Hepatitis: Canada

Shaheen AA, Myers RP. · Liver Unit, Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada. · HIV Clin Trials. · Pubmed #18215981 No free full text.

Abstract: BACKGROUND: Accurately staging hepatitis C virus (HCV)-related fibrosis is crucial for treatment decisions and prognostication. Our objective was to systematically review studies describing the accuracy of serum marker panels for predicting fibrosis in HIV/HCV-coinfected patients. METHOD: Studies comparing serum marker panels with biopsy in HIV/HCV-coinfected patients were identified. Random effects meta-analyses and areas under summary receiver operating characteristics curves (AUC) examined test accuracy for detecting significant fibrosis (F2-4) and cirrhosis. Heterogeneity was explored using meta-regression. RESULTS: Five studies (n = 574) including four fibrosis measures (APRI [n = 4 studies], Forns' [n = 2], FibroTest [n = 1], SHASTA [n = 1]) met the inclusion criteria. The prevalence of significant fibrosis and cirrhosis were 51% and 16%, respectively. For the prediction of significant fibrosis, the summary AUC was 0.82 (95% CI 0.78-86) and diagnostic odds ratio was 7.8 (5.1-11.9). For cirrhosis, these figures were 0.83 (0.69-0.97) and 11.0 (4.6-26.2), respectively. Meta-regression including study factors (methodological quality and biopsy adequacy), patient characteristics (age, gender, CD4 count), and fibrosis measure failed to identify important predictors of accuracy. CONCLUSION: Available fibrosis marker panels have acceptable performance for identifying significant fibrosis and cirrhosis in HIV/HCV-coinfected patients but are not yet adequate to replace liver biopsy. Additional studies are necessary to identify the optimal measure.

Haines T, Stringer B. · Occupational and Environmental Medicine Program, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences at McMaster University, Hamilton, ON. · Can Oper Room Nurs J. · Pubmed #18193724 No free full text.

Abstract: In 1991, Bernadette Stringer, a long time BC Nurses' Union health and safety representative, learned about the death of a 48 year old Victoria, B.C., OR nurse who had sustained a hepatitis C contaminated needlestick. This incident led to a study evaluating the hands-free technique's ability to decrease the risk of percutaneous injury, glove tear and mucocutaneous contamination during surgery that Ms. Stringer carried out in partial fulfillment of her Ph.D. (granted in 1998, by McGill University's Joint Departments of Epidemiology, Biostatistics and Occupational Health, in the Faculty of Medicine). That study's main findings were published in 2002 in one of the British Medical Journal's publications, Occupational and Environmental Medicine. The following article will discuss aspects of Bev Holmwood's case, review the literature on the hands-free technique, and describe a new study that has again evaluated the hands-free technique's effectiveness.

Anonychuk AM, Tricco AC, Bauch CT, Pham B, Gilca V, Duval B, John-Baptiste A, Woo G, Krahn M. · Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada. · Pharmacoeconomics. · Pubmed #18088156 No free full text.

Abstract: Hepatitis A vaccines have been available for more than a decade. Because the burden of hepatitis A virus has fallen in developed countries, the appropriate role of vaccination programmes, especially universal vaccination strategies, remains unclear. Cost-effectiveness analysis is a useful method of relating the costs of vaccination to its benefits, and may inform policy. This article systematically reviews the evidence on the cost effectiveness of hepatitis A vaccination in varying populations, and explores the effects of methodological quality and key modelling issues on the cost-effectiveness ratios.Cost-effectiveness/cost-utility studies of hepatitis A vaccine were identified via a series of literature searches (MEDLINE, EMBASE, HSTAR and SSCI). Citations and full-text articles were reviewed independently by two reviewers. Reference searching, author searches and expert consultation ensured literature saturation. Incremental cost-effectiveness ratios (ICERs) were abstracted for base-case analyses, converted to $US, year 2005 values, and categorised to reflect various levels of cost effectiveness. Quality of reporting, methodological issues and key modelling issues were assessed using frameworks published in the literature.Thirty-one cost-effectiveness studies (including 12 cost-utility analyses) were included from full-text article review (n = 58) and citation screening (n = 570). These studies evaluated universal mass vaccination (n = 14), targeted vaccination (n = 17) and vaccination of susceptibles (i.e. individuals initially screened for antibody and, if susceptible, vaccinated) [n = 13]. For universal vaccination, 50% of the ICERs were <$US20 000 per QALY or life-year gained. Analyses evaluating vaccination in children, particularly in high incidence areas, produced the most attractive ICERs. For targeted vaccination, cost effectiveness was highly dependent on the risk of infection.Incidence, vaccine cost and discount rate were the most influential parameters in sensitivity analyses. Overall, analyses that evaluated the combined hepatitis A/hepatitis B vaccine, adjusted incidence for under-reporting, included societal costs and that came from studies of higher methodological quality tended to have more attractive cost-effectiveness ratios. Methodological quality varied across studies. Major methodological flaws included inappropriate model type, comparator, incidence estimate and inclusion/exclusion of costs.

