Isoniazid-Related Hepatic Failure in Children: A Survey of Liver Transplantation Centers

Background. Isoniazid (INH) therapy for tuberculosis carries a known risk for hepatoxicity, and leads to hepatic failure in a small subset of patients. This incidence has been described for adults, but is uncertain in children. Our aim was to estimate the incidence of pediatric referrals for INH-related liver failure, and to describe the characteristics and outcomes of these patients. Methods. The 84 U.S. centers performing pediatric liver transplants between 1987 and 1997 were surveyed regarding patients with INH-induced liver failure. Additional transplant statistics were obtained from the United Network for Organ Sharing. Estimates of the number of children taking preventive INH were derived from a nationwide public health database. Results. Twenty cases of INH-related liver failure were found during a 10-year period. Four patients (20%) recovered spontaneously; 10 (50%) underwent orthotopic liver transplantation (OLT), while six (30%) died awaiting OLT. Mean age at presentation was 9.8 years (range 1.3–17). Mean length of INH therapy was 3.3 months (range 0.5–9). Notably, five patients seen for symptoms of hepatitis were initially told not to stop treatment. INH-associated liver failure accounted for 0.2% (8 of 4679) of all pediatric OLTs, and 14% (8/56) of transplants for drug hepatoxicity. The estimated incidence of liver failure was up to 3.2/100,000 for children on prophylactic INH. Conclusions. While INH-associated liver failure in children is rare, discontinuation at the onset of symptoms does not assure recovery. This indicates a need for increased awareness of hepatotoxicity risk, expanded biochemical monitoring for children receiving INH, and prompt withdrawal in symptomatic patients.

[1]  E. L. Kendig,et al.  Isoniazid hepatotoxicity in children. , 2015, The American review of respiratory disease.

[2]  F. T. ten Kate,et al.  Do serum ALAT values reflect the inflammatory activity in the liver of patients with chronic viral hepatitis? , 2008, Liver.

[3]  V. Debari,et al.  Assessment of age-related isoniazid hepatotoxicity during treatment of latent tuberculosis infection* , 2006, Current medical research and opinion.

[4]  A. Woolf,et al.  Acetaminophen Poisoning: an Evidence-Based Consensus Guideline for Out-of-Hospital Management , 2006, Clinical toxicology.

[5]  T. Self,et al.  Isoniazid hepatotoxicity associated with treatment of latent tuberculosis infection: a 7-year evaluation from a public health tuberculosis clinic. , 2005, Chest.

[6]  L. D’Antiga,et al.  Isoniazid-related fulminant hepatic failure in a child: assessment of the native liver’s early regeneration after auxiliary partial orthotopic liver transplantation , 2004, Transplant international : official journal of the European Society for Organ Transplantation.

[7]  J. Fitzgerald,et al.  A meta-analysis of the effect of Bacille Calmette Guérin vaccination on tuberculin skin test measurements , 2002, Thorax.

[8]  M. Voigt,et al.  Prevalence and interaction of hepatitis B and latent tuberculosis in Vietnamese immigrants to the United States , 2002, American Journal of Gastroenterology.

[9]  S. Buskin,et al.  Hepatotoxicity associated with isoniazid preventive therapy: a 7-year survey from a public health tuberculosis clinic. , 1999, JAMA.

[10]  E. Björnsson,et al.  Liver reactions to oral low-dose tetracyclines. , 1997, Scandinavian journal of gastroenterology.

[11]  T. Schaberg,et al.  Risk factors for side-effects of isoniazid, rifampin and pyrazinamide in patients hospitalized for pulmonary tuberculosis. , 1996, The European respiratory journal.

[12]  M. Døssing,et al.  Liver injury during antituberculosis treatment: an 11-year study. , 1996, Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[13]  David J Weber,et al.  Isoniazid-related fatal hepatitis. , 1996, The Western journal of medicine.

[14]  R. Lawrence,et al.  Hepatotoxicity and transaminase measurement during isoniazid chemoprophylaxis in children. , 1995, The Pediatric infectious disease journal.

[15]  F. J. Farrell,et al.  Treatment of hepatic failure secondary to isoniazid hepatitis with liver transplantation , 1994, Digestive Diseases and Sciences.

[16]  B. Meyers,et al.  Acute hepatic failure in seven patients after prophylaxis and therapy with antituberculous agents. Successful treatment with orthotopic liver transplantation. , 1994, Transplantation.

[17]  T. Starzl,et al.  Successful liver transplantation for isoniazid-induced hepatic failure--a case report. , 1994, Transplantation.

