Acute Hepatitis B Virus Infection Research Articles

T cell immunopathogenesis and immunotherapeutic strategies for chronic hepatitis B virus infection

Hepatitis B is caused by the host immune response and T cells play a major role in the immunopathogenesis. More importantly, T cells not only destroy hepatocytes infected by hepatitis B virus (HBV), but also control HBV replication or eradicate HBV in a noncytolytic manner. Therefore, analysis of T cell immune response during acute and chronic HBV infection is important to develop a strategy for successful viral control, which could lead to immunotherapy for terminating persistent HBV infection. There have been many attempts at immunotherapy for chronic HBV infection, and some have shown promising results. High viral load has been shown to suppress antiviral immune responses and immunoinhibitory signals have been recently elucidated, therefore, viral suppression by nucleos(t)ide analogs, stimulation of antiviral immune response, and suppression of the immunoinhibitory signals must be combined to achieve desirable antiviral effects.

A Case of Hepatitis B Virus/human Immunodeficiency Virus Coinfection in a Patient Who Achived Hepatitis B Surface Antigen Seroclearance After Interferon Therapy Followed by Antiretroviral Therapy without Developing Immune Reconstitution Inflammatory Syndrome

Coinfection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) is common worldwide. The current guidelines for the treatment of HIV infection recommend that HIV patients coinfected with HBV receive antiretoroviral therapy (ART) with two nucleoside analogs against HBV. However, an increase in liver enzymes that is usually attributed to HBV immune reconstitution inflammatory syndrome (IRIS) sometimes occurs in HBV/HIV-coinfected patients after the commencement of ART. We report a case of HBV/HIV-coinfection in which the chronic hepatitis B was successfully treated using interferon (IFN) therapy followed by ART without the development of IRIS. A Japanese man in thirties was referred to our hospital because of an acute HIV infection two months after the diagnosis of an acute HBV infection, which had progressed to a chronic HBV infection. The laboratory test results were as follows:hepatitis B surface antigen (HBsAg) positive, hepatitis B e antigen (HBeAg) positive, HBV DNA level of 8.8 Log copies/mL, HBV genotype A, alanine aminotransferase of 834 IU/L, HIV RNA level of 5 Log copies/mL, and a CD4+ T cell count of 437/microL. The initial treatment was natural IFNalpha therapy for chronic hepatitis B, and HBeAg seroclearance was achieved 20 weeks after the start of therapy. Four months after the end of IFN therapy for 24 weeks, ART including tenofovir and emtricitabine against HBV was commenced. Six months after starting ART, the patient's serum HBV DNA level had decreased and become undetectable and HBsAg seroclearance was achieved without an elevation in liver enzymes. The present case suggests that IFN therapy prior to ART contributes to a successful outcome for chronic hepatitis B patients coinfected with HIV, if the HIV status does not require the immediate start of ART.

Economic Analysis 20 Years after the Introduction of Universal HBV Immunisation in Bulgaria

ABSTRACTThe aim of this study was to evaluate the main economic results 20 years after the introduction of obligatory immunisation against hepatitis B virus (HBV) in Bulgaria. Prospective epidemiology and retrospective cost analysis was done. During the period 1992–2010 information was collected about the number of vaccinated individuals in the new born cohorts, and about the reported acute HBV infection cases per year in Bulgaria. The number of averted cases was calculated. Only direct medical costs were included in the analysis: the cost of ambulatory pharmacotherapy after hospital discharge of acute cases, hospital charges for acute cases, yearly pharmacotherapy of chronic hepatitis B, cost of hospitalisation due to chronic hepatitis B, and cost of cirrhosis and hepatocellular carcinoma as the most common complication of HBV infection. The net health benefits were analyzed in two scenarios—for the whole period, and for the last 10 years after considering only the acute or both the acute and chronic cases therapy.For the whole period, the investments still prevail over the benefits because of the relative parity between the total number of infections and averted cases. The latter is true for both scenarios—considering only the acute cases cost, and considering both the acute and chronic cases, as well as the complications cost. If the calculations are repeated only for the last 10 years of the observed period (2001 - 2010), the investments nearly equalize the benefits, most evidently in the second scenario, probably due to the highest number of averted chronic cases and hospitalizations.Universal vaccination against HBV is socially beneficial for the Bulgarian population. Its positive economic effects became visible during the last 10 years since its introduction in the immunisation calendar.

