anti-HBc IgM Research Articles

A comprehensive serological and supplemental evaluation of hepatitis B "seroyield" blood donors: A cross-sectional study from a tertiary healthcare center in India.

Background:The present study addressed the interesting findings of supplemental evaluation of hepatitis B “seroyield” donors.Materials and Methods:Each blood donor sample was tested for anti-human immunodeficiency virus type I (HIV-I)/HIV type II (HIV-II), HBsAg, and anti-hepatitis C virus (HCV) antibody by enhanced chemiluminescence method and subjected to individual donor-nucleic acid testing (NAT) for HIV-I, hepatitis B virus (HBV), and HCV. NAT test was performed using the eSAS system, Procleix Ultrio Assay, Novartis Diagnostics, CA, US. Confirmation of HBsAg was done using HBsAg Confirmatory Kit (Ortho Clinical Diagnostics, Johnson & Johnson, USA) and viral load assessment was done using Cobas TaqMan real time-polymerase chain reaction (RT-PCR) assay (Roche Molecular Systems, Branchburg, NJ, USA). To provide information on the stage of infection, specimens were tested for anti-HBc total (IgG + IgM), anti-HBc IgM and HBeAg. HBeAg-negative samples were tested for anti-HBe antibody.Results:A total of 60 hepatitis B seroyield donors which showed mean initial sample/cutoff of 1.6 with enhanced chemiluminescence assay were investigated further for confirmation of disease status. All 60 cases were confirmed positive with neutralization assay (VITROS HBsAg Confirmatory Kit) while no target was detected on viral load assessment with RT-PCR. Sixteen donors were HBeAg positive (4 IgM anti-HBc positive and 12 IgM anti-HBc negative) and 44 were IgM anti-HBc negative, anti-HBc total positive, and anti-HBe positive.Conclusion:About 7.7% of HBsAg positive and NAT nonreactive donors (nondetectable HBV DNA) could be potentially infectious (HBeAg positive), whereas rest of the donors were consistent with chronic HBV infection.

Inappropriate use of serological tests for hepatitis B virus in Evliya Celebi Education and Research Hospital of Dumlupinar University, Kütahya

Since hepatitis B virus (HBV) infections may cause serious clinical symptoms and become chronic, the appropriate use and interpretation of laboratory tests in diagnosis is crucial. Implementation of serological tests for all HBV markers leads to high cost, labour force and time loss, so diagnostic algorithms are used for this purpose. The aims of this retrospective study were to detect the number of unnecessary test requests in HBV infection serology and financial burden as its consequence and to find out the reasons and ways of solutions. Three-years records of microbiology laboratory of Dumlupinar University Evliya Celebi Training and Research Hospital, Kutahya, Turkey, between 2011-2013 were analysed for the detection of unnecessary test requests and a total of 179.640 HBV serological test results were evaluated. Serological tests requested more than one on the same day and HBeAg, anti-HBe and anti-HBc IgM tests required from the patients with natural immunity or vaccinated ones were considered as unnecessary test requests. The main reasons of unnecessary test requests were detected as follows; unable to check the previous HBV test results in HIMS (Hospital Information Management System) owing to restricted of time, not being friendly user of HIMS, not trusting the test results, not knowing diagnostics algorithms, requiring of the tests by secretaries or other staff like nurses, not questioning HBV vaccination and requiring screening tests because of the defensive medicine. Survey questions prepared to search these reasons and awareness level of diagnostic algorithms were handed and asked to fill out 146 physicians working at clinics which made over 100 unnecessary requests in 3 years. Total numbers of unnecessary requested serological HBV tests were 5415 (3.01%) and total financial burden for our hospital in three years was 42.256 TL (18.373 USD) according to the notifications of Turkish Social Security Institution. It was determined that the most unnecessary test requests were HBeAg (44.86%), anti-HBe (37.75%) and anti-HBc IgM (37.41%). The most unnecessary test requests were made by internal medicine, obstetrics and gynaecology, general surgery and cardiology clinics, respectively. According to questionnaires filled by the 100 clinicians, the most common causes of unnecessary tests were hepatitis test requests from hospitalized patients for screening (96%), the tests required by secretary or nurse (62%), pre-surgical screening tests (53%) and lack of knowledge about diagnostic algorithms (42%). In conclusion, it is suggested that test requests should be restricted by using screening algorithms and in-service training should be provided, tests required by secretary or nurse should be stopped and previous test results should be conveyed to the clinicians actively through HIMS in order to prevent unnecessary test requests causing economic and workforce loss in HBV infection serology. These measures can provide early and true diagnosis for the patients and also will reduce the economic loss.

