Presentation on theme: "Acute fatty liver versus HELLP syndrome in obstetric ICU: why and how to differentiate? BY Bahaa-El-Din Ewees MD."— Presentation transcript:
1Acute fatty liver versus HELLP syndrome in obstetric ICU: why and how to differentiate? BY Bahaa-El-Din Ewees MD
2Physiological changes in liver tests during normal pregnancy Normal RangeBilirubinUnchanged or slightly decreaseAminotransferasesUnchangedProthrombin timeAlkaline phosphataseIncreases 2 to 4-foldFibrinogenIncreases 50%GlobulinIncreases in α and ß globulinsα -fetoproteinModerate rise, esp. with twinsWBCIncreasesCeruloplasminCholesterolIncreases 2-foldTriglyceridesDecreases in gamma-globulinHemoglobinDecrease in later pregnancy
3Abnormal liver function tests occur in 3 - 5% of pregnancies for different reasons Liver diseases in pregnancyliver disorders that occur only in the setting of pregnancyliver disorders that occur coincidentally with pregnancy
4Liver diseases in pregnancy coincidental with pregnancyOnly in thesetting of pregnancyChronic liver diseases e.g.:cholestatic liver disease,autoimmune hepatitis,Wilson disease,viral hepatitis, etc…not associated withpreeclampsiaPreeclampsia-associatedThe preeclampsiaitselfHyperemesisgravidarumHELLP-syndromeIntrahepatic cholestasisof pregnancyAFLP
6Severe preeclampsia is complicated in 2-12% of cases (0. 2-0 Severe preeclampsia is complicated in 2-12% of cases ( % of all pregnancies) by hemolysis (H), elevated liver tests (EL), and low platelet count (LP), the HELLP syndrome.Etiology: microangiopathic hemolytic anemia + vascular endothelial injury fibrin deposition in blood vessels + platelet activation & consumption, small to diffuse areas of hemorrhage and necrosis large hematomas + capsular tears + intraperitoneal bleeding.
8Most patients: 27 - 36 weeks’ gestation, but 25% in postpartum period.Can occur with any parity and age but commoner in white, multiparous & older pts.
9some patients have no obvious preeclampsia Clinical Picture:Most patientsLess commonlyupper abd. pain& tendernessjaundiceuncommon (5%)renal failure+ uric acidNauseavomitingDIHypertensionproteinuriaMalaiseheadacheAntiphospholipidsyndromeEdemaweight gainsome patients have no obvious preeclampsia
10Diagnosis requires the presence of all 3 laboratory criteria: HemolysisEL…………………Elevated Liver TestsLP……………Low PlateletsLDH>600 U/L↑ indirect bilirubinAST> 70U/L<150,000Based on platelet count, may be:severe/ Class 1 (platelets 50,000),moderate/Class 2 (50 –99,000),mild/Class 3 (100 –150,000).Lately, DIC, pulmonary edema, placental abruption, and retinal detachment may be present.
11Aminotransferase: variable, from mild to 10 – 20 fold, Bilirubin: usually < 5 mg/dL.Liver CT:subcapsular hematomas,intra-parenchymal hemorrhage, or infarctionhepatic rupture.Histologically: focal hepatocyte necrosis, periportal hemorrhage, and fibrin deposits.
12CT abdomen of a woman with severe HELLP syndrome (39 weeks) CT abdomen of a woman with severe HELLP syndrome (39 weeks). A large subcapsular hematoma extends over the Lt lobe; Rt lobe has heterogeneous, hypodense appearance due to widespread necrosis, with “sparing” of the areas of lt lobe (compare perfusion with the normal spleen).
14The only definitive treatment is delivery Hospitalization & ICU care for:antepartum stabilization of BP and DIC,seizure prophylaxis,fetal monitoring.The only definitive treatment is deliverygestational age24-34 wkpregnancy is > 34 wkcorticosteroids for 48 h(fetal lung maturity)immediate inductiondelivery
15Corticosteroids which cross the placenta (betamethasone or dexamethasone,)for hoursfetal lung maturityimproves maternalplatelet count.Tried treatment modalities for patients withongoing or newly developing symptomsplasmapheresisAntithrombotics(Heparin, aspirin)plasma exchangewith FFPdialysis
16continue close monitoring of the mother After deliverycontinue close monitoring of the motherUp to 48 h postpartumRARELYpersistent or worseninglab. Abnormalitiesby 4th postpartum dayworsening thrombocytopenia& increasing LDH levelsMay beAfter 48 hMost lab. values normalizePostpartumcomplications5 daysnormalization of platelets
22Acute fatty liver of pregnancy (AFLP) is a rare but serious maternal illness that occurs in the third trimester of pregnancy.Incidence: 1/ to 1/ pregnancies.Maternal mortality: 18%Fetal mortality: 23%.More common in nulliparous women and with multiple gestation.
