Acute Hepatitis B Outbreaks Related to Fingerstick Blood Glucose Monitoring in Two Assisted Living Facilities

OBJECTIVES: To establish the etiology for outbreaks of hepatitis B virus (HBV) infections at two assisted living facilities (ALFs) and devise appropriate control measures. DESIGN: Multisite outbreak investigations, retrospective cohort. SETTING: Two ALFs in Illinois. PARTICIPANTS: Facility A residents (n=120) and Facility B residents (n=105) and nursing staff (n=6). MEASUREMENTS: For Facility A, a retrospective cohort study to identify risk factors for HBV infection through serological testing of all residents and a medical record extraction. For Facility A and B, investigation of fingerstick blood glucose monitoring techniques. For Facility B, serological HBV testing of nurses and residents receiving fingerstick blood glucose monitoring. RESULTS: At Facility A, five confirmed acute, two probable acute, and one probable chronic HBV infections were identified in the 109 residents tested. All of the eight identified residents with HBV infection had diabetes mellitus. HBV deoxyribonucleic acid (DNA) sequences from the chronic and acute cases were identical. Transmission of HBV was associated with fingerstick blood glucose monitoring (relative risk (RR)=28.5, 95% confidence interval (CI)=1.6–498; P<.001) and insulin injections (RR=7.4, 95% CI=1.3–40.8; P=.03). At Facility B, seven of 21 residents (33.3%) receiving fingerstick blood glucose monitoring had evidence of recent HBV infection. CONCLUSION: Nurses probably transmitted HBV infection from resident to resident during fingerstick blood glucose monitoring in two separate ALFs, causing outbreaks. Awareness of the high risk for HBV transmission during procedures for the care of diabetes mellitus was limited. Following established infection control measures is critical to prevent spread of this highly contagious virus.     

Prevalence of hepatitis B in haemodialysis nursing staff in athens

Background: Healthcare workers are at high risk of acquiring hepatitis B and particularly haemodialysis staff. The aim of the study was to examine the prevalence of hepatitis B markers in haemodialysis nurses and to explore the determinants of the infection. Patients and methods: Two hundred and sixteen haemodialysis nurses from 20 haemodialysis units in Athens completed an anonymous questionnaire, their blood samples were taken and tested for hepatitis B virus (HBV) markers. Results: The prevalence of positive HBsAg among nurses was 0.5%. Anti‐HBc positivity due to past exposure to HBV was 12.5%. A total of 87.5% of the participants had immunity to HBV. Multivariate analysis demonstrated that previous exposure to HBV was related positively with the age of the haemodialysis nursing staff [odd ratios (OR): 1.115, 95% CI: 1.014–1.226, P = 0.025]. Conclusion: The prevalence of HBV in the haemodialysis nursing staff in Athens is low, the vaccination coverage and the immunity to HBV are high in comparison to previous reports.     

Risks associated with hepatitis A and hepatitis B in patients with hepatitis C.

Individuals with hepatitis C virus (HCV) are at risk for acquiring hepatitis A virus (HAV) or hepatitis B virus (HBV) because of shared risk factors. A number of organizations recommend vaccination against HAV and HBV for patients with HCV. The rationale for vaccinating these patients is to prevent hepatic superinfections. Acute HAV superinfection causes more severe disease, acute hepatic failure, and higher fatality rates in patients with underlying chronic liver disease, specifically chronic HBV infection and chronic HCV infection. Available data, although limited, suggest that HBV coinfection with HAV and HCV causes more severe hepatic injury than infection with HAV or HCV alone. At standard doses, hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild-to-moderate hepatitis C or chronic liver disease. Regardless of disease severity, vaccination should be routinely administered to patients upon diagnosis of HCV infection. Early vaccination is important because response to vaccination is reduced as liver disease progresses. Prevaccination and postvaccination serology testing is recommended in specific populations. A new combination hepatitis A and hepatitis B vaccine has been shown to be as safe and effective as monovalent hepatitis A and B vaccines and is currently under review by the United States Food and Drug Administration. A combination vaccine would offer ease of administration and convenience and could increase compliance in patients with hepatitis C or other chronic liver disease: two groups that should be more aggressively targeted by healthcare professionals.     