Türkiye’de İlk Kez Saptanan Hepatit B Virus Genotip E Enfeksiyonu

Clinical studies reported from Turkey indicate that hepatitis B virus (HBV) genotype D is more prevalent than other genotypes. Epidemiological and clinical information on genotype H infection is currently limited. Genotype H infection is most likely due to its regional (Central and South America) prevalence throughout the world. The aim of this report is to present the first HBV genotype H infection in a chronic hepatitis B patient in Turkey. Laboratory findings of a 42 years old male patient admitted to our hospital revealed HBsAg (+), anti-HBs (-), HBeAg (-), anti-HBe (+), anti-HBc IgM (-), anti-HBc IgG (+), anti-HAV IgG (+), HBV-DNA: 5.689.776 IU/ml and high liver enzymes (ALT: 223 U/L, AST: 121 U/L). History of the patient indicated no risk factor (intravenous drug use, blood transfusion, suspicious sexual contact) related to HBV transmission. Since liver ultrasonography showed multiple hemangiomas, biopsy was performed and histologic activity index was found as 6/18 and fibrosis as 2/6, according to modified Knodell score system. HBV DNA isolated from the serum sample of the patient was amplified by polymerase chain reaction and polymerase gene segment of HBV was directly sequenced. UPGMA method was used for phylogenetic analysis, and the genotype of the virus was identified accordingly. The nucleotide sequence was compared to those from the international DNA data bank (GenBank). The genotyping of the patient revealed that the isolated HBV was genotype H. Treatment with tenofovir disoproxil fumarate was initiated and the patient responded to the treatment. This finding suggested that other HBV genotypes, except the predominant genotype D may also be in circulation in Turkey. In conclusion, detection of epidemiologic and molecular characteristics of HBV genotype H which is related to chronic hepatitis, seems to be necessary in order to better understand its circulation and progression around the world.

Occult hepatitis B virus infection with positive hepatitis B e antigen

BackgroundHepatitis B e antigen (HBeAg) is a marker to indicate active replication of hepatitis B virus (HBV). Occult HBV infection (OBI), referred to persistence of HBV DNA in serum and/or liver without detectable serum hepatitis B surface (HBsAg), usually has low HBV DNA levels. The presence of HBeAg in OBI is unusual. MethodsWe report 2 patients who presented negative for HBsAg but positive for HBeAg and HBV DNA. HBV markers were quantified in the longitudinal sera in a period of 1–2years. The HBV DNA sequences were analyzed in 2 patients' sera and 1 patient's liver. ResultsBoth patients were also positive for total anti-HBs and anti-HBc but negative for anti-HBe and anti-HBc IgM. HBV DNA levels were 234–567IU/ml in case 1 and 42–1130IU/ml in case 2. The alignment analysis of the S gene showed that HBV in both patients was genotype C, serotype adr. Cloning analysis of the a determinant of HBsAg showed that the immune escape mutants were predominant in both patients over the follow-up period. The HBV had double mutations (A1762T and G1764A) in the basal core promoter but had no mutation in the pre C/C gene in both patients. ConclusionsThe patients with negative HBsAg but positive HBeAg may represent a unique type of OBI. Test for HBeAg would be critical to identifying such type of OBI.

GB virus C Viremia and Anti-E2 Antibody Response Among Hemodialysis Patients in Gorgan, Iran.

Background:GB Virus C is a blood-borne virus and a member of Flaviviridae, like hepatitis C that is distributed globally and puts hemodialysis patients at high risk of developing liver disease. The clinical significance of GBV-C in this population remains unclear.Objectives:The current study aimed to evaluate GBV-C infection among hemodialysis patients.Patients and Methods:Totally, 149 patients receiving hemodialysis were included in the study. The detection of GBV-C sequences in plasma was done by the nested Reverse transcription polymerase chain reaction (RT-PCR) using specific primers selected from highly conserved regions of 5' UTR of GBV-C and antibodies to the envelope protein of GBV-C (anti-E2 GBV-C antibody) were analyzed by also serological methods. In addition, Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb) IgM, anti- Hepatitis C virus (HCV) and anti- hepatitis E virus (HEV) Ab was determined in patients who were GBV-C RNA and anti-E2 GBV-C antibody positive.Results:The total prevalence of GBV-C infection was 14.7% (95%CI: 0.09-0.21) among patients receiving hemodialysis. The rate of GBV-C viremia and anti-E2 antibody positivity were 6.04% and 10.73%, respectively. Among the subjects who were positive for GBV-C, 27.27% (95% CI: 0.02-0.09), 45.45% (95% CI: 0.03-0.11), 59.9% (95% CI: 0.06-0.16) and 0% (95% CI: 0.01-0.07) were positive for anti-HCV, anti-HBsAg, anti-HBc IgM and anti-(HEV) Ab, respectively. In addition, the rate of both anti-HBc IgM /anti-HCV/ HBsAg and anti-HBc IgM /anti-HCV positivity in GBV-C infected cases were 9.09%. The liver enzymes were normal in all of them. There was significant difference between GBV-C exposures with viral hepatitis co-infection, but there was no correlation between GBV-C exposure with gender, age, ethnicity, time on dialysis and history of blood transfusions. A relatively high frequency of positivity GBV-C-exposure among hemodialysis patients suggested that the transmission route for GBV-C may be nosocomial transmission, and via transfusions.Conclusions:The current study found a relatively high frequency of positivity GBV-C-exposure among the patients receiving hemodialysis in the area understudy. Nosocomial transmission seems to be the main route of GBV-C infection in the area.

Direct role of antibody-secreting B cells in the severity of chronic hepatitis B.

