Abstract
Liver transplantation (OLTx) has become a common life-saving procedure for individuals with chronic advanced liver disease. It is also used in the clinical treatment of patients with fulminant hepatic failure and those with primary neoplastic disease of the liver. Despite its overall success in restoring meaningful life to those who undergo the procedure, the posttransplant life of a liver allograft recipient is not without hazard. A common problem following liver transplantation is the finding of abnormal liver injury tests reflecting a “hepatitis” that can not be ascribed to allograft rejection. The majority of such cases are a consequence of either a technically flawed operation, drug-induced liver injury, or one or another form of viral hepatitis. Each of these problems is discussed in the following clinical review.
Similar content being viewed by others
References
Wright HI, Bou-Abboud CF, Hassanein T, Block GD, Demetris AJ, Starzl TE, Van Thiel DH: Disease recurrence and rejection following liver transplantation for autoimmune chronic active liver disease. Transplantation 53:136–139, 1992
Portman B, O'Grady J, Williams R: Disease recurrence following orthotopic liver transplantation. Transplant Proc 18(suppl 4):136–143, 1986
Neuhaus P, Broelsch CH, Ringe B, et al: Results of biliary reconstruction after liver transplantation. Transplant Proc 16:1225–1227, 1984
Iwatsuki S, Shaw BW Jr, Starzl TE: Biliary tract complications in liver transplantation under cyclosporin-steroid therapy. Transplant Proc 15:1288–1291, 1983
Lerut J, Gordon RD, Iwatsuki S, et al: Biliary tract complications in human orthotopic liver transplantation. Transplantation 43:47–50, 1987
Ringe B, Olkhafer K, Bunzendahl H, et al: Analysis of biliary complications following orthotopic liver transplantation. Transplant Proc 21:2472–2476, 1989
Wall WJ, Grant DR, Mimeault RE, et al: Biliary reconstruction in liver transplantation. Can J Surg 32:97–100, 1989
Koneru B, Zajko AB, Sher L, et al: Obstructing mucocele of the cystic duct after transplantation of the liver. Surg Gynecol Obstet 168:394–396, 1989
Halff G, Todo S, Hall R, et al: Late complications with the gallbladder conduit biliary reconstruction after transplantation. Transplantation 48:537–539, 1989
Mika SK: The terminal distribution of the hepatic artery with special reference to arterio-portal anastomosis. J Anat 100:651–663, 1966
Shaw BW Jr, Gordon RD, Iwatsuki S, et al: Hepatic retransplantation. Transplant Proc 17:264–271, 1985
Paulsen AW, Brajtbord D, Klintmalm GB, et al: Intraoperative measurements related to subsequent hepatic graft failure. Transplant Proc 21:2337–2338, 1989
Quiroga J, Colina I, Demetris J, Starzl TE, Van Thiel DH: Causes and timing of first allograft failure in orthotopic liver transplantation: A study in 177 consecutive patients undergoing liver retransplantation. Hepatology 14:1054–1062, 1991
Tzakis AG, Gordon RD, Shaw BW Jr, et al: Clinical presentation of hepatic artery thrombosis after liver transplantation in the cyclosporine era. Transplantation 40:667–671, 1985
Klintmalm BG, Olson LM, Nery JR, et al: Treatment of hepatic artery thrombosis after liver transplantation with immediate vascular reconstruction: A report of three cases. Transplant Proc 20(suppl 1):610–612, 1988
Mazzaferro V, Esquivel CO, Makowka L, et al: Hepatic artery thrombosis after pediatric liver transplantation: Medical or surgical event? Transplantation 47:971–977, 1989
Lerut J, Tzakis AG, Bron K, et al: Complications of venous reconstruction in human orthotopic liver transplantation. Ann Surg 205:404–414, 1987
Wozney P, Zajko AB, Bron KM, et al: Vascular complications after liver transplantation: A 5-year experience. AJR 147:657–663, 1986
Zajko AB, Campbell WL, Logsdon GA, et al: Cholangiographic findings in hepatic artery occlusion after liver transplantation. AJR 149:485–489, 1987
