Advertisement

Liver Disease of Pregnancy: Clinical Aspects

  • Rowen K. Zetterman
  • Rodney S. Markin

Abstract

The development of liver injury during pregnancy is unusual and occurs in less than 0.2% of cases. Jaundice develops in only 1 in 1500 pregnancies.1 Liver injury can occur as a consequence of or coincident with pregnancy (Table I) developing in any trimester or even postpartum, depending on its etiology (Table II). The most common cause of liver injury in the pregnant patient is acute viral hepatitis accounting for up to 40% of cases. An enterically transmitted form of non-A, non-B (NANB) hepatitis has recently been observed that may cause an increased mortality rate in pregnant women. To date, it has only been observed in patients in or from developing countries. In some areas, such as Scandinavia or Chile, intrahepatic cholestasis of pregnancy occurs with high frequency and may account for 10–20% of jaundice during pregnancy. Other forms of liver injury are unusual during pregnancy.

Keywords

Liver Injury Obstet Gynecol Intrahepatic Cholestasis Hyperemesis Gravidarum HELLP Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Haemmerli UP: Jaundice during pregnancy with special emphasis on recurrent jaundice during pregnancy and its differential diagnosis. Acta Med Scand 179(suppl):1–111, 1966.Google Scholar
  2. 2.
    Pritchard JA: Changes in blood volume during pregnancy and delivery. Anesthesia 26:393–397, 1965.CrossRefGoogle Scholar
  3. 3.
    Everson GT, McKinley C, Lawson M, et al: Gallbladder function in the human female: Effect of the ovulatory cycle, pregnancy and contraceptive steroids. Gastroenterology 82:711–719, 1982.PubMedGoogle Scholar
  4. 4.
    Kern FJ, Everson GT, DeMark B, et al: Biliary lipids, bile acids and gallbladder function in the human female: Effects of pregnancy and the ovulatory cycle. J Clin Invest 68:1229–1242, 1981.PubMedCrossRefGoogle Scholar
  5. 5.
    McKay DG, Merrill SJ, Weiner AE, et al: The pathologic anatomy of eclampsia, bilateral renal cortical necrosis, pituitary necrosis, and other acute fatal complications of pregnancy, and its possible relationship to the generalized Schwartzman phenomenon. Am J Obstet Gynecol 66:507–539, 1953.PubMedGoogle Scholar
  6. 6.
    Adams RH, Gordon J, Comes B: Hyperemesis gravidarum. I. Evidence of hepatic dysfunction. Obstet Gynecol 31:659–664, 1968.PubMedCrossRefGoogle Scholar
  7. 7.
    Sheeham HL: The pathology of hyperemesis and vomiting of late pregnancy. J Obstet Gynecol Br Emp 4b:685–689, 1939.CrossRefGoogle Scholar
  8. 8.
    Larrey D, Rueff B, Feldmann G, et al: Recurrent jaundice caused by recurrent hyperemesis gravidarum. Gut 25:1414–1415, 1984.PubMedCrossRefGoogle Scholar
  9. 9.
    Furhoff AK, Hellstrom K: Jaundice in pregnancy: A followup study of the series of women originally reported by L. Thorling. Acta Med Scand 193:259–266, 1973.PubMedCrossRefGoogle Scholar
  10. 10.
    Page EW: On the pathogenesis of pre-eclampsia and eclampsia. J Obstet Gynaecol Commonw 79:883–894, 1972.CrossRefGoogle Scholar
  11. 11.
    Worley RJ: Pathophysiology of pregnancy-induced hypertension. Clin Obstet Gynecol 27:821–835, 1984.PubMedCrossRefGoogle Scholar
  12. 12.
