Chronic Delta Research Articles

SAT352 - Integrated safety analysis of 24-week data from three phase 2 and one phase 3 clinical trials of bulevirtide monotherapy given at 2 mg and 10 mg dose level for treatment of chronic hepatitis delta

SAT352 - Integrated safety analysis of 24-week data from three phase 2 and one phase 3 clinical trials of bulevirtide monotherapy given at 2 mg and 10 mg dose level for treatment of chronic hepatitis delta

THU340 - Increased lymphocyte trafficking and myeloid activation in patients with chronic hepatitis delta

THU340 - Increased lymphocyte trafficking and myeloid activation in patients with chronic hepatitis delta

THU194 - Fate of HDV-specific CD8+ T cells during bulevirtide monotherapy in patients with chronic hepatitis delta

THU194 - Fate of HDV-specific CD8+ T cells during bulevirtide monotherapy in patients with chronic hepatitis delta

OS149 - Treatment with bulevirtide improves patient-reported outcomes in patients with chronic hepatitis delta: An exploratory analysis of a Phase 3 trial at 48 weeks

OS149 - Treatment with bulevirtide improves patient-reported outcomes in patients with chronic hepatitis delta: An exploratory analysis of a Phase 3 trial at 48 weeks

SAT379 - Bulevirtide 2 mg/day monotherapy in patients with chronic hepatitis delta with or without cirrhosis: a multicenter european cohort real-life study

SAT379 - Bulevirtide 2 mg/day monotherapy in patients with chronic hepatitis delta with or without cirrhosis: a multicenter european cohort real-life study

THU405 - Chronic hepatitis delta with normal ALT and hepatitis D viremia

THU405 - Chronic hepatitis delta with normal ALT and hepatitis D viremia

SAT351 - Integrated efficacy analysis of 24-week data from two phase 2 and one phase 3 clinical trials of bulevirtide monotherapy given at 2 mg or 10 mg dose level for treatment of chronic hepatitis delta

SAT351 - Integrated efficacy analysis of 24-week data from two phase 2 and one phase 3 clinical trials of bulevirtide monotherapy given at 2 mg or 10 mg dose level for treatment of chronic hepatitis delta

GS006 - Efficacy and safety of bulevirtide monotherapy given at 2 mg or 10 mg dose level once daily for treatment of chronic hepatitis delta: week 48 primary end point results from a phase 3 randomized, multicenter, parallel design study

GS006 - Efficacy and safety of bulevirtide monotherapy given at 2 mg or 10 mg dose level once daily for treatment of chronic hepatitis delta: week 48 primary end point results from a phase 3 randomized, multicenter, parallel design study

THU411 - Clinical features predictive of cirrhosis in a large cohort of patients with chronic hepatitis delta infection- Insights from the D-LIVR trial

THU411 - Clinical features predictive of cirrhosis in a large cohort of patients with chronic hepatitis delta infection- Insights from the D-LIVR trial

Recent breakthroughs in the treatment of chronic hepatitis Delta.

Hepatitis Delta virus (HDV) is responsible for the most aggressive form of chronic hepatitis, which may evolve towards cirrhosis, hepatocellular carcinoma and death within few years. During the last 30 years the only available therapy was interferon or peg-IFN, which was characterized by poor tolerability and modest results. The detailed knowledge of the HDV replication cycle and its interaction with HBV allowed the introduction of new drugs which are currently in phase II or III of experimentation. Basically, bulevirtide, to date the only one approved by EMA, inhibits the entry of the virus into the hepatocytes and hence its intrahepatic spread; lonafarnib inhibits the pharnesylation process of the L-HDAg, which is critical for the assembly of the HDV virion; the nucleic acid polymers (NAPs) mainly block the production/release of HBsAg. The available clinical trials with these compounds showed an excellent anti-viral activity against HDV.

