Transfusion-Transmitted Hepatitis B Virus: Minimizing the Risk

One of the major concerns in transfusion medicine is minimizing the risk for transfusion-transmitted infections, including hepatitis B virus (HBV).¹ In the last few decades, HBV vaccination programs and the implementation of blood safety measures have contributed to a steady reduction in the risk for HBV transfusion transmission.² Commonly employed blood safety measures include the selection of donors on the basis of risk-behavior assessments and the testing of blood donations, using several sensitive techniques: the hepatitis B antigen (HBsAG) assay, hepatitis B core antibody (anti-HBc) testing, and recently, HBV Nucleic Acid Testing (NAT).^2,3

The overall approach to HBV transfusion-transmission risk reduction and the choice of screening techniques depend on a range of local/regional factors such as the prevalence of HBV, the HBV vaccination rate, the availability of laboratory equipment and suitable donors, economic factors, and so on.³

Despite the use of effective risk reduction measures, the ultimate goal of zero residual risk remains out of reach.² In a recent study, researchers postulated that the residual risk for HBV transfusion-transmission is “associated with the preseroconversion window period and occult HBV infection characterized by the absence of detectable HBsAg and extremely low levels of HBV DNA.”² A different study pointed out several factors that likely influence HBV transfusion-transmission, including the volume of plasma transfused/viral load, the immune status of both recipient and donor with respect to HBV, and the infecting strain of HBV.⁴

In an interview with Infectious Disease Advisor, Christoph Niederhauser, PD, PhD, head of laboratory diagnostics and research & development diagnostics at Interregional Blood Transfusion SRC, Bern, Switzerland, discussed the challenges that remain in minimizing the risk for HBV transfusion-transmitted infection.

Infectious Disease Advisor: Which testing strategies are currently available/employed for hepatitis B virus blood screening, and how effective are they?

Christoph Niederhauser, PD, PhD: At this time, several different strategies are applied across countries. The most common strategy used worldwide is probably the HBsAg screening of all donations. In countries with a low-level HBV prevalence and in those with sufficient funds, anti-HBc screening is used as an additional safety measure. Many industrialized countries also perform HBV NAT ranging from pools of 96 donations down to individual donation testing. If highly sensitive HBV NAT screening is performed, or when HBsAg screening in combination with anti-HBc testing is applied, then the safety of blood components is very high.

Infectious Disease Advisor: Which criteria determine the choice of HBV screening strategy?

Dr Niederhauser: The choice of HBV screening strategy depends heavily on the HBV epidemiological situation and the financial capacity of the concerned country. In countries with a low HBV prevalence and sufficient funds, anti-HBc is used in conjunction with HBsAg screening of all donations. As mentioned earlier, several industrialized countries are also implementing HBV NAT.

Infectious Disease Advisor: What are the main causes/unresolved issues behind residual risk for HBV transfusion transmission?

Dr Niederhauser: One topic that is still a major focus of HBV research is what to do with the so-called occult hepatitis B cases (OBI). OBI is defined as the presence of HBV DNA in the absence of detectable HBsAg.⁵ There is an ongoing debate about the potential of donors with OBI to transmit HBV infection via transfusion, as well as the exact viral load necessary for transmission. Furthermore, it is still being debated whether one can abolish HBsAg testing in countries where highly sensitive HBV NAT assays are in use. This debate stems from cost-benefit considerations.

Infectious Disease Advisor: Where are improvements still needed before the ultimate goal of zero residual risk can be achieved?

Dr Niederhauser: A zero residual risk will never be reached with a high probability. Also, in the field of transfusion safety, the cost-benefit considerations should, and hopefully will, be considered in the not-too-distant future. On a more positive note, future vaccination strategies and new HBV drugs will probably help prevent transfusion-transmitted HBV cases and, at the same time, reduce the fear of morbidity resulting from HBV-contaminated blood components.

Infectious Disease Advisor: Which measures are used for prevention of HBV transfusion transmission, and what are their advantages/disadvantages?

Dr Niederhauser: The most important measure for preventing HBV transfusion-transmitted infections was the implementation of HBsAg testing of all blood donations in the early 1970s. Since then, anti-HBc screening and, later on, HBV NAT testing in minipools or in individual donations was introduced. In some countries, the safety of blood products has been further increased by the introduction of pathogen reduction systems for platelets and transfusion plasma. These additional safety measures and pathogen reduction systems have increased the safety of blood components but have also, inadvertently, increased the overall cost of safe blood products. Other introduced measures have concentrated on the blood donor.

Today’s blood donor selection process requires that donors fill out a broad questionnaire and ensures that they are well-informed about the dangers of transmitting infections. This approach has helped build an extensive pool of nonremunerated, intrinsically motivated blood donors. HBV vaccination programs in the general population have also increased the safety of blood components, at a reduced cost and with added benefit for the general population.

References

1. Seo DH, Whang DH, Song EY, et al. Occult hepatitis B virus infection and blood transfusion. World J Hepatol. 2015;7(3):600-606.
2. Candotti D, Laperche S. Hepatitis B virus blood screening: need for reappraisal of blood safety measures?Front Med. 2018;5:29.
3. Niederhauser C. Reducing the risk of hepatitis B virus transfusion-transmitted infection. J Blood Med. 2011;2:91-102.
4. Candotti D, Boizeau L, Laperche S. Occult hepatitis B infection and transfusion-transmission risk.Transfus Clin Biol. 2017;24(3):189-195.
5. Kwak MS, Kim YJ. Occult hepatitis B virus infection. World J. Hepatol. 2014;6(12):860-869.