Gebelik Kolestazı -Cholestasis of Pregnancy - www.jinekolojivegebelik.com

4,108 views

Published on

Gebelik Kolestazı -Cholestasis of Pregnancy - www.jinekolojivegebelik.com

Published in: Health & Medicine
1 Comment
16 Likes
Statistics
Notes
  • Fioricet is often prescribed for tension headaches caused by contractions of the muscles in the neck and shoulder area. Buy now from http://www.fioricetsupply.com and make a deal for you.
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
No Downloads
Views
Total views
4,108
On SlideShare
0
From Embeds
0
Number of Embeds
106
Actions
Shares
0
Downloads
0
Comments
1
Likes
16
Embeds 0
No embeds

No notes for slide

Gebelik Kolestazı -Cholestasis of Pregnancy - www.jinekolojivegebelik.com

  1. 1. INTRAHEPATIC CHOLESTASIS OF PREGNANCY Dr .Ashraf Fouda Ob/Gyn. Consultant Damietta General Hospital E. mail : ashraffoda@hotmail.com
  2. 2. Introduction <ul><li>Intrahepatic cholestasis is characterized by: pruritus and mild jaundice usually occurring in the last trimester of pregnancy. </li></ul><ul><li>It can, however, occur earlier in gestations. </li></ul>
  3. 3. Incidence <ul><li>It has an uneven worldwide incidence of 1 in 1,000 to 1 in 10,000 deliveries. </li></ul>
  4. 4. <ul><li>The disease is reported to affect up to 14 % of pregnancies in Chile. </li></ul><ul><li>Gonzalez et al . determined the prevalence of intrahepatic cholestasis of pregnancy in Chile to be 4.7 % in singleton pregnancies. </li></ul>Introduction
  5. 5. <ul><li>In twin pregnancies, the incidence was 21 %. </li></ul><ul><li>The disease is also common in the Swedish population. </li></ul><ul><li>Berg et al. reported the incidence in Sweden to be between 1 and 1.5 % . </li></ul><ul><li>In their study, the incidence of intrahepatic cholestasis of pregnancy had a distinct seasonal variation , peaking in November . </li></ul>Introduction
  6. 6. <ul><li>This disorder is much less common in the United States , but appears to have a familial predisposition in Sweden. </li></ul><ul><li>In 1987, Wilson reported the first case of intrahepatic cholestasis of pregnancy in an African-American patient . </li></ul><ul><li>Abedin et al. found that cholestasis of pregnancy occurred in up to 1.5 % of Asian women of Pakistani and Indian origin. </li></ul>Introduction
  7. 7. <ul><li>Intrahepatic cholestasis tends to recur in subsequent pregnancies , but the severity may vary from one pregnancy to the next. </li></ul><ul><li>In their Chilean study, Gonzalez et al. reported a recurrence rate of 70 % in singleton pregnancies. </li></ul>Introduction
  8. 8. <ul><li>Locatelli et al. found cholestasis of pregnancy in 16 % of patients with hepatitis C compared with 1 % of controls , suggesting that individuals with hepatitis C are more prone to cholestasis of preganacy. </li></ul>Introduction
  9. 9. Clinical Manifestations <ul><li>Patients with intrahepatic cholestasis usually begin having pruritus at night . </li></ul><ul><li>It progresses, and the patient is soon experiencing bothersome pruritus continuously. </li></ul><ul><li>Approximately 2 weeks later , clinical jaundice will develop in 50 % of cases. </li></ul><ul><li>The jaundice is usually mild , soon plateaus, and remains constant until delivery. </li></ul>
  10. 10. <ul><li>The pruritus worsens with the onset of jaundice, and the patient's skin can become excoriated. </li></ul><ul><li>The symptoms usually abate within 2 days after delivery. </li></ul>Clinical Manifestations
  11. 11. <ul><li>The differential diagnosis must include: </li></ul><ul><li>Viral hepatitis and </li></ul><ul><li>Gallbladder disease. </li></ul>Clinical Manifestations
  12. 12. <ul><li>There is usually no fever or abdominal discomfort , as in hepatitis , and </li></ul><ul><li>No nausea or vomiting, as seen in hepatitis and gallbladder disease. </li></ul>Clinical Manifestations
  13. 13. Laboratory Findings <ul><li>Serum alkaline phosphatase levels are increased 5- to 10-fold in intrahepatic cholestasis of pregnancy. </li></ul><ul><li>Alkaline phosphatase, however, is normally increased in pregnancy. </li></ul><ul><li>This is due to placental production of this enzyme. </li></ul>
  14. 14. <ul><li>Serum and urinary excretion of total sulfated progesterone metabolites are increased in cholestasis of pregnancy, whereas glucuronide metabolites are unchanged or low . </li></ul><ul><li>This shows that there is a primary change in the reductase metabolism of progesterone in cholestasis of pregnancy. </li></ul>Laboratory Findings
  15. 15. <ul><li>Bilirubin is elevated, but usually not above 5 mg/dl. </li></ul><ul><li>Most is the direct, conjugated form. </li></ul><ul><li>Serum 5'-nucleotidase levels are also increased. </li></ul>Laboratory Findings