Signature of chronic hepatitis B virus infection in nails and hair

BackgroundHepatitis B virus (HBV) is detected in extrahepatic tissues of individuals with HBV infection. Whether nails and hair contain HBV has been unknown.MethodsWe examined two patient groups: those with chronic HBV infection alone (n = 71), and those with both chronic HBV and hepatitis delta virus (HDV) infections (n = 15). HBV DNA in the patients’ fingernails and hair were measured by real-time PCR. Hepatitis B surface antigen (HBsAg) of fingernails was evaluated by an enzyme immunoassay. HDV RNA in fingernails was measured by real-time PCR. Immunochemical staining was performed on nails. We used chimeric mice with humanized livers to evaluate the infectivity of nails.ResultsOf the 71 pairs of HBV-alone nail and hair samples, 70 (99%) nail and 60 (85%) hair samples were positive for β-actin DNA. Of those 70 nail samples, 65 (93%) were HBV DNA-positive. Of the 60 hair samples, 49 (82%) were HBV DNA-positive. The serum HBV DNA level of the nail HBV DNA-positive patients was significantly higher than that of the nail HBV DNA-negative patients (p < 0.001). The hair HBV DNA-positive patients’ serum HBV DNA level was significantly higher compared to the hair HBV DNA-negative patients (p < 0.001). The nail HBV DNA level was significantly higher than the hair HBV DNA level (p < 0.001). The nails and hair HBV DNA levels were correlated (r = 0.325, p < 0.05). A phylogenetic tree analysis of the complete genome sequence of HBV isolated from nails and hair identified the infection source. Of the 64 nail samples, 38 (59%) were HBsAg-positive. All 15 pairs of chronic HBV/HDV infection nail and hair samples were β-actin DNA-positive. However, nail HBV DNA was detected in two patients (13%). None of the 15 patients were positive for hair HBV DNA. Nail HDV RNA was detected in three patients (20%). Of the 15 patients, eight (53%) were nail HBsAg-positive. HBsAg and hepatitis delta (HD) antigen were detected in the nails by immunochemical staining. Chimeric mice were not infected with PBS containing HBsAg and HBV DNA elucidated from nails.ConclusionsNails and hair were the reservoir of HBV DNA. Moreover, nails can contain HBsAg, HDV RNA, and HD antigen.

Efficacy and Safety of Bulevirtide plus Tenofovir Disoproxil Fumarate in Real-World Patients with Chronic Hepatitis B and D Co-Infection.

Background: The hepatitis B and D virus (HBV/HDV) hepatocyte entry inhibitor bulevirtide (BLV) has been available in Europe since July 2020, after the registrational trial MYR202. Real-life data on the efficacy and safety of BLV are sparse. Methods: We have analysed the course of treatment with BLV (2 mg/day) plus tenofovir disoproxil fumarate (TDF) (245 mg/day) in patients with chronic hepatitis delta (CHD). Virologic (≥2 log reduction in HDV RNA or suppression of HDV RNA below the lower limit of detection) and biochemical (normalisation of serum ALT) treatment responses after 24 weeks were defined according to the MYR202 trial. Results: Seven patients were recruited (four with liver cirrhosis Child–Pugh A). After 24 weeks, a virologic response was observed in five of seven and a biochemical response was seen in three of six patients with elevated serum ALT at baseline. Extended treatment data > 48 weeks were available in three cases: two presented with continuous virologic and biochemical responses and in one individual an HDV-RNA breakthrough was observed. Adverse effects were not recorded. Conclusions: The first real-life data of the approved dosage of 2 mg of BLV in combination with TDF confirm the safety, tolerability, and efficacy of the registrational trial MYR202 for a treatment period of 24 weeks and beyond.

MiRNome profiling of circulating extracellular vesicles in patients with chronic hepatitis delta treated with pegylated interferon alpha

Introduction: MicroRNAs (miRNAs) are short noncoding RNAs involved in the epigenetic regulation of multiple signalling pathways including modulation of viral replication and host immune antiviral response. Specific circulating miRNAs profiles have been associated both with the progression of chronic hepatitis C and with the response to interferon (IFN) treatment in chronic hepatitis B patients. However, data in patients with chronic hepatitis delta virus (HDV) infection are missing.

Bulevirtide monotherapy at low and high dose in patients with chronic hepatitis delta: 24 weeks interim data of the phase 3 MYR301 study

Bulevirtide monotherapy at low and high dose in patients with chronic hepatitis delta: 24 weeks interim data of the phase 3 MYR301 study

Divergent patterns of hbv-rna and hbcrag levels in untreated chronic hepatitis delta: a large european cross-sectional study

Methods: Consecutive patients with untreated CHD were enrolled in this investigator driven cross-sectional study in two EU centers. All the standard clinical and virological characteristics were collected. HDV RNA was quantified by sensitive and specific assays (Robogene or a local validated in-house assay). Serum HBV RNA was quantified by an automated real-time PCR based investigational assay (cobas® 6800, Roche Diagnostics, Pleasanton, Ca, USA, LLOQ 10 cp/mL) while serum HBcrAg levels were measured using LUMIPULSE® G HBcrAg assay (Fujirebio Europe, LLOQ 3 log10 U/mL).

Comparative performance analysis between manual and automatic RNA extraction to quantify HDV RNA by RoboGene 2.0 kit in untreated and bulevirtide-treated HDV patients

Background & Aim. Diagnosis and management of Chronic Delta Hepatitis (CHD) requires highly sensitive and reliable tests for HDV RNA quantification coupled with automated lab procedures to optimize time and resources. Aim of the study was to compare two different extraction methods to quantify HDV RNA levels in untreated and Bulevertide (BLV)-treated HDV patients.

