liver disease with pregnancy.ppt

LIVER DISEASES LIVER DISEASES WITH PREGNANCYWITH PREGNANCY

Dr Walid Abdalla MohamedDr Walid Abdalla Mohamed Obstetrics & Gynecology Dept. Obstetrics & Gynecology Dept.

Faculty of MedicineFaculty of MedicineZagazig Zagazig University University

IntroductionIntroductionLiver disease is a rare complication of Liver disease is a rare complication of pregnancy, but when it occurs it may pregnancy, but when it occurs it may do so in a dramatic and tragic fashion do so in a dramatic and tragic fashion for both mother and infant. Diseases for both mother and infant. Diseases such as acute fatty liver of pregnancy such as acute fatty liver of pregnancy (AFLP) may begin (AFLP) may begin gradually gradually with mild with mild symptoms and liver enzyme symptoms and liver enzyme abnormalities but, if left untreated, abnormalities but, if left untreated, can progress to jaundice, liver failure, can progress to jaundice, liver failure, and death.and death.

(Bacq & Riely , 2004)(Bacq & Riely , 2004)

• Some of the normal physiologic changes of Some of the normal physiologic changes of pregnancy can mimic abnormalities pregnancy can mimic abnormalities associated with liver disease. associated with liver disease.

• Telangiectasia, particularly on the chest, Telangiectasia, particularly on the chest, back, and face, and palmer erythema back, and face, and palmer erythema occur in up to 60 percent of normal occur in up to 60 percent of normal pregnant women but disappear after pregnant women but disappear after deliverydelivery..

(Riely, 2001)

Anatomical, Physiological, and Anatomical, Physiological, and Biochemical changes during Biochemical changes during

pregnancy.pregnancy.

Anatomic Changes:Anatomic Changes:

• Liver weight increases during pregnancy has not Liver weight increases during pregnancy has not been documented. Liver size is difficult to been documented. Liver size is difficult to estimate in pregnancy, but records fail to show estimate in pregnancy, but records fail to show any substantial increase in liver weight in any substantial increase in liver weight in comparison with nonpregnant controls.comparison with nonpregnant controls.

• Therefore, detection of hepatomegaly is strong Therefore, detection of hepatomegaly is strong

evidence for the presence of liver disease.evidence for the presence of liver disease.(Fagan, 1986)(Fagan, 1986)

Summary of physiologicalSummary of physiological and biochemical and biochemical changes in the changes in the liver during pregnancyliver during pregnancy

• Increased:• Alkaline phosphatase levels rise threefold or fourfold due to• placental production• Clotting factor changes create a hypercoagulable state• Decreased:• Gallbladder contractility• Uric acid levels• Albumin, total protein, and antithrombin III concentrations

• No change:• Liver aminotransferase levels (aspartate

aminotransferase,• alanine aminotransferase(more specific as it

rises only in liver injury), gamma-glutamyl transferase)

• Bilirubin level• Prothrombin time

Spectrum of liver diseases in Spectrum of liver diseases in pregnancypregnancy

(Fleming & Zein, 2005)(Fleming & Zein, 2005)

• Liver diseases induced by pregnancyLiver diseases induced by pregnancy– First trimesterFirst trimester

• Hyperemesis gravidarumHyperemesis gravidarum

– Second and third trimestersSecond and third trimesters• Intrahepatic cholestasis of pregnancyIntrahepatic cholestasis of pregnancy• HELLP syndromeHELLP syndrome (hemolysis, elevated liver enzymes, (hemolysis, elevated liver enzymes,

low platelet counts) low platelet counts) • Acute fatty liver of pregnancyAcute fatty liver of pregnancy

• Liver diseases coincidental with but not Liver diseases coincidental with but not induced by pregnancyinduced by pregnancy– Acute viral hepatitis and other viral infectionsAcute viral hepatitis and other viral infections– Alcohol-related diseasesAlcohol-related diseases– Gallstone diseaseGallstone disease– Budd-Chiari syndromeBudd-Chiari syndrome

• Preexistent liver diseasesPreexistent liver diseases– Portal hypertension, cirrhosis, primary biliary Portal hypertension, cirrhosis, primary biliary

cirrhosiscirrhosis– Autoimmune hepatitisAutoimmune hepatitis– Wilson diseaseWilson disease– Chronic infection with hepatitis B or hepatitis Chronic infection with hepatitis B or hepatitis

C virusC virus– Alcoholic liver diseaseAlcoholic liver disease



– Second and third trimestersSecond and third trimesters• Intrahepatic cholestasis of pregnancyIntrahepatic cholestasis of pregnancy• HELLP syndromeHELLP syndrome (hemolysis, elevated liver enzymes, (hemolysis, elevated liver enzymes,

low platelet counts) low platelet counts) • Acute fatty liver of pregnancyAcute fatty liver of pregnancy

Hyperemesis gravidarumHyperemesis gravidarum

Def:* severe nausea and vomiting and unresponsive to simple dietary modification and anti-emetics.

* vomiting suffiecently severe to produce weight loss, dehydration ,alkalosis from loss of hydrochloric acid and hypokalemia

incidences : vary and appear to be ethnic and familial prediction and the risk increase among-obesity, nulliparity, and twin gestation.

hospitalization rate is about 0.5-0.8 % and with those have previous history up to 20% require hospitalization.

Pregnancy-Unique Quantification of Emesis/Nausea (PUQE) index: Total score is sum of replies to each of the three questions. Nausea Score: Mild NVP = ≤6; Moderate NVP = 7–12; Severe NVP = ≥13

•Etiology:- High or rapid rise in serum level of pregnancy related hormones (HSG,E2, progesterone,placental growth hormone, prolactin,thyroxine and adreno-cortical hormone)-There is some studies implicated psychological component - for unknown reason a female fetus increase the risk by 1.5 folds.

• There is small evidence for the association between hyperemesis and H.pylori infection.

• Complications: - Acute renal failure from dehydration , and

may require 5 day dialysis when S. creatinine reach 10.7 mg/l

-Life-threating complication of retching include Mallory-weiss tears, rupture esophagus, pneumothorax and pneumomediastinum

Mallory Weiss tear syndrome

• Thiamine deficiency will lead to Wernicke encephalopathy half of patient have the triad of : ( confusion,ocular findings and Ataxia) and MR imaging findings , late sequelae are common and include blindness,convulsions and coma

• Vitamin K deficiency may lead to maternal coagulopathy and fetal intracranial hemorrhage.

• Laboratory testing demonstrates abnormal Laboratory testing demonstrates abnormal liver values in up to 50% of affected liver values in up to 50% of affected patients; the most sensitive test is the ALT, patients; the most sensitive test is the ALT, which may rise as high as 1000 U.which may rise as high as 1000 U.

• Severely affected patients also have Severely affected patients also have elevations in bilirubin. elevations in bilirubin.

Antiemetic therapy is helpfulAntiemetic therapy is helpful rectal or oral rectal or oral as first lineas first line

Improvement in the nausea and vomiting Improvement in the nausea and vomiting and resolution of the liver test abnormalities and resolution of the liver test abnormalities occur when most affected patients are occur when most affected patients are given intravenous fluids and put to gut restgiven intravenous fluids and put to gut rest, , correct dehydration , ketonemia and acid correct dehydration , ketonemia and acid base imbalances.base imbalances.