A pediatric case of hepatitis B virus subgenotype A2 in Japan

Hepatitis B virus (HBV) has been classified into 10 major genotypes, and HBV genotypes C and B are found in the majority of Japanese patients. However, the prevalence of genotype A has been increasing in patients with chronic or acute hepatitis. Here we report a pediatric case of HBV subgenotype A2. A 2-year-old girl was referred to our hospital for liver damage caused by HBV infection. During the pregnancy, her father had developed acute sporadic hepatitis B. The child was born without any complications. She did not receive HBV vaccination at birth because her mother was negative for HBs antigen at the pre-delivery screening; however, her mother developed acute hepatitis B 2 months after delivery. At that time, HBs antigen was detected in the current patient. Phylogenetic full-length sequence analysis revealed HBV subgenotype A2. HBV sequencing was not performed for her parents; therefore, the intrafamilial transmission routes in these cases are unclear, although the authors speculate that, for the current patient, mother-to-child transmission may have occurred. This report illustrates the pitfalls of the selective vaccination strategy in Japan for preventing HBV infection. Universal vaccination to prevent HBV infection might be useful in Japan.     

Eight years of hepatitis B vaccination in Colombia with a recombinant vaccine: factors influencing hepatitis B virus infection and effectiveness.

OBJECTIVE: To evaluate the effectiveness of a recombinant hepatitis B vaccine used in endemic areas of Colombia, as well as risk factors associated with hepatitis B virus (HBV) infection and carriage after vaccine introduction. METHODS: A cross-sectional study was carried out in urban and rural areas of the Colombian Amazon, a highly endemic area for hepatitis B infection. Children under 12 years of age and their mothers were selected for the study using one-stage cluster sampling (N=2145) and were examined for HBV serological markers and antibodies against surface antigen (anti-HBs). RESULTS: There has been a reduction of 60-75% in the prevalence of HBV infection and hepatitis B surface antigen (HBsAg) carriage since HBV vaccination was introduced. Receiving the first dose of HBV vaccine at more than two months after birth was one of the factors associated with HBV carrier status. Maternal HBV infection was also associated with infection in the child. CONCLUSIONS: The recombinant Cuban hepatitis B vaccine has contributed to the reduction of the infection in this highly endemic area, though further efforts are required to improve timely vaccination for children at high risk.     

Hepatitis B virus coinfection in human immunodeficiency virus-infected patients: A review

Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Due to the shared modes of transmission, coinfection with HBV and human immunodeficiency virus (HIV) is not uncommon. It is estimated that 10% of HIV-infected patients worldwide are coinfected with HBV. In areas where an HBV vaccination program is implemented, the HBV seroprevalence has declined significantly. In HIV/HBV-coinfected patients, HBV coinfection accelerates immunologic and clinical progression of HIV infection and increases the risk of hepatotoxicity when combination antiretroviral therapy (cART) is initiated, while HIV infection increases the risk of hepatitis events, cirrhosis, and end-stage liver disease related to chronic HBV infection. With the advances in antiviral therapy, concurrent, successful long-term suppression of HIV and HBV replication can be achieved in the cART era. To reduce the disease burden of HBV infection among HIV-infected patients, adoption of safe sex practices, avoidance of sharing needles and diluent, HBV vaccination and use of cART containing tenofovir disoproxil fumarate plus emtricitabine or lamivudine are the most effective approaches. However, due to HIV-related immunosuppression, using increased doses of HBV vaccine and novel approaches to HBV vaccination are needed to improve the immunogenicity of HBV vaccine among HIV-infected patients.     

Poor response to HBV vaccination and strategies to enhance immunogenicity

Abstract   Hepatitis B vaccination has been proved to be effective in preventing acute and chronic hepatitis B virus (HBV) infection, fulminant hepatitis, and hepatocellular carcinoma. Approximately 5 to 15% of infants and at least 5 to 10% of most healthy adult population failed to produce protective levels of antibodies to HBV vaccination.
The main causes of poor response to HBV vaccination includes intrauterine infection, vaccine escape mutants, genetic hypo-or non-responsiveness to hepatitis B surface antigen (HBsAg) and immune compromised host.
Strategies to enhance immunogenicity to HBV vaccination are as the following: (1) overcome intrauterine or perinatal transmission by antiviral therapy for high risk pregnant women during last trimester, or immediately after birth with HBV hyperimmune globulin for the neonates; (2) higher dosage or more doses of HBV vaccine; (3) better vaccines ; (4) enhance host immune status; (5) better compliance of the vaccines.
In conclusion, current hepatitis B vaccination has been proved to be effective in controlling acute and chronic HBV infection and its complication. Yet further efforts to improve its efficacy generally and in high risk subjects and in immune compromised hosts are needed.     

