Use of OKT3 is associated with early and severe recurrence of hepatitis C after liver transplantation

Hugo R. Rosen, Christopher R. Shackleton, Lisa Higa, Ian M. Gralnek, Dana A. Farmer, Sue V. McDiarmid, Curtis Holt, D. Pharm, Klaus J. Lewin, Ronald W. Busuttil, Paul Martin

Research output: Contribution to journalArticle

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Abstract

Objective: To determine whether increased immunosuppression is a contributor to poor outcome in hepatitis C-infected orthotopic liver transplant (OLT) recipients, we retrospectively analyzed the consequences of using OKT3 in our program for steroid-resistant rejection (SRR). Methods: We compared the histological recurrence of HCV in two contemporary cohorts of OLT recipients. Group 1 consisted of HCV-positive patients who received OKT3 for SRR (n = 19). Group 2 (n = 33) consisted of age-, gender-, and initial immunosuppression-matched HCV-positive controls who were treated with at least one steroid pulse for acute cellular rejection but who did not require treatment with OKT3. Liver biopsies were obtained per protocol within the first month and as necessary to evaluate abnormalities in serum liver chemistries. Results: Mean and median follow-up were comparable for the two groups. Recurrence of HCV was diagnosed by histological verification and was documented in 16 of 19 (84.2%) group 1 patients versus 17 of 33 (51.5%) group 2 patients (p = 0.03). The interval to recurrence was significantly shorter in patients who received OKT3 (p = 0.028). Logistic regression identified OKT3 as a significant risk factor for the recurrence of HCV within the first year post-OLT (p = 0.0004). The histological severity score, based on the most recent liver biopsy at long-term follow-up or the explant biopsy if the patient required retransplantation, was significantly higher in group 1. Moreover, cirrhosis was demonstrable in a greater proportion of allografts in patients who had received OKT3 at some point (26.3% vs. 6%, p = 0.028). Long- term follow-up revealed a trend toward higher alanine aminotransferase levels (p = 0.05) and total bilirubin (p = 0.08) in group 1 patients. Conclusions: Our data suggest that allograft hepatitis in patients with preexisting HCV occurs earlier and with greater severity in patients treated with OKT3 for SRR, compared with age-, gender-, and initial immunosuppression-matched contemporary controls. Treatment of SRR with OKT3 may jeopardize long-term allograft function and survival in HCV-infected recipients by enhancing viral hepatitis recurrence. Clearly, the recognition of recurrent HCV and differentiation from acute cellular rejection remains a crucial issue in managing the OLT recipient with HCV.

Original languageEnglish
Pages (from-to)1453-1457
Number of pages5
JournalAmerican Journal of Gastroenterology
Volume92
Issue number9
StatePublished - Oct 9 1997
Externally publishedYes

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Muromonab-CD3
Hepatitis C
Liver Transplantation
Recurrence
Liver
Steroids
Immunosuppression
Allografts
Biopsy
Hepatitis
Alanine Transaminase
Bilirubin
Fibrosis
Logistic Models
Transplants
Survival

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Rosen, H. R., Shackleton, C. R., Higa, L., Gralnek, I. M., Farmer, D. A., McDiarmid, S. V., ... Martin, P. (1997). Use of OKT3 is associated with early and severe recurrence of hepatitis C after liver transplantation. American Journal of Gastroenterology, 92(9), 1453-1457.

Use of OKT3 is associated with early and severe recurrence of hepatitis C after liver transplantation. / Rosen, Hugo R.; Shackleton, Christopher R.; Higa, Lisa; Gralnek, Ian M.; Farmer, Dana A.; McDiarmid, Sue V.; Holt, Curtis; Pharm, D.; Lewin, Klaus J.; Busuttil, Ronald W.; Martin, Paul.

In: American Journal of Gastroenterology, Vol. 92, No. 9, 09.10.1997, p. 1453-1457.