    Killam AP, Dillard SH, Patton RC, et al: Pregnancy-induced hypertension complicated by acute liver disease and disseminated intravascular coagulation. Am J Obstet Gynecol 123:823–828, 1975.PubMedGoogle Scholar
  13. 13.
    Weistein L: Syndrome of hemolysis, elevated liver enzymes and low platelet count: A severe consequence of hypertension in pregnancy. Am J Obstet Gynecol 142:159–167, 1982.Google Scholar
  14. 14.
    MacKenna J, Dover NL, Brame RG: Preeclampsia associated with hemolysis, elevated liver enzymes and low platelets—An obstetric emergency. Obstet Gynecol 62:751–754, 1983.PubMedGoogle Scholar
  15. 15.
    Sibai BM, Taslimi MM, El-Nazer A, et al: Maternal-perinatal outcome associated with the syndrome of hemolysis, elevated liver enzymes and low platelets in severe preeclampsia-eclampsia. Am J Obstet Gynecol 155:501–509, 1986.PubMedGoogle Scholar
  16. 16.
    Antia FP, Bharadwaj TP, Watsa MC, et al: Liver in normal pregnancy, preeclampsia and eclampsia. Lancet 2:776–778, 1958.PubMedCrossRefGoogle Scholar
  17. 17.
    Arias F, Mancilla-Jimenez R: Hepatic fibrinogen deposits in preeclampsia. N Engl J Med 295:578–582, 1976.PubMedCrossRefGoogle Scholar
  18. 18.
    Long RG, Scheuer PJ, Sherlock S: Pre-eclampsia presenting with deep jaundice. J Clin Pathol 30:212–215, 1977.PubMedCrossRefGoogle Scholar
  19. 19.
    Goodlin RC, Holdt D: Impending gestosis. Obstet Gynecol 58:743–745, 1981.PubMedGoogle Scholar
  20. 20.
    Goodlin RC, Zetterman RK: When your pregnant patient develops jaundice. Contemp Obstet Gynecol 24:27–44, 1984.Google Scholar
  21. 21.
    Manas KJ, Welsh JD, Rankin RA, et al: Hepatic hemorrhage without rupture in preeclampsia. N Engl J Med 312:424–426, 1985.PubMedCrossRefGoogle Scholar
  22. 22.
    Dammann HG, Hagemann J, Runge M, et al: In vivo diagnosis of massive hepatic infarction by computed tomography. Dig Dis Sci 27:73–79, 1982.PubMedCrossRefGoogle Scholar
  23. 23.
    Riely CA: The liver in preeclampsial/eclampsia: The tip of the iceberg. Am J Gastroenterol 81:1218–1219, 1986.PubMedGoogle Scholar
  24. 24.
    Rolfes DB, Ishak KG: Liver disease in toxemia in pregnancy. Am J Gastroenterol 81:1138–1144, 1986.PubMedGoogle Scholar
  25. 25.
    Biska, Waxman B: Rupture of the liver associated with pregnancy: A review of the literature and report of 2 cases. Obstet Gynecol Surv 31:763–773, 1976.CrossRefGoogle Scholar
  26. 26.
    Henny P, Lim AE, Brummelkamp WH, et al: A review of the importance of acute multidisciplinary treatment following spontaneous rupture of the liver capsule during pregnancy. Surg Gyn Obstet 156:593–598, 1983.Google Scholar
  27. 27.
    Stalter KD, Sterling WA: Hepatic subcapsular hemorrhage associated with pregnancy. Surgery 98:112–114, 1985.PubMedGoogle Scholar
  28. 28.
    Sommer DG, Greenway GD, Bookstein J, et al: Hepatic rupture with toxemia of pregnancy: Angiographic diagnosis. AJR 132:455–456, 1979.PubMedGoogle Scholar
  29. 29.
    Loevinger EH, Vujic I, Lee WM, et al: Hepatic rupture associated with pregnancy: Treatment with transcatheter embolotherapy. Obstet Gynecol 65:281–284, 1985.PubMedGoogle Scholar
  30. 30.
    Goodlin RC, Anderson JC, Hodgson PE: Conservative treatment of liver hematoma in the postpartum period. J Reprod Med 30:368–370, 1985.PubMedGoogle Scholar
  31. 31.
    Woodhouse DR: Conservative management of spontaneous rupture of the liver in pregnancy. Br J Obstet Gynaecol 93:1097–1099, 1986.PubMedCrossRefGoogle Scholar
  32. 32.
    Weiner CP, Brandt J: Plasma antithrombin III activity: An aid in the diagnosis of preeclampsia-eclampsia. Am J Obstet Gynecol 142:275–281, 1982.PubMedGoogle Scholar
  33. 33.
    Goodlin RC: Severe preeclampsia. Another great imitator. Am J Obstet Gynecol 125:747–753, 1976.PubMedGoogle Scholar
  34. 34.
    Lin CC, Lindheimer MD, River P, et al: Fetal outcome in hypertensive disorders of pregnancy. Am J Obstet Gynecol 142:255–260, 1982.PubMedGoogle Scholar
  35. 35.
    Svanborg A: A study of recurrent jaundice in pregnancy. Acta Obstet Gynecol Scand 33:434–444, 1954.PubMedCrossRefGoogle Scholar
  36. 36.
    Thorling L: Jaundice in pregnancy: A clinical study. Acta Med Scand 302 (suppl):1–123, 1955.Google Scholar
  37. 37.
    Reyes H, Gonzalez MC, Ribalta J, et al: Prevalence of intrahepatic cholestasis of pregnancy in Chile. Ann Intern Med 88:487–493, 1978.PubMedGoogle Scholar
  38. 38.
    Reyes H: The enigm of intrahepatic cholestasis of pregnancy: Lessons from Chile. Hepatology 2:87–96,1982.PubMedCrossRefGoogle Scholar
  39. 39.
    Forkman B, Ganrot PO, Genser G, et al: Plasma protein pattern in recurrent cholestasis of pregnancy. Scand J Clin Lab Invest 124 (suppl 29):89–99, 1972.CrossRefGoogle Scholar
  40. 40.
    Wilson JAP: Intrahepatic cholestasis of pregnancy with marked elevation of transaminases in a black American. Dig Dis Sci 32:665–668, 1987.PubMedCrossRefGoogle Scholar
  41. 41.
    Furhoff AK, Hellstrom K: Jaundice in pregnancy. A follow-up study of the series of women originally reported by L. Thorling. Acta Med Scand 193:259–266, 1973.PubMedCrossRefGoogle Scholar
  42. 42.
    Drill VA: Benign cholestatic jaundice of pregnancy and benign cholestatic jaundice from oral contraceptives. Am J Obstet Gynecol 119:165–174, 1974.PubMedGoogle Scholar
  43. 43.
    Berg B, Helm G, Petersohn L, et al: Cholestasis of pregnancy: Clinical and laboratory studies. Acta Obstet Gynecol Scand 65:107–113, 1986.CrossRefGoogle Scholar
  44. 44.
    Arfwedson H: Generalized pruritis in pregnancy: Symptom of liver dysfunction. Obstet Gynecol 7:274–276, 1956.PubMedGoogle Scholar
  45. 45.
    Misra PS, Evanov FA, Wessely Z, et al: Idiopathic intrahepatic cholestasis of pregnancy. Am J Gastroenterol 73:54–59, 1980.PubMedGoogle Scholar
  46. 46.
    Kreek MJ, Sleisenger MH, Jeffries GH: Recurrent cholestatic jaundice of pregnancy with demonstrated estrogen sensitivity. Am J Med 43:795–803, 1967.PubMedCrossRefGoogle Scholar
  47. 47.
    Orellano-Alcalde JM, Domingues JP: Jaundice and oral contraceptive drugs. Lancet 2:1278–1280, 1966.CrossRefGoogle Scholar
  48. 48.
    dePagler AGF, VanBerge Henegouwen GP, tenBokkel JA, et al: Familial benign recurrent intrahepatic cholestasis: Interrelation with intrahepatic cholestasis of pregnancy and from oral contraceptives. Gastroenterology 71:202–207, 1976.Google Scholar
  49. 49.
    Cohen L, Lewis C, Arias IM: Pregnancy, oral contraceptives and chronic familial jaundice with predominately conjugated hyperbilirubinemia (Dubin-Johnson syndrome). Gastroenterology 62:1182–1190, 1972.PubMedGoogle Scholar
  50. 50.
    Laatikainen T, Tulenheimo A: Maternal serum bile acid levels and fetal distress in cholestasis of pregnancy. Int J Gynaecol Obstet 22:91–94, 1984.PubMedCrossRefGoogle Scholar
  51. 51.
    Johnson P, Samsioe G, Gustafson A: Studies in cholestasis of pregnancy. I. Clinical aspects and liver function tests. Acta Obstet Gynecol Scand 54:77–84, 1975.PubMedCrossRefGoogle Scholar
  52. 52.
    Reyes H, Radrigan ME, Gonzalez MC, et al: Steatorrhea in patients with intrahepatic cholestasis of pregnancy. Gastroenterology 93:584–590, 1987.PubMedGoogle Scholar
  53. 53.
    Eliakim M, Sadovsky E, Stein O, et al: Recurrent cholestatic jaundice of pregnancy. Arch Intern Med 117:696–705, 1966.PubMedCrossRefGoogle Scholar
  54. 54.
    Adlercreutz H, Svanborg A, Anberg A: Recurrent jaundice in pregnancy. I. A clinical and ultrastructural study. Am J Med 42:335–347, 1967.PubMedCrossRefGoogle Scholar
  55. 55.
    Holzbach RT, Sanders JH: Recurrent intrahepatic cholestasis of pregnancy. JAMA 193:204–206, 1965.CrossRefGoogle Scholar
  56. 56.
    Kreek MJ, Weser E, Sleisenger MH, et al: Idiopathic cholestasis of pregnancy: The response to challenge with synthetic estrogen, ethinyl estradiol. N Engl J Med 277:1391–1395, 1965.CrossRefGoogle Scholar
  57. 57.
    Reyes H, Ribalta J, Gonzalez MC, et al: Sulfobromophthalein clearance tests before and after ethinyl estradiol administration, in women and men with familial history of intrahepatic cholestasis of pregnancy. Gastroenterology 81:226–231, 1981.PubMedGoogle Scholar
  58. 58.
    Reid R, Ivey KJ, Rencoret RH, et al: Fetal complications of obstetric cholestasis. Br Med J 1:870–872, 1976.PubMedCrossRefGoogle Scholar
  59. 59.
    Costoya AL, Leontic EA, Rosenberg HG, et al: Morphological study of placental terminal villi in intrahepatic cholestasis of pregnancy: Histochemistry, light and electron microscopy. Placenta 1:361–368, 1980.PubMedCrossRefGoogle Scholar
  60. 60.
    Espinoza J, Barnafi L, Schnaidt E: The effect of phenobarbital on intrahepatic cholestasis of pregnancy. Am J Obstet Gynecol 119:234–238, 1974.PubMedGoogle Scholar
  61. 61.
    Frezza M, Pozzato G, Chiesa L, et al: Reversal of intrahepatic cholestasis of pregnancy in women after high dose S-adenosyl-l-methionine administration. Hepatology 4:274–278, 1984.PubMedCrossRefGoogle Scholar
  62. 62.
    Moore HC: Acute fatty liver of pregnancy. J Obstet Gynecol Br Emp 63:189–198, 1956.CrossRefGoogle Scholar
  63. 63.
    Pockros PJ, Peters RL, Reynolds TB: Idiopathic fatty liver of pregnancy: Findings in ten cases. Medicine (Baltimore) 63:1–11, 1984.Google Scholar
  64. 64.
    Sheehan HL: The pathology of acute yellow atrophy and delayed chloroform poisoning. J Obstet Gynecol Br Emp 47:49–62, 1940.CrossRefGoogle Scholar
  65. 65.
    Ober WB, LeCompte PM: Acute fatty metamorphosis of the liver associated with pregnancy. Am J Med 19:743–758, 1955.PubMedCrossRefGoogle Scholar
  66. 66.
    Kahil MF, Fred HL, Brown H, et al: Acute fatty liver of pregnancy. Arch Intern Med 113:63–69, 1964.PubMedCrossRefGoogle Scholar
  67. 67.
    Bernuau J, Degott C, Nouel O, et al: Non-fatal acute fatty liver of pregnancy. Gut 24:340–344, 1983.PubMedCrossRefGoogle Scholar
