Porcine-derived pancreatic enzyme replacement therapy may be linked to chronic hepatitis E virus infection in cystic fibrosis lung transplant recipients.

OBJECTIVES: In high-income countries hepatitis E virus (HEV) is an uncommonly diagnosed porcine-derived zoonoses. After identifying disproportionate chronic HEV infections in persons with cystic fibrosis (pwCF) postlung transplant, we sought to understand its epidemiology and potential drivers. DESIGN: All pwCF post-transplant attending our regional CF centre were screened for HEV. HEV prevalence was compared against non-transplanted pwCF and with all persons screened for suspected HEV infection from 2016 to 2022 in Alberta, Canada. Those with chronic HEV infection underwent genomic sequencing and phylogenetic analysis. Owing to their swine derivation, independently sourced pancreatic enzyme replacement therapy (PERT) capsules were screened for HEV. RESULTS: HEV seropositivity was similar between transplanted and non-transplanted pwCF (6/29 (21%) vs 16/83 (19%); p=0.89). Relative to all other Albertans investigated for HEV as a cause of hepatitis (n=115/1079, 10.7%), pwCF had a twofold higher seropositivity relative risk and this was four times higher than the Canadian average. Only three chronic HEV infection cases were identified in all of Alberta, all in CF lung transplant recipients (n=3/29, 10.3%). Phylogenetics confirmed cases were unrelated porcine-derived HEV genotype 3a. Ninety-one per cent of pwCF were taking PERT (median 8760 capsules/person/year). HEV RNA was detected by RT-qPCR in 44% (47/107) of PERT capsules, and sequences clustered with chronic HEV cases. CONCLUSION: PwCF had disproportionate rates of HEV seropositivity, regardless of transplant status. Chronic HEV infection was evident only in CF transplant recipients. HEV may represent a significant risk for pwCF, particularly post-transplant. Studies to assess HEV incidence and prevalence in pwCF, and potential role of PERT are required.

Hepatitis B virus genotype surveillance in Canadian blood donors and a referred patient population, 2016-2021.

BACKGROUND AND OBJECTIVES: Hepatitis B virus (HBV) genotypes (A-H) have a distinct geographic distribution and are highly associated with the country of birth. Canada has experienced increased immigration over the past decade, primarily from regions where HBV is endemic. This study investigated the proportions and trends of HBV genotypes within blood donor and clinical populations of Canada over the period 2016-2021. MATERIALS AND METHODS: Study samples involved two cohorts: (1) Canadian blood donors (n = 246) deferred from donation due to HBV test positivity and (2) chronic HBV patients from across Canada (clinically referred population, n = 3539). Plasma or serum was extracted, and the surface antigen and/or polymerase-coding region was amplified and sequenced to determine genotype by phylogenetic analysis. RESULTS: Six (A-E, G) and eight (A-H) HBV genotypes were detected among deferred blood donors and the clinically referred population, respectively. Differences in HBV genotype proportions between the two cohorts were observed across Canada. Males comprised most of the referred population among genotypes A-E (p < 0.0001), except for genotypes B and C. The median age was younger among blood donors (36 years [range 17-72]) compared with the referred population (41 years [range 0-99]). Distinct trends of increasing (E, referred; B, blood donor) and decreasing genotype prevalence were observed over the study period. CONCLUSION: HBV genotypes in Canada are highly diverse, suggesting a large immigrant population. Observed trends in genotype prevalence and proportional differences among cohorts imply shifts among the HBV-infected population of Canada, which warrants continued surveillance.

An international review of the characteristics of viral nucleic acid-amplification testing (NAT) reveals a trend towards the use of smaller pool sizes and individual donation NAT.

