Acute Hepatitis B Virus Cases Research Articles

Impact of the Universal Implementation of Adolescent Hepatitis B Vaccination in Spain.

The aim of this study was to analyse the impact of the introduction of universal adolescent HBV vaccination on the incidence of acute hepatitis B virus (HBV) infections. Acute HBV cases reported to the Spanish National Epidemiological Surveillance Network between 2005 and 2021 were included. For regions starting adolescent vaccination in 1991-1993 and in 1994-1996, HBV incidence rates were compared by calculating the incidence rate ratio (IRR) and 95% confidence interval (CI). We also analysed the 2017 Spanish national seroprevalence survey data. The overall acute HBV incidence per 100,000 persons was 1.54 in 2005 and 0.64 in 2021 (p < 0.001). The incidence in 2014-2021 was lower for regions that started adolescent vaccination in 1991-1993 rather than in 1994-1996 (IRR 0.76; 95% CI 0.72-0.83; p < 0.001). In the 20-29 age group, incidence in regions that started adolescent vaccination in 1991-1993 was also lower (IRR 0.87; 95% CI 0.77-0.98; p = 0.02 in 2005-2013 and IRR 0.71; 95% CI 0.56-0·90; p < 0.001 in 2014-2021). Anti-HBc prevalence in the 35-39 age group was lower in the regions that started vaccination earlier, although the difference was not statistically significant (p = 0.09). Acute HBV incidence decreased more in the young adult population in regions that began adolescent vaccination earlier. Maintaining high universal vaccination coverage in the first year of life and in at-risk groups is necessary to achieve HBV elimination by 2030.

Effectiveness of Hepatitis B Vaccination Campaign in Italy: Towards the Control of HBV Infection for the First Time in a European Country.

Background: In 1991, a mass immunization campaign against the hepatitis B virus (HBV) for children and teenagers was introduced in Italy. This study evaluated the impact of the immunization campaign on the incidence and modes of HBV transmission. Method: Acute HBV cases of viral hepatitis were reported to the National Surveillance System (SEIEVA). Hepatitis A cases reported to the same system were used as controls to calculate the adjusted odds ratios and the population attributable risk for potential risk factors. Results: The incidence of acute HBV declined from 5.0 in 1990 to 0.4 in 2019 per 100,000 population. The fall was almost total in people targeted by the campaign: in 2019, zero cases (100% reduction) in the age-group 0–14 years and 0.1 cases per 100,000 population (99.4% reduction) in the age-group 15–24 years were reported. In the decade 2010–2019, nearly one-fifth (19.3%) of cases occurred in foreigners. Intravenous drug use is no longer a risk factor (OR = 0.7; 95% CI = 0.5–1.02). Beauty treatments, risky sexual exposure, and household contact with an HBsAg carrier were found to be independent predictors of acute hepatitis B. Conclusions: The HB vaccination campaign proved effective in minimising acute HBV in Italy. Control of the infection is close to being reached for the first time in Europe.

Characterization of Acute and Chronic Hepatitis B Virus Genotypes in Canada.

ObjectiveThe prevalence and distribution of hepatitis B virus (HBV) genotypes in Canada is not known. Genotypic analysis may contribute to a better understanding of HBV strain distribution and transmission risk.MethodsHBV surface antigen (HBsAg) positive samples of acute (n = 152) and chronic (n = 1533) HBV submitted for strain analysis or reference genotype testing between 2006 and 2012 were analyzed. The HBsAg coding region was amplified to determine the HBV genotype by INNO-LiPA assay or sequence analysis. Single and multivariate analyses were used to describe genotypes’ associations with known demographic and behavioral risk factors for 126 linked cases of acute HBV.ResultsNine genotypes were detected (A to I), including mixed infections. Genotype C (HBV/C) dominated within chronic infections while HBV/D and A prevailed among acute HBV cases. History of incarceration and residing with a chronic HBV carrier or injection drug user were the most frequently reported risks for acute HBV infection. Over time, HBV/A increased among both acute and chronic infections, and HBV/C and HBV/D decreased among chronic infections.ConclusionChronic and acute HBV genotypes in Canada differ in the relative distribution and their associations with known risk factors, suggesting different routes of transmission and clinical progression of infection.

