Tuberculosis in liver transplant recipients: A systematic review and meta‐analysis of individual patient data

Mycobacterium tuberculosis (MTB) causes substantial morbidity and mortality in liver transplant recipients. We examined the efficacy of isoniazid latent Mycobacterium tuberculosis infection (LTBI) treatment in liver transplant recipients and reviewed systematically all cases of active MTB infection in this population. We found 7 studies that evaluated LTBI treatment and 139 cases of active MTB infection in liver transplant recipients. Isoniazid LTBI treatment was associated with reduced MTB reactivation in transplant patients with latent MTB risk factors (0.0% versus 8.2%, P = 0.02), and isoniazid‐related hepatotoxicity occurred in 6% of treated patients, with no reported deaths. The prevalence of active MTB infection in transplant recipients was 1.3%. Nearly half of all recipients with active MTB infection had an identifiable pretransplant MTB risk factor. Among recipients who developed active MTB infection, extrapulmonary involvement was common (67%), including multiorgan disease (27%). The short‐term mortality rate was 31%. Surviving patients were more likely to have received 3 or more drugs for MTB induction therapy (P = 0.003) and to have been diagnosed within 1 month of symptom onset (P = 0.01) and were less likely to have multiorgan disease (P = 0.01) or to have experienced episodes of acute transplant rejection (P = 0.02). Compared with the general population, liver transplant recipients have an 18‐fold increase in the prevalence of active MTB infection and a 4‐fold increase in the case‐fatality rate. For high‐risk transplant candidates, isoniazid appears safe and is probably effective at reducing MTB reactivation. All liver transplant candidates should receive a tuberculin skin test, and isoniazid LTBI treatment should be given to patients with a positive skin test result or MTB pretransplant risk factors, barring a specific contraindication. Liver Transpl 15:894–906, 2009. © 2009 AASLD.

[1]  T. Lie,et al.  [Tuberculosis following liver transplantation]. , 2008, Deutsche Medizinische Wochenschrift.

[2]  O. Manuel,et al.  Comparison of Quantiferon‐TB Gold With Tuberculin Skin Test for Detecting Latent Tuberculosis Infection Prior to Liver Transplantation , 2007, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[3]  S. Chu,et al.  Clinical Features and Outcome of Tuberculosis in Solid Organ Transplant Recipients , 2007, The American journal of the medical sciences.

[4]  F. Sinatra,et al.  Isoniazid-Related Hepatic Failure in Children: A Survey of Liver Transplantation Centers , 2007, Transplantation.

[5]  A. Jahng,et al.  Safety of Treatment of Latent Tuberculosis Infection in Compensated Cirrhotic Patients During Transplant Candidacy Period , 2007, Transplantation.

[6]  T. Kiuchi,et al.  Liver transplantation without isoniazid prophylaxis for recipients with a history of tuberculosis , 2007, Clinical transplantation.

[7]  L. D'Albuquerque,et al.  Liver Transplantation from Deceased Donors Serologically Positive for Chagas Disease , 2007, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[8]  J. Perkins,et al.  Are we reporting the same thing? , 2007, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[9]  S. Fan,et al.  Implications for management of Mycobacterium tuberculosis infection in adult‐to‐adult live donor liver transplantation , 2007, Liver international : official journal of the International Association for the Study of the Liver.

[10]  T. Shim,et al.  Clinical Characteristics of Tuberculosis in Liver or Heart Transplant Recipients , 2006 .

[11]  R. Idilman,et al.  Antituberculous therapy–induced fulminant hepatic failure: Successful treatment with liver transplantation and nonstandard antituberculous therapy , 2006, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[12]  M. McCulloch,et al.  Liver transplantation at Red Cross War Memorial Children's Hospital. , 2006, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde.

[13]  Melonie P. Heron,et al.  Deaths: preliminary data for 2004. , 2006, National vital statistics reports : from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System.

[14]  G. Guaraldi,et al.  Posttransplant Mycobacterium tuberculosis disease following liver transplantation and the need for cautious evaluation of Quantiferon TB GOLD results in the transplant setting: a case report. , 2006, Transplantation proceedings.

[15]  E. Toyota,et al.  [A case of pulmonary tuberculosis complicated with an orthotopic liver transplantation]. , 2006, Kekkaku : [Tuberculosis].

[16]  M. Haberal,et al.  Evaluation of neurologic complications by brain MRI in kidney and liver transplant recipients. , 2006, Transplantation proceedings.

