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.

Hepatitis delta virus genome RNA synthesis initiates at position 1646 with a non-templated guanosine

Hepatitis delta virus (HDV) is a significant human pathogen that causes acute and chronic liver disease; there is no licensed therapy. HDV is a circular negative-sense ssRNA virus that produces three RNAs in infected cells: genome, antigenome and mRNA; the latter encodes hepatitis delta antigen, the viral protein. These RNAs are synthesized by host DNA-dependent RNA polymerase acting as an RNA-dependent RNA polymerase. Although HDV genome RNA accumulates to high levels in infected cells, the mechanism by which this process occurs remains poorly understood. For example, the nature of the 5’ end of the genome, including the synthesis start site and its chemical composition, are not known. Analysis of this process has been challenging because the initiation site is part of an unstable precursor in the rolling circle mechanism by which HDV genome RNA is synthesized. In this study, circular HDV antigenome RNAs synthesized in vitro were used to directly initiate HDV genome RNA synthesis in transfected cells, thus enabling detection of the 5’ end of the genome RNA. The 5’ end of this RNA is capped, as expected for a Pol II product. Initiation begins at position 1646 on the genome, which is located near the loop end proximal to the start site for HDAg mRNA synthesis. Unexpectedly, synthesis begins with a guanosine that is not conventionally templated by the HDV RNA. IMPORTANCE Hepatitis delta virus (HDV) is a unique virus that causes severe liver disease. It uses host RNA Polymerase II to copy its circular RNA genome in a unique and poorly understood process. Although the virus RNA accumulates to high levels within infected cells, it is not known how synthesis of the viral RNA begins, nor even where on the genome synthesis starts. Here, we identify the start site for the initiation of HDV genome RNA synthesis as position 1646, which is at one end of the closed hairpin-like structure of the viral RNA. The 5’ end of the RNA is capped, as expected for Pol II products. However, RNA synthesis begins with a guanosine that is not present in the genome. Thus, although HDV uses Pol II to synthesize the viral genome, some details of the initiation process are different. These differences could be important for successfully targeting virus replication.

A Rapid Point-of-Care Test for the Serodiagnosis of Hepatitis Delta Virus Infection

Hepatitis Delta virus (HDV) is a satellite of the Hepatitis B virus (HBV) and causes severe liver disease. The estimated prevalence of 15–20 million infected people worldwide may be underestimated as international diagnostic guidelines are not routinely followed. Possible reasons for this include the limited awareness among healthcare providers, the requirement for costly equipment and specialized training, and a lack of access to reliable tests in regions with poor medical infrastructure. In this study, we developed an HDV rapid test for the detection of antibodies against the hepatitis delta antigen (anti-HDV) in serum and plasma. The test is based on a novel recombinant large hepatitis delta antigen that can detect anti-HDV in a concentration-dependent manner with pan-genotypic activity across all known HDV genotypes. We evaluated the performance of this test on a cohort of 474 patient samples and found that it has a sensitivity of 94.6% (314/332) and a specificity of 100% (142/142) when compared to a diagnostic gold-standard ELISA. It also works robustly for a broad range of anti-HDV titers. We anticipate this novel HDV rapid test to be an important tool for epidemiological studies and clinical diagnostics, especially in regions that currently lack access to reliable HDV testing.

Constraint of Base Pairing on HDV Genome Evolution

The hepatitis delta virus is a single-stranded circular RNA virus, which is characterized by high self-complementarity. About 70% of the genome sequences can form base-pairs with internal nucleotides. There are many studies on the evolution of the hepatitis delta virus. However, the secondary structure has not been taken into account in these studies. In this study, we developed a method to examine the effect of base pairing as a constraint on the nucleotide substitutions during the evolution of the hepatitis delta virus. The method revealed that the base pairing can reduce the evolutionary rate in the non-coding region of the virus. In addition, it is suggested that the non-coding nucleotides without base pairing may be under some constraint, and that the intensity of the constraint is weaker than that by the base pairing but stronger than that on the synonymous site.

Comprehensive Analysis of Hepatitis Delta Virus Assembly Determinants According to Genotypes: Lessons From a Study of 526 Hepatitis Delta Virus Clinical Strains

