Hepatitis delta virus: From infection to new therapeutic strategies

Abstract

The hepatitis delta virus (HDV) is a small RNA virus that encodes a single protein and which requires the hepatitis B virus (HBV)-encoded hepatitis B surface antigen (HBsAg) for its assembly and transmission. HBV/HDV co-infections exist worldwide and show a higher prevalence among selected groups of HBV-infected populations, specifically intravenous drug users, practitioners of high-risk sexual behaviours, and patients with cirrhosis and hepatocellular carcinoma. The chronic form of HDV-related hepatitis is usually severe and rapidly progressive. Patterns of the viral infection itself, including the status of co-infection or super-infection, virus genotypes (both for HBV and HDV), and persistence of the virus’ replication, influence the outcome of the accompanying and manifested liver disease. Unfortunately, disease severity is burdened by the lack of an effective cure for either virus type. For decades, the main treatment option has been interferon, administered as mono-therapy or in combination with nucleos(t)ide analogues. While its efficacy has been reported for different doses, durations and courses, only a minority of patients achieve a sustained response, which is the foundation of eventual improvement in related liver fibrosis. The need for an efficient therapeutic alternative remains. Research efforts towards this end have led to new treatment options that target specific steps in the HDV life cycle; the most promising among these are myrcludex B, which inhibits virus entry into hepatocytes, lonafarnib, which inhibits farnesylation of the viral-encoded L-HDAg large hepatitis D antigen, and REP-2139, which interferes with HBsAg release and assembly.

Low prevalence of hepatitis delta infection in Cuban HBsAg carriers: Prospect for elimination

“…For the HDV-PCR positive patient, RNA was undetectable after 1 year of Interferon treatment and the liver enzymes were normal suggesting a virological and biochemical response. Although this is the first choice of HDV treatment and decreases the HDV viral load in most patients, only 25% of the patients have undetectable levels of RNA afterward ( 1 , 6 , 38 , 39 ). A follow up is needed to verify whether the treatment has a sustained virological response over time, even beyond 24 weeks after treatment suspension ( 1 ).…”

“…Genotype 1 is present worldwide, while genotypes 2–8 were found in more specific geographical areas: HDV-2 and –4 are of Asian origin. HDV-3 is found in South America and HDV-5 to 8 were reported mainly from Africa and more recently in Brazil ( 1 , 6 – 8 ).…”

“…HDV-3 has been reported in connection with a severe form of fulminant hepatitis, while HDV-4 is often related to mild liver disease although a variant of genotype 4 seems to increase the risk for progression to chronic hepatitis and cirrhosis. The more recently identified genotypes 5–8 from Africa are less well characterized ( 6 – 8 ).…”

Retrospective Evaluation of Hepatitis Delta Virus Seroprevalence in HBsAg-Positive Patients

“…HDAg; küçük (S-HDAg) ve büyük (L-HDAg) olmak üzere iki izoformda bulunur ve her biri HDV yaşam döngüsünde belirli bir rol üstlenir. S-HDAg 195 amino asitten oluşur ve RNA replikasyonunu desteklerken, L-HDAg 214 amino asitten oluşur ve virion paketlemesi için gereklidir (3) .…”

“…Fulminan hepatite neden olabilir ve kronikleşme oranı %80'in üzerindedir. Süper enfeksiyonun tanısı; HBsAg taşıyan hastalarda pozitif anti-HDV IgM ve negatif anti-HBc IgM testine dayanır ve akut faz sırasında HBV replikasyonunun baskılanması da söz konusudur (3,4) . Klinik uygulama kılavuzları, HBV ile enfekte olan tüm hastalarda veya HBV açısından yüksek riskli popülasyonlarda HDV taraması yapılmasını önermektedir (5) .…”