Approach to liver disease occurring during pregnancy

Approach to liver disease occurring during pregnancyNaghshineh E .MD

1liver diseases that are specific to pregnancy, or multisystem diseases unique to pregnancypregnancy-related physiologic changes that may worsen the severity of, or predispose to hepatobiliary diseases diseases that are unassociated with pregnancy but can occur during pregnancyPregnancy can also occur in women with underlying chronic liver disease2Liver disease in pregnancy2THE LIVER DURING NORMAL PREGNANCYPhysical examination Spider angiomas and palmar erythema

3Liver disease in pregnancy3Ultrasound examination :Fasting gallbladder volume and residual volume after contraction may be increasedPathologySerum proteins and lipids : albumin , Serum total cholesterol and triglyceride

4Liver disease in pregnancy4serum fibrinogen increases in late pregnancy.

5Liver disease in pregnancy5Hyperemesis gravidarumIntrahepatic cholestasis of pregnancyAcute fatty liver of pregnancyHELLPpreeclampsia6Liver disease in pregnancy6PATTERNS OF HEPATOBILIARY DISEASE IN PREGNANCY jaundicePruritusabdominal painnausea, vomitingliver biochemical test abnormalities7Liver disease in pregnancy7American College of Gastroenterology Guidelines: Liver disease in the pregnant patientgestational age of the pregnancy is the best guideHyperemesis gravidarum in the 1st trimesterCholestasis of pregnancy .in the 2th ,3th trimesterHELLP .in the second half AFLPin the 3thPreeclampsia...in the 3th8Liver disease in pregnancy8Evaluation of liver disease in pregnancy

9Liver disease in pregnancy9Case 1A 26-year-old woman gravida 3 para 2 currently in her 10th week with a singleton gestation is hospitalized with intractable nausea, vomiting, and dehydrationDuring her two prior pregnancies, she also had severe nausea and vomiting, which resolved early in the second trimester. 10Liver disease in pregnancy10Her physical examination is notable for dry mucus membranes, and a gravid uterusShe has no abdominal pain, and does not have a palpable liver or spleen

11Liver disease in pregnancy11What is your first diagnosis?

12Liver disease in pregnancy12ALT (175 IU/L), AST (122 IU/L), serum total bilirubin (2.1 mg/dL)Amylase and lipase are normalThe albumin is slightly decreased from normal valuesLiver biochemical tests prior to pregnancy are not availableA right upper quadrant ultrasound is normal. Urinalysis shows elevated ketones.13Liver disease in pregnancy13Serology for hepatitis A, B, and C is negative, antinuclear antibodies are absent, and serum protein electrophoresis is normal TSH is normalObstetrical ultrasound examination demonstrates a normal singleton gestation.14Liver disease in pregnancy14patient's clinical course and occurrence of symptoms early during pregnancy are consistent with hyperemesis gravidarum

15Liver disease in pregnancy15Common criteria for diagnosis of hyperemesis are persistent vomiting accompanied by weight loss exceeding 5 percent of prepregnancy body weight and ketonuria unrelated to other causes16Liver disease in pregnancy16Abnormal 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/LHyperbilirubinemia can occur, but rarely exceeds 4 mg/dL

17Liver disease in pregnancy17Serum 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

18Liver disease in pregnancy18Preeclampsia, 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 presentthrombocytopenia is common19Liver disease in pregnancy19Case 2A 23-year-old woman gravida 2 para 1 currently at 35 weeks with a singleton gestation is referred from a dermatologist for intractable itchingThe itching is primarily on the palms of her hands and soles of her feetIt is present day and night, and keeps her from sleeping. 20Liver disease in pregnancy20The patient also had itching during her first pregnancy in which the fetus died in utero in the third trimester21Liver disease in pregnancy21What is your first diagnosis?