BACKGROUND AND OBJECTIVES: Nucleic acid-amplification testing (NAT) is used for screening blood donations/donors for blood-borne viruses. We reviewed global viral NAT characteristics and NAT-yield confirmatory testing used by blood operators. MATERIALS AND METHODS: NAT characteristics and NAT-yield confirmatory testing used during 2019 was surveyed internationally by the International Society of Blood Transfusion Working Party Transfusion-Transmitted Infectious Diseases. Reported characteristics are presented herein. RESULTS: NAT was mainly performed under government mandate. Human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV) NAT was performed on all donors and donation types, while selective testing was reported for West Nile virus, hepatitis E virus (HEV), and Zika virus. Individual donation NAT was used for HIV, HCV and HBV by ~50% of responders, while HEV was screened in mini-pools by 83% of responders performing HEV NAT. Confirmatory testing for NAT-yield samples was generally performed by NAT on a sample from the same donation or by NAT and serology on samples from the same donation and a follow-up sample. CONCLUSION: In the last decade, there has been a trend towards use of smaller pool sizes or individual donation NAT. We captured characteristics of NAT internationally in 2019 and provide insights into confirmatory testing approaches used for NAT-yields, potentially benefitting blood operators seeking to implement NAT.

International review of blood donation nucleic acid amplification testing.

BACKGROUND AND OBJECTIVES: Nucleic acid amplification testing (NAT), in blood services context, is used for the detection of viral and parasite nucleic acids to reduce transfusion-transmitted infections. This project reviewed NAT for screening blood donations globally. MATERIALS AND METHODS: A survey on NAT usage, developed by the International Society of Blood Transfusion Working Party on Transfusion-transmitted Infectious Diseases (ISBT WP-TTID), was distributed through ISBT WP-TTID members. Data were analysed using descriptive statistics. RESULTS: Forty-three responses were received from 32 countries. Increased adoption of blood donation viral screening by NAT was observed over the past decade. NAT-positive donations were detected for all viruses tested in 2019 (proportion of donations positive by NAT were 0.0099% for human immunodeficiency virus [HIV], 0.0063% for hepatitis C virus [HCV], 0.0247% for hepatitis B virus [HBV], 0.0323% for hepatitis E virus [HEV], 0.0014% for West Nile virus [WNV] and 0.00005% for Zika virus [ZIKV]). Globally, over 3100 NAT-positive donations were identified as NAT yield or solely by NAT in 2019 and over 22,000 since the introduction of NAT, with HBV accounting for over half. NAT-positivity rate was higher in first-time donors for all viruses tested except WNV. During 2019, a small number of participants performed NAT for parasites (Trypanosoma cruzi, Babesia spp., Plasmodium spp.). CONCLUSION: This survey captures current use of blood donation NAT globally. There has been increased NAT usage over the last decade. It is clear that NAT contributes to improving blood transfusion safety globally; however, there is a need to overcome economic barriers for regions/countries not performing NAT.

The molecular epidemiology of hepatitis E virus genotype 3 in Canada.

Autochthonous hepatitis E virus (HEV) infection is increasingly reported in industrialized countries and is mostly associated with zoonotic HEV genotype 3 (HEV-3). In this study, we examined the molecular epidemiology of 63 human clinical HEV-3 isolates in Canada between 2014 and 2022. Fifty-five samples were IgM positive, 45 samples were IgG positive and 44 were IgM and IgG positive. The majority of the isolates belong to the subtypes 3a, 3b, and 3j, with high sequence homology to Canadian swine and pork isolates. There were a few isolates that clustered with subtypes 3c, 3e, 3f, 3h, and 3g, and an isolate from chronic infection with a rabbit strain (3ra). Previous studies have demonstrated that the isolates from pork products and swine from Canada belong to subtypes 3a and 3b, therefore, domestic swine HEV is likely responsible for the majority of clinical HEV cases in Canada and further support the hypothesis that swine serve as the main reservoirs for HEV-3 infections. Understanding the associated risk of zoonotic HEV infection requires the establishment of sustainable surveillance strategies at the interface between humans, animals, and the environment within a One-Health framework.