Chronic hepatitis B involves different immune cells. The direct role of antibody-secreting B cells in the severity of chronic hepatitis B unclear. In this study, the number of plaque forming cells [PFC-(IgG, IgM, anti-HBc IgG, and anti-HBc IgM)], liver function tests (LFT) [alkaline phosphatase (ALP), alanine aminotransferase (ALT), and total serum bilirubin (TSB)], the levels of IL-10 in sera and in lymphocyte cultures, the number of CD4(+) and CD8(+) cells were measured in the peripheral blood of patients and in the controls. In addition, the hepatocytotoxic effect of anti-HBc and anti-HBe in vitro was studied. The largest number of PFCs was observed in the peripheral blood of patients with chronic hepatitis B. This was concomitant with a decrease in CD4(+) /CD8(+) ratio versus this ratio in asymptomatic HBV carriers and in healthy volunteers (P < 0.05). An increase in immunoglobulin (IgG and IgM) levels, anti-HBc IgG, and anti-HBc IgM levels and LFTs in peripheral blood of patients with chronic hepatitis B was seen. Anti-HBc induced hepatocytotoxicity in vitro. The expression of mRNA and protein for IL-10 production was observed at a significant level in culture of lymphocytes isolated from patients with chronic hepatitis B. In addition, a high level of IL-10 was found only in the sera of patients with chronic hepatitis B. It is concluded that the antibody-secreting B cells and the antibodies, which are produced, play an important role in the severity of chronic hepatitis B, which was related negatively with CD4(+) /CD8(+) ratio and positively with IL-10 expression.

Molecular analysis of the interspousal transmission of hepatitis B virus in two Japanese patients who acquired fulminant hepatitis B after 50 and 49 years of marriage

A 71-year-old (C1I) and 69-year-old (C2I) Japanese female contracted fulminant hepatitis B after 50 and 49 years of marriage, respectively. Both index cases exhibited high levels of anti-HBc IgM antibodies (24.2 and 31.5 S/CO, respectively), suggestive of acute hepatitis B virus (HBV) infection, although they had no discernible risk factors for HBV infection, except for chronically HBV-infected spouses with detectable HBV DNA (3.3 log copies/ml [C1S: 72-year-old] and 7.2 log copies/ml [C2S: 71-year-old]). The HBV genotype/subgenotype was identical in each couple (B/B1 or C/C2). The HBV isolates from the index cases and spouses shared a nucleotide sequence identity of 99.5% and 99.7%, respectively, over the entire genome, and these four isolates had the highest nucleotide sequence identity of only 97% to HBV isolates deposited in DNA databases. Phylogenetic trees confirmed a close relationship of the HBV isolates between C1I and C1S and between C2I and C2S, supported by a high bootstrap value of 100% within each couple, indicating the transfer of HBV infection between spouses. These four isolates shared a precore mutation of G1896A known to be associated with fulminant hepatitis B. Although the history of sexual contact within a reasonable incubation period was obscure for one stable, monogamous couple (C1I and C1S), the other couple had a monogamous sexual relationship within six months prior to disease onset. This study indicates that two elderly Japanese patients with fulminant hepatitis B acquired HBV infection via interspousal (most likely sexual) transmission during long-lasting marriages.

Defining the Delta Virus Positivity in Hepatitis B Virus Infections

OZET Objective: The aim of this study was to retrospectively analyze the frequency of anti-hepatitis delta virus (anti-HDV) antibody in hepatitis B virus surface antigen (HBsAg)-positive cases. Materials and Methods: Anti-HDV and anti-hepatitis B virus core antigen (antiHBc) IgM seropositivity was researched using ELISA method in patients who attended the clinical microbiology laboratory at Ondokuz Mayis University Medical Faculty Hospital between August 2005 and August 2010 and were determined to be positive for HBsAg. Results: A total of 2314 HBsAg-positive patients were included in this study. AntiHDV positivity was detected in 36 (1.56%) of them. By taking the anti-HBc IgM seropositivity as reference, among patients who had positive delta antibody, 33 (91.67%) subjects were evaluated as “super-infection” and 3 (8.33%) patients were evaluated as “co-infection”. Conclusion: Although anti-HDV positivity in our region is relatively lower than in the other regions, emphasis should be given to the prevention and monitoring researches due to the high level of mortality and morbidity of the illness. (Viral Hepatitis Journal 2014; 20(2): 64-66)