[17]  A. Ayhan,et al.  Disseminated peritoneal tuberculosis mimicking advanced‐stage endodermal sinus tumor: a case report , 2006, International journal of gynecological cancer : official journal of the International Gynecological Cancer Society.

[18]  J. Fortún,et al.  Is Liver Transplantation Advisable for Isoniazid Fulminant Hepatitis in Active Extrapulmonary Tuberculosis? , 2005, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[19]  B. Meyers Mycobacterium tuberculosis infection in solid organ transplant recipients. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[20]  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.

[21]  C. Chee,et al.  Tuberculosis: public health aspects. Re: Tuberculosis post-liver transplantation: a rare but complicated disease. , 2005, Annals of the Academy of Medicine, Singapore.

[22]  J. Caylà,et al.  Severe hepatotoxicity due to anti-tuberculosis drugs in Spain. , 2005, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[23]  P. Tambyah,et al.  Tuberculosis post-liver transplantation: a rare but complicated disease. , 2005, Annals of the Academy of Medicine, Singapore.

[24]  E. Bouza,et al.  Mycobacterium tuberculosis infection in recipients of solid organ transplants. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[25]  Sung‐Gyu Lee,et al.  Adult-to-adult living donor liver transplantation at the Asan Medical Center. , 2004, Yonsei medical journal.

[26]  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.

[27]  J. Heo,et al.  Auxiliary partial orthotopic liver transplantation in the treatment of acute liver failure: a case report. , 2004, Transplantation proceedings.

[28]  M. McCulloch,et al.  LIVER TRANSPLANTATION FOR CHILDREN – RED CROSS CHILDREN’S HOSPITAL EXPERIENCE , 2004 .

[29]  J. Fitzgerald,et al.  Successful treatment of multidrug-resistant tuberculosis following drug-induced hepatic necrosis requiring liver transplant. , 2004, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[30]  Mark S Roberts,et al.  Survival after liver transplantation in the United States: A disease‐specific analysis of the UNOS database , 2004, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[31]  S. Issa,et al.  Isolated hepatic tuberculosis in a transplanted liver , 2004, Transplant infectious disease : an official journal of the Transplantation Society.

[32]  J. Torre-Cisneros,et al.  TUBERCULOSIS IN THE TRANSPLANT CANDIDATE: IMPORTANCE OF EARLY DIAGNOSIS AND TREATMENT , 2004, Transplantation.

[33]  J. Cleveland,et al.  Guidelines for infection control in dental health-care settings--2003. , 2003, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[34]  V. Jha,et al.  Tuberculosis in organ transplant recipients. , 2003, Transplantation proceedings.

[35]  Z. Memish,et al.  Does tuberculin skin test predict tuberculosis in patients with end-stage liver disease? , 2003, Saudi Medical Journal.

[36]  Update: Adverse Event Data and Revised American Thoracic Society/CDC Recommendations against the Use of Rifampin and Pyrazinamide for Treatment of Latent Tuberculosis Infection—US, 2003 , 2003 .

[37]  P. Nyckowski,et al.  Liver transplantation in hepatitis C virus-related cirrhosis. , 2003, Transplantation proceedings.

[38]  D. Kunimoto,et al.  Severe hepatotoxicity associated with rifampin-pyrazinamide preventative therapy requiring transplantation in an individual at low risk for hepatotoxicity. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[39]  B. Meyers,et al.  Intracranial Tuberculoma in a Liver Transplant Patient: First Reported Case and Review of the Literature , 2003, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[40]  H. El‐Serag,et al.  Association Between Hepatitis C Infection and Other Infectious Diseases: A Case For Targeted Screening? , 2003, American Journal of Gastroenterology.

[41]  M. Navasa,et al.  Diagnosis and treatment of latent tuberculosis infection in liver transplant recipients in an endemic area , 2002, Transplantation.

[42]  S. K. Lee,et al.  Adult-to-adult living donor liver transplantation at the Asan Medical Center, Korea. , 2002, Asian journal of surgery.

[43]  Nina Singh,et al.  Safety and efficacy of isoniazid chemoprophylaxis administered during liver transplant candidacy for the prevention of posttransplant tuberculosis. , 2002, Transplantation.

[44]  M. Ozkahya,et al.  Mycobacterium tuberculosis infection and laboratory diagnosis in solid‐organ transplant recipients , 2002, Clinical transplantation.

[45]  M. Reichler,et al.  Evaluation of investigations conducted to detect and prevent transmission of tuberculosis. , 2002, JAMA.