Rat Hepatitis E Virus in Norway Rats, Ontario, Canada, 2018-2021.

We tested liver samples from 372 Norway rats (Rattus norvegicus) from southern Ontario, Canada, during 2018-2021 to investigate presence of hepatitis E virus infection. Overall, 21 (5.6%) rats tested positive for the virus. Sequence analysis demonstrated all infections to be rat hepatitis E virus (Rocahepevirus ratti genotype C1).

Identification and characterization of a G-quadruplex structure in the pre-core promoter region of hepatitis B virus covalently closed circular DNA.

Approximately 250 million people worldwide are chronically infected with the hepatitis B virus (HBV) and are at increased risk of developing cirrhosis and hepatocellular carcinoma. The HBV genome persists as covalently closed circular DNA (cccDNA), which serves as the template for all HBV mRNA transcripts. Current nucleos(t)ide analogs used to treat HBV do not directly target the HBV cccDNA genome and thus cannot eradicate HBV infection. Here, we report the discovery of a unique G-quadruplex structure in the pre-core promoter region of the HBV genome that is conserved among nearly all genotypes. This region is central to critical steps in the viral life cycle, including the generation of pregenomic RNA, synthesis of core and polymerase proteins, and genome encapsidation; thus, an increased understanding of the HBV pre-core region may lead to the identification of novel anti-HBV cccDNA targets. We utilized biophysical methods (circular dichroism and small-angle X-ray scattering) to characterize the HBV G-quadruplex and the effect of three distinct G to A mutants. We also used microscale thermophoresis to quantify the binding affinity of G-quadruplex and its mutants with a known quadruplex-binding protein (DHX36). To investigate the physiological relevance of HBV G-quadruplex, we employed assays using DHX36 to pull-down cccDNA and compared HBV infection in HepG2 cells transfected with wild-type and mutant HBV plasmids by monitoring the levels of genomic DNA, pregenomic RNA, and antigens. Further evaluation of this critical host-protein interaction site in the HBV cccDNA genome may facilitate the development of novel anti-HBV therapeutics against the resilient cccDNA template.

Research partnerships between blood services and public health authorities: An international, cross-sectional survey.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic has brought to the fore how blood services can partner with public health (PH) authorities to inform decisions. Yet the scope of partnerships between blood services and PH authorities is inadequately documented. We explored how blood services partner with PH authorities outside the scope of COVID-19. MATERIALS AND METHODS: On 19 January 2022, survey was sent to employees of blood services located throughout the world. Survey questions mainly pertained to partnerships with PH authorities, including how blood specimens are used and collected. RESULTS: Twenty-seven recipients-4 (14.8%) in Africa, 3 (11.1%) in Asia, 9 (33.3%) in Europe, 6 (22.2%) in North America, 2 (7.4%) in Oceania and 3 (11.1%) in South America-completed the survey. Fifteen recipients (55.6%) indicated their blood service was directly or indirectly supervised by PH authorities. Twenty-four recipients (88.9%) indicated currently using or planning to use blood donor data or samples for PH research or pathogen surveillance. A substantial proportion of respondents reported using samples or results from non-routine tests for the surveillance of non-transfusion-transmitted infectious disease pathogens (n = 13 [48.1%]); samples or results of non-routine tests for PH research unrelated to pathogens (n = 10 [37.0%]); donor data for PH research unrelated to pathogens (n = 12 [44.4%]) and donor data for PH research unrelated to transfusion safety (n = 11 [40.7%]). Fourteen (51.9%) had established (or planned to establish) longitudinal cohorts and 19 (70.4%) biobanks. CONCLUSION: The majority of responding blood services were already involved in or planned to be involved in PH research or pathogen surveillance.

Current challenges of severe acute respiratory syndrome coronavirus 2 seroprevalence studies among blood donors: A scoping review.