Outbreak of hepatitis A in the injecting drug user and homeless populations in Bristol: control by a targeted vaccination programme and possible parenteral transmission

OBJECTIVE: To study the use of hepatitis A virus (HAV) vaccination in controlling an outbreak of HAV in inner-city Bristol among injecting drug users (IDUs). To study whether hepatitis C virus (HCV) and hepatitis B virus (HBV) co-infection increases morbidity. DESIGN: Community-based cohort study. SETTING: Avon Health Authority area, UK. PARTICIPANTS: All laboratory-confirmed cases of HAV infection notified in 2000. INTERVENTION: Administration of a targeted vaccination, education and liaison programme. MAIN OUTCOME MEASURES: Number of cases of HAV before and after introduction of HAV vaccination programme. Mortality and number of patients requiring hospital admission. Association of HCV and HBV co-infection with hospital admission. RESULTS: Ninety cases of HAV were reported in the first 6 months of 2000, of whom a substantial number were IDUs and/or inner-city hostel residents. In the second 6 months of 2000, following the introduction of a vaccination programme among homeless people, hostel residents, and IDUs, the number of HAV cases fell to 33. Sixteen patients had evidence of HCV co-infection. No patient had chronic HBV infection. Two patients died as a result of HAV, and two subsequently died from drug misuse. Fifty-six per cent of HCV-co-infected patients required admission to hospital compared with 28% non-HCV-co-infected patients. CONCLUSIONS: This is the first reported successful use of vaccination to control an outbreak of HAV in a population of IDUs and to prevent transmission to the wider population. HCV co-infection appears to increase the severity of HAV illness, as demonstrated by increased incidence of hospital admission.     

Spectrum of hepatitis B and renal involvement

Renal involvement in hepatitis B occurs in various spectrums and its knowledge is important for clinicians in management of patients. The renal diseases most commonly associated with hepatitis B virus (HBV) infection include membranous nephropathy, membranoproliferative glomerulonephritis and Polyarteritis nodosa. The widespread use of hepatitis B vaccination has decreased the incidence of HBV‐related renal diseases. The incidence of HBV infection in dialysis patients has significantly decreased over the past few decades because of screening of blood products for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody, implementation of infection control measures and hepatitis B vaccination. The definition of acute kidney injury has been recently modified in cirrhotic population, helping in prognosis and prediction of mortality. The most common etiologies of acute kidney injury in this cirrhotic population, which account for 80% to 90% of all cases, include volume depletion, acute tubular necrosis and hepatorenal syndrome. Treatment with oral nucleoside/tide analogues (NA) brought a new paradigm in the management of HBsAg positive glomerulonephritis, kidney transplant recipients and dialysis patients, resulting in effective viral suppression, reduced hepatic complications and improved patient survival, without compromising renal allograft outcome. NAs are cleared by the kidneys and therefore their dosage has to be adjusted in all patients with impaired renal function. This article reviews the recent knowledge of the pathogenesis and treatment of HBV‐related glomerulonephritis and discusses the management of hepatitis B in patients on dialysis, kidney transplant recipients and cirrhotics, which is continuously evolving.     

Twenty-year survey of the epidemiology of hepatitis B in Denmark: effect of immigration

Implementation of hepatitis B virus (HBV) vaccination is being considered in Denmark. Therefore, a 20 y survey on the epidemiology of HBV infection was performed. All notified cases of acute HBV infection in Denmark from 1982 to 2002 were reviewed retrospectively and all available data from 1970 to 2001 on the prevalence of hepatitis B surface antigen (HBsAg) in different groups of the Danish population were studied. The notified annual incidence of acute HBV infection has declined from more than 200 cases to fewer than 50 cases in 2001. In the indigenous population there has been a similar decline in prevalence of HBsAg carriers, from 0.15 to 0.03%, but owing to immigration of new HBsAg carriers from developing countries the overall number of carriers has not changed. The small effect of immigration on the incidence of acute HBV infections as well as the decreasing prevalence of HBsAg carriers among Danes should be taken into account when planning new vaccination strategies in Denmark.     