[46]  Elsie Lee,et al.  Evolution and current use of the tuberculin test. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[47]  B. Portmann,et al.  LATE CELLULAR REJECTION IN PAEDIATRIC LIVER TRANSPLANTATION: AETIOLOGY AND OUTCOME , 2002, Transplantation.

[48]  P D Davies,et al.  A case-control study of lifestyle risk factors associated with tuberculosis in Liverpool, North-West England , 2001, European Respiratory Journal.

[49]  R. Freeman,et al.  Tuberculosis transmitted through transplantation. , 2001, The Journal of infection.

[50]  P. Ljungman,et al.  Prophylactic measures in the solid-organ recipient before transplantation. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[51]  T. Starzl,et al.  Causes of death after liver transplantation in 4000 consecutive patients: 2 to 19 year follow-up. , 2001, Transplantation proceedings.

[52]  T. Kiuchi,et al.  [Liver transplantation and tuberculosis]. , 2000, Kekkaku : [Tuberculosis].

[53]  D. Kahn,et al.  History of liver transplantation at the University of Cape Town and Groote Schuur Hospital. , 2000, South African journal of surgery. Suid-Afrikaanse tydskrif vir chirurgie.

[54]  M. McCulloch,et al.  Liver transplantation in children--the Red Cross War Memorial Children's Hospital experience. , 2000, South African journal of surgery. Suid-Afrikaanse tydskrif vir chirurgie.

[55]  M. McCulloch,et al.  Ten years of liver transplantation at Groote Schuur Hospital. , 2000, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde.

[56]  N. Singh,et al.  The current management of infectious diseases in the liver transplant recipient. , 2000, Clinics in liver disease.

[57]  N. Heaton,et al.  Mycobacterium tuberculosis infection in pediatric liver transplant recipients , 2000, The Pediatric infectious disease journal.

[58]  G. Preciso,et al.  [Fulminant liver failure caused by antitubercular drugs. Report of a clinical case]. , 2000, Minerva anestesiologica.

[59]  G. Alexander,et al.  Liver transplantation for hepatitis C virus related cirrhosis. , 2000, Bailliere's best practice & research. Clinical gastroenterology.

[60]  N. Bean,et al.  Surveillance for foodborne-disease outbreaks--United States, 1993-1997. , 2000, MMWR. CDC surveillance summaries : Morbidity and mortality weekly report. CDC surveillance summaries.

[61]  Charles M. Miller,et al.  Central nervous system complications in liver transplant recipients – incidence, timing, and long‐term follow‐up , 2000, Clinical transplantation.

[62]  H. Grønbaek,et al.  [Intramedullary tuberculous abscess in a patient with liver transplantation]. , 2000, Ugeskrift for læger.

[63]  G. Papanicolaou,et al.  Tuberculosis in orthotopic liver transplant patients: increased toxicity of recommended agents; cure of disseminated infection with nonconventional regimens. , 2000, Transplantation.

[64]  P. Trigo,et al.  Tuberculosis in liver transplant patients. , 1999, Transplantation proceedings.

[65]  C. Dye,et al.  Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. , 1999, JAMA.

[66]  E. Keeffe,et al.  Risk of tuberculosis in tuberculin skin test-positive liver transplant patients. , 1999, Clinical Infectious Diseases.

[67]  T. Kanematsu,et al.  The significance of measuring the serum total bile acids levels during orthotopic liver transplantation. , 1999, Hepato-Gastroenterology.

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

[69]  J. Wiederkehr,et al.  Isolated tuberculosis of the pancreas after orthotopic liver transplantation. , 1999, Liver transplantation and surgery : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[70]  R. Elwood,et al.  Severe hepatic complications of antituberculous therapy. , 1999, The Canadian journal of infectious diseases = Journal canadien des maladies infectieuses.

[71]  T. Shima,et al.  Suppression of skin reactivity to purified protein derivative by hepatitis C virus among HTLV-I carriers in Japan. , 1998, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[72]  Nina Singh,et al.  Mycobacterium tuberculosis infection in solid-organ transplant recipients: impact and implications for management. , 1998, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[73]  M. Kollef,et al.  The impact of comorbidity on mortality following in-hospital diagnosis of tuberculosis. , 1998, Chest.

[74]  J. Barkun,et al.  Prolonged ciprofloxacin therapy fails to prevent reactivation tuberculosis. , 1998, Clinical Infectious Diseases.

[75]  Nina Singh,et al.  Pulmonary Nodules in Liver Transplant Recipients , 1997, Medicine.

