Atezolizumab plus bevacizumab as first-line treatment of unresectable hepatocellular carcinoma: interim analysis results from the phase IIIb AMETHISTA trial.

Background: The treatment of advanced hepatocellular carcinoma (HCC) with atezolizumab and bevacizumab led to significant improvements in overall survival (OS), progression-free survival (PFS), and response rate compared with sorafenib in the phase III IMbrave150 trial. The etiology of background liver disease can differ between Eastern and Western populations, leading to a potentially different impact of systemic therapies; therefore the unequal representation must be considered in the IMbrave150 trial. To provide further data on the safety and effectiveness of atezolizumab and bevacizumab, the phase IIIb AMETHISTA (Atezolizumab plus bevacizumab in METastatic HCC Italian Safety TriAl) ran in a Western (Italian) population of patients with advanced HCC.

Absence of Viral Replication Is Associated With Improved Outcome in Anti-HCV-Positive Patients With Hepatocellular Carcinoma.

Background And Aims: Presence of active hepatitis C virus (HCV) infection may influence the outcome of patients treated for hepatocellular carcinoma (HCC), although this issue has never been adequately assessed in a large series of patients. The aim of this study was to evaluate whether the presence of active HCV affects the survival of patients treated for HCC.

Methods: This study assessed the outcome of 3123 anti-HCV-positive patients with HCC, subdivided according to the presence of active HCV infection or previous sustained virological response (SVR).

"Pleiotropic" Effects of Antibiotics: New Modulators in Human Diseases.

Antibiotics, widely used medications that have significantly increased life expectancy, possess a broad range of effects beyond their primary antibacterial activity. While some are recognized as adverse events, others have demonstrated unexpected benefits. These adjunctive effects, which have been defined as "pleiotropic" in the case of other pharmacological classes, include immunomodulatory properties and the modulation of the microbiota.

Endothelial Dysfunction and Liver Cirrhosis: Unraveling of a Complex Relationship.

Endothelial dysfunction (ED) is the in the background of multiple metabolic diseases and a key process in liver disease progression and cirrhosis decompensation. ED affects liver sinusoidal endothelial cells (LSECs) in response to different damaging agents, causing their progressive dedifferentiation, unavoidably associated with an increase in intrahepatic resistance that leads to portal hypertension and hyperdynamic circulation with increased cardiac output and low peripheral artery resistance. These changes are driven by a continuous interplay between different hepatic cell types, invariably leading to increased reactive oxygen species (ROS) formation, increased release of pro-inflammatory cytokines and chemokines, and reduced nitric oxide (NO) bioavailability, with a subsequent loss of proper vascular tone regulation and fibrosis development.

International consensus statement on microbiome testing in clinical practice.

There is growing interest in the potential exploitation of the gut microbiome as a diagnostic tool in medicine, but evidence supporting its clinical usefulness is scarce. An increasing number of commercial providers offer direct-to-consumer microbiome diagnostic tests without any consensus on their regulation or any proven value in clinical practice, which could result in considerable waste of individual and health-care resources and potential drawbacks in the clinical management of patients. We convened an international multidisciplinary expert panel to standardise best practices of microbiome testing for clinical implementation, including recommendations on general principles and minimum requirements for their provision, indications, pre-testing protocols, method of analyses, reporting of results, and potential clinical value.

Perioperative administration of albumin in adult patients undergoing liver transplantation: A systematic review.

Hypoalbuminemia is a risk factor for mortality in patients with end-stage liver disease (ESLD) and in those undergoing orthotopic liver transplantation (OLT), since it represents a biomarker of post-operative delayed functional recovery of the graft. Despite albumin infusion during and after OLT is frequently adopted in recipients with hypoalbuminemia, it remains unclear whether this procedure could improve post OLT clinical outcomes. Observational studies indicated that treatment with albumin after OLT might be beneficial in reducing ascites and acute kidney injury (AKI) development.

Gut microbiome and metabolic dysfunction-associated steatotic liver disease: Pathogenic role and potential for therapeutics.

Gut microbiota plays key functions in the human body, and its alteration is associated with several human disorders. Moreover, its manipulation is being investigated as a potential therapeutic strategy. In this narrative review we will dissect the involvement of the gut microbiota and of the gut-liver axis on metabolic dysfunction-associated steatotic liver disease (MASLD).

Promising PD-1 antagonists for liver cancer: an evaluation of phase II and III results.

Introduction: Hepatocellular carcinoma (HCC), the most common primary liver cancer, is a major cause of cancer-related morbidity and mortality. Limited treatment options for advanced stages highlight the need for effective therapies.

Areas Covered: This review explores immune checkpoint inhibitors (ICIs), specifically PD-1, PD-L1, and CTLA-4 inhibitors, as emerging treatments for advanced HCC.

Hepatocellular-Carcinoma-Derived Organoids: Innovation in Cancer Research.

Hepatocellular carcinomas (HCCs) are highly heterogeneous malignancies. They are characterized by a peculiar tumor microenvironment and dense vascularization. The importance of signaling between immune cells, endothelial cells, and tumor cells leads to the difficult recapitulation of a reliable in vitro HCC model using the conventional two-dimensional cell cultures.

Anaphylaxis after SonoVue: A Case Report and a Literature Review.

SonoVue (Bracco, Milan, Italy) is a drug used in ultrasonography for the purpose of increasing the echogenicity of blood or fluids by improving the signal-to-noise ratio. : We described a case of anaphylaxis due to SonoVue and performed a literature review. : We reported a case of anaphylaxis secondary to the administration of SonoVue and described all the 13 literature cases.

Link between persistent, unexplained gamma-glutamyltransferase elevation and porto-sinusoidal vascular disorder.