  16. 16. <ul><li>If intrahepatic cholestasis lasts for several weeks, liver dysfunction may result in: </li></ul><ul><li>Decreased vitamin K reabsorption or </li></ul><ul><li>Decreased prothrombin production , leading to a prolongation of the prothrombin time. </li></ul>Laboratory Findings
  17. 17. <ul><li>Serum transaminase levels are usually normal or moderately elevated , remaining well below the levels associated with viral hepatitis. </li></ul><ul><li>Serum cholesterol and triglyceride levels may also be markedly elevated . </li></ul>Laboratory Findings
  18. 18. <ul><li>The serum bile acids (chenodeoxycholic acid, deoxycholic acid, and cholic acid) are increased . </li></ul><ul><li>The levels are often more than 10 times the normal concentration. </li></ul><ul><li>These acids are deposited in the skin and probably cause the extreme pruritus. </li></ul>Laboratory Findings
  19. 19. <ul><li>The degree of pruritus , however, is not always related to the serum level of bile acids. </li></ul><ul><li>To make the diagnosis of intrahepatic cholestasis of pregnancy, the fasting levels of serum bile acids should be at least three times the upper limit of normal. </li></ul>Laboratory Findings
  20. 20. <ul><li>Elevation of serum bile acids alone cannot be used to make the diagnosis. </li></ul><ul><li>The patient must also have clinical symptoms . </li></ul><ul><li>Serum transaminase levels may also be elevated 5 to 10 times normal . </li></ul><ul><li>Reyes et al. found that serum copper is significantly higher and selenium levels are significantly lower in individuals with cholestasis of pregnancy. </li></ul>Laboratory Findings
  21. 21. <ul><li>Wojcicka-Jagodzinska and colleagues reported that carbohydrate metabolism is disturbed in patients with intrahepatic cholestasis of pregnancy. </li></ul><ul><li>These patients should therefore be screened for gestational diabetes when the diagnosis of cholestasis is made. </li></ul>Laboratory Findings
  22. 22. <ul><li>Histologically , the periportal areas show no change, and the hepatocellular architecture remains undisturbed. </li></ul><ul><li>The centrilobular areas , however, reveal dilated bile canaliculi , many containing bile plugs. </li></ul><ul><li>Ultrastructurally , there appears to be some destruction and atrophy of microvilli in the bile canaliculi. </li></ul><ul><li>These changes tend to regress after pregnancy . </li></ul>Laboratory Findings
  23. 23. Perinatal Outcome <ul><li>The risk of: </li></ul><ul><li>Preterm birth and </li></ul><ul><li>Fetal death may be increased in patients suffering from intrahepatic cholestasis of pregnancy. </li></ul>
  24. 24. <ul><li>Fisk and Storey studied 83 pregnancies complicated by intrahepatic cholestasis over a 10-year period . </li></ul><ul><li>Meconium staining occurred in 45 % of the pregnancies, spontaneous preterm labor occurred in 44 % , and intrapartum fetal distress complicated 22 %. </li></ul><ul><li>Of the 86 infants, 2 were stillborn and 1 died soon after birth. </li></ul><ul><li>The overall perinatal mortality in this group of patients was 35 per 1,000 . </li></ul>Perinatal Outcome
  25. 25. <ul><li>Nonstress tests , </li></ul><ul><li>Serial ultrasonography to assess amniotic fluid volume, and </li></ul><ul><li>Estriol determinations failed to predict fetal compromise. </li></ul><ul><li>Early intervention was indicated in 49 pregnancies, 12 because of suspected fetal distress. </li></ul>Perinatal Outcome
  26. 26. <ul><li>In light of this study, antepartum fetal heart rate testing and intense surveillance should be undertaken in gravidas with intrahepatic cholestasis of pregnancy. </li></ul>Perinatal Outcome
  27. 27. <ul><li>It may also be prudent to induce labor at term or when amniotic fluid studies indicate fetal lung maturity. </li></ul>Perinatal Outcome
  28. 28. <ul><li>Heinonen and Kirkinen reviewed 91 cases of cholestasis in pregnancy in Finland from 1990 to 1996. </li></ul><ul><li>The cesarean section rate was 10 % higher in the group of women with cholestasis. </li></ul><ul><li>The risk of preterm delivery was higher and the need for neonatal intensive care was also higher . </li></ul>Perinatal Outcome
  29. 29. <ul><li>Matos et al. report a full-term infant with unexplained intracerebral hemorrhage in a patient with cholestasis of pregnancy. </li></ul>Perinatal Outcome
  30. 30. Management <ul><li>Treatment is aimed at reducing the intense pruritus. </li></ul><ul><li>Diphenhydramine, hydroxyzine , and other antihistamines help only slightly. </li></ul>
