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What exactly is HBsAg and HBsAb? What exactly is the difference between HBsAg and HBsAb? Are they antibodies that protect against the HBV or is it the actual virus?

1 Answer

Joëlle

Aug 19, 2016

Answer:

Ag is the antigen and Ab is the antibody.

Explanation:

First it is important to know the difference between and antibody (Ab) and an antigen (Ag):

  • Antibody = protein produced by the immune system to ‘neutralize’ all (toxic) molecules foreign to the body.
  • Antigen = a foreign and/or toxic molecule that induces an immune response.

Now the difference in this example:

  • HBsAb = Hepatitis B surface antibody that is produced because the body has been exposed to the Hepatitis B virus (HBV).
  • HBsAg = Hepatitis B surface antigen, this is the part of the virus that induces an immune response.

Presence of either HBsAb and/or HBsAg mean different things:

  • Presence of HBsAb = the body has been exposed to HBV. It usually appears about one month after the virus has disappeared. This means someone is no longer contagious when HBsAB is present. Also, it protects the body from getting HBV in the future.
  • Presence of HBsAg = early sign of an active infection with HBV, people are contagious in this stage.
  • Presence of both HBsAb and HBsAg = sometimes this occurs and means that the body is fighting off the infection, but people are still contagious.

There is also another test for HBV that tests for the presence of the Hepatitis B e-antigen (HBeAg). This antigen is only present during an active HBV infection. It can be used to determine how contagious someone is and to determine the effectiveness of treatment.

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Medicine (Baltimore). 2017 Nov; 96(44): e8518.
Published online 2017 Nov 3. doi:  [ 10.1097/MD.0000000000008518 ]
PMCID: PMC5682831
PMID: 29095312

Hepatitis B virus infection in an HBsAb-positive lymphoma patient who received chemotherapy

A case report
Fu-Biao Kang , MD, PhD,a, Ling Wang , MD,b and Dian-Xing Sun , MDa

Fu-Biao Kang

aLiver Disease Diagnosis and Treatment Center, Bethune International Peace Hospital

Find articles by Fu-Biao Kang

Ling Wang

bOrthopedic Research Institute, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China.

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Dian-Xing Sun

aLiver Disease Diagnosis and Treatment Center, Bethune International Peace Hospital

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Monitoring Editor: Wael Alkhiary.
Author information Article notes Copyright and License information Disclaimer
aLiver Disease Diagnosis and Treatment Center, Bethune International Peace Hospital
bOrthopedic Research Institute, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China.
Correspondence: Fu-Biao Kang, Liver Disease Diagnosis and Treatment Center, Bethune International Peace Hospital, Shijiazhuang, Hebei, People’s Republic of China (e-mail: [email protected] ).
Received 2017 Jun 18; Revised 2017 Sep 28; Accepted 2017 Oct 12.
Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc.
This is an open access article distributed under the Creative Commons Attribution-NoDerivatives License 4.0, which allows for redistribution, commercial and non-commercial, as long as it is passed along unchanged and in whole, with credit to the author. http://creativecommons.org/licenses/by-nd/4.0

Abstract

Rationale:

Tumor chemotherapy could weaken the immune system of patients, which might enhance the body sensitivities to the exogenous pathogens, among which the hepatitis B virus (HBV) infection should be concerned because of the higher chances of infection and the severe outcomes, especially in East Asia. The titer level of hepatitis B surface antibody (HBsAb) higher than 10 IU/L is considered to offer immunocompetent individuals adequate protection. However, whether this level is enough to the tumor patients during chemotherapy remains unclear.

Patient concerns:

A 58-year-old female lymphoma patient was admitted to our hospital for asthenia, nausea, vomiting, and abnormal liver function lasting over 1 week and diagnosed as acute hepatitis B. The patient just finished a course of chemotherapy with CHOP regimen and had recent record (78.61 IU/L) of HBsAb positive. The only risk of infection we could found was that the patient had received blood transfusion shortly after chemotherapy from a donor who was recovering from an asymptomatic acute HBV infection.