Webert KE, Cserti CM, Hannon J, Lin Y, Pavenski K, Pendergrast JM, Blajchman MA. · Medical, Scientific, and Research Affairs, Canadian Blood Services, Hamilton, Edmonton and Toronto, Canada. · Transfus Med Rev. · Pubmed #18063190 No free full text.

Abstract: Significant progress has been made in reducing the risk of pathogen transmission to transfusion recipients. Nonetheless, there remains a continuing risk of transmission of viruses, bacteria, protozoa, and prions to recipients. These include many of the viruses for which specific screening tests exist as well as pathogens for which testing is currently not being done, including various species of bacteria, babesiosis, variant Creutzfeld-Jacob disease, hepatitis A virus, human herpes virus 8, chikungunya virus, Chagas disease, and malaria. Pathogen inactivation (PI) technologies potentially provide an additional way to protect the blood supply from emerging agents and also provide additional protection against both known and as-yet-unidentified agents. However, the impact of PI on product quality and recipient safety remains to be determined. The purpose of this consensus conference was to bring together international experts in an effort to consider the following issues with respect to PI: implementation criteria; licensing requirements; blood service and clinical issues; risk management issues; cost-benefit impact; and research requirements. These proceedings are provided to make available to the transfusion medicine community the considerable amount of important information presented at this consensus conference.

Ayeni OA, Ayeni OO, Jackson R. · Department of Plastic Surgery, McMaster Medical Centre, Hamilton, ON, Canada. · J Cutan Med Surg. · Pubmed #18042335 No free full text.

Abstract: BACKGROUND: Scarification involves cutting or making an incision into the skin and then allowing the wound to heal, leaving a permanent scar. The purpose of this article is to examine the origins of scarification and its social and medical significance in sub-Saharan Africa. METHODS: We conducted a computerized search in the MEDLINE electronic database with combinations of the following terms: scarification, tribal marks, keloid, hypertrophic scar, Africa, and sub-Saharan Africa. Inclusion criteria were studies published in English involving human participants. We reviewed the bibliography of each article that met our inclusion criteria for additional relevant studies. We abstracted data on the historical, social, and medical aspects of scarification from eligible studies. RESULTS: This review of scarification in sub-Saharan Africa highlights the complex interplay that exists between biology and society. Photographs, artwork, and literary descriptions reveal that scarification results in hypertrophic or atrophic scars, although these types of scars are often mistakenly referred to as keloids. In terms of the procedural aspects of scarification, specific tools and substances were consistently used by various ethnic groups. Although much is known about the history of scarification as a form of identification in Africa, it appears that the practice also had medical applications. Scarification was used to treat conditions such as epilepsy, although it was also known to exacerbate conditions such as sarcoidosis, lichen planus, and psoriasis. Evolving cultural beliefs, in addition to the association of scarification with an increased risk of contracting hepatitis B and human immunodeficiency virus (HIV), are contemporary threats to this long-standing practice. CONCLUSIONS: Given the remarkably consistent appearance of scars that are described in the literature and depicted in images, scarification does not appear to be a random or accidental occurrence. Instead, it is a deliberate attempt to reproduce a custom that has been perfected after many years of practice in sub-Saharan Africa.

Cooper CL. · University of Ottawa Hospital, Division of Infectious Diseases-The Ottawa Hospital, The Ottawa Hospital-General Campus, Room G12, 501 Smyth Road, Ottawa, ON, Canada, K1H 8L6. · Dig Dis Sci. · Pubmed #18041585 No free full text.