Outbreak of Group A Streptococcus at a Pediatric Long Term Care Facility

ISSUE: On July 10, 2013, a rural hospital contacted the State Health Department (SHD) to report an infection prevention breach in colonoscope reprocessing. On January 3, 2013, the hospital introduced a newmodel of colonoscope with an auxiliary water channel not present on previous models; this channel was neither cleaned nor disinfected. Patient notification was performed by the hospital, in coordination with SHD. An investigation into the potential for bloodborne pathogen (BBP) transmission was initiated. PROJECT: Between January 3 and July 18, 277 patients received colonoscopies; patients were cross-matched with SHD’s disease surveillance system to identify BBP infections. Patients were notified via mail and testing for hepatitis C virus (HCV) (total antibody with reflex to HCV polymerase chain reaction), human immunodeficiency virus (HIV) (total antibody), and hepatitis B virus (HBV) (surface antigen(HBsAg) and core immunoglobulin M antibody (anti-HBc IgM)) was recommended. For patient procedures less than six months before their initial blood test, repeat testing six months post-procedure date was recommended. SHD laboratory and contract reference laboratory performed testing. Due to the small patient population, HIV Results will not presented. RESULTS: Prior to testing, three patients were known to be infected with a BBP. As of December 1, 269 patients have been tested, two expired before notification, and six declined testing. Of those tested, 175 have completed their testing, 49 are eligible to receive their secondblood test buthave not returned, and45havenot completed their testing because sixmonths have not elapsed since their procedure. No acute infections have been identified; five patients were newly identifiedashaving laboratoryevidenceof aclearedHCVinfection, andone patient tested positive for anti-HBc IgM but negative for HBsAg. LESSON LEARNED: Risk of BBP transmission following inadequate colonoscope disinfection is believed low. When new colonoscopes are introduced, hospitals must be vigilant in providing adequate training on cleaning and disinfection. Thus far, SHD reports no evidence of transmission despite uninfected patients undergoing procedures on days as individuals infected with a BBP. SHD engagement is crucial when infection control breaches warrant large-scale patient notifications. SHDs can uniquely provide technical assistance, coordinate testing, and determine risk of transmission.

Hepatitis B core IgM antibodies (anti HBcIgM), a serological marker for eradicating transfussion associated hepatitis B virus (TAHBV) infection in low income countries

Background: The safety of blood products is one of the major problems concernedwith the transfusionmedicine. A definite hazard of transmission of hepatitis B to recipients of blood screen for Hepatitis B surface Antigen (HBsAg) when such donor is at the ‘window phase’ exist. The possibility of achieving zero risk of Transfusion Associated Hepatitis B Virus (TAHBV) infection is highly dependent on DNA testing of all collected units of blood before transfusion. This is not feasible in low income countries including Nigeria due to cost. At present, HBsAg detection is the only diagnostic screening test for HBV infection identification in the blood transfusion centers of Nigeria. Hepatitis B core IgM antibody (anti-HBc IgM) is gaining prominence as a useful alternative in reducing TAHBV infection. The present study was aimed at evaluating adoption of anti-HBc IgM an additional screening assay for blood donation since anti-HBc detection is not mandatory in Nigeria. Methods & Materials: Two hundred and seventy-three (Male =246, F =27; Age range:18-50 Mean:24.9years) apparently healthy blood donors in Ibadanwere enrolled in the study between October andDecember2012; their demographicdatawasobtained. The frequency of HBsAg and its corresponding antibody (HBsAb), as well as Hepatitis B envelope antigen and its corresponding antibody (HBeAg and Ab) were assessed using standard enzyme link Immunosorbent assay EELISA) technique. Anti-HBcIgM was also assessed in donors negative or positive for HBsAg using same method. Results: The prevalence of anti-HBc IgM was 4.4%. Twelve (11 Males and 1 female) had anti-HBc IgM as the only marker of HBV infection. Prevalence of HBsAg, HBsAb, HBeAg and HBeAb were 14(5.1%), 95(34.8%), 2(14.3%) and 3(21.4%) respectively. Conclusion: The findings of the current study recommends that all blood units should be tested for anti -HBc IgM to understand the infectivity status of the blood donors in the window period and to discardblood if zero risk of TransfusionAssociatedHepatitis BVirus (TAHBV) infection will be achieved in Nigeria.

Hepatocellular carcinoma in a long-term sustained virological responder following pegylated-interferon plus ribavirin combination therapy for chronic hepatitis C

Background: The safety of blood products is one of the major problems concernedwith the transfusionmedicine. A definite hazard of transmission of hepatitis B to recipients of blood screen for Hepatitis B surface Antigen (HBsAg) when such donor is at the ‘window phase’ exist. The possibility of achieving zero risk of Transfusion Associated Hepatitis B Virus (TAHBV) infection is highly dependent on DNA testing of all collected units of blood before transfusion. This is not feasible in low income countries including Nigeria due to cost. At present, HBsAg detection is the only diagnostic screening test for HBV infection identification in the blood transfusion centers of Nigeria. Hepatitis B core IgM antibody (anti-HBc IgM) is gaining prominence as a useful alternative in reducing TAHBV infection. The present study was aimed at evaluating adoption of anti-HBc IgM an additional screening assay for blood donation since anti-HBc detection is not mandatory in Nigeria. Methods & Materials: Two hundred and seventy-three (Male =246, F =27; Age range:18-50 Mean:24.9years) apparently healthy blood donors in Ibadanwere enrolled in the study between October andDecember2012; their demographicdatawasobtained. The frequency of HBsAg and its corresponding antibody (HBsAb), as well as Hepatitis B envelope antigen and its corresponding antibody (HBeAg and Ab) were assessed using standard enzyme link Immunosorbent assay EELISA) technique. Anti-HBcIgM was also assessed in donors negative or positive for HBsAg using same method. Results: The prevalence of anti-HBc IgM was 4.4%. Twelve (11 Males and 1 female) had anti-HBc IgM as the only marker of HBV infection. Prevalence of HBsAg, HBsAb, HBeAg and HBeAb were 14(5.1%), 95(34.8%), 2(14.3%) and 3(21.4%) respectively. Conclusion: The findings of the current study recommends that all blood units should be tested for anti -HBc IgM to understand the infectivity status of the blood donors in the window period and to discardblood if zero risk of TransfusionAssociatedHepatitis BVirus (TAHBV) infection will be achieved in Nigeria.