BACKGROUND AND OBJECTIVES: Blood donors are increasingly being recognized as an informative resource for surveillance. We aimed to review severe acute respiratory syndrome coronavirus 2 seroprevalence studies conducted among blood donors to investigate methodological biases and provide guidance for future research. MATERIALS AND METHODS: We conducted a scoping review of peer-reviewed and preprint publications between January 2020 and January 2021. Two reviewers used standardized forms to extract seroprevalence estimates and data on methodology pertaining to population sampling, periodicity, assay characteristics, and antibody kinetics. National data on cumulative incidence and social distancing policies were extracted from publicly available sources and summarized. RESULTS: Thirty-three studies representing 1,323,307 blood donations from 20 countries worldwide were included (sample sizes ranged from 22 to 953,926 donations). The majority of the studies (79%) reported seroprevalence rates <10% (ranging from 0% to 76% [after adjusting for waning antibodies]). Overall, less than 1 in 5 studies reported standardized seroprevalence rates to reflect the demographics of the general population. Stratification by age and sex were most common (64% of studies), followed by region (48%). A total of 52% of studies reported seroprevalence at a single time point. Overall, 27 unique assay combinations were identified, 55% of studies used a single assay and only 39% adjusted seroprevalence rates for imperfect test characteristics. Among the nationally representative studies, case detection was most underrepresented in Kenya (1:1264). CONCLUSION: By the end of 2020, seroprevalence rates were far from reaching herd immunity. In addition to differences in community transmission and diverse public health policies, study designs and methodology were likely contributing factors to seroprevalence heterogeneity.

Ribavirin Does Not Enhance Hepatitis B Virus Nucleotide Antiviral Activity: A Pilot Study.

PURPOSE: There is a need for effective and affordable treatments that achieve hepatitis B virus (HBV) functional cure and prevent long-term complications. The use of immune-modulators combined with HBV antivirals is a promising therapeutic strategy to achieve these goals. Based on ribavirin (RBV) monotherapy data, we hypothesized that RBV could improve virological responses when used in combination with tenofovir.  Methods: In this randomized, open label, controlled pilot trial, we evaluated RBV (n=4) dosed for the initial 24 weeks of treatment versus no RBV (n=4) in tenofovir recipients dosed over 48 weeks.  Results: Although well tolerated and safe in combination with tenofovir, RBV demonstrated no beneficial effects on virologic, biochemical or immunological markers of chronic HBV infection over 48 weeks of serial evaluation.  Conclusions: Our data does not suggest a HBV-specific immunomodulatory effect or an impact of RBV on HBV virological and antigen suppression.

Distinct Hepatitis B and HIV co-infected populations in Canada.

Due to shared modes of exposure, HIV-HBV co-infection is common worldwide. Increased knowledge of the demographic and clinical characteristics of the co-infected population will allow us to optimize our approach to management of both infections in clinical practice. The Canadian Hepatitis B Network Cohort was utilized to conduct a cross-sectional evaluation of the demographic, biochemical, fibrotic and treatment characteristics of HIV-HBV patients and a comparator HBV group. From a total of 5996 HBV-infected patients, 335 HIV-HBV patients were identified. HIV-HBV patients were characterized by older median age, higher male and lower Asian proportion, more advanced fibrosis and higher anti-HBV therapy use (91% vs. 30%) than the HBV-positive / HIV seronegative comparator group. A history of reported high-risk exposure activities (drug use, high-risk sexual contact) was more common in HIV-HBV patients. HIV-HBV patients with reported high-risk exposure activities had higher male proportion, more Caucasian ethnicity and higher prevalence of cirrhosis than HIV-HBV patients born in an endemic country. In the main cohort, age ≥60 years, male sex, elevated ALT, the presence of comorbidity and HCV seropositivity were independent predictors of significant fibrosis. HIV seropositivity was not an independent predictor of advanced fibrosis (adj OR 0.75 [95%CI: 0.34-1.67]). In conclusion, Canadian co-infected patients differed considerably from those with mono-infection. Furthermore, HIV-HBV-infected patients who report high-risk behaviours and those born in endemic countries represent two distinct subpopulations, which should be considered when engaging these patients in care.