“Never Events”: Hepatitis B Outbreaks and Patient Notifications Resulting from Unsafe Practices during Assisted Monitoring of Blood Glucose, 2009–2010

Despite sustained public health efforts to publicize the risk of hepatitis B virus (HBV) infection outbreaks during assisted monitoring of blood glucose (AMBG), outbreaks continue to occur. Here, we highlight several outbreaks and patient notifications due to AMBG, discuss prevention initiatives, and highlight gaps that remain. We reviewed available data and information from investigations of health care-associated HBV infection outbreaks and patient notification events associated with AMBG in the United States between 2009 and 2010. Four HBV infection outbreaks were reported, all in assisted living facilities. Common infection control breaches included use of reusable finger stick devices, which are intended for personal use, on multiple persons; use of BG meters for more than one person without cleaning and disinfection between each use; and comingling of contaminated and clean equipment and supplies. Twenty-nine (88%) of the 33 residents who acquired acute HBV infection as part of these outbreaks received AMBG. Compared with those who did not, residents undergoing AMBG had significantly increased risk of acquiring acute HBV infection (relative risk: 27.7, 95% confidence interval: 10.3 to 74.4). During two patient notifications, approximately 320 persons were recommended to undergo bloodborne pathogen testing after being placed at risk for exposure to another person's blood when personal-use multilancet finger stick devices were selected for use on multiple persons. Misperception on the risk for bloodborne pathogen transmission and confusion regarding selection and appropriate use of BG monitoring devices for AMBG remain a problem. In addition to public health outreach and infection control recommendations, clear labeling, packaging, instructions for device use, and appropriate device marketing will assist in infection prevention efforts.

Reverse vertical transmission of hepatitis B virus (HBV) infection from a transfusion-infected newborn to her mother

Clinical cases of viral infections possibly involving the transfusion of blood components are systematically investigated. Serological and molecular markers of hepatitis B virus were used including HBsAg, anti-HBc, anti-HBs, HBV DNA, and viral load. Full genome sequencing and phylogenetic analyses were performed. An acute HBV infection was diagnosed in the mother of a 16-month-old daughter who had been transfused at age three weeks with one quarter of a regular red cell concentrate (RCC). The repeat donor of the index donation was free of HBV markers in two previous donations but seroconverted to anti-HBc and anti-HBs 3 months post-donation of a unit containing only low level of HBV DNA. One other newborn recipient of the same RCC was asymptomatically HBV infected. A third newborn recipient whose mother had been HBV vaccinated and carried moderate level of anti-HBs was not infected. Full length nucleotide sequence identity between HBV strains from the mother and the two infected transfusion recipients provided evidence of the transfusion origin of all three infections in the absence of donor sequence. Reverse vertical HBV transmission was likely the result of casual mother contact with a baby carrying extremely high viral load. The blood products intended to immunodeficient newborn should be submitted to more thorough viral testing considering their increased susceptibility to infections.

Outbreak of acute hepatitis B virus infections associated with podiatric care at a psychiatric long-term care facility

Effective measures exist to prevent health care-associated hepatitis B virus (HBV) transmission, yet outbreaks continue to occur. In 2008, the Los Angeles County Department of Public Health identified an outbreak of HBV infections among psychiatric long-term care facility residents. Residents underwent HBV serologic testing and were classified as acutely infected, chronically infected, susceptible, or immune. Persons residing in the facility during 2008 were enrolled in a retrospective cohort study to identify risk factors for acute HBV infection. We assessed infection control practices at the facility. Nine of 81 residents (11%) enrolled in the cohort study had acute HBV infection. Five of 15 residents (33%) undergoing podiatric care on a single day subsequently developed acute infection (rate ratio, 4.33; 95% confidence interval, 1.18-15.92). Infection control observations of the consulting podiatrist revealed opportunities for cross-contamination of instruments with blood. Other potential health care and behavioral modes of transmission were identified as well. Residents were offered HBV vaccination, and infection control recommendations were implemented by the podiatrist and facility. Of the multiple potential transmission modes identified, exposure to HBV during podiatry was likely the dominant mode in this outbreak. Long-term care facilities should ensure compliance with infection control standards among staff and consulting health care providers.