Prevalence, risk factors and genotypes of hepatitis B infection among HIV-infected patients in the State of MS, Central Brazil

ObjectivesA cross-sectional study on prevalence of HBV and HDV infection, risk factors and genotype distribution of HBV infection was conducted among 848 HIV-infected patients in Mato Grosso do Sul, Central Brazil. MethodsSerum samples of 848 participants were tested for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) and hepatitis surface antibody (anti-HBs). HBsAg positive samples were tested for anti-HBc IgM, HBeAg, anti-HBe, anti-HCV, and total anti-HDV. HBsAg and anti-HBc positive were subjected to DNA extraction. Viral DNA was amplified by semi-nested PCR for the regions pre-S/S and then purified and genotyped/subgenotyped by direct sequencing. Student's t-test, chi-square test and Fisher's exact test were used to compare variables and to evaluate association between HBV positivity (defined as anti-HBc and/or HBsAg positivity) and risk factors. ResultsAmong the 848 HIV infected patients investigated 222 had serological markers of HBV infection. The prevalence rate of HIV-HBV coinfection was 2.5% (21/848; 95% CI: 1.4–3.5%); 484 (57.1%) patients were susceptible for HBV infection. There were no cases of anti-HDV positive and only one (0.1%) anti-HCV-positive case among the HIV-HBV coinfected patients. Male gender, increasing age, family history of hepatitis, use of illicit drug, and homosexual activity were independent factors associated with HBV exposure. The phylogenetic analysis based on the S gene region revealed the presence of genotypes D (76.9%), F (15.4%) and A (7.7%) in the study sample. ConclusionThis study demonstrates the low prevalence of HIV-HBV infection and also highlights the need for early vaccination against HBV as well as testing for HBV, HCV and HDV in all HIV-infected individuals.

Hepatobiliary Quiz—9 (2014)

1.Regarding acute hepatitic illnesses in patients with chronic hepatitis B (CHB) infection the following are TRUE:1.Most common cause is flare of hepatitis B2.Flare of hepatitis B is more common in HBeAg negative individuals3.Flares of hepatitis B can be due to activation of immune system or due to reactivation of hepatitis B virus4.Reactivation of hepatitis B virus invariably occurs in the setting of immunosupression5.Reactivation of hepatitis B virus does not occur in HBsAg negative patients2.Regarding differentiation of acute hepatitis B infection from flare of chronic hepatitis B the following are TRUE EXCEPT:1.Presence of serum IgM anti-HBc is pathognomonic for acute hepatitis B infection2.In acute hepatitis B infection the 19s subtype of IgM anti-HBc is more common3.IgG anti-HBc can be seen in both acute hepatitis B as well as reactivation of chronic hepatitis B infection4.Hepatitis B DNA levels are higher in acute hepatitis B infection5.HBsAg and HBeAg titres are lower in acute hepatitis B infection3.Regarding pathogenesis and clinical features of Wilson disease the following are TRUE:1.Wilson disease occurs due to mutations in ATP7A gene2.Wilson disease is inherited in an autosomal recessive pattern3.Wilson disease has a definite phenotype–genotype correlation4.Liver disease manifests at earlier age than neurological disease5.Most patients with neurological presentation of Wilson disease will have underlying liver disease4.Regarding the diagnosis of Wilson disease the following are TRUE:1.Kayser–Fleischer ring is almost universally present in patients with neurological Wilson disease2.Total serum copper is reduced in Wilson disease3.Low ceruloplasmin levels are specific for Wilson disease4.d-Penicillamine challenge test is useful to diagnose Wilson disease in adults and asymptomatic siblings of affected patients5.Testing for H1069Q mutation is useful to establish the diagnosis in Indian patients5.Regarding treatment of Wilson disease the following are TRUE EXCEPT:1.Zinc acts by increasing urinary excretion of copper2.d-Penicillamine may cause initial worsening of neurological symptoms3.Trientine is contraindicated in patients intolerant to d-Penicillamine4.Ammonium tetrathiomolybdate may be useful for patients whose neurological disease worsens with other chelators5.Development of anemia or leukopenia during chelation therapy may be due to copper deficiency6.Regarding the pathophysiology of neonatal hemochromatosis the following are TRUE:1.Neonatal hemochromatosis is a hereditary disorder2.Gestational alloimmune liver disease (GALD) is the probable cause of neonatal hemochromatosis3.GALD is an IgM mediated disease4.Complement mediated hepatocyte injury via the classical pathway is the hallmark of GALD5.Histopathological changes are panlobular, and typically spare the portal tracts7.Regarding presentation and diagnosis of neonatal hemochromatosis the following are TRUE:1.Most cases will present after few weeks of birth with liver failure2.Hepatic transaminase levels are very high3.α-fetoprotein levels are very high4.Serum ferritin is very high and transferrin levels are low5.Presence of extrahepatic siderosis is helpful in making the diagnosis8.Regarding treatment and prevention of neonatal hemochromatosis the following are TRUE:1.Iron chelators are useful2.Plasma exchange and intravenous immunoglobulin (IVIg) are therapy of choice3.Liver injury in neonatal hemochromatosis is irreversible with therapy4.Liver transplantation has excellent success rates5.Women with prior affected babies should receive IVIg prophylaxis in subsequent pregnancies9.Regarding donor selection for deceased donor liver transplantation the following are TRUE EXCEPT:1.The ideal donor is less than 40 years of age and has trauma as cause of death2.Ideal donor includes donation after cardiac death3.Ideally the serum sodium of the donor should be below 150 mEq/L4.Exogenous hormone therapy like thyroid hormones and corticosteroids given prior to organ procurement in brain dead donors improves transplantation outcomes5.The Model for End-stage Liver Disease (MELD) score is the best predictor of post-transplant outcomes10.Regarding extended criteria donors for deceased liver transplantation the following are TRUE:1.Cold ischemia time is an important determinant of post-transplant outcomes in grafts from extended criteria donors2.High levels of hepatic transaminases in the donor are a contraindication for liver donation3.The risk of transmission of malignancy via hepatic graft is about 1%4.Organs from donors with previously treated low grade malignancies may be considered for transplantation5.Outcomes from liver grafts from non-heart beating donors are invariably poor