Spontaneous Flares of Chronic Hepatitis B Virus in Hepatitis Be Antigen Negative Carriers Who Subsequently Clear Hepatitis B Surface Antigen.

BACKGROUND: Acute exacerbations of chronic hepatitis B virus (HBV) infections can occur in HBV-infected, hepatitis e antigen (HBeAg)-negative patients in the absence of recent withdrawal of antiviral or immunosuppressive therapies. Whether these spontaneous "flares" predict subsequent loss of hepatitis B surface antigen (HBsAg) has yet to be determined. OBJECTIVES: To document the percent of patients who experience spontaneous HBV flares and severity of the flares in chronic HBeAg-negative carriers. METHODS: A retrospective review of an HBV database identified and followed HBeAg-negative patients for biochemical evidence of flares (ALT > 5× normal) and subsequent HBsAg status. Patients that subsequently cleared HBsAg were matched 1:1 with those who remained HBsAg positive. RESULTS: Of 1299 HBeAg-negative patients followed for 10.2 ± 6.1 years, 88 (6.8%) developed spontaneous HBV flares. Flares occurred in 14/115 (12.2%) patients who subsequently cleared HBsAg and 4/111 (3.6%) matched patients who remained HBsAg positive (p = 0.025). The severity of flares was similar in the two study cohorts. Following multivariate analyses, only low HBV-DNA levels at baseline identified patients likely to subsequently clear HBsAg. CONCLUSIONS: Although more common in patients who subsequently clear HBsAg, spontaneous HBV flares do not predict subsequent HBsAg clearance.

Horizontal Transmission of Hepatitis B Virus From Mother to Child Due to Immune Escape Despite Immunoprophylaxis.

Hepatitis B virus (HBV) vaccination starting at birth is approximately 95% effective in preventing mother-to-child transmission to infants born to HBV-infected mothers. A higher risk of transmission is associated with birth to a highly viremic mother, often due to transplacental exposure, while later horizontal transmission is much less common, particularly following complete vaccination. This study reports a case of infection in an older child despite appropriate immunoprophylaxis starting at birth and an apparent protective immune response post-vaccination. Two immune escape mutations within the antigenic determinant of the surface antigen-coding region were observed in the child's dominant HBV sequence, whereas the maternal HBV variant lacked mutations at both sites. Ultra-deep sequencing confirmed the presence of 1 mutation at low levels within the maternal HBV quasispecies population, suggesting early exposure to the child followed by viral evolution resulting in immunoprophylaxis escape and chronic infection.

Long-Term Follow-up and Quantitative Hepatitis B Surface Antigen Monitoring in North American Chronic HBV Carriers.

INTRODUCTION: Quantitative hepatitis B surface antigen (qHBsAg) combined with HBV DNA may be useful for predicting chronic hepatitis B (CHB) activity and nucleoside analogue (NA) response. MATERIAL AND METHODS: In this retrospective cohort study we evaluated qHBsAg levels according to CHB disease phase and among patients on treatment. Random effect logistic regression analysis was used to analyze qHBsAg change with time in the NA-treated cohort. RESULTS: 545 CHB carriers [56% M, median age 48 y (IQR 38-59), 73% Asian] had qHBsAg testing. In the untreated group (44%), 8% were classified as immune tolerant, 10% immune clearance, 40% inactive, and 43% had HBeAg- CHB and the median HBsAg levels were 4.6 (IQR 3.4-4.9), 4.0 (IQR 3.4-4.5), 2.9 (IQR 1.4-3.8), and 3.2 log IU/mL (IQR 2.6-4.0), respectively; p < 0.001. In the NA-treated group (28% entecavir, 68% tenofovir, 4% lamivudine), no significant change in qHBsAg levels occured with time. However, 19% of patients on long-term NA had sustained qHBsAg < 2 log10 IU/mL. CONCLUSION: qHBsAg titers were associated with CHB phase and remained stable in those on long-term NA. A significant number of treated patients had low-level qHBsAg, of which some may be eligible for treatment discontinuation without risk of flare.