Abstract: Combination antiretroviral therapy often controls HIV disease, may indirectly slow HCV progression, and creates an immune environment which may optimize HCV drug therapy response. Monitoring for antiretroviral-related liver adverse events is vital. However, this complication infrequently causes clinically significant liver toxicity. HCV antiviral therapy should, in most cases, be reserved for those abstaining from alcohol and achieving HIV RNA suppression and immune restoration on combination antiretroviral therapy or for those with nadir CD4 counts above 350 cells/mul. Given the high prevalence of HBV and HCV co-infection, chronic viral hepatitis will influence the health and treatment of HIV-infected individuals for the foreseeable future.

Neuman MG, Sha K, Esguerra R, Zakhari S, Winkler RE, Hilzenrat N, Wyse J, Cooper CL, Seth D, Gorrell MD, Haber PS, McCaughan GW, Leo MA, Lieber CS, Voiculescu M, Buzatu E, Ionescu C, Dudas J, Saile B, Ramadori G. · In Vitro Drug Safety and Biotechnology, Department of Pharmacology, Biophysics and Global Health, Institute of Drug Research, University of Toronto, Toronto, ON, Canada. · Dig Dis Sci. · Pubmed #17994278 No free full text.

Abstract: Hepatitis C viral infection (HCV) results in liver damage leading to inflammation and fibrosis of the liver and increasing rates of hepatic decompensation and hepatocellular carcinoma (HCC). However, the host's immune response and viral determinants of liver disease progression are poorly understood. This review will address the determinants of liver injury in chronic HCV infection and the risk factors leading to rapid disease progression. We aim to better understand the factors that distinguish a relatively benign course of HCV from one with progression to cirrhosis. We will accomplish this task by discussion of three topics: (1) the role of cytokines in the adaptive immune response against the HCV infection; (2) the progression of fibrosis; and (3) the risk factors of co-morbidity with alcohol and human immunodeficiency virus (HIV) in HCV-infected individuals. Despite recent improvements in treating HCV infection using pegylated interferon alpha (PEGIFN-alpha) and ribavirin, about half of individuals infected with some genotypes, for example genotypes 1 and 4, will not respond to treatment or cannot be treated because of contraindications. This review will also aim to describe the importance of IFN-alpha-based therapies in HCV infection, ways of monitoring them, and associated complications.

Heathcote EJ. · University of Toronto, Ontario, Canada. · Clin Med. · Pubmed #17990715 No free full text.

Abstract: The natural history of individuals chronically infected with hepatitis B typically fluctuates, with periods of active viral replication with or without an associated hepatitis and sometimes prolonged periods of spontaneous viral suppression and inactive liver disease. In the majority, this chronic infection is clinically silent unless either liver failure and/or hepatocellular carcinoma (HCC) supervenes. Thus proactive steps are needed to first identify those with hepatitis B infection and to then serially monitor those found to be chronically infected for both level of alanine aminotransferase (ALT) and hepatitis B virus DNA (HBV-DNA) (using sensitive polymerase chain reaction techniques. Antiviral therapy significantly reduces the risk of liver disease progression and HCC in those with ongoing viral replication > 10(5) c/mL and advanced hepatic fibrosis. The decision of when to initiate (possibly lifelong) treatment has to be made judiciously. Before introducing therapy both patient and physician must recognise the need for compliance with both treatment and viral surveillance so as to minimise the development of drug resistance. Drug resistance needs to be identified prior to recurrence of hepatitis (rise in ALT) to prevent hepatic decompensation, this necessitates serial HBV-DNA testing.

Sherman M. · Department of Medicine, University of Toronto, Toronto, Ontario, Canada. · Clin Liver Dis. · Pubmed #17981230 No free full text.

Abstract: Good management of patients at risk for the development of hepatocellular carcinoma includes regular ultrasound surveillance, and aggressive management of lesions detected at ultrasound. Good radiology and good pathology are essential to the appropriate management of these small lesions. With good quality testing it is possible to cure the majority of HCCs using minimally invasive techniques such as radiofrequency ablation. Such an approach has the potential to convert HCC from a disease in which incidence more or less equaled mortality to one in which cure is frequently possible.

Sockalingam S, Shammi C, Stergiopoulos V. · Department of Psychiatry, Centre for Addiction and Mental Health, Toronto, ON. · Br J Hosp Med (Lond). · Pubmed #17974293 No free full text.

Abstract: Interferon-alpha is the mainstay of hepatitis C treatment and has been linked to several neuropsychiatric complications, including depression, anxiety, mania, psychosis and cognitive changes. This article reviews the management of neuropsychiatric adverse effects and the risks of interferon-alpha treatment to psychiatric patients.

