Host Immune Response in Chronic Hepatitis Delta: Implications for Pathogenesis and Therapy.

Chronic hepatitis delta (CHD) represents the most severe form of viral hepatitis due to rapid disease progression towards liver cancer, leading to high morbidity and mortality. Hepatitis delta virus (HDV) can only infect individuals who are infected with hepatitis B. So far, there is no cure or vaccine for HDV.

Investigating hepatic fibrosis heterogeneity by three-dimensional imaging in metabolic dysfunction-associated steatotic liver disease.

Although liver biopsy is a well-established technique to assess fibrosis it has several limitations, including invasive nature, semi-quantitative assessment methods, significant sampling and observer variability, making precise assessment of hepatic fibrosis challenging. Accurate and reliable modalities are crucial for clinical trials to characterize hepatic fibrosis monitorization effectively. We aimed to perform 3-dimensional imaging of optically transparent liver samples by light-sheet microscopy (LSM) to quantify extracellular matrix (ECM) proteins.

Frequency, Severity and Impact of Pegylated Interferon Alpha-Associated Flares in Hepatitis D Infection.

We analysed the frequency, severity and impact of hepatitis flares in a large Phase 2 study investigating pegylated interferon-alfa-2a (PEG-IFNa) for the treatment of hepatitis D. In the HIDIT-II study, 120 patients were treated for 96 weeks with PEG-IFNa (180 μg weekly) in combination with tenofovir disoproxil fumarate (TDF, 300 mg once daily) or placebo. Hepatitis flares were defined as ALT increases above 10 times the upper limit of normal or increases of more than 2.

Integrative proteo-transcriptomic characterization of advanced fibrosis in chronic liver disease across etiologies.

Chronic hepatic injury and inflammation from various causes can lead to fibrosis and cirrhosis, potentially predisposing to hepatocellular carcinoma. The molecular mechanisms underlying fibrosis and its progression remain incompletely understood. Using a proteo-transcriptomics approach, we analyze liver and plasma samples from 330 individuals, including 40 healthy individuals and 290 patients with histologically characterized fibrosis due to chronic viral infection, alcohol consumption, or metabolic dysfunction-associated steatotic liver disease.

The Course of COVID-19 Infection in Patients With Chronic Hepatitis Delta.

In coronavirus disease 2019 (COVID-19), older age and co-morbidities are associated with mortality. Among liver disease aetiologies alcoholic liver disease was associated with mortality. Chronic hepatitis delta (CHD) had not been studied.

Long-term outcome of hepatitis delta in different regions world-wide: Results of the Hepatitis Delta International Network.

Background And Aims: Chronic hepatitis delta represents a major global health burden. Clinical features of hepatitis D virus (HDV) infection vary largely between different regions worldwide. Treatment approaches are dependent on the approval status of distinct drugs and financial resources.

An updated assessment of hepatitis delta prevalence among adults in Canada: A meta-analysis.

Foreign-born (FB) persons represent a large proportion of adults with chronic hepatitis B (CHB) in Canada due to higher prevalence rates in countries of birth for FB persons. Suboptimal awareness and low rates of hepatitis delta virus (HDV) testing contribute to underdiagnosis and gaps in accurate estimates of Canada HDV prevalence. We aim to provide an assessment of CHB and HDV prevalence in Canada using a comprehensive literature review and meta-analysis.

Hepatitis delta virus infection in Turkey: A meta-analysis of prevalence.

Objectives: Hepatitis delta virus (HDV) infection has been granted orphan disease status by the US Food and Drug Administration and the European Medicines Agency owing to its rarity and relatively limited research and treatment options. Turkey is considered an endemic country for the virus. We aimed to provide a current and updated country- and region-specific HDV infection prevalence.

Atherosclerotic cardiovascular disease risk profile of patients with chronic hepatitis B treated with tenofovir alafenamide or tenofovir disoproxil fumarate for 96 weeks.

Background: Patients with chronic hepatitis B (CHB) who switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) show changes in lipid profiles.

Aim: To evaluate how these changes affect cardiovascular risk.

Methods: This pooled analysis, based on two large prospective studies, evaluated fasting lipid profiles of patients with CHB who were treated with TAF 25 mg/day or TDF 300 mg/day for 96 weeks.

Five-year follow-up of 96 weeks peginterferon plus tenofovir disoproxil fumarate in hepatitis D.

Background & Aims: Until recently, pegylated interferon-alfa-2a (PEG-IFNa) therapy was the only treatment option for patients infected with hepatitis D virus (HDV). Treatment with PEG-IFNa with or without tenofovir disoproxil fumarate (TDF) for 96 weeks resulted in HDV RNA suppression in 44% of patients at the end of therapy but did not prevent short-term relapses within 24 weeks. The virological and clinical long-term effects after prolonged PEG-IFNa-based treatment of hepatitis D are unknown.

PAGE-B incorporating moderate HBV DNA levels predicts risk of HCC among patients entering into HBeAg-positive chronic hepatitis B.

