The purpose of this study was to analyze the impact of OKT3 on the frequency and severity of CMV and herpes simplex virus (HSV) infections in adult liver transplant recipients. OKT3 treatment is associated with a higher risk of disseminated CMV infection, particularly in patients with primary CMV infection. It also increased the frequency of symptomatic HSV infection in HSV-seropositive liver transplant recipients

Dummer, JS

Ho, M

Kusne, S

Makowka, L

Singh, N

Starzl, TE

English

PubMed

D-Scholarship@Pitt

ler proved to have (he three patients \Vall perhaps un ',erious side effects ,ive candida infect: '11 IOn IS I ustrated by the fa tents with no ong . ct OlOg hen the diagnosis . . Was dlons. We feel that the ! protocol are so gOOd Iy comparing Amph-e \mph-B prophylaXis' h. IS .lpS unet Ical. Instead le last month widened mph-B prophylaxis to .plant can~idates who .lr neomycIn treatment vma. 'i: t!ct of lhqP~~~~~n~~~~megaloDirus and Herpes Simplex Virus Infections After Liver Transplantation N. Singh, J.S. Dummer, S. Kusne, L. Makowka. T.E. Starzl, and M. Ho I NFECTION with the herpes group of viruses. in particular, cytomegalovirus (CMV), is a significant cause of morbidity and mortality in organ transplant recipients. Immunosuppressive regimens containing anti-thymocyte globulin (ATG) have been shown to be associated with a higher frequency of symptomatic CMV disease.' Another anti-lymphocyte preparation, OKT3, is a murine monoclonal antibody that has proved effica-cious in treating allograft rejection. The pur-pose of this study was to analyze the impact of OKT3 on the frequency and severity of CMV and herpes simplex virus (HSV) infections in adult liver transplant recipients. METHODS The study population consisted of 121 consecutive adult patients who underwent orthotopic liver transplan-tation at our institution between January 1984 and Sep-tember 1985, who survived for at least 72 hours postoper-alively, and for whom preoperative serum samples were available. Standard immunosuppression consisted of cyclosporine (CsA) and corticosteroids (20 mg/d ofpred-nisone). Rejection episodes were treated with additional steroids. Azathioprine (AzA) was usually administered to reduce the CsA dosage in patients experiencing nephro-toxicity. For more severe degrees of rejection OKT3 was administered. CMV infection was diagnosed by virus isolation or by changes in serological ti ter (seroconversion or a fourfold or greater rise CMV antibody titer). Ninety-three patients were evaluable for CMV infection. Clinical diseases caused by CMV were of the following types: febrile viral syndrome, localized CMV disease, and dis-seminated CMV disease. HSV infection was defined as the presence of typical symptomatic oral/ genital ulcers or histological evidence of tissue invasion. Ninety-five of 121 patients were seropositive for HSV antibodies pretrans-plant. RESULTS Table 1 shows the relationship of symptom-atic CMV disease to the immunosuppressives used. Thirty-two of 53 patients who received OKT3 developed CMV infection. Thirteen (40%) or these developed symptoms. including seven with a viral syndrome and six with disseminated CMV disease, Five of six patients with disseminated CMV disease had primary CMV infection. Of 23 patients with CMV infection who did not receive OKT3, 14 (60%) were symptomatic, including nine with a viral syndrome and five with localized CMV disease. Thus the number of symptomatic patients among those who received OKT3 did not differ significantly from those who did not receive OKT3 (40% v 60%). However. dis-seminated CMV infection occurred in six (\ 8%) of 32 patients who received OKT3 but in none of 23 patients who did not get OKT3 (P = .06). Of 95 recipients seropositive for HSV anti-bodies. 39 (41 %) developed typical mucocuta-neous HSV lesions including 29 patients with oral HSV and ten with genital HSV. Two patients developed HSV esophagitis, and two had HSV hepatitis. The group treated with OKT3 had more symptomatic illness due to HSV (22 of 54, 54%) as compared with patients who did not get OKT3 (13 of 41, 32%) (P = .05). DISCUSSION AND CONCLUSION Several studies have documented increased morbidity associated with CMV infection in renal transplant patients receiving ATG. Our data show that the frequency of overall symp-tomatic CMV disease was not influenced by OKT3. OKT3, however, appeared to increase From the Departments of Medicine and Surgery. University of Pittsburgh School of Medicine. Supported in part by National Institutes of Health Grant 1 ROI AI 19377. Address reprint requests to M. Ho. MD, Crabtree Hail A427. University of Pittsburgh, Pittsburgh, PA 15261. ©1988 by Grune & Strallon, Inc. 0041-1345/88/2001-1241$03.00/0 Transplantation Proceedings. Vol XX. No 1. Suppl 1 (February!. 1988: pp 661-662 661 662 Table 1. Relationship of Symptomatic CMV Disease to Additional Immunosuppression Additional Total Evaluable No. With Viral No. With Localized Immunosuppression Patients No. Infected No. Symptomatic Syndrome CMV Disease OKT3- 53 32- 13 (40%) 7 0 6t No OKT3 40 23t 14 (60%) 9 5 0 Total patients 93 55 27 16 5 6 - All patients treated with OKT3 got additional steroids; 1 7 of 32 infected patients also received Aza. tProportion of patients with disseminated CMV disease treated with OKT3 compared with patients who did not OKT3 (P - .06). tTwenty patients received additional steroids only. two received additional Aza only. and one patient did not race;... additional immunosuppression. the risk of disseminated CMV disease, partic-ularly in patients with primary CMV infec-tion. These findings may help to identify patients at highest risk for severe or fatal CMV infection. As reported in other organ allograft recip-ient groups, most HSV infections are due to reactivation of latent virus.2 A few studies have correlated the use of antilymphocyte preparations with an increased risk of reacti-vation and symptomatic illness due to HSV. Similar data are not available for OKT3, but we observed a higher frequency symptomatic HSV infections in OKT3. treated, seropositive patients. Most of these were mucocutaneous infections and therefore not life threatening. In conclusion, OKT3 treatment is asso-ciated with a higher risk of disseminated CMV infection, particularly in patients with primary CMV infection. It also increased the frequency of symptomatic HSV infection in HSV -seropositive liver transplant recipients. REFERENCES I. Bia Ml, Andiman W, Gaudio K, et al: Transplanta-tion 40:610, 1985 2. Armstrong lA, Evans AS, Rao N, et al: Infect Immun 14:970, 1976 exper tion a Expe Ran 22 kg I portojl sian. f intravc autotr: mens < 14,21 detail! ogy w: Clini TWI liver c prima sclera synth, all ha cr pal with first used mg/~ week startc perm Tram 

Impact of OKT3 therapy on cytomegalovirus and herpes simplex virus infections after liver transplantation

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Impact of OKT3 therapy on cytomegalovirus and herpes simplex virus infections after liver transplantation

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