HBV-Associated Acute Liver Failure After Immunosuppression and Risk of Death

Constantine J. Karvellas, Filipe S. Cardoso, Michelle Gottfried, K. Rajender Reddy, A. James Hanje, Daniel Ganger, William M. Lee, W. M. Lee, Anne M. Larson, Iris Liou, Oren Fix, Michael Schilsky, Timothy M McCashland, J. Eileen Hay, Natalie Murray, A. Obaid S. Shaikh, Andres Blei, Daniel Ganger, Atif Zaman, Steven H.B. HanRobert Fontana, Brendan McGuire, Raymond T. Chung, Alastair Smith, Robert Brown, Jeffrey Crippin, Edwin Harrison, Adrian Reuben, Santiago Munoz, Rajender Reddy, R. Todd Stravitz, Lorenzo Rossaro, Raj Satyanarayana, Tarek Hassanein, Constantine J. Karvellas, Jodi Olson, Ram Subramanian, James Hanje

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background & Aims Acute liver failure (ALF) caused by hepatitis B virus (HBV) infection can occur after immunosuppressive treatment and be fatal, although it might be preventable. We aimed to characterize the causes, clinical course, and short-term outcomes of HBV-associated ALF after immune-suppressive therapy, compared with patients with HBV-associated ALF without immunosuppression (control subjects). Methods We performed a retrospective multicenter study of 156 consecutive patients diagnosed with HBV-associated ALF (22 with a solid or blood malignancy) enrolled in the Acute Liver Failure Study Group registry from January 1998 through April 2015. We collected data on results of serologic and hepatic biochemistry analyses, grade of hepatic encephalopathy, Model for End-Stage Liver Disease score, and King's College criteria. We also collected data on clinical features, medical therapies, and complications in the first 7 days following study enrollment. Logistic regression was used to identify factors associated with transplant-free survival at 21 days in HBV-associated ALF (the primary outcome). Results Among patients with HBV-associated ALF, 28 cases (18%) occurred after immunosuppressive therapy (15 patients received systemic corticosteroids and 21 received chemotherapy); and 128 cases did not (control subjects, 82%). Significantly greater proportions of patients with HBV-associated ALF after immunosuppression were nonwhite persons, and had anemia or thrombocytopenia than controls (P <.02 for all). The serologic profile of HBV infection, severity of liver failure (based on MELD score), and complications (hepatic encephalopathy or need for mechanical ventilation, vasopressors, or renal replacement therapy) were similar between the groups (P >.17 for all). Factors associated with 21 day transplant-free survival were increased MELD score (odds ratio ∼OR, 0.894 (95% confidence interval 0.842-0.949 per increment), requirement for mechanical ventilation (OR 0.111(0.041-0.300), and immunosuppressive therapy (OR 0.274(0.082-0.923)). Conclusions Within a cohort study of patients with HBV-associated ALF, 18% had received immunosuppressive therapy. Significantly smaller proportions of patients with HBV-associated ALF after immunosuppression survive beyond 21 days than patients with HBV-associated ALF who did not receive immunosuppression. Patients undergoing chemotherapy should be screened for HBV infection and given appropriate antiviral therapies to reduce preventable mortality.

Original languageEnglish (US)
Pages (from-to)113-122
Number of pages10
JournalClinical Gastroenterology and Hepatology
Volume15
Issue number1
DOIs
StatePublished - Jan 1 2017

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Acute Liver Failure
Hepatitis B virus
Immunosuppression
Immunosuppressive Agents
Virus Diseases
Therapeutics
Transplants
Drug Therapy
End Stage Liver Disease
Survival
Hepatic Encephalopathy
Artificial Respiration
Thrombocytopenia
Biochemistry
Curriculum
Multicenter Studies
Antiviral Agents
Registries
Anemia
Adrenal Cortex Hormones

Keywords

  • Acute Liver Failure
  • Chemotherapy
  • Hepatitis B
  • Immunosuppression

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Karvellas, C. J., Cardoso, F. S., Gottfried, M., Reddy, K. R., Hanje, A. J., Ganger, D., ... Hanje, J. (2017). HBV-Associated Acute Liver Failure After Immunosuppression and Risk of Death. Clinical Gastroenterology and Hepatology, 15(1), 113-122. https://doi.org/10.1016/j.cgh.2016.06.008