  68. 68.
    Riely CA, Latham PS, Romero R, et al: Acute fatty liver of pregnancy: A reassessment based on observations in nine patients. Ann Intern Med 106:703–706, 1987.PubMedGoogle Scholar
  69. 69.
    Hou SH, Levin S, Ahola S, et al: Acute fatty liver of pregnancy: Survival with early cesarean section. Dig Dis Sci 29:449–452, 1984.PubMedCrossRefGoogle Scholar
  70. 70.
    Ebert EC, Sun EA, Wright SH, et al: Does early diagnosis and delivery in acute fatty liver of pregnancy lead to improvement in maternal and infant survival? Dig Dis Sci 29:453–455, 1984.PubMedCrossRefGoogle Scholar
  71. 71.
    Pockros PJ, Reynolds TB: Acute fatty liver of pregnancy. Dig Dis Sci 30:601–602, 1985.PubMedCrossRefGoogle Scholar
  72. 72.
    Haemmerli UP: Jaundice during pregnancy with special emphasis on recurrent jaundice during pregnancy and its differential diagnosis. Acta Med Scand 444 (suppl):1–111, 1966.Google Scholar
  73. 73.
    Hague WM, Fenton DW, Duncan SLB, et al: Acute fatty liver of pregnancy. J R Soc Med 76:652–659, 1983.PubMedGoogle Scholar
  74. 74.
    Burroughs AK, Seong NH, Dojcinov DM, et al: Idiopathic acute fatty liver of pregnancy in 12 patients. Q J Med 204:481–497, 1982.Google Scholar
  75. 75.
    Rolfes DB, Ishak KG: Acute fatty liver of pregnancy: A clinicopathologic study of 35 cases. Hepatology 5:1149–1158, 1985.PubMedCrossRefGoogle Scholar
  76. 76.
    Sun E, Decker J, Wright S, et al: Acute fatty liver of pregnancy: Criteria for early diagnosis and management. Gastroenterology 80:1296, 1981.Google Scholar
  77. 77.
    Hatfield AK, Stein JH, Greenberger NJ, et al: Idiopathic acute fatty liver of pregnancy: Death from extrahepatic manifestations. Dig Dis 17:167–178, 1972.CrossRefGoogle Scholar
  78. 78.
    Kunelis CT, Peters RL, Edmondson HA: Fatty liver of pregnancy and its relationship to tetracycline therapy. Am J Med 38:359–377, 1965.PubMedCrossRefGoogle Scholar
  79. 79.
    Brown MS, Reddy KR, Hensley GT, et al: The initial presentation of fatty liver of pregnancy mimicking acute viral hepatitis. Am J Gastroenterol 82:554–557, 1987.PubMedGoogle Scholar
  80. 80.
    Holzbach RT: Acute fatty liver of pregnancy with disseminated intravascular coagulation. Obstet Gynecol 43:740–744, 1974.PubMedGoogle Scholar
  81. 81.
    Cano RI, Delman MR, Pitchumoni CS, et al: Acute fatty liver of pregnancy complicated by disseminated intravascular coagulation. JAMA 231:159–161, 1975.PubMedCrossRefGoogle Scholar
  82. 82.
    Laursen B, Frost L, Mortensen JZ, et al: Acute fatty liver of pregnancy with complicating disseminated, intravascular coagulation. Acta Obstet Gynecol Scand 62:403–407, 1983.PubMedCrossRefGoogle Scholar
  83. 83.
    Riely CA: Acute hepatic failure at term. Postgrad Med 68:118–127, 1980.PubMedGoogle Scholar
  84. 84.
    Eisele JW, Barker EA, Smuckler EA: Lipid content in the liver of fatty metamorphosis of pregnancy. Am J Pathol 81:545–560, 1975.PubMedGoogle Scholar
  85. 85.
    Malatjalian DA, Bradley BWD: Acute fatty liver of pregnancy: Light and electron microscopic studies. Gastroenterology 84:1384, 1983.Google Scholar
  86. 86.
