Approach to liver disease occurring during pregnancy

1. Approach to liver disease occurring during pregnancy Naghshineh E .MD

2. liver diseases that are specific to pregnancy, or multisystem diseases unique to pregnancy • pregnancy-related physiologic changes that may worsen the severity of, or predispose to hepatobiliary diseases • diseases that are unassociated with pregnancy but can occur during pregnancy • Pregnancy can also occur in women with underlying chronic liver disease Liver disease in pregnancy

3. THE LIVER DURING NORMAL PREGNANCY • Physical examination — Spider angiomas and palmar erythema Liver disease in pregnancy

4. Ultrasound examination :Fasting gallbladder volume and residual volume after contraction may be increased • Pathology • Serum proteins and lipids : albumin , Serum total cholesterol and triglyceride Liver disease in pregnancy

5. serum fibrinogen increases in late pregnancy. Liver disease in pregnancy

6. Hyperemesis gravidarum • Intrahepatic cholestasis of pregnancy • Acute fatty liver of pregnancy • HELLP • preeclampsia Liver disease in pregnancy

7. PATTERNS OF HEPATOBILIARY DISEASE IN PREGNANCY • jaundice • Pruritus • abdominal pain • nausea, vomiting • liver biochemical test abnormalities Liver disease in pregnancy

8. American College of Gastroenterology Guidelines: Liver disease in the pregnant patient • gestational age of the pregnancy is the best guide • Hyperemesis gravidarum……in the 1st trimester • Cholestasis of pregnancy …….in the 2th ,3th trimester • HELLP ………………………………….in the second half • AFLP……………………………………in the 3th • Preeclampsia……………………...in the 3th Liver disease in pregnancy

9. Evaluation of liver disease in pregnancy Liver disease in pregnancy

10. Case 1 • A 26-year-old woman gravida 3 para 2 currently in her 10th week with a singleton gestation is hospitalized with intractable nausea, vomiting, and dehydration • During her two prior pregnancies, she also had severe nausea and vomiting, which resolved early in the second trimester. Liver disease in pregnancy

11. Her physical examination is notable for dry mucus membranes, and a gravid uterus • She has no abdominal pain, and does not have a palpable liver or spleen Liver disease in pregnancy

12. What is your first diagnosis? Liver disease in pregnancy

13. ALT (175 IU/L), AST (122 IU/L), serum total bilirubin (2.1 mg/dL) • Amylase and lipase are normal • The albumin is slightly decreased from normal values • Liver biochemical tests prior to pregnancy are not available • A right upper quadrant ultrasound is normal. • Urinalysis shows elevated ketones. Liver disease in pregnancy

14. Serology for hepatitis A, B, and C is negative, • antinuclear antibodies are absent, and serum protein electrophoresis is normal • TSH is normal • Obstetrical ultrasound examination demonstrates a normal singleton gestation. Liver disease in pregnancy

15. patient's clinical course and occurrence of symptoms early during pregnancy are consistent with hyperemesis gravidarum Liver disease in pregnancy

16. Common criteria for diagnosis of hyperemesis are persistent vomiting accompanied by weight loss exceeding 5 percent of prepregnancy body weight andketonuriaunrelated to other causes Liver disease in pregnancy

17. Abnormal liver enzyme values occur in approximately 50 percent • The most striking abnormality is an increase in serum aminotransferases • in the low hundreds or two to three times the upper limit of normal, and rarely as high as 1000 U/L • Hyperbilirubinemia can occur, but rarely exceeds 4 mg/dL Liver disease in pregnancy

18. Serum amylase and lipase may increase as much as 5-fold (as opposed to a 5- to 10-fold increase in acute pancreatitis) and are of salivary rather than pancreatic origin Liver disease in pregnancy

19. Preeclampsia, HELLP syndrome and acute fatty liver of pregnancy are also causes of pregnancy-related nausea and vomiting, but : • onset is in the latter half of pregnancy (usually the third trimester) • hypertension is usually present • thrombocytopenia is common Liver disease in pregnancy

20. Case 2 • A 23-year-old woman gravida 2 para 1 currently at 35 weeks with a singleton gestation is referred from a dermatologist for intractable itching • The itching is primarily on the palms of her hands and soles of her feet • It is present day and night, and keeps her from sleeping. Liver disease in pregnancy

21. The patient also had itching during her first pregnancy in which the fetus died in utero in the third trimester Liver disease in pregnancy

22. What is your first diagnosis? Liver disease in pregnancy

23. Intrahepatic cholestasis of pregnancy • Intrahepatic cholestasis of pregnancy (ICP) occurs in the second and thirdtrimester • is characterized by pruritus and an elevation in serum bile acid concentrations • For unknown reasons the disease is seen more commonly in the colder months Liver disease in pregnancy

24. PATHOGENESIS • The cause of ICP is unknown but genetic, hormonal, and environmental factors are likely involved Liver disease in pregnancy

25. Estrogens and progesterone • It is recommended that progesterone treatment be avoided in pregnant women with a previous history of ICP and immediately withdrawn when cholestasis occurs during pregnancy Liver disease in pregnancy

26. CLINICAL MANIFESTATIONS • Pruritus may precede laboratory abnormalities • Abdominal pain is uncommon • Encephalopathy or other stigmata of liver failure are unusual • Physical examination is nonspecific • may show excoriations due to scratching • Jaundice occurs in less than 10 percent Liver disease in pregnancy

27. Laboratory findings • Serum total bile acid concentrations increase in ICP, and may be the first or only laboratory abnormality • Serum cholic acid increases more than chenodeoxycholicacid • most women with an elevated bile acid ratio also have elevated total bile acid levels; as a result, obtaining a ratio does not enhance diagnostic performance • The ratio of glycine/taurine conjugates is decreased Liver disease in pregnancy