HBV-Associated Acute Liver Failure After Immunosuppression and Risk of Death. / Karvellas, Constantine J.; Cardoso, Filipe S.; Gottfried, Michelle; Reddy, K. Rajender; Hanje, A. James; Ganger, Daniel; Lee, William M.; Lee, W. M.; Larson, Anne M.; Liou, Iris; Fix, Oren; Schilsky, Michael; McCashland, Timothy M; Hay, J. Eileen; Murray, Natalie; Shaikh, A. Obaid S.; Blei, Andres; Ganger, Daniel; Zaman, Atif; Han, Steven H.B.; Fontana, Robert; McGuire, Brendan; Chung, Raymond T.; Smith, Alastair; Brown, Robert; Crippin, Jeffrey; Harrison, Edwin; Reuben, Adrian; Munoz, Santiago; Reddy, Rajender; Stravitz, R. Todd; Rossaro, Lorenzo; Satyanarayana, Raj; Hassanein, Tarek; Karvellas, Constantine J.; Olson, Jodi; Subramanian, Ram; Hanje, James.

In: Clinical Gastroenterology and Hepatology, Vol. 15, No. 1, 01.01.2017, p. 113-122.

Research output: Contribution to journalArticle

Karvellas, CJ, Cardoso, FS, Gottfried, M, Reddy, KR, Hanje, AJ, Ganger, D, Lee, WM, Lee, WM, Larson, AM, Liou, I, Fix, O, Schilsky, M, McCashland, TM, Hay, JE, Murray, N, Shaikh, AOS, Blei, A, Ganger, D, Zaman, A, Han, SHB, Fontana, R, McGuire, B, Chung, RT, Smith, A, Brown, R, Crippin, J, Harrison, E, Reuben, A, Munoz, S, Reddy, R, Stravitz, RT, Rossaro, L, Satyanarayana, R, Hassanein, T, Karvellas, CJ, Olson, J, Subramanian, R & Hanje, J 2017, 'HBV-Associated Acute Liver Failure After Immunosuppression and Risk of Death', Clinical Gastroenterology and Hepatology, vol. 15, no. 1, pp. 113-122. https://doi.org/10.1016/j.cgh.2016.06.008
Karvellas CJ, Cardoso FS, Gottfried M, Reddy KR, Hanje AJ, Ganger D et al. HBV-Associated Acute Liver Failure After Immunosuppression and Risk of Death. Clinical Gastroenterology and Hepatology. 2017 Jan 1;15(1):113-122. https://doi.org/10.1016/j.cgh.2016.06.008
Karvellas, Constantine J. ; Cardoso, Filipe S. ; Gottfried, Michelle ; Reddy, K. Rajender ; Hanje, A. James ; Ganger, Daniel ; Lee, William M. ; Lee, W. M. ; Larson, Anne M. ; Liou, Iris ; Fix, Oren ; Schilsky, Michael ; McCashland, Timothy M ; Hay, J. Eileen ; Murray, Natalie ; Shaikh, A. Obaid S. ; Blei, Andres ; Ganger, Daniel ; Zaman, Atif ; Han, Steven H.B. ; Fontana, Robert ; McGuire, Brendan ; Chung, Raymond T. ; Smith, Alastair ; Brown, Robert ; Crippin, Jeffrey ; Harrison, Edwin ; Reuben, Adrian ; Munoz, Santiago ; Reddy, Rajender ; Stravitz, R. Todd ; Rossaro, Lorenzo ; Satyanarayana, Raj ; Hassanein, Tarek ; Karvellas, Constantine J. ; Olson, Jodi ; Subramanian, Ram ; Hanje, James. / HBV-Associated Acute Liver Failure After Immunosuppression and Risk of Death. In: Clinical Gastroenterology and Hepatology. 2017 ; Vol. 15, No. 1. pp. 113-122.