Research output: Contribution to journalArticle

Rosen, HR, Shackleton, CR, Higa, L, Gralnek, IM, Farmer, DA, McDiarmid, SV, Holt, C, Pharm, D, Lewin, KJ, Busuttil, RW & Martin, P 1997, 'Use of OKT3 is associated with early and severe recurrence of hepatitis C after liver transplantation', American Journal of Gastroenterology, vol. 92, no. 9, pp. 1453-1457.
Rosen HR, Shackleton CR, Higa L, Gralnek IM, Farmer DA, McDiarmid SV et al. Use of OKT3 is associated with early and severe recurrence of hepatitis C after liver transplantation. American Journal of Gastroenterology. 1997 Oct 9;92(9):1453-1457.
Rosen, Hugo R. ; Shackleton, Christopher R. ; Higa, Lisa ; Gralnek, Ian M. ; Farmer, Dana A. ; McDiarmid, Sue V. ; Holt, Curtis ; Pharm, D. ; Lewin, Klaus J. ; Busuttil, Ronald W. ; Martin, Paul. / Use of OKT3 is associated with early and severe recurrence of hepatitis C after liver transplantation. In: American Journal of Gastroenterology. 1997 ; Vol. 92, No. 9. pp. 1453-1457.
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abstract = "Objective: To determine whether increased immunosuppression is a contributor to poor outcome in hepatitis C-infected orthotopic liver transplant (OLT) recipients, we retrospectively analyzed the consequences of using OKT3 in our program for steroid-resistant rejection (SRR). Methods: We compared the histological recurrence of HCV in two contemporary cohorts of OLT recipients. Group 1 consisted of HCV-positive patients who received OKT3 for SRR (n = 19). Group 2 (n = 33) consisted of age-, gender-, and initial immunosuppression-matched HCV-positive controls who were treated with at least one steroid pulse for acute cellular rejection but who did not require treatment with OKT3. Liver biopsies were obtained per protocol within the first month and as necessary to evaluate abnormalities in serum liver chemistries. Results: Mean and median follow-up were comparable for the two groups. Recurrence of HCV was diagnosed by histological verification and was documented in 16 of 19 (84.2{\%}) group 1 patients versus 17 of 33 (51.5{\%}) group 2 patients (p = 0.03). The interval to recurrence was significantly shorter in patients who received OKT3 (p = 0.028). Logistic regression identified OKT3 as a significant risk factor for the recurrence of HCV within the first year post-OLT (p = 0.0004). The histological severity score, based on the most recent liver biopsy at long-term follow-up or the explant biopsy if the patient required retransplantation, was significantly higher in group 1. Moreover, cirrhosis was demonstrable in a greater proportion of allografts in patients who had received OKT3 at some point (26.3{\%} vs. 6{\%}, p = 0.028). Long- term follow-up revealed a trend toward higher alanine aminotransferase levels (p = 0.05) and total bilirubin (p = 0.08) in group 1 patients. Conclusions: Our data suggest that allograft hepatitis in patients with preexisting HCV occurs earlier and with greater severity in patients treated with OKT3 for SRR, compared with age-, gender-, and initial immunosuppression-matched contemporary controls. Treatment of SRR with OKT3 may jeopardize long-term allograft function and survival in HCV-infected recipients by enhancing viral hepatitis recurrence. Clearly, the recognition of recurrent HCV and differentiation from acute cellular rejection remains a crucial issue in managing the OLT recipient with HCV.",
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AU - Rosen, Hugo R.

AU - Shackleton, Christopher R.

AU - Higa, Lisa

AU - Gralnek, Ian M.

AU - Farmer, Dana A.

AU - McDiarmid, Sue V.

AU - Holt, Curtis

AU - Pharm, D.

AU - Lewin, Klaus J.

AU - Busuttil, Ronald W.

AU - Martin, Paul

PY - 1997/10/9

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N2 - Objective: To determine whether increased immunosuppression is a contributor to poor outcome in hepatitis C-infected orthotopic liver transplant (OLT) recipients, we retrospectively analyzed the consequences of using OKT3 in our program for steroid-resistant rejection (SRR). Methods: We compared the histological recurrence of HCV in two contemporary cohorts of OLT recipients. Group 1 consisted of HCV-positive patients who received OKT3 for SRR (n = 19). Group 2 (n = 33) consisted of age-, gender-, and initial immunosuppression-matched HCV-positive controls who were treated with at least one steroid pulse for acute cellular rejection but who did not require treatment with OKT3. Liver biopsies were obtained per protocol within the first month and as necessary to evaluate abnormalities in serum liver chemistries. Results: Mean and median follow-up were comparable for the two groups. Recurrence of HCV was diagnosed by histological verification and was documented in 16 of 19 (84.2%) group 1 patients versus 17 of 33 (51.5%) group 2 patients (p = 0.03). The interval to recurrence was significantly shorter in patients who received OKT3 (p = 0.028). Logistic regression identified OKT3 as a significant risk factor for the recurrence of HCV within the first year post-OLT (p = 0.0004). The histological severity score, based on the most recent liver biopsy at long-term follow-up or the explant biopsy if the patient required retransplantation, was significantly higher in group 1. Moreover, cirrhosis was demonstrable in a greater proportion of allografts in patients who had received OKT3 at some point (26.3% vs. 6%, p = 0.028). Long- term follow-up revealed a trend toward higher alanine aminotransferase levels (p = 0.05) and total bilirubin (p = 0.08) in group 1 patients. Conclusions: Our data suggest that allograft hepatitis in patients with preexisting HCV occurs earlier and with greater severity in patients treated with OKT3 for SRR, compared with age-, gender-, and initial immunosuppression-matched contemporary controls. Treatment of SRR with OKT3 may jeopardize long-term allograft function and survival in HCV-infected recipients by enhancing viral hepatitis recurrence. Clearly, the recognition of recurrent HCV and differentiation from acute cellular rejection remains a crucial issue in managing the OLT recipient with HCV.

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