  31. 31. <ul><li>Cholestyramine is an anionbinding resin that interrupts the enterohepatic circulation, reducing the reabsorption of bile acids. </li></ul><ul><li>A total of 8 to 16 g/day in three to four divided doses is often helpful in relieving pruritus. </li></ul><ul><li>It is most effective if started as soon as the pruritus is noted, before it becomes severe. </li></ul><ul><li>It often takes up to 2 weeks to work . </li></ul>Cholestyramine
  32. 32. <ul><li>Because cholestyramine also interferes with vitamin K absorption , the prothrombin time should be checked at least weekly . </li></ul><ul><li>If prolonged , parenteral vitamin K should be administered. </li></ul><ul><li>When the prothrombin time returns to normal, the frequency of injections can be decreased. </li></ul>Cholestyramine
  33. 33. <ul><li>Cholestyramine causes a sensation of bloating and often results in constipation. </li></ul><ul><li>Cholestyramine also can interfere with the absorption of other ingested medications, including prenatal vitamins . </li></ul><ul><li>If the patient cannot tolerate cholestyramine, antacids containing aluminum may be used to bind bile acids. </li></ul><ul><li>These medications are usually not as effective as cholestyramine. </li></ul>Management
  34. 34. <ul><li>Phenobarbital, in a dose of up to 90 mg daily given at bedtime , can be helpful. </li></ul><ul><li>Phenobarbital induces hepatic microsomal enzymes, increasing bile salt secretion and bile flow. </li></ul><ul><li>This medication usually takes more than 1 week to be effective . </li></ul><ul><li>It has not been shown to change the serum concentration of bile acids. </li></ul>Management
  35. 35. <ul><li>It is important to remember that phenobarbital must not be given within 2 hours of cholestyramine , or the phenobarbital will be bound and excreted without being absorbed. </li></ul><ul><li>The key to treating pregnancy-induced cholestasis is to begin therapy as soon as the diagnosis is made. </li></ul>Management
  36. 36. <ul><li>Dexamethasone has also been used with some success in treating pregnancy-induced cholestasis. </li></ul><ul><li>Dexamethasone suppresses fetal—placental estrogen production, which is out of balance in the patient with cholestasis of pregnancy. </li></ul><ul><li>Leslie et al., however, have shown that downstream placental production of estrogen is compromised in patients with cholestasis of pregnancy. </li></ul>Management
  37. 37. <ul><li>Two studies have investigated using guar gum , a gelforming fiber that increases fecal elimination of bile acids, to treat the pruritus associated with pregnancy-induced cholestasis. </li></ul><ul><li>This dietary fiber was randomly assigned to 24 of 48 women with cholestasis of pregnancy in Finland . </li></ul>Management
  38. 38. <ul><li>In patients taking the guar gum , bile acids remained stable, whereas they increased in those taking the placebo. </li></ul><ul><li>Pruritus improved in those taking guar gum and worsened in the placebo group. </li></ul><ul><li>Similar results were obtained in 48 patients in a more recent study in Finland. </li></ul>Management
  39. 39. <ul><li>The two most recently studied medications for the treatment of intrahepatic cholestasis of pregnancy are S-adenyl-methionine (SAM-e) and ursodeoxycholic acid (UDCA). </li></ul>Management
  40. 40. <ul><li>SAM-e may work by reversing estrogen-induced impairment of bile secretion. </li></ul><ul><li>UDCA is a naturally occurring hydrophilic bile acid that replaces other more cytotoxic bile acids. </li></ul>Management
  41. 41. <ul><li>Nicastri et al . studied 32 women with intrahepatic cholestasis. </li></ul><ul><li>There were four study groups : </li></ul><ul><li>The first group received DCA; </li></ul><ul><li>The second SAM-e; </li></ul><ul><li>The third both drugs; and </li></ul><ul><li>The fourth received placebo. </li></ul><ul><li>A combination of both drugs was more effective than either drug alone. </li></ul>Management
  42. 42. <ul><li>Palma et al. compared 1 g daily of UDCA with a placebo over 3 weeks and found a significant decrease in pruritus and a significant decrease in liver function studies . </li></ul><ul><li>Other studies have shown similar results. </li></ul><ul><li>It appears that the proper dosage of UDCA is 14 to 16 mg/kg/day. </li></ul>Management
  43. 43. <ul><li>Because of intolerable pruritus and the possible impact on perinatal outcome , delivery may be undertaken at term or as soon as fetal lung maturity has been documented. </li></ul><ul><li>Jaundice usually disappears within 2 days after delivery . </li></ul>Management
  44. 44. <ul><li>The patient should be counseled that the condition may recur during subsequent pregnancies. </li></ul><ul><li>It is also important to note that some patients may manifest symptoms of intrahepatic cholestasis when taking oral contraceptives . </li></ul>Management
  45. 45. Thank you

×