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abstract = "Background & Aims Acute liver failure (ALF) caused by hepatitis B virus (HBV) infection can occur after immunosuppressive treatment and be fatal, although it might be preventable. We aimed to characterize the causes, clinical course, and short-term outcomes of HBV-associated ALF after immune-suppressive therapy, compared with patients with HBV-associated ALF without immunosuppression (control subjects). Methods We performed a retrospective multicenter study of 156 consecutive patients diagnosed with HBV-associated ALF (22 with a solid or blood malignancy) enrolled in the Acute Liver Failure Study Group registry from January 1998 through April 2015. We collected data on results of serologic and hepatic biochemistry analyses, grade of hepatic encephalopathy, Model for End-Stage Liver Disease score, and King's College criteria. We also collected data on clinical features, medical therapies, and complications in the first 7 days following study enrollment. Logistic regression was used to identify factors associated with transplant-free survival at 21 days in HBV-associated ALF (the primary outcome). Results Among patients with HBV-associated ALF, 28 cases (18{\%}) occurred after immunosuppressive therapy (15 patients received systemic corticosteroids and 21 received chemotherapy); and 128 cases did not (control subjects, 82{\%}). Significantly greater proportions of patients with HBV-associated ALF after immunosuppression were nonwhite persons, and had anemia or thrombocytopenia than controls (P <.02 for all). The serologic profile of HBV infection, severity of liver failure (based on MELD score), and complications (hepatic encephalopathy or need for mechanical ventilation, vasopressors, or renal replacement therapy) were similar between the groups (P >.17 for all). Factors associated with 21 day transplant-free survival were increased MELD score (odds ratio ∼OR, 0.894 (95{\%} confidence interval 0.842-0.949 per increment), requirement for mechanical ventilation (OR 0.111(0.041-0.300), and immunosuppressive therapy (OR 0.274(0.082-0.923)). Conclusions Within a cohort study of patients with HBV-associated ALF, 18{\%} had received immunosuppressive therapy. Significantly smaller proportions of patients with HBV-associated ALF after immunosuppression survive beyond 21 days than patients with HBV-associated ALF who did not receive immunosuppression. Patients undergoing chemotherapy should be screened for HBV infection and given appropriate antiviral therapies to reduce preventable mortality.",
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author = "Karvellas, {Constantine J.} and Cardoso, {Filipe S.} and Michelle Gottfried and Reddy, {K. Rajender} and Hanje, {A. James} and Daniel Ganger and Lee, {William M.} and Lee, {W. M.} and Larson, {Anne M.} and Iris Liou and Oren Fix and Michael Schilsky and McCashland, {Timothy M} and Hay, {J. Eileen} and Natalie Murray and Shaikh, {A. Obaid S.} and Andres Blei and Daniel Ganger and Atif Zaman and Han, {Steven H.B.} and Robert Fontana and Brendan McGuire and Chung, {Raymond T.} and Alastair Smith and Robert Brown and Jeffrey Crippin and Edwin Harrison and Adrian Reuben and Santiago Munoz and Rajender Reddy and Stravitz, {R. Todd} and Lorenzo Rossaro and Raj Satyanarayana and Tarek Hassanein and Karvellas, {Constantine J.} and Jodi Olson and Ram Subramanian and James Hanje",
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TY - JOUR

