Risk for immune-mediated graft dysfunction in liver transplant recipients with recurrent HCV infection treated with pegylated interferon

Josh Levitsky, Maria Isabel Fiel, John P. Norvell, Edward Wang, Kymberly D. Watt, Michael P. Curry, Sumeet Tewani, Timothy M McCashland, Maarouf A. Hoteit, Abraham Shaked, Samuel Saab, Amanda C. Chi, Amy Tien, Thomas D. Schiano

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Abstract

Background & Aims: Patients with recurrent hepatitis C virus infection treated with pegylated interferon (PEG) after liver transplantation can develop severe immune-mediated graft dysfunction (IGD) characterized by plasma cell hepatitis or rejection. Methods: We conducted a multicenter case-control study of 52 liver transplant recipients with hepatitis C to assess the incidence of, risk factors for, and outcomes of PEG-IGD. Data from each patient were compared with those from 2 matched patients who did not develop PEG-IGD (n = 104). We performed a multivariate analysis of risk factors and analyzed treatment and outcomes of graft dysfunction subtypes. Results: Overall incidence of PEG-IGD during a 10-year study period was 7.2%. Risk factors included no prior PEG therapy (odds ratio = 5.3; P <.0001), therapy with PEGα-2a (odds ratio = 4.7; P =.03), and immune features (mainly plasma cell hepatitis) on pre-PEG therapy liver biopsies (odds ratio = 3.9; P =.005). The PEG-IGD group had lower long-term patient (61.5% vs 91.3% of controls) and graft (38.5% vs 85.6% of controls) survival and higher rates of retransplantation (34.6% vs 6.7% of controls) (all, P <.0001), without increases in sustained virologic response. Variables associated with increased mortality included acute rejection as the PEG-IGD sub-type (hazard ratio [HR] = 2.4; P =.002), a high level of alkaline phosphatase at PEG initiation (HR = 1.003; P =.005), and lack of a sustained virologic response (HR = 3.3; P =.04). Variables associated with graft failure included a high level of alkaline phosphatase at PEG initiation (HR = 1.002; P =.04) and lack of a sustained virologic response (HR = 2.1; P =.04). Conclusions: PEG-IGD has high morbidity and mortality and is not associated with increased rates of virologic response. It is important to avoid PEG therapy in liver transplant recipients with specific clinical, biochemical, and histologic risk factors for PEG-IGD.

Original languageEnglish (US)
JournalGastroenterology
Volume142
Issue number5
DOIs
StatePublished - Jan 1 2012

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Interferons
Liver Diseases
Transplants
Interferon-gamma
Infection
Odds Ratio
Plasma Cells
Hepatitis
Alkaline Phosphatase
Liver
Transplant Recipients
Mortality
Incidence
Virus Diseases
Therapeutics
Hepatitis C
Hepacivirus
Liver Transplantation
Case-Control Studies
Multivariate Analysis

Keywords

  • Immune Response
  • Immunosuppression
  • Organ Transplantation
  • Viral Hepatitis

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Risk for immune-mediated graft dysfunction in liver transplant recipients with recurrent HCV infection treated with pegylated interferon. / Levitsky, Josh; Fiel, Maria Isabel; Norvell, John P.; Wang, Edward; Watt, Kymberly D.; Curry, Michael P.; Tewani, Sumeet; McCashland, Timothy M; Hoteit, Maarouf A.; Shaked, Abraham; Saab, Samuel; Chi, Amanda C.; Tien, Amy; Schiano, Thomas D.

In: Gastroenterology, Vol. 142, No. 5, 01.01.2012.

Research output: Contribution to journalArticle

Levitsky, J, Fiel, MI, Norvell, JP, Wang, E, Watt, KD, Curry, MP, Tewani, S, McCashland, TM, Hoteit, MA, Shaked, A, Saab, S, Chi, AC, Tien, A & Schiano, TD 2012, 'Risk for immune-mediated graft dysfunction in liver transplant recipients with recurrent HCV infection treated with pegylated interferon', Gastroenterology, vol. 142, no. 5. https://doi.org/10.1053/j.gastro.2012.01.030
Levitsky, Josh ; Fiel, Maria Isabel ; Norvell, John P. ; Wang, Edward ; Watt, Kymberly D. ; Curry, Michael P. ; Tewani, Sumeet ; McCashland, Timothy M ; Hoteit, Maarouf A. ; Shaked, Abraham ; Saab, Samuel ; Chi, Amanda C. ; Tien, Amy ; Schiano, Thomas D. / Risk for immune-mediated graft dysfunction in liver transplant recipients with recurrent HCV infection treated with pegylated interferon. In: Gastroenterology. 2012 ; Vol. 142, No. 5.
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abstract = "Background & Aims: Patients with recurrent hepatitis C virus infection treated with pegylated interferon (PEG) after liver transplantation can develop severe immune-mediated graft dysfunction (IGD) characterized by plasma cell hepatitis or rejection. Methods: We conducted a multicenter case-control study of 52 liver transplant recipients with hepatitis C to assess the incidence of, risk factors for, and outcomes of PEG-IGD. Data from each patient were compared with those from 2 matched patients who did not develop PEG-IGD (n = 104). We performed a multivariate analysis of risk factors and analyzed treatment and outcomes of graft dysfunction subtypes. Results: Overall incidence of PEG-IGD during a 10-year study period was 7.2{\%}. Risk factors included no prior PEG therapy (odds ratio = 5.3; P <.0001), therapy with PEGα-2a (odds ratio = 4.7; P =.03), and immune features (mainly plasma cell hepatitis) on pre-PEG therapy liver biopsies (odds ratio = 3.9; P =.005). The PEG-IGD group had lower long-term patient (61.5{\%} vs 91.3{\%} of controls) and graft (38.5{\%} vs 85.6{\%} of controls) survival and higher rates of retransplantation (34.6{\%} vs 6.7{\%} of controls) (all, P <.0001), without increases in sustained virologic response. Variables associated with increased mortality included acute rejection as the PEG-IGD sub-type (hazard ratio [HR] = 2.4; P =.002), a high level of alkaline phosphatase at PEG initiation (HR = 1.003; P =.005), and lack of a sustained virologic response (HR = 3.3; P =.04). Variables associated with graft failure included a high level of alkaline phosphatase at PEG initiation (HR = 1.002; P =.04) and lack of a sustained virologic response (HR = 2.1; P =.04). Conclusions: PEG-IGD has high morbidity and mortality and is not associated with increased rates of virologic response. It is important to avoid PEG therapy in liver transplant recipients with specific clinical, biochemical, and histologic risk factors for PEG-IGD.",
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AU - Levitsky, Josh

