Hepatitis E Virus in Domestic Ruminants and Virus Excretion in Milk-A Potential Source of Zoonotic HEV Infection.

The hepatitis E virus is a serious health concern worldwide, with 20 million cases each year. Growing numbers of autochthonous HEV infections in industrialized nations are brought on via the zoonotic transmission of HEV genotypes 3 and 4. Pigs and wild boars are the main animal reservoirs of HEV and play the primary role in HEV transmission. Consumption of raw or undercooked pork meat and close contact with infected animals are the most common causes of hepatitis E infection in industrialized countries. However, during the past few years, mounting data describing HEV distribution has led experts to believe that additional animals, particularly domestic ruminant species (cow, goat, sheep, deer, buffalo, and yak), may also play a role in the spreading of HEV. Up to now, there have not been enough studies focused on HEV infections associated with animal milk and the impact that they could have on the epidemiology of HEV. This critical analysis discusses the role of domestic ruminants in zoonotic HEV transmissions. More specifically, we focus on concerns related to milk safety, the role of mixed farming in cross-species HEV infections, and what potential consequences these may have on public health.

Genetic diversity, haplotype analysis, and prevalence of Hepatitis B virus MHR mutations among isolates from Kenyan blood donors.

BACKGROUND: The rapid spread of HBV has resulted in the emergence of new variants. These viral genotypes and variants, in addition to carcinogenic risk, can be key predictors of therapy response and outcomes. As a result, a better knowledge of these emerging HBV traits will aid in the development of a treatment for HBV infection. However, many Sub-Saharan African nations, including Kenya, have insufficient molecular data on HBV strains circulating locally. This study conducted a population-genetics analysis to evaluate the genetic diversity of HBV among Kenyan blood donors. In addition, within the same cohort, the incidence and features of immune-associated escape mutations and stop-codons in Hepatitis B surface antigen (HBsAg) were determined. METHODS: In September 2015 to October 2016, 194 serum samples were obtained from HBsAg-positive blood donors residing in eleven different Kenyan counties: Kisumu, Machakos, Uasin Gishu, Nairobi, Nakuru, Embu, Garissa, Kisii, Mombasa, Nyeri, and Turkana. For the HBV surface (S) gene, HBV DNA was isolated, amplified, and sequenced. The sequences obtained were utilized to investigate the genetic and haplotype diversity within the S genes. RESULTS: Among the blood donors, 74.74% were male, and the overall mean age was 25.36 years. HBV genotype A1 (88.14%) was the most common, followed by genotype D (10.82%), genotype C (0.52%), and HBV genotype E (0.52%). The phylogenetic analysis revealed twelve major clades, with cluster III comprising solely of 68 blood donor isolates (68/194-35.05%). A high haplotype diversity (Hd = 0.94) and low nucleotide diversity (π = 0.02) were observed. Kisumu county had high number of haplotypes (22), but low haplotype (gene) diversity (Hd = 0.90). Generally, a total of 90 haplotypes with some consisting of more than one sequence were observed. The gene exhibited negative values for Tajima's D (-2.04, p<0.05) and Fu's Fs (-88.84). Several mutations were found in 139 isolates, either within or outside the Major Hydrophilic Area (MHR). There were 29 mutations found, with 37.9% of them situated inside the "a" determinant. The most common mutations in this research were T143M and K122R. Escape mutations linked to diagnostic failure, vaccination and immunoglobulin treatment evasion were also discovered. Also, one stop-codon, W163STP, inside the MHR, was found in one sample from genotype A. CONCLUSION: In Kenya, HBV/A1 is still the most common genotype. Despite limited genetic and nucleotide diversity, haplotype network analysis revealed haplotype variance among HBV genotypes from Kenyan blood donors. The virological properties of immune escape, which may be the source of viral replication endurance, were discovered in the viral strains studied and included immune-escape mutations and stop-codon. The discovery of HBsAg mutations in MHR in all isolates highlighted the need of monitoring MHR mutations in Kenya.