. Corticosteroid therapy has. Corticosteroid therapy has been reported been reported withwith little little success. success.however pt treated by however pt treated by corticosteroids have fewer readmissioncorticosteroids have fewer readmission

• Thiamine is given 100 mg to prevent Wernicke encephalopathy

• if severe unresponsive vomiting appropriate steps should be taken to exclude underlying disease( gastroenteritis,cholecystitis, pancreatitis,hepatitis peptic ulcer , preeclampsia and AFLP

• it was found that high level of thyroxine is implicated in hyperemesis more than HCG level

• If associated psychiatric and social factors improvement while hospitalization occur but may relapse after discharge in these situation assistance with psychosocial problem is beneficial

• Its important to know that

Patients affected with hyperemesis gravidarum Patients affected with hyperemesis gravidarum have no increased rate of prematurity, infants have no increased rate of prematurity, infants with low birth weight, or infants with birth with low birth weight, or infants with birth defectsdefects. .



– Second and third trimestersSecond and third trimesters• Intrahepatic cholestasis of pregnancyIntrahepatic cholestasis of pregnancy• Preeclampsia, eclampsia, and the HELLP syndromePreeclampsia, eclampsia, and the HELLP syndrome• (hemolysis, elevated liver enzymes, low platelet (hemolysis, elevated liver enzymes, low platelet

counts) counts) • Acute fatty liver of pregnancyAcute fatty liver of pregnancy

Intrahepatic Cholestasis of Intrahepatic Cholestasis of PregnancyPregnancy

• The syndrome has been variously called The syndrome has been variously called recurrent jaundice of pregnancy, cholestatic recurrent jaundice of pregnancy, cholestatic jaundice of pregnancy,jaundice of pregnancy,ictrus gravidarum,ictrus gravidarum, jaundice of late pregnancy, and hepatosis of jaundice of late pregnancy, and hepatosis of pregnancy. ICP, however, is the preferred term, pregnancy. ICP, however, is the preferred term, because jaundice is inconstant in any type of because jaundice is inconstant in any type of cholestatic disorder. cholestatic disorder.

(Gonzalez-Peralva et al., 1996)(Gonzalez-Peralva et al., 1996)

• The frequency of ICP is clearly higher The frequency of ICP is clearly higher among certain ethnic groups, including among certain ethnic groups, including Scandinavians and Chileans. In the latter Scandinavians and Chileans. In the latter group, ICP may appear in 2.4% or more of group, ICP may appear in 2.4% or more of pregnancies, the highest reported pregnancies, the highest reported incidence in the world. The incidence is incidence in the world. The incidence is quite high (20.9%) in twin pregnancies.quite high (20.9%) in twin pregnancies.

• Several studies have demonstrated a Several studies have demonstrated a familial and genetic predisposition to the familial and genetic predisposition to the syndrome in Sweden, Chile, and the United syndrome in Sweden, Chile, and the United States.States.

(Lammert, et al., 2000)(Lammert, et al., 2000)

Clinical Clinical presentationpresentation• Pruritus is the dominant and initial Pruritus is the dominant and initial

symptom and appears in the third trimester in symptom and appears in the third trimester in more than 70% of cases. Most of the more than 70% of cases. Most of the remaining patients date their onset of remaining patients date their onset of symptoms to the second trimester.symptoms to the second trimester.some cases some cases reported in the first trimester with reported in the first trimester with hyperplacentosis and a triploid fetus.hyperplacentosis and a triploid fetus.

• The symptom may become very severe and The symptom may become very severe and usually involves the trunk and the extremities, usually involves the trunk and the extremities, including the palms and the soles of the feet. including the palms and the soles of the feet. As a result of the pruritus, insomnia, fatigue, As a result of the pruritus, insomnia, fatigue, and even mental disturbances have been and even mental disturbances have been reported reported

Many patients report the appearance of dark Many patients report the appearance of dark urine without frank jaundice shortly after urine without frank jaundice shortly after the onset of pruritus. Only a minority of the onset of pruritus. Only a minority of patients develop obvious jaundice, and this patients develop obvious jaundice, and this is usually mild.is usually mild.

It is notable that abdominal pain, biliary colic, It is notable that abdominal pain, biliary colic, fever, anorexia, nausea, vomiting, and fever, anorexia, nausea, vomiting, and arthralgias are absent. arthralgias are absent.

• The improvement in both pruritus and The improvement in both pruritus and jaundice begins to occur quite promptly jaundice begins to occur quite promptly after delivery, most often within 24 hours. after delivery, most often within 24 hours. However, jaundice may continue for However, jaundice may continue for several days after delivery, and some of several days after delivery, and some of the abnormal chemistry profiles persist for the abnormal chemistry profiles persist for as long as several months.as long as several months.

• Subsequent pregnancies are frequently Subsequent pregnancies are frequently accompanied by recurrences of the accompanied by recurrences of the syndromesyndrome..

Biochemical ChangesBiochemical Changes CLINICAL FEATURES BIOCHEMICAL CHANGES

PruritusJaundice*

No Anorexia or malasie 2nd or 3rd trimester onset*

Recurrent*Familial*

Serum bile acidAlkaline Phosphatase5' NucleotidaseGGTPBilirubin (total)AST/ALTProthrombin timeCholesterolTriglyceride

10-to 100 fold7- to 10 fold Two FoldsNormal to slight Normal to 5 mg/dL not exceed 250 U/LNormal to twofoldsTwo to Fourfolds Normal to twofolds

Effects on the MotheEffects on the Motherr

• Although earlier reports suggested that the only Although earlier reports suggested that the only effect of ICP on the mother was related to the effect of ICP on the mother was related to the discomfort of pruritus, more recent studies have discomfort of pruritus, more recent studies have suggested more serious complications. These suggested more serious complications. These include an increased risk of postpartum include an increased risk of postpartum hemorrhage, especially in those given hemorrhage, especially in those given cholestyramine, and an increased risk for the cholestyramine, and an increased risk for the development of gallstones after pregnancy.development of gallstones after pregnancy.

(Glantz, et al., 2005)(Glantz, et al., 2005)

Effects on the FetusEffects on the Fetus• The implications of ICP for the fetus are The implications of ICP for the fetus are

considerably more ominous. An increased considerably more ominous. An increased incidence of prematurity and fetal death has been incidence of prematurity and fetal death has been reported in several studies. Fetal distress is reported in several studies. Fetal distress is reported in one third of patients, leading to reported in one third of patients, leading to ccesarean section in 30% to 60% of cases and esarean section in 30% to 60% of cases and prematurity in over 50% in some series. Stillbirths prematurity in over 50% in some series. Stillbirths are recorded in more than 9%. These outcomes are recorded in more than 9%. These outcomes are more likely if the disorder begins earlier in are more likely if the disorder begins earlier in pregnancy. Thus, ICP very clearly increases the pregnancy. Thus, ICP very clearly increases the risks to the fetus. risks to the fetus.

