Hepatitis B and C serologic profiles of Canadian organ donors and recipients: retrospective 10-year review at a single center.

BACKGROUND: Hepatitis C virus (HBV) and hepatitis C virus (HCV) are important causes of hepatitis and can be transmitted from organ donor to recipient. This study aimed to determine HBV and HCV serologic profiles of a population of Canadian solid organ transplant (SOT) donors and recipients, including prevalence of recipient HBV immunity. METHODS: Data on age, gender, organ transplanted, and pre-transplant HBV and HCV serology for SOT donors and recipients at a Canadian hospital from 2001 to 2011 were obtained from a transplant database. RESULTS: There were 2455 recipients (2205 adults, 250 children), and 1559 donors. Over 50% of adult and 44% of pediatric recipients were HBV non-immune pre-transplant. Pediatric recipients were more likely to have HBV vaccine immunity than were adult recipients (48.8% vs. 28.9%, P < 0.001). Prevalence of HBV vaccine immunity was highest in renal recipients (48.3% in adult, 63.2% in pediatric recipients). Recipient HBV vaccine immunity increased from 5.8% in 2001 to 44.5% in 2011 (P < 0.001). Of 134 adult recipients with prior HBV infection, 59 (44%) were co-infected with HCV. Only 0.6% of adult non-liver recipients had acute or chronic HBV infection and 3.2% were anti-HCV positive. Only 2 donors had acute or chronic HBV infection, 29 had prior HBV infection, 9 were isolated hepatitis B core antibody positive, and 15 were anti-HCV positive. CONCLUSIONS: The prevalence of HBV vaccine immunity in SOT candidates is low, but increased from 2001 to 2011. Opportunities for quality improvement in pre-transplant HBV immunization exist. HCV co-infection is common in recipients with prior HBV infection. Prevalence of HCV infection in non-liver transplant recipients is low.

Outcomes of Lung Transplantation in Recipients With Hepatitis C Virus Infection.

Hepatitis C virus (HCV) infection negatively impacts patient and graft survival following nonhepatic solid organ transplantation. Most data, however, are in kidney transplant, where despite modest impact on outcomes, transplantation is recommended for those with mild to moderate hepatic fibrosis given overall benefit compared to remaining on dialysis. In lung transplantation (LuTx), there is little data on outcomes and international guidelines are vague on the criteria under which transplant should be considered. The University of Alberta Lung Transplant Program routinely considers patients with HCV for lung transplant based on criteria extrapolated from the kidney transplant literature. Here we describe the outcomes of 27 HCV-positive, compared to 443 HCV-negative LuTx recipients. Prior to transplant, five patients were treated for HCV and cured. At the time of transplant, 14 patients remained HCV RNA positive. The 1-, 3-, and 5-year survival were similar in HCV RNA-positive versus -negative recipients at 93%, 77%, and 77% versus 86%, 75%, and 66% (p = 0.93), respectively. Long-term follow-up in eight patients demonstrated no significant progression of fibrosis. In our cohort, HCV did not impact LuTx outcomes and in the era of interferon-free HCV therapies this should not be a barrier to LuTx.

Solid organ transplantation from hepatitis B virus-positive donors: consensus guidelines for recipient management.

Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non-liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti-HBc+) donors. Organs from anti-HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non-liver recipients but is not recommended in immune non-liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost-effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.

Donor-derived bacteremia in liver transplant recipients despite antibiotic prophylaxis.

As the disparity between the number of candidates listed for transplant and the number of donors continues to grow, marginal organ donors are increasingly utilized. This includes bacteremic donors which may carry an increased risk of transmission of infection. It is recommended that recipients of organs from bacteremic donors receive antibiotic prophylaxis based on the susceptibilities of the donor isolate to prevent transmission. Here, we present four cases of donor-derived bacteremia, despite appropriate antimicrobial prophylaxis, in four liver transplant recipients. Transmitted pathogens included Staphylococcus aureus in two cases, and Escherichia coli and Group B Streptococcus each in one case. Interestingly, none of the nonhepatic organs (n=10) utilized from these bacteremic donors resulted in transmissions. These cases highlight the fact that risk of transmission from bacteremic donors is not eliminated with antimicrobial therapy in the donor and recipient. As no transmissions occurred in recipients of nonhepatic organs from these donors, these cases also suggest that liver recipients may be at higher risk of donor transmitted bacteremia.