Criteria for hepatitis B virus screening and validation of blood components in Italy: the position of the SIMTI HBV working group.

The screening strategies for the detection of blood donors potentially able to transmit an infection to the recipient of their blood or blood products have always included clinical, behavioural and laboratory criteria in an attempt to construct a multi-barrier system that most effectively guarantees transfusion safety1. These criteria are necessarily modified over time as further knowledge is acquired and new laboratory tests become available. Hepatitis B virus (HBV) causes the blood-borne viral infection for which serological markers for screening have been available for the longest time. Indeed, the introduction of a test to detect the hepatitis B surface antigen (HBsAg) at the beginning of the 1970s certainly contributed to a drastic reduction in the number of HBV transfusion-transmitted infections. However, despite continuous improvements in the sensitivity of this test, transfusion-related transmission of hepatitis B has not been completely eliminated and in some countries an additional serological investigation (the search for antibodies against HBV core antigen, anti-HBc) was introduced. Testing for these antibodies was initially used as a surrogate marker for the detection of non-A, non-B hepatitis in the mid-1980s, but after the availability of a specific test for hepatitis C virus (HCV), it returned to being of specific relevance in the screening for HBV infection. More recently, a test to detect HBV DNA was introduced for the screening of blood donors. Crucially, this test can detect an acute HBV infection earlier than HBsAg and anti-HBc tests, thus reducing the so called window period during which an infected donors may harbour large amounts of infectious viral particles in the absence of serological markers and/or signs and symptoms of an ongoing infection2. Furthermore, DNA testing allows the identification of a number of donors -including periodic donors-characterised by the absence of HBsAg in the presence of HBV DNA with or without anti-HBs, anti-HBc and/or anti-HBe antibodies. These latter serological profiles are defined as occult HBV infection (OBI) in agreement with the Consensus Conference held in Taormina in 20083. In these cases, the amount of HBV DNA -when detectable- is usually very low (<100–200 IU/mL). On the basis of the serological profile, OBI can be distinguished into seropositive (anti-HBc and/or anti-HBs positive) or seronegative (anti-HBc and anti-HBs negative) types3. The tests that, at present, are mandatory in Italy for the prevention of transfusion-related transmission of HBV include HBsAg (using several commercially available last-generation immunoassays kits) and HBV DNA detection (50% of blood units are tested in pools of 6 samples by Roche Cobas Taqscreen MPX on the Cobas s 201 platform [Roche Instruments Center, Rotkreuz, Switzerland] and 50% in single tests by Novartis Ultrio [Emerville, CA] with comparable analytical and clinical sensitivity4,5). In addition, other serological tests are performed, with a heterogeneous distribution across the country, in part as an additional criterion for the validation of blood components (i.e. anti-HBc) and in part as an evaluation of the immunological status of the donor (i.e. anti-HBs). A national survey organised by the Italian Society of Transfusion Medicine and Immunohaematology (SIMTI) in 20096 found that 78 (43%) of 181 Transfusion Services (TS) that replied to a specific questionnaire routinely performed anti-HBc and that 53 of these 78 (68%) TS were located in Northern Italy Regions. In most of the TS (81%) participating in the study, this test was carried out in first-time donors only, while in the remaining (19%) it was carried out in all donors. Fifty percent of the TS that performed this test used a positive result for anti-HBc as a criterion to exclude antibody-positive donors from donating while the remaining TS did not. Thus, there are profound differences in the behaviour of TS, resulting from the persistence of criteria based on serological parameters and criteria derived from the introduction of the new molecular biology tests. In the light of this, SIMTI set up a Working Group charged with the task of defining the screening tests for HBV capable of guaranteeing the highest levels of safety compatible with the possibility of ensuring timely and appropriate transfusion therapy in the specific Italian epidemiological context, with the currently available technology.

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.