(Glantz, et al., 2004)(Glantz, et al., 2004)

TreatmentTreatment

• Therapy is directed at alleviating pruritus in the Therapy is directed at alleviating pruritus in the mother. Ursodeoxycholic acid has been used mother. Ursodeoxycholic acid has been used successfully in the treatment of cholestasis. successfully in the treatment of cholestasis. Improvement in both liver function test results and Improvement in both liver function test results and the symptom of pruritus has been documented in the symptom of pruritus has been documented in women with ICP treated with a standard women with ICP treated with a standard 15mg/kg/day dosage. A larger dosage, 20 to 25 15mg/kg/day dosage. A larger dosage, 20 to 25 mg/kg/day has been shown to be effective with no mg/kg/day has been shown to be effective with no adverse affects on either mother or baby.adverse affects on either mother or baby.

(Mazella et al., 2001)

• Phenobarbital in a dosage of 100 mg/day has Phenobarbital in a dosage of 100 mg/day has been reported to be effective in approximately been reported to be effective in approximately 50% of patients.50% of patients.

• Cholestyramine may be somewhat effective and Cholestyramine may be somewhat effective and is usually given in a dosage of 4 g four or five is usually given in a dosage of 4 g four or five times per day. times per day.

• Cholestyramine may worsen the malabsorption of Cholestyramine may worsen the malabsorption of fats and fat-soluble vitamins. Therefore, the fats and fat-soluble vitamins. Therefore, the prothrombin time must be monitored in patients prothrombin time must be monitored in patients treated with this regimen, and parenteral vitamin treated with this regimen, and parenteral vitamin K should be given before delivery.K should be given before delivery.

(Eloranta et al., 2002)(Eloranta et al., 2002)

• Antihistamininc and topical emollients may Antihistamininc and topical emollients may give some relifgive some relif..

• Some investigators recommend elective Some investigators recommend elective induction at 38 weeks or as early as 36 induction at 38 weeks or as early as 36 weeks in the presence of jaundice or if the weeks in the presence of jaundice or if the fetus's lungs have matured.fetus's lungs have matured.



– Second and third trimestersSecond and third trimesters• Intrahepatic cholestasis of pregnancyIntrahepatic cholestasis of pregnancy• HELLP syndromHELLP syndrome e (hemolysis, elevated liver enzymes, (hemolysis, elevated liver enzymes,

low platelet counts)low platelet counts) • Acute fatty liver of pregnancyAcute fatty liver of pregnancy

HELLP SyndromeHELLP Syndrome

• The HELLP syndrome is a multi-system disease The HELLP syndrome is a multi-system disease variant of severe preeclampsia that is variant of severe preeclampsia that is characterized by microangiopathic hemolytic characterized by microangiopathic hemolytic anemia (MAH)anemia (MAH) abnormal peripheral smear, abnormal peripheral smear, increased bilirubin <1.2 mg/dL, and increased increased bilirubin <1.2 mg/dL, and increased lactic dehydrogenase > 600 IU/L;, lactic dehydrogenase > 600 IU/L;,

• Elevated liver enzymes aspartate Elevated liver enzymes aspartate aminotransferase (AST) ≥ 72 IU/L, lactate aminotransferase (AST) ≥ 72 IU/L, lactate dehydrogenase (LDH) > 600 IU/ dehydrogenase (LDH) > 600 IU/ , ,

• TThrombocytopenia (platelet count, <100,000/ hrombocytopenia (platelet count, <100,000/ mm3), and, in the syndrome’s most severe form, mm3), and, in the syndrome’s most severe form, DIC. DIC.

• HELLP syndrome is more common among older HELLP syndrome is more common among older multiparous women.multiparous women.

• HELLP syndrome affects up to 20% of HELLP syndrome affects up to 20% of pregnancies involving severe preeclampsia. pregnancies involving severe preeclampsia.

• Although up to 11% of the cases occur before 27 Although up to 11% of the cases occur before 27 weeks of gestation, most cases (70%) occur weeks of gestation, most cases (70%) occur between 27 and 36 weeks of gestation and between 27 and 36 weeks of gestation and about a third occur after delivery. Exacerbations about a third occur after delivery. Exacerbations may occur after delivery, followed by recovery may occur after delivery, followed by recovery within 72 hours.within 72 hours.

(Martin et al., 1999)

• Clinical presentation:Clinical presentation:• Frequent presenting symptoms include nausea, Frequent presenting symptoms include nausea,

malaise, epigastric or right upper quadrant malaise, epigastric or right upper quadrant abdominal pain (65%–90% of cases), and abdominal pain (65%–90% of cases), and edema. In a large series, HELLP syndrome was edema. In a large series, HELLP syndrome was observed with DIC (21% of patients), abruption observed with DIC (21% of patients), abruption placenta (16%), acute renal failure (8%), and placenta (16%), acute renal failure (8%), and pulmonary edema (6%). The maternal mortality pulmonary edema (6%). The maternal mortality rate is approximately 1% to 4%, and the perinatal rate is approximately 1% to 4%, and the perinatal mortality rate ranges from 10% to 20%, mortality rate ranges from 10% to 20%, depending on gestational age and severity of the depending on gestational age and severity of the condition at the time of delivery. condition at the time of delivery.

(Sibai et al., 1993)

Maternal morbidity in HELLP syndrome can Maternal morbidity in HELLP syndrome can be classified into the following four be classified into the following four categories (in decreasing order of categories (in decreasing order of frequency)frequency)

• Coagulation disorders associated with Coagulation disorders associated with hemorrhagic complications,hemorrhagic complications,

• Cardiopulmonary dysfunction,Cardiopulmonary dysfunction,• Central nervous system disorder andCentral nervous system disorder and• Hepatic or gastrointestinal dysfunction.Hepatic or gastrointestinal dysfunction.(Isler et al., 1999)

• Women with HELLP syndrome should be Women with HELLP syndrome should be considered to be at increased risk for considered to be at increased risk for obstetrical complications in subsequent obstetrical complications in subsequent pregnancies (preterm deliveries, IUGR, pregnancies (preterm deliveries, IUGR, abruption-placenta), and the risk for abruption-placenta), and the risk for recurrence ranges from 4% to 25% . recurrence ranges from 4% to 25% . Infants born to mothers with HELLP Infants born to mothers with HELLP syndrome are at risk for thrombocytopenia.syndrome are at risk for thrombocytopenia.

