Diagnosed Patients With Chronic Hepatitis B and Delta Virus in Italy in 2024: An Estimation From a National Real-World Database.

Background And Aims: Hepatitis B (HBV) and Hepatitis Delta virus (HDV) infection have undergone significant changes in Italy over the past few decades, but reliable and updated prevalence of chronic hepatitis B (CHB) and Delta (CHD) data are lacking. The aim of the study was to describe the epidemiology of CHB and CHD in Italy in 2024, based on real-world data.

Methods: The number of patients with a healthcare expenditure exemption for CHB (016.

Hepatitis B Immunoglobulins Withdrawal in Hepatitis B Virus Mono-Infected Liver Transplant Recipients: An Italian Multicentre Prospective Study.

Background & Aims: Despite recommendations from scientific societies that hepatitis B immunoglobulin (HBIG) can be safely discontinued, centres across Europe continue to use the combination nucleoside analogues (NAs) plus HBIG for long-term prophylaxis against hepatitis B virus (HBV) recurrence after liver transplant (LT). The aim of this study was to evaluate the safety of HBIG withdrawal in a cohort of LT recipients on long-term HBIG+NAs.

Methods: All patients under third-generation NAs + HBIG and who adhered to the INSIGHT-B protocol were followed up after HBIG withdrawal, in a multicentre, prospective, Italian cohort study, to evaluate the risk of HBV reactivation.

Long-term effectiveness, safety, and liver stiffness dynamics of PBC treatment with obeticholic acid in real-world.

Background & Aims: Several studies have assessed the short-term effectiveness and safety of obeticholic acid (OCA) in the real-world setting. We aimed to extend knowledge on the real-world effectiveness and safety of OCA treatment by expanding sample size and follow-up, and by exploring changes in liver stiffness measurement (LSM) over time.

Methods: The RECAPITULATE project involves centres belonging to the "Italian PBC registry" and/or the "Club Epatologi Ospedalieri" PBC working group.

Rapid whole-blood immune profiling reveals heterogeneous HBV-specific T cell response patterns independent of clinical disease phases.

Background & Aims: There is an unmet need for immunological biomarkers in chronic HBV infection (CHB), where patient management relies on virological and biochemical markers despite the crucial role of virus-specific T cells in controlling viral replication and disease progression. Here, we developed the HBV-cytokine release assay (HBV-CRA), a rapid, point-of-care test, to define whether HBV-specific T cell functional patterns are linked with conventional disease phase classifications.

Methods: Peptides covering pan-genotype HBV proteomes were utilized to trigger cytokine release by HBV-specific T cells in whole blood.

Hepatitis D Virus Infection: Pathophysiology, Epidemiology and Treatment. Report From the Third Delta Cure Meeting 2024.

Chronic infection with hepatitis delta virus (HDV) leads to rapid progression of liver disease, cirrhosis and complications such as end-stage liver disease and hepatocellular carcinoma. In recent years, understanding of the HDV life cycle has increased significantly; however, much remains unknown about the pathogenesis, host-virus interactions and the role of the immune system in HDV persistence and control. Challenges remain in the diagnosis of HDV, not only because of the lack of standardised assays, but also because of limited access and availability in resource-limited countries.

Dynamics of HBV biomarkers during nucleos(t)ide analog treatment: A 14-year study.

Background: Circulating HBsAg, HBV RNA, and hepatitis B core-related antigen (HBcrAg) are potential biomarkers for the response to nucleos(t)ide analog (NA) treatment discontinuation in patients with chronic hepatitis B (CHB). We retrospectively investigated the long-term kinetics of HBsAg, HBV RNA, and HBcrAg in HBeAg-negative patients treated with NA for up to 14 years in a prospective cohort study.

Methods: Ninety-six patients (mean age 65 y, 77% male, 52% with cirrhosis, all HBV genotype D) who were undergoing first (n=33, group A) or second-line (n=63, group B) treatment with tenofovir disoproxil fumarate were included.