Intervention:

The patient was administered with entecavir and glycyrrhizic acid agent, and then the disease was resolved successfully with hepatitis B surface antigen serological conversion.

Lessons:

Tumor chemotherapy might have weakened the immune system of the patient and enhanced the body sensitivities to hepatitis B virus, then led to the infection. We concluded that HBsAb-positive status, at least “weakly positive,” might not enough to provide protection for tumor patients on chemotherapy though this level was enough for health individuals and donors recuperating from subclinical acute hepatitis B might be another potential risk of HBV infection.

Keywords: chemotherapy, hepatitis B surface antigens, hepatitis B, lymphoma

1. Introduction

Tumor chemotherapy can weaken the immune system of patients, which not only induces the reactivation of latent infections, such as tuberculosis bacteria, hepatitis B virus, and cytomegalovirus, but also enhances the body sensitivities to the exogenous pathogens.[ 1 – 3 ] Different antitumor drugs have different influence mechanisms to the immune system, including myelosuppression, cytotoxicity, and antiproliferation and apoptosis-induced effects. The hepatitis B virus (HBV) infection is an issue that should be concerned during and after tumor chemotherapy, one reason is the higher chances of HBV infection in tumor patients, especially in East Asia, and another reason lies in the fact that HBV infection in immune compromised patients may lead to severe outcomes, such as liver failure.[ 1 , 4 ] Several studies have indicated that the tumor patients undergoing chemotherapy with inactive HBV infection, which is defined as negative or low virus load and normal liver enzyme could develop active viral replication and liver function damage.[ 2 ] The same findings even could be seen in patients with single hepatitis B core antibody (HBcAb) positive.[ 3 ] Tumor chemotherapy may impress the specific antiviral immune response and disrupt the balance of immune system and HBV. Studies found that common chemotherapy drugs, such as cyclophosphamide and prednisone, could suppress the HBV specific humoral and cellular immunity via different mechanisms.[ 5 – 6 ] Based on above, the risk of HBV infection is greatly increased during and after tumor chemotherapy. This is why the tumor patients undergoing chemotherapy were listed as one of high risk groups in the guidelines of China and world health organization and were recommended to accept prophylactic injection of HBV vaccine and monitor the antibody level to maintain effective immune protection.[ 7 – 8 ]

2. Case presentation

Here we report a 58-year-old Chinese woman with lymphoma was admitted to our hospital for asthenia, nausea, vomiting, and abnormal liver function lasting over 1 week. On admission, her serology was found to be positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg), negative for hepatitis B surface antibody (HBsAb) and negative for antibodies of hepatitis C virus, hepatitis A virus, hepatitis E virus, and human immunodeficiency virus. Her serum blood hepatitis B virus-deoxyribonucleic acid (HBVDNA) concentration was 2.05 × 106 copies/mL (limit of detection by polymerase chain reaction: 500 copies/mL). Her alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) levels were 581 U/L (normal 0–45 U/L), 324 U/L (normal 0–37U/L), and 38.4 μmol/L (normal 0–19.1 μmol/L), respectively. Her albumin, globulin, α-fetoprotein, and complete blood counts were all within the upper limits of normal. The enhanced computed tomography scan of the upper abdomen showed no abnormal imaging result. Based on typical clinical findings and previous history, the patient was diagnosed as acute hepatitis B. Then, the patient was administered for antiviral treatment with entecavir (0.5 mg daily) and glycyrrhizic acid agent. After 4 weeks’ treatment, her serum ALT and AST levels were decreased to almost normal limits and the HBVDNA concentration fell below detectable levels (500 copies/mL). Six weeks after entecavir therapy initiation, the patient presented E antigen serological conversion and her HBsAg disappeared after 9 weeks. Twelve weeks after treatment, her hepatitis B surface antibody (HBsAb) was tested for positive and then stopped entecavir administration (Fig. (Fig.11 ).

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Figure 1

Time courses of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatitis B virus-deoxyribonucleic acid (HBVDNA) levels, and hepatitis B serological markers (HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb). The time admitted to the hospital was considered as 0 week.

