatocellular carcinoma (HCC) according to Couinaud’s anatomical division in cirrhotic patients. Methods: Between 2020 and 2021, a total of 322 HCC nodules were diagnosed in 217 cirrhotic patients who underwent computed tomography (CT) or magnetic resonance imaging (MRI) for the evaluation of suspicious nodules (>1 cm) detected during ultrasound surveillance. For each patient, the segmental position of the HCC nodule was recorded according to Couinaud’s description.