Acute hepatitis B outbreaks in 2 skilled nursing facilities and possible sources of transmission: North Carolina, 2009-2010.

Acute hepatitis B virus (HBV) infections have been reported in long-term care facilities (LTCFs), primarily associated with infection control breaks during assisted blood glucose monitoring. We investigated HBV outbreaks that occurred in separate skilled nursing facilities (SNFs) to determine factors associated with transmission. Outbreak investigation with case-control studies. Two SNFs (facilities A and B) in Durham, North Carolina, during 2009-2010. Residents with acute HBV infection and controls randomly selected from HBV-susceptible residents during the outbreak period. After initial cases were identified, screening was offered to all residents, with repeat testing 3 months later for HBV-susceptible residents. Molecular testing was performed to assess viral relatedness. Infection control practices were observed. Case-control studies were conducted to evaluate associations between exposures and acute HBV infection in each facility. Six acute HBV cases were identified in each SNF. Viral phylogenetic analysis revealed a high degree of HBV relatedness within, but not between, facilities. No evaluated exposures were significantly associated with acute HBV infection in facility A; those associated with infection in facility B (all odds ratios >20) included injections, hospital or emergency room visits, and daily blood glucose monitoring. Observations revealed absence of trained infection control staff at facility A and suboptimal hand hygiene practices during blood glucose monitoring and insulin injections at facility B. These outbreaks underscore the vulnerability of LTCF residents to acute HBV infection, the importance of surveillance and prompt investigation of incident cases, and the need for improved infection control education to prevent transmission.

More Lessons From the Taiwanese Hepatitis B Virus Vaccine Program

In this issue of The Journal of Infectious Diseases, the Taiwan National Children’s Hospital group, under the capable leadership of Dr Mei-Hwei Chang, has once again used carefully constructed national surveillance data to teach us something about hepatitis B virus (HBV) infection in young subjects who received neonatal HBV vaccine. As one would predict, the highest rates for acute HBV infection were in unvaccinated individuals. Also, as expected, rates of acute HBV infection were lower in vaccinated birth cohorts aged 15–24 years than in unvaccinated birth cohorts, demonstrating once again the efficacy of the universal newborn vaccination program. The biggest disappointment was that, due to breakthrough HBV infection from mother-to-infant transmission, vaccinated infants (0.78 per 100 000) had higher rates than those aged 1–14 years (0.04 per 100 000), who had the lowest rates. It is disconcerting that the 8 infants who were born to mothers with hepatitis B e antigen, and who developed acute HBV infection in the first year of life, were not given neonatal hepatitis B immunoglobulin (in accordance with Taiwan national vaccine policy). Although the authors discuss this problem and acknowledge that the combination of active and passive vaccination for all infants born to hepatitis B surface antigen (HbsAg)–positive women is 85%–95% effective in preventing transmission, it is puzzling that the authors do not recommend a change in the Taiwan national vaccine policy to that effect. The authors also do not comment on the fact that the infants were given the first dose of recombinant HBV vaccine at 2–43 days of life instead of within 12 hours of birth, as per the recommendation of the American Academy of Pediatrics. It is also unfortunate that there is no clinical information available to inform us whether the cases of acute HBV in vaccinated subjects differed phenotypically from cases in unvaccinated subjects. Likewise, with somewhat incomplete information, it is difficult to know if reporting physicians could be 100% accurate in differentiating acute HBV from acute on chronic HBV infection, because a liver biopsy and previous serology were necessary for that distinction but not always available. Although the success of the aggressive universal infant vaccine program was mentioned only in passing, it is important to acknowledge the tremendous achievement this program (95% vaccine coverage beginning in 2001) has already demonstrated by its efficacy in reducing rates of chronic HBV, fulminant HBV, and hepatocellular carcinoma in children. Certainly, the decline in acute HBV cases in Taiwan from 2001 to 2008 is a remarkable success. The most useful and cost-effective conclusions from this careful study are that energetic follow-up during the first 12 months of life should be focused on infants born to HbsAg-positive mothers and that, in a country like Taiwan where HBV is endemic, vaccine efforts could be focused on subjects $25 years of age who have not benefited from the universal newborn vaccination program. Given the cost in terms of both human suffering from chronic HBV liver disease and hepatocellular carcinoma and related public health expenditures, we should all continue to admire the Taiwan National Children’s Group for their efforts to analyze how best to reduce those costs, and to learn from them.

