The Prevalence and Serological Association of Hepatitis D Virus Genotypes in Taiwan

Hepatitis Delta Virus (HDV) is an RNA virus that requires the presence of hepatitis B surface antigen (HBsAg) to propagate into hepatocytes, with Genotype I being more prevalent globally. However, the prevalence of HDV genotypes in Taiwan is unknown. Accordingly, a cohort including 24 chronic HBV patients who received nucleos(t)ides (NUCs) between January 2002 and July 2018 was used to determine HDV genotypes and genotype specific serological association in chronic HBV carriers. HDV-positive genotypes in 18/24 (75%) males and 6/24 (25%) females were identified among chronic HBV patients. Viremia was lower in HDV-IV patients than in patients affected with other HDV genotypes (1.34 log10 copies/mL vs. 3.30 log10 copies/mL; p = 0.009). A logistics regression analysis revealed that HDV-IV was inversely proportional to HDV RNA (odds ratio [OR]/95% confidence intervals [CI]: 0.370/0.164–0.830; p = 0.017). The serologic association study indicated lower levels of creatinine (p = 0.047) and HDV-RNA (p = 0.009) in the HDV-IV group than the non-HDV-IV group but did not indicate any significant differences in the AST, ALT, bilirubin levels or other laboratory test factors. The three genotypes evident in Taiwan were HDV-I (4/24, 16.7%), HDV-II (6/24, 25.0%), and HDV-IV (14/24, 58.3%), and HDV-IV is the predominant HDV genotype in Taiwan. These results anticipate a clear understanding of HDV genotype serological association in chronic HBV carriers.

A Mathematical Analysis of HDV Genotypes: From Molecules to Cells

Hepatitis D virus (HDV) is classified according to eight genotypes. The various genotypes are included in the HDVdb database, where each HDV sequence is specified by its genotype. In this contribution, a mathematical analysis is performed on RNA sequences in HDVdb. The RNA folding predicted structures of the Genbank HDV genome sequences in HDVdb are classified according to their coarse-grain tree-graph representation. The analysis allows discarding in a simple and efficient way the vast majority of the sequences that exhibit a rod-like structure, which is important for the virus replication, to attempt to discover other biological functions by structure consideration. After the filtering, there remain only a small number of sequences that can be checked for their additional stem-loops besides the main one that is known to be responsible for virus replication. It is found that a few sequences contain an additional stem-loop that is responsible for RNA editing or other possible functions. These few sequences are grouped into two main classes, one that is well-known experimentally belonging to genotype 3 for patients from South America associated with RNA editing, and the other that is not known at present belonging to genotype 7 for patients from Cameroon. The possibility that another function besides virus replication reminiscent of the editing mechanism in HDV genotype 3 exists in HDV genotype 7 has not been explored before and is predicted by eigenvalue analysis. Finally, when comparing native and shuffled sequences, it is shown that HDV sequences belonging to all genotypes are accentuated in their mutational robustness and thermodynamic stability as compared to other viruses that were subjected to such an analysis.

Predominance of HBV Genotype B and HDV Genotype 1 in Vietnamese Patients with Chronic Hepatitis

Hepatitis delta virus (HDV) coinfection will additionally aggravate the hepatitis B virus (HBV) burden in the coming decades, with an increase in HBV-related liver diseases. Between 2018 and 2019, a total of 205 HBV patients clinically characterized as chronic hepatitis B (CHB; n = 115), liver cirrhosis (LC; n = 21), and hepatocellular carcinoma (HCC; n = 69) were recruited. HBV surface antigen (HBsAg), antibodies against surface antigens (anti-HBs), and core antigens (anti-HBc) were determined by ELISA. The presence of hepatitis B viral DNA and hepatitis delta RNA was determined. Distinct HBV and HDV genotypes were phylogenetically reconstructed and vaccine escape mutations in the “a” determinant region of HBV were elucidated. All HBV patients were HbsAg positive, with 99% (n = 204) and 7% (n = 15) of them being positive for anti-HBc and anti-HBs, respectively. Anti-HBs positivity was higher among HCC (15%; n = 9) compared to CHB patients. The HBV-B genotype was predominant (65%; n = 134), followed by HBV-C (31%; n = 64), HBV-D, and HBV-G (3%; n = 7). HCC was observed frequently among young individuals with HBV-C genotypes. A low frequency (2%; n = 4) of vaccine escape mutations was observed. HBV-HDV coinfection was observed in 16% (n = 33) of patients with the predominant occurrence of the HDV-1 genotype. A significant association of genotypes with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzyme levels was observed in HBV monoinfections. The prevalence of the HDV-1 genotype is high in Vietnam. No correlation was observed between HDV-HBV coinfections and disease progression when compared to HBV monoinfections.

Mis-Genotyping of Some Hepatitis D Virus Genotype 2 and 5 Sequences Using HDVdb

Evidence that Hepatitis D virus (HDV) genotype is involved in HDV infection pathogenesis is increasing. Indeed, HDV genotypes have been shown to be linked to different outcomes in terms of liver fibrosis and treatment response. Herein, we show that the promising HDVdb genotyping tool available online can lead to wrong genotyping results. The current HDVdb algorithm should be carefully considered as a “beta-version” and warrants algorithm core corrections, as soon as possible, for an optimal and beneficial use.

Molecular epidemiology and clinical characteristics of hepatitis delta virus (HDV) infected patients with elevated transaminases in Shanghai, China

Background: Patients coinfected with HBV and hepatitis D virus (HDV) have a greater risk of HCC and cirrhosis. The current study was undertaken to assess HDV genotype distribution and determine clinical characteristics of hepatitis delta virus (HDV) among HBsAg positive individuals in Shanghai.Method: This retrospective study involved 225 serum samples from HBsAg positive hospitalized patients from October 2010 to April 2013. HDV-specific RT-nested PCR was used to amplify HDV RNA. HDV genotypes were characterized by Next-generation sequencing (NGS), followed by phylogenetic analyses. HDV/HBV co-infected patients and HBV mono-infected patients were compared clinically and virologically.Results: Out of the 225 HBsAg-positive serum samples with elevated transaminases, HDV-RNA was identified in 11 (4.9%) patients. The HBV loads in the HDV positive group were significantly lower than the HDV negative HBV-infected patients. The aminotransferase enzymes were significantly higher in HDV/HBV co-infected compared to HDV negative patients (P<0.05). Phylogenetic analyses indicated that HDV-2 genotype being the predominant genotype, other HDV genotypes were not observed. HDV/HBV patients were significantly associated with a rather unfavourable clinical outcome.Conclusion： In summary, our study showed that the prevalence of HDV infection in patients with elevated transaminases is not low and the predominance of HDV genotype 2 infection in Shanghai. This finding helps us to better understand the correlation of HDV/HBV co-infection. Moreover, Next-generation sequencing (NGS) technologies provide a rapid, precise method for generating HDV genomes to define infecting genotypes.

Molecular epidemiology and clinical characteristics of hepatitis delta virus (HDV) infected patients with elevated transaminases in Shanghai, China

Background: Patients coinfected with HBV and hepatitis D virus (HDV) have a greater risk of HCC and cirrhosis. The current study was undertaken to assess HDV genotype distribution and determine clinical characteristics of hepatitis delta virus (HDV) among HBsAg positive individuals in Shanghai.Method: This retrospective study involved 225 serum samples from HBsAg positive hospitalized patients from October 2010 to April 2013. HDV-specific RT-nested PCR was used to amplify HDV RNA. HDV genotypes were characterized by Next-generation sequencing (NGS), followed by phylogenetic analyses. HDV/HBV co-infected patients and HBV mono-infected patients were compared clinically and virologically.Results: Out of the 225 HBsAg-positive serum samples with elevated transaminases, HDV-RNA was identified in 11 (4.9%) HBsAg positive patients. The HBV loads in the HDV positive group were significantly lower than the HDV negative HBV-infected patients. The aminotransferase enzymes were significantly higher in HDV/HBV co-infected compared to HDV negative patients (P<0.05). Phylogenetic analyses indicated that HDV-2 genotype being the predominant genotype, other HDV genotypes were not observed. HDV/HBV patients were significantly associated with a rather unfavourable clinical outcomeConclusion： In summary, our study showed that the prevalence of HDV infection in patients with elevated transaminases is not low and the predominance of HDV genotype 2 infection in Shanghai. This finding helps us to better understand the correlation of HDV/HBV co-infection. Moreover, Next-generation sequencing (NGS) technologies provide a rapid, precise method for generating HDV genomes to define infecting genotypes.

Characterization of the Full-Length Genome Sequences and Phylogenetic Analysis of HDV Strains Isolated from Patients with Chronic HBV and HDV Infection in Kyrgyz Republic

Objective. The purpose of our work was molecular genetic characterization of the hepatitis D virus isolates, circulating in the region with high prevalence of HBV + HDV super-infection. Materials and methods. The study material was 64 blood serum samples obtained from Kyrgyz Republic residents - patients with chronic viral hepatitis B+D. The hepatitis D virus complete genomes were sequenced, followed by phylogenetic analysis. Results and discussion. Based on the phylogenetic analysis of 64 HDV samples, it was shown that HDV genotype 1 (96.9 %) predominates in the examined group compared with HDV genotype 2 (3.1 %). Sequences were submitted to GenBank under access No MN984407 through MN984470. When assessing the genetic variability over the examined HDV genotype 1 samples, the maximum genetic distance was 12,49 %, and the minimum – 7,41 %. Within individual clusters, the genetic distance averaged from 2.6 % to 8.5 %. Among the sequences in GenBank, the closest resemblance to the HDV-2 Kyr41 and Kyr43 samples (nucleotide identity was 92.31 % and 89.57 %, respectively) was shown for the virus described earlier in Yakutia (AJ309880). To study the genetic relationships between the analyzed HDV genotype 1 strains in comparison with the HDV reference sequences, the predicted amino acid sequence was studied (111–214). Although hepatitis B preventive measures, including vaccination, have reduced the hepatitis D incidence, there is no effective way to prevent HDV infection in HBV carriers in endemic areas. The HDV sequence molecular-genetic characterization in this study, as well as the viral genomic sequence phylogenetic analysis, will help identify pathogen transmission pathways to control and / or prevent the spread of infection.

Molecular epidemiology and clinical characteristics of hepatitis delta virus (HDV) infected patients with elevated transaminases in Shanghai, China

Background: Patients coinfected with HBV and hepatitis D virus (HDV) have a greater risk of HCC and cirrhosis. The current study was undertaken to assess HDV genotype distribution and determine clinical characteristics of hepatitis delta virus (HDV) among HBsAg positive individuals in Shanghai.Method: This retrospective study involved 225 serum samples from HBsAg positive hospitalized patients from October 2010 to April 2013. HDV-specific RT-nested PCR was used to amplify HDV RNA. HDV genotypes were characterized by Next-generation sequencing (NGS), followed by phylogenetic analyses. HDV/HBV co-infected patients and HBV mono-infected patients were compared clinically and virologically.Results: Out of the 225 HBsAg-positive serum samples with elevated transaminases, HDV-RNA was identified in 11 (4.9%) HBsAg positive patients. The HBV loads in the HDV positive group were significantly lower than the HDV negative HBV-infected patients. The aminotransferase enzymes were significantly higher in HDV/HBV co-infected compared to HDV negative patients (P<0.05). Phylogenetic analyses indicated that HDV-2 genotype being the predominant genotype, other HDV genotypes were not observed. HDV/HBV patients were significantly associated with a rather unfavourable clinical outcomeConclusion： In summary, our study showed that the prevalence of HDV infection in patients with elevated transaminases is not low and the predominance of HDV genotype 2 infection in Shanghai. This finding helps us to better understand the correlation of HDV/HBV co-infection. Moreover, Next-generation sequencing (NGS) technologies provide a rapid, precise method for generating HDV genomes to define infecting genotypes.