Background & Aims: Porto-sinusoidal vascular disorder (PSVD) is a group of vascular disorders characterized by lesions involving portal venules and sinusoids, irrespective of the presence of portal hypertension. Liver biopsy is essential for diagnosis. In a single-center study, we demonstrated high rates of PSVD in patients with persistently elevated gamma-glutamyltransferase (GGT).

Role of Gut Microbial Metabolites in the Pathogenesis of Primary Liver Cancers.

Hepatobiliary malignancies, which include hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are the sixth most common cancers and the third leading cause of cancer-related death worldwide. Hepatic carcinogenesis is highly stimulated by chronic inflammation, defined as fibrosis deposition, and an aberrant imbalance between liver necrosis and nodular regeneration. In this context, the gut-liver axis and gut microbiota have demonstrated a critical role in the pathogenesis of HCC, as dysbiosis and altered intestinal permeability promote bacterial translocation, leading to chronic liver inflammation and tumorigenesis through several pathways.

Lynch Syndrome and Thyroid Nodules: A Single Center Experience.

Background: Lynch syndrome (LS) is a genetic disease with increased risk of colorectal cancer and other malignancies. There are few reported cases of thyroid cancer in LS patients. The aim of this study is to investigate the presence of thyroid nodules in LS patients and to explore their association with the genetic features of the disease.

A holistic evaluation of patients with chronic Hepatitis D virus (HDV) infection enrolled in the Italian PITER-B and delta cohort.

Background And Aims: We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility.

Methods: This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model.

Mitochondria-Derived Vesicles, Sterile Inflammation, and Pyroptosis in Liver Cancer: Partners in Crime or Innocent Bystanders?

Alterations in cellular signaling, chronic inflammation, and tissue remodeling contribute to hepatocellular carcinoma (HCC) development. The release of damage-associated molecular patterns (DAMPs) upon tissue injury and the ensuing sterile inflammation have also been attributed a role in HCC pathogenesis. Cargoes of extracellular vesicles (EVs) and/or EVs themselves have been listed among circulating DAMPs but only partially investigated in HCC.

Vaccine Responses in Patients with Liver Cirrhosis: From the Immune System to the Gut Microbiota.

Vaccines prevent a significant number of deaths annually. However, certain populations do not respond adequately to vaccination due to impaired immune systems. Cirrhosis, a condition marked by a profound disruption of immunity, impairs the normal immunization process.

Management of Portal Hypertension in Patients with Hepatocellular Carcinoma on Systemic Treatment: Current Evidence and Future Perspectives.

The management of CSPH in patients undergoing systemic treatment for HCC has emerged as a critical concern due to the absence of reliable diagnostic criteria and uncertainties surrounding therapeutic approaches. This review aims to underscore the primary pathophysiological aspects linking HCC and PH, while also addressing the current and emerging clinical strategies for the management of portal hypertension. A review of studies from January 2003 to June 2023 was conducted using the PubMed database and employing MeSH terms, such as "hepatocellular carcinoma", "immune checkpoint inhibitors", "systemic therapy", "portal hypertension", "variceal bleeding" and "tyrosine kinase inhibitors".

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.

Gut Microbiota in Primary Sclerosing Cholangitis: From Prognostic Role to Therapeutic Implications.

Background: Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease of unknown etiology characterized by biliary inflammation and periductal fibrosis. The gut microbiota plays a crucial role in the pathogenesis of PSC by regulating bile acid metabolism, inflammation, and immune response. On the other hand, liver disease progression affects the composition of the gut microbiota, fostering these mechanisms in a mutual detrimental way.

Hug sign in intraprocedural cone-beam-CT to predict short-term response to combined treatment of hepatocellular carcinoma.

Objectives: Combined treatment of ablation and chemoembolization for hepatocellular carcinoma represents a promising therapy to increase treatment efficacy and improve patient survival. The "hug sign" is a recently introduced radiological sign consisting in deposition of beads/contrast agent during transarterial chemoembolization in the hyperemic area surrounding the post-ablation volume, seen during intraprocedural unenhanced cone-beam CT, that may indicate intraprocedural success. Aim of our retrospective study was to analyze the usefulness of the "hug sign" at the intraprocedural unenhanced cone-beam CT as an early predictor of response to combined treatment, based on the hug sign angle.

Effect of Low-Dose Alcohol Consumption on Chronic Liver Disease.

Although alcohol is one of the most important etiologic agents in the development of chronic liver disease worldwide, also recognized as a promoter of carcinogenesis, several studies have shown a beneficial effect of moderate consumption in terms of reduced cardiovascular morbidity and mortality. Whether this benefit is also present in patients with liver disease due to other causes (viral, metabolic, and others) is still debated. Although there is no clear evidence emerging from guidelines and scientific literature, total abstention from drinking is usually prescribed in clinical practice.

Trends in liver transplantation for primary sclerosing cholangitis.

Background: Primary sclerosing cholangitis is a cholestatic disease with a low prevalence in Italy. Indications for liver transplantation and the time of listing are not stated.

Aim: We performed a national survey to investigate the listing criteria, comorbidities, and outcomes.

Peculiarity of Autoimmune Hepatitis Triggered by SARS-CoV-2 Infection.

Introduction: Recently, medical interest has been growing in SARS-CoV-2 infection and its multiorgan involvement, including the liver. Up until now, a few reports have described autoimmune hepatitis (AIH) triggered by SARS-CoV-2 infection, but no data are available about the specific liver inflammatory infiltrate and cluster of differentiation. We report a case of AIH triggered by SARS-CoV-2 infection, with a particular focus on its histological and mainly immunohistochemical features.