The Re-Emergence of Hepatitis E Virus in Europe and Vaccine Development.

Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. Transmission of HEV mainly occurs via the fecal-oral route (ingesting contaminated water or food) or by contact with infected animals and their raw meat products. Some animals, such as pigs, wild boars, sheep, goats, rabbits, camels, rats, etc., are natural reservoirs of HEV, which places people in close contact with them at increased risk of HEV disease. Although hepatitis E is a self-limiting infection, it could also lead to severe illness, particularly among pregnant women, or chronic infection in immunocompromised people. A growing number of studies point out that HEV can be classified as a re-emerging virus in developed countries. Preventative efforts are needed to reduce the incidence of acute and chronic hepatitis E in non-endemic and endemic countries. There is a recombinant HEV vaccine, but it is approved for use and commercially available only in China and Pakistan. However, further studies are needed to demonstrate the necessity of applying a preventive vaccine and to create conditions for reducing the spread of HEV. This review emphasizes the hepatitis E virus and its importance for public health in Europe, the methods of virus transmission and treatment, and summarizes the latest studies on HEV vaccine development.

The Plant Viruses and Molecular Farming: How Beneficial They Might Be for Human and Animal Health?

Plant viruses have traditionally been studied as pathogens in the context of understanding the molecular and cellular mechanisms of a particular disease affecting crops. In recent years, viruses have emerged as a new alternative for producing biological nanomaterials and chimeric vaccines. Plant viruses were also used to generate highly efficient expression vectors, revolutionizing plant molecular farming (PMF). Several biological products, including recombinant vaccines, monoclonal antibodies, diagnostic reagents, and other pharmaceutical products produced in plants, have passed their clinical trials and are in their market implementation stage. PMF offers opportunities for fast, adaptive, and low-cost technology to meet ever-growing and critical global health needs. In this review, we summarized the advancements in the virus-like particles-based (VLPs-based) nanotechnologies and the role they played in the production of advanced vaccines, drugs, diagnostic bio-nanomaterials, and other bioactive cargos. We also highlighted various applications and advantages plant-produced vaccines have and their relevance for treating human and animal illnesses. Furthermore, we summarized the plant-based biologics that have passed through clinical trials, the unique challenges they faced, and the challenges they will face to qualify, become available, and succeed on the market.

Plant-Derived Recombinant Vaccines against Zoonotic Viruses.

Emerging and re-emerging zoonotic diseases cause serious illness with billions of cases, and millions of deaths. The most effective way to restrict the spread of zoonotic viruses among humans and animals and prevent disease is vaccination. Recombinant proteins produced in plants offer an alternative approach for the development of safe, effective, inexpensive candidate vaccines. Current strategies are focused on the production of highly immunogenic structural proteins, which mimic the organizations of the native virion but lack the viral genetic material. These include chimeric viral peptides, subunit virus proteins, and virus-like particles (VLPs). The latter, with their ability to self-assemble and thus resemble the form of virus particles, are gaining traction among plant-based candidate vaccines against many infectious diseases. In this review, we summarized the main zoonotic diseases and followed the progress in using plant expression systems for the production of recombinant proteins and VLPs used in the development of plant-based vaccines against zoonotic viruses.

An outbreak of hepatitis C virus attributed to the use of multi-dose vials at a colonoscopy clinic, Waterloo Region, Ontario.