Barry M, Cooper C. · University of Ottawa, The Ottawa Hospital, Division of Infectious Diseases, Room G12-501 Smyth Road, Ottawa, K1H 8L6, ON, Canada. · Expert Opin Biol Ther. · Pubmed #17961095 No free full text.

Abstract: Existing hepatitis B virus (HBV) vaccines produce seroprotective titers in > 90% of healthy adult recipients following 3 doses administered over 6 months. The durability of this response is variable. Vaccine efficacy is greatly diminished in immune compromised patients. Given the high worldwide prevalence and burden of disease produced by chronic HBV infection, vaccines capable of producing high rates of durable seroprotective HBV surface antibody titers are required. Immunostimulatory sequences (ISS) containing repeating sequences of cytosine phosphoguanosine (CpG) dinucleotide motifs have emerged as useful tools for modulating immune responses. Dynavax Technologies produced a synthetic oligodexynucleotide (ODN) containing these motifs, resulting in an unmethylated cytosine and phosphoguanosine ODN called 1018 ISS. Dynavax's hepatitis B virus vaccine HEPLISAV is comprised of 1018 ISS mixed with recombinant hepatitis B surface antigen. Clinical trials, to date, have shown that HEPLISAV produces rapid, high titer, sustained seroprotection in healthy adults and vaccine hyporesponsive populations. Although additional supporting data are required, this represents a promising strategy to facilitate worldwide HBV prevention efforts.

Heathcote EJ. · University of Toronto, Toronto, ON, Canada. · J Viral Hepat. · Pubmed #17958648 No free full text.

Abstract: The combination of pegylated interferon (IFN) with ribavirin is the standard of care for chronic hepatitis C. Response rates range from 50 to 90% for genotype 1 and 2/3 which also differ in the duration of treatment (48 vs 24 weeks, respectively). Therapy if given with weight-based dosing may be shortened from 24 to 12, 14 or 16 weeks (genotypes 2 and 3), and from 48 to 24 weeks (genotype 1) in case of hepatitis C virus (HCV) clearance at week 4, without reducing sustained virologic response (SVR). Conversely, prolonging treatment for 72 weeks in those with only a decrease of viral load at week 4, i.e. "slow responders" increases SVR rates by preventing relapse. In spite of such progress, over half of patients are relapsers or nonresponders. If the previous treatment was suboptimal, retreatment with higher doses or longer duration may be beneficial unless an individual was a 'null responder' previously. New promising anti-HCV molecules (antiproteases and antipolymerases), some with potent antiviral activity, are in phase II trials but appear to require the addition of IFN and ribavirin to maintain viral suppression. Other immunomodulatory agents such as new IFN or therapeutic vaccines and alternatives to ribavirin are also under development. Future regimens should improve efficacy and provide shorter and better-tolerated combination therapy.

Chen W, Liu J, Gluud C. · Toronto Western Hospital, University Health Network, University of Toronto, Liver Clinic, Room 181, 6B Fell Pav, 399 Bathurst St, Toronto, Ontario, Canada, M5T 2S8. · Cochrane Database Syst Rev. · Pubmed #17943781 No free full text.