Vaccination against hepatitis b in patients with chronic liver disease

The prevalence of chronic liver disease is increasing, while at the same time, many at-risk populations are witnessing a resurgence of hepatitis B virus (HBV) infection. Thus, more patients are likely to have multiple causes of liver disease, as risk factors often overlap. Such patients may develop either acute viral hepatitis superimposed on pre-existing chronic liver disease or chronic infection with two hepatitis viruses. Patients with chronic HBV and hepatitis C virus coinfection have more severe laboratory abnormalities, more hepatic fibrosis, and greater frequency of cirrhosis, in addition to more complications of cirrhosis and a higher incidence of hepatocellular carcinoma. Acute hepatitis B superimposed on chronic hepatitis C may result in fulminant hepatitis, although this outcome is not as well proven as the increased morbidity of chronic hepatitis B and C coinfection. Both acute and chronic coinfection with HBV can be prevented. Vaccines for hepatitis B are safe in patients with chronic liver disease of a variety of causes and are effective, particularly if used early. Early vaccination against hepatitis B, as well as hepatitis A, should be part of the routine management of chronic liver disease.     

Selective functional deficit in dendritic cell--T cell interaction is a crucial mechanism in chronic hepatitis B virus infection

Summary. A defect in specific T cell immunity has long been assumed to be the central mechanism of persistent Hepatitis B virus (HBV) infection. Recent studies on HBV transgenic mice have suggested, however, that functional deficit of dendritic cells (DC) was an underlying cause for the T cell dysfunction. The functions of monocyte‐derived DC were determined by studying 75 subjects that included chronic hepatitis B patients with low or high HBV load; antibody to hepatitis B surface antigen (anti‐HBs) positive individuals who had recovered completely from previous acute HBV infection; healthy donors who had received hepatitis B vaccination and were anti‐HBs positive; and immunologically naïve to HBV or the vaccine individual. Impaired interactions between monocyte‐derived DC and T cells were shown in chronic HBV infection patients, especially in those with active virus replication. The dysfunctions included: (i) failure of DC to increase human leukocyte antigen (HLA‐II), B7 expression and interleukin‐12 secretion in responses to hepatitis B surface antigen (HBsAg), (ii) defective induction of T cell proliferative response to HBsAg, (iii) failure to activate T cells to produce cytokines and (iv) deficit in the induction of antigen specific cytotoxic T lymphocytes (CTLs). In vitro treatment of DC with tumour necrosis factor‐α improved HLA‐II and B7 expression, as well as Th cell and CTL responses. It is concluded that defective DC‐T cell interactions may account for the specific T cell immune defects in chronic HBV infection. Immunotherapy that aims at restoring DC functions could offer a new opportunity for effectively managing persistent HBV infections.     

The relationship of hepatitis B virus infection between adults and their children in Guangxi Province, China

BACKGROUND/AIM: This study aimed to describe the seroepidemiology of hepatitis B virus (HBV) infection, with emphasis on transmission of HBV infection between adults and their children. METHODS: We analyzed the hepatitis sero-survey data collected from 2132 persons aged 1-59 years (624 families) in Guangxi Province, China, 1992. Blood was tested for the presence of the hepatitis B surface antigen (HBsAg), the antibody to hepatitis B core antigen (anti-HBc), and the antibody to hepatitis B surface antigen (anti-HBs). RESULTS: Of the 2132 persons surveyed, 119 (5.6%) reported receiving HBV vaccination. Among those persons who did not receive HBV vaccination, 19% were HBsAg positive (current HBV infection) and 57% had a past HBV infection (they were HBsAg negative and either anti-HBc positive or anti-HBs positive). Among 519 children aged 1-10 years who did not receive HBV vaccination, 21% had current HBV infection and 37% had past HBV infection. Among 289 children of both parents who were HBsAg negative, 16% had current HBV infection and 36% had past HBV infection. CONCLUSIONS: The high prevalence of community-acquired HBV infection in children and the low HBV vaccination coverage in Guangxi should alert public health agencies to re-examine their current policies for preventing HBV transmission.     