Chronic hepatitis B carriers with acute on chronic liver failure show increased HBV surface gene mutations, including immune escape variants.

BACKGROUND: The pathogenesis of acute-on-chronic liver failure (ACLF) in chronic hepatitis B (CHB) is not well understood. The aim of this study was to investigate whether there is an association between HBV polymerase (P)/overlapping surface (S) gene and basal core promoter (BCP)/precore (PC) variants and development of ACLF in CHB. METHODS: Two CHB patient cohorts were compared: (i) ACLF (N = 12) (11/12 M, median age 52 yrs., 5/9 genotype C, 6/12 HBeAg+), (ii) 27 treatment native CHB carriers (15/27 M, median age 44 yrs., 9 genotype B, 10 genotype C, 1 genotype A, 5 genotype D, 2 genotype E). Clonal sequencing of PCR-amplified HBV P/S and BCP/PC gene fragments was done and HBV diversity, frequency of immune escape (IE) and drug resistance (DR) mutations and mutations in BCP/PC gene (G1896A and A1762T/G1764A), were compared between each group. RESULTS: Our data showed the incidence of IE and clusters of mutations in the HBV S region was significantly greater in ACLF patients vs. treatment naïve CHB patients (p < 0.05). Additionally, a significantly higher frequency of G1896A and A1762T/G1764A mutations were found in HBeAg negative than in ACLF patients (p < 0.0001). CONCLUSION: In our study, ACLF was not associated with a specific genomic mutation. However, higher frequency of IE mutations along with various mutations clustering in the HBV S region could contribute to or be an outcome of ACLF in CHB infection. (words 226).

Hepatitis B infection is highly prevalent among patients presenting with jaundice in Kenya.

BACKGROUND: Viral hepatitis is a major concern worldwide, with hepatitis A (HAV) and E (HEV) viruses showing sporadic outbreaks while hepatitis B (HBV) and C (HCV) viruses are associated with chronic hepatitis, cirrhosis and hepatocellular carcinoma. The present study determined the proportion, geographic distribution and molecular characterization of hepatitis viruses among patients seeking medical services at hospitals throughout Kenya. METHODS: Patients presenting with jaundice at four selected hospitals were recruited (n = 389). Sera were tested for the presence of antibody to hepatitis viruses A through E, and HBV surface antigen (HBsAg). Nucleic acid from anti-HAV IgM antibody and HBsAg positive samples was extracted, amplified and sequenced. RESULTS: Chronic HBV infection was the leading cause of morbidity among patients with symptoms of liver disease seeking medical help. Incident HCV, HEV and HDV infection were not detected among the patients in this study, while the proportion of acute HAV was low; HAV IgM positivity was observed in 6.3 % of patients and sequencing revealed that all cases belonged to genotype 1B. HCV seropositivity upon initial screening was 3.9 % but none were confirmed positive by a supplementary immunoblot assay. There was no serological evidence of HDV and acute HEV infection (anti-HEV IgM). HBsAg was found in 50.6 % of the patients and 2.3 % were positive for IgM antibody to the core protein, indicating probable acute infection. HBV genotype A was predominant (90.3 %) followed by D (9.7 %) among HBV DNA positive specimens. Full genome analysis showed HBV/D isolates having similarity to both D4 and D6 subgenotypes and D/E recombinant reference sequences. Two recombinant sequences demonstrated > 4 % nucleotide divergence from other previously known D/E recombinants. CONCLUSIONS: HBV is highly prevalent among patients seeking care for symptoms consistent with hepatitis, compared to the general population. Molecular characterization of HBV isolates indicated recombinant strains that may give rise to new circulating variants. There is a need to document the prevalence, clinical manifestation and distribution of the variants observed. HAV genotype 1B, prevalent in Africa, was observed; however, the absence of HCV, HDV and acute HEV in this study does not rule out their presence in Kenya.