(Sibai et al., 1995)(Sibai et al., 1995)

differential diagnosis of HELLP differential diagnosis of HELLP syndromesyndrome

Thrombotic coagulopathies Consumptive disorders

Miscellaneous

Hemolytic uremic syndromeThrombotic

thrombocytopenia purpuraDrug-induced hemolytic

anemiaSepsisDIC

AFLPSepsisDICAbruptio placentaeAmniotic fluid

embolism

Systemic lupusAntiphospholipid

syndromeCholecystitisAppendicitis

Laboratory investigationLaboratory investigation

Risk factors for HELLP syndrome include the Risk factors for HELLP syndrome include the following:following:

• LDH level, > 1400 IU/LLDH level, > 1400 IU/L• AST level, > 150 IU/LAST level, > 150 IU/L• ALT level, > 100 IU/LALT level, > 100 IU/L• Platelet count, < 50,000/mm3Platelet count, < 50,000/mm3• Uric acid level, > 7.8 mg/dLUric acid level, > 7.8 mg/dL• Creatinine level, > 1.0Creatinine level, > 1.0• Creatine phosphokinase level, > 200 IU/LCreatine phosphokinase level, > 200 IU/L

Liver functionLiver function• Patients usually are not jaundiced. Total bilirubin Patients usually are not jaundiced. Total bilirubin

concentration rarely exceeds 1 to 2 mg. concentration rarely exceeds 1 to 2 mg. • HELLP syndrome rarely leads to subcapsular HELLP syndrome rarely leads to subcapsular

hemorrhage; hepatic rupture often leads to death of hemorrhage; hepatic rupture often leads to death of the mother and fetus. Typically, these patients the mother and fetus. Typically, these patients present with shock and hemoperitoneum. The present with shock and hemoperitoneum. The condition also may manifest hepatic infarcts with condition also may manifest hepatic infarcts with associated fevers, high levels of aminotranferase associated fevers, high levels of aminotranferase (N5000 IU/L), and anemia. (N5000 IU/L), and anemia.

(Krueger et al., 1995)

Therapy and outcomeTherapy and outcome

• The maternal morbidity rate has been reported The maternal morbidity rate has been reported to be as high as 24%, but it ranges between 1% to be as high as 24%, but it ranges between 1% to 4% in optimal medical environments. In to 4% in optimal medical environments. In patients who died, the mean gestational age was patients who died, the mean gestational age was 31 weeks, and death was attributed to sepsis, 31 weeks, and death was attributed to sepsis, hemorrhagic shock, intracerebral insults, and hemorrhagic shock, intracerebral insults, and cardiac pulmonary failure. Investigators found cardiac pulmonary failure. Investigators found 16% maternal death rate attributed to hepatic 16% maternal death rate attributed to hepatic complications. complications.

(Martin et al., 1999)

• The neonatal mortality rate associated The neonatal mortality rate associated with HELLP syndrome (10%–20%) has with HELLP syndrome (10%–20%) has been attributed to placenta ischemia been attributed to placenta ischemia leading to abruption, extreme prematurity, leading to abruption, extreme prematurity, and intrauterine asphyxia. Factors and intrauterine asphyxia. Factors associated with perinatal survival in associated with perinatal survival in preterm pregnancies with HELLP preterm pregnancies with HELLP syndrome include achievement of a birth syndrome include achievement of a birth weight of at least 600g, elapsed time of 48 weight of at least 600g, elapsed time of 48 hours after medical therapy with steroids hours after medical therapy with steroids for perinatal lung maturity, and caesarian for perinatal lung maturity, and caesarian delivery. delivery.

(Barton & Sibai, 1992)(Barton & Sibai, 1992)

• Termination of pregnancy and the removal Termination of pregnancy and the removal of the chorionic villi is the only therapy that of the chorionic villi is the only therapy that minimizes maternal and fetal compromise. minimizes maternal and fetal compromise. Timing of delivery depends on the severity Timing of delivery depends on the severity of the maternal condition , fetal condition, of the maternal condition , fetal condition, placenta reserve, and gestational age. placenta reserve, and gestational age.

• HELLP syndrome - antepartum HELLP syndrome - antepartum managementmanagement

• assess and stabilize the maternal conditionassess and stabilize the maternal condition• correct coagulopathy if DIC is presentcorrect coagulopathy if DIC is present• give intravenous magnesium sulfate to prevent seizuresgive intravenous magnesium sulfate to prevent seizures• provide treatment for severe hypertension to prevent provide treatment for severe hypertension to prevent

strokestroke• transfer to tertiary center if appropriatetransfer to tertiary center if appropriate• if subcapsular hematoma of liver, computed if subcapsular hematoma of liver, computed

tomography or ultrasound of the abdomentomography or ultrasound of the abdomen

• HELLP syndrome - antepartum HELLP syndrome - antepartum managementmanagement– evaluate fetal well-beingevaluate fetal well-being

• non stress testnon stress test• biophysical profilebiophysical profile

– timing of deliverytiming of delivery• if > 34 weeks gestation, deliverif > 34 weeks gestation, deliver• if < 34 weeks gestation, administer corticosteroids, if < 34 weeks gestation, administer corticosteroids,

then deliver in 48 hoursthen deliver in 48 hours

• HELLP syndrome - management for HELLP syndrome - management for cesarean birthcesarean birth– use general anesthesia if platelet count is use general anesthesia if platelet count is

< 75,000 / mm < 75,000 / mm33

– transfuse 5 to 10 units of platelets before transfuse 5 to 10 units of platelets before surgery if platelet count is < 50,000 / mmsurgery if platelet count is < 50,000 / mm33

– leave vesicouterine peritoneum openleave vesicouterine peritoneum open– install subfascial draininstall subfascial drain

• HELLP syndrome - management for HELLP syndrome - management for cesarean birthcesarean birth– schedule secondary closure of skin incision schedule secondary closure of skin incision

or subcutaneous drain or subcutaneous drain – administer postoperative transfusions as administer postoperative transfusions as

neededneeded– perform intensive monitoring for at least 48 perform intensive monitoring for at least 48

hours postpartumhours postpartum– consider dexamethasone (10 mg IV every 12 consider dexamethasone (10 mg IV every 12

hours) until postpartum resolution of disease hours) until postpartum resolution of disease occursoccurs



– Second and third trimestersSecond and third trimesters• Intrahepatic cholestasis of pregnancyIntrahepatic cholestasis of pregnancy• Preeclampsia, eclampsia, and the HELLP syndromePreeclampsia, eclampsia, and the HELLP syndrome

(hemolysis, elevated liver enzymes, low platelet counts) (hemolysis, elevated liver enzymes, low platelet counts) • Acute fatty liver of pregnancyAcute fatty liver of pregnancy

Acute Fatty Liver of PregnancyAcute Fatty Liver of Pregnancy

• Sheehan, first recognized this disorder as a distinct syndrome in 1940..

• He named it Acute yellow atrophy but it is He named it Acute yellow atrophy but it is now more commonly known as acute fatly now more commonly known as acute fatly liver of pregnancy. liver of pregnancy.

(Sheehan, 1940)(Sheehan, 1940)

• (AFLP) is rare,, with a reported incidence (AFLP) is rare,, with a reported incidence of 1 in 13,000 to 1 in 16,000 deliveries.of 1 in 13,000 to 1 in 16,000 deliveries.

• Preeclampsia is present in 50% or more of Preeclampsia is present in 50% or more of cases of AFLP and may play a role in its cases of AFLP and may play a role in its origin. origin.

(Vigil-De, 2001)(Vigil-De, 2001)

• Reports of occasional recurrent cases and Reports of occasional recurrent cases and an association with a deficiency of long-an association with a deficiency of long-chain 3-hydroxyacyl-cocnzyme A chain 3-hydroxyacyl-cocnzyme A (LCHAD)(LCHAD) dehydrogenase, raise the interesting notion dehydrogenase, raise the interesting notion that, at least in some instances, this that, at least in some instances, this disease results from andisease results from an inborn error of inborn error of metabolism.metabolism.