BACKGROUND: Hepatitis C virus (HCV) transmission has been epidemiologically linked to healthcare settings, particularly out-of-hospital settings such as endoscopy clinics and hemodialysis clinics. These have been largely attributed to lapses in infection prevention and control practices (IPAC). OBJECTIVE: To describe the public health response to an outbreak of HCV that was detected among patients of a colonoscopy clinic in Ontario, and to highlight the risks of using multi-dose vials and the need for improved IPAC practices in out-of-hospital settings. METHODS: Screening for HCV was conducted on patients and staff who attended or worked at the clinic within the same timeframe as the index case's procedure. Blood samples from positive cases underwent viral sequencing. Inspections of the clinic assessed IPAC practices, and a chart review was done to identify plausible mechanisms for transmission. OUTCOME: A total of 38% of patients who underwent procedures at the clinic on the same day as the index case tested positive for HCV. Genetic sequencing showed a high degree of similarity in the HCV genetic sequence among the samples positive for HCV. Chart review and clinic inspection identified use of multi-dose vials of anesthesia medication across multiple patients as the plausible mechanism for transmission. CONCLUSION: Healthcare workers, especially those in out-of-hospital procedural/surgical premises, should be vigilant in following IPAC best practices, including those related to the use of multi-dose vials, to prevent the transmission of bloodborne infections in healthcare settings.

Characterization of occult hepatitis B in high-risk populations in Kenya.

Occult hepatitis B infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in the liver or serum in the absence of detectable HBV surface antigen (HBsAg). OBI poses a risk for the development of cirrhosis and hepatocellular carcinoma. The prevalence of OBI in Kenya is unknown, thus a study was undertaken to determine the prevalence and molecular characterization of OBI in Kenyan populations at high risk of HBV infection. Sera from two Nairobi cohorts, 99 male sex workers, primarily having sex with men (MSM-SW), and 13 non-MSM men having HIV-positive partners, as well as 65 HBsAg-negative patients presenting with jaundice at Kenyan medical facilities, were tested for HBV serological markers, including HBV DNA by real-time PCR. Positive DNA samples were sequenced and MSM-SW patients were further tested for hepatitis C virus (HCV) infection. Of the 166 HBsAg-negative samples tested, 31 (18.7%; 95% confidence interval [CI] 13.5-25.3) were HBV DNA positive (i.e., occult), the majority (20/31; 64.5%) of which were HBV core protein antibody positive. HCV infection was not observed in the MSM-SW participants, although the prevalence of HBsAg positivity was 10.1% (10/99; 95% CI 5.6-17.6). HBV genotype A was predominant among study cases, including both HBsAg-positive and OBI participants, although the data suggests a non-African network transmission source among MSM-SW. The high prevalence of HBV infection among MSM-SW in Kenya suggests that screening programmes be instituted among high-risk cohorts to facilitate preventative measures, such as vaccination, and establish entry to treatment and linkage to care.

Rat Hepatitis E Virus Linked to Severe Acute Hepatitis in an Immunocompetent Patient.

Hepatitis E virus (HEV) is a major public health concern in developing countries where the primary transmission is via contaminated water. Zoonotic HEV cases have been increasingly described in Europe, Japan, and the United States, with pigs representing the main animal reservoir of infection. We report an unusual acute hepatitis infection in a previously healthy man caused by a rat HEV with a considerably divergent genomic sequence compared with other rat HEV strains. It is possible that rat HEV is an underrecognized cause of hepatitis infection, and further studies are necessary to elucidate its potential risk and mode of transmission.

Hepatitis E in Canadian blood donors.

BACKGROUND: Hepatitis E virus (HEV) is a virus of emerging importance to transfusion medicine as studies on blood donors and other populations demonstrate that the prevalence of endemic cases is higher than previously recognized and the risk to vulnerable transfusion recipients is not insignificant. STUDY DESIGN AND METHODS: We carried out an HEV prevalence study on 13,993 Canadian blood donors with polymerase chain reaction (PCR) testing on all donors and antibody testing on a subset of 4102 donors. HEV antibody-positive and age- and sex-matched antibody-negative donors were invited to participate in a scripted telephone interview about risk factors. RESULTS: There were no PCR-positive samples found (95% confidence interval [CI], 0%-0.026%). The seroprevalence of HEV in our tested population was 5.9% (95% CI, 5.16%-6.59%). HEV antibody positivity was associated with male sex and increasing age. In case-control analysis history of living outside Canada (odds ratio [OR], 2.9; 95% CI, 1.56-5.32) and contact with farm animals (OR, 1.5; 95% CI, 1.01-2.28) were associated with HEV seropositivity. CONCLUSION: This is the largest data set to date on HEV infection in Canada. Results suggest low lifetime exposure to HEV and that infectious donations are rare.

