HIV and hepatitis C virus RNA in seronegative organ and tissue donors

The objective of our study was to determine whether nucleic acid testing could detect HIV RNA or hepatitis C virus (HCV) RNA in a large series of seronegative organ and tissue donors, and whether this technique should be routinely used to improve viral safety of grafts. We studied 2236 organ donors, 636 tissue donors, and 177 cornea donors. We identified five HCV RNA-positive donors in 2119 HCV-seronegative organ donors, and one HCV RNA-positive donor in 631 HCV-seronegative tissue donors. No HIV-seronegative, HIV RNA-positive donor was identified. Our data suggest that routine nucleic acid testing of organ and tissue donors might increase viral safety in transplantation.     

Liver‐specific deceased donor risk indices

In order to assess the quality of the donor liver, procuring surgeons should accurately evaluate not only general donor risk indices, such as donor age, causes of brain death and cold ischemic time, but also consider the specific donor risk indices. In this review, we focus on liver‐specific deceased donor risk indices, including liver steatosis, anti‐hepatitis B core (HBc) positive or hepatitis C virus (HCV) positive donors, hypernatremia and anatomical variations. Liver steatosis is strongly associated with poor graft function after liver transplantation. Liver with more than 40–50% macrosteatosis should not be used. However, at present the quantity of fatty livers lack accepted standards. The computerized image analysis programs should be used to automate the determination of fat content in liver biopsy specimens. Liver grafts from anti‐HBc positive donors can be safely used, preferentially in hepatitis B surface antigen (HBsAg) positive or anti‐HBc/anti‐HBs positive recipients. HCV positive allografts free from fibrosis or severe inflammation are a safe option for HCV positive recipients. The procurement team should consider liver biopsy to evaluate these HCV positive allografts. Donor serum sodium over 150 mm may predict a higher rate of graft primary non‐functions. Recently, however, some investigators reported the sodium level likely has little clinical impact on post‐transplant liver function. The incidence of hepatic artery variations has been reported to be approximately 30%. To avoid injuries, it is very important to know and identify these variations with precision at the time of organ procurement.     

HCV-Positive Allograft Use in Heart Transplantation Is Associated With Increased Access to Overdose Donors and Reduced Waitlist Mortality Without Compromising Outcomes

BackgroundBecause of ongoing shortages of donors for heart transplantation, the use of donor candidates whose availabilities are the result of drug overdoses (ODs) has become increasingly prevalent, even though these donors carry a high preponderance of the now curable hepatitis C virus (HCV). This study investigated temporal trends and regional variabilities in HVC-positive (HCV+) allograft use in heart transplantation and assessed the relationship between the use of HCV+ graft donors and the use of OD donors as well as assessing waitlist and post-transplant outcomes.Methods and ResultsA retrospective review of the United Network for Organ Sharing database assessed adults listed for heart transplantation. Patients were stratified both temporally into pre-HCV and HCV eras related to HCV+ graft use trends and regionally by degree of HCV+ allograft use. Regions of high HCV+ donor use were associated with an increase in OD donor access by 7.8% across eras compared to 0.4% in low HCV+ donor-use regions. One-year waitlist mortality decreased from 4.7% to 2.5% across eras in high HCV+ donor-use regions (P= 0.001) and remained roughly the same as before in low HCV+ donor-use regions (3.0% vs 2.4%; P= 0.244.). Post-transplant survival at 1 year remained similar across eras.ConclusionsHCV+ donor allograft use can help to optimize donor use, decreasing waitlist mortality without compromising early survival. Ongoing assessment is essential to ensure long-term safety and efficacy of using HCV+ donors.     

