Predominance of HBV Genotype B and HDV Genotype 1 in Vietnamese Patients with Chronic Hepatitis.
ABSTRACT: 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.
Project description:In 1991, Peru launched the first vaccination program against hepatitis B in children aged under 5 years in the hyperendemic [hepatitis B virus (HBV) and hepatitis D virus (HDV)] province of Abancay. We conducted a cross-sectional study to determine the prevalence of HBV and HDV infections, 23 years after the launch of the vaccination program, as well as the post-vaccine response against hepatitis B in terms of prevalence of hepatitis B surface antibody (anti-HBs ?10 mUI/ml). Among 3165 participants aged from 0 to 94 years, the prevalence rates of hepatitis B surface antigen (HBsAg), and hepatitis B core antibody (total anti-HBc) were 1.2% [95% confidence interval (CI) 0.85-1.64%], and 41.67% (95% CI 39.95-43.41%), respectively. The prevalence rate of anti-HBs at protective levels (?10 mUI/ml) in individuals who HBsAg and anti-HBc negative was 66.36% (95% CI 64.15-68.51%). The prevalence rate of HBsAg in children aged <15 years was nil, and among adult HBsAg carriers, the prevalence of hepatitis D antibody (anti-HDV) was 5.26% (2/38; 95% CI 0.64-17.74). These findings showed that HBV prevalence has changed from high to low endemicity, 23 years following implementation of the vaccination program against hepatitis B, and HDV infection was not detected in those aged <30 years.
Project description:Non invasive immunologic markers of virus-induced liver disease are unmet needs. We tested the clinical significance of quantitative total and IgM-anti-HBc in well characterized chronic-HBsAg-carriers. Sera (212) were obtained from 111 HBsAg-carriers followed-up for 52 months (28-216) during different phases of chronic-HBV-genotype-D-infection: 10 HBeAg-positive, 25 inactive-carriers (HBV-DNA?2000IU/ml, ALT<30U/L), 66 HBeAg-negative-CHB-patients and 10 with HDV-super-infection. In 35 patients treated with Peg-IFN±nucleos(t)ide-analogues (NUCs) sera were obtained at baseline, end-of-therapy and week-24-off-therapy and in 22 treated with NUCs (for 60 months, 42-134m) at baseline and end-of-follow-up. HBsAg and IgM-anti-HBc were measured by Architect-assays (Abbott, USA); total-anti-HBc by double-antigen-sandwich-immune-assay (Wantai, China); HBV-DNA by COBAS-TaqMan (Roche, Germany). Total-anti-HBc were detectable in all sera with lower levels in HBsAg-carriers without CHB (immune-tolerant, inactive and HDV-superinfected, median 3.26, range 2.26-4.49 Log10 IU/ml) versus untreated-CHB (median 4.68, range 2.76-5.54 Log10 IU/ml), p<0.0001. IgM-anti-HBc positive using the chronic-hepatitis-cut-off" (0.130-S/CO) were positive in 102 of 212 sera (48.1%). Overall total-anti-HBc and IgM-anti-HBc correlated significantly (p<0.001, r=0.417). Total-anti-HBc declined significantly in CHB patients with response to Peg-IFN (p<0.001) and in NUC-treated patients (p<0.001); the lowest levels (median 2.68, range 2.12-3.08 Log10 IU/ml) were found in long-term responders who cleared HBsAg subsequently. During spontaneous and therapy-induced fluctuations of CHB (remissions and reactivations) total- and IgM-anti-HBc correlated with ALT (p<0.001, r=0.351 and p=0.008, r=0.185 respectively). Total-anti-HBc qualifies as a useful marker of HBV-induced-liver-disease that might help to discriminate major phases of chronic HBV infection and to predict sustained response to antivirals.