22Liver disease in pregnancy22Intrahepatic cholestasis of pregnancyIntrahepatic cholestasis of pregnancy (ICP) occurs in the second and third trimesteris characterized by pruritus and an elevation in serum bile acid concentrationsFor unknown reasons the disease is seen more commonly in the colder months

23Liver disease in pregnancy23PATHOGENESISThe cause of ICP is unknown but genetic, hormonal, and environmental factors are likely involved24Liver disease in pregnancy24Estrogens 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 pregnancy25Liver disease in pregnancy25CLINICAL MANIFESTATIONSPruritus may precede laboratory abnormalities Abdominal pain is uncommonEncephalopathy or other stigmata of liver failure are unusual Physical examination is nonspecificmay show excoriations due to scratchingJaundice occurs in less than 10 percent26Liver disease in pregnancy26Laboratory findings Serum total bile acid concentrations increase in ICP, and may be the first or only laboratory abnormality Serum cholic acid increases more than chenodeoxycholic acidmost 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 decreased27Liver disease in pregnancy27elevations in alkaline phosphatase, 5' nucleotidase, and total and direct bilirubin concentrationsTotal bilirubin levels rarely exceed 6 mg/dLgamma glutamyl transpeptidase (GGT) are normal or modestly elevatedaminotransferases may reach values greater than 1000 U/LThe prothrombin time is usually normalprolonged prothrombin times reflect vitamin K deficiency due to cholestasis or to the use of bile acid sequestrants rather than liver dysfunction.28Liver disease in pregnancy28ULTRASONOGRAPHY the biliary ducts are not dilated and hepatic parenchyma appears normal29Liver disease in pregnancy29DIAGNOSISMost women are diagnosed during the second or third trimesterThe diagnosis of ICP is based upon the presence of pruritus associated with elevated total serum bile acids levels and/or aminotransferases30Liver disease in pregnancy30PATHOLOGYis rarely necessary for the diagnosishistopathology is characterized by cholestasis without inflammation Bile plugs in hepatocytes and canaliculi predominate in zone 3The portal tracts are unaffected.31Liver disease in pregnancy31TREATMENTUDCA 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)

32Liver disease in pregnancy32Complications of cholestasishypoprothrombinemia induced by vitamin K deficiency; should be treated before delivery to prevent hemorrhage.33Liver disease in pregnancy33Cholestasis recurs during subsequent pregnancies in 60 to 70 percentincreased risk for gallstonessome 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 delivery34Liver disease in pregnancy34Hormonal contraceptioncontraceptives with a low dose of estrogen can be initiated after normalization of liver function testscheck liver function tests after three or six months of such contraception.35Liver disease in pregnancy35FETAL FOLLOW-UP AND OUTCOMEIn contrast to the favorable prognosis for mothers, ICP carries significant risk for the fetus

fetal prematuritymeconium stained amniotic fluidintrauterine demiseneonatal respiratory distress syndrome36Liver disease in pregnancy36Timing of delivery 37 wk

35-37 wk :Severe itchingJaundicePrior fetal death37Liver disease in pregnancy37Case 3A 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 jaundiceHer blood pressure is mildly elevatedUrinalysis shows trace proteinaminotransferases range between 200 to 500 glucose is in the low-normal rangeWhite blood cell count and prothrombin time are elevated38Liver disease in pregnancy38What is your diagnosis ?

39Liver disease in pregnancy39Acute fatty liver of pregnancycharacterized 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 rule40Liver disease in pregnancy40EPIDEMIOLOGY 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.41Liver disease in pregnancy41CLINICAL MANIFESTATIONS Acute fatty liver occurs typically in the third trimesterThe disease is always present before delivery, although it is not always diagnosed prior to delivery

Symptom?

42Liver disease in pregnancy42The most frequent initial symptoms are nausea or vomiting 75 percent abdominal pain :50 percentAnorexiaJaundiceone-half of patients have signs of preeclampsia at presentation or at some time during the course of illness

43Liver disease in pregnancy43infection major intraabdominal bleedingTransient 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

44Liver disease in pregnancy44Laboratory tests aminotransferase ranging from modest values up to 1000 Serum bilirubin levels are also usually elevatedThe 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 insufficiencyAcute renal failure and hyperuricemia are often present45Liver disease in pregnancy45DIAGNOSISmade 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.46Liver disease in pregnancy46TREATMENT AND COURSEthe primary treatment is prompt delivery, usually emergently, after maternal stabilization47Liver disease in pregnancy47Maternal 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 pulmonary edemaHypoglycemia is common and all patients should have glucose monitored until normal liver function returns48Liver disease in pregnancy48The liver tests and coagulopathy usually start to normalize shortly after delivery