Human hepatitis Delta virus (HDV) infection is associated to the most severe viral hepatic disease, including severe acute liver decompensation and progression to cirrhosis, and hepatocellular carcinoma. HDV is a satellite of hepatitis B virus (HBV) that requires the HBV envelope proteins for assembly of HDV virions. HDV and HBV exhibit a large genetic diversity that extends, respectively to eight (HDV-1 to -8) and to ten (HBV/A to/J) genotypes. Molecular determinants of HDV virion assembly consist of a C-terminal Proline-rich domain in the large Hepatitis Delta Antigen (HDAg) protein, also known as the Delta packaging domain (DPD) and of a Tryptophan-rich domain, the HDV matrix domain (HMD) in the C-terminal region of the HBV envelope proteins. In this study, we performed a systematic genotyping of HBV and HDV in a cohort 1,590 HDV-RNA-positive serum samples collected between 2001 to 2014, from patients originated from diverse parts of the world, thus reflecting a large genetic diversity. Among these samples, 526 HBV (HBV/A, B, C, D, E, and G) and HDV (HDV-1, 2, 3, and 5 to -8) genotype couples could be obtained. We provide results of a comprehensive analysis of the amino-acid sequence conservation within the HMD and structural and functional features of the DPD that may account for the yet optimal interactions between HDV and its helper HBV.

The Prevalence of Hepatitis D Virus in Reactive HBsAg Blood Donors at Department of Pathology, LUMHS Jamshoro

Background: The hepatitis delta virus (HDV) is a defective hepatotropic virus that only affects patients infected with the hepatitis B virus (HBV). Infection with the hepatitis delta virus can cause acute hepatitis, including the fulminant presentation or spontaneously resolving infection and chronic infection Aim: The present study's aim was to determine the prevalence of the Hepatitis D virus in reactive HBsAg blood donors at Diagnostic and Research Lab Hyderabad. Materials and Methods: This cross-sectional study was conducted on 434 blood donors at the Pathology department (Diagnostic and Research Laboratory) Civil Hospital, Hyderabad from January 2017 to December 2017. All the healthy individuals who visited at Diagnostic and Research Laboratory of Civil Hospital, LUMHS Hyderabad as blood donors with specific age groups of either gender were included in this study. All the individuals underwent Hepatitis screening. All of those cases that were noted with positive HBV further underwent HDV screening test. All the data was recorded in the proforma for the purposed of analysis. SPSS version 20 was used for data analysis. Results: Of the total 434 blood donors, 420 (96.8%) were male and 14 (3.2%) were female. The overall mean age was 31.65±4.67 years with an age range of 18 to 60 years. Out of 434, the incidence of positive delta virus was 62 (14.3%) while the remaining 372 (85.7%) were negative delta hepatitis blood donors. The prevalence of delta hepatitis blood donors with respect to age distribution were as follows; 18-30 years had 208 (48%), 31-40 years had 188 (27%), 41-50 years 69 (16%), and 51-60 years 39 (9%). Of the total 62 positive delta hepatitis, the prevalence of males and females was 98.4% and 1.6% respectively. All the donor’s blood group was divided into +O, +B, +A, +AB, -O, -A, and –B with their respective prevalence was 48.6%, 22.6%. 11.5%, 8.8%, 2.5%, 3.5%, and 2.5% whereas their frequency in positive tested delta hepatitis was 36 (58.1%), 7 (11.3%), 10 (16.1%), 6 (9.7%), 1 (1.6%), 2 (3.2%), and 0 (0%) respectively. Conclusion: It is concluded that the prevalence of HDV is 14.3% in Hepatitis B reactive healthy donors. This is a higher prevalence as compared to previously published studies. No such adequate recent data is available at the local level. More research is needed on this event, to provide adequate knowledge, which will be helpful to clinical and laboratory investigators, and physicians to reduce the burden of liver disease caused by HBV and HDV co-infection. Keywords: Hepatitis delta virus; HBsAg reactivity; Blood donors;

The global hepatitis delta virus (HDV) epidemic: what gaps to address in order to mount a public health response?

Background Co-infection between hepatitis B virus (HBV) and hepatitis delta virus (HDV) causes the severest chronic hepatitis and is associated with a high risk of cirrhosis and hepatocellular carcinoma (HCC). The Global Health Sector Strategy on Viral Hepatitis called for the elimination of hepatitis (− 65% mortality and − 90% incidence) by 2030. Our aims were to summarize key points of knowledge and to identify the gaps that need to be addressed to mount a public health response to HDV. Methods We performed a current literature review in terms of epidemiology by WHO regions, genotypes distribution and their pathogenicity, factors associated with HDV infection, mortality due to HDV infection, testing strategies and treatment. Results Prevalence of infection and genotypes are heterogeneous distributed, with highest prevalence in foci around the Mediterranean, in the Middle East, and in Central, Northern Asia and Eastern Asia. Persons who inject drugs (PWID) and migrants from highly endemic areas are highly affected. While antibody detection tests are available, HDV RNA tests of current infection are not standardized nor widely available. The few therapeutic options, including lofartinib, are not widely available; however several new and promising agents have entered clinical trials. Conclusion HDV infection is an poorly known cause of chronic liver disease. To mount a public health response, we need a better description of the HDV epidemic, standardized testing strategies and better treatment options.