Project description:Hepatitis B virus X protein (HBx) plays a crucial role in the development of hepatocellular carcinoma (HCC). However, the significance of circulating antibody to hepatitis B virus X antigen (anti-HBx) in sera remains unclear. In the present study, we examined the titers of anti-HBx (IgG) in the sera from 173 patients with chronic hepatitis B (CHB), 106 liver cirrhosis (LC), and 61 HCC by enzyme-linked immunosorbent assay (ELISA), respectively. Our data showed that the positive rates of anti-HBx were higher in sera of LC (40.6%) and HCC (34.4%) than those of CHB (10.4%), P < .05. In all 40 patients with anti-HBx+ out of 340 patients, 39 (97.5%) were HBsAg/HBeAg/anti-HBc+ and 1 (2.5%) was anti-HBs+ (P < .01), suggesting that anti-HBx in sera is a marker of HBV replication rather than a protective antibody. Thus, our findings reveal that circulating anti-HBx in sera is one of the markers of development of LC and HCC mediated by HBV.
Project description:The study aimed to determine the association of additional N-glycosylation mutations in the major hydrophilic region (MHR) of hepatitis B virus (HBV) S gene with hepatocellular carcinoma (HCC) occurrence in HBsAg/anti-HBs coexistent patients. A total of 288 HBsAg/anti-HBs coexistent patients and 490 single HBsAg-positive patients were enrolled, including 193 with HCC, 433 with chronic hepatitis B (CHB), and 152 with acute-on-chronic liver failure (ACLF). The HBV S genes were amplified from serum and sequenced. The frequency of additional N-glycosylation mutations was significantly higher in HCC patients (12.37%) than in CHB patients (4.39%) and ACLF patients (2.63%). The frequency escalated by an order of single HBsAg-positive non-HCC (1.61%), single HBsAg-positive HCC (5.98%), HBsAg/anti-HBs coexistent non-HCC (8.01%), and HBsAg/anti-HBs coexistent HCC (22.36%). Twelve kinds of mutations/mutation patterns were detected, five of which have not been reported. Multivariate analysis showed that age > 40 years [<i>OR</i>, 3.005; 95% CI, 1.177-7.674; <i>P</i> = 0.021], alpha-fetoprotein > 10 ng/mL [<i>OR</i>, 4.718; 95% CI, 2.406-9.251; <i>P</i> <0.001], cirrhosis [<i>OR</i>, 6.844; 95% CI, 2.773-16.891, <i>P</i> < 0.001], Hepatitis B e antigen negativity [<i>OR</i>, 2.218; 95% CI, 4.335, <i>P</i> = 0.020], and additional N-glycosylation mutation [<i>OR</i>, 2.831; 95% CI, 1.157-6.929; <i>P</i> = 0.023] were independent risk factors for HCC in HBsAg/anti-HBs coexistent patients. Dynamical analysis showed that the additional N-glycosylation mutations existed 1-4 years prior to HCC occurrence in eight of 18 patients observed. In conclusion, the dditional N-glycosylation mutations together with HBsAg/anti-HBs coexistence might serve as a predictive indicator for HCC occurrence in chronic HBV-infected patients.
Project description:<h4>Background</h4>Viral hepatitis (hepatitis A, B, C, D and E) remains a public health problem in Peru, with a high disease burden. There are limited data on the prevalence of viral hepatitis at a national level, and none reported for over two decades. In this study, the prevalence rates of hepatitis A (HAV), B (HBV), C (HCV), D (HDV) and E virus (HEV) infections in the Peruvian population were determined to provide updated baseline data that would help guide the development of strategies aimed at reducing the transmission of viral hepatitis in Peru.<h4>Methods</h4>We conducted a cross-sectional, population-based study in the 25 regions of Peru. The study included participants of both sexes, aged 15-69 years, who had lived for >6 months in a specific region of Peru. Serum samples were analyzed by ELISA for anti-HAV (IgG), anti-HBs ≥10 mUI/ml, anti-HCV, anti-HDV and anti-HEV (IgG) antibodies, and by chemiluminescence for the HBV surface antigen (HBsAg) and antibodies against the core HBV antigen (anti-HBc IgM and IgG).<h4>Results</h4>In a total of 5183 study participants, the prevalence rates of anti-HAV (IgG), HBsAg, total anti-HBc IgG, anti-HBs ≥10 mUI/ml, anti-HCV and anti-HEV (IgG) were 98.4% [95% confidence interval (CI) 98.0-98.7), 0.4% (95% CI 0.21-0.55), 10.1% (95% CI 9.4-11.0), 60% (95% CI 58.5-61.2), 0.1% (95% CI 0.02-0.25), and 14% (95% CI 13.1-15.0%), respectively. The prevalence of anti-HDV among HBsAg carriers was 15% (3/20).<h4>Conclusions</h4>The prevalence of HAV and HEV in the population aged 15-69 years in Peru is high, while the prevalence of HBV and HDV has changed from intermediate to low endemicity level and the prevalence of HCV is low. These findings would prove useful in the development of new strategies aimed at reducing the transmission of viral hepatitis in Peru, with a view to ultimately eliminating these infections in the future.