It’s worth noting that the patient had been vaccinated against hepatitis B 8 years ago and had reliable records of HBsAb positive. The latest test for HBsAb was nearly 8 weeks before hospitalization, when she was preparing to receive tumor chemotherapy. The exact titer was 78.6 IU/L, far more 7 times than 10 IU/L, the level which should provide enough protection and no need for revaccination according to the guidelines or position papers from the United States, China and World Health Organization (WHO).[ 7 – 9 ] In addition, her HBcAb and hepatitis B e antibody (HBeAb) levels were found to be negative, which suggested that HBsAb positive result was probably not to the result from postinfection immunity but vaccination.

About 4 months ago, the patient was diagnosed as diffuse large B-cell lymphoma and then received the CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisone) regimen. Significant side effects included anorexia, hair loss, and decreased leukocytes and platelets, whereas liver enzyme and bilirubin remained normal all the time. Symptomatic hepatitis B virus infection appears about 4 weeks after the chemotherapy ends. Calculating based on the patient’s medical history and the incubation period of hepatitis B virus infection, the time point when she required the infection should be during the chemotherapy or in a very short time after it. Then, we decided to investigate her medical history in details even earlier from her latest HBsAb tested positive. According to her narration, she rested at home most of the time without suspect contact and injury. No invasive manipulation was executed during this period. Only one platelet unit was transfused for improvement of thrombocytopenia during the course of chemotherapy, about 5 weeks before the patient developed obvious acute hepatitis related symptoms. The donor’s tests were recorded as bellows: normal liver function, weakly positive for HBsAb (6.82 IU/L), and negative for HBsAg, HBcAb, and HBeAb.

We then found the blood donor and asked for another investigation about 12 weeks after donating. The donor is a 28-year-old unmarried healthy male who had no history of hepatitis B and was not received hepatitis B virus vaccination. Like before, liver function test was normal and HBVDNA concentration was lower than the detectable limit (500 copies/mL). Surprisingly, obvious changes were found in serological markers of HBV, including HBsAb (255.82 IU/L), which was much higher than that tested 12 weeks ago, weakly positive HBcAb and positive HBeAb, which were all negative before blood donating. Based on above data, we concluded that the donor should be an asymptomatic acute HBV infected person and were recovering when he donated blood 12 weeks ago.

3. Discussion

Cyclophosphamide and doxorubicin are all nonspecific cell cycle antineoplastic drugs, which can interact with or inhibit intracellular DNA and RNA and block the proliferation of cells.[ 10 ] Quick proliferative cells, including tumor cells and marrow cells and immune cells are more sensitive to this kind of drugs. Vincristine can inhibit microtubule assembly and induce tubulin self-association into coiled spiral aggregates, which are prone to influencing the same kinds of fast dividing cells as cyclophosphamide. Prednisone, as a kind of glucocorticoids, is thought to have a general suppressive effect on immunity, especially on specific cellular and humoral immune responses.[ 6 ] Interestingly, however, The HBV serological protective marker HBsAb had been found much higher than 10 IU/mL before the patient accepted the chemotherapy, which is considered to have full protective effect on hepatitis B virus. Because of the retrospective analysis, we couldn’t understand if the HBsAb titer of this patient declined after chemotherapy. To evaluate whether tumor chemotherapy could exert influence on the level of antibody, we selected 5 diffuse large B-cell lymphoma patients with HBsAb positive, detected the antibody levels before and after they underwent chemotherapy with CHOP regimen. The small-sample study and the case report above were approved by the International Review Board of Bethune International Peace Hospital. Both written and oral consents were obtained before the patients were rolled, and relevant data provided to the researchers were anonymized. Surprisingly, no obvious changes of HBsAb levels were found before and after chemotherapy (Fig. (Fig.2A).2 A). We also detected HBsAg epitope-specific cytotoxic T lymphocyte (CTL) responses by enzyme-linked immunospot assay (ELISPOT), which were achieved by patients’ peripheral blood mononuclear cells (PBMCs) incubated with HBV S region peptide 335–343 (WLSLLVPFV, 20 μg/mL), recombinant human interleukin-2 (rhIL-2, 50IU/mL) along with proper concentrations of rhIL-7 and rhIL-15 for 48 hours. Results showed that dramatic drops of epitope-specific CTL responses could be found after tumor chemotherapy ended (Fig. (Fig.2B).2 B). In theory, chemotherapy drugs above can inhibit both innate and specific immune responses. But for the intracellular microorganisms, such as hepatitis B virus, specific cellular immunity may play a key role in keeping the virus from invading and replicating.[ 11 ] This may explain why tumor patients receiving chemotherapy are prone to be infected with hepatitis B virus. For the tumor patients undergoing chemotherapy, HBsAb level beyond 10 IU/mL might not be used as security criteria and could not provide adequately protective effect.

