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. 1982 Jun;23(6):465–474. doi: 10.1136/gut.23.6.465

Liver disease after bone marrow transplantation.

M J Farthing, M L Clark, J P Sloane, R L Powles, T J McElwain
PMCID: PMC1419702  PMID: 7042484

Abstract

Liver dysfunction occurs after bone marrow transplantation but the relative importance of graft versus host disease and other factors, such as infection, radiation, and drugs, has not been clearly established. We have studied liver status before and after bone marrow transplantation in 43 consecutive patients and have related this to survival and factors that are recognised to cause liver injury. Minor abnormalities of liver tests occurred in 21% of patients before grafting but this did not influence survival or the development of liver disease after transplantation. During the first 50 days after grafting, 83% of patients had abnormal liver tests which were more severe in patients who subsequently died. Alanine transaminase was significantly higher in non-survivors and appeared to predict survival early after transplantation. Only non-survivors developed clinical signs of liver disease. Severe liver disease was always associated with graft versus host disease and atypia of the small bile ducts was the most useful histological marker of hepatic involvement with this disease. Two of the patients with hepatic graft versus host disease also has hepatic veno-occlusive disease and three fatalities had opportunistic infection of the liver, although, in the latter, death was not due primarily to liver dysfunction. Previous hepatitis and androgen therapy could not be implicated as important causes of hepatic damage but chemotherapy for acute leukaemia and conditioning regimens for bone marrow transplantation appear to be the most important factors in the development of hepatic veno-occlusive disease.

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Selected References

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  1. Aubrey D. A. Massive hepatic necrosis after cyclophosphamide. Br Med J. 1970 Sep 5;3(5722):588–588. doi: 10.1136/bmj.3.5722.588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bagheri S. A., Boyer J. L. Peliosis hepatis associated with androgenic-anabolic steroid therapy. A severe form of hepatic injury. Ann Intern Med. 1974 Nov;81(5):610–618. doi: 10.7326/0003-4819-81-5-610. [DOI] [PubMed] [Google Scholar]
  3. Berk P. D., Popper H., Krueger G. R., Decter J., Herzig G., Graw R. G., Jr Veno-occlusive disease of the liver after allogeneic bone marrow transplantation: possible association with graft-versus-host disease. Ann Intern Med. 1979 Feb;90(2):158–164. doi: 10.7326/0003-4819-90-2-158. [DOI] [PubMed] [Google Scholar]
  4. Beschorner W. E., Pino J., Boitnott J. K., Tutschka P. J., Santos G. W. Pathology of the liver with bone marrow transplantation. Effects of busulfan, carmustine, acute graft-versus-host disease, and cytomegalovirus infection. Am J Pathol. 1980 May;99(2):369–386. [PMC free article] [PubMed] [Google Scholar]
  5. Calne R. Y., White D. J., Pentlow B. D., Rolles K., Syrakos T., Ohtawa T., Smith D. P., McMaster P., Evans D. B., Herbertson B. M. Cyclosporin A: preliminary observations in dogs with pancreatic duodenal allografts and patients with cadaveric renal transplants. Transplant Proc. 1979 Mar;11(1):860–864. [PubMed] [Google Scholar]
  6. Celle G., Dodero M., Bogliolo G., Mansi C., Pannacciulli I. Chronic treatment with azathioprine and cyclophosphamide in rats: structural and functional effects on small intestine and liver. G E N. 1977 Jan-Mar;31(3):179–184. [PubMed] [Google Scholar]
  7. Dahl M. G., Gregory M. M., Scheuer P. J. Liver damage due to methotrexate in patients with psoriasis. Br Med J. 1971 Mar 20;1(5750):625–630. doi: 10.1136/bmj.1.5750.625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dahl M. G., Gregory M. M., Scheuer P. J. Methotrexate hepatotoxicity in psoriasis--comparison of different dose regimens. Br Med J. 1972 Mar 11;1(5801):654–656. doi: 10.1136/bmj.1.5801.654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jacobs P., Miller J. L., Uys C. J., Dietrich B. E. Fatal veno-occlusive disease of the liver after chemotherapy, whole-body irradiation and bone marrow transplantation for refractory acute leukaemia. S Afr Med J. 1979 Jan 6;55(1):5–10. [PubMed] [Google Scholar]
  10. Krüger G. R., Berard C. W., DeLellis R. A., Graw R. G., Jr, Yankee R. A., Leventhal B. G., Rogentine G. N., Herzig G. P., Halterman R. H., Henderson E. S. Graft-versus-host disease. Morphologic variation and differential diagnosis in 8 cases of HL-A matched bone marrow transplantation. Am J Pathol. 1971 May;63(2):179–202. [PMC free article] [PubMed] [Google Scholar]
  11. Kun L. E., Camitta B. M. Hepatopathy following irradiation and adriamycin. Cancer. 1978 Jul;42(1):81–84. doi: 10.1002/1097-0142(197807)42:1<81::aid-cncr2820420113>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  12. Lee C. C., Castles T. R., Kintner L. D. Single-dose toxicity of cyclophosphamide (NSC-26271) in dogs and monkeys. Cancer Chemother Rep 3. 1973 Jan;4(1):51–76. [PubMed] [Google Scholar]
  13. Lerner K. G., Kao G. F., Storb R., Buckner C. D., Clift R. A., Thomas E. D. Histopathology of graft-vs.-host reaction (GvHR) in human recipients of marrow from HL-A-matched sibling donors. Transplant Proc. 1974 Dec;6(4):367–371. [PubMed] [Google Scholar]
  14. Lewin K., Millis R. R. Human radiation hepatitis. A morphologic study with emphasis on the late changes. Arch Pathol. 1973 Jul;96(1):21–26. [PubMed] [Google Scholar]
  15. Ludwig J. Drug effects on the liver: a tabular compilation of drugs and drug-related hepatic diseases. Dig Dis Sci. 1979 Oct;24(10):785–796. doi: 10.1007/BF01317213. [DOI] [PubMed] [Google Scholar]
  16. Powles R. L., Barrett A. J., Clink H., Kay H. E., Sloane J., McElwain T. J. Cyclosporin A for the treatment of graft-versus-host disease in man. Lancet. 1978 Dec 23;2(8104-5):1327–1331. doi: 10.1016/s0140-6736(78)91971-2. [DOI] [PubMed] [Google Scholar]
  17. Powles R. L., Morgenstern G., Clink H. M., Hedley D., Bandini G., Lumley H., Watson J. G., Lawson D., Spence D., Barrett A. The place of bone-marrow transplantation in acute myelogenous leukaemia. Lancet. 1980 May 17;1(8177):1047–1050. doi: 10.1016/s0140-6736(80)91497-x. [DOI] [PubMed] [Google Scholar]
  18. Reed G. B., Jr, Cox A. J., Jr The human liver after radiation injury. A form of veno-occlusive disease. Am J Pathol. 1966 Apr;48(4):597–611. [PMC free article] [PubMed] [Google Scholar]
  19. Sale G. E., Lerner K. G., Barker E. A., Shulman H. M., Thomas E. D. The skin biopsy in the diagnosis of acute graft-versus-host disease in man. Am J Pathol. 1977 Dec;89(3):621–636. [PMC free article] [PubMed] [Google Scholar]
  20. Sale G. E., Storb R., Kolb H. Histopathology of hepatic acute graft-versus-host disease in the dog. A double blind study confirms the specificity of small bile duct lesions. Transplantation. 1978 Aug;26(2):103–106. doi: 10.1097/00007890-197808000-00009. [DOI] [PubMed] [Google Scholar]
  21. Shulman H. M., McDonald G. B., Matthews D., Doney K. C., Kopecky K. J., Gauvreau J. M., Thomas E. D. An analysis of hepatic venocclusive disease and centrilobular hepatic degeneration following bone marrow transplantation. Gastroenterology. 1980 Dec;79(6):1178–1191. [PubMed] [Google Scholar]
  22. Slavin R. E., Santos G. W. The graft versus host reaction in man after bone marrow transplantation: pathology, pathogenesis, clinical features, and implication. Clin Immunol Immunopathol. 1973 Jul;1(4):472–498. doi: 10.1016/0090-1229(73)90005-6. [DOI] [PubMed] [Google Scholar]
  23. Slavin R. E., Woodruff J. M. The pathology of bone marrow transplantation. Pathol Annu. 1974;9(0):291–344. [PubMed] [Google Scholar]
  24. Sloane J. P., Farthing M. J., Powles R. L. Histopathological changes in the liver after allogeneic bone marrow transplantation. J Clin Pathol. 1980 Apr;33(4):344–350. doi: 10.1136/jcp.33.4.344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Storb R., Epstein R. B., Graham T. C., Thomas E. D. Methotrexate regimens for control of graft-versus-host disease in dogs with allogeneic marrow grafts. Transplantation. 1970 Mar;9(3):240–246. doi: 10.1097/00007890-197003000-00007. [DOI] [PubMed] [Google Scholar]
  26. Storb R., Prentice R. L., Thomas E. D. Treatment of aplastic anemia by marrow transplantation from HLA identical siblings. Prognostic factors associated with graft versus host disease and survival. J Clin Invest. 1977 Apr;59(4):625–632. doi: 10.1172/JCI108680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Storb R., Thomas E. D., Weiden P. L., Buckner C. D., Clift R. A., Fefer A., Fernando L. P., Giblett E. R., Goodell B. W., Johnson F. L. Aplastic anemia treated by allogeneic bone marrow transplantation: a report on 49 new cases from Seattle. Blood. 1976 Dec;48(6):817–841. [PubMed] [Google Scholar]
  28. Storring R. A., Jameson B., McElwain T. J., Wiltshaw E. Oral non-absorbed antibiotics prevent infection in acute non-lymphoblastic leukaemia. Lancet. 1977 Oct 22;2(8043):837–840. doi: 10.1016/s0140-6736(77)90779-6. [DOI] [PubMed] [Google Scholar]
  29. Tefft M., Mitus A., Jaffe N. Irradiation of the liver in children: acute effects enhanced by concomitant chemotherapeutic administration? Am J Roentgenol Radium Ther Nucl Med. 1971 Jan;111(1):165–173. doi: 10.2214/ajr.111.1.165. [DOI] [PubMed] [Google Scholar]
  30. Thomas E. D., Buckner C. D., Banaji M., Clift R. A., Fefer A., Flournoy N., Goodell B. W., Hickman R. O., Lerner K. G., Neiman P. E. One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation. Blood. 1977 Apr;49(4):511–533. [PubMed] [Google Scholar]
  31. Thomas E. D., Buckner C. D., Clift R. A., Fefer A., Johnson F. L., Neiman P. E., Sale G. E., Sanders J. E., Singer J. W., Shulman H. Marrow transplantation for acute nonlymphoblastic leukemia in first remission. N Engl J Med. 1979 Sep 13;301(11):597–599. doi: 10.1056/NEJM197909133011109. [DOI] [PubMed] [Google Scholar]
  32. Thomas E. D., Storb R., Clift R. A., Fefer A., Johnson L., Neiman P. E., Lerner K. G., Glucksberg H., Buckner C. D. Bone-marrow transplantation (second of two parts). N Engl J Med. 1975 Apr 24;292(17):895–902. doi: 10.1056/NEJM197504242921706. [DOI] [PubMed] [Google Scholar]
  33. Woodruff J. M., Hansen J. A., Good R. A., Santos G. W., Slavin R. E. The pathology of the graft-versus-host reaction (GVHR) in adults receiving bone marrow transplants. Transplant Proc. 1976 Dec;8(4):675–684. [PubMed] [Google Scholar]
  34. Woods W. G., Dehner L. P., Nesbit M. E., Krivit W., Coccia P. F., Ramsay N. K., Kim T. H., Kersey J. H. Fatal veno-occlusive disease of the liver following high dose chemotherapy, irradiation and bone marrow transplantation. Am J Med. 1980 Feb;68(2):285–290. doi: 10.1016/0002-9343(80)90368-x. [DOI] [PubMed] [Google Scholar]

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