HBsAg Isoforms as Innovative Biomarkers in Predicting Virological Response to Bulevirtide in Patients With Chronic Hepatitis D.

Background And Aims: HDV exploits HBV surface-protein (HBsAg) for entering into hepatocytes. HBsAg consists of 3 isoforms: Large- (L-HBs, predominantly present in virions and mediating binding to NTCP-receptor), Middle- (M-HBs) and Small-HBsAg (S-HBs). Here, we investigated the kinetics of HBs isoforms under bulevirtide treatment (BLV).

Comparing methods for plasma HDV RNA quantification in bulevirtide-treated and untreated patients with HDV.

Background & Aims: Accurate HDV RNA quantification is crucial for diagnosis and management of chronic hepatitis delta (CHD), yet a significant variability between assays exists. We compared three methods to quantify HDV RNA levels in untreated and bulevirtide (BLV)-treated patients with CHD.

Methods: Frozen plasma from untreated and BLV-treated patients with CHD were tested in a single-center retrospective study using three different assays: Robogene 2.

Real-world effectiveness and safety of bulevirtide monotherapy for up to 96 weeks in patients with HDV-related cirrhosis.

Background & Aims: Bulevirtide (BLV) 2 mg/day is EMA approved for the treatment of compensated chronic HDV infection; however, real-world data in large cohorts of patients with cirrhosis are lacking.

Methods: Consecutive HDV-infected patients with cirrhosis starting BLV 2 mg/day from September 2019 were included in a European retrospective multicenter real-world study (SAVE-D). Patient characteristics before and during BLV treatment were collected.

Noninvasive Assessment of Portal Hypertension in Patients With Primary Biliary Cholangitis Is Affected by Severity of Cholestasis.

Background & Aims: Noninvasive tests (NITs) for ruling-out clinical significant portal hypertension (CSPH) and high-risk varices (HRVs) in patients with primary biliary cholangitis (PBC) and compensated advanced chronic liver disease (cACLD) are lacking. We evaluated NITs in these patients and the influence of cholestasis on their performance.

Methods: Consecutive patients from the "Italian PBC registry" and 2 United Kingdom large-volume PBC referral centers with upper endoscopy within 6 months from biochemical evaluation and transient elastography were included.

Differential HBV RNA and HBcrAg patterns in untreated patients with chronic hepatitis delta.

Background & Aims: Serum HBV RNA and hepatitis B core-related antigen (HBcrAg) levels have been proposed as useful biomarkers in the management of patients with HBV; however, their role in chronic hepatitis delta (CHD) is currently unknown.

Methods: Consecutive untreated patients with CHD were enrolled in a cross-sectional study in three EU centers. Clinical and virological characteristics were collected.

HBcrAg values may predict virological and immunological responses to pegIFN-α in NUC-suppressed HBeAg-negative chronic hepatitis B.

Objective: Selected populations of patients with chronic hepatitis B (CHB) may benefit from a combined use of pegylated interferon-alpha (pegIFN-α) and nucleos(t)ides (NUCs). The aim of our study was to assess the immunomodulatory effect of pegIFN-α on T and natural killer (NK) cell responses in NUC-suppressed patients to identify cellular and/or serological parameters to predict better T cell-restoring effect and better control of infection in response to pegIFN-α for a tailored application of IFN-α add-on.

Design: 53 HBeAg-negative NUC-treated patients with CHB were randomised at a 1:1 ratio to receive pegIFN-α-2a for 48 weeks, or to continue NUC therapy and then followed up for at least 6 months maintaining NUCs.

Sodium taurocholate cotransporting polypeptide (NTCP) polymorphisms may influence HDV RNA load and early response to bulevirtide.

Background & Aims: Genetic polymorphisms in the sodium taurocholate cotransporting peptide (NTCP encoded by SLC10A1) have been described, but their role in untreated and treated patients with chronic hepatitis delta (CHD) remains unknown. Virological response (VR) to the NTCP inhibitor bulevirtide (BLV) was achieved at week 48 by >70% of patients with CHD, but nearly 15% experienced virological non-response (VNR) or partial response (PR). This study aimed to evaluate whether NTCP genetic polymorphisms affect baseline HDV RNA load and response to BLV in patients with CHD.