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Figure 2

The effects of chemotherapy on HBV specific humoral and cellular immune responses in HBsAb-positive diffuse large B-cell lymphoma patients. A, The changes of HBsAb titers (IU/mL) in lymphoma patients before and after chemotherapy (n = 5). B, ELISPOT data showing the number of IFN-γ SFCs per million peripheral blood mononuclear cells (PBMCs) on stimulation with HBV S region peptide 335–343 (WLSLLVPFV, 20 μg/mL), recombinant human interleukin-2 (rhIL-2, 50IU/mL) along with proper concentrations of rhIL-7 and rhIL-15 for 48 hours in lymphoma patients before and after chemotherapy (n = 5). P values are shown.

In the retrospective investigation, we highly doubt that this patient’s HBV infection was from a blood donor who was recuperating from subclinical HBV infection, for the patient received the donor’s platelets because of chemotherapy induced thrombocytopenia. Interestingly, the donor showed HBsAb weakly positive and liver function normal before blood donating, whereas when we investigated after 6 weeks dramatic increase of HBsAb titer was marked and HBcAb and HBeAb both turned positive. We concluded that the donor suffered from subclinical HBV infection might still carry a tiny amount of HBV virus in the peripheral blood though HBsAg serological convention had occurred. We usually think that the risk of HBV infection via blood transfusion mainly come from the window period of donors.[ 12 ] Although this case hinted that the recovery stage of acute HBV infection might be regarded as occult HBV infection and be another dangerous period to the blood donors. Occult HBV infection is very easily misdiagnosed because of HBsAg negative, even along with HBsAb positive. The higher requirements should be put forward to screen blood donors, especially for the immune compromised recipients, such as tumor patients receiving chemotherapy.

Though the weak HBsAb titer might be not enough to provide protection for tumor patients on chemotherapy, the effective protection level of HBsAb remains uncertain. Additional case reports and detailed mechanisms will be needed in the future.

4. Conclusions

The case reported here demonstrated that tumor chemotherapy with the CHOP regimen might have weakened the immune system of this lymphoma patient and enhanced the body sensitivities to hepatitis B virus, then led to the infection, though she had a reliable record of HBsAb positive. We concluded that HBsAb-positive status, at least “weakly positive,” might not enough to provide protection for tumor patients on chemotherapy though this level was enough for health individuals. This case also suggested that the blood from donors recuperating from subclinical acute hepatitis B might still be infectious and cannot easily be screened though general serological methods before donation. This period might be another potential risk of transfusion transmitted HBV infection besides “window phase.”

Footnotes

Abbreviations: ALT = alanine aminotransferase, AST = aspartate aminotransferase, CTL = cytotoxic T lymphocyte, ELISPOT = enzyme-linked immunospot assay, HBcAb = hepatitis B core antibody, HBeAg = hepatitis B e antigen, HBsAb = hepatitis B surface antibody, HBsAg = hepatitis B surface antigen, HBV = hepatitis B virus, HBVDNA = hepatitis B virus-deoxyribonucleic acid, PBMCs = peripheral blood mononuclear cells, TBIL = total bilirubin.

The authors declare no conflicts of interest.

References

[1] Yeo W, Chan PK, Zhong S, et al.
Frequency of hepatitis B virus reactivation in cancer patients undergoing cytotoxic chemotherapy: a prospective study of 626 patients with identification of risk factors. J Med Virol
2000;62:299–307. [ PubMed ]
[2] Voican CS, Mir O, Loulergue P, et al.
Hepatitis B virus reactivation in patients with solid tumors receiving systemic anticancer treatment. Ann Oncol
2016;27:2172–84. [ PubMed ]
[3] Papadopoulos N, Deutsch M, Manolakopoulos S, et al.
Efficacy of prophylactic antiviral therapy and outcomes in HBsAg-negative, anti-HBc-positive patients receiving chemotherapy: a real-life experience. Eur J Gastroenterol Hepatol
2017;29:56–60. [ PubMed ]
[4] Li HR, Huang JJ, Guo HQ, et al.
Comparison of entecavir and lamivudine in preventing hepatitis B reactivation in lymphoma patients during chemotherapy. J Viral Hepat
2011;18:877–83. [ PubMed ]
[5] Shurlygina AV, Mel’nikova EV, Trufakin VA.
Chronodependent effect of interleukin-2 on mouse spleen cells in the model of cyclophosphamide immunosuppression. Bull Exp Biol Med
2015;158:471–4. [ PubMed ]
[6] Ashwell JD, Lu FW, Vacchio MS.
Glucocorticoids in T cell development and function. Annu Rev Immunol
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[7] Hou JL, lai W.
The guideline of prevention and treatment for chronic hepatitis B: a 2015 update. Zhonghua Gan Zang Bing Za Zhi
2015;23:888–905. [ PubMed ]
[8] U.S. Public Health Service. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis. MMWR Recomm Rep
2001;50:1–52. [ PubMed ]
[9] WHO Publication. Hepatitis B vaccines: WHO position paper–recommendations. Vaccine
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[10] Rinaldi L, Perini P, Calabrese M, et al.
Cyclophosphamide as second-line therapy in multiple sclerosis: benefits and risks. Neurol Sci
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[11] Guidotti LG, Isogawa M, Chisari FV.
Host-virus interactions in hepatitis B virus infection. Curr Opin Immunol
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[12] Allain JP, Cox L.
Challenges in hepatitis B detection among blood donors. Curr Opin Hematol
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Hepatitis B Blood Tests

iStock 80254013 MEDIUMThe “Hepatitis B Panel” of Blood Tests

Only one sample of blood is needed for a hepatitis B blood test, but the “Hepatitis B Panel” includes three parts. All three test results are needed to fully understand whether a person is infected or not. Below is an explanation of the 3-part “Hepatitis B Panel” of blood test results.

  1. HBsAg (Hepatitis B surface antigen) – A “positive” or “reactive” HBsAg test result means that the person is infected with hepatitis B. This test can detect the actual presence of the hepatitis B virus (called the “surface antigen”) in your blood. If a person tests “positive,” then further testing is needed to determine if this is a new “acute” infection or a “chronic” hepatitis B infection. A positive HBsAg test result means that you are infected and can spread the hepatitis B virus to others through your blood.
  2. anti-HBs or HBsAb (Hepatitis B surface antibody) – A “positive” or “reactive” anti-HBs (or HBsAb) test result indicates that a person is protected against the hepatitis B virus. This protection can be the result of receiving the hepatitis B vaccine or successfully recovering from a past hepatitis B infection. This test is not routinely included in blood bank screenings. A positive anti-HBs (or HBsAb) test result means you are “immune” and protected against the hepatitis B virus and cannot be infected. You are not infected and cannot spread hepatitis B to others.
  3. anti-HBc or HBcAb (Hepatitis B core antibody) – A “positive” or “reactive” anti-HBc (or HBcAb) test result indicates a past or current hepatitis B infection. The core antibody does not provide any protection against the hepatitis B virus (unlike the surface antibody described above). This test can only be fully understood by knowing the results of the first two tests (HBsAg and anti-HBs). A positive anti-HBc (or HBcAb) test result requires talking to your health care provider for a complete explanation of your hepatitis B status.