Project description:BACKGROUND: Fresh-frozen plasma (FFP) may contain antibodies to hepatitis B surface antigen (HBsAg, anti-HBs). These anti-HBs may lead to a misinterpretation of the actual hepatitis B immune status. Furthermore, they may not only confer protection against hepatitis B virus (HBV), but may also favor the selection of HBsAg mutants. CASE REPORT: We report a case of de novo HBV infection in a HBV-naïve recipient with alcoholic liver disease, who received a liver from a donor with antibodies to hepatitis B core antigen (HBcAg, anti-HBc) and anti-HBs. RESULTS: A lookback investigation revealed the following: 1) Due to anti-HBs passively acquired through FFP, the recipient was considered immune to HBV and did not receive anti-HBV prophylaxis. 2) Within 1 year after transplantation he developed hepatitis B in absence of any elevated liver enzymes after the anti-HBs by FFP declined. 3) Despite an infection with HBV-containing wild-type HBcAg, the patient did not seroconvert to anti-HBc positivity. 4) The replicating HBV encoded two HBsAg mutations, first sQ129R and 4 months later sP127S. They map to the highly conserved "?" determinant of the HBsAg loop. CONCLUSION: 1) Passive transfer of anti-HBs from FFP led to an erroneous pretransplant diagnosis of HBV immunity when the patient was in fact HBV-naïve. 2) HBsAg mutations might have been selected in escape from donor's actively produced anti-HBs and the recipient's anti-HBs by FFP might have favored this selection. 3) It is doubtful whether hepatitis B immunoglobulin could have prevented the reactivation. 4) Antiviral prophylaxis would have been crucial.
Project description:BACKGROUND: The role of MCP1-2518 A/G in hepatitis B virus (HBV) infection is controversial. Our aim was to evaluate the frequency distribution of MCP1-2518 A/G (rs1024611) polymorphic variants in hemodialysis (HD) patients without or with type 2 diabetes in relation to serological markers of HBV infection. MATERIAL AND METHODS: HD patients (n=170, 48 with diagnosis of type 2 diabetes), who tested positive for total antibodies to HBV core antigen (anti-HBc), underwent MCP1 genotyping using polymerase chain reaction-restriction fragment length polymorphism assay. Anti-HBc was accompanied by antibodies to HBV surface antigen (anti-HBs) in 127 individuals. In anti-HBc-positive/anti-HBs-negative patients, HBV surface antigen (HBsAg) was shown in 15 patients and isolated anti-HBc were present in 28 patients. The distribution of MCP1 genotypes in anti-HBc-positive patients was compared to that in healthy subjects (n=437) and anti-HBc-negative HD patients (n=754). RESULTS: There were no significant differences (Ptrend >0.05) in distribution of MCP1 genotypes between anti-HBc-positive patients, anti-HBc-negative subjects, and controls, regardless of anti-HBs or diabetic status. The MCP1-2518G allele prevalence was higher in HBsAg-positive/anti-HBs-negative patients defined as HBV carriers compared to MCP1-2518G allele frequency shown in groups composed of HBsAg-negative HD individuals and controls (50% vs. 28%, Ptrend 0.022). CONCLUSIONS: A frequency distribution of MCP1 polymorphic variants is not associated with anti-HBs development in response to HBV infection in HD patients, independent of diabetic status, but the MCP1-2518G allele may predispose to HBsAg persistence (HBV carrier status).