Prevalence of H. Pylori Infection in Non-Cirrhotic Patients with Chronic Delta Hepatitis

Objective: The relationship between Hepatitis Delta infection and Helicobacter infection in patients with non-cirrhotic hepatitis B infection was retrospectively investigated. Material and Methods: Stool samples of 117 patients included with Delta hepatitis infection in the study At total 36 of them were tested for H. Pylori infection. To detect H. Pylori, stool samples were tested using a commercial stool H. Pylori antigen assay. Results: Of these, 13 (19%) patients had H. Pylori seropositivity in the Hepatitis B infection group and 23 (48%) patients tested positive for H. Pylori infection in hepatitis delta infection group. There was a statistically significant difference between groups regarding H. Pylori seropositivity by the faecal test (p= 0.001). Conclusion: This study provides new knowledge on H. Pylori infection and reflects the need for evidence-based and comorbid dieases-oriented guidelines in the field of gastroenterology.

New actors come into play against hepatitis delta.

Currently chronic hepatitis delta (CHD) represents the most severe form of chronic viral hepatitis. The risk of developing cirrhosis, hepatocellular carcinoma (HCC) and decompensated liver disease is 2-3 times greater in hepatitis delta virus (HDV) infection than in hepatitis B virus (HBV). For instance, in a study carried out in Italy including 299 CHD patients followed for 28 years, 82 (27%) developed cirrhosis, and among these, 46 (56%) developed HCC. The real number of subjects infected by HDV worldwide remains unknown due to the lack of information in many areas, though it has been suggested that the rate of HBsAg carriers co-infected by HDV may be situated between 4.5 and 18%.

Hépatite Delta : épidémiologie, diagnostic, histoire naturelle et traitements

Hepatitis B virus is a small enveloped RNA virus, which replicates independently but requires the hepatitis B virus (HBV) to provide the envelope proteins necessary for the assembly of its own viral particles. Approximately 5% of chronic hepatitis B virus carriers are infected with HDV. HBV vaccination remains the best preventive treatment for HDV. All HBV patients should be screened for HDV (anti-HDV serology). In case of positive HDV serology, HDV replication (HDV RNA) should be investigated using a sensitive and specific technique. Hepatitis Delta is often complicated by cirrhosis and hepatocellular carcinoma (HCC). For this reason, every patient with Delta cirrhosis should be screened for HCC by abdominal ultrasound every 6 months. The historical treatment was based on PEG-IFN with many side effects. A new treatment has been approved, Bulevirtide (Hepcludex®) an HDV/HBV entry inhibitor, for any patient with chronic hepatitis Delta infection (CHD) with active replication (except in decompensated cirrhosis), at a dose of 2mg/day by subcutaneous injection. The exact duration on-treatment is unknown, thus treatment should be continued if clinical benefit is observed.

Can Interferon Therapy Change the Natural Course of Hepatitis Delta Infection?: a Clinical and Pathological Study

Chronic delta hepatitis (CDH) has a worse outcome than other types of viral hepatitis. High-dose, long-term alpha interferon (IFN-α) is the approved treatment and may ameliorate the course of infection. We evaluated long-term histological outcomes of CDH patients treated with IFN-α. Patients with histologically proved noncirrhotic CDH who were treated with high-dose IFN-α for at least 1 year were classified as cirrhotic or noncirrhotic at the end of treatment. Noncirrhotic patients also had posttreatment liver biopsies. Patients were designated histologically responsive or nonresponsive on the basis of fibrosis status. Histological, virological, and biochemical courses were analyzed. Forty-eight patients were treated with IFN-α (conventional and/or pegylated) for a median of 24 months with a posttreatment follow-up of 5 years. During the follow-up, cirrhosis developed in 24 patients, 5 of whom were decompensated. There was no difference between pre- and posttreatment fibrosis scores for 24 noncirrhotic patients at the end of follow-up. Among patients, 13% (n = 6) had decreased, 21% (n = 10) had steady, and 16% (n = 8) had increased fibrosis scores. Persistent viral response (PVR) was achieved in 16 patients (33%). Twenty percent of the entire group was histologically responsive (decreasing or steady fibrosis scores with improved necroinflammatory scores), while nearly 80% had histological progression/cirrhosis. PVR was significantly associated with histological response. The long-term natural course of patients who were treated with high dose IFN-α for at least 1 year was evaluated clinically and histologically. Despite the association of PVR with histological response, IFN-α treatment did not change the natural course of CDH; clinical and histological progression continued in two-thirds of the cases despite treatment.