Elazığ Harput Devlet Hastanesi Çalışanlarında Hepatit B ve C Seroprevalansı

Aim: To evaluate the seroprevalence of hepatitis B and C infections among health-care workers in Elazig Harput State Hospital. Methods: Hepatitis B and C virus markers (HBsAg, Anti-HBs, AntiHBc IgM, Anti-HBc IgG, Anti-HCV) of 498 health-care persons were retrospectively investigated in this study between July-August 2007 in Elazig Harput State Hospital. Results: A total 20 (4%) health-care workers were positive for HBsAg, 174 (34.9%) for anti-HBs, 4 (0.8%) for anti-HBs as well as anti-HBc IgG, and 2 (0.4%) for anti-HCV. There were no statistical significant differences in point of HBsAg positivity among health-care workers (p>0.05). Anti-HBs positivity was statistically significant high among nurses compared to the others health-care workers (p=0.001). A total 308 (61.8%) health-care workers were seronegative against hepatitis B. Conclusion: The high seronegativity rate against hepatitis B among health-care workers has shown to need to vaccination and education for hepatitis B infection

Imported acute viral hepatitis E. case report

Case report We present the case of a 54 year-old female patient, which was admitted to the Clinical Hospital for Infectious Diseases “Toma Ciorba” with 38.5°C temperature, with epigastric and right hypochondriac pain, abdominal discomfort, and jaundice. The clinical exam showed abdominal tenderness on palpation in the epigastric region and in the right hypocondrium, the liver being 2-3 cm below the right costal margin, and the spleen 1-2 cm. Before the admission, the onset of the symptoms was sudden with up to 40°C temperature, pain in the right hypochondrium, permanent nausea, fatigability, decreased appetite and dark urine. Laboratory examination showed: total bilirubin 31.0 μmol/L; direct 7.6; ALAT 1500 U/L; ASAT1300 U/L; alkaline phosphatase726 U/L; GGTP279 U/L; prothrombin index 56%. Personal records: in 2007 the diagnosis of chronic viral hepatitis C was established; bilirubin, ASAT and thymol test with normal values. Markers of viral hepatitis: total anti-HCV positive; total anti-HBc positive; antiHAV IgM negative; anti-HBc IgM negative; anti-HCV IgM positive; anti HDV IgM negative; total anti HDV negative; anti-CMV IgM negative; anti-CMV IgG positive; anti-EBV-VCA IgMnegative; anti EBV-VCA IgG positive; anti-HBs negative; anti-HEV IgM O3positive; anti HEV IgG O3positive. From the epidemiological history it was established that five years before she had travelled to Bulgaria. Instrumental investigations: ultrasonographic examination the liver, right lobe 15.5 cm; the left lobe 6.0 cm; the spleen 12.3x5.0 cm; portal vein 1.0 cm; splenic vein 0.7 cm; FibroScan: the average coefficient of hepatic elasticity 6.8 kPa, which corresponds to F0-F1 stage of hepatic fibrosis (according to the Metavir scale). Symptomatic and pathogenetic administered treatment resulted in clinical and biochemical improvement. The patient was monitored clinically and biochemically at 1 and 2 months. Cytolysis syndrome tests had normal values.

