Natural history and treatment of chronic delta hepatitis

Abstract

Chronic delta hepatitis (CDH) represents a severe form of chronic viral hepatitis, induced by the hepatitis delta virus (HDV) in conjunction with the hepatitis B virus (HBV). Delta hepatitis may lead to disease in humans through co-infection. The former leads to acute hepatitis which clinically can range from mild hepatitis to fulminant hepatitis and death. Severe or fulminant hepatitis is more often observed with HBV-HDV co-infection compared to HBV mono-infection. Chronic infection after acute hepatitis B + D co-infection is infrequent and similar to the rate in mono-infected patients. CDH develops in 70-90% of patients with superinfection. CDH runs a more progressive course than chronic hepatitis B and may lead to cirrhosis within 2 years in 10-15% of patients. However, as with any immune-mediated disease, different patterns of progression, ranging from mild to severe progressive disease, are observed. Active replication of both HBV and HDV may be associated with a more progressive disease pattern. Further, different HDV and HBV genotypes may contribute to various disease outcomes. CDH may be frequently associated with hepatocellular carcinoma development although recent studies provided conflicting results. The only established therapy for CDH is treatment with interferons for a duration of at least 1 year. On treatment, 6 month HDV RNA assessment may give clues as to whether to stop treatment at 1 year or continue beyond 1 year. New approaches to treatment of CDH are an urgent need of which the use of prenylation inhibitors appears the most promising.

Pegylated interferon-based treatment in patients with advanced liver disease due to chronic delta hepatitis

“…Chronic delta hepatitis (CDH) represents the most severe form of chronic viral hepatitis (1)(2)(3). As a sharp paradox to this and in contrast to the progress achieved in chronic hepatitis B (CHB) and CHC treatment, management of CDH has changed little in recent years.…”

Delta Hepatitis

“…Bordier et al provided the first preclinical data supporting the in vivo efficacy of prenylation inhibition as a novel antiviral therapy with potential application to HDV [84]. Using glucosidase inhibitors in HDV infection could prevent the secretion of virions from the hepatocytes, but these molecules may stimulate oncogenic pathways in terms of hepatocellular carcinoma [85,86]. New agents that can affect the interactions between the large HDV antigen and HBsAg in the HDV virion will be a hope in treatment of HDV infection [35].…”

Treatment of Chronic Delta Hepatitis: A Nine-Year Retrospective Analysis

“…We enrolled patients who were positive for HbsAg and HDV antibodies (IgG-anti-HDV) and positive for serum HDV RNA for at least 6 months, and had chronic hepatitis, as assessed by liver histology. Other inclusion criteria were as follows: age > 18 years; compensated liver function; no previous use of any antiviral therapy; correlation with clinical evaluation; daily alcohol consumption < 50 g; absence of contraindication to antiviral treatment, particularly platelet and polymorphonuclear counts ≥ 75.000/mm 3 …”

“…These patients pose a major therapeutic challenge, because most of them have advanced liver disease (2). CDH may lead to cirrhosis within 2 years in 10-15% of patients and may be frequently associated with hepatocellular carcinoma (3). Despite recent advances in the treatment of chronic viral hepatitis, therapy of chronic hepatitis D is not yet satisfactory (4).…”