Clinical CharacteristicsClinical Characteristics

• AFLP occurs in the latter half of pregnancy, AFLP occurs in the latter half of pregnancy, usually close to term. As with HELLP syndrome, usually close to term. As with HELLP syndrome, affected patients may present after delivery. It is affected patients may present after delivery. It is reported to occur more commonly in a reported to occur more commonly in a first first pregnancy pregnancy and in the presence of and in the presence of multiple multiple pregnancypregnancy, also prevalent in , also prevalent in preeclampsiapreeclampsia. . There are reports of an association between There are reports of an association between AFLP and gestation of a AFLP and gestation of a malemale fetus. fetus.

(Castro et al., 1999)(Castro et al., 1999)

• Affected women have nonspecific Affected women have nonspecific symptoms, including, prominently, nausea symptoms, including, prominently, nausea and vomiting, malaise and fatigue, and vomiting, malaise and fatigue, jaundice, thirst, headache, and altered jaundice, thirst, headache, and altered mental status. These can be signs and mental status. These can be signs and symptoms of acute hepatic failure. symptoms of acute hepatic failure.

• In severe cases that go untreated, there is In severe cases that go untreated, there is progression over hours or days to progression over hours or days to fulminant hepatic failure, with hepatic fulminant hepatic failure, with hepatic coma, hypo-glycemia, severe coma, hypo-glycemia, severe coagulopathy with hemorrhage from the coagulopathy with hemorrhage from the gastrointestinal tract or the uterus and gastrointestinal tract or the uterus and death. death.

• Most affected women have signs of Most affected women have signs of coexistent preeclampsia, including modest coexistent preeclampsia, including modest elevations in blood pressure,elevations in blood pressure,odema and odema and protienuriaprotienuria. .

With or without polyuria, frequently is an early With or without polyuria, frequently is an early symptom in AFLP.symptom in AFLP.

The patient may drink 2 or 3 liters of liquids The patient may drink 2 or 3 liters of liquids overnight. it often exceeds the magnitude of overnight. it often exceeds the magnitude of vomiting. It has been interpreted as a transient vomiting. It has been interpreted as a transient diabetes insipidus.diabetes insipidus.

(Cammu et al., 1987)(Cammu et al., 1987)

Polydipsia

Laboratory testsLaboratory tests

Clinical features Biochemical changes

Nausea, Vomiting Malaise, FatigueJaundice Abd. PainPreeclampsiaComapolydipsiaBleedingOnset in second half of gestation;

postpartum onset possible

Bilirubin (total)AST/ALTGGTPProthrombin timeFibrinogen Uric acidAmmoniaGlucoseLeukocytesplatelets

Slight , normalnormal to 1000 USlight,

• Imaging may be useful; fat in the liver has Imaging may be useful; fat in the liver has been demonstrated in AFLP with been demonstrated in AFLP with ultrasonography and CT scanningultrasonography and CT scanning however none are particulary reliable with however none are particulary reliable with poor sensitivitypoor sensitivity..

• Liver biopsy is not indicated for diagnosisLiver biopsy is not indicated for diagnosis

(Barton et al., 1998)(Barton et al., 1998)

Characteristics of HEELP syndrome and AFLPCharacteristics of HEELP syndrome and AFLP

HELLP AFLP

Early Platelet count, 50,000-150,000/mm3

LDH level, 600-1400 IU/LBilirubin/PT levels, Normal

Early Platelet count, >100,000/mm3

Uric acid – abnormalLDH level, normalPT- AbnormalBilirubin/ levels, abnormal

Late Platelet count, <50,000/mm3

LDH level, >1400 IU/LBilirubin/PT levels, abnormal

late Platelet count, <100,000/mm3

LDH level, < 600 IU/LHypoglycemiaPT Abnormal

ComplicationsComplications

cerebral edema, cerebral edema, renal failure (60%),renal failure (60%),hypoglycemia (53%), hypoglycemia (53%), infections (45%)infections (45%)gastrointestinal hemorrhage (33%), gastrointestinal hemorrhage (33%), coagulopathy (30%), coagulopathy (30%), fetal death fetal death severe postpartum hemorrhagesevere postpartum hemorrhage

MANAGMENTMANAGMENTAll patients should be hospitalized as soon as All patients should be hospitalized as soon as

the diagnosis of AFLP is suspected the diagnosis of AFLP is suspected Moderate or severely affected patients Moderate or severely affected patients

(encephalopathic, deeply jaundiced, with a (encephalopathic, deeply jaundiced, with a prothrombin time less than 40% of the prothrombin time less than 40% of the control), or with any extrahepatic control), or with any extrahepatic complications, should be attended in complications, should be attended in intensive care units. intensive care units.

it seems convenient to maintain glucose it seems convenient to maintain glucose infusions . Because of the risk of a sudden infusions . Because of the risk of a sudden hypoglycemia until a full metabolic recovery hypoglycemia until a full metabolic recovery is obtained.is obtained.

Treatment of AFLP begins with delivery. The Treatment of AFLP begins with delivery. The route should be guided by obstetric route should be guided by obstetric indications. Cesarean section is not always indications. Cesarean section is not always necessary; vaginal delivery can be necessary; vaginal delivery can be accomplished.accomplished.

• With delivery, With delivery, resolve of hepatic dysfunctions resolve of hepatic dysfunctions begins, the initial sign of improvement being a begins, the initial sign of improvement being a fall in prothrombin time elevation.fall in prothrombin time elevation.

• The management should include maximal The management should include maximal support in an intensive care unit by a team support in an intensive care unit by a team that includes both obstetricians and that includes both obstetricians and hepatologists. Liver transplantation for AFLP hepatologists. Liver transplantation for AFLP has been reported.has been reported.

(Paternoster et al., 2004)

• There are no residua after AFLP, and complete There are no residua after AFLP, and complete recovery of the affected patient should be recovery of the affected patient should be expected. Cases of recurrent AFLP, as well as expected. Cases of recurrent AFLP, as well as cases ofcases of nonketotic hypoglycemia in the nonketotic hypoglycemia in the offspring, have been reportedoffspring, have been reported

• There are two problems develop around these There are two problems develop around these time one is DI due to elevated vasopressinase time one is DI due to elevated vasopressinase cause by diminsihed production of inactivating cause by diminsihed production of inactivating enzyme another is acute pancreatitis.enzyme another is acute pancreatitis.

PRE-EXISTENT LIVER PRE-EXISTENT LIVER DISEASEDISEASE

• Pregnancy is uncommon in women with Pregnancy is uncommon in women with established liver cirrhosis, including primary established liver cirrhosis, including primary biliary cirrhosis, because they tend to be past biliary cirrhosis, because they tend to be past childbearing age or infertile due to the condition. childbearing age or infertile due to the condition. A life-threatening complication of liver cirrhosis A life-threatening complication of liver cirrhosis is variceal bleeding associated with portal is variceal bleeding associated with portal hypertension. Treating bleeding esophageal hypertension. Treating bleeding esophageal varices with nonselective beta-blockers, band varices with nonselective beta-blockers, band ligation, and octreotide is safe and effective ligation, and octreotide is safe and effective during pregnancy.during pregnancy.