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.

Safety and efficacy of off-label bulevirtide monotherapy in patients with HDV with decompensated Child-B cirrhosis-A real-world case series.

Background And Aims: Chronic hepatitis D is the most debilitating form of viral hepatitis frequently progressing to cirrhosis and subsequent decompensation. However, the HDV entry inhibitor bulevirtide is only approved for antiviral treatment of patients with compensated disease. We aimed for the analysis of real-world data on the off-label use of bulevirtide in the setting of decompensated liver cirrhosis.

Real-world effectiveness of voxilaprevir/velpatasvir/sofosbuvir in patients following DAA failure.

Background & Aims: Voxilaprevir/velpatasvir/sofosbuvir (VOX/VEL/SOF) is highly effective for re-treatment of direct-acting antiviral (DAA)-experienced patients with chronic HCV infection. In the present study, predictors of virologic treatment response were analyzed in an integrative analysis of three large real-world cohorts.

Methods: Consecutive patients re-treated with VOX/VEL/SOF after DAA failure were enrolled between 2016 and 2021 in Austria, Belgium, Germany, Italy, Spain and Switzerland.

Modelling HDV kinetics under the entry inhibitor bulevirtide suggests the existence of two HDV-infected cell populations.

Background & Aims: Bulevirtide (BLV) was approved for the treatment of compensated chronic hepatitis D virus (HDV) infection in Europe in 2020. However, research into the effects of the entry inhibitor BLV on HDV-host dynamics is in its infancy.

Methods: Eighteen patients with HDV under nucleos(t)ide analogue treatment for hepatitis B, with compensated cirrhosis and clinically significant portal hypertension, received BLV 2 mg/day.

Quantification of serum HDV RNA by Robogene 2.0 in HDV patients is significantly influenced by the extraction methods.

Background And Aim: Management of chronic hepatitis delta (CHD) requires reliable tests for HDV RNA quantification. The aim of the study was to compare two extraction methods for the quantification of HDV RNA in untreated and bulevirtide (BLV)-treated CHD patients.

Methods: Frozen sera from untreated and BLV-treated CHD patients were tested in a single-centre study for HDV RNA levels (Robogene 2.

Liver stiffness measurement as a noninvasive method for the diagnosis of liver cirrhosis in patients with chronic hepatitis D virus infection.

Background: Noninvasive tests (NITs) have been proposed as an alternative to liver biopsy for diagnosing liver cirrhosis. The evidence of NIT performance in patients with chronic hepatitis D (CHD) is limited.

Aims: To evaluate the diagnostic performance of liver stiffness measurement (LSM) and other NITs in CHD patients.

Quantification of circulating HBV RNA expressed from intrahepatic cccDNA in untreated and NUC treated patients with chronic hepatitis B.

Objective: A convenient, reproducible biomarker of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) transcriptional activity is lacking. We measured circulating HBV RNA (cirB-RNA) in untreated and nucleos(t)ide analogues (NUC) treated chronic hepatitis B (CHB) patients to define its correlation with intrahepatic viral markers and HBV core-related antigen (HBcrAg).

Design: Paired liver biopsy and serum samples were collected from 122 untreated and 30 NUC-treated CHB patients.

Hepatitis D virus infection: Pathophysiology, epidemiology and treatment. Report from the first international delta cure meeting 2022.

Chronic infection with hepatitis delta virus (HDV) affects between 12-20 million people worldwide and represents the most severe form of viral hepatitis, leading to accelerated liver disease progression, cirrhosis and its complications, such as end-stage-liver disease and hepatocellular carcinoma. From the discovery of HDV in 1977 by Prof. Mario Rizzetto, knowledge on the HDV life cycle and mechanisms of viral spread has expanded.