Hepatitis B Related Serological Events In Hematopoietic Stem Cell Transplant Patients and Efficacy Of Lamivudine Prophylaxis Against Reactivation

IntroductionRemote Hepatitis B Infection (RHBI) is an immunological stage in the life cycle of Hepatitis B virus (HBV). It is characterized by the persistence of HBV DNA at low level within the liver or blood of people infected in past. As a result HBsAg, HBeAg and HBV DNA in serum are negative while Anti-HBs and/or Anti-HBc IgG are positive with normal liver enzymes. In Hematopoietic stem cell transplant (HSCT) patients, reactivation of RHBI leads to increased HBV replication and increased HBV DNA titres in blood and/or HBsAg or HBeAg positivity. There may be loss or gain of Anti-HBs and/or Anti-HBc IgG. The importance of recognizing this stage with a potential for reactivation is highlighted by the fact that: 1) HBV reactivation can lead to fulminant hepatitis & 2) Anti-HBV therapy such as lamivudine can prevent HBV reactivation. In this study we have aimed to determine the incidence of RHBI and HBV reactivation in our patients, the role of lamivudine in preventing HBV reactivation and the pattern of change in serological markers after reactivation. MethodsAll patients undergoing HSCT from March 2010 to May 2013 were included. Pre transplant, all patients were tested by ELISA for HBsAg, Anti-HBs, Anti-HBc IgM and Anti-HBc IgG. Post transplant, at the time of deranged liver function, all patients were tested for HBsAg, Anti-HBs, Anti-HBc IgM, Anti-HBc IgG, Anti-HCV, Anti-HEV and Anti-HAV. HBV DNA and HCV RNA were tested by polymerase chain reaction. RHBI was defined as positive Anti-HBc IgG and/or Anti-HBs (without history of HBV vaccination) with negative HBsAg and Anti-HBc IgM and normal liver function. HBV reactivation was defined as increase in transaminases to more than 3 times the upper limit of normal with HBV DNA and/or Anti-HBs and/or Anti-HBc IgG positivity (HBsAg and Anti-Hbc IgM being negative) at the time of deranged liver function. Lamivudine at a dose of 100 mg/d or 3 mg/kg/d (children <12 years) was given to all but one patient with Anti-HBc IgG positivity pre transplant irrespective of Anti-HBs positivity (Prophylaxis Group). Patients who had only Anti-HBs positivity did not receive prophylaxis (No Prophylaxis Group). Data was analyzed to explore the role of prophylactic lamivudine in preventing HBV reactivation and to determine the pattern of change of HBV serological markers at the time of reactivation. The time to respond to lamivudine was calculated as the interval from start of prophylaxis to normalization of liver enzymes. ResultsTwo hundred five patients underwent HSCT (autologous - 103 and allogeneic - 102) from March 2010 to May 2013. Twenty-eight (14%) patients were diagnosed to have RHBI (autologous-9, allogeneic-19). Thirteen patients did not receive prophylactic lamivudine (No-Prophylaxis Group) while 15 patients received prophylactic lamivudine (Prophylaxis Group). Twelve (92%) patients in No-Prophylaxis Group developed HBV reactivation while none (0%) in the Prophylaxis Group (P<0.001). The incidence of HBV reactivation was 10% (21 of 205 patients) which included 11 (52%) with only Anti-HBs positive, 1 with only Anti-HBc IgG positive and nine (43%) with all HBV serological markers negative (i.e. no evidence of RHBI) pre transplant. Six of these 9 patients sero-converted (5 - Anti-HBc IgG and 1 - Anti-HBs positive) at the time of reactivation. Seven (33%) developed HBV viremia at the time of HBV reactivation, of which 6 were Anti-HBs negative pre transplant. In contrast, of the patients with undetectable HBV DNA at the time of reactivation (14 patients), only 4(29%) were Anti-HBs negative pre transplant (P=0.0237). Seven (33%) patients were on steroids and 9(43%) were on cyclosporine at the time of reactivation. All patients responded to lamivudine within a median time of 17 days. ConclusionsIncidence of RHBI in patients undergoing HSCT is high in our setting.Lamivudine prophylaxis protects against HBV reactivation post transplant. We would recommend lamivudine prophylaxis in patients with RHBI with isolated Anti-HBs positivity in addition to those with Anti-HBc IgG positivity given the high rate of HBV reactivation in these patients.All serological markers for Hepatitis B being negative pre transplant does not preclude HBV reactivation post transplant. Therefore, all serological markers for HBV should be repeated at the time of deranged liver functions post transplant.Anti-HBs positivity pre transplant decreases the risk of HBV viremia at the time of reactivation. Disclosures:No relevant conflicts of interest to declare.

British HIV Association guidelines for the management of hepatitis viruses in adults infected with HIV 2013

British <scp>HIV A</scp>ssociation guidelines for the management of hepatitis viruses in adults infected with <scp>HIV</scp> 2013