A Proinflammatory Role for Interleukin-22 in the Immune Response to Hepatitis B Virus

T-helper (Th)17 cells that secrete interleukin (IL)-22 have immunomodulatory and protective properties in the liver and other tissues. IL-22 induces expression of proinflammatory genes but is also mitogenic and antiapoptotic in hepatocytes. Therefore, it could have multiple functions in the immune response to hepatitis B virus (HBV). We examined the role of IL-22 in regulating liver inflammation in HBV transgenic mice and measured levels of IL-22 in HBV-infected patients. In HBV transgenic mice, injection of a single dose of IL-22 increased hepatic expression of proinflammatory genes but did not directly inhibit virus replication. When splenocytes from HBV-immunized mice were transferred into HBV transgenic mice, the severity of the subsequent liver damage was ameliorated by neutralization of IL-22. In this model, IL-22 depletion did not affect interferon gamma-mediated noncytopathic inhibition of virus replication initiated by HBV-specific cytotoxic T cells, but it significantly inhibited recruitment of antigen-nonspecific inflammatory cells into the liver. In patients with acute HBV infections, the percentage of Th17 cells in peripheral blood and concentration of IL-22 in serum were significantly increased. IL-22 appears to be an important mediator of the inflammatory response following recognition of HBV by T cells in the liver. These findings might be relevant to the development of cytokine-based therapies for patients with HBV infection.

Economic Analysis of Hepatitis B Screening and Treatment

Economic Analysis of Hepatitis B Screening and Treatment

Nosocomial outbreak of hepatitis B virus infection involving two hospitals in the Republic of Ireland

The routes of nosocomial hepatitis B virus (HBV) transmission have changed over the years. Initiatives to prevent transfusion-associated HBV and healthcare worker-to-patient transmission have had a positive impact on these transmission routes. Recent reports of outbreaks of nosocomial HBV have implicated breaches in standard precautions as important causes of HBV transmission. This report describes a nosocomial outbreak of HBV infection in the Republic of Ireland, which occurred between January 2005 and March 2006. The outbreak was detected following identification of a case of acute HBV infection in a patient whose only risk factor was a recent surgical procedure. The extensive multi-agency investigation that followed revealed that the patient was one of five cases of acute HBV infection and that four separate transmission events between infectious cases had occurred in two different hospitals over a 15-month period. A definitive cause for each transmission event was not identified, although lapses in adherence to standard precautions, safe injection and phlebotomy practices could not be ruled out. Two secondary cases of acute HBV infection in community contacts of two of the nosocomial cases were identified. Phylogenetic analysis proved a useful tool in confirming infection with a pre-core HBV mutant and viral transmission between the seven patients. Apatient notification exercise involving 1028 potentially exposed patients found no evidence of additional cases of nosocomial HBV infection. These findings highlight the importance of consistent application of standard precautions.

Does antiviral therapy for hepatitis B and C prevent hepatocellular carcinoma?

Approximately 75% to 80% of hepatocellular carcinomas (HCC) worldwide are attributed to chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infection. Thus, effective prevention of HBV and HCV infection and progression from acute HBV and HCV infection to chronic hepatitis, cirrhosis and HCC might prevent as many as 450,000 deaths from HCC each year. The most effective approach to preventing HCC is to prevent HBV and HCV infection through vaccination. Indeed HBV vaccine is the first vaccine demonstrated to prevent cancers. However, a vaccine for HCV is not available and for persons who are chronically infected with HBV or HCV, antiviral therapy is the only option for preventing HCC. Direct evidence supporting a benefit of antiviral therapy on the prevention of HCC has been shown in a few randomized controlled trials. There is abundant evidence that antiviral therapy, in patients with long-term virological response, can improve liver histology, providing indirect support that antiviral therapy may prevent HCC by slowing progression of liver disease and possibly even reversing liver damage. Nevertheless, the risk of HCC remains in patients with chronic HBV or chronic HCV infection if treatment is initiated after cirrhosis is established. These data indicate that treatment might be of greater benefit if instituted earlier in the course of chronic hepatitis B or C. Safer, more effective, and more affordable antiviral therapies are needed for both hepatitis B and hepatitis C so more patients can benefit from treatment and more HCCs can be prevented.