Abstract: BACKGROUND: Trials have assessed bile acids for patients with viral hepatitis, but no consensus has been reached regarding their usefulness. OBJECTIVES: To assess the beneficial and harmful effects of bile acids for viral hepatitis. SEARCH STRATEGY: Searches were performed in The Cochrane Hepato-Biliary Group Controlled Trials Register (July 2007), The Cochrane Library (Issue 1, 2007), MEDLINE (July 2007), EMBASE (July 2007), Science Citation Index Expanded (July 2007), and Chinese Biomedical Database (July 2007). SELECTION CRITERIA: Randomised clinical trials comparing any dose or duration of bile acids versus placebo or no intervention for viral hepatitis were included, irrespective of language, publication status, or blinding. Co-interventions were allowed in the included randomised clinical trials. DATA COLLECTION AND ANALYSIS: Two authors extracted the data independently. The methodological quality of the trials was evaluated with respect to generation of the allocation sequence, allocation concealment, double blinding, and follow-up. The outcomes were presented as relative risks (RR) or weighted mean differences (WMD) with 95% confidence intervals (CI). MAIN RESULTS: We identified 29 randomised trials of bile acids for hepatitis B or C; none were of high methodological quality. We were unable to extract data from two trials. In one trial, ursodeoxycholic acid (UDCA) versus placebo for acute hepatitis B significantly reduced the risk of hepatitis B surface antigen positivity at the end of treatment and serum HBV DNA level at the end of follow-up. In another trial, UDCA versus no intervention for chronic hepatitis B significantly reduced the risk of having abnormal serum transaminase activities at the end of treatment. Twenty-five trials compared bile acids (21 trials UDCA; four trials tauro-UDCA) versus placebo or no intervention with or without co-interventions for chronic hepatitis C. Bile acids did not significantly reduce the risk of having detectable serum HCV RNA (RR 0.99, 95% CI 0.91 to 1.07), cirrhosis, or portal and periportal inflammation score at the end of treatment. Bile acids significantly decreased the risk of having abnormal serum alanine aminotransferase activity at the end of treatment (RR 0.82, 95% CI 0.76 to 0.90) and follow-up (RR 0.91, 95% CI 0.85 to 0.98). Bile acids significantly increased the Knodell score (WMD 0.20, 95% CI 0.08 to 0.31) at the end of treatment. No severe adverse events were reported. We did not identify trials including patients with hepatitis A, acute hepatitis C, hepatitis D, or hepatitis E. AUTHORS' CONCLUSIONS: Bile acids lead to a significant improvement in serum transaminase activities in hepatitis B and C but have no effects on the clearance of virus. There is insufficient evidence either to support or to refute effects on long-term outcomes including hepatocellular carcinoma, hepatic decompensation, and liver related mortality. Randomised trials with high methodological quality are required before clinical use is considered.

Steben M, Duarte-Franco E. · Direction Risques Biologiques, Environnementaux et Occupationnels, Institut National de Santé Publique du Québec, 190, boulevard Crémazie Est, Montréal, Québec, Canada H2P 1E2. · Gynecol Oncol. · Pubmed #17938014 No free full text.

Abstract: More than 120 different types of the human papillomavirus (HPV) have been isolated; >40 of these types infect the epithelial lining of the anogenital tract and other mucosal areas. In the majority of individuals, HPV infections are transient and asymptomatic with most new infections resolving within 2 years. Epidemiological data from the U.S. National Health and Nutrition Examination Survey determined that the prevalence of HPV infection in a representative sample of women was highest in those aged 20-24 years (44.8%). HPV infection has been firmly established as the primary cause of cervical cancer. It is not clearly understood why HPV infections resolve in certain individuals and result in cervical intraepithelial neoplasias in others, but several factors are thought to play a role; including individual susceptibility, immune status and nutrition, endogenous and exogenous hormones, tobacco smoking, parity, co-infection with other sexually transmitted agents such as HIV, herpes simplex virus type 2 and Chlamydia trachomatis as well as viral characteristics such as HPV type, concomitant infection with other types, viral load, HPV variant and viral integration. Worldwide, pooled data from case-control studies indicated that HPV DNA could be detected in 99.7% of women with histologically confirmed squamous cell cervical cancer compared with 13.4% of control women. Both HPV infection and cervical cancer are associated with a substantial economic burden. Pharmacoeconomic data from the United States indicate that HPV infection and HIV were associated with similar total direct medical costs, and HPV infection was more costly than genital herpes and hepatitis B combined in the 15-25 age group. Furthermore, false-negative pap smears from women with precancerous lesions are among the most frequent reasons for medical malpractice litigation in the United States.

De P, Cox J, Boivin JF, Platt RW, Jolly AM. · Department of Epidemiology and Biostatistics, McGill University, Montreal, Canada. · Addiction. · Pubmed #17935581 No free full text.

Abstract: AIM: To examine the scientific evidence regarding the association between characteristics of social networks of injection drug users (IDUs) and the sharing of drug injection equipment. METHODS: A search was performed on MEDLINE, EMBASE, BIOSIS, Current Contents, PsycINFO databases and other sources to identify published studies on social networks of IDUs. Papers were selected based on their examination of social network factors in relation to the sharing of syringes and drug preparation equipment (e.g. containers, filters, water). Additional relevant papers were found from the reference list of identified articles. RESULTS: Network correlates of drug equipment sharing are multi-factorial and include structural factors (network size, density, position, turnover), compositional factors (network member characteristics, role and quality of relationships with members) and behavioural factors (injecting norms, patterns of drug use, severity of drug addiction). Factors appear to be related differentially to equipment sharing. CONCLUSIONS: Social network characteristics are associated with drug injection risk behaviours and should be considered alongside personal risk behaviours in prevention programmes. Recommendations for future research into the social networks of IDUs are proposed.