Improving access to care by allowing self-referral to a hepatitis C clinic.

BACKGROUND: Estimates suggest that more than 250,000 Canadians are infected with hepatitis C virus (HCV), but less than 10% have been treated. Access to specialists in Canada is usually via health care professional (HCP) referral and, therefore, may be a barrier to HCV care. However, clinics that operate in conjunction with the Hepatitis Support Program, Edmonton, Alberta, allow self-referral. It is hypothesized that this improves access to care without increasing inappropriate referrals. OBJECTIVE: To compare the baseline characteristics and outcomes of HCV patients who self-referred with those who were HCP-referred. METHODS: Data were collected from the Hepatitis Support Program HCV database and chart reviews. RESULTS: Between December 17, 2002, and December 31, 2007, 1563 patients were referred including 336 self- (21.5%) and 1227 HCP-referrals (78.5%). Self- and HCP-referred patients were similar in terms of age (mean [+/- SD] 43.0+/-10.3 years versus 43.9+/-10.0 years, respectively; P=0.18), sex (56.8% versus 62.0% [men], respectively; P=0.08) and risk factors for HCV (P=0.3), with 49.7% and 52.6%, respectively, identifying injection drug use as the primary risk factor. The two groups had similar HCV genotype distributions and liver biopsy fibrosis scores with similar treatment rates (31.3% versus 33.2%; P=0.6). Treatment outcomes were excellent (sustained virological response 40.2% for genotype 1, 67% for genotypes 2 and 3) in patients completing therapy and were similar between the two groups. CONCLUSION: Self-referred patients comprised 21.5% of patients accessing care in the clinic. Self- and HCP-referred patients had similar characteristics, treatment rates and outcomes. Facilitating self referral to an HCV clinic can improve access to care, including risk reduction education and HCV treatment.

Oseltamivir: a clinical and pharmacological perspective.

Oseltamivir is the ethyl ester prodrug of the antiviral molecule, oseltamivir carboxylate, a potent and selective inhibitor of influenza A and B neuraminidase (NA) (sialidase). It is highly bioavailable in capsule and suspension formulations and, after conversion to the active metabolite in the liver, distributes throughout the body, including the upper and lower respiratory tract. Oseltamivir carboxylate is 3% bound to human plasma proteins and eliminated through the kidneys by a first-order process as unchanged drug by glomerular filtration and tubular secretion by an anionic transporter system. Given these characteristics, its potential for adverse interactions with other drugs appears limited to those arising from competitive inhibition of excretion by the renal tubular epithelial cell anionic transporter. The terminal plasma elimination half-life is 1.8 h in healthy adults. Renal clearance is inversely related to renal function and averages 23 h after oral administration in individuals with creatinine clearance < 30 ml/min. In vitro studies have demonstrated potent antiviral activity against all strains of influenza A and B tested including avian H5N1 and H9N2 strains recently implicated in human cases in Hong Kong. Studies of both experimental and naturally-occurring influenza in humans have demonstrated efficacy in both the prevention and treatment of influenza A and B infection. The drug is well-tolerated with the only clinically important side effect being mild gastrointestinal upset. Resistance has been uncommonly seen after clinical use; the highest incidence was 5.5% in children treated for influenza A infection for 5 days. Viruses that develop resistance appear to be less virulent in laboratory animals and to replicate less efficiently than parent strains. Although oseltamivir and the M2 ion channel inhibitors, amantadine and rimantadine, have not been directly compared in clinical trials, the greater breadth of spectrum of oseltamivir, its modest side effect profile compared to amantadine and its lesser propensity to engender the emergence of transmissible drug-resistant strains all suggest strongly that oseltamivir is a significant new agent for the prevention and treatment of influenza. A series of controlled trials comparing M2 ion channel inhibitor drugs and the new neuraminidase (NA) inhibitor agents are now needed to test this hypothesis and thereby to further advance the science of antiviral drug use to control influenza.