Hepatitis B virus and hepatocellular carcinoma at the miRNA level

To study Hepatitis B virus (HBV) infection and its association with hepatocellular carcinoma (HCC) at the miRNA level. Three cellular models were used to investigate miRNA expression changes during HBV infection: human HepG2 hepatoblastoma cell line as a model without HBV infection; HepG2 cell line transfected with a 1.3-fold full-length HBV genome as an acute infection model; and HepG2.2.15 cell line, which is derived from HepG2 and stably transfected with a complete HBV genome, as a chronic infection model. The miRNA levels were examined using microarray technology. To explore the relationship between HBV infection and HCC genesis at the miRNA level, we downloaded from national center for biotechnology information Gene Expression Omnibus an miRNA expression dataset derived from HCC patients, most of whom are HBV carriers. We compared the miRNA expression alterations during HBV infection with those in HCC patients, by analyzing miRNA expression change profiles statistically. Seventy-seven and 48 miRNAs were differentially expressed during acute and chronic HBV infection, respectively. Among these miRNAs, 25 were in common, the intersection of which was significant under the hypergeometric test (P = 1.3 × 10⁻¹¹). Fourteen miRNAs were observed to change coherently in the acute and chronic infections, with one upregulated and 13 downregulated. Eleven showed inverse changes during the two phases of infection; downregulated in the acute infection and upregulated in the chronic infection. The results imply that common and specific mechanisms exist at the miRNA level during acute and chronic HBV infection. Besides, comparative analysis of the miRNA expression changes during HBV infection with those in HCC indicates that, although miRNA expression changes during HBV infection are distinct from those in HCC patients (P < 2.2 × 10⁻¹⁶), they exhibited significant correlations (P = 0.0229 for acute infection; P = 0.0084 for chronic infection). Perturbation of miRNA expression during chronic HBV infection was closer to that in HCC patients than that during acute HBV infection. This observation implies the contribution of miRNAs to HCC genesis from HBV infection. According to their patterns of differential expression in acute and chronic HBV infection, as well as in HCC, miRNAs of potential research interest could be identified, such as miR-18a/miR-18b, miR-106a, miR-221 and miR-101. For instance, the gradient expression alteration of miR-221 in the above three phases, which is downregulated in acute HBV infection, normally expressed in chronic HBV infection, and upregulated in HCC, indicates that it may be a key effector for progression of the disease. Our analysis provides insights into HBV infection and related HCC in relation to miRNAs, and reveals some candidate miRNAs for future studies.

Pathogenesis of occult chronic hepatitis B virus infection

Occult hepatitis B infection (OBI) is characterized by hepatitis B virus (HBV) DNA in serum in the absence of hepatitis B surface antigen (HBsAg) presenting HBsAg-negative and anti-HBc positive serological patterns. Occult HBV status is associated in some cases with mutant viruses undetectable by HBsAg assays; but more frequently it is due to a strong suppression of viral replication and gene expression. OBI is an entity with world-wide diffusion. The failure to detect HBsAg, despite the persistence of the viral DNA, is due in most cases to the strong suppression of viral replication and gene expression that characterizes this "occult" HBV infection; although the mechanisms responsible for suppression of HBV are not well understood. The majority of OBI cases are secondary to overt HBV infection and represent a residual low viremia level suppressed by a strong immune response together with histological derangements which occurred during acute or chronic HBV infection. Much evidence suggests that it can favour the progression of liver fibrosis and the development of hepatocellular carcinoma.