Public health response to a large-scale endoscopy infection control lapse in a nonhospital clinic.

OBJECTIVE: To determine whether transmission of blood-borne pathogens (BBPs) (hepatitis B virus [HBV], hepatitis C virus [HCV] and HIV) occurred as a result of endoscopy reprocessing failures identified during an inspection of a nonhospital endoscopy clinic in 2011. METHODS: The present analysis was a retrospective cohort study. Registered notification letters were mailed to 6992 patients who underwent endoscopy from 2002 to 2011 at one Canadian nonhospital endoscopy clinic, informing them of the infection control lapse and offering BBP testing. Multimedia communications and a telephone line supplemented notification. A retrospective study of patients with BBPs was performed with viral genetic testing and risk factor assessment for eligible patients. Risk for infection among patients whose procedure was within seven days of a known positive patient was compared with those whose procedure was performed more than seven days after a known postive patient. The seven-day period was selected as the period most likely to present a risk for transmission based on the documented cleaning procedures at the clinic and the available literature on virus survival. RESULTS: Ninety-five percent (6628 of 6992) of patients/estates were contacted and 5042 of 6728 (75%) living patients completed BBP testing. Three were newly diagnosed with HBV and 14 with HCV. Twenty-three and 48 tested positive for previously known HBV or HCV, respectively, 367 were immune to HBV due to natural infection and one was immune to HBV due to immunization. None tested positive for HIV. Sequencing did not reveal any relationships among the 46 unique case patients with viral genetic test results available. Ninety-three percent of patients reported alternative risk factors for BBP. An increased risk for infection among those who underwent a procedure within seven days of a known HBV or HCV case was not demonstrated. CONCLUSIONS: Endoscopy reprocessing failures were not associated with an increased risk for BBP among individuals tested.

OBJECTIF: Lors de l'inspection d'une clinique d'endoscopie non hospitalière en 2011, déterminer si des pathogènes à diffusion hématogène (PDH; virus de l'hépatite B [VHB], virus de l'hépatite C [VHC] et VIH) sont transmis à cause de la défaillance du retraitement de l'endoscopie. MÉTHODOLOGIE: Dans la présente étude de cohorte rétrospective, les chercheurs ont posté une lettre recommandée à 6 992 patients qui avaient subi une endoscopie entre 2002 et 2011 dans une clinique canadienne d'endoscopie non hospitalière pour les informer d'une défaillance du contrôle des infections et leur offrir un test de dépistage des PDH. Les communications multimédias et les appels téléphoniques ont complété cet avis. Les chercheurs ont effectué une étude rétrospective des patients ayant des PDH au moyen de tests génétiques viraux et d'une évaluation des facteurs de risque des patients admissibles. Ils ont comparé le risque d'infection entre les patients dont l'intervention avait eu lieu dans les sept jours suivant celle d'un patient positif connu ceux dont l'intervalle dépassait sept jours. Cette période de sept jours était la plus susceptible de constituer un risque de transmission compte tenu des mesures de nettoyage attestées à la clinique et les publications sur la survie des virus. RÉSULTATS: Les chercheurs ont pris contact avec 95 % (6 628 cas sur 6 692) des patients et des successions, et 5 042 des 6 728 (75 %) patients vivants ont effectué le test de dépistage des PDH. Trois ont obtenu un nouveau diagnostic de VHB et 14, de VHC. De plus, 23 et 48 ont obtenu des résultats positifs à un VHB ou à un VHC déjà connu, respectivement, 367 étaient immuns au VHB en raison d'une infection naturelle et un, grâce à la vaccination. Aucun n'a obtenu de résultat positif au VIH. Le séquençage a révélé l'absence de lien entre les 46 cas uniques de patients pour qui les résultats du test génétique étaient disponibles. Aussi, 93 % des patients ont signalé d'autres facteurs de risques de PDH. Par ailleurs, on n'a pu démontrer d'augmentation du risque d'infection chez les personnes qui avaient subi une intervention dans les sept jours suivant un cas connu de VHB ou de VHC. CONCLUSIONS: L'échec de retraitement de l'endoscopie ne s'associait pas à une augmentation du risque de PDH chez les personnes qui subissaient un test de dépistage.