Hepatitis B and hepatitis C virus and chronic kidney disease

The most common cause of liver disease in patients with chronic kidney disease (CKD) remains infection by hepatitis B virus (HBV) and/or hepatitis C virus (HCV). The adverse effects of HBV and/or HCV infections upon survival in patients with CKD have been repeatedly confirmed. An excess risk of death in HBsAg positive or anti-HCV antibody-positive patients may be at least partially attributed to chronic liver disease with its attendant complications. A negative impact of HCV infection on survival after renal transplantation has been linked to extrahepatic complications, including chronic glomerulonephritis, sepsis, chronic allograft nephropathy, post-transplantation diabetes mellitus, and abnormal metabolism of calcineurin-inhibitors. Transmission of HCV infection by grafts from HCV-infected donors has been unequivocally demonstrated. Registry analyses suggest that recipients of kidneys from anti-HCV antibody positive donors are at increased risk of mortality. Renal grafts from HCV-infected donors should be restricted to viremic anti-HCV positive recipients. Several drugs have been recently licensed for therapy of HBV infection but availabledata in patients with CKD is mostly limited to experience with lamivudine. The standard of care for hepatitis C infection in patients on regular dialysis is monotherapy with conventional interferon, according to recent guidelines. Only dire circumstances justify interferon use after renal transplantation.     

No increased mortality from donor or recipient hepatitis B‐ and/or hepatitis C‐positive serostatus after related‐donor allogeneic hematopoietic cell transplantation

Limited data exist on allogeneic transplant outcomes in recipients receiving hematopoietic cells from donors with prior or current hepatitis B (HBV) or C virus (HCV) infection (seropositive donors), or for recipients with prior or current HBV or HCV infection (seropositive recipients). Transplant outcomes are reported for 416 recipients from 121 centers, who received a human leukocyte antigen‐identical related‐donor allogeneic transplant for hematologic malignancies between 1995 and 2003. Of these, 33 seronegative recipients received grafts from seropositive donors and 128 recipients were seropositive. The remaining 256 patients served as controls. With comparable median follow‐up (cases, 5.9 years; controls, 6.7 years), the incidence of treatment‐related mortality, survival, graft‐versus‐host disease, and hepatic toxicity, appears similar in all cohorts. The frequencies of hepatic toxicities as well as causes of death between cases and controls were similar. Prior exposure to HBV or HCV in either the donor or the recipient should not be considered an absolute contraindication to transplant.     

Successful heart‐kidney transplantation from a Hepatitis C viremic donor to negative recipient: One year of follow‐up

Every year the number of patients waiting for a heart transplant increases faster than the number of available donor organs. Some potential donor organs are from donors with active communicable diseases, including hepatitis C virus (HCV), potentially making donation prohibitive. The advent of direct‐acting antiviral agents for HCV has drastically changed the treatment of HCV. Recently, these agents have been used to treat HCV in organ donor recipients who acquired the disease from the donor organ. We report a case of heart‐kidney transplantation from an HCV viremic donor to HCV negative recipient with successful treatment and sustained virologic response.     

Outcomes of liver transplantation using Hepatitis B core-positive liver grafts: Implications for prophylaxis

The number of patients listed for liver transplantation has outpaced the number of transplants that can be performed. This disparity between transplant candidates and the availability of donor grafts has led to an increase in mortality for patients waiting for liver transplantation. One strategy used to increase the donor pool has been the utilization of expanded donor grafts, such as those from donors with hepatitis B core antibody (anti-HBc). However, use of anti-HBc-positive grafts can potentially place the recipient at risk of de novo post-transplant hepatitis B virus (HBV) infection. The spectrum of liver disease from de novo hepatitis B ranges from mild hepatitis to graft loss. Fortunately, the risk of de novo HBV infection can be decreased with administration of oral nucleosides or nucleotides and hepatitis B immunoglobulin to the recipient. This review focuses on the epidemiology, natural history, and prophylactic strategies to reduce the risk of de novo hepatitis B in liver transplant recipients who receive anti-HBc-positive grafts.     

Extended criteria donors in liver transplantation Part I: reviewing the impact of determining factors

The definition and factors of extended criteria donors have already been set; however, details of the various opinions still differ in many respects. In this review, we summarize the impact of these factors and their clinical relevance. Elderly livers must not be allocated for hepatitis C virus (HCV) positives, or patients with acute liver failure. In cases of markedly increased serum transaminases, donor hemodynamics is an essential consideration. A prolonged hypotension of the donor does not always lead to an increase in post-transplantation graft loss if post-OLT care is proper. Hypernatremia of less than 160 mEq/L is not an absolute contraindication to accept a liver graft per se. The presence of steatosis is an independent and determinant risk factor for the outcome. The gold standard of the diagnosis is the biopsy. This is recommended in all doubtful cases. The use of HCV+ grafts for HCV+ recipients is comparable in outcome. The leading risk factor for HCV recurrence is the actual RNA positivity of the donor. The presence of a proper anti-HBs level seems to protect from de novo HBV infection. A favourable outcome can be expected if a donation after cardiac death liver is transplanted in a favourable condition, meaning, a warm ischemia time < 30 minutes, cold ischemia time < 8–10 hours, and donor age 50–60 years. The pathway of organ quality assessment is to obtain the most relevant information (e.g. biopsy), consider the co-existing donor risk factors and the reserve capacity of the recipient, and avoid further technical issues.     