Demetris AJ, Jaffe R, Starzl TE: A review of adults and pediatric post-transplant liver pathology. Pathol Annu 22:347–386, 1987
Burke GW, Ascher NL, Hunter D, et al: Orthotopic liver transplantation: nonoperative management of early, acute portal vein thrombosis Surgery 104:924–928, 1988
Scantlebury V, Zajko A, Esquivel C, et al: Successful reconstruction of late portal vein stenosis after hepatic transplantation. Arch Surg 124:503–505, 1989
Rouch DA, Emond JC, Ferrari M, et al: The successful management of portal vein thrombosis after hepatic transplantation with the splenorenal shunt. Surg Gynecol Obstet 166:311–316, 1988
Van Thiel DH, Fagiuoli S, Wright HI, Rodriguez-Rilo H, Silverman W: Biliary Complications of liver transplantation: A review for gastroenterologists and surgeons not at a transplant center. Gastrointes Endosc (in press)
Iwatsuki S, Shaw BW, Starzl TE: Biliary tract complications in liver transplantation under cyclosporine-steroid therapy. Transplant Proc 15:1288–1291, 1983
Vicente E, Perkins JD, Sterioff S, et al: Biliary tract complications following orthotopic liver transplantation. Clin Transplant 1:138–142, 1987
Lerut J, Gordon RD, Iwatsuki, S, et al: Biliary tract complications in human orthotopic liver transplantation. Transplantation 43:47–51, 1987
Schade RR, Guglielmi A, Van Thiel DH, et al: Cholestasis in heart transplant recipients treated with cyclosporine. Transplant Proc 15:2757–2760, 1983
Klintmalm GBG, Iwatsuki S, Starzl TE: Cyclosporin A hepatotoxicity in 66 renal allograft recipients. Transplantation 32:488–489, 1981
Todo S, Podesta L, ChapChap P, et al: Orthotopic liver transplantation in dogs receiving FK 506. Transplant Proc 19(suppl 6):64–67, 1987
Todo S, Ueda Y, Demetris AJ et al: Immunosuppression of canine, monkey, and baboon allografts by FK 506 with special reference to synergism with other drugs, and to tolerance induction. Surgery 104:239–249, 1988
McDonald GB, Triumali N: Intestinal and liver toxicity of neoplastic drugs. West J Med 140:250–295, 1984
Weitz H, Gakel JM, Possinger K, et al: Venoocclusive disease of the liver in patients receiving immunosuppressive therapy. Virchow's Arch (Pathol Anat) 395:245–253, 1982
Marubbio AT, Danielson B: Hepatic venoocclusive disease in a renal transplant patient receiving azathioprine. Gastroenterology 69:739–743, 1975
De Pinho RA, Goldberg CS, Lefkowitch JH: Azathioprine and the liver. Evidence favoring idiosyncratic, mixed cholestatic-hepatocellular injury in humans. Gastroenterology 86:162–165, 1984
Sterneck M, Wiesner R, Asher N, Roberts J, Ferrel L, Ludwig J, Lake J: Azathioprine hepatotoxicity after liver transplantation. Hepatology 14:806–810, 1991
Lewis JH, Zimmerman HJ, Benson GD, Ishak KG: Hepatic injury associated with ketoconazole therapy. Gastroenterology 86:503–513, 1984
Stricker BHCh, Blok APR, Bronkhorst FB, Van Parys GE, Desmet VJ: Ketoconazole-associated hepatic injury; A clinicopathological study of 55 cases. J Hepatol 3:399–406, 1986
Lake-Bakaar G, Scheuer PJ, Sherlock S: Hepatic reactions associated with ketoconazole in the United Kingdom. Br Med J 294:419–422, 1987
Knight TE, Shikuma CY, Knight J: Ketoconazole-induced fulminant hepatitis necessitating liver transplantation. J Am Acad Dermatol 25:398–400, 1991
Gasbarrini A, Borle AB, Van Thiel DH: Ca2+ channel blockers do not protect isolated perfused rat hepatocytes from anoxic injury. Biochim Biophys Acta (in press)
Brodsky SJ, Cutler SS, Weiner DA, Klein MD: Hepatotoxicity due to treatment with verapamil. Ann Intern Med 94:490–491, 1981
Shah G, Demetris AJ, Gavaler JS, Lewis JH, Todo S, Starzl TE, Van Thiel DH: Incidence, prevalence and clinical course of hepatitis C in liver transplantation: Experience in 317 donor and recipient pairs. Gastroenterology 103:323–329, 1992
Lake JR, Wright TL: Liver transplantation for patients with hepatitis B: What have we learned from our results? Hepatology 13:796–799, 1991
Wright TL, Donegan E, Hsu HH, Ferrel L, Lake JR, Kim M, Combs C, Fennessy S, Roberts JP, Asher NL, Greenberg HB: Recurrent and acquired hepatitis C viral infection in liver transplant recipients. Gastroenterology 103:317–322, 1992
Colledan M, Gislon M, Doglia M, et al: Liver transplantation in patients with B viral hepatitis and delta infection. Transplant Proc 19:4073–4076, 1987
Rizzetto M, Macagno S, Chiaberge E, et al: Liver transplantation in hepatitis delta virus disease. Lancet 2:469–471 1987
Todo S, Demetris AJ, Van Thiel DH, Fung JJ, Starzl TE: Orthotopic liver transplantation for patients with hepatitis B virus (HBV) related liver disease. Hepatology 13:619–626, 1991
Rakela J: Recurrent hepatitis B infection in hepatic allografts. Mayo Clin Proc 64:597–599, 1989
Yoffe B, Müller R: Liver transplantation in patients with HBV infection: Implications of extrahepatic HBV infection.In Viral Hepatitis and Liver Disease. FB Hollinger SM Lemon, HS Margolis (eds). Baltimore, Williams & Wilkins, 1991, pp 813–819
Omata M: Significance of extrahepatic replication of hepatitis B virus. Hepatology 12:364–366, 1990
Lednar WM, Lemon SM, Kirkpatrick JW, et al: Frequency of illness associated with hepatitis A virus infection in adults. Am J Epidemiol 122:226–233, 1985
Yao G: Clinical spectrum and natural history of viral hepatitis A in a 1988 Shanghai epidemic.In Viral Hepatitis and Liver Disease. FB Hollinger, SM Lemon, HS Margolis (eds). Baltimore, Williams & Wilkins, 1991, pp 76–78.
Balayan MS: HEV infection: Historical perspectives, global epidemiology and clinical features.In Viral Hepatitis and Liver Disease. FB Hollinger, SM Lemon, HS Margolis (eds). Baltimore, Williams & Wilkins, 1991, pp 498–507
Wertheim RA, Brooks BJ Jr, Rodriguez FH Jr, Lesesne HR, Jennette JC: Fatal herpetic hepatitis in pregnancy. Obstet Gynecol 62(suppl):38S-42S, 1983
Van Thiel DH, Dindzans VJ, Gavaler JS, Tarter RE: The postoperative problems and management of the liver transplant recipient. Prog Liver Dis 9:657–685, 1990
Alexander JA, Demetris AJ, Gavaler JS, Makowka L, Starzl TE, Van Thiel DH: Pancreatitis following liver transplantation. Transplantation 45:1062–1065, 1988
Demetris AJ, Jaffe R, Sheahan DG, et al: Recurrent hepatitis B in liver allograft recipients. Differentiation between viral hepatitis B and rejection. Am J Pathol 125:161–172, 1986
Davies SE, Portmann B, O'Grady JG, Aldis PM, Chaggar K, Alexander GJM, Williams R: Hepatic histology following transplantation for chronic hepatitis B virus infection including a unique pattern of fibrosing cholestatic hepatitis. Hepatology 13:150–157, 1991
Corman JL, Putnam CW, Iwatsuki S, et al: Liver allograft. Its use in chronic active hepatitis with macronodular cirrhosis, hepatitis B surface antigen. Arch Surg 114:75–78, 1979
Block GD, Van Thiel DH, Todo S, Starzl TE: Interferonalfa-2b improves survival in patients transplanted for chronic liver failure due to hepatitis B. J Hepatol (in press)
Van Thiel DH, Wright HI, Gavaler JS, Fung J, Starzl TE: Interferon therapy of hepatitis following transplantation under FK 506 or cyclosporine A. Transplant Proc 23:3052–3053, 1991
Wright HI, Gavaler JS, Van Thiel DH: Preliminary experience with α 2b interferon therapy of viral hepatitis in liver allograft recipients. Transplantation 53:121–124, 1992
Smedile A, Marzano A, Farci P, Chiaberge E, Abate A, Ottobrelli A, Brunetto MR, Rosina F, Durazzo M, Verme G, Bonino F, Rizzetto M: Liver transplant for viral hepatitis. Recurrence of reinfection. J Hepatol 13:S134-S137, 1991
Van Thiel DH, Fung JJ, Todo S, Demetris AJ, Starzl TE: Liver transplantation for viral liver disease.In Viral Hepatitis and Liver Disease. FB Hollinger, SM Lemon, HS Margolis (eds). Baltimore. Williams & Wilkins, 1991, pp 629–631
Fung J, Ostberg L, Shapiro R, Todo S, Demetris A, Starzl TE: Human monoclonal antibody against hepatitis B surface antigen in preventing recurrent hepatitis B following liver transplantation.In Viral Hepatitis and Liver Disease. FB Hollinger, SM Lemon, HS Margolis (eds). Baltimore, Williams & Wilkins, 1991, pp 651–654
Ming W, Todo S, Fung JJ, Van Thiel DH, Starzl TE, Demetris AJ: Analysis of hepatitis B viral antigen expression in liver allografts: Correlation with HBV serology and histopathology. Hepatology (in press)
Samuel D, Bismuth H, Methieu D, et al: Passive immunoprophylaxis after liver transplantation in HBsAg positive patients. Lancet 337:813–815, 1991
Hsu HM, Chen DS, Chuang CH, Lu JCF, Two DM, Lee CC, Lu HC, Cheng SH, Wang Chen C, Lo KJ, Shih CJ, Sung JL, The Hepatitis Control Committee, The Hepatitis Steering Committee: Efficacy of a mass hepatitis B vaccination program in Taiwan. JAMA 260:2231–2235, 1988
Pereira BJG, Milford EL, Kirkman RL, Levey AS: Transmission of hepatitis C virus by organ transplantation. N Engl J Med 321:454–460, 1991
Diethelm AG, Roth D, Gerguson RM, Schiff ER, Hardy MA, Starzl TE, Miller J, Van Thiel DH, Najarian JS: Transmission of HCV by organ transplantation. N Engl J Med 326:410–411, 1992 (letter)
Davis CL: The prevention of cytomegalovirus disease in renal transplantation. Am J. Kidney Dis 16:175, 1990
Paya CV, Hermans PE, Smith TF, et al: Efficacy of gancyclovir in liver and kidney transplant recipients with severe cytomegalovirus infection. Transplantation 46:229–234, 1988
Hanto DW, Frizzera G, Peczalska G, et al: Epstein-Barr virus induced B cell lymphoma after renal transplantation: Acyclovir therapy and transition from polyclonal to monoclonal B cell proliferation. N Engl J Med 306:913–918, 1982
Awad J, Peters MG, Brunt E, Hanto DW: Herpes viral hepatitis in liver transplant recipients. Clin Transplant 6:16–20, 1992
Demetris AJ, Jaffe R, Starzl TE: A review of adults and pediatric post-transplant liver pathology. Pathol Annu 22:347–386, 1987
Demetris AJ, Kakizoe S, Oguma S: Pathology of liver transplantation.In Hepatic Transplantation. JW William (ed). Philadelphia, WB Saunders, 1990, pp 60–113
O'Brien J, Campoli-Richards DM: Acyclovir—an updated review of its antiviral activity, pharmacokinetic properties, and therapeutic efficacy. Drugs 37:233, 1989
Breinig MK, Zitelli B, Starzl TE, Ho M: Epstein-Barr virus, cytomegalovirus and other viral infections in children after liver transplantation. J Infect Dis 157:273–279, 1987
Ho M, Miller G, Atchison RW, et al: Epstein-Barr virus infections and DNA hybridization studies post-transplantation lymphoma and lymphoproliferative lesions. J Infect Dis 152:876–886, 1985
Nalesnik MA, Makowka L, Starzl TE: The diagnosis and treatment of post-transplant lymphoproliferative disease. Curr Prob Surg 25:37–47, 1988
Psacharopoulos HT, Morat AP, Davies M, Portmann B, Silk DBA, Williams R: Fulminant hepatic failure in childhood. An analysis of 31 cases. Arch Dis Childhood 52:252–258, 1980
Singh N, Dummer JS, Kusne S, et al: Infections with cytomegalovirus and other herpes viruses in 121 liver transplant recipients: transmission by donated organ and the effect of OKT3 antibodies. J Infect Dis 158:124–131, 1988
Paya CV, Hermans PE, Wiesner RH, et al: Cytomegalovirus hepatitis in liver transplantation: prospective analysis of 93 consecutive orthotopic liver transplantations. J Infect Dis 160:752, 1989
Koneru B, Atchison R, Jaffe R, Van Thiel DH, Starzl TE: Serological Studies of adenoviral hepatitis following pediatric liver transplantation. Transplant Proc 22:1547–1548, 1990
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fagiuoli, S., Shah, G., Wright, H.I. et al. Types, causes, and therapies of hepatitis occurring in liver transplant recipients. Digest Dis Sci 38, 449–456 (1993). https://doi.org/10.1007/BF01316498
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01316498