Establishing diagnostic criteria for occult hepatitis B virus infections in community based populations.

Present diagnostic criteria for occult hepatitis B virus (HBV) infection requires blood or liver samples to test positive for at least two HBV DNA targets in hepatitis B surface antigen (HBsAg) negative individuals. These criteria were derived from studies involving referred or selected patient populations. The objective of the present study was to determine whether the present definition of occult HBV infection also applies within a nonselected community based population. HBV DNA testing was performed in 1,007 HBsAg negative sera by real time PCR with primer sets targeting the Enhancer I (ENHI), precore/core and surface/polymerase (S) genomic regions. Real time PCR positive cases were analyzed further by nested PCR. The results were then correlated with serologic findings among HBV DNA negative and occult positive individuals. Fifty-five sera (5.5%) were positive for at least one of the three genomic regions. Positive results with at least two primer/probe sets (thereby satisfying present diagnostic criteria for occult HBV infection) were identified in 8 (0.8%) samples (3 ENHI plus S, 2 ENHI plus precore/core and 3 having positive results with all three primer/probe sets). The prevalence of HBV serologic markers in samples that tested positive for only one primer set were similar to those of HBV DNA negative matched controls, thereby arguing against their representing occult infection. The results of this study suggest that the present diagnostic criteria for occult HBV infection are also appropriate for population based studies. However, further studies are required to confirm that impression.

Characterization of hepatitis B virus genotypes and quantitative hepatitis B surface antigen titres in North American tertiary referral liver centres.

BACKGROUND & AIMS: Hepatitis B virus (HBV) genotype and quantitative hepatitis B surface antigen (qHBsAg) have been related to clinical outcome. In this nationwide cross-sectional study, we aimed to investigate the epidemiology and clinical significance of HBV genotype and qHBsAg in patients with chronic hepatitis B (CHB). METHODS: Six hundred and thirty patients with CHB were seen in four urban tertiary referral centres in Canada. HBV genotype was determined by line probe assay (INNO-LIPA) and HBV DNA quantified by commercial PCR (Roche TaqMan, sensitivity <55 IU/ml or AMPLICOR, sensitivity <60 IU/ml). Titres of qHBsAg were determined by an in-house assay based on the WHO standard (calibration range 0.24-62.5 IU/ml). RESULTS: In 630 patients (57% male, 69% Asian, median age 42 years), 21% were hepatitis B e antigen positive and the median alanine aminotransferase was 29 U/L. The HBV genotype distribution was A (16%), B (29%), C (31%), D (16%), E (6%). HBV genotype was strongly associated with ethnicity, but neither genotype nor qHBsAg correlated with the degree of fibrosis. In the treatment-naïve patients, the baseline qHBsAg levels correlated with HBV DNA (r = 0.2517, P < 0.0008). The median qHBsAg levels were lowest in patients with genotype B (P < 0.0001), but no significant correlation was noted with all other HBV genotypes. CONCLUSIONS: In this large North American HBV epidemiological study, genotypes B and C were the most common; however, all genotypes (A-E) were observed with varied distribution nationwide. Baseline qHBsAg significantly correlated with HBV DNA and with HBV genotype B, but not with liver fibrosis.