Exposure of hepatitis C virus-negative recipients to > or =2 infected blood donors

This study analyzed 4 cases of hepatitis C virus (HCV)-naive transfusion recipients who developed hepatitis after receiving blood from >1 HCV-infected donor. One recipient was exposed to 4 donors, 2 were exposed to 3 donors, and 1 was exposed to 2 donors. For 3 recipients, the strain from 1 of the donors predominated in all follow-up samples collected for 8-40 months. For 2 recipients, the strain from the second donor was occasionally detectable with sensitive strain-specific assays. For the fourth recipient, the initially dominant strain was later supplanted by a strain from the other donor. Simultaneous exposure to multiple HCV strains may result in concomitant infection by >1 strain, although a single strain rapidly establishes its dominance. These observations are compatible with the presence of competition among infecting HCV strains that results in the dominance of 1 strain and competitive exclusion or suppression of other strains.     

The clinical consequences of utilizing donation after cardiac death liver grafts into hepatitis C recipients

Abstract  

Chronic liver failure from hepatitis C virus (HCV) remains the leading indication for liver transplantation (LT). Donation after cardiac death (DCD) donors are becoming a more frequent source of liver grafts. Hepatitis C recipients of standard donation after brain death (DBD) allografts may have inferior long-term results, and more so when expanded criteria organs are used. Given the nature of DCD grafts, a focus on the consequences to HCV recipients is of major importance. We analyzed the graft outcomes in HCV and non-HCV liver transplant recipients of DCD grafts.     

High seroprevalence of asymptomatic viral haemoparasites among prospective blood donors in Nigeria

Objective:To determine the prevalence of viral haemoparasites in prospective Nigerian blood donors.Methods:Ethical clearance was obtained and informed consent questionnaires were distributed to blood donors to obtain their demographical data.A total of 186 blood donors from LAUTECH Teaching Hospital,Osogbo were tested for hepatitis A virus(HAV),hepatitis B virus(HBV) and hepatitis C virus(HCV) using rapid test kit and Enzyme Linked Immunosorbent Assay.Results:The highest prevalence of blood transmitted infections was 182(97.85%) while the prevalence of HIV,HAV,HBV and HCV were 6.45%,97.85%,14.52% and 3.23% respectively.Highest seroprevalence for hepatitis A,B and C occurred among low risk occupation.There was no significant association between all the hepatitis viruses and demographic factors except occupation with P value of 0.002 7.Hepatitis A,B and C seropositive blood donors on average tend to have PCV within the normal reference range.Out of the 27 hepatitis B positive blood donors,22 were donating blood for the first time while 5 were repeat donors.None of the hepatitis C seropositive donors have been exposed to blood or any form of its products and were all donating blood for the first time.However,the distribution of donor type for HAV is random.Conclusions:The presence of HAV,HBV,HCV and HIV among prospective donors in Nigeria particularly the alarming prevalence of HAV.These infections can be transmitted to recipients if proper screening is not carried out,hence they should be included as a routine test for blood donors.     

Extended-criteria donors in liver transplantation Part II: reviewing the impact of extended-criteria donors on the complications and outcomes of liver transplantation

