From MASH to HCC: the role of Gas6/TAM receptors.

Metabolic dysfunction-associated steatohepatitis (MASH) is the replacement term for what used to be called nonalcoholic steatohepatitis (NASH). It is characterized by inflammation and injury of the liver in the presence of cardiometabolic risk factors and may eventually result in the development of hepatocellular carcinoma (HCC), the most common form of primary liver cancer. Several pathogenic mechanisms are involved in the transition from MASH to HCC, encompassing metabolic injury, inflammation, immune dysregulation and fibrosis.

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.

Identification of the Best Cut-Off Value of PIVKA-II for the Surveillance of Patients at Risk of Hepatocellular Carcinoma Development.

Patients with cirrhosis are at risk of hepatocellular carcinoma (HCC) development and, according to current guidelines, should undergo surveillance by ultrasound at six month intervals. Due to the known limitations of surveillance strategies based on ultrasonography, the use of tumor biomarkers, although debated, is common practice in many centers. The aim of the study was to identify the best cut-off value for one of such biomarkers, protein induced by vitamin K absence, or antagonist-II (PIVKA-II).

17β-Oestradiol Protects from Hepatitis C Virus Infection through Induction of Type I Interferon.

Background And Aims: Sex hormones are widely recognised to act as protective factors against several viral infections. Specifically, females infected by the hepatitis C virus display higher clearance rates and reduced disease progression than those found in males. Through modulation of particle release and spread, 17β-oestradiol controls HCV's life cycle.

HSD17B13 and other liver fat-modulating genes predict development of hepatocellular carcinoma among HCV-positive cirrhotics with and without viral clearance after DAA treatment.

Background: Genetic predisposition to accumulate liver fat (expressed by a polygenic risk score, GRS, based on the number of at-risk alleles of PNPLA3, TM6SF2, MBOAT7 and GCKR) may influence the probability of developing hepatocellular carcinoma (HCC) after hepatitis C treatment. Whether this holds true taking into account carriage of the HSD17B13:TA splice variant, also affecting lipogenesis, and achievement of viral clearance (SVR), is unknown.

Methods: PNPLA3, TM6SF2, MBOAT7, GCKR and HSD17B13 variants were determined in a cohort of 328 cirrhotic patients free of HCC before starting treatment with direct acting antivirals (DAA).

Radioembolization vs sorafenib in locally advanced hepatocellular carcinoma with portal vein tumor thrombosis: A propensity score and Bayesian analysis.

Objective: In this study we aimed to compare patient outcomes between the use of transarterial radioembolization (TARE) and sorafenib in patients with hepatocellular carcinoma (HCC) and intrahepatic portal vein tumor thrombosis (PVTT).

Methods: A total of 65 patients with HCC and intrahepatic PVTT treated in five Italian hospitals between 2012 and 2018 were included in the analysis. Those with any previous treatment, extension of PVTT to the main portal tract and extrahepatic involvement were excluded.

Periostin Circulating Levels and Genetic Variants in Patients with Non-Alcoholic Fatty Liver Disease.

Circulating periostin has been suggested as a possible biomarker in non-alcoholic fatty liver disease (NAFLD) in Asian studies. In the present study, we aimed to test its still controversial relevance in a Caucasian population. In patients with histologically-proven NAFLD (N.

Interplay of and Variants in Modulating the Risk of Hepatocellular Carcinoma among Hepatitis C Patients.

A single-nucleotide polymorphism causing a C to G change in the gene (rs738409) is associated with disease severity and development of hepatocellular carcinoma (HCC) in nonalcoholic fatty liver disease; the insertion variant rs72613567:TA of the 17-hydroxysteroid dehydrogenase type 13 () mitigates this detrimental effect. Our aim was to evaluate if the same holds true in chronic hepatitis C virus infection (HCV). With a case control retrospective study design, we selected 110 patients who developed HCC on a background of HCV infection, matching each patient for sex and age (±30 months) to three HCV-infected, non-HCC patients.

Liver Stiffness, Not Fat Liver Content, Predicts the Length of QTc Interval in Patients with Chronic Liver Disease.