28. elevations in alkaline phosphatase, 5' nucleotidase, and total and direct bilirubin concentrations • Total bilirubin levels rarely exceed 6 mg/dL • gamma glutamyltranspeptidase (GGT) are normal or modestly elevated • aminotransferases may reach values greater than 1000 U/L • The prothrombin time is usually normal • prolonged prothrombin times reflect vitamin K deficiency due to cholestasis or to the use of bile acid sequestrantsrather than liver dysfunction. Liver disease in pregnancy

29. ULTRASONOGRAPHY • the biliary ducts are not dilated and hepatic parenchyma appears normal Liver disease in pregnancy

30. DIAGNOSIS • Most women are diagnosed during the second or third trimester • The diagnosis of ICP is based upon the presence of pruritus associated with elevated total serum bile acids levels and/or aminotransferases Liver disease in pregnancy

31. PATHOLOGY • is rarely necessary for the diagnosis • histopathology is characterized by cholestasis without inflammation • Bile plugs in hepatocytes and canaliculi predominate in zone 3 • The portal tracts are unaffected. Liver disease in pregnancy

32. TREATMENT • UDCA is considered as the first line treatment for ICP(500 BID or 300 TDS) • Hydroxyzine (25 to 50 mg/day) • Cholestyramine (8 to 16 g/day) Liver disease in pregnancy

33. Complications of cholestasis • hypoprothrombinemia induced by vitamin K deficiency; should be treated before delivery to prevent hemorrhage. Liver disease in pregnancy

34. Cholestasis recurs during subsequent pregnancies in 60 to 70 percent • increased risk for gallstones • some women who develop ICP have underlying liver disease : • women in whom ICP is suspected and/or who have elevated serum aminotransferase during pregnancy should be tested for chronic hepatitis (especially hepatitis C) • liver function tests should be checked several months after the delivery Liver disease in pregnancy

35. Hormonal contraception • contraceptives with a low dose of estrogen can be initiated after normalization of liver function tests • check liver function tests after three or six months of such contraception. Liver disease in pregnancy

36. FETAL FOLLOW-UP AND OUTCOME • In contrast to the favorable prognosis for mothers, ICP carries significant risk for the fetus • fetal prematurity • meconium stained amniotic fluid • intrauterine demise • neonatal respiratory distress syndrome Liver disease in pregnancy

37. Timing of delivery • 37 wk • 35-37 wk : • Severe itching • Jaundice • Prior fetal death Liver disease in pregnancy

38. Case 3 • A 32 year-old woman gravida 1 para 0 with a singleton gestation at 34 weeks of gestation is admitted to the hospital with a three-day history of nausea and vomiting, malaise, and jaundice • Her blood pressure is mildly elevated • Urinalysis shows trace protein • aminotransferases range between 200 to 500 • glucose is in the low-normal range • White blood cell count and prothrombin time are elevated Liver disease in pregnancy

39. What is your diagnosis ? Liver disease in pregnancy

40. Acute fatty liver of pregnancy • characterized by microvesicular fatty infiltration of hepatocytes, is a disorder which is unique to human pregnancy • early diagnosis and prompt delivery have dramatically improved the prognosis, and maternal mortality should now be the exception rather than the rule Liver disease in pregnancy

41. EPIDEMIOLOGY • is rare with an approximate incidence of 1 in 7000 to 1 in 20,000 deliveries • It is more common with multiple gestations and possibly in women who are underweight. Liver disease in pregnancy

42. CLINICAL MANIFESTATIONS • Acute fatty liver occurs typically in the third trimester • The disease is always present before delivery, although it is not always diagnosed prior to delivery • Symptom? Liver disease in pregnancy

43. The most frequent initial symptoms are nausea or vomiting 75 percent • abdominal pain :50 percent • Anorexia • Jaundice • one-half of patients have signs of preeclampsia at presentation or at some time during the course of illness Liver disease in pregnancy

44. infection • major intraabdominal bleeding • Transient polyuria and polydipsia due to central diabetes insipidus • pancreatitis, which can be severe. Pancreatitis generally becomes apparent only after development of hepatic and renal dysfunction Liver disease in pregnancy

45. Laboratory tests • aminotransferase ranging from modest values up to 1000 • Serum bilirubin levels are also usuallyelevated • The platelet count may be decreased with or without other signs of disseminated intravascular coagulation (DIC) • Severely affected patients also have elevations in serum ammonia, prolongation of prothrombin time, and hypoglycemia caused by hepatic insufficiency • Acute renal failure and hyperuricemia are often present Liver disease in pregnancy

46. DIAGNOSIS • made clinically based upon the setting, presentation, and compatible laboratory and imaging results • Laboratory tests that are helpful include serum aminotransferases, serum bilirubin, coagulation studies, electrolytes, serum glucose, uric acid level and creatinine, and a white blood cell count. Liver disease in pregnancy

47. TREATMENT AND COURSE • the primary treatment is prompt delivery, usually emergently, after maternal stabilization Liver disease in pregnancy

48. Maternal stabilization requires glucose infusion and reversal of coagulopathy • Attention should be paid to the women's overall fluid status because the low plasmatic oncotic pressure can lead to pulmonaryedema • Hypoglycemia is common and all patients should have glucose monitored until normal liver function returns Liver disease in pregnancy

49. The liver tests and coagulopathy usually start to normalize shortly after delivery Liver disease in pregnancy

50. RECURRENCE • Acute fatty liver can recur in subsequent pregnancies Liver disease in pregnancy