Project description:BACKGROUND:Occult Hepatitis B virus (HBV) infection (OBI) is defined as the presence of HBV-DNA in the liver or serum with undetectable hepatitis B surface antigen (HBsAg). Hemodialysis (HD) patients are at risk of acquiring parenterally transmitted infections. OBJECTIVES:The aim of this study was to assess the prevalence of OBI in HD patients. PATIENTS AND METHODS:A hundred HBsAg negative HD patients were included in this study from main dialysis units in Tehran, Iran. HBsAg, hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti-HBc) and liver enzymes levels were examined in all subjects. The presence of HBV-DNA was determined in plasma samples using real-time PCR. RESULTS:A hundredpatients with a mean age of 58.5 ± 16.1 years were enrolled in this study. In total, 56.7% were male and 43.3% female. Anti-HBs, anti-HBc, anti-HCV and anti-HIV were detected in 56.7%, 2%, 5.2% and 1% of patients, respectively. Isolated anti-HBc was detected in 2% of cases. HBV-DNA was detected in 1% of HBsAg negative patients. CONCLUSIONS:This study showed a low rate of isolated anti-HBc and occult HBV infection in HD patients. It can be due to improvement of people's knowledge about HBV transmission routes, HBV vaccination of HD patients and regular surveillance of HBV infection.
Project description:Sudan is a highly endemic area for hepatitis B virus (HBV), and >5% of blood donors are chronically infected. To examine potential strategies to improve HBV blood safety, 404 replacement donor samples previously screened for HBV surface antigen (HBsAg) were tested for antibody to HBV core (anti-HBc), anti-surface antigen (anti-HBs), and HBV DNA. Of 145 anti-HBc-containing samples (36%) identified, 16 retested were HBsAg positive (11%). Anti-HBs was detected in 43/77 (56%) anti-HBc-reactive samples. Six samples were HBsAg(-)/anti-HBc(+)/anti-HBs(+) and contained HBV DNA, meeting the definition of occult HBV infection (OBI). OBIs had low HBV DNA loads (<10 IU/ml) and were genotype B (n = 1) or genotype D (n = 5). Pre-S/S and/or whole genome sequences were obtained from 47 randomly selected HBsAg-positive donors added to the previous 16. Genotype E was identified in 27 strains (57.5%), genotype D in 19 strains (40.5%), and genotype A2 in 1 strain (2%). Two outlier strains within genotype D ultimately were identified as recombinants of genotypes D and E with identical recombination points, suggesting circulating, infectious, recombinant strains. Anti-HBc screening does not appear to be a sustainable blood safety strategy because of the cost and the negative impact on the Sudanese blood supply, even when reduced by anti-HBs testing. Being at the junction between two main African HBV genotypes, genetic recombination occurred and became part of the molecular epidemiology of HBV in Sudan.
Project description:HDV infection causes severe liver disease, the global health burden of which may be underestimated due to limited epidemiological data. HDV depends on HBV for infection, but recent studies indicated that dissemination can also be supported by other helper viruses such as HCV. We used a rapid point-of-care test and an ELISA to retrospectively test for antibodies against the Hepatitis Delta antigen (anti-HDV-Ab) in 4103 HBsAg-positive and 1661 HBsAg-negative, anti-HCV-positive sera from China and Germany. We found that the HDV seroprevalence in HBsAg-positive patients in China is limited to geographic hotspots (Inner Mongolia: 35/251, 13.9%; Xinjiang: 7/180, 3.9%) and high-risk intravenous drug users (HBV mono-infected: 23/247, 9.3%; HBV-HCV co-infected: 34/107, 31.8%), while none of the 2634 HBsAg carriers from other metropolitan regions were anti-HDV-Ab-positive. In Germany, we recorded an HDV seroprevalence of 5.3% in a university hospital environment. In a cohort of HBsAg-negative, anti-HCV-positive patients that were not exposed to HBV before (anti-HBc-negative), HDV was not associated with HCV mono-infection (Chinese high-risk cohort: 0/365, 0.0%; German mixed cohort: 0/263, 0.0%). However, 21/1033 (2.0%) high-risk HCV patients in China with markers of a previously cleared HBV infection (anti-HBc-positive) were positive for anti-HDV-Ab, with two of them being positive for both HDV and HCV RNA but negative for HBV DNA. The absence of anti-HDV-Ab in HCV mono-infected patients shows that HCV cannot promote HDV transmission in humans.