Identification of Acute Vaccine‐Preventable Hepatitis in Individuals with Chronic Hepatitis in British Columbia between 1991 and 2007

In British Columbia (BC), hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccines are provincially funded for persons with chronic hepatitis infections. To assess the effectiveness of BC public health follow-up of HBV and hepatitis C virus (HCV) cases and immunization policy by determining the number of vaccine-preventable acute hepatitis infections reported following a chronic HBV or HCV diagnosis, by examining demographic characteristics and by observing temporal trends. All newly identified cases of HAV, HBV and HCV between 1991 and October 2007 were extracted from the BC integrated Public Health Information System and linked to ascertain cases of hepatitis suprainfection. Between 1991 and October 2007, 30 BC residents with chronic HBV and 104 with HCV were subsequently diagnosed with HAV. Acute HBV was identified in 162 persons previously diagnosed with HCV. Significantly more men than women developed hepatitis suprainfection (P<0.0001), but women were of a younger age when they were diagnosed with HAV (P=0.02) and acute HBV (P=0.0002). HAV suprainfection cases among those with HCV peaked in 1998 at 33 cases and declined to zero cases in 2007. In comparison, HBV suprainfection among individuals with chronic HCV peaked in 1996 at 26 cases and declined to two cases in 2007. Cases of HAV and acute HBV have declined among HCV-infected individuals. However, despite the availability of publicly funded vaccines for high-risk groups, a substantial number of acute HBV infections post-HCV identification are still identified, indicating that follow-up and vaccination coverage should be improved in these populations.

Robust Hepatitis B Virus Genotyping by Mass Spectrometry

Genotyping of hepatitis B virus (HBV) is important for tracking HBV infections, prognosticating the development of severe liver disease, and predicting outcomes of therapy. Current genotyping methods can be laborious and costly and rely on subjective data interpretation. To identify less expensive but equally reliable alternatives, we compared "gold standard" sequencing to a novel mass spectrometry approach. Sera from individuals with acute or chronic HBV infection (n = 756), representing all genotypes, were used to PCR amplify the HBV S gene. All amplicons were subjected to base-specific cleavage and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). The resulting mass peak patterns were used to identify HBV genotype by automated comparison to peak patterns simulated from reference sets of HBV sequences of known genotypes. The MALDI-TOF MS data and phylogenetic analysis of HBV sequences produced completely concordant results. Several parameters such as genetic relatedness of tested HBV variants to the reference set, chronic infections, and the quality of PCR products can lower the MS score but never affected the accuracy of the genotype call. This new streamlined MS-based method provides for rapid and accurate HBV genotyping, produces automated data reports, and is therefore suitable for routine use in diagnostic settings.

The persistence in the liver of residual duck hepatitis B virus covalently closed circular DNA is not dependent upon new viral DNA synthesis

Residual hepatitis B virus (HBV) DNA can be detected following the resolution of acute HBV infection. Our previous work using duck hepatitis B virus (DHBV) infected ducks, indicated that ~ 80% of residual DHBV DNA in the liver is in the covalently closed circular DNA (cccDNA) form, suggesting that viral DNA synthesis is suppressed. The current study asked more directly if maintenance of residual DHBV cccDNA is dependent upon ongoing viral DNA synthesis. Ducks that recovered from acute DHBV infection were divided into 2 groups and treated with the antiviral drug, Entecavir (ETV), or placebo. No major differences in the stability of cccDNA or levels of residual cccDNA were observed in liver biopsy tissues taken 95 days apart from ETV treated and placebo control ducks. The data suggest that residual DHBV cccDNA is highly stable and present in a cell population with a rate of turnover similar to normal, uninfected hepatocytes.

Five hepatitis B outbreaks in care homes in the UK associated with deficiencies in infection control practice in blood glucose monitoring

Healthcare-associated hepatitis B virus (HBV) outbreaks have been reported in the USA and from several countries in Europe. Patient-to-patient transmission of HBV in these settings has been linked to several different types of exposure but one of the most common exposures implicated is the use of 'finger-stick' lancet devices for blood glucose testing. This article is an account of the investigations into a series of HBV outbreaks linked to the use of lancing devices in community healthcare settings in the UK. Between February 2004 and December 2006, nine individuals with acute HBV infection were reported to five local units of the Health Protection Agency. Investigations identified a further 12 individuals with HBV infection in residents in these settings. The epidemiological and environmental evidence suggests that HBV transmission occurred mostly from a significant breakdown in infection control measures in blood glucose testing. The occurrence of these outbreaks has highlighted the confusion that exists and the need for clear recommendations regarding the use of such devices in the UK.

