Hepatitis D: Clinical Features and Therapy

Rizzetto, M.

doi:10.1159/000282077

Cited by 26 publications

(19 citation statements)

References 52 publications

(31 reference statements)

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“…A similar decreasing rate in HDV seropositivity was also seen in Spain [40]. Unfortunately this decline has not continued in the last decade [41]. The prevalence of HDV detected in 21 Italian centers in 2006 was 8.1% (95 of 1179 patients); this rate was similar to the prevalence in 1997 [42].…”

Section: Introductionsupporting

confidence: 54%

Delta Hepatitis

Günşar

2012

RHC

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Section: Introductionsupporting

confidence: 54%

Delta Hepatitis

Günşar

2012

RHC

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“…Chronic hepatitis D is thus considered a nearly incurable liver disease. Moreover, since HDV does not produce its own enzymatic proteins (21,30), there is no room for typical antiviral therapeutic approaches based on the use of specific inhibitors of viral enzymes (20). Natural recovery from HDV infection is a rare event, usually occurring only in the event of HBsAg seroclearance (21,35), thus confirming that studying the mechanisms of HBV and HDV interplay may have great importance not only from the virological point of view but also in identifying new methods for the cure of HDV-related diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, however, the currently available anti-HBV treatments [nucleos(t)ide analogs and alpha interferon] have no or very little effect on HBV S gene expression and intracellular cccDNA contents, and consequently, they are largely ineffective against HDV hepatitis (5,20,34). To reach the goal of HBV eradication, new drugs able to prevent reinfection of hepatocytes or inducing depletion of cccDNA must be produced, and these drugs would also be a true solution for HDV infection.…”

Section: Discussionmentioning

confidence: 99%

Replicative and Transcriptional Activities of Hepatitis B Virus in Patients Coinfected with Hepatitis B and Hepatitis Delta Viruses

Pollicino

Raffa

Santantonio

et al. 2011

J Virol

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Hepatitis B virus (HBV) and hepatitis delta virus (HDV) interplay was investigated by examining liver and serum samples from 21 coinfected and 22 HBV-monoinfected patients with chronic liver disease. Different real-time PCR assays were applied to evaluate intrahepatic amounts of HBV DNA, covalently closed circular DNA (cccDNA), pregenomic RNA (pgRNA), pre-S/S RNAs, and HDV RNA. Besides HBV DNA and HDV RNA levels, HBsAg concentrations in the sera were also determined. HDV-coinfected cases showed significantly lower median levels of serum HBV DNA (؊5 log), intrahepatic relaxed-circular DNA (؊2 log), and cccDNA (؊2 log) than those of HBV-monoinfected cases. Interestingly, pgRNA and pre-S/S RNA amounts were significantly lower (both ؊1 log) in HDV-positive patients, whereas serum HBsAg concentrations were comparable between the two patient groups. Pre-S/S RNA and HBsAg amounts per cccDNA molecule were higher in HDV-positive patients (3-fold and 1 log, respectively), showing that HBV replication was reduced, whereas synthesis of envelope proteins was not specifically decreased. The ratios of cccDNA to intracellular total HBV DNA showed a larger proportion of cccDNA molecules in HDV-positive cases. For these patients, both intrahepatic and serum HDV RNA amounts were associated with cccDNA but not with HBsAg or HBV DNA levels. Finally, HBV genomes with large deletions in the basal core promoter/precore region were detected in 5/21 HDV-positive patients but in no HDV-negative patients and were associated with lower viremia levels. These findings provide significant information about the interference exerted by HDV on HBV replication and transcription activities in the human liver.Hepatitis delta virus (HDV) is a worldwide diffuse pathogen commonly associated with severe forms of liver disease (9,21,22,35). HDV can establish infection only in individuals with continuing hepatitis B virus (HBV) infection, since it requires obligatory helper functions provided by HBV for in vivo infection. In particular, HDV needs to borrow the envelope proteins produced by HBV, and consequently, the two viruses share the same outer coats, consisting of the HBV surface antigen (HBsAg) (21,35). In spite of this, HDV and HBV are completely different in terms of genome replication, with both showing several aspects that make their life cycles nearly unique among agents infecting animals. Very briefly, HDV is a small RNA virus with a single-stranded and circular genome of approximately 1,700 nucleotides (nt) that is replicated using a host RNA polymerase and contains a ribozyme able to selfcleave and self-ligate the circular HDV genome (30). In contrast, HBV is a closed, circular, partially double-stranded DNA virus of 3.2 kb containing four partially overlapping open reading frames that replicates via the formation of a circular covalently closed DNA (cccDNA) which serves as a template for the production of virus mRNAs, including an RNA pregenome that is reverse transcribed in the cytoplasm of hepatocytes for the synthesis of the DNA molecule...