PROSPECTS OF THE USE "STIMFORTE" IN CHRONIC HEPATITIS B

Despite the fact that over the last few years downward trend in the incidence of acute forms of viral hepatitis B continues, the incidence of chronic hepatitis B (CHV) has increased by 2.5 times since 1998. To date, there are a sufficient number of antiviral drugs, but their use is associated with a set of contraindications, as well as the development of resistance. In this study there was performed an evaluation of a new national drug " Stimforte " in patients with chronic viral hepatitis B (CVHB - DNA positive, HBsAg - positive) at the stage of exacerbation. In the study there were included 28 patients with chronic hepatitis B (HBsAg positive), at different grades of activity, at a stage of viral replication. The diagnosis of chronic hepatitis B was made on the presence in a history acute viral hepatitis for more than 1 year, complaints, hepatolienal, astenovegetative, cytolytic syndromes, the presence of DNA-HBV, anti-HBcore IgM, HBsAg. After 1 course of treatment with " Stimforte " the well-being of patients has improved: in 30% of patients asthenic- vegetative syndrome had disappeared, weakness, fatigue and dyspeptic symptoms were decreased. The use of "Stimforte" in chronic hepatitis B with positive HBsAg at the stage of exacerbation contributed to a more rapid normalization of such indices as ALT, AST, compared with those in the control group. Long-term biochemical and virological remission was achieved in 40 %. It is established that during the treatment the viral load was reduced progressively until the undetectable or low level of HBV DNA and anti-HBc IgM disappeared. In only one case an allergic reaction was observed, which has not hindered to perform a complete course of treatment. No other side effects were detected. The inclusion of the drug "Stimforte" in the complex therapy of patients with exacerbation of chronic hepatitis B reduces the time of recovery of immune status and functional activity of IFN system and contributes to reduction of the viral load or elimination of the virus.

Rare Case of Rituximab-associated Hepatitis B Virus Reactivation with Co-existence of IgM Anti-Hepatitis A and IgM Anti-Hepatitis E Antibodies

Purpose: A 68-year-old Caucasian man was seen in the hospital for abnormal LFTs. He carried a diagnosis of HHV-8 related plasmablastic T-cell lymphoma. He had undergone treatment with cyclosporine, doxorubicin, vincristine, and prednisone, with initial remission of disease; however, he developed recurrence and was subsequently treated with rituximab 8 months prior to presentation. Before the initiation of chemotherapy, the patient underwent testing for hepatitis B (HBV), which demonstrated he was HBV surface antigen (HBsAg) negative, anti-HBV surface antibody (anti-HBS) positive, and IgM anti-HBV core antibody (anti-HBc IgM) negative. A total anti-HBV core antibody (anti-HBc total) was not checked prior to starting therapy. On the current admission, total bilirubin was 7.9 mg/dL with conjugated fraction of 4.7 mg/dL. AST was elevated to 830 U/L, ALT to 1591 U/L, and alkaline phosphatase to 189 U/L. Serum ANA was positive at a titer of <1:80 and anti-smooth muscle antibody was negative. Ceruloplasmin was noted at 44 mg/dL. Serologies demonstrated HBsAg to be positive, anti-HBs negative, anti-HBc total positive, anti-HBc IgM positive, HBeAg positive, and anti-HBe negative. HBV PCR found 5.81 Log IU viral particles. Furthermore, his hepatitis A virus (HAV) total antibody was positive, and the anti-HAV IgM antibody was reactive. His anti-hepatitis E virus (HEV) IgM antibody was also detected, and anti-HEV IgG was negative. Hepatitis D antibody was negative. Liver biopsy showed irregular hepatic plates with hepatocyte dropout, peri-portal inflammation, multiple apoptotic bodies, and ballooning degeneration. Stage one to two fibrosis was found. Tenofovir 300 mg daily was started for reactivated HBV, and his AST, ALT, and bilirubin declined to normal 16 weeks later. Acute hepatitis resulting from co-infection with multiple hepatotropic viruses may occur. In some instances, the mechanism by which they are contracted and risk factors for their exposure are shared. In the developing world, several case reports and series have described instances where patients presented with serologic evidence for acute infection from both HAV and HEV. These studies have generally been performed in the setting of sporadic cases with clinical syndromes of acute hepatitis. However, the use of serologic testing to establish diagnoses of acute HAV or HEV in these settings is problematic. Serologic tests were designed for cases in which the pretest probability and clinical suspicion for exposure to acute HEV or HAV were high (i.e., epidemic outbreaks or travel to endemic areas). Whether the presence of anti-HAV and HEV in the setting of such sporadic cases are indicative of true co-infection or represent false positive results remains debatable.

Molecular Epidemiology and Clinical Characteristics of Hepatitis B Identified through the French Mandatory Notification System

Background & AimsStrains responsible for acute hepatitis B infections (AHB) in France have not been characterized. This study was first designed to analyze the molecular epidemiology of AHB and second to describe the differences between AHB and chronic hepatitis B (CHB) exacerbations.MethodsThis prospective study was based on the French mandatory notification system for AHB. 147 samples corresponding to declared cases were shipped to a central laboratory for classification as AHB or CHB according to the level of anti-HBc IgM and anti-HBc avidity.ResultsBased on biological marker values and file examination, 75 cases (59%) were classified as AHB. Independently of the acute or chronic status, genotype A (57%), D (22%) and E (14%) were the most prevalent and no phylogenetic clustering was observed among HBV sequences (n=68). Precore or basal core-promoter variants were not particularly associated with disease severity but were more prevalent in CHB. No antiviral resistant strains or immune-escape HBsAg was observed. HBV viral loads in AHB or CHB were comparable but with opposite distributions. ALT levels reached 10 times the upper normal value in 94% of AHB but only in 24% of CHB.ConclusionsAfter rigorous classification, no major difference at the genetic level was found between HBV strains isolated from AHB and CHB. Absence of potentially deleterious variant detection is reassuring. When based upon HBsAg and anti-HBc IgM determination, AHB notification may falsely include more than 40% CHB, leading to an important risk of bias in national surveillance programs of AHB.