Elimination of hepatocellular carcinoma and acute hepatitis B in children 25 years after a hepatitis B newborn and catch-up immunization program

Alaska Native people experience the highest rates of acute and chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) in the United States. We examined the effect of a universal newborn immunization with hepatitis B vaccine and mass population screening immunization program initiated in 1984 on rates of HBV and HCC in children 25 years later. During this time, the population of Alaska Native people grew from an estimated 75,000 to 130,000 persons. A surveillance system to detect acute HBV infection in Alaska Native facilities was established in 1981. Cases of HCC in children under 20 years of age were identified using a National Cancer Institute (NCI)-funded Cancer Registry established in 1969 coupled with an active surveillance program of screening persons with chronic HBV semiannually for alpha-fetoprotein since 1982. The incidence of acute symptomatic HBV infection in persons <20 years of age fell from cases 19/100,000 in 1981-1982 to 0/100,000 in 1993-1994. No cases of acute HBV have occurred in children since 1992. The incidence of HCC in persons <20 years decreased from 3/100,000 in 1984-1988 to zero in 1995-1999 and no cases have occurred since 1999. The number of identified hepatitis B surface antigen-positive children <20 years in the Alaska Native population declined from 657 in 1987 to two in 2008. Universal newborn vaccination coupled with mass screening and immunization of susceptible Alaska Natives has eliminated HCC and acute symptomatic HBV infection among Alaska Native children and this approach is the best way to prevent HBV-related disease in children.

The new epidemiology of hepatitis B in the United States

Although the incidence of hepatitis B virus (HBV) in the United States is decreasing, it remains an important health issue, with nearly 2 million people currently infected and a 7% to 30% lifetime mortality rate. Vaccination has markedly decreased the number of acute HBV cases, especially in children and adolescents; however, there continues to be a substantial incidence of new infections in intravenous drug users and persons with high-risk sexual behavior and of newly recognized disease in immigrants. Perinatal transmission has been significantly reduced with universal infant vaccination, and transfusion/iatrogenic infection has been nearly eradicated by screening blood products and vaccinating at-risk medical professionals. HBV infection rates vary with respect to racial and geographic distribution as well as known risk factors. The Asian/Pacific Islander population continues to have the highest rate (prevalence) of infection in the United States. Further advances in screening and vaccination must be made to further reduce the incidence and prevalence of HBV in the United States.

Genotype D amongst injection drug users with acute hepatitis B virus infection in British Columbia

The eight genotypes of hepatitis B virus (HBV) exhibit distinct geographical distributions. This study identified HBV genotypes and transmission modes associated with acute infection in British Columbia (BC), Canada, from 2001 to 2005. Seventy cases of acute HBV in BC were identified from laboratory reports using a standardized case definition. Interviews for risk factors and hepatitis history were conducted for each case. HBV genotypes were determined by BLAST comparison analysis of the surface (S) or preS gene sequence. To illustrate the distribution of genotypes identified amongst acute cases in BC, an annotated map was produced showing the global occurrence of HBV genotypes. The majority of acute HBV cases occurred in Caucasian, Canadian-born males, with 30% of cases reporting injection drug use (IDU) and 21% reporting incarceration. The most common genotype observed was genotype D (62.9%), followed by genotypes A (18.6%), C (11.4%), B (4.3%), and E (1.4%). A significant association was observed between Genotype D and IDU (P = 0.0025) and previous incarceration (P = 0.0067). Phylogenetic analysis of the S gene sequence demonstrated identical or high genetic relatedness amongst genotype D viral strains (86% sub-genotype D3), thus verifying transmission clustering amongst BC injection drug users. The association between acute HBV genotype and reported transmission modes has not been previously described in North America. Tracking of genotypes can help identify disease transmission patterns and target at-risk populations for preventive immunization.