[76]  D. Paterson,et al.  Rapidly fatal bacteremia due to Staphylococcus aureus producing both enterotoxins A and B in a liver transplant recipient. , 1997, Clinical Infectious Diseases.

[77]  C. Cantarell,et al.  Clinical presentation and outcome of tuberculosis in kidney, liver, and heart transplant recipients in Spain. Spanish Transplantation Infection Study Group, GESITRA. , 1997, Transplantation.

[78]  Y. Yamaoka,et al.  A hepatic graft tuberculosis transmitted from a living-related donor. , 1997, Transplantation.

[79]  Y. Yamaoka,et al.  Experience of tacrolimus-based immunosuppression in living-related liver transplantation complicated with graft tuberculosis: interaction with rifampicin and side effects. , 1996, Transplantation Proceedings.

[80]  J. Rodés,et al.  [Severe hepatotoxicity of tuberculostatic agents. Increase in the incidence]. , 1996, Gastroenterologia y hepatologia.

[81]  K. Sugimachi,et al.  Tuberculosis following liver transplantation: report of a case and review of the literature , 1996, Transplant international : official journal of the European Society for Organ Transplantation.

[82]  B. Meyers,et al.  Isoniazid hepatotoxicity after orthotopic liver transplantation. , 1996, The Mount Sinai journal of medicine, New York.

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

[84]  J. Tweddell,et al.  Pulmonary tuberculosis after lung-liver transplantation from cystic fibrosis. , 1996, The Pediatric Infectious Disease Journal.

[85]  L. Folgueira,et al.  Rapid diagnosis of Mycobacterium tuberculosis bacteremia by PCR , 1996, Journal of clinical microbiology.

[86]  E. Sokal,et al.  Orthotopic liver transplantation for Crigler-Najjar type I disease in six children. , 1995, Transplantation.

[87]  M. L. de la Mata,et al.  Importance of surveillance mycobacterial cultures after liver transplantation. , 1995, Transplantation.

[88]  L. Ferrell,et al.  HEPATIC GRANULOMAS FOLLOWING LIVER TRANSPLANTATION CLINICOPATHOLOGIC FEATURES IN 42 PATIENTS , 1995, Transplantation.

[89]  S. Kline,et al.  Outbreak of tuberculosis among regular patrons of a neighborhood bar. , 1995, The New England journal of medicine.

[90]  R. Busuttil,et al.  Mycobacterial infections after pediatric liver transplantation: a report of three cases and review of the literature. , 1995, Journal of pediatric gastroenterology and nutrition.

[91]  W. Bechstein,et al.  Tuberculosis in liver transplant recipients: recurrence after transplantation? , 1994, Transplantation proceedings.

[92]  W. Bechstein,et al.  Outcome of severe pneumonias after orthotopic liver transplantation. , 1994, Transplantation Proceedings.

[93]  N. Weiss,et al.  Tuberculosis risk factors in adults in King County, Washington, 1988 through 1990. , 1994, American journal of public health.

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

[95]  B. Meyers,et al.  Tuberculosis in liver transplant patients. , 1994, Transplantation.

[96]  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.

[97]  L. Jeyaseelan,et al.  A double-blind randomized controlled trial of primary isoniazid prophylaxis in dialysis and transplant patients. , 1994, Transplantation.

[98]  K. Dohi,et al.  A comparative study of two-layer cold storage with perfluorochemical alone and University of Wisconsin solution for rat pancreas preservation. , 1994, Transplantation.

[99]  P. Ruutu,et al.  Effect of immunosuppressive therapy on the clinical presentation and outcome of tuberculosis. , 1993, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

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

[101]  L. Reichman,et al.  Liver transplantation: an unheralded probable risk for tuberculosis. , 1992, Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[102]  R. Chaisson,et al.  Treatment of tuberculosis in patients with advanced human immunodeficiency virus infection. , 1991, The New England journal of medicine.

[103]  M. Höfer,et al.  271. Tuberkulose nach lebertransplantation , 1987, Archiv fuer Klinische Chirurgie.

[104]  T. To,et al.  The significance of the tuberculin skin test in elderly persons. , 1987, Annals of internal medicine.

[105]  F. Mühlbacher,et al.  [Liver transplantation--indications and postoperative course]. , 1986, Wiener Klinische Wochenschrift.

[106]  D. Snider Bacille Calmette-Guérin vaccinations and tuberculin skin tests. , 1985, JAMA.