Extended-criteria donors (ECDs) have an impact on early allograft dysfunction (EAD), biliary complications, relapse of hepatitis C virus (HCV), and survivals. Early allograft dysfunction was frequently seen in grafts with moderate and severe steatosis. Donors after cardiac death (DCD) have been associated with higher rates of graft failure and biliary complications compared to donors after brain death. Extended warm ischemia, reperfusion injury and endothelial activation trigger a cascade, leading to microvascular thrombosis, resulting in biliary necrosis, cholangitis, and graft failure. The risk of HCV recurrence increased by donor age, and associated with using moderately and severely steatotic grafts. With the administration of protease inhibitors sustained virological response was achieved in majority of the patients. Donor risk index and EC donor scores (DS) are reported to be useful, to assess the outcome. The 1-year survival rates were 87% and 40% respectively, for donors with a DS of 0 and 3. Graft survival was excellent up to a DS of 2, however a DS >2 should be avoided in higher-risk recipients. The 1, 3 and 5-year survival of DCD recipients was comparable to optimal donors. However ECDs had minor survival means of 85%, 78.6%, and 72.3%. The graft survival of split liver transplantation (SLT) was comparable to that of whole liver orthotopic liver transplantation. SLT was not regarded as an ECD factor in the MELD era any more. Full-right-full-left split liver transplantation has a significant advantage to extend the high quality donor pool. Hypothermic oxygenated machine perfusion can be applied clinically in DCD liver grafts. Feasibility and safety were confirmed. Reperfusion injury was also rare in machine perfused DCD livers.     

Hepatitis C transmission from viremic donors in hematopoietic stem cell transplant

Transmission of hepatitis C virus (HCV) to recipients of hematopoietic stem cell transplant (HSCT) occurs frequently from HCV viremic donors and causes complications. Here, we report the outcomes of 3 cases from our 265 allogeneic HSCTs, whose donors had HCV infections. Successful prevention of HCV transmission was noted in 1 recipient by pretreatment of the donor with peginterferon/ribavirin to undetectable levels of HCV viremia before stem cell harvest. This case stressed the important role of effective antiviral therapy and HCV RNA seronegativity before cell harvest for prevention of HCV transmission in HSCT.     

Comparison of prevalence rates of microbiological markers between bone/tissue donations and new blood donors in Scotland

BACKGROUND AND OBJECTIVES: Blood-borne virus prevalence rates of samples accompanying tissue donors are not widely available. This article compares the rates in Scottish bone/tissue donors with those of new blood donors for the 7-year period, 1998-2004. MATERIALS AND METHODS: Data were collated from existing internal reports. Age distributions of the donor populations were obtained by extracting information from existing computer databases. RESULTS: Scottish bone/tissue donors were found to have a fourfold higher prevalence for hepatitis B virus (HBV), a 1.6-fold higher prevalence for hepatitis C virus (HCV), an 11-fold higher prevalence for human T-cell lymphotropic virus (HTLV) and a 34-fold higher prevalence for syphilis compared with new blood donors. Excluding confirmed positives, the repeat-reactive rates for bone/tissue donors were similar to those of new blood donors. CONCLUSIONS: The data demonstrated that the prevalence of blood-borne viruses in Scottish bone/tissue donors is higher than in new blood donors. We believe that the different age profiles of the two donor populations plays a significant role.     

Should antihepatitis B virus core positive or antihepatitis C virus core positive subjects be accepted as organ donors for liver transplantation?

Since the introduction of liver transplantation as a routine surgical procedure for the treatment of end-stage liver disease, there has been an increasing gap between the number of available grafts and the number of patients on the waiting list. This has led transplant centers to expand the donor pool by different means. One of them has been the introduction of living donor liver transplantation. Other strategies include using less than optimal allografts from deceased donors, the so-called marginal donors, which include the use of grafts from older subjects, livers with moderate amounts of steatosis, or from donors with markers of past or current infection with hepatitis viruses who have absent or minimal liver biochemical or histologic injury. In this review, we will focus on the current use of allografts from donors with antihepatitis B core antibody and/or antibodies against hepatitis C virus in cadaveric and living donor liver transplantation.     

Prevention of hepatitis B virus infection from hepatitis B core antibody-positive donor graft using hepatitis B immune globulin and lamivudine in living donor liver transplantation.

