Summary
Current treatment of chronic hepatitis D viral infection with interferons is poorly tolerated and effective only in a minority of patients. Despite delta virus causing the most severe form of ...chronic viral hepatitis, no other treatments are available. After many years of inactivity, there is now hope for new treatment approaches for delta virus and some are likely to enter clinical practice in the near future. Four new treatment approaches are currently being evaluated in phase 2 studies. These involve the hepatocyte entry inhibitor myrcludex B, the farnesyl transferase inhibitor lonafarnib, the nucleic acid inhibitor REP 2139 Ca and pegylated interferon lambda. Results obtained so far are promising, and phase 3 studies are expected shortly. This review summarizes the available data on the efficacy and safety of these new drugs.
Hepatitis D virus (HDV) infection leads to the most severe form of chronic viral hepatitis and requires the attention of a liver specialist. In this review, I will recapitulate recent advances in the ...management of HDV, present background information on HDV infection as well as current chronic hepatitis D treatment, briefly examine the HDV life cycle and discuss new management strategies.
Chronic infection with hepatitis B virus and hepatitis delta virus (HDV) is difficult to treat. In this randomized trial, patients treated with peginterferon alfa-2a, with or without adefovir, were ...more likely to have HDV RNA clearance than those treated with adefovir alone.
Hepatitis delta virus (HDV) is a defective RNA virus that requires coinfection with hepatitis B virus (HBV) to replicate. The HDV genome is encapsidated by hepatitis B surface antigen (HBsAg), which forms the viral envelope. The virus was first identified in 1977 in the serum of long-term carriers of HBsAg and was noted to have an increased prevalence among patients with liver damage.
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In long-term carriers of HBV, HDV infection can result in fulminant acute hepatitis or severe chronic hepatitis, often progressing to cirrhosis and hepatocellular carcinoma.
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Eight HDV genotypes have been suggested,
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and both HDV and HBV . . .
Summary Background Therapies for chronic hepatitis delta virus (HDV) infection are unsatisfactory. Prenylation is essential for HDV and inhibition abrogates HDV production in experimental models. In ...a proof-of-concept study, we aimed to assess the effect on HDV RNA levels, safety, and tolerability of the prenylation inhibitor lonafarnib in patients with chronic delta hepatitis. Methods In this phase 2A double-blind, randomised, placebo-controlled study, patients aged 18 years or older with chronic HDV infection were randomly assigned (3:1 in group 1 and 2:1 in group 2) to receive lonafarnib 100 mg (group 1) or lonafarnib 200 mg (group 2) twice daily for 28 days with 6 months' follow-up. Participants were randomised by random-number tables blocked in groups of four without stratification. Both groups enrolled six treatment participants and two placebo participants. Group 1 placebo patients received open-label lonafarnib as group 2 participants. The primary therapeutic endpoint was a decrease in HDV RNA viral titre in serum and the primary safety endpoint was the ability to tolerate the drug at the prescribed dose for the full 4-week duration, defined as drug discontinuation due to intolerance or grade 3/4 adverse events. This trial is registered with ClinicalTrials.gov , number NCT01495585. Findings Between Jan 19, 2012, and April 28, 2014, 14 patients were enrolled, of whom eight were assigned to group 1 and six were assigned to group 2. At day 28, compared with placebo, mean log HDV RNA declines from baseline were −0·73 log IU/mL in group 1 (95% CI 0·17–1·31; p=0·03) and −1·54 log IU/mL in group 2 (1·21–1·93; p<0·0001). Lonafarnib serum concentrations correlated with HDV RNA change ( r2 =0·78, p<0·0001). Model fits show that hepatitis B surface antigen (HBsAg) remained stable after a short pharmacological delay (0·75 days SE 0·24), lonafarnib effectiveness in blocking HDV production was greater in group 2 than in group 1 (0·952 SE 0·06 vs 0·739 0·05, p<0·001), and the HDV half-life was 1·62 days (0·07). There was no evidence of virological resistance. Adverse events were mainly mild to moderate with group 1 patients experiencing diarrhoea in three patients (50%) and nausea in two patients (33%) and in group 2 with all patients (100%) experiencing nausea, diarrhoea, abdominal bloating, and weight loss greater than 2 kg (mean of 4 kg). No treatment discontinuations occurred in any treatment groups. Interpretation Treatment of chronic HDV with lonafarnib significantly reduces virus levels. The decline in virus levels significantly correlated with serum drug levels, providing further evidence for the efficacy of prenylation inhibition in chronic HDV. Funding National Institute of Diabetes and Digestive and Kidney Diseases and National Cancer Institute, National Institutes of Health , and Eiger Biopharmaceuticals Inc.