23PathophysiologyDefects in intramitochondrial fatty acid beta-oxidation (enzymatic mutations in fatty acid oxidation).Heterozygous woman gets a homozygous fetus fetal fatty acids accumulatereturn to the mother’s circulationextra load of long-chain fatty acidstriglyceride accumulation hepatic fat deposition & impaired maternal hepatic function.
27Laboratory findings (Cont.) liver biopsyImaging studies (US & CT)most definitive testInconsistentoften not doned. t. coagulopathyswollen, pale hepatocytesin the central zonesSo, diagnosis isusually based onclinical & lab. findingsfindingsmicrovesicular fatty infiltration(frozen section with oil red staining)
28Histological appearance of the liver in AFLP. (A) Sudan stain (low power) shows diffuse fatty infiltration (red staining) involving predominantly zone 3, with relative sparing of periportal areas.(B) Hematoxylin-eosin stain (high power) shows hepatocytes stuffed with microvesicular fat (free fatty acids) and centrally located nuclei.
30Treatment involvesearly recognition & diagnosisimmediate terminationof pregnancy+If no obstetric indication, normal delivery is preferred to CS ( % of major intra-abdominal bleeding)Careful attention to the infant: risk of cardiomyopathy, neuropathy, myopathy, nonketotic hypoglycemia, hepatic failure, and death.
32Usually Sometimes Rarely By dayspostpartumliver enzymes& encephalopathyimprovelaboratory abnormalitiespersist after delivery& may initially worsen duringfirst postpartum weekSometimespatients progress to fulminant hepatic failurewith need for liver transplantation.RarelyMost patients improve in 1 to 4 weeks postpart
33With advances in supportive management, the maternal mortality is now 7%-18% and fetal mortality 9%-23%.Complications:Infectious and bleeding remain the most life threatening.Liver transplantation has a very limited role because of the great potential for recovery with delivery.
35HELLPAFLP% Pregnancies0.2%–0.6%0.005%–0.01%Onset/trimester3 or postpartumFamily historyNoOccasionallyPresence of preeclampsiaYes50%Typical clinical featuresHemolysis (anemia)Thrombocytopenia (50,000 often)Liver failure with coagulopathy, encephalopathyhypoglycemia, DICAminotransfer-asesMild, but may be up to fold risetypical but variable
36<5 mg/dL unless massive necrosis HELLPAFLPBilirubin<5 mg/dL unless massive necrosisoften >5 mg/dL, higher if severeHepatic imagingHepatic infarctsHematomas, ruptureFatty infiltrationHistologyPatchy/extensivenecrosis, periportal hge, fibrin depositsMicrovesicular fat in zone 3Maternal mortality1%–25%7%–18%Fetal/perinatal mortality11%9%–23%Recurrence in subsequentPregnancies4%–19%fatty acid oxidation defect %No fatty acid oxidation defect rare
38Major Risks AFLP HELLP DIC Infections & bleeding (most life threatening).DICARFHypoglycemiaARDSpulmonary edemaPancreatitis (develop after onsetof hepatic & renal dysfunctionneed serial screeningof serum lipase and amylasefor several days afterhepatic dysfunction)stroke & seizuresliver hges(most life-threatening)
39Therapeutic Options AFLP HELLP Late Early FFP Plasmapheresis glucoseAntithrombotics:(heparin, antithrombin,low dose aspirin)Liver transplant(limited role)Liver transplantMore definite role roleSteroids: rapid clinical &lab. improvementBlood transfusion
40Follow-up Precautions: A deficiency in long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) is thought to be associated with the development of AFLP.Under normal circumstances, an individual that is heterozygous for enzymatic mutations in fatty acid oxidation will not have abnormal fatty oxidation.
41Affected patients should be screened for defects in fatty acid oxidation as recurrence in subsequent children is 25%, and recurrence of AFLP in mothers is also possible.Presymptomatic diagnosis of FAOD with The application of tandem mass spectrometry to newborn screening is an effective way to identify most FAOD patients presymptomaticallyreduce morbidity and avoid mortality
42Current management of pts with FAOD includes long-term dietary therapy of: fasting avoidance,low-fat/high-carbohydrate dietrestriction of long-chain fatty acