Hepatitis D Virus Superinfection Research Articles

Superinfection of other hepatitis viruses on top of chronic hepatitis B: The more, the worse

Superinfection of other hepatitis viruses on top of chronic hepatitis B: The more, the worse

Hepatitis B virus/hepatitis D virus epidemiology: Changes over time and possible future influence of the SARS-CoV-2 pandemic.

Hepatitis D virus (HDV) is a defective liver-tropic virus that needs the helper function of hepatitis B virus (HBV) to infect humans and replicate. HDV is transmitted sexually or by a parenteral route, in co-infection with HBV or by super-infection in HBV chronic carriers. HDV infection causes acute hepatitis that may progress to a fulminant form (7%-14% by super-infection and 2%-3% by HBV/HDV co-infection) or to chronic hepatitis (90% by HDV super-infection and 2%-5% by HBV/HDV co-infection), frequently and rapidly progressing to cirrhosis or hepatocellular carcinoma (HCC). Peg-interferon alfa the only recommended therapy, clears HDV in only 10%-20% of cases and, consequently, new treatment strategies are being explored. HDV endemicity progressively decreased over the 50 years from the identification of the virus, due to improved population lifestyles and economic levels, to the use of HBV nuclei(t)side analogues to suppress HBV replication and to the application of universal HBV vaccination programs. Further changes are expected during the severe acute respiratory syndrome coronavirus-2 pandemic, unfortunately towards increased endemicity due to the focus of healthcare towards coronavirus disease 2019 and the consequently lower possibility of screening and access to treatments, lower care for patients with severe liver diseases and a reduced impulse to the HBV vaccination policy.

HBV/HDV management after liver transplantation: Review

Chronic hepatitis B is a worldwide health problem. Hepatitis D virus (HDV) is a dependent virus that relies on hepatitis B virus (HBV) to synthesize the pathogenic genomes. This may lead to HDV and HBV coinfection or superinfection that results in rapid liver damage that may lead to various serious complications, such as acute liver failure, cirrhosis, and hepatocellular cancer requiring liver transplantation. However, post-transplant HBV reactivation is always a concern as it can be detrimental to allograft function, leading to poor survival. The mainstay strategy to prevent this has been prophylaxis with hepatitis B immunoglobulin (HBIG) and potent anti-viral drugs. This treatment option has been investigated over the years in terms of appropriate dosing, duration and combination. Furthermore, with the advent of more potent antivirals there have been suggestions to use them as a monotherapy. Although, currently there is no effective therapy available for HDV, but the success of the liver transplantation in these patients is dependent on preventing HBV recurrence. Therefore, there has been a continuous effort to come up with an effective treatment plan that is effective and economical. In this review, we discuss the available treatment options for HBV/HDV after liver transplantation.

Delta hepatitis: Toward improved diagnostics.

Delta hepatitis: Toward improved diagnostics.

Safety and efficacy of REP 2139 and pegylated interferon alfa-2a for treatment-naive patients with chronic hepatitis B virus and hepatitis D virus co-infection (REP 301 and REP 301-LTF): a non-randomised, open-label, phase 2 trial

REP 2139 clears circulating hepatitis B virus (HBV) surface antigen (HBsAg), enhancing the restoration of functional control of HBV infection by immunotherapy. We assessed the safety and efficacy of REP 2139 and pegylated interferon alfa-2a in patients with chronic HBV and hepatitis D virus (HDV) co-infection. In this open-label, non-randomised, phase 2 trial, patients aged 18-55 years, who were treatment naive, hepatitis B e antigen [HBeAg] negative, anti-hepatitis D antigen [HDAg] positive, and HDV RNA positive, with serum HBsAg concentrations of more than 1000 IU/mL, and a history of HDV infection for 6 months or more before treatment, were recruited at Toma Ciorbă Hospital of Infectious Diseases in Chișinău, Moldova. Patients were excluded if they had HDV superinfection, liver infections other than HBV and HDV, or liver cirrhosis. Patients received 500 mg intravenous REP 2139 once per week for 15 weeks, followed by combined therapy with 250 mg intravenous REP 2139 and 180 μg subcutaneous pegylated interferon alfa-2a once per week for 15 weeks, then monotherapy with 180 μg pegylated interferon alfa-2a once per week for 33 weeks. The primary endpoints assessed at the end of treatment were the safety and tolerability of the treatment regimen, analysed in the intention-to-treat population. Secondary outcomes included the proportion of patients with serum HBsAg less than 50 IU/mL, the proportion of patients with suppressed HBV DNA, and the proportion of patients who maintained these responses through follow-up. The REP 301 trial is registered with ClinicalTrials.gov, number NCT02233075. We also did an additional follow-up at 1 year after the end of treatment, as an interim analysis of the REP 301-LTF trial (planned duration 3 years), registered with ClinicalTrials.gov, number NCT02876419, which is ongoing but not recruiting patients. Between Sept 8, 2014, and Jan 27, 2015, we enrolled 12 patients into the REP 301 study. All 12 patients experienced at least one adverse event during treatment: two (17%) patients experienced anaemia, eight (67%) neutropenia, and ten (83%) thrombocytopenia. Five (42%) patients had raised alanine aminotransferase levels, four (33%) had raised aspartate aminotransferase levels, and two (17%) had increased bilirubin concentrations. Four (33%) patients had a serious adverse event, and 12 (100%) patients had treatment-emergent lab abnormalities. Six patients had HBsAg levels less than 50 IU/mL by the end of treatment (all <0·05 IU/mL); five maintained this level of suppression at the end of 1 year follow-up. Six patients had hepatitis B surface antibody (anti-HBs) titres above 10 mIU/mL at the end of treatment (five had maximum anti-HBs concentrations of 7681-86 532 mIU/mL during treatment), which were maintained at the end of 1 year follow-up in these five patients. Elevated alanine and aspartate aminotransferase concentrations and profound elevations of anti-HBs titres were restricted to patients who had HBsAg levels of less than <1 IU/mL before the introduction of pegylated interferon alfa-2a. Nine patients had suppressed HBV DNA (<10 IU/mL]) at the end of treatment, which was maintained by seven patients and newly established in an eighth patient at the end of 1 year follow-up. 11 patients became HDV RNA negative during treatment, with nine remaining HDV RNA negative at the end of treatment; seven of these patients remained HDV RNA negative by the end of 1 year follow-up. By the end of 1 year follow-up, normalisation of serum aminotransferases occurred in nine of 12 patients. Combined REP 2139 and pegylated interferon alfa-2a therapy is safe, well tolerated, and establishes functional control of HBV and HDV co-infection and normalisation of serum aminotransferases in a high proportion of patients 1 year after therapy. This combination therapy approach might provide a new treatment option for patients with HBV and HDV co-infection. Replicor.

HDV RNA replication is associated with HBV repression and interferon-stimulated genes induction in super-infected hepatocytes

Hepatitis D virus (HDV) super-infection of Hepatitis B virus (HBV)-infected patients is the most aggressive form of viral hepatitis. HDV infection is not susceptible to direct anti-HBV drugs, and only suboptimal antiviral responses are obtained with interferon (IFN)-alpha-based therapy. To get insights on HDV replication and interplay with HBV in physiologically relevant hepatocytes, differentiated HepaRG (dHepaRG) cells, previously infected or not with HBV, were infected with HDV, and viral markers were extensively analyzed. Innate and IFN responses to HDV were monitored by measuring pro-inflammatory and interferon-stimulated gene (ISG) expression. Both mono- and super-infected dHepaRG cells supported a strong HDV intracellular replication, which was accompanied by a strong secretion of infectious HDV virions only in the super-infection setting and despite the low number of co-infected cells. Upon HDV super-infection, HBV replication markers including HBeAg, total HBV-DNA and pregenomic RNA were significantly decreased, confirming the interference of HDV on HBV. Yet, no decrease of circular covalently closed HBV DNA (cccDNA) and HBsAg levels was evidenced. At the peak of HDV-RNA accumulation and onset of interference on HBV replication, a strong type-I IFN response was observed, with interferon stimulated genes, RSAD2 (Viperin) and IFI78 (MxA) being highly induced. We established a cellular model to characterize in more detail the direct interference of HBV and HDV, and the indirect interplay between the two viruses via innate immune responses. This model will be instrumental to assess molecular and immunological mechanisms of this viral interference.

Evaluation of Patients with Hepatitis Delta Virus Infection at First Admission in Izmir, Turkey

Objective: To present the clinical and laboratory findings of patients with hepatitis D virus (HDV) at first admission to hospital. Design This retrospective study was conducted on patients with HDV infection at a State Hospital in Turkey. Setting Department of Infectious Diseases, Turkish Ministry of Health, Karsiyaka State Hospital, Izmir, Turkey. Subjects Some 35 982 samples were tested between 2004 and 2010; HBsAg-positive samples were subsequently tested for anti-HDV antibodies. Main Outcome Data of patients with anti-HDV seropositivity recorded at first admission. Results Among 1216 detected chronic HBV infections, a total of 26 (2.1%) cases of seropositive anti-HDV were diagnosed. Twelve of the study group were men, 14 were women. The mean age was 43.30 years (range, 24-79 years). Hepatitis B surface antigen (HBsAg) was positive in all patients, and hepatitis B envelope antigen (HBeAg) was negative in 19 (73.1%). HBV DNA levels were above 2000 IU/mL in six (23.1%) patients, whereas it was below 2000 IU/mL in the remainder. The mean alanine aminotransferase (ALT) and alpha-fetoprotein levels were 59.3 IU/mL (range, 21-152 IU/mL) and 1.9 IU/mL (range, 1.1-3.8 IU/mL), respectively. Liver biopsy was performed in 12 (46.2%) patients in the study group. The mean fibrosis score was 1.9 and the mean histologic activity index was 9.1. Conclusion Although HDV super infection has been associated with more severe liver disease and accelerated progression to cirrhosis, moderate fibrotic activity and histologic scores were seen at the first admission at our institution. Therefore, delta virus infection should be considered in patients with mild ALT elevation, even if HBV DNA levels are below 2000 IU/mL.

Increasing Incidence of Recent Hepatitis D Virus Infection in HIV-Infected Patients in an Area Hyperendemic for Hepatitis B Virus Infection

Superinfection with hepatitis D virus (HDV) may increase the risk for hepatitis flares and chronic hepatic complications in patients with chronic hepatitis B virus (HBV) infection. This retrospective observational study aimed to examine the incidence of and factors associated with recent HDV superinfection among individuals coinfected with human immunodeficiency virus (HIV) and HBV. Anti-HDV immunoglobulin G (IgG) was sequentially determined in 375 HIV/HBV-coinfected patients to estimate the HDV incidence between 1992 and 2012. Plasma HDV and HBV loads and HBV surface antigen (HBsAg) levels were determined for the HDV seroconverters. A nested case-control study was conducted to identify the associated factors with HDV seroconversion. Phylogenetic analysis was performed using HDV sequences amplified from HDV seroconverters and HDV-seropositive patients at baseline. During 1762.4 person-years of follow-up [PYFU], 16 patients seroconverted for HDV, with an overall incidence rate of 9.07 per 1000 PYFU, which increased from 0 in 1992-2001, to 3.91 in 2002-2006, to 13.26 per 1000 PYFU in 2007-2012 (P < .05). Recent HDV infection was associated with elevated aminotransferase and bilirubin levels and elevated rapid plasma reagin titers. Of the 12 patients with HDV viremia, 2 were infected with genotype 2 and 10 with genotype 4. HBsAg levels remained elevated despite a significant decline of plasma HBV DNA load with combination antiretroviral therapy that contained lamivudine and/or tenofovir. Our findings show that the incidence of recent HDV infection in HIV/HBV-coinfected patients increased significantly from 1992-2001 to 2007-2011, and was associated with hepatitis flares and syphilis.

Prime/Boost Immunization with DNA and Adenoviral Vectors Protects from Hepatitis D Virus (HDV) Infection after Simultaneous Infection with HDV and Woodchuck Hepatitis Virus

Hepatitis D virus (HDV) superinfection of hepatitis B virus (HBV) carriers causes severe liver disease and a high rate of chronicity. Therefore, a vaccine protecting HBV carriers from HDV superinfection is needed. To protect from HDV infection an induction of virus-specific T cells is required, as antibodies to the two proteins of HDV, p24 and p27, do not neutralize the HBV-derived envelope of HDV. In mice, HDV-specific CD8(+) and CD4(+) T cell responses were induced by a DNA vaccine expressing HDV p27. In subsequent experiments, seven naive woodchucks were immunized with a DNA prime and adenoviral boost regimen prior to simultaneous woodchuck hepatitis virus (WHV) and HDV infection. Five of seven HDV-immunized woodchucks were protected against HDV infection, while acute self-limiting WHV infection occurred as expected. The two animals with the breakthrough had a shorter HDV viremia than the unvaccinated controls. The DNA prime and adenoviral vector boost vaccination protected woodchucks against HDV infection in the setting of simultaneous infection with WHV and HDV. In future experiments, the efficacy of this protocol to protect from HDV infection in the setting of HDV superinfection will need to be proven.

Hepatitis D virus: an update

Hepatitis D virus (HDV) infection involves a distinct subgroup of individuals simultaneously infected with the hepatitis B virus (HBV) and characterized by an often severe chronic liver disease. HDV is a defective RNA agent needing the presence of HBV for its life cycle. HDV is present worldwide, but the distribution pattern is not uniform. Different strains are classified into eight genotypes represented in specific regions and associated with peculiar disease outcome. Two major specific patterns of infection can occur, i.e. co-infection with HDV and HBV or HDV superinfection of a chronic HBV carrier. Co-infection often leads to eradication of both agents, whereas superinfection mostly evolves to HDV chronicity. HDV-associated chronic liver disease (chronic hepatitis D) is characterized by necro-inflammation and relentless deposition of fibrosis, which may, over decades, result in the development of cirrhosis. HDV has a single-stranded, circular RNA genome. The virion is composed of an envelope, provided by the helper HBV and surrounding the RNA genome and the HDV antigen (HDAg). Replication occurs in the hepatocyte nucleus using cellular polymerases and via a rolling circle process, during which the RNA genome is copied into a full-length, complementary RNA. HDV infection can be diagnosed by the presence of antibodies directed against HDAg (anti-HD) and HDV RNA in serum. Treatment involves the administration of pegylated interferon-α and is effective in only about 20% of patients. Liver transplantation is indicated in case of liver failure.

Prevalence of human immunodeficiency virus and its association with hepatitis B, C, and D virus infections among incarcerated male substance abusers in Taiwan

Taiwan has been facing a rising epidemic of human immunodeficiency virus (HIV) infection since 2004. Injection drug users comprised 38.5% of accumulated HIV cases by 2007. This cross-sectional study investigated the seroprevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and HIV infection in 753 male substance users who were detained in a detoxification center in Taoyuan, Taiwan. The subjects were enrolled into the study consecutively between February and October, 2005. The seroprevalence rates of HIV antibodies, HCV antibodies, and HBV surface antigens among all subjects, and HDV antibodies among HBV carriers were 6.9% (95% confidence interval [CI]: 5.19-8.95), 30.5% (95% CI: 27.23-33.93), 16.9% (95% CI: 14.24-19.71) and 13.7% (95% CI: 8.19-21.04), respectively. Subjects in the heroin injection group had significantly higher rates of HIV infection, HCV infection and HDV superinfection (25.5%, 89.6%, and 38.7%) than those in the heroin non-injection group (0.9%, 24.5%, and 6.25%), the methamphetamine group (0.3%, 8.1%, and 6.7%), and the club drug group (1%, 3%, and 0%; P < 0.001). The odds of HCV, HIV, or HDV infection were 74.7, 63.8, and 11.1 higher, respectively, for heroin injection drug users than for non-injection drug users (P < 0.0001). Compared to HIV-negative individuals, the odds of being a heroin injector and the odds of HCV co-infections were 64-fold and 149-fold higher, respectively, in HIV-positive individuals. The impact of HBV, HCV, and HDV infection on the HIV epidemic in Taiwan should be monitored closely.

Positive Selection of Hepatitis Delta Antigen in Chronic Hepatitis D Patients

Liver disease may become ameliorated in some patients with chronic hepatitis D virus (HDV) infection. We present here a study based on longitudinal sampling to investigate the viral dynamics in chronic HDV infection. We examined the HDV variants from different time points, especially those before and after the elevation of serum aminotransferase levels. The datasets from each patient were tested for positive selection by using maximum-likelihood methods with heterogeneous selective pressures along the nucleotide sequence. An average of 4.9%, ranging from 3.1 to 6.8%, of the entire delta antigen sites was regulated by a diversifying selection. Most of the positively selected sites were associated with immunogenic domains. Likelihood ratio tests revealed a significant fitness of positive selection over neutrality of the hepatitis delta antigen gene in all patients. We further adapted a neural network method to predict potential cytotoxic T ligand epitopes. Among the HLA-A*0201 cytotoxic T ligand epitopes, three consistent epitopes across all three genotypes were identified: amino acids (aa) 43 to 51, 50 to 58, and 114 to 122. Three patients (60%) had sites evolving under positive selection in the epitope from aa 43 to 51, and four patients (80%) had sites evolving under positive selection in the epitope from aa 114 to 122. The discovery of immunogenic epitopes, especially cytotoxic-T-lymphocyte ligands, associated with chronic HDV infection may be crucial for further development of novel treatments or designs in vaccine for HDV superinfection.

Genotypes and Viremia of Hepatitis B and D Viruses Are Associated With Outcomes of Chronic Hepatitis D Patients

Genotypes and viremia of hepatitis D virus (HDV) and hepatitis B virus (HBV) may be associated with outcomes. This study evaluated the impact of viral genotypes and viremia on outcomes of dual HBV and HDV infection. Viremia and viral genotypes were analyzed in 194 consecutive chronic hepatitis B patients with HDV superinfection and correlated with outcomes. The numbers of HBV genotype A, B, C, and nonclassified were 4, 57, 23, and 110, respectively. There were 51 genotype I HDV, 74 genotype II HDV, 8 genotype IV HDV, and 61 nonclassified HDV genotype. In a median follow-up of 135 months, 24 progressed to cirrhosis and 41 developed hepatocellular carcinoma. Patients infected with genotype I HDV had a lower remission rate (15.2% vs 40.2%; P = .007) and more adverse outcomes (cirrhosis, hepatocellular carcinoma, or mortality) (52.2% vs 25.0%; P= .005) than those with genotype II HDV. Patients infected with genotype C HBV had a lower remission rate (0 vs 32.1%; P = .005) and more adverse outcomes (70.0% vs 33.9%; P = .005) than those with genotype B HBV. The presence of HBV or HDV viremia was associated with lower remission rates compared with those negative for both (26.4% and 24.3% vs 69.2%; P < .001). In multivariate analysis, age, genotype C HBV, and genotype I HDV were independent factors associated with adverse outcomes. In chronic HBV and HDV dual infections, older age, genotype I HDV, and genotype C HBV correlated with adverse outcomes.

Recent updates in hepatitis vaccination and the prevention of hepatocellular carcinoma.

Recent updates in hepatitis vaccination and the prevention of hepatocellular carcinoma.

Minimal role of GB virus-C/hepatitis G virus in fulminant and subfulminant hepatitis in Taiwan.

The role of GB virus-C/hepatitis G virus (GBV-C/HGV) in fulminant hepatitis (FH) and subfulminant hepatitis (SFH) remains unclear. Thirty-two FH or SFH patients, with adequate clinical information and serum specimens, were studied. Serum samples were tested for hepatitis markers and genomes of hepatitis A-E viruses, as well as GBV-C/HGV. Of the cases of FH/SFH studied, one (3%) was caused by anti-tuberculosis agents, 26 (81%) had hepatotropic virus infection, and five (16%) had no identifiable cause. Of the 26 patients with hepatotropic virus infection, five had acute hepatitis B infection (one with acute hepatitis D virus (HDV) co-infection), one had acute hepatitis C infection, 16 were hepatitis B surface antigen carriers with reactivation or superimposed by unidentified agent(s) (two had triple virus infections), three were hepatitis B carriers with HDV superinfection, and one had GBV-C/HGV infection in addition to exposure to halothane. GBV-C/HGV-RNA was detected in only three of 32 patients (9%) and all had a history of blood transfusion or co-existing causative factors. Of the 26 patients with hepatotropic virus infection, 18 were tested for antibodies against GBV-C/HGV envelope protein and seven were reactive, suggesting past infection. The role of GBV-C/HGV in causing FH and SFH is minimal in Taiwan and HBV infection remains the major aetiology. These findings also suggest the existence of as yet unrecognized agents, responsible for such catastrophic illnesses.

Hepatitis D viremia following orthotopic liver transplantation involves a typical HDV virion with a hepatitis B surface antigen envelope.

Patients receiving orthotopic liver transplantation (OLT) because of type D hepatitis frequently exhibit what appears to be an autonomous, or "isolated," hepatitis D virus (HDV) infection following the transplantation, with no evidence of hepatitis B virus (HBV) in the graft or in the serum. These observations have led to the hypothesis that HBV might not always be required for HDV infection, or that HDV could exist as a latent infection until rescued by HBV. Alternatively, an apparently autonomous HDV infection could be explained by coinfection of a small number of hepatocytes with both viruses following transplantation, with a very low level of HBV expression that supports low-level HDV propagation. Our results are consistent with the latter hypothesis. Sensitive polymerase chain reaction (PCR)-based analysis of HBV and HDV viremia in transplantation patients with HDV infection previously characterized as isolated showed that HDV viremia was not independent of HBV viremia. Additional analyses, including PCR amplification, buoyant density analysis in a CsCl gradient, and immunoprecipitation with monoclonal hepatitis B surface antigen antibodies (anti-HBs), indicated that the posttransplant HDV particle is typical: it contains full-length HDV RNA and an envelope of hepatitis B surface antigen (HBsAg) and is not different from that found during the acute and chronic stages of HDV superinfection or coinfection. Moreover, an experimental test of the first hypothesis in chimpanzees did not support the idea that HDV can persist for several weeks as an isolated, latent infection that can be rescued subsequently by HBV. The data indicate, therefore, that latent HDV infection is not a factor in OLT recipients. We conclude that the HDV virion in the posttransplantation setting is typical, and that HDV viremia following OLT requires the helper function of HBV infection.

Decreasing hepatitis D virus infection in Taiwan: an analysis of contributory factors.

Superinfection of hepatitis D virus (HDV) among hepatitis B virus (HBV) carriers is mainly through heterosexual contact in Taiwan. This study investigated the change of HDV endemicity and its associated contributory factors. Seventy-seven patients with acute HDV superinfection among 527 consecutive exacerbating hepatitis B surface antigen (HBsAg) carriers were identified over the past 12 years. The prevalence decreased significantly by each 3-year period from June 1983 to May 1995 (23.7, 15.5, 13.1 and 4.2%, respectively, P < 0.001). This trend was more significant in the hepatitis B e antigen (HBeAg)-negative group (P < 0.001) than in the HBeAg-positive group (P = 0.073). Subjects with a history of paid sex and prostitutes were also recruited for analysis both in 1989 and 1996. Although not statistically significant, there was a trend showing a decrease in the prevalence of serum antibody against HDV (anti-HDV) in each risk group: it was lower in 1996 among HBsAg-positive brothel-goers (10.3 vs 6.9%), licensed prostitutes (54.5 vs 50%) and unlicensed prostitutes (36.1 vs 30.8%). Accumulation of anti-HDV-positive subjects in risk groups may mask the actual decrease of new HDV-infected cases. The prevalence of the HBsAg carrier rate among all prostitutes has significantly decreased (18.3 vs 12.2%, P = 0.015). The efficacy of each preventive strategy was examined and mapped with the trend. It was concluded that active preventive measures directed against promiscuity and sexually transmitted disease and the promotion of disposable needles may have contributed to the decrease in HDV endemicity.

Prevalence and type of precore hepatitis B virus mutants in hepatitis D virus superinfection and its clinical implications.

To study the prevalence and type of the hepatitis B e antigen (HBeAg)-negative mutant in hepatitis D virus (HDV) superinfection, the precore region of hepatitis B virus (HBV) was analyzed by cycle sequencing. Of the 58 samples sequenced, 24 were wild type and 34 carried mutants. The precore stop mutation (TAG) at the 28th codon was found in 32 cases, other mutations were found in 7, and double mutations were found in 5. The absence of HBeAg showed a substantial agreement with the presence of mutants (kappa value, 0.74). Of the acute hepatitis patients, HDV replication and clinical manifestations were not significantly different between those with mutant and wild type virus, except that those with mutant virus were older (mean age, 48 vs. 28 years; P < .002). The absence of HBeAg in these patients is mainly due to HDV superinfection in older HBV carriers who already had precore mutant.

Natural history of hepatitis D viral superinfection: Significance of viremia detected by polymerase chain reaction

Background/Aims : Polymerase chain reaction (PCR) is very sensitive. The aim of the study was to reevaluate viral replication in hepatitis D virus (HDV) superinfection by PCR. Methods : HDV and hepatitis B virus (HBV) were detected by PCR in 185 patients. Results : The acute hepatitis group had the highest detection rate of HDV RNA compared with chronic hepatitis, cirrhosis, hepatocellular carcinoma, and remission groups (63 of 64 vs. 35 of 47, 17 of 23, 19 of 30, and 7 of 21) and the highest alanine aminotransferase (ALT) levels (mean, 1741 U/L vs. 266 to 27 U/L; P < 0.05). The detection rate of HBV DNA was the lowest in the acute group (41%) compared with 66%, 70%, 80%, and 57% in the remaining groups ( P < 0.02). At the chronic stage, 13%–25% of cases had HDV RNA, and 30%–48% of cases had HBV DNA detected by PCR but not by traditional method. HDV RNA was associated with ALT levels in horizontal and longitudinal analyses. Conclusions : HDV superinfection may be divided into the following three phases: acute phase, active HDV replication and suppression of HBV with high ALT levels; chronic phase, decreasing HDV and reactivating HBV with moderate ALT levels; and late phase, development of cirrhosis and hepatocellular carcinoma caused by replication of either virus or remission resulting from marked reduction of both viruses.

Hepatitis D virus superinfection remains a rare occurrence in non-drug abusers in Hong Kong

Recent studies from Taiwan reported an increased prevalence of hepatitis D virus (HDV) superinfection as well as a spread of HDV infection to non-drug abusers. We examined the current prevalence of HDV superinfection in Hong Kong by testing sera from a large cohort of patients with acute and chronic hepatitis B virus (HBV) infection, collected between January 1988 and December 1990, for IgG antibody to HDV (anti-HDV). Anti-HDV was detected in 13 (93%) of 14 parenteral drug abusers who had HBV-related chronic liver disease. However, anti-HDV was detected in only one (0.15%) of 664 non-drug abusers who had chronic HBV infection and none of 31% patients with acute hepatitis B. We concluded that HDV superinfection remains a rare occurrence in non-drug abusers in Hong Kong.