(Helmy &Hayes, 2001)(Helmy &Hayes, 2001)

• Ursodeoxycholic acid (FDA category B) at Ursodeoxycholic acid (FDA category B) at doses of 10 to 13 mg/kg is treatment of doses of 10 to 13 mg/kg is treatment of choice for primary biliary cirrhosis and may choice for primary biliary cirrhosis and may be continued during pregnancy and be continued during pregnancy and breastfeeding.breastfeeding.

(Sternlieb, 2005)(Sternlieb, 2005)

• The presence of severe portal hypertension with The presence of severe portal hypertension with esophageal varices is associated with an esophageal varices is associated with an increased risk of hemorrhage during pregnancy. increased risk of hemorrhage during pregnancy.

The use of sclerotherapy for bleeding varices The use of sclerotherapy for bleeding varices during pregnancy may provide a safe alternative during pregnancy may provide a safe alternative to portacaval anastomosis and has been to portacaval anastomosis and has been reported to be effective.reported to be effective.

(Pauzner et al., 1991)(Pauzner et al., 1991)

• Women with autoimmune hepatitis can Women with autoimmune hepatitis can become pregnant and can still carry a become pregnant and can still carry a successful pregnancy. The course of the successful pregnancy. The course of the disease is unpredictable. Although disease is unpredictable. Although spontaneous remission may occur, spontaneous remission may occur, maternal death and exacerbation during maternal death and exacerbation during pregnancy and after delivery have been pregnancy and after delivery have been reported.reported.

(Heneghan et al., 2001)(Heneghan et al., 2001)

Corticosteroids are the treatment of choice in Corticosteroids are the treatment of choice in autoimmune hepatitis and appear to be safe in autoimmune hepatitis and appear to be safe in pregnancy. They seem to induce rapid remission pregnancy. They seem to induce rapid remission of autoimmune hepatitis, whether during the initial of autoimmune hepatitis, whether during the initial onset or during a flare. Although azathioprine is in onset or during a flare. Although azathioprine is in FDA category D (positive evidence of risk), we FDA category D (positive evidence of risk), we have little evidence that it is toxic in pregnancy. have little evidence that it is toxic in pregnancy. Data from patients with inflammatory bowel Data from patients with inflammatory bowel disease suggest it is likely to be safe in pregnancy disease suggest it is likely to be safe in pregnancy at dosages less than 100mg/day.at dosages less than 100mg/day.

(Moskovitiz et al., 2004)(Moskovitiz et al., 2004)

Wilson disease is a rare disorder Wilson disease is a rare disorder characterized by cirrhosis, neurological characterized by cirrhosis, neurological abnormalities, and less commonly abnormalities, and less commonly hematological and renal dysfunction .hematological and renal dysfunction .

D-Penicillamine and trientine have been D-Penicillamine and trientine have been used during pregnancy. However, the used during pregnancy. However, the dosage should be reduced to the minimum dosage should be reduced to the minimum necessary dose, which is about 25% to necessary dose, which is about 25% to 50% of the dose the patient had been 50% of the dose the patient had been taking before the pregnancy.taking before the pregnancy.

(Roberts & Schilsky, 2003)(Roberts & Schilsky, 2003)

• Zinc is the agent of choice for Wilson Zinc is the agent of choice for Wilson disease during pregnancy because of its disease during pregnancy because of its safety for the fetus. It should be safety for the fetus. It should be maintained throughout the pregnancy at maintained throughout the pregnancy at 50 mg three times a day.50 mg three times a day.

(Brewer et al., 2000)(Brewer et al., 2000)

Liver diseases coincidental Liver diseases coincidental with but not induced by with but not induced by

pregnancypregnancy

Liver diseases coincidental with but not Liver diseases coincidental with but not induced by pregnancyinduced by pregnancy– Acute viral hepatitis and other viral infectionsAcute viral hepatitis and other viral infections– Alcohol-related diseasesAlcohol-related diseases– Gallstone diseaseGallstone disease– Budd-Chiari syndromeBudd-Chiari syndrome

Hepatitis AHepatitis ACharacteristics Hepatitis A

Older name Infectious hepatitis

Virus type RNA

Virus size 27 nm

Incubation period 15 – 50 days

Transmission Fecal – oral

Vertical transmission to fetus Not observed

Serologic diagnosis Hepatitis A antibody IgM and IgG types

Maximum infectivity Prodrome

Carrier state None

Acute clinical forms Asymptomatic to fulminant

Chronic clinical forms None

• The clinical syndrome of acute HAV infection The clinical syndrome of acute HAV infection consists of vague flu-like symptoms with fatigue, consists of vague flu-like symptoms with fatigue, weakness, nau sea, and loss of appetite. The weakness, nau sea, and loss of appetite. The onset is usually abrupt. A variety of extrahepatic onset is usually abrupt. A variety of extrahepatic manifestations including myalgia, arthralgias, manifestations including myalgia, arthralgias, arthritis, and urticaria, may occur. arthritis, and urticaria, may occur.

• Other forms of HAV infection include cholestatic Other forms of HAV infection include cholestatic hepatitis, with a prolonged course marked by hepatitis, with a prolonged course marked by itching and jaundice. itching and jaundice.

(Willner, et al., 1998)(Willner, et al., 1998)

• The characteristic changes in liver function The characteristic changes in liver function test findings include marked elevations in test findings include marked elevations in AST and ALT. Most often, these reach AST and ALT. Most often, these reach levels of 1000 to 2000 U during the early levels of 1000 to 2000 U during the early part of the infection. Elevations in bilirubin part of the infection. Elevations in bilirubin and alkaline phosphatase also occur but and alkaline phosphatase also occur but are more unpredictable. are more unpredictable.

(Fiore, et al., 2003)(Fiore, et al., 2003)

• There is substantial evidence that pregnancy does There is substantial evidence that pregnancy does not alter the course of HAV infection. However, a not alter the course of HAV infection. However, a higher incidence of fulminant disease during higher incidence of fulminant disease during pregnancy has been reported in developing pregnancy has been reported in developing nations. Concurrent malnutrition has been a nations. Concurrent malnutrition has been a suspected cause. If the course of HAV infection is suspected cause. If the course of HAV infection is severe, it may precipitate severe, it may precipitate premature labor premature labor in in women in the third trimester of pregnancy.women in the third trimester of pregnancy. There is There is no evidence that HAV causes birth defects, and no evidence that HAV causes birth defects, and there is no evidence of maternal-fetal transmissionthere is no evidence of maternal-fetal transmission. .

(Atkinson, et al., 2002)(Atkinson, et al., 2002)

• Clinical management of pregnant patients with Clinical management of pregnant patients with HAV infection does not differ from that of those HAV infection does not differ from that of those who are not pregnant. However, hospitalization who are not pregnant. However, hospitalization may be indicated, specially during the last may be indicated, specially during the last trimester and in the presence of severe anorexia, trimester and in the presence of severe anorexia, nausea, and vomiting.nausea, and vomiting.