A foot-drop case

Dr. Montano: A 42-year-old man was admitted to our department because of migratory arthromyalgias predominantly involving large joints, with painful swelling for the prior 3 weeks. He had used large doses of non-steroid antiinflammatory drugs with limited pain control. The patient was eupneic and apyretic demonstrating pain and swelling of the left hand, and erythema and edema of the right leg and foot. Blood pressure and heart rate were, respectively, 120/80 mmHg and 80 beats/min. The remaining clinical history and physical examination were otherwise negative. The electrocardiogram and the chest X-ray were normal. Compressive ultrasound scan of the legs, looking for a deep venous thrombosis, was normal. Routine laboratory findings were within the normal ranges except for hypertransaminasemia (AST 287, ALT 740); for this reason an abdominal ultrasound scan was performed, but showed only a mild hepatosplenomegaly. Serologic profile revealed previous Epstein–Barr and cytomegalovirus infections, and detected hepatitis B virus (HBV) IgM antibodies, HBsAg and HBeAg, thus showing an acute HBV infection. Autoimmune screening (ANCA and ANA autoantibodies, rheumatoid factor, autoantibodies against gliadin and transglutaminase) were all normal as were the thyroid function tests. The migratory arthralgias were treated with tramadol, with a significant reduction in pain. Intravenous fluids were administered, and a specific diet for hepatic disease was prescribed; the patient was subsequently discharged with the diagnosis of ‘‘migratory arthralgias in an acute hepatitis B infection’’. A month after discharge, the patient was readmitted to our department for dysesthesias and hypoesthesia of both feet (predominantly the right) associated with motor deficits. On neurologic examination, flexion, extension and rotation movements of the right foot were not possible for the patient, and the Achilles tendon reflex was absent. The patient also showed a deficit in right thigh flexion with steppage gait, and a deficit in left foot extension. Laboratory findings showed a leukocytosis (12,000 WBC) and C-reactive protein (CRP) elevation (170 mg/l). A magnetic resonance (MR) examination of the spine was performed to test the hypothesis of spondylo-diskitis or multiple discopathies, but was normal. To evaluate the motor deficit, an electromyography (EMG) was performed. It revealed an acute axonal multineuropathy involving the right common peroneal nerve and the left femoral nerve, associated with chronic axonal damage in some of the studied districts. In particular, This case record was selected for the ‘‘Casi Clinici Gymnasium’’ session at the 2009 SIMI Annual Congress in Rome, and was reviewed by a Committee composed of Maria Domenica Cappellini and Luigi Pagliaro.

Multiple Clusters of Hepatitis Virus Infections Associated With Anesthesia for Outpatient Endoscopy Procedures

Hepatitis B virus (HBV) and hepatitis C virus (HCV) can be transmitted during administration of intravenous anesthesia when medication vials are used for multiple patients using incorrect technique. We investigated an outbreak of acute HBV and HCV infections among patients who received anesthesia during endoscopy procedures from the same anesthesiologist (anesthesiologist 1), in 2 different gastroenterology clinics. Chart reviews, patient interviews, clinic site visits and infection control assessments, and molecular sequencing of patient isolates were performed. Patients treated by anesthesiologist 1 on specific procedure days were offered testing for blood-borne pathogens. Endoscopy and anesthesia procedures were reviewed; HCV quasispecies analysis was performed. Six cases of outbreak-associated HCV infection and 6 cases of outbreak-associated HBV infection were identified in clinic 1. One outbreak-associated HCV infection was identified in clinic 2. HCV quasispecies sequences from the patients were nearly identical (96.9%-100%) to those from source patients with chronic viral hepatitis. All affected patients in both clinics received propofol from anesthesiologist 1, who inappropriately used a single-patient-use vial of propofol for multiple patients. Reuse of syringes to redose patients, with resulting contamination of medication vials used for subsequent patients, likely resulted in viral transmission. Twelve persons acquired HBV and HCV infections (6 hepatitis C, 5 hepatitis B, and 1 coinfection) in 2 separate offices as a result of receiving anesthesia from anesthesiologist 1. Gastroenterologists are urged to review carefully the injection, medication handling, and other infection control practices of all staff under their supervision, including providers of anesthesia services.