    Weber FL, Snodgrass PJ, Powell DE, et al: Abnormalities of hepatic mitochondrial urea-cycle enzyme activities and hepatic ultrastructure in acute fatty liver of pregnancy. J Lab Clin Med 94:27–41, 1979.PubMedGoogle Scholar
  87. 87.
    Schultz JC, Adamson JS, Workman WW, et al: Fatal liver disease after intravenous administration of tetracycline in high dosage. N Engl J Med 269:999–1004, 1963.PubMedCrossRefGoogle Scholar
  88. 88.
    Schiffer MA: Fatty liver associated with administration of tetracycline in pregnant and nonpregnant women. Am J Obstet Gynecol 96:326–332, 1966.PubMedGoogle Scholar
  89. 89.
    Wenk RG, Gebhardt FC, Bhagavan BS, et al: Tetracycline-associated fatty liver of pregnancy, including possible pregnancy risk after chronic dermatologie use of tetracycline. J Reprod Med 26:135–141, 1981.PubMedGoogle Scholar
  90. 90.
    Sherlock S: Acute fatty liver of pregnancy and the microvesicular fat diseases. Gut 24:265–269, 1983.PubMedCrossRefGoogle Scholar
  91. 91.
    Breen KJ, Perkins KW, Mistilis SP, et al: Idiopathic acute fatty liver of pregnancy. Gut 11:822–825, 1970.PubMedCrossRefGoogle Scholar
  92. 92.
    Davies MH, Wilkinson SP, Hanid MA, et al: Acute liver disease with encephalopathy and renal failure in late pregnancy and the early puerperiun. Br J Obstet Gynecol 87:1005–1014, 1980.CrossRefGoogle Scholar
  93. 3.
    Campillo B, Bernauau J, Witz M-O, et al: Ultrasonography in acute fatty liver of pregnancy. Ann Intern Med 105:383–384, 1986.Google Scholar
  94. 94.
    McKee CM, Weir PE, Foster JH, et al: Acute fatty liver of pregnancy and diagnosis by computed tomography. Br Med J 292;291–292, 1986.Google Scholar
  95. 95.
    Riely CA: Acute fatty liver of pregnancy—1984. Dig Dis Sci 29: 456–457, 1984Google Scholar
  96. 96.
    Duma RJ, Dowling EA, Alexander HC, et al: Acute fatty liver of pregnancy: Report of a surviving patient studied with serial liver biopsies. Ann Intern Med 63:851–858, 1956.Google Scholar
  97. 97.
    Rohs LS: Subcapsular hematoma in fatty liver of pregnancy. J Forensic Sci 31:1509–1513, 1986.Google Scholar
  98. 98.
    Minuk GY, Lui RC, Kelly jK: Rupture of the liver associated with acute fatty liver of pregnancy. Am J. Gastroenterol 82:457–460, 1987.Google Scholar
  99. 99.
    Sakamoto S, Tsuji Y, Koga S, et al: Idiopathic fatty liver of pregnancy with a subsequent uncomplicated pregnancy and a progressive increase in serum cholinesterase activity in the third trimester, Hepatogastroenterology 33:9–10, 1986.Google Scholar
  100. 100.
    MacKenna J, Pupkin M, Grenshaw C, et al: Acute fatty metamorphosis of the liver: A report of two patients who survived. Am J. Obstet Gynecol 127:400–404, 1977.Google Scholar
  101. 101.
    Jenkins WJ, Darling MR: Idiopathic acute fatty liver of pregnancy: Subsequent uncomplicated pregnancy. J Obstet Gynecol 1:100–101, 1980.Google Scholar

Copyright information

© Plenum Publishing Corporation 1989

Authors and Affiliations

  • Rowen K. Zetterman
    • 1
    • 2
  • Rodney S. Markin
    • 3
  1. 1.Section of Digestive Diseases and Nutrition, Department of Internal MedicineUniversity of Nebraska Medical CenterUSA
  2. 2.Veterans Administration Medical CenterOmahaUSA
  3. 3.Department of Pathology and MicrobiologyUniversity of Nebraska Medical CenterOmahaUSA

Personalised recommendations