Chronic hepatitis delta represents the most severe form of chronic viral hepatitis. The current treatment of hepatitis delta virus (HDV) infection consists of the use of interferons and is largely ...unsatisfactory. Several new compounds are currently in development for the treatment of HDV infection. However, surrogate markers that can be used to develop clinical endpoints in HDV infection are not well defined. In the current manuscript, we aimed to evaluate the existing data on treatment of HDV infection and to suggest treatment goals (possible “trial endpoints”) that could be used across different clinical trials.
Background and Aim: Decisions on public health issues are dependent on reliable epidemiological data. A comprehensive review of the literature was used to gather country‐specific data on risk ...factors, prevalence, number of diagnosed individuals and genotype distribution of the hepatitis C virus (HCV) infection in selected European countries, Canada and Israel.
Methodology: Data references were identified through indexed journals and non‐indexed sources. In this work, 13 000 articles were reviewed and 860 were selected based on their relevance.
Results: Differences in prevalence were explained by local and regional variances in transmission routes or different public health measures. The lowest HCV prevalence (≤0.5%) estimates were from northern European countries and the highest (≥3%) were from Romania and rural areas in Greece, Italy and Russia. The main risk for HCV transmission in countries with well‐established HCV screening programmes and lower HCV prevalence was injection drug use, which was associated with younger age at the time of infection and a higher infection rate among males. In other regions, contaminated glass syringes and nosocomial infections continue to play an important role in new infections. Immigration from endemic countries was another factor impacting the total number of infections and the genotype distribution. Approximately 70% of cases in Israel, 37% in Germany and 33% in Switzerland were not born in the country. In summary, HCV epidemiology shows a high variability across Europe, Canada and Israel.
Conclusion: Despite the eradication of transmission by blood products, HCV infection continues to be one of the leading blood‐borne infections in the region.
( 2) Despite these observations and in striking contrast to HBV or hepatitis C virus, treatment for HDV has not changed in more than 3 decades and consists of the off‐label use of conventional or ...pegylated interferon alfa (PEG‐IFN alfa) for the chronic viral hepatitis setting. ...a clinical concern might be the fate of retained HBsAg in hepatocytes. ...we do not know if combination treatment using a staggered approach is better than simultaneous combination treatment.
The role of low levels of HDV‐RNA during and after interferon therapy of hepatitis D is unknown. We re‐analysed HDV RNA in 372 samples collected in the HIDIT‐2 trial (Wedemeyer et al, Lancet ...Infectious Diseases 2019) with the Robogene assay (RA; Jena Analytics). Data were compared with the previously reported in‐house assay (IA). We detected HDV‐RNA in one‐third of samples previously classified as undetectable using the highly sensitive RA. Low HDV viraemia detectable at week 48 or week 96 was associated with a high risk for post‐treatment relapse, defined as HDV RNA positivity in both assays at week 120. HDV RNA relapses occurred in 10/15 (67%) patients with detectable low HDV RNA at week 48 and in 10/13 (77%) patients with low viraemia samples at week 96. In contrast, the post‐treatment relapse rate was lower in patients with undetectable HDV RNA in both assays during treatment.
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