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“…Most patients with superinfection develop a progressive form of chronic hepatitis, and it often manifests as a worsening clinical illness in a previously stable chronic carrier of HBV. Clinical illness with superinfection can be rapidly progressive, leading to cirrhosis within 2 years in 10% -15% of patients (Rizzetto 2010).…”

Section: Clinical Manifestations and Pathogenesis Of Viral Hepatitismentioning

confidence: 99%

Viral Hepatitis: Past and Future of HBV and HDV

Thomas

Yoneda

Schiff

2015

Cold Spring Harbor Perspectives in Medicine

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Viral hepatitis is a significant disease afflicting hundreds of millions of people. Hepatitiscausing viruses initiate significant morbidity and mortality by establishing both acute and chronic infections, and several of these viruses are specifically associated with the development of hepatocellular carcinoma (HCC). Consequently, intense research efforts are focused on increasing our understanding of virus biology and on improving antiviral therapy. Even though viral hepatitis can be caused by several viruses from a range of virus families, the discovery of components of the hepatitis B virus (HBV) became a catalyst for the development of diagnostic assays that differentiate between these viruses as well as strategies for novel methods of vaccine development. Improvements in both the treatment and prevention of viral hepatitis are advancing rapidly. However, HBV, along with the associated infection by the hepatitis D virus, is still among the most common pathogens afflicting humans.O ver the past 50 years we have witnessed major advances in the study of the epidemiology, diagnosis, pathogenesis, natural history, treatment, and prevention of viral hepatitis. Viral hepatitis A, B, C, D, and E are well defined. There are safe and effective vaccines for hepatitis A and B, but not yet for hepatitis C. Hepatitis E vaccines have been developed more recently. Treatment for hepatitis B virus (HBV) infection is effective in rendering patients HBV DNA negative, stopping necroinflammation and often resulting in regression of fibrosis. Monumental achievements in the treatment of hepatitis C virus (HCV) infection have led to interferon (IFN)-and ribavirin-free curative oral therapy with combinations of direct antiviral agents, and we are quickly approaching short-term pangenotypic curative regimens.In this review, we highlight the historical evolution of viral hepatitis, and this monograph specifically addresses the status of hepatitis B and D. Clearly, the challenge is to cure hepatitis B with finite therapy that will eradicate covalently closed circular DNA (cccDNA) and eliminate the possibility of reactivation of viremia without persistence of hepatitis B. Thus, hepatitis D virus (HDV) infections will also resolve because HDV requires HBV envelope proteins for the production of infectious virus particles. However, even with the eradication of hepatitis B and C viremia, progression of cirrhosis in some and the risk for hepatocellular carcinoma (HCC) will haunt us for decades.Throughout the world over the past century, viral hepatitis has emerged as a significant public health issue afflicting hundreds of millions of Editors:

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Hepatitis D: Clinical Features and Therapy

Cited by 26 publications

References 52 publications

Delta Hepatitis

Delta Hepatitis

Replicative and Transcriptional Activities of Hepatitis B Virus in Patients Coinfected with Hepatitis B and Hepatitis Delta Viruses

Viral Hepatitis: Past and Future of HBV and HDV

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