Background & Aims: Recent studies reported that moderate HBV DNA levels are significantly associated with hepatocellular carcinoma (HCC) risk in hepatitis B e antigen (HBeAg)-positive, non-cirrhotic patients with chronic hepatitis B (CHB). We aimed to develop and validate a new risk score to predict HCC development using baseline moderate HBV DNA levels in patients entering into HBeAg-positive CHB from chronic infection.

Methods: This multicenter cohort study recruited 3,585 HBeAg-positive, non-cirrhotic patients who started antiviral treatment with entecavir or tenofovir disoproxil fumarate at phase change into CHB from chronic infection in 23 tertiary university-affiliated hospitals of South Korea (2012-2020).

Quality-of-life scores improve after 96 weeks of PEG-IFNa-2a treatment of hepatitis D: An analysis of the HIDIT-II trial.

Background & Aims: Infection with the hepatitis D virus (HDV) causes the most severe form of viral hepatitis with a high risk to develop clinical complications of liver disease. In addition, hepatitis delta has been shown to be associated with worse patient-reported outcomes. Until recently, only pegylated interferon alfa could be used to treat hepatitis delta.

Emerging drugs for hepatitis D.

Introduction: Chronic hepatitis delta (CHD) is the most severe form of chronic viral hepatitis. Until recently, its treatment consisted of pegylated interferon alfa (pegIFN) use.

Areas Covered: Current and new drugs for treating CHD.

Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries.

Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021.

Management of Biliary Complications in Liver Transplant Recipients with Duct-To-Duct Anastomosis: A Single-Center Experience.

Background: The aims of this study were to investigate biliary complications in liver transplant recipients with choledochocholedocho stomy anastomosis, to identify the risk factors for the development of such complications, and to evaluate the success of endoscopic approaches in liver transplant recipients.

Methods: Between January 2013 and May 2021, a total of 238 patients with liver diseases underwent liver transplantation: 174 recipients undergoing choledochocholedochostomy anastomosis were included in the analysis.

Results: Their median age was 54.

Non-invasive fibrosis markers for assessment of liver fibrosis in chronic hepatitis delta.

Assessment of liver fibrosis by non-invasive means is clinically important. Studies in chronic hepatitis delta (CHD) are scarce. We evaluated the performance of eight serum fibrosis markers [fibrosis-4 score (FIB-4), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), age-platelet index (API), AST-to platelet-ratio-index (APRI), Goteborg University Cirrhosis Index (GUCI), Lok index, cirrhosis discriminant score (CDS) and Hui score] in CHD and chronic hepatitis B (CHB).

Modeling the Interplay between HDV and HBV in Chronic HDV/HBV Patients.

Hepatitis D virus is an infectious subviral agent that can only propagate in people infected with hepatitis B virus. In this study, we modified and further developed a recent model for early hepatitis D virus and hepatitis B virus kinetics to better reproduce hepatitis D virus and hepatitis B virus kinetics measured in infected patients during anti-hepatitis D virus treatment. The analytical solutions were provided to highlight the new features of the modified model.

Treatment endpoints for chronic hepatitis D.

Management of chronic hepatitis D (CHD) has entered a new era. In this new era, the virus entry inhibitor bulevirtide has received conditional approval as a treatment for compensated CHD. Three phase 3 studies with two new compounds are ongoing for the treatment of CHD.

A Rapid Point-of-Care Test for the Serodiagnosis of Hepatitis Delta Virus Infection.

Hepatitis Delta virus (HDV) is a satellite of the Hepatitis B virus (HBV) and causes severe liver disease. The estimated prevalence of 15-20 million infected people worldwide may be underestimated as international diagnostic guidelines are not routinely followed. Possible reasons for this include the limited awareness among healthcare providers, the requirement for costly equipment and specialized training, and a lack of access to reliable tests in regions with poor medical infrastructure.

A phase 2 dose-finding study of lonafarnib and ritonavir with or without interferon alpha for chronic delta hepatitis.

Background And Aims: Proof-of-concept studies demonstrated lonafarnib (LNF), a first-in-class oral prenylation inhibitor, efficacy in patients infected with HDV. The lonafarnib with ritonavir for HDV-2 (LOWR-2) study's aim was to identify optimal combination regimens of LNF + ritonavir (RTV) ± pegylated interferon alpha (PEG-IFNα) with efficacy and tolerability for longer-term dosing. Here we report the safety and efficacy at end of treatment for up to 24 weeks.

The global hepatitis delta virus (HDV) epidemic: what gaps to address in order to mount a public health response?

Background: Co-infection between hepatitis B virus (HBV) and hepatitis delta virus (HDV) causes the severest chronic hepatitis and is associated with a high risk of cirrhosis and hepatocellular carcinoma (HCC). The Global Health Sector Strategy on Viral Hepatitis called for the elimination of hepatitis (- 65% mortality and - 90% incidence) by 2030. Our aims were to summarize key points of knowledge and to identify the gaps that need to be addressed to mount a public health response to HDV.