BACKGROUND: Hepatic grafts from hepatitis B surface antigen-negative and anti-core antibody (HBcAb)-positive donors have been shown to transmit hepatitis B virus (HBV) infection. Recently, it has been reported that combined hepatitis B immune globulin (HBIG) and lamivudine therapy is effective in the prevention of hepatitis B recurrence after living donor liver transplantation (LDLT). In this report, we assessed the efficacy of combined HBIG and lamivudine therapy in preventing HBV transmission by graft with HBcAb-positive donors. METHODS: We studied 22 patients who had undergone LDLT with allografts from HBcAb-positive living donors at Gunma University Hospital and Kyushu University Hospital. Long-term combined HBIG and lamivudine therapy were administrated to all recipients. Serum samples from the donor and recipient were tested for HBcAb, HBV DNA, and hepatitis B surface antibody. Liver biopsies from grafts were tested for HBV DNA. RESULTS: All recipients were HBcAb negative before LDLT. All of the donor livers were HBV DNA positive at the time of LDLT. All of the recipients had HBsAb titers greater than 300 mIU/ml 4 weeks after LDLT, and remained 100 mIU/ml thereafter. None of the recipients have become infected with HBV with a follow-up of 25-86 months. CONCLUSIONS: Perioperative combined HBIG and lamivudine therapy can prevent HBV infection in recipients who receive liver grafts from HBcAb-positive donors.     

Marrow transplantation from hepatitis C virus seropositive donors: transmission rate and clinical course

Bone marrow transplant recipients are at risk for acquiring hepatitis C infection from the donated marrow. Twelve patients who were hepatitis C virus (HCV) RNA-negative pretransplant received marrow from anti-HCV seropositive donors. HCV RNA was present in the sera of seven of these donors. After transplant, serial serum specimens were obtained from all marrow recipients for determination of HCV RNA and aminotransferase levels. All seven recipients of marrow from HCV RNA-positive donors were HCV RNA-positive after marrow infusion; none cleared virus from the serum. All five recipients of marrow from anti-HCV seropositive, HCV RNA-negative donors remained free of HCV RNA in serum up to day 100. Abnormal serum aminotransferases were common in both HCV RNA- negative and HCV RNA-positive marrow recipients. One HCV-infected recipient developed marked elevation in aminotransferases after immunosuppressive drugs were stopped. We conclude that the presence of HCV RNA in the serum of marrow donors is an accurate predictor of HCV infection in marrow recipients. The acute infection was subclinical in all patients. The long-term risk of chronic hepatitis C virus infection in these patients remains to be determined.     

Tissue donation and virus safety: more nucleic acid amplification testing is needed

A. Pruss, G. Caspari, D.H. Krüger, J. Blümel, C.M. Nübling, L. Gürtler, W.H. Gerlich. Tissue donation and virus safety: more nucleic acid amplification testing is needed.
Transpl Infect Dis 2010: 12: 375–386. All rights reserved Abstract: In tissue and organ transplantation, it is of great importance to avoid the transmission of blood‐borne viruses to the recipient. While serologic testing for anti‐human immunodeficiency virus (HIV)‐1 and ‐2, anti‐hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg), anti‐hepatitis B core antigen (HBc), and Treponema pallidum infection is mandatory, there is until now in most countries no explicit demand for nucleic acid amplification testing (NAT) to detect HIV, hepatitis B virus (HBV), and HCV infection. After a review of reports in the literature on viral transmission events, tissue‐specific issues, and manufacturing and inactivation procedures, we evaluated the significance of HIV, HCV, and HBV detection using NAT in donors of various types of tissues and compared our results with the experiences of blood banking organizations. There is a significant risk of HIV, HCV, and HBV transmission by musculoskeletal tissues because of their high blood content and the high donor–recipient ratio. If no effective virus inactivation procedure for musculoskeletal tissue is applied, donors should be screened using NAT for HIV, HCV, and HBV. Serologically screened cardiovascular tissue carries a very low risk of HIV, HCV, or HBV transmission. Nevertheless, because effective virus inactivation is impossible (retention of tissue morphology) and the donor–recipient ratio may be as high as 1:10, we concluded that NAT should be performed for HIV, HCV, and HBV as an additional safety measure. Although cornea allografts carry the lowest risk of transmitting HIV, HCV, and HBV owing to corneal physiology, morphology, and the epidemiology of corneal diseases, NAT for HCV should still be performed. If the NAT screening of a donor for HIV, HCV, and HBV is negative, quarantine storage of the donor tissue seems dispensable. In view of numerous synergistic effects with transfusion medicine, it would be advantageous for tissue banks to cooperate with blood bank laboratories in performing virological tests.