• In rare circumstances in which the mother has In rare circumstances in which the mother has acute HAV infection at the time of delivery, acute HAV infection at the time of delivery, immune serum globulin may be administered to immune serum globulin may be administered to the infant. Even under these conditions, the risk the infant. Even under these conditions, the risk of transmission to the infant seems very small. of transmission to the infant seems very small.

(Fiore, et al., 2003) (Fiore, et al., 2003)

Hepatitis BHepatitis BCharacteristics Hepatitis B

Older name Serum hepatitis

Virus type DNA

Virus size 42 nm


Transmission Parentral or body fluid

Vertical transmission to fetus Common

Serologic diagnosis HBs Ag, HBs Ab, IgM, and IgG typesHBe Ag, Ab, Hepatitis B virus DNA

Maximum infectivity Prodrome or HBe Ag Positive

Carrier state 5 – 10%

Acute clinical forms Asymptomatic to fulminant

Chronic clinical forms Chronic persistent hepatitisChronic active hepatitisCirrhosis

The incidence of the HBV carrier state The incidence of the HBV carrier state among pregnant women is variable and among pregnant women is variable and depends on the patient group studied. The depends on the patient group studied. The incidence of HBV carriers is considerably incidence of HBV carriers is considerably higher in populations in which drug abuse higher in populations in which drug abuse or with high incidence of sexual or with high incidence of sexual promiscuity.promiscuity.

(Van Zonneveld, et al., 2003)(Van Zonneveld, et al., 2003)

• Evidence suggests that transmission of Evidence suggests that transmission of HBV to infants is common when mothers HBV to infants is common when mothers have have acute infection in the third trimesteracute infection in the third trimester or when they are chronic carriers of HBV or when they are chronic carriers of HBV infection and have infection and have positive results of positive results of serum tests for HBeAg or HBV DNA.serum tests for HBeAg or HBV DNA.

(Su, et al., 2004)(Su, et al., 2004)

• In women with chronic hepatitis B infection, In women with chronic hepatitis B infection, taking lamivudine ( nucleotide analogue taking lamivudine ( nucleotide analogue used against HIV and HBV alone or with used against HIV and HBV alone or with combination with other anti-viral) before combination with other anti-viral) before becoming pregnant and continuing to take it becoming pregnant and continuing to take it throughout the pregnancy has been throughout the pregnancy has been reported to lower rates of transmission of reported to lower rates of transmission of the virus from mother to newborn. the virus from mother to newborn.

(Su, et al., 2004)(Su, et al., 2004)

• The administration of hyperimmune The administration of hyperimmune globulin and HBV vaccine protects 90% to globulin and HBV vaccine protects 90% to 95% of infants from HBV infection. 95% of infants from HBV infection.

It is recommended that 0.5 ml, of HBIG be It is recommended that 0.5 ml, of HBIG be given at birth and that three doses of HBV given at birth and that three doses of HBV vaccine be given beginning at birth.vaccine be given beginning at birth.

(Sehgal, et al., 1992)(Sehgal, et al., 1992)

Hepatitis CHepatitis CCharacteristics Hepatitis C

Older name Non A non B hepatitis

Virus type RNA

Virus size 30-60 nm


Transmission Parentral sporadic

Vertical transmission to fetus Uncommon

Serologic diagnosis Hepatitis C antibodyRNA by PCR

Maximum infectivity HIV co- infected

Carrier state 50 – 85%

Acute clinical forms Asymptomatic to sever relapsing

Chronic clinical forms Chronic persistent hepatitisChronic active hepatitisCirrhosis

• The rate of vertical transmission of hepatitis The rate of vertical transmission of hepatitis C is less than 5%. The risk is higher if the C is less than 5%. The risk is higher if the mother is co-infected with mother is co-infected with human human immunodeficiency virus (HIV)immunodeficiency virus (HIV), , if she is if she is viremic at the time of deliveryviremic at the time of delivery, i, if her viral f her viral DNA load is greater than 1 million copies/mlDNA load is greater than 1 million copies/ml, , and and if the time from the rupture of if the time from the rupture of membranes to delivery is more than 6 hoursmembranes to delivery is more than 6 hours. .

• The mode of delivery does not seem to The mode of delivery does not seem to influence the rate of transmission from influence the rate of transmission from mother to child.mother to child.

(Ceci et al., 2001)(Ceci et al., 2001)

• Breastfeeding is not considered a risk Breastfeeding is not considered a risk factor for transmission, even though viral factor for transmission, even though viral RNA has been detected in breast milk. .RNA has been detected in breast milk. .

(Steininger et al., 2003)(Steininger et al., 2003)

• Newborns of infected mothers should be Newborns of infected mothers should be tested at 12 to 18 months of age, when IgG tested at 12 to 18 months of age, when IgG antibodies to hepatitis C virus that may antibodies to hepatitis C virus that may have passively transferred from the have passively transferred from the placenta to the fetus would have been lost, placenta to the fetus would have been lost, and the persistence of hepatitis C viral RNA and the persistence of hepatitis C viral RNA would indicate infection with hepatitis C.would indicate infection with hepatitis C.

(Ferrero et al., 2003)(Ferrero et al., 2003)

• Interferon is in FDA category C, and Interferon is in FDA category C, and ribavirin is in category X. Both drugs are ribavirin is in category X. Both drugs are contraindicated in pregnancy. If a woman contraindicated in pregnancy. If a woman gets pregnant while on combination gets pregnant while on combination therapy, then both drugs should be therapy, then both drugs should be stopped, and she should be advised that stopped, and she should be advised that she has already put the fetus at risk of she has already put the fetus at risk of teratogenicityteratogenicity.

(Resti et al., 2003)

Herpes simplex virusHerpes simplex virus

• It can cause fulminant liver failure and death if It can cause fulminant liver failure and death if infection occurs during pregnancy, and the rate infection occurs during pregnancy, and the rate of transmission to the fetus can reach 30% to of transmission to the fetus can reach 30% to 50% if the primary episode occurs at delivery. 50% if the primary episode occurs at delivery.

• About 90% of pregnant women with this About 90% of pregnant women with this infection have abnormal liver enzyme tests infection have abnormal liver enzyme tests and an abnormal prothrombin time. and an abnormal prothrombin time. Acyclovir (FDA pregnancy category B) is Acyclovir (FDA pregnancy category B) is very effective if promptly given at doses of very effective if promptly given at doses of 400 mg three times daily for 5 to 7 days, 400 mg three times daily for 5 to 7 days, and early delivery is not required.and early delivery is not required.

(Nigro , et al., 2003)(Nigro , et al., 2003)

CytomegalovirusCytomegalovirus

• InfectionInfection may remain asymptomatic in may remain asymptomatic in pregnant women, and the prognosis is pregnant women, and the prognosis is favorable. The risk of transmission to the favorable. The risk of transmission to the fetus and of congenital abnormalities is fetus and of congenital abnormalities is highest when acute infection occurs in the highest when acute infection occurs in the first 22 weeks of pregnancy. Termination of first 22 weeks of pregnancy. Termination of the pregnancy may be an option after the pregnancy may be an option after appropriate counseling regarding the appropriate counseling regarding the potential serious risks to the infected fetus.potential serious risks to the infected fetus.