Transmission of hepatitis D virus between spouses: A longitudinal study of the first reported Canadian case.

In chronic hepatitis B (CHB), hepatitis D virus (HDV) superinfection can lead to acute liver failure. The incidence of HDV superinfection is unknown, but is often detected in immigrants from HDV endemic countries. In this report, we characterize long-term clinical and virological outcomes in a hepatitis B virus (HBV) infected carrier before and after HDV superinfection, acquired from their spouse having HBV/HDV co-infection. A 38 year-old Mongolian male with CHB on anti-HBV therapy developed acute liver failure following HDV superinfection. Although he recovered, avoiding the need for liver transplant, HDV serological and molecular markers of infection persisted for the subsequent 16-month follow-up period, suggesting the development of CHB/HDV co-infection. The source of his HDV was from his wife of 10 years, a 34-year old Mongolian female known to have inactive CHB/HDV co-infection but who was not on anti-HBV therapy. Phylogenetic analysis of the complete HDV genome from the couple showed >99% similarity, with post-transmission longitudinal sequence revealing specific nucleotide substitutions between both spouse's HDV genome sequences. This study highlights the ongoing risk of HDV superinfection due to long-term co-habitation or sexual transmission in CHB patients. The fact that transmission occurred after almost a decade of marriage may be due to host immune or environmental factors that created a more favorable condition for transmission.

Review of Laboratory Tests used in Monitoring Hepatitis B Response to Pegylated Interferon and Nucleos(t)ide Analog Therapy.

There are only two currently approved classes of hepatitis B virus (HBV) antiviral agents, pegylated interferon (Peg-IFN), and nucleos(t)ide analogs (NAs) for chronic HBV infection. Although Peg-IFN is used for a finite 48-week duration and offers a greater chance of sustained off-treatment virological response, it is poorly tolerated and can only be offered to selected patients. The NAs are well tolerated but require prolonged therapy due to risk of relapse with treatment cessation. There is evolving data that novel virological assays (e.g., quantitative hepatitis B surface antigen, quantitative hepatitis B core antigen, quantitative antibody to core protein) in combination with hepatitis B genotype and more sensitive HBV DNA polymerase chain reaction (PCR) assays may be useful to predict response to IFN as well as off-treatment NA durability. Utilization of these clinical laboratory tests may be important given the development of novel anti-HBV therapies, hoping to achieve a cure for chronic hepatitis B infection.

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.

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

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

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.

Hepatitis B and hepatitis C viral infections in patients with chronic lymphocytic leukemia.

BACKGROUND: Whether chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections contribute to the pathogenesis and/or course of chronic lymphocytic leukemia is unclear. OBJECTIVE: To document the prevalences of HBV and HCV infections in chronic lymphocytic leukemia patients, and to determine whether infected patients experience more aggressive disease than those without infection. METHODS: Patient sera were screened for antibodies to HBV core antigen and HCV (anti-HCV) using ELISA; both sera and peripheral blood lymphocytes were further tested (regardless of antibody results) for HBV-DNA and HCV-RNA using real-time polymerase chain reaction. Prognostic markers for chronic lymphocytic leukemia included Rai stage, IgVH mutational status, ß2-microglobulin levels, Zap-70 and CD38 status. RESULTS: Fourteen of 222 (6.3%) chronic lymphocytic leukemia patients and two of 72 (2.8%) healthy controls tested positive for previous or ongoing HBV infection (OR 2.4 [95% CI 0.5 to 7.7]; P=0.25) while four of 222 (1.8%) chronic lymphocytic leukemia patients and one of 72 (1.4%) controls tested positive for HCV markers (OR 1.3 [95% CI 0.2 to 6.4]; P=0.81). The levels and distribution of the various indicators of aggressive chronic lymphocytic leukemia disease were similar among HBV- and HCV-infected and uninfected patients. Survival times were also similar. Occult HBV and HCV infection (HBV-DNA or HCV-RNA positive in the absence of diagnostic serological markers) were uncommon in chronic lymphocytic leukemia patients (0.5% and 1.8%, respectively). CONCLUSIONS: The results of the present study do not support the hypothesis that HBV or HCV infections play an important role in the pathogenesis or course of chronic lymphocytic leukemia.