49Liver disease in pregnancy49RECURRENCEAcute fatty liver can recur in subsequent pregnancies50Liver disease in pregnancy50Case 4A 23-year-old woman gravida 1 para 0 currently with twin gestations at 32 weeks is hospitalized with hypertension, for which methyldopa had been prescribed earlier in her pregnancyDespite treatment, she continues to be mildly hypertensive and is developing a progressive rise in serum aminotransferases, which are over 85Hepatitis serology and markers for autoimmune hepatitis are negative. Her platelet count, peripheral blood smear, urinalysis, and right upper quadrant ultrasound are normal51Liver disease in pregnancy51The differential diagnosis in this case includes:

preeclampsiatoxicity due to methyldopa early acute fatty liver of pregnancy52Liver disease in pregnancy52HELLP syndromecharacterized by hemolysis with a microangiopathic blood smear, elevated liver enzymes, and a low platelet count15 to 20 percent of affected patients do not have antecedent hypertension or proteinuria

53Liver disease in pregnancy53INCIDENCE AND ONSET OF DISEASE HELLP develops in approximately 1 to 2 per 1000 pregnancies overall and in 10 to 20 percent of women with severe preeclampsia/eclampsia

The majority of cases are diagnosed between 28 and 36 weeks of gestation54Liver disease in pregnancy54CLINICAL MANIFESTATIONS

55Liver disease in pregnancy55Symptoms typically develop in the third trimester, (second trimester or postpartum disease )The most common clinical presentation is abdominal pain and tenderness in the midepigastrium, right upper quadrant, or below the sternum nausea, vomiting, and malaiseHypertension (blood pressure 140/90) and proteinuria56Liver disease in pregnancy56Serious maternal morbidity may be present at initial presentation or develop shortly thereafterdisseminated intravascular coagulation (DIC)abruptio placentaeacute renal failurepulmonary edemasubcapsular liver hematomaretinal detachment 57Liver disease in pregnancy57Microangiopathic hemolytic anemiasigns suggestive of hemolysis include an elevated indirect bilirubin and a low serum haptoglobin concentration (25 mg/dL).Platelet count 100,000 cells/microLTotal bilirubin 1.2 mg/dLSerum AST 70 IU/L.58Liver disease in pregnancy58MANAGEMENTThe cornerstone of therapy is delivery

Pregnancies 34 weeks of gestationNonreassuring tests of fetal status (eg, biophysical profile, fetal heart rate testing)Presence of severe maternal disease: multiorgan dysfunction, DIC, liver infarction or hemorrhage, renal failure, or abruptio placenta.59Liver disease in pregnancy59Platelet transfusionsignificant maternal bleeding (spontaneous or from surgical incisions)less than 20,000 cells/microLpreoperative platelet count greater than 40,000 to 50,000 cells/microL60Liver disease in pregnancy60NVD OR CS?cesarean delivery is probably preferable in pregnancies less than 30 to 32 weeks of gestation if the cervix is unfavorable for induction61Liver disease in pregnancy61Role of dexamethasone PLT< 100000 ???62Liver disease in pregnancy62chronic liver diseasePregnancy is unusual in women with severe chronic liver disease. Most such women are not of child-bearing age, or, because of the associated anovulatory state, they are infertile63Liver disease in pregnancy63CIRRHOSIS AND PORTAL HYPERTENSION Some women with cirrhosis can sustain pregnancy without any worsening of hepatic function others may develop jaundice with progressive liver failure, ascites, and hepatic coma64Liver disease in pregnancy64The increase in total blood volume associated with pregnancy may worsen pre-existing portal hypertension

upper endoscopy to look for varices before pregnancy65Liver disease in pregnancy65Hepatitis B virusPregnancy is generally well tolerated by women who are chronic carriers of hepatitis B virus The overall risk of HBV transmission from the mother to infant is about 40 percent.Transmission at birth is more likely if the mother is hepatitis B e antigen (HBeAg) positive or has high circulating levels of HBV DNAPrenatal screening of all pregnant women for HBsAg is now performed routinely in many countries66Liver disease in pregnancy66Hepatitis C virusWomen chronically infected with hepatitis C virus (HCV) can have an uneventful pregnancy without worsening of liver disease or other adverse effects on the mother or fetus Transmission of the virus from mother to infant occurs in about 5 to 10 percent of infants born to anti-HCV positive womenno evidence that breastfeeding is a risk for infection 67Liver disease in pregnancy67THANK YOU68Liver disease in pregnancy68