[18]  S. Nelson,et al.  Hepatotoxicity associated with acetaminophen usage in patients receiving multiple drug therapy for tuberculosis. , 1994, Chest.

[19]  D. Snider,et al.  Isoniazid-associated hepatitis deaths: a review of available information. , 1992, The American review of respiratory disease.

[20]  W. Maddrey,et al.  Perspective: preventive isoniazid therapy and the liver. , 1992, Chest.

[21]  R. Nemir,et al.  Tuberculosis in children 10 years of age and younger: three decades of experience during the chemotherapeutic era. , 1991, Pediatrics.

[22]  J. E. Hansen.  Twenty isoniazid-associated deaths in one state. , 1990, The American review of respiratory disease.

[23]  C. Chan,et al.  Isoniazid-rifampin-induced hepatitis in hepatitis B carriers. , 1990, Gastroenterology.

[24]  P. Steiner,et al.  Incidence of hepatotoxicity in children receiving isoniazid chemoprophylaxis. , 1989, The Pediatric infectious disease journal.

[25]  E. Klatt,et al.  Fatal isoniazid hepatitis in a child. , 1986, Pediatric infectious disease.

[26]  S. Manios,et al.  Hepatotoxic reactions in children with severe tuberculosis treated with isoniazid‐rifampin , 1985, Pediatric infectious disease.

[27]  D. Snider,et al.  Hepatotoxicity from isoniazid and rifampin among children treated for tuberculosis. , 1983, Pediatrics.

[28]  D. Solomon,et al.  Toxic effects of isoniazid in tuberculosis chemoprophylaxis. Role of biochemical monitoring in 1,000 patients. , 1979, JAMA.

[29]  S. Hadjiyiannis,et al.  Isoniazid liver injury during chemoprophylaxis in children. , 1979, Archives of disease in childhood.

[30]  D. Snider,et al.  Isoniazid-related hepatitis: a U.S. Public Health Service cooperative surveillance study. , 1978, The American review of respiratory disease.

[31]  B. Bernstein,et al.  Aspirin-induced hepatotoxicity and its effect on juvenile rheumatoid arthritis. , 1977, American journal of diseases of children.

[32]  D. Pessayre,et al.  Isoniazid-rifampin fulminant hepatitis. A possible consequence of the enhancement of isoniazid hepatotoxicity by enzyme induction. , 1977, Gastroenterology.

[33]  I. Litt,et al.  Isoniazid hepatitis in adolescents. , 1976, The Journal of pediatrics.

[34]  M. Ament,et al.  Fatal hepatic necrosis due to isoniazid chemoprophylaxis in a 15-year-old girl. , 1976, The Journal of pediatrics.

[35]  U. Thorgeirsson,et al.  Isoniazid liver injury: clinical spectrum, pathology, and probable pathogenesis. , 1976, Annals of internal medicine.

[36]  K. Ishak,et al.  Isoniazid-associated hepatitis in 114 patients. , 1975, Gastroenterology.

[37]  P. Beaudry,et al.  Liver enzyme disturbances during isoniazid chemoprophylaxis in children. , 1974, The American review of respiratory disease.

[38]  T. Sterling,et al.  American Thoracic Society Documents An Official ATS Statement : Hepatotoxicity of Antituberculosis Therapy , 2006 .

[39]  F. F. Fountain.  Tuberculosis update. , 2001, Tennessee medicine : journal of the Tennessee Medical Association.

[40]  J. Crippin.  Acetaminophen hepatotoxicity: potentiation by isoniazid. , 1993, The American journal of gastroenterology.

[41]  J. Boguikouma,et al.  [Hepatotoxicity of the combination of isoniazid-rifampicin in African children. Role of malnutrition and HB virus]. , 1989, Archives francaises de pediatrie.

[42]  Iuat.  Efficacy of various duration of isoniazid preventive therapy for tuberculosis : five years follow-up in the IUAT trial , 1982 .

[43]  Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. International Union Against Tuberculosis Committee on Prophylaxis. , 1982, Bulletin of the World Health Organization.

[44]  P. Q. Edwards.  Isoniazid-associated hepatitis. , 1976, Bulletin of the International Union against Tuberculosis.

[45]  W. Bailey,et al.  Disturbed hepatic function during isoniazid chemoprophylaxis. Monitoring the hepatic function of 427 hospital employees receiving isoniazid chemoprophylaxis for tuberculosis. , 1973, The American review of respiratory disease.

[46]  R. Garibaldi,et al.  Isoniazid-associated hepatitis. Report of an outbreak. , 1972, The American review of respiratory disease.