Serological Profile of Pretransplantation Liver Patients

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Serological Profile of Pretransplantation Liver Patients I.d.F.S.F. Boin, Y.L. Boteon, R.S.B. Stucchi, M.I.W. Pereira, T.C.B. Portugal, and E.Y. Udo ABSTRACT Introduction. A liver transplantation is the first choice of treatment for patients with hepatic insufficiency due to chronic diseases. Infections in the postoperative period represent one of the main causes of mortality in these cases. However, few articles have evaluated the predominance of certain infectious diseases and their influence on postoperative mortality. Methods. We retrospectively evaluated the medical records of 236 patients who underwent liver transplantation from January 1997 to January 2007. In these records we checked the serological profiles for these diseases: toxoplasmosis, syphilis, human T lymphotropic virus (HTLV) I and II infection, Chagas disease, hepatitis A, hepatitis B, hepatitis C, paracoccidioidomycosis, tuberculosis, acquired immunodeficiency syndrome, cytomegalovirus (CMV), and mononucleosis (Epstein-Barr virus [EBV]). The statistical analysis was performed by table frequencies. Results. CMV showed positivity (CMV-IgG) in 94.7% of patients, 95.8% for EBV, 33.3% for toxoplasmosis, 47.9% for hepatitis C, and 5% for hepatitis B. Conclusion. Our analysis showed the importance of serological investigations and diagnostic examinations before the transplantation procedure, seeking to minimize possible reactivation of the disease after the use of immunosuppression drugs, particularly in the first 6 months after transplantation, or even to avoid a primary infection. RTHOTOPIC LIVER transplantation (OLT) is the treatment of first choice for patients with liver failure due to chronic hepatic illnesses. Nowadays, the majority of services report survival rates of over 85% after 1 year with a good quality of life.1,2 Infections in postoperative patients undergoing OLT are a common cause of morbidity and mortality. One study reported a mortality rate of 26% in the postoperative period with 88% of deaths associated with infections.1,2 However, few analyses have reported the prevalence of

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prior infectious illnesses and their influence on morbidity and mortality in the posttransplantation period. Several infectious illnesses can be evaluated by serology in the preoperative period. Toxoplasmosis caused by ToxoFrom the Unit of Liver Transplantation, State University of Campinas, Unicamp-SP/Brazil. Address reprint requests to Ilka Boin, Rua Aldo Oliveira Barbosa 184, Campinas/SP, Brazil CEP 13086-030. E-mail: [email protected] 0041-1345/10/$–see front matter doi:10.1016/j.transproceed.2010.01.011 491

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plasma gondi, a protozoan found world-wide, represents a risk for death of patients with immunodeficiency acquired due to immune-depression therapy. It can develop in kidney, heart, or liver recipients, although the described cases are few after OLT. However, when reported, it has been associated with fatal illness, pneumonia, and retinal injury.3 Cytomegalovirus (CMV) is the biggest cause of morbidity among solid organ transplantation patients causing serious manifestations in CMV-immunoglobulin (IgG) negative recipients or when recipient reactivation occurs after latent infection. Syphilis caused by Treponema pallidum is acquired through sexual contact or the hematogenic pathway. Patients with a depressed immune system are the biggest risk group for the development of tertiary syphilis if the illness is not treated. No syphilis transmission case from the transplantation of solid organs has been noted; however, the risk of syphilis from donation is approximately 0.15%.4 Human T lymphotropic virus (HTLV) I and II are retroviruses. The immune depression after transplantation increases the risk of infection, reduces the latency, and increases the clinical development of infection.5 Chagas disease is an endemic zoonosis of South America caused by the protozoan Trypanosoma cruzi. It has been estimated that since 2002 there have been no more cases of transmission of the illness from donated organs.6 A recipient with a positive serology can have a reinfection illness in a serious form in the postoperative period. Epstein-Barr virus (EBV) is a herpesvirus whose latency has a long life in B lymphocytes; it is a cause of morbidity and mortality after OLT.7,8 Hepatitis A virus (HAV) is caused by an RNA virus with oral-fecal transmission. Three cases have been described of recurrent HAV after OLT.9 If the liver recipient has a negative serology, vaccination is required before surgery. Hepatitis B virus (HBV) often leads to liver cirrhosis and terminal hepatic illness. Currently, the treatment of HBV permits these patients to undergo transplantation with a risk of hepatitis reactivation. Hepatitis C virus (HCV) in the United States causes more than 50% of all OLTs.10 However, the presence of the HCV infection (anti-HCV positivity) leads to reinfection among 20%– 40% of recipients after OLT with gradual graft damage and cirrhosis over the following 5 to 10 years.11 Paracoccidioidomycosis is a common fungal infection in the Latin American population, although its occurrence in organ transplant recipients is rare with only 2 described cases in the literature, and 1 of reactivation as a complication some years after the procedure.12 Tuberculosis represents a serious complication in solid organ transplants. Its occurrence rate after OLT is from 0.9%–2.3%.13 Human immunodeficiency virus (HIV) infection was an absolute contra-indication to OLT due to the bad prognosis attributed to these patients. Recent studies have found that the results of OLT in these patients are good with no evidence of acceleration of the infection after the procedure.14 The objective of this present study was to determine the serological profile of patients undergoing OLT.