Lawee D. · Department of Family and Community Medicine at the University of Toronto in Ontario. · Can Fam Physician. · Pubmed #17872846 links to  free full text

This publication has no abstract.

Paterson BL, Backmund M, Hirsch G, Yim C. · University of New Brunswick, Faculty of Nursing, Fredericton, NB, Canada. <> · Int J Drug Policy. · Pubmed #17854724 No free full text.

Abstract: In the past decade, there has been an increasing emphasis by researchers regarding the stigmatization of people who are hepatitis C positive as they seek health care. Because the vast majority of people with hepatitis C have a history of injection drug use, they are frequently assumed by practitioners to be injection drug users (IDUs), blamed for acquiring the disease, and viewed as irresponsible, immoral, and unworthy. Such stigmatization may cause people who have hepatitis C to avoid testing, treatment and care, as well as to not disclose their hepatitis C or injection drug use to practitioners. The purpose of this paper is to critically examine the representation of stigmatization in 21 published research reports from 1995 to 2006, with a specific focus on how these depictions have shaped the current understanding of interventions to address stigmatization of people with hepatitis C by health care practitioners. We will identify two themes in this literature: (1) hepatitis C-related stigmatization in health care settings arises primarily from practitioners' negative views of injection drug use, and (2) practitioners' negative attitudes toward people with hepatitis C are the result of their lack of awareness and/or information about the disease and/or about injection drug use. We will illustrate that similar themes have informed anti-stigma initiatives in other diseases, notably HIV/AIDS and mental illness, which have had little sustained effect in changing practitioners' behaviour toward the stigmatized population. In conclusion, we will call for research that considers factors beyond the individual practitioner as contributing to the stigmatization of people with hepatitis C, such as social, structural and institutional forces that shape practitioners' interactions with people with hepatitis C in health care settings.

Shaheen AA, Wan AF, Myers RP. · Liver Unit, Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada. · Am J Gastroenterol. · Pubmed #17850410 No free full text.

Abstract: BACKGROUND: The accurate diagnosis of hepatitis C virus (HCV)-related fibrosis is crucial for prognostication and treatment decisions. Due to the limitations of biopsy, noninvasive alternatives including FibroTest and FibroScan have been developed. Our objective was to systematically review studies describing the accuracy of these tests for predicting HCV-related fibrosis. METHODS: Studies comparing FibroTest or FibroScan versus biopsy in HCV patients were identified via an electronic search. Random effects meta-analyses and areas under summary receiver operating characteristics curves (AUC) were examined to characterize test accuracy for significant fibrosis (F2-4) and cirrhosis. Heterogeneity was explored using meta-regression. RESULTS: Twelve studies were identified, 9 for FibroTest (N = 1,679) and 4 for FibroScan (N = 546). In heterogeneous analyses for significant fibrosis, the AUCs for FibroTest and FibroScan were 0.81 (95% CI 0.78-84) and 0.83 (0.03-1.00), respectively. At a threshold of approximately 0.60, the sensitivity and specificity of the FibroTest were 47% (35-59%) and 90% (87-92%). For FibroScan (threshold approximately 8 kPa), corresponding values were 64% (50-76%) and 87% (80-91%), respectively. Methodological quality, the length of liver biopsy specimens, and inclusion of special populations did not explain the observed heterogeneity. However, the diagnostic accuracy of both measures was associated with the prevalence of significant fibrosis and cirrhosis in the study populations. For cirrhosis, the summary AUCs for FibroTest and FibroScan were 0.90 (95% CI not calculable) and 0.95 (0.87-0.99), respectively. CONCLUSIONS: FibroTest and FibroScan have excellent utility for the identification of HCV-related cirrhosis, but lesser accuracy for earlier stages. Refinements are necessary before these tests can replace liver biopsy.

Shaheen AA, Myers RP. · Liver Unit, Division of Gastroenterology, Department of Medicine; University of Calgary, Calgary, Alberta, Canada. · Hepatology. · Pubmed #17705266 No free full text.