(Benachi A, et al., 2003)(Benachi A, et al., 2003)

Alcohol useAlcohol use

• Women are two to four times more likely Women are two to four times more likely than men to develop alcoholic liver than men to develop alcoholic liver disease for the same amount of alcohol disease for the same amount of alcohol ingested, and they exhibit a tendency to ingested, and they exhibit a tendency to disease progression even with abstinence.disease progression even with abstinence.

(Pares et al., 1986) (Pares et al., 1986)

• Continued drinking during pregnancy may Continued drinking during pregnancy may lead to miscarriage, stillbirth, prematurity, lead to miscarriage, stillbirth, prematurity, growth retardation, and the fetal alcohol growth retardation, and the fetal alcohol syndrome (growth retardation, behavioral syndrome (growth retardation, behavioral disturbances, disturbances, ccardiac defects, spinal ardiac defects, spinal defects, and craniofacial anomalies). defects, and craniofacial anomalies). Alcohol abstinence throughout pregnancy Alcohol abstinence throughout pregnancy should be emphasized.should be emphasized.

(Lemoine et al., 2003)(Lemoine et al., 2003)

Gallstone diseaseGallstone disease

• Pregnancy is a risk factor for sludge and Pregnancy is a risk factor for sludge and gallstone formation. By the end of the third gallstone formation. By the end of the third trimester, 10% to 12% of pregnant women trimester, 10% to 12% of pregnant women have gallstones. Most gallstones disappear have gallstones. Most gallstones disappear spontaneously without causing symptoms. spontaneously without causing symptoms. If symptoms develop, the treatment may be If symptoms develop, the treatment may be conservative or surgical, depending on the conservative or surgical, depending on the severity of the symptoms. severity of the symptoms.

• Laparoscopic surgery seems to be safe Laparoscopic surgery seems to be safe and should be considered. The optimal and should be considered. The optimal time for it appears to be during the second time for it appears to be during the second trimester, when fetal organogenesis is trimester, when fetal organogenesis is completed and the size of the uterus does completed and the size of the uterus does not interfere with the surgery. not interfere with the surgery.

(Halpern , 1998)(Halpern , 1998)

Budd-Chiari syndromeBudd-Chiari syndrome

• Budd-Chiari syndrome is very rare and Budd-Chiari syndrome is very rare and often insidious, manifesting after delivery. It often insidious, manifesting after delivery. It is characterized by thrombosis of the is characterized by thrombosis of the hepatic veins and portal hypertension. Its hepatic veins and portal hypertension. Its clinical manifestations include ascites, clinical manifestations include ascites, hepatomegaly, and abdominal pain.hepatomegaly, and abdominal pain.

(Singh et al., 2000)(Singh et al., 2000)

• Proper diagnosis and management require Proper diagnosis and management require imaging studies such as Doppler imaging studies such as Doppler ultrasonography and CT and liver biopsy. ultrasonography and CT and liver biopsy. Treatment with anticoagulants, Treatment with anticoagulants, thrombolytics (warfarin is contraindicated in thrombolytics (warfarin is contraindicated in pregnancy), diuretics, and portocaval pregnancy), diuretics, and portocaval shunting may be required. Liver shunting may be required. Liver transplantation is indicated when hepatic transplantation is indicated when hepatic decompensation develops.decompensation develops.

(Deltenre et al., 2001)(Deltenre et al., 2001)

Pregnancy Following Liver Pregnancy Following Liver TransplantationTransplantation

• Pregnancy after liver transplantation is Pregnancy after liver transplantation is often successful, but it must be regarded as often successful, but it must be regarded as a high risk, associated with hypertension, a high risk, associated with hypertension, preeclampsia, intrauterine growth preeclampsia, intrauterine growth retardation, and prematurity. It is best retardation, and prematurity. It is best delayed until 1 to 2 years after grafting. delayed until 1 to 2 years after grafting. Pregnancy planned at least 2 years after Pregnancy planned at least 2 years after liver transplantation with stable allograft liver transplantation with stable allograft function can have excellent maternal and function can have excellent maternal and neonatal outcome. neonatal outcome.

((Nagy et al., 2003Nagy et al., 2003))

• In most female recipients studied, In most female recipients studied, pregnancy does not appear to cause pregnancy does not appear to cause excessive or irreversible problems in graft excessive or irreversible problems in graft function if the function of transplanted function if the function of transplanted organ is stable prior to pregnancy, organ is stable prior to pregnancy, including twins if the woman has stable including twins if the woman has stable hepatic function before pregnancy. hepatic function before pregnancy.

(Nagy et al., 2003)(Nagy et al., 2003)

• In female recipients in contrast to the In female recipients in contrast to the general population, general population, a high incidence of low a high incidence of low birth-weightbirth-weight and and prematurityprematurity has been a has been a consistent outcome. consistent outcome. IImmunosuppressive mmunosuppressive agents may cause hypertension, agents may cause hypertension, preeclampsia and renal dysfunction in preeclampsia and renal dysfunction in these recipientsthese recipients.. However, there has been However, there has been no specific pattern of malformation in their no specific pattern of malformation in their newborns or any apparent increase in the newborns or any apparent increase in the incidence of small-for-gestational-age incidence of small-for-gestational-age newborns. newborns.

(Armenti et al., 2000)(Armenti et al., 2000)

• immunosuppression during pregnancyimmunosuppression during pregnancy is is not teratogenicnot teratogenic and does not lead to and does not lead to congenital anomalies.congenital anomalies.

• Nearly 70% of pregnancies after systemic Nearly 70% of pregnancies after systemic administration of administration of tacrolimustacrolimus resulted in a resulted in a favourable outcome without any significant favourable outcome without any significant effect on intrauterine growth.effect on intrauterine growth.

(Jabiry et al., 2005)

• Also, it was found that Also, it was found that tacrolimustacrolimus may may decrease the incidence of onset of decrease the incidence of onset of hypertension and toxemia of pregnancy. hypertension and toxemia of pregnancy. Thus, during pregnancy, the female recipient Thus, during pregnancy, the female recipient may continue the immunosuppressive may continue the immunosuppressive regimen to stabilize the transplanted liver regimen to stabilize the transplanted liver function but prevent the effect on the function but prevent the effect on the intrauterine growth. intrauterine growth.

• To the present, 37 cases of pregnancies To the present, 37 cases of pregnancies after liver transplantation have been after liver transplantation have been reported worldwide. reported worldwide.

• In conclusion:In conclusion:

Under careful monitoring a childbearing age Under careful monitoring a childbearing age woman with stable and adequate liver woman with stable and adequate liver function may have a successful pregnancy function may have a successful pregnancy and a delivery after liver transplantation.and a delivery after liver transplantation.

(Pan et al., 2007) (Pan et al., 2007)

liver disease with pregnancy.ppt

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