BOIN, BOTEON, STUCCHI ET AL

METHODS The medical records of 236 patients undergoing OLT before December 2008 were evaluated retrospectively. The data were collected before the transplantation or obtained from the Organ Procurement Organization. The profile was composed of serological tests of HAV, HBV, and HCV; paracoccidioidomycosis; CMV, syphilis; HTLV I and II; Chagas disease; T gondii, and a positive test for tuberculosis was considered when the result of the Mantoux skin test was larger than 10 mm. The tests were classified as reactive or non-reactive, in accordance with laboratory data performed by the Service of Clinical Pathology of the HC-Unicamp.

RESULTS

Of the 236 patients, 68.2% were males and 31.8% were females of overall average age of 44 years. The positive test results were as follows: 95.5% HAV; 5% HBsAg, 36.7% anti-HBs and 22.4% anti-HBc; 47.9% antiHCV; 0.4% Chagas disease; 66.7% toxoplasmosis; 1.2% syphilis; 94.7% CMV-IgG; 0.8% paracoccidioidomycosis; and 95.8% EBV-IgG. The serology for acquired immunodeficiency syndrome (AIDS) caused by HIV infection was negative in all of the patients. HTLV I and II serologies were positive in 0.8%, and 2.8% had Mantoux test results ⬎10 mm. We observed disease recurrences after OLT; 47% had evidence of HCV histological; 11% had CMV and 2.8% had HVB. Only 1 patient had HVB recurrence after the surgery. DISCUSSION

The results for HBV were similar to the literature and the presence of anti-HBc and anti-HBs in solid organ recipients may be a protective factor conferring resistance to this infection in the postoperative period.15,16 The high prevalence (36.7%) of patients reactive with anti-HBs can be attributed to the HBV vaccination of this population. The more prevalent pathology observed in this study was HCV reaching a frequency of 47.92%. It is the most common etiology for OLT. HCV recurrence is is practically universal and can lead to organ damage.16 An association between alterations in organ prognosis and postoperative survival has not been described when the donor is HCVpositive even when the recipient is HCV-negative.16 CMV infection is described as the most frequent infectious complication in OLT recipients.16,17–20 In our sample 94.7% of the patients were infected. Although the number of seronegative recipients was low for this virus, there is the possibility of CMV reactivation mainly when the CMVnegative recipients received a liver from a positive donor associated with immunosuppressive therapy or antirejection treatment. The occurrence of Mycobacterium tuberculosis varies among different regions; the estimated frequency ranges from 0.7%–2.3% with a mortality rate of up to 30%.21 Our results showed 2.8% positivity for tuberculosis before transplantation; these patients were treated with isoniazid. Only 1 patient had disease recurrence after surgery.

SEROLOGICAL PROFILE

EBV infects approximately 95% of the world-wide population.16 The present study showed a frequency of 95.8%. The primary infection occurring in recipients without previous contact with EBV receiving organs from infected donors can cause uncontrolled proliferation of infected B cells leading to posttransplantation lymphoproliferative disease. These patients must be monitored for the risk of development of this condition, although the probability remains low.16 It is estimated that 15.8% of people from 12 to 49 years of age in the United States are seropositive for toxoplasmosis. Transmission to the liver transplant is extremely uncommon, although it can be fatal, with 4 cases confirmed to be related to the organ donor.18,19 In the present study, the T gondii frequency was 33.3%, which is a sufficiently high for concern about the occurrence of a primary infection whose diagnosis is rare, but should be taken into account when there is an early postoperative febrile state.18,19 We observed a low occurrence of HTLV I and II, HIV, tuberculosis, AIDS, syphilis, Chagas disease, and paracoccidioidomycosis similar to the literature.2,21 In conclusion, evaluating serologies before transplantation can help to minimize possible reinfections or primary infections after immunosuppressive therapy in organ transplantation.

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