AU - Fiel, Maria Isabel

AU - Norvell, John P.

AU - Wang, Edward

AU - Watt, Kymberly D.

AU - Curry, Michael P.

AU - Tewani, Sumeet

AU - McCashland, Timothy M

AU - Hoteit, Maarouf A.

AU - Shaked, Abraham

AU - Saab, Samuel

AU - Chi, Amanda C.

AU - Tien, Amy

AU - Schiano, Thomas D.

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N2 - Background & Aims: Patients with recurrent hepatitis C virus infection treated with pegylated interferon (PEG) after liver transplantation can develop severe immune-mediated graft dysfunction (IGD) characterized by plasma cell hepatitis or rejection. Methods: We conducted a multicenter case-control study of 52 liver transplant recipients with hepatitis C to assess the incidence of, risk factors for, and outcomes of PEG-IGD. Data from each patient were compared with those from 2 matched patients who did not develop PEG-IGD (n = 104). We performed a multivariate analysis of risk factors and analyzed treatment and outcomes of graft dysfunction subtypes. Results: Overall incidence of PEG-IGD during a 10-year study period was 7.2%. Risk factors included no prior PEG therapy (odds ratio = 5.3; P <.0001), therapy with PEGα-2a (odds ratio = 4.7; P =.03), and immune features (mainly plasma cell hepatitis) on pre-PEG therapy liver biopsies (odds ratio = 3.9; P =.005). The PEG-IGD group had lower long-term patient (61.5% vs 91.3% of controls) and graft (38.5% vs 85.6% of controls) survival and higher rates of retransplantation (34.6% vs 6.7% of controls) (all, P <.0001), without increases in sustained virologic response. Variables associated with increased mortality included acute rejection as the PEG-IGD sub-type (hazard ratio [HR] = 2.4; P =.002), a high level of alkaline phosphatase at PEG initiation (HR = 1.003; P =.005), and lack of a sustained virologic response (HR = 3.3; P =.04). Variables associated with graft failure included a high level of alkaline phosphatase at PEG initiation (HR = 1.002; P =.04) and lack of a sustained virologic response (HR = 2.1; P =.04). Conclusions: PEG-IGD has high morbidity and mortality and is not associated with increased rates of virologic response. It is important to avoid PEG therapy in liver transplant recipients with specific clinical, biochemical, and histologic risk factors for PEG-IGD.

AB - Background & Aims: Patients with recurrent hepatitis C virus infection treated with pegylated interferon (PEG) after liver transplantation can develop severe immune-mediated graft dysfunction (IGD) characterized by plasma cell hepatitis or rejection. Methods: We conducted a multicenter case-control study of 52 liver transplant recipients with hepatitis C to assess the incidence of, risk factors for, and outcomes of PEG-IGD. Data from each patient were compared with those from 2 matched patients who did not develop PEG-IGD (n = 104). We performed a multivariate analysis of risk factors and analyzed treatment and outcomes of graft dysfunction subtypes. Results: Overall incidence of PEG-IGD during a 10-year study period was 7.2%. Risk factors included no prior PEG therapy (odds ratio = 5.3; P <.0001), therapy with PEGα-2a (odds ratio = 4.7; P =.03), and immune features (mainly plasma cell hepatitis) on pre-PEG therapy liver biopsies (odds ratio = 3.9; P =.005). The PEG-IGD group had lower long-term patient (61.5% vs 91.3% of controls) and graft (38.5% vs 85.6% of controls) survival and higher rates of retransplantation (34.6% vs 6.7% of controls) (all, P <.0001), without increases in sustained virologic response. Variables associated with increased mortality included acute rejection as the PEG-IGD sub-type (hazard ratio [HR] = 2.4; P =.002), a high level of alkaline phosphatase at PEG initiation (HR = 1.003; P =.005), and lack of a sustained virologic response (HR = 3.3; P =.04). Variables associated with graft failure included a high level of alkaline phosphatase at PEG initiation (HR = 1.002; P =.04) and lack of a sustained virologic response (HR = 2.1; P =.04). Conclusions: PEG-IGD has high morbidity and mortality and is not associated with increased rates of virologic response. It is important to avoid PEG therapy in liver transplant recipients with specific clinical, biochemical, and histologic risk factors for PEG-IGD.

KW - Immune Response

KW - Immunosuppression

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