[107]  M. Sciaccaluga [Measurement of the intradermal reaction to PPD in chronic hepatitis and in cirrhosis. Basic research]. , 1975, Minerva Medica.

[108]  N. J. Ehrenkranz,et al.  Tuberculosis outbreak in a general hospital: evidence for airborne spread of infection. , 1972, Annals of internal medicine.

[109]  D. T. Carr The tuberculin skin test. , 1972, The American review of respiratory disease.

[110]  P. Diamond,et al.  Frequency of negative intermediate-strength tuberculin sensitivity in patients with active tuberculosis. , 1971, The New England journal of medicine.

[111]  G. Fuchs CRITERIA FOR PROPHYLAXIS IN INACTIVE TUBERCULOSIS. , 1965, Archives of Environmental Health An International Journal.

[112]  L. Tanoue Meta-analysis: New Tests for the Diagnosis of Latent Tuberculosis Infection: Areas of Uncertainty and Recommendations for ResearchMenzies D, Pai M, Comstock G (McGill Univ, Montreal; Johns Hopkins Univ, Baltimore, Md) Ann Intern Med 146:340–354, 2007§ , 2008 .

[113]  Trends in tuberculosis incidence--United States, 2006. , 2007, MMWR. Morbidity and mortality weekly report.

[114]  M. Zoli,et al.  Isolated hepatic tuberculoma after orthotopic liver transplantation: a case report , 2006, Internal and emergency medicine.

[115]  L. Tanoue Update: Adverse Event Data and Revised American Thoracic Society/CDC Recommendations Against the Use of Rifampin and Pyrazinamide for Treatment of Latent Tuberculosis Infection—United States, 2003 , 2006 .

[116]  M. Makuuchi,et al.  Resection of a Pulmonary Lesion After Liver Transplantation: Report of a Case , 2005, Surgery Today.

[117]  W. Bechstein,et al.  Mycobacterial infection after liver transplantation , 2004, Langenbecks Archiv für Chirurgie.

[118]  S. Agarwal,et al.  Prospective randomised trial of isoniazid prophylaxis in renal transplant recipient , 2004, International Urology and Nephrology.

[119]  M. Montejo,et al.  [Infection after orthotopic liver transplantation: analysis of the first 120 consecutive cases]. , 2000, Revista clínica española (Ed. impresa).

[120]  M. Montejo,et al.  Infección después del trasplante hepático ortotópico: análisis de los 120 primeros casos consecutivos , 2000 .

[121]  Nina Singh,et al.  Infections in solid organ transplant recipients. , 2000, Current opinion in infectious diseases.

[122]  A. López San Román,et al.  [Febrile syndrome and adrenal lesion in a patient receiving a hepatic transplant]. , 1998, Revista clínica española (Ed. impresa).

[123]  C. Godfraind,et al.  Cerebellar tuberculous abscess in a liver transplant patient. , 1997 .

[124]  L. Soto-Ramírez,et al.  [Treatment of tuberculosis]. , 1997, Gaceta medica de Mexico.

[125]  R. Higgins,et al.  Mycobacterium tuberculosis after liver transplantation: Management and guidelines for prevention , 1992 .

[126]  L. Ferrell,et al.  Mycobacterial infection after liver transplantation: A report of three cases and review of the literature , 1992 .

[127]  Larke Rp,et al.  Relationship between tuberculin reactivity and hepatitis B virus infection in the Northwest Territories. , 1991 .

[128]  R. Larke,et al.  Relationship between tuberculin reactivity and hepatitis B virus infection in the Northwest Territories. , 1991, Arctic medical research.

[129]  H. Sharp Liver failure in post-hepatitis A following 5 months of prophylactic isoniazid , 1989 .

[130]  A. Falk,et al.  Prophylaxis with isoniazid in inactive tuberculosis. A Veterans Administration Cooperative Study XII. , 1978, Chest.

[131]  W. Halota,et al.  [Tuberculin reactions in patients with acute viral hepatitis (author's transl)]. , 1978, Przeglad lekarski.

[132]  S. Radhakrishna,et al.  Alternative models for the development of tuberculosis disease following infection with tubercle bacilli. , 1976, Bulletin of the International Union against Tuberculosis.

[133]  F. Pak [Dynamics of tuberculin reaction in patients with pulmonary tuberculosis, who acquired epidemic hepatitis]. , 1966, Problemy tuberkuleza.

[134]  Pak Fp [Dynamics of tuberculin reaction in patients with pulmonary tuberculosis, who acquired epidemic hepatitis]. , 1966 .