Mutation spectra of the surface-protein-coding region of the HBV genome in HBV-vaccinated and non-vaccinated individuals in Hungary

Hepatitis B virus (HBV) infection has a major effect on health care systems, with about one-third of the world's population currently infected with the virus. There is an effective vaccine against HBV, which contains a recombinant "surface antigen" produced in an expression vector. Vaccination has proved to be successful in Hungary: the number of acute HBV cases has decreased in the past 10 years. Although an increasing number of publications report on "vaccine-escape" HBV variants which can infect HBV-vaccinated individuals, such mutant HBV strains have not yet been detected in Hungary. We therefore surveyed two risk groups for vaccine-escape or immunoglobulin-escape HBV mutations in Hungary: 28 actively and/or passively HBV-immunized children of HBV carrier mothers who proved to be HBsAg and/or anti-HBc positive and 40 symptomless HBV carrier pregnant women (presumably carrying genotype B or C). We focused on the coding sequences of the "a" immundominant region of the surface protein. We could not detect the G145R amino acid substitution associated with vaccine escape mutant virus. However, we could map other mutations potentially affecting the immunodominant "a" region of the HBV surface protein.

Molecular epidemiology of acute hepatitis B in the Netherlands in 2004: nationwide survey

To gain insight into hepatitis B virus (HBV) transmission in the Netherlands, epidemiological data and sera were collected from reported cases of acute HBV infections in the Netherlands in 2004. Cases were classified according to mode of transmission. A fragment of the S-gene of HBV (648 bp) was amplified, sequenced, and subjected to phylogenetic analysis. Of the 291 acute HBV cases reported in 2004, 158 (54%) were available for genotyping. Phylogenetic analysis identified 6 genotypes: A (64%), B (3%), C (3%), D (21%), E (5%) and F (5%). Of HBV infected men having sex with men, 86% were infected with genotype A, accounting for 43% of all patients infected with this genotype. There were only three reported cases of injecting drug use of which one was available for sequencing (genotype A). Unlike the genotype A cluster, sequences within the genotype B-E clusters were heterogenic. Within genotype F, several isolates had identical sequences, but patients could not be epidemiologically linked. Sexual transmission, particularly by men having sex with men was the most important transmission route for HBV. Injecting drug use plays a minor role. Genotype A is predominant in the Netherlands, especially among men having sex with men. In addition to imported strains, there seems to be a pool of related but non-identical strains circulating among chronic carriers in the migrant population, from which occasionally new patients are infected, primarily by heterosexual transmission.

A Cross-Sectional Analysis of Acute Hepatitis B Virus Reported to the Vancouver Coastal Health Authority from 2000 to 2003

Acute hepatitis B virus (HBV) transmission remains a significant public health problem despite effective vaccination and prophylaxis strategies. Vancouver, British Columbia, has a large ethnic community from endemic areas, which may further impact on the epidemiology of acute HBV. A cross-sectional study of factors associated with acute HBV cases reported to the Vancouver Coastal Health Authority (Vancouver, British Columbia) from 2000 to 2003 is reported. New seropositive cases of hepatitis B surface antigen were reported to the Vancouver Coastal Health Authority Office of Communicable Disease Control. Patients meeting both clinical and laboratory criteria for acute HBV were interviewed by telephone for demographic and risk behaviour information. Risk behaviours within the last six months before disease onset were ranked on efficiency of transmission in a mutually exclusive risk category. There were 78 patients of identified acute HBV in Vancouver from 2000 to 2003. The overall incidence rate was 3.38 per 100,000 person years. Outside of Canada, Asia was the most common place of birth (29.5%). The three most frequently identified risk factors were men who have sex with men (21.9%), heterosexual activity with two or more partners (14.0%) and intravenous drug use (14.0%). Sexual contact with an HBV carrier was identified in 9.4% of patients. Sexual transmission is a major mode in the spread of HBV in Vancouver. Existing public education, surveillance and vaccination strategies for HBV need to be strengthened to address those engaging in risky behaviours.