Therapeutic vaccination in chronic hepatitis B: preclinical studies in the woodchuck model

Summary.  Interferon-α and nucleoside analogues are available for the treatment of chronic hepatitis B virus (HBV) infection but do not lead to a satisfactory result. New findings about the immunological control of HBV during acute infection suggest the pivotal role of T-cell mediated immune responses. Several preclinical and clinical trials were undertaken to explore the possibility of stimulating specific immune responses in chronically infected animals and patients by vaccination. However, vaccination with commercially available HBV vaccines in patients and immunization in woodchucks with core or surface proteins of woodchuck hepatitis virus (WHV) did not result in effective control of HBV and WHV infection, suggesting that new formulations of therapeutic vaccines are needed. Some new approaches combining antiviral treatments with nucleoside analogues, DNA vaccines and protein vaccines were tested in the woodchuck model. It could be shown that therapeutic vaccinations are able to stimulate specific B- and T-cell responses and to achieve transient suppression of viral replication. These results suggest the great potential of therapeutic vaccination in combination with antivirals to reach an effective and sustained control of HBV infection.     

Is Hepatitis A More Severe in Patients with Chronic Hepatitis B and Other Chronic Liver Diseases?

There are several published case series of acute hepatitis A, with coverage ranging from epidemics to case reports, that provide information regarding the clinical course and outcome of hepatitis A in patients with underlying chronic hepatitis B virus (HBV) infection (1–12). Only a few reports have addressed the outcome of hepatitis A in patients with other chronic liver diseases (2, 13). Some, but not all, of these reports suggest that hepatitis A superimposed on chronic hepatitis B or other chronic liver diseases is associated with higher peak laboratory abnormalities, more severe disease, including fulminant hepatic failure, and a higher case fatality rate. In addition, analysis of HBsAg titer and serum markers of HBV replication, including HBeAg, HBV DNA, and DNA polymerase, reveals suppression of HBV replication. With the availability of hepatitis A virus (HAV) vaccine in many countries and its imminent approval for use in the United States, the issue of whether or not patients with chronic liver diseases, including chronic HBV infection, should be a target group for vaccination to prevent hepatitis A warrants consideration. The purpose of this review is to analyze the published literature addressing the clinical course and outcome of acute hepatitis A in patients with chronic HBV infection and other chronic liver diseases to determine if hepatitis A is more severe in these patients.     

Lower Hepatitis G Virus Infection Prevalence Compared to Hepatitis B and C Virus Infection Prevalences

To more accurately determine the seroprevalence of hepatitis G virus (HGV) infection, we surveyed antibody to HGV (anti-E2) by enzyme-linked immunosorbent assay (ELISA) and HGV RNA by nested polymerase chain reaction (PCR) in 298 residents of a hepatitis C virus (HCV)-endemic area of Japan and in 225 hemodialysis patients. We then compared these findings with known HCV and hepatitis B virus (HBV) infection prevalences. Anti-E2 and HGV RNA prevalences were 32 (10.7%) and 5 (1.7%) in the residents and 24 (10.7%) and 10 (4.4%) in the hemodialysis patients, respectively. Anti-E2 and HGV RNA concurrence was found in two of the hemodialysis patients. Total HGV marker (anti-E2 and/or HGV RNA) prevalences [37 (12.4%) in residents and 32 (14.2%) in hemodialysis patients], were significantly lower than the prevalences of antibody to HCV (anti-HCV) by ELISA [59 (19.8%) and 96 (42.7%)], and antibody to hepatitis B core antigen (anti-HBc) by radioimmunoassay (RIA) [87 (29.2%) and 101 (44.9%)] (P < 0.05). The anti-HCV prevalence in subjects with total HGV marker was significantly higher than in those without total HGV marker. There was no significant difference in anti-HBc prevalence between those with and without total HGV marker. The viremic rate was highest in HCV infection (HCV RNA by PCR/anti-HCV) (83.2%), with HGV infection (HGV RNA/total HGV marker) (21.7%) intermediate, and HBV infection (hepatitis B surface antigen by RIA/anti-HBc) (5.3%) lowest (P < 0.05). These findings indicate that HGV infection was less endemic than HCV and HBV. HGV was eliminated naturally more frequently than HCV infection and less frequently than HBV infection.     

