Retrospective study of the prevalence and clinical significance of hepatitis B virus precore and basal core promoter variants.

BACKGROUND: Hepatitis B virus (HBV) precore (PC) and basal core promoter (BCP) variants are well known; however, their prevalence in North America is unclear, especially among hepatitis B e antigen-negative patients. OBJECTIVE: To investigate the prevalence of PC/BCP mutations and their clinical significance. METHODS: One hundred twenty-eight patients positive for both hepatitis B surface antigen and hepatitis B e antibody were selected, and PC/BCP mutations were identified using a line probe assay. The subjects' charts were reviewed for race/ethnicity, HBV genotype, HBV viral load, sex, liver enzyme levels, imaging and biopsy results up to 10 years before the study. RESULTS: The prevalence of PC and BCP variants were 47.6% and 62.5%, respectively. Older age was associated with aspartate aminotransferase-to-platelet index ratio (APRI) ≥0.7 (P=0.011) and abnormal imaging/biopsy results (P=0.0008). Although the presence of BCP variant(s) was associated with APRI ≥0.7 (P=0.029), it was not associated with abnormal imaging/biopsy results. The combination of age ≥50 years and the presence of BCP variant(s) was associated with abnormal imaging/biopsy results, suggestive of either cirrhosis or hepatocellular carcinoma (not observed with PC mutation). Neither sex or genotype, or median HBV viral load showed significant influence on any of these outcomes. CONCLUSIONS: The present study suggests that the prevalence of PC and BCP mutations are higher than what has been previously reported. One potential explanation would be increased immigration in the past decade. Considering the potential public health and clinical implications of these variants, long-term multicentre and prospective studies could further unravel the uncertainty around these variants.

Seroprevalence of human T-cell lymphotropic viruses types 1 and 2 antibodies in hepatitis C virus-positive patients: manitoba, Canada, 2012-2014.

Human T-cell lymphotropic viruses types 1 and 2 are probably among the most neglected blood-borne pathogens that have experienced significant changes in their epidemiology since discovery, which could be attributed to globalization and intravenous drug use practices as well as enhanced screening recommendations; however, systematic prevalence studies, especially in high-risk populations in North America, are not updated.

HCV antigen testing for the diagnosis of hepatitis C infection: a cost-efficient algorithm.

BACKGROUND: In North America, diagnosis of active hepatitis C virus (HCV) infection is currently performed using RNA testing which is highly sensitive and specific but is associated with three major limitations: lability of RNA molecules, higher costs, and longer turn-around time as compared with commercially-available HCV core antigen testing. In the current study, a new HCV core antigen assay product was evaluated for the diagnosis of HCV infection and its cost reducing potential. METHODS: Ninety plasma specimens positive for HCV RNA along with 25 negative HCV specimens were used for HCV antigen assay. Twenty-four specimens positive for a panel of agents were used for possible cross-reactivity. Sixty-four HCV antibody-positive specimens with negative HCV RNA and indeterminate HCV immunoblot results were also employed. RESULTS: In the first group, 78/90 (86.6%) tested positive for HCV antigen with regression analysis showing no significant deviation from linearity. None of the prenatal specimens tested positive for HCV antigen. Non-specific reactions were not observed. In the HCV antibody-indeterminate group, only 2/64 (3.1%) were antigen positive. In the last group, none of the HCV antibody very-low-positive specimens tested positive for HCV antigen. Both inter- and intra-run reproducibility of 100% were noted. The cost analysis showed a minimum of 52.13% reduction in costs associated with qualitative RNA testing. CONCLUSIONS: Considering the complexity of HCV infection diagnosis and the significant cost and turn-around time burden it imposes on clinical laboratories, HCV antigen testing seems an attractive adjunct to the current battery of laboratory diagnosis that demands more attention.

Novel microsphere-based method for detection and typing of 46 mucosal human papillomavirus types.

We have developed a novel microsphere-based genotyping method for 46 mucosal human papillomavirus (HPV) types. HPV DNA was amplified by PCR using general primers and typed by hybridization to HPV type-specific probes coupled to sortable microspheres based on the Luminex xMAP technology. Hybridization to each probe was specific for each HPV type without cross-hybridization and sensitive enough to allow typing of HPV contained in clinical specimens. The method was validated with direct sequencing and the Roche Linear Array genotyping method.

Hepatitis C virus infection among First Nation and non-First Nation people in Manitoba, Canada: a public health laboratory study.

Demographic information and laboratory test results on 136 169 clinical serum specimens submitted to the public health laboratory in Manitoba, Canada, for hepatitis C virus (HCV) testing between January 1995 and December 2003 were analyzed. The difference in the clearance rates of HCV infection, without therapeutic intervention, and the HCV genotypes infecting First Nation and non-First Nation people were studied. The rates of co-infection of HCV-positive individuals with other hepatitis viruses were also compared between the two study groups. The results of the analyses of the data indicated that there was a 4.4-fold increase in the number of specimens tested and a 4.9-fold decrease in HCV antibody (anti-HCV) positive cases during the study period. The proportion of specimens submitted for testing from First Nation individuals was lower than their proportion in the Manitoba population. Our study also indicated that there was a significantly higher proportion of First Nation patients who had self-limiting infection (patients cleared the infection and became HCV RNA negative without anti-HCV treatment) in comparison to non-First Nation patients. The proportion of First Nation females who had self-limiting infection was significantly higher than non-First Nation females. HCV genotype 1 infection represented more than 60% of HCV infection in Manitoba. The rate of individuals positive for the hepatitis A virus antibody in the HCV-positive population was higher among First Nation than non-First Nation individuals. On the other hand, there were more HCV-infected First Nation patients than non-First Nation patients who were not immune to the hepatitis B virus. The data indicate that fewer First Nation patients seek anti-HCV therapy in comparison to non-First Nation. In conclusion, the differences in the rates of HCV self-limiting infection between First Nation and non-First Nation individuals in Manitoba may reflect the genetic differences between the two cohorts, which may consequently affect the immune response to the HCV infection.

Parvovirus B19 associated adult Henoch Schönlein purpura.

BACKGROUND: Parvovirus B19 has recently been implicated in various vasculitic syndromes including Henoch Schönlein purpura (HSP), Wegener's granulomatosis and microscopic polyarteritis. The association was established through serology, the identification of DNA in the peripheral blood and affected tissues and more recently by RNA localization to cutaneous capillary endothelium. However, direct localization of the viral DNA to the glomerular and cutaneous endothelium in HSP in correlation with the histopathologic findings has not been demonstrated. METHODS: Skin and kidney biopsy tissues were processed for hematoxylin and eosin, immunofluorescent, polymerase chain reaction (PCR) and reverse transcriptase in situ PCR studies. CASE PRESENTATION: A 64-year-old-female presented with palpable purpura and nephrotic range proteinuria. Kidney and skin biopsies showed IgA-associated mesangioproliferative glomerulonephritis and IgA-associated leukocytoclastic vasculitis, respectively. A diagnosis of HSP was rendered. Her clinical course was refractory to prednisone. Parvovirus B19 DNA and tumor necrosis factor alpha DNA were identified in the dermal and glomerular capillary endothelial cells and surrounding dermal inflammatory cells. CONCLUSION: This is the first documentation of B19 localization to dermal and glomerular capillary endothelium in HSP. It is important to recognize parvovirus B19-associated adult HSP cases, as the treatment of choice is intravenous gamma globulin in concert with anti-TNFalpha therapy. In contrast immunosuppressive therapy may lead to a persistent and/or worsening disease course.