Epidemiological study of hepatitis B virus infection in Manitoba, Canada, 1992–2003

In comparison with other Canadian provinces and most Western countries, the province of Manitoba maintains a different vaccination policy for hepatitis B. This policy provides selective antenatal screening for hepatitis B in women and an inoculation program for hepatitis B vaccination for fourth-grade pupils. There has been increasing concern for this policy with regard to its influence on secular trends of acute hepatitis B incidence in Manitoba. This created a need to summarise the epidemiological characteristics of hepatitis B virus (HBV) infection in Manitoba and to allocate finances and human resources for future prevention programs. The Cadham Provincial Laboratory in Winnipeg, a Canadian Public Health Laboratory, is responsible for testing all specimens for diagnosis of various common infectious diseases in Manitoba. During the period from 1 January 1992 to 31 December 2003, a total of 285,946 clinical specimens were submitted to this laboratory, which confirmed 310 cases of acute HBV and 7,556 cases of chronic HBV infection. A total of 18,168 individuals were identified as having vaccine-induced immune status. The incidence rate of acute HBV infection has significantly decreased from 6.52/100,000 person-years in 1996 to 0.86/100,000 person-years in 2003. Annual prevalence rates of chronic HBV infection in Manitoba increased slightly from 42.96 cases/100,000 population in 1992 to 71.47 cases/100,000 population in 2003. Incidence rates were generally higher in men than in women at all age groups, with values of 2.65 and 1.65 per 100,000 population, respectively (chi-square=15.768, p value <0.001). The highest incidence rate for both males and females was observed in the age group 30-34 years. The North Eastman and Winnipeg Regional Health Authorities showed significantly higher incidence rates of acute hepatitis B compared with the other nine Regional Health Authorities. Selective hepatitis B vaccination programs for children in Manitoba had achieved the greatest success in the prevention of vertical and horizontal transmission. There is an urgent need to develop cost-effective harm-reduction strategies for hepatitis B prevention among adults (aged 30-34) and groups at risk in Manitoba.

Occult hepatitis B virus after acute self-limited infection persisting for 30 years without sequence variation

Background/Aims: After acute self-limited hepatitis B virus (HBV) infection, serological loss of viral antigens and appearance of anti-HBs is generally believed to signify viral clearance. Latent and occult HBV infection appearing decades after self-limited hepatitis B has not been reported, nor has the evolutionary rate of HBV DNA over the same observation period. Methods: DNA from serum and leukocytes from 16 patients with acute self-limited hepatitis B 30 years earlier was tested by polymerase chain reaction and positive samples were sequenced. Liver tissue from four patients was also tested. Additionally, another 10 HBV strains isolated from acute HBV cases in 1969–72 were compared to 11 strains isolated from acute cases in 1998–99 in the same community. Results: HBV DNA was detected in liver from two patients, but not in serum or leukocytes. The HBV strains detected in liver showed complete homology, in the sequences analyzed, to the strains originally infecting these patients. Ten strains from 1998–99 were identical in pre-S and core promoter/precore regions to strains from the same community isolated 30 years earlier. Conclusions: HBV can persist as an occult infection three decades after acute, apparently self-limited hepatitis B, and both the mutation and evolutionary rates of HBV DNA are low.

Hepatitis B in Latin America: epidemiological patterns and eradication surgery

A comprehensive epidemiological analysis of hepatitis B virus (HBV) endemicity and transmission in Latin America was carried out to suggest policies and strategies for the use of hepatitis B vaccine in the region. The pattern of HBV endemicity based on available data from blood bank screening programmes and clinical and epidemiological studies varied widely: it was low in temperature South America, Mexico and some Caribbean islands; moderate in Brazil, Andean countries, part of central American and the Carribean; and high in Hispaniola, St. Kitts/Nevis and in the Amazon basin (parts of Brazil, Peru, Venezuela, Colombia). Statistical estimates of HBV_related morbidity showed that > 150 000 acute HBV cases occur per year. As the endemicity of HBV varies considerably, different prevention strategies should be applied in this area. The highest priority should be the prevention of perinatal and early childhood transmission, but vaccination of adults belonging to high-risk groups should also be recommended.