Abstract: The development of noninvasive markers of liver fibrosis is a clinical and research priority. The aspartate aminotransferase-to-platelet ratio index (APRI) is a promising tool with limited expense and widespread availability. Our objective was to systematically review the performance of the APRI in hepatitis C virus (HCV)-infected patients. Random effects meta-analyses and areas under summary receiver operating characteristic curves (AUC) were examined to characterize APRI accuracy for significant fibrosis (stages 2-4) and cirrhosis. In 22 studies (n = 4,266), the summary AUCs of the APRI for significant fibrosis and cirrhosis were 0.76 [95% confidence interval (CI), 0.74-0.79] and 0.82 (95%CI, 0.79-0.86), respectively. For significant fibrosis, an APRI threshold of 0.5 was 81% sensitive and 50% specific. At a 40% prevalence of significant fibrosis, this threshold had a negative predictive value (NPV) of 80%, but could reduce the necessity of liver biopsy by only 35%. For cirrhosis, a threshold of 1.0 was 76% sensitive and 71% specific. At a 15% cirrhosis prevalence, the NPV of this threshold was 91%. Higher APRI thresholds had suboptimal positive predictive values except in settings with a high prevalence of cirrhosis. APRI accuracy was not affected by the prevalence of advanced fibrosis, or study and biopsy quality. However, the accuracy for cirrhosis was greater in studies including human immunodeficiency virus (HIV)/HCV-co-infected patients. CONCLUSION: The major strength of the APRI is the exclusion of significant HCV-related fibrosis. Future studies of novel markers should demonstrate improved accuracy and cost-effectiveness compared with this economical and widely available index.

Greig JD, Todd EC, Bartleson CA, Michaels BS. · Public Health Agency of Canada, Laboratory for Foodborne Zoonoses, 160 Research Lane, Unit 206, Guelph, Ontario, Canada NIG 5B2. · J Food Prot. · Pubmed #17685355 No free full text.

Abstract: Food workers in many settings have been responsible for foodborne disease outbreaks for decades, and there is no indication that this is diminishing. The Committee on Control of Foodborne Illnesses of the International Association for Food Protection was tasked with collecting and evaluating any data on worker-associated outbreaks. A total of 816 reports with 80,682 cases were collected from events that occurred from 1927 until the first quarter of 2006. Most of the outbreaks reviewed were from the United States, Canada, Europe, and Australia, with relatively few from other parts of the world, indicating the skewed set of data because of availability in the literature or personal contact. Outbreaks were caused by 14 agents: norovirus or probable norovirus (338), Salmonella enterica (151), hepatitis A virus (84), Staphylococcus aureus (53), Shigella spp. (33), Streptococcus Lancefield groups A and G (17), and parasites Cyclospora, Giardia, and Cryptosporidium (23). Streptococcal, staphylococcal, and typhoid outbreaks seem to be diminishing over time; hepatitis A virus remains static, whereas norovirus and maybe nontyphoidal Salmonella are increasing. Multiple foods and multi-ingredient foods were identified most frequently with outbreaks, perhaps because of more frequent hand contact during preparation and serving.

MacDonald MR, Veniamin SM, Guo X, Xia J, Moon DA, Magor KE. · Department of Biological Sciences, Biological Sciences Building, University of Alberta, Edmonton, Canada. · Cytogenet Genome Res. · Pubmed #17675860 No free full text.

Abstract: We review our progress using genomics approaches to examine key antiviral defenses of the White Pekin mallard duck, Anas platyrhynchos. Our interest stems from the fact that ducks are the natural host of avian influenza, and are an important animal model for hepatitis B research. First, we have conducted an expressed sequence tag (EST) project and identified more than 200 immune relevant genes in the duck. Our analysis of these genes allows us to evaluate the homology between ducks and their closest genetic model organism, the chicken. We have also constructed genomic and cDNA libraries from the same individual duck, allowing us to directly compare expressed sequences with those present in the genome. These resources allow us to determine the organization and expression of regions of the genome important in antiviral defenses. Here we examine the organization of the immunoglobulin heavy chain locus, the Major Histocompatibility Complex class I region, the lectin immunoreceptors and Toll-like receptor 7. We discuss our research-in-progress in the context of the immune defense against viruses, particularly influenza.

Beaulieu PL. · Boehringer Ingelheim (Canada) Ltd, Research and Development, 2100 Cunard Street, Laval, Québec H7S 2G5, Canada. · Curr Opin Investig Drugs. · Pubmed #17668364 No free full text.