The severity of fatty liver at ultrasound has been associated with QT length, a finding invoked to explain the excess cardiovascular risk of patients with fatty liver. However, the ability of ultrasound to stage accurately the severity of fatty liver is limited, with fibrosis a major confounder. Here, we aimed to verify the alleged relationship between fat liver content and QT length using a technique apt at discriminating steatosis from fibrosis noninvasively, i.

Stereotactic Body Radiation Therapy as an Alternative Treatment for Patients with Hepatocellular Carcinoma Compared to Sorafenib: A Propensity Score Analysis.

Background And Aims: Stereotactic body radiation therapy (SBRT) has emerged as a safe and effective treatment for patients with hepatocellular carcinoma (HCC), but its role in patients with advanced HCC is not yet defined. In this study, we aim to assess the efficacy and safety of SBRT in comparison to sorafenib treatment in patients with advanced HCC.

Methods: We included 901 patients treated with sorafenib at six tertiary centers in Europe and Asia and 122 patients treated with SBRT from 13 centers in Germany and Switzerland.

Gas6/TAM Signaling Components as Novel Biomarkers of Liver Fibrosis.

Liver fibrosis consists in the accumulation of extracellular matrix components mainly derived from activated hepatic stellate cells. This is commonly the result of chronic liver injury repair and represents an important health concern. As liver biopsy is burdened with many drawbacks, not surprisingly there is great interest to find new reliable noninvasive methods.

Red Cell Distribution Width and Platelet Count as Biomarkers of Pulmonary Arterial Hypertension in Patients with Connective Tissue Disorders.

Introduction/objective: In the present paper, we aimed to test the value of the red cell distribution width (RDW) coefficient of variation as a candidate biomarker for pulmonary arterial hypertension (PAH) in patients with connective tissue disorders (CTD), correlating it with the degree of cardiopulmonary impairment in these patients.

Methods: The study population included = 141 patients with CTD and = 59 patients affected by pulmonary hypertension of other etiologies, all referred to the Pulmonary Hypertension Clinic of the Cardiology Division of an Academic Hospital in Northern Italy for evaluation (including right catheterization). Clinical, instrumental, and laboratory data were collected and related to RDW and other full blood count indexes.

Identification of mutations in circulating cell-free tumour DNA as a biomarker in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is increasing globally. Prognostic biomarkers are urgently needed to guide treatment and reduce mortality. Tumour-derived circulating cell-free DNA (ctDNA) is a novel, minimally invasive means of determining genetic alterations in cancer.

Improvement of insulin sensitivity in diabetic and non diabetic patients with chronic hepatitis C treated with direct antiviral agents.

Background: The increased incidence of type 2 diabetes mellitus among hepatitis C virus (HCV) infected patients is likely due to viral-induced insulin resistance (IR). Indeed, control of diabetes in these patients benefits of successful antiviral treatment; whether the same applies to subtler alterations of glucose metabolism is unknown. We aimed to fill this gap.

B2-Lymphocyte responses to oxidative stress-derived antigens contribute to the evolution of nonalcoholic fatty liver disease (NAFLD).

Recent evidence implicates adaptive immunity as a key player in the mechanisms supporting hepatic inflammation during the progression of nonalcoholic fatty liver disease (NAFLD). In these settings, patients with NAFLD often show an increase in the circulating levels of antibodies against oxidative stress-derived epitopes (OSE). Nonetheless, the actual role of humoral immunity in NAFLD is still unclear.

Treatment Stage Migration Maximizes Survival Outcomes in Patients with Hepatocellular Carcinoma Treated with Sorafenib: An Observational Study.

Background: Level I evidence supports the use of sorafenib in patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma, where heterogeneity in efficacy exists due to varying clinicopathologic features of the disease.

Aim: We evaluated whether prior treatment with curative or locoregional therapies influences sorafenib-specific survival.

Methods: From a prospective data set of 785 consecutive patients from international specialist centres, 264 patients (34%) were treatment naïve (TN) and 521 (66%) were pre-treated (PT), most frequently with transarterial chemoembolization ( = 413; 79%).