Hepatitis C virus late relapse after sustained virologic response from interferon and ribavirin treatment as confirmed by RNA sequencing.

Hepatitis C virus (HCV) viremia is unusual (<5%) after successful treatment, defined as sustained virologic response (SVR) or undetectable HCV PCR 12 to 24 weeks after therapy. We present a case of late virologic relapse (de novo infection was excluded by RNA sequencing) after SVR followed by spontaneous viral clearance.

Seroprevalence of hepatitis B and C virus infections: Results from the 2007 to 2009 and 2009 to 2011 Canadian Health Measures Survey.

BACKGROUND: Chronic hepatitis B (HBV) and C (HCV) virus infections can lead to liver failure, liver cancer, and death. In Canada, prevalence studies of HBV and HCV have been limited to regional and special populations. DATA AND METHODS: Data are from cycles 1 (2007 to 2009) and 2 (2009 to 2011) of the Canadian Health Measures. Socio-demographic, health and lifestyle information was obtained via a household questionnaire; blood samples collected at mobile examination centres were used to identify present and resolved HBV infections, vaccine-induced HBV immunity, and HCV infections. RESULTS: The seroprevalence of present HBV infection among the population aged 14 to 79 was 0.4%, representing an estimated 111,800 individuals. Another 4.2% had evidence of a previous HBV infection. Nearly 30% had vaccine-induced HBV immunity. The seroprevalence of HCV infection was 0.5%, representing an estimated 138,600. More than half of people with laboratory-confirmed HBV and 70% with laboratory-confirmed HCV were unaware of their infections. INTERPRETATION: This is the first Canadian study to report laboratory-confirmed seroprevalence of HBV and HCV infections based on a nationally representative household sample. Substantial percentages of younger Canadians have vaccine-induced HBV immunity.

Pretreatment resistance to hepatitis C virus protease inhibitors boceprevir/telaprevir in hepatitis C virus subgenotype 1a-infected patients from Manitoba.

BACKGROUND: Traditional therapy with pegylated interferon and ribavirin combined with the new protease inhibitors boceprevir or telaprevir has demonstrated improved outcomes in hepatitis C virus (HCV)-infected patients. Prevalence data regarding pre-existing drug-resistant variants to these two new virus inhibitors in the Canadian population are not available. OBJECTIVE: To detect pre-existing mutations conferring resistance to boceprevir and/or telaprevir in Canadian patients infected with HCV genotype 1a. METHODS: Resistance-associated mutations (RAMs) were evaluated in 85 patients infected with HCV genotype 1a who had not yet received antiviral therapy. The NS3 protease gene was sequenced and common RAMs were identified based on a recently published list. RESULTS: The overall prevalence of pre-existing RAMs to boceprevir and telaprevir was higher compared with other similar studies. All of the observed RAMs were associated with a low level of resistance. A surprisingly high proportion of patients had the V55A RAM (10.6%). None of the mutations associated with a high level of resistance were observed. The simultaneous presence of two low-level resistance mutations (V36L and V55A) was observed in only one patient. Three other patients had both T54S RAM and V55I mutations, which may require a higher concentration of the protease drugs. The prevalence of various mutations in Aboriginal Canadian patients was higher (37.5%) compared with Caucasians (16.39%) (P=0.038). CONCLUSIONS: The present study was the first to investigate pre-existing drug resistance to boceprevir/telaprevir in Canadian HCV-infected patients. A relatively high proportion of untreated HCV genotype 1a patients in Manitoba harbour low-level RAMs, especially patients of Aboriginal descent, which may contribute to an increased risk of treatment failure.