Acute hepatitis B: the limits of maintaining patient confidentiality

Household contacts of hepatitis B (HBV) are at risk of infection, and guidelines advise vaccination of these contacts in addition to sexual partners (along with traditional high-risk groups). We present a case of intrafamilial transmission of acute hepatitis B virus (HBV) following failure to self-disclose status to family members. Complex confidentiality issues can arise following a diagnosis of HBV infection.     

Correlation of hepatitis B surface antigen clearance with the route of hepatitis B virus infection

We studied 563 consecutive adults with acute hepatitis B hospitalized from May 1981 to May 1983 and their habitual heterosexual partners. Radio-immunoassays for the detection of serological markers of hepatitis A virus (HAV) and hepatitis B virus (HBV) and enzyme-immunoassay for the detection of IgM antibody to hepatitis B core antigen (IgM anti-HBc) were used. Of the 563 patients, 503 (89.7%) were hepatitis B surface antigen (HBsAg) positive and 60 (10.7%) were HBsAg negative on admission. Absence of HBsAg on admission was observed significantly more frequently in patients infected possibly by the heterosexual route than in the remaining patients (23.3% versus 6.6%; P less than 0.001). This finding was independent of sex. These data show that the route of HBV infection rather than the sex appears to have a more important role in the rapid clearance of HBsAg.     

Eliminating the Blood: Ongoing Outbreaks of Hepatitis B Virus Infection and the Need for Innovative Glucose Monitoring Technologies

Background

As part of routine diabetes care, capillary blood is typically sampled using a finger-stick device and then tested using a handheld blood glucose meter. In settings where multiple persons require assistance with blood glucose monitoring, opportunities for bloodborne pathogen transmission may exist.

Methods

Reports of hepatitis B virus (HBV) infection outbreaks in the United States that have been attributed to blood glucose monitoring practices were reviewed and summarized.

Results

Since 1990, state and local health departments investigated 18 HBV infection outbreaks, 15 (83%) in the past 10 years, that were associated with the improper use of blood glucose monitoring equipment. At least 147 persons acquired HBV infection during these outbreaks, 6 (4.1%) of whom died from complications of acute HBV infection. Outbreaks appear to have become more frequent in the past decade, primarily affecting long-term care residents with diabetes. Each outbreak was attributed to glucose monitoring practices that exposed HBV-susceptible persons to blood-contaminated equipment that was previously used on HBV-infected persons. The predominant unsafe practices were the use of spring-loaded finger-stick devices on multiple persons and the sharing of blood glucose testing meters without cleaning and disinfection between uses.

Conclusion

Hepatitis B virus infection outbreaks associated with blood glucose monitoring have occurred with increasing regularity in the Unites States and may represent a growing but under-recognized problem. Advances in technology, such as the development of blood glucose testing meters that can withstand frequent disinfection and noninvasive glucose monitoring methods, will likely prove useful in improving patient safety.     

What did we learn from the Shanghai hepatitis A epidemic?

A major outbreak of hepatitis A (HAV), associated with consumption of raw clams, occurred in Shanghai, China in 1988. Over 300 000 cases were reported, of which 47 (0.015%) were fatal. An elevated mortality rate was observed in hepatitis B surface antigen (HBsAg)-positive patients (0.05%). The majority of these patients were also hepatitis B e antigen (HBeAg)-positive, indicating active liver disease and high viral replication rates. The increased mortality in hepatitis B virus (HBV)/HAV coinfected individuals is hypothesized to be the result of T-cell-mediated destruction of HBV-infected hepatocytes, enhanced by acute HAV infection. Following recovery from HAV there is an increase in HBV expression and activated cytotoxic cells and subsequent cytolysis. Patients with chronic HBV infection are clearly at considerable risk of severe disease and increased mortality in the event of HAV infection. The period of greatest risk is during the immunoeliminative phase of HBV infection, which generally occurs in early adulthood. With the prevalence of HBV approaching 10% in this group, there is a clear opportunity for benefit from vaccination.