Cardiac dysfunction as an early predictor of portal hypertension in chronic hepatitis C.

Background: Cirrhotic cardiomyopathy is characterized by a set of cardiovascular modifications observed in advanced chronic liver disease. The aim of this study was to investigate cardiovascular alterations in chronic liver disease with different stages of fibrosis and to correlate cardiac involvement with endoscopic complications of portal hypertension.

Methods: Seventy patients with chronic hepatitis C-related chronic liver disease and 20 sex- and age-matched controls underwent clinical evaluation, hepatic transient elastography, and echocardiography.

Integration of the cancer-related inflammatory response as a stratifying biomarker of survival in hepatocellular carcinoma treated with sorafenib.

Background And Aims: Response to sorafenib is highly variable in hepatocellular carcinoma (HCC). Baseline inflammatory parameters and treatment toxicities may improve survival prediction in patients on sorafenib therapy.

Results: 442 patients with advanced stage HCC on sorafenib were recruited (follow-up 5096 person-months at risk).

17,β-estradiol inhibits hepatitis C virus mainly by interference with the release phase of its life cycle.

Background & Aims: Oestrogen and oestrogen-mediated signalling protect from hepatitis C virus through incompletely understood mechanisms. We aimed to ascertain which phase(s) of hepatitis C virus life cycle is/are affected by oestrogens.

Methods: Huh7 cells infected with the JFH1 virus (genotype 2a) were exposed to dehydroepiandrosterone, testosterone, progesterone and 17β-estradiol (tested with/without its receptor antagonist fulvestrant).

The ALBI grade provides objective hepatic reserve estimation across each BCLC stage of hepatocellular carcinoma.

Background & Aims: Overall survival (OS) is a composite clinical endpoint in hepatocellular carcinoma (HCC) due to the mutual influence of cirrhosis and active malignancy in dictating patient's mortality. The ALBI grade is a recently described index of liver dysfunction in hepatocellular carcinoma, based solely on albumin and bilirubin levels. Whilst accurate, this score lacks cross-validation, especially in intermediate stage HCC, where OS is highly heterogeneous.

[Therapeutic decisions and treatment with sorafenib in hepatocellular carcinoma: final analysis of GIDEON study in Italy].

Introduction: Sorafenib, an oral multikinase inhibitor, is the only targeted agent approved for the treatment of patients with hepatocellular carcinoma (HCC) after demonstration to increase overall survival compared to placebo in two randomized phase III study. GIDEON (Global Investigation of therapeutic DEcisions in HCC and Of its treatment with sorafeNib) is the largest, global, non-interventional, prospective study of patients with uHCC (n>3200) treated with sorafenib in real-life clinical practice conditions. Here we report the final analysis of safety and efficacy in the Italian cohort of patients.

Evaluation of the red cell distribution width as a biomarker of early mortality in hepatocellular carcinoma.

Background: The red cell distribution width is a biomarker of early mortality across various disease states.

Aim: To verify whether it may refine estimates of survival in hepatocellular carcinoma.

Methods: The red cell distribution width measured at diagnosis was analyzed in relationship to mortality by any cause both in a retrospective training cohort (N=208), and in an independent prospectively collected validation cohort (N=106) of patients with hepatocellular carcinoma.

Fibrosis progression in HCV carriers with mild hepatitis who possess the high-repetition variant of the DRD4 gene, a genetic marker for binge-drinking and risk-seeking behavior: a longitudinal study.

Background: Alcohol is a major determinant of the outcome of chronic hepatitis C virus (HCV) infection, but self-reported drinking habits lack reliability. We hypothesized that carriage of high-repetition variants (HRV) of the variable number of tandem repeats (VNTR) in exon III of the dopamine receptor D4 gene, linked to binge-drinking and risk-seeking behavior, might be a proxy measure of alcohol consumption, and aimed to verify whether it may affect histologic outcome.

Methods: A cohort of HCV patients with normal or near-normal aminotransferases (N = 128) underwent a liver biopsy as part of diagnostic work-up.