Abstract: The severe health conditions associated with chronic HCV infection remain a global concern. Small-molecule drugs that specifically target essential virally encoded enzymes have not yet progressed to market, and the current standard of care continues to rely on a combination of pegylated IFN with ribavirin. This therapy has serious side effects and a significant proportion of patients infected with HCV genotype 1 (the major genotype in industrialized countries) have an unsatisfactory outcome with this therapy. Major advances have been realized in the development of specific non-nucleoside inhibitors of the viral NS5B RNA-dependent RNA polymerase. This well-characterized replicative enzyme is a highly drugable target that, in addition to its active site, features at least three known allosteric binding pockets that regulate RNA synthesis and are suitable for inhibitor design. Clinical proof-of-concept for allosteric non-nucleoside HCV polymerase inhibitors has been reported and several compounds have progressed into preclinical studies. It is likely that in the future NS5B inhibitors will form an integral part of more effective anti-HCV therapies, combining the use of small-molecule antiviral drugs with or without the assistance of immune modulators such as IFNs in order to minimize the emergence of resistance.

Keystone JS, Hershey JH. · Division of Infectious Disease, Department of Medicine, Tropical Disease Unit, Toronto General Hospital, University of Toronto, Toronto, Ontario M5G 2C4, Canada. · Int J Infect Dis. · Pubmed #17643334 No free full text.

Abstract: Hepatitis A virus (HAV) and hepatitis B virus (HBV) are vaccine-preventable. Current recommendations advocate vaccination of non-immune adults at risk of exposure, including travelers to HAV or HBV endemic areas, individuals with high risk of contracting a sexually transmitted infection, and some correctional facility inmates. We review the use of an accelerated schedule to administer the combination hepatitis A and hepatitis B vaccine (Twinrix). Administering three doses over three weeks and a fourth at 12 months provides rapid initial protection of most individuals for whom the standard 6-month vaccination schedule would not be suitable, including last-minute travelers and short-term correctional facility inmates. Furthermore, we consider the role of a universal vaccination strategy in preventing the spread of HAV and HBV.

Tauskela JS. · National Research Council, Institute for Biological Sciences, Synaptic Pathophysiology Group, Ottawa, ON K1A 0R6, Canada. · IDrugs. · Pubmed #17642004 No free full text.

Abstract: MitoQ is an orally active antioxidant that has the ability to target mitochondrial dysfunction. The agent is currently under development by Antipodean Pharmaceuticals Inc in phase II clinical trials for Parkinson's disease and liver damage associated with HCV infection. MitoQ has demonstrated encouraging preclinical results in numerous studies in isolated mitochondria, cells and tissues undergoing oxidative stress and apoptotic death. MitoQ aims to not only mimic the role of the endogenous mitochondrial antioxidant coenzyme Q10 (CoQ10), but also to augment substantially the antioxidant capacity of CoQ to supraphysiological levels in a mitochondrial membrane potential-dependent manner. MitoQ represents the first foray into the clinic in an attempt to deliver an antioxidant to an intracellular region that is responsible for the formation of increased levels of potentially deleterious reactive oxygen species. Results from the clinical trials with MitoQ will have important repercussions on the relevance of a mitochondrial-targeted approach.

Raman M, Allard JP. · University of Calgary Medical Clinic, Faculty of Medicine, Room G055, 3330 Hospital Dr. N.W., Calgary, AB, Canada. · Appl Physiol Nutr Metab. · Pubmed #17622278 No free full text.

Abstract: Parenteral nutrition is a life-saving therapy in patients with intestinal failure. One of the major causes of morbidity and mortality in patients receiving long-term total parenteral nutrition (TPN) is liver disease. Early on, there is steatosis, which can evolve to steatohepatitis and eventually to cholestasis of varying severity. The etiology of parenteral nutrition related liver disease is multifactorial. Provision of excess calories in the TPN solution, along with lipids administered >1 g/kg are thought to increase the risk of parenteral nutrition related liver disease. Other factors such as nutrient deficiencies and nutrient toxicities may also play a role in the pathogenesis of liver disease, along with sepsis and the lack of enteral stimulation. Non-pharmacological management strategies for TPN-related liver disease include enteral stimulation, optimal TPN composition, and avoidance of excess carbohydrate and lipid calories. Pharmacological therapy with ursodeoxycholic acid and antibiotic therapy to reduce the risk of bacterial translocation and sepsis should be considered. Early referral for transplantation should be considered in patients with evidence of portal hypertension. This review focuses on the clinical aspects, pathogenesis, and management strategies of parenteral nutrition-related liver disease in adult patients.