T1 - HBV-Associated Acute Liver Failure After Immunosuppression and Risk of Death

AU - Karvellas, Constantine J.

AU - Cardoso, Filipe S.

AU - Gottfried, Michelle

AU - Reddy, K. Rajender

AU - Hanje, A. James

AU - Ganger, Daniel

AU - Lee, William M.

AU - Lee, W. M.

AU - Larson, Anne M.

AU - Liou, Iris

AU - Fix, Oren

AU - Schilsky, Michael

AU - McCashland, Timothy M

AU - Hay, J. Eileen

AU - Murray, Natalie

AU - Shaikh, A. Obaid S.

AU - Blei, Andres

AU - Ganger, Daniel

AU - Zaman, Atif

AU - Han, Steven H.B.

AU - Fontana, Robert

AU - McGuire, Brendan

AU - Chung, Raymond T.

AU - Smith, Alastair

AU - Brown, Robert

AU - Crippin, Jeffrey

AU - Harrison, Edwin

AU - Reuben, Adrian

AU - Munoz, Santiago

AU - Reddy, Rajender

AU - Stravitz, R. Todd

AU - Rossaro, Lorenzo

AU - Satyanarayana, Raj

AU - Hassanein, Tarek

AU - Karvellas, Constantine J.

AU - Olson, Jodi

AU - Subramanian, Ram

AU - Hanje, James

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Background & Aims Acute liver failure (ALF) caused by hepatitis B virus (HBV) infection can occur after immunosuppressive treatment and be fatal, although it might be preventable. We aimed to characterize the causes, clinical course, and short-term outcomes of HBV-associated ALF after immune-suppressive therapy, compared with patients with HBV-associated ALF without immunosuppression (control subjects). Methods We performed a retrospective multicenter study of 156 consecutive patients diagnosed with HBV-associated ALF (22 with a solid or blood malignancy) enrolled in the Acute Liver Failure Study Group registry from January 1998 through April 2015. We collected data on results of serologic and hepatic biochemistry analyses, grade of hepatic encephalopathy, Model for End-Stage Liver Disease score, and King's College criteria. We also collected data on clinical features, medical therapies, and complications in the first 7 days following study enrollment. Logistic regression was used to identify factors associated with transplant-free survival at 21 days in HBV-associated ALF (the primary outcome). Results Among patients with HBV-associated ALF, 28 cases (18%) occurred after immunosuppressive therapy (15 patients received systemic corticosteroids and 21 received chemotherapy); and 128 cases did not (control subjects, 82%). Significantly greater proportions of patients with HBV-associated ALF after immunosuppression were nonwhite persons, and had anemia or thrombocytopenia than controls (P <.02 for all). The serologic profile of HBV infection, severity of liver failure (based on MELD score), and complications (hepatic encephalopathy or need for mechanical ventilation, vasopressors, or renal replacement therapy) were similar between the groups (P >.17 for all). Factors associated with 21 day transplant-free survival were increased MELD score (odds ratio ∼OR, 0.894 (95% confidence interval 0.842-0.949 per increment), requirement for mechanical ventilation (OR 0.111(0.041-0.300), and immunosuppressive therapy (OR 0.274(0.082-0.923)). Conclusions Within a cohort study of patients with HBV-associated ALF, 18% had received immunosuppressive therapy. Significantly smaller proportions of patients with HBV-associated ALF after immunosuppression survive beyond 21 days than patients with HBV-associated ALF who did not receive immunosuppression. Patients undergoing chemotherapy should be screened for HBV infection and given appropriate antiviral therapies to reduce preventable mortality.

AB - Background & Aims Acute liver failure (ALF) caused by hepatitis B virus (HBV) infection can occur after immunosuppressive treatment and be fatal, although it might be preventable. We aimed to characterize the causes, clinical course, and short-term outcomes of HBV-associated ALF after immune-suppressive therapy, compared with patients with HBV-associated ALF without immunosuppression (control subjects). Methods We performed a retrospective multicenter study of 156 consecutive patients diagnosed with HBV-associated ALF (22 with a solid or blood malignancy) enrolled in the Acute Liver Failure Study Group registry from January 1998 through April 2015. We collected data on results of serologic and hepatic biochemistry analyses, grade of hepatic encephalopathy, Model for End-Stage Liver Disease score, and King's College criteria. We also collected data on clinical features, medical therapies, and complications in the first 7 days following study enrollment. Logistic regression was used to identify factors associated with transplant-free survival at 21 days in HBV-associated ALF (the primary outcome). Results Among patients with HBV-associated ALF, 28 cases (18%) occurred after immunosuppressive therapy (15 patients received systemic corticosteroids and 21 received chemotherapy); and 128 cases did not (control subjects, 82%). Significantly greater proportions of patients with HBV-associated ALF after immunosuppression were nonwhite persons, and had anemia or thrombocytopenia than controls (P <.02 for all). The serologic profile of HBV infection, severity of liver failure (based on MELD score), and complications (hepatic encephalopathy or need for mechanical ventilation, vasopressors, or renal replacement therapy) were similar between the groups (P >.17 for all). Factors associated with 21 day transplant-free survival were increased MELD score (odds ratio ∼OR, 0.894 (95% confidence interval 0.842-0.949 per increment), requirement for mechanical ventilation (OR 0.111(0.041-0.300), and immunosuppressive therapy (OR 0.274(0.082-0.923)). Conclusions Within a cohort study of patients with HBV-associated ALF, 18% had received immunosuppressive therapy. Significantly smaller proportions of patients with HBV-associated ALF after immunosuppression survive beyond 21 days than patients with HBV-associated ALF who did not receive immunosuppression. Patients undergoing chemotherapy should be screened for HBV infection and given appropriate antiviral therapies to reduce preventable mortality.

KW - Acute Liver Failure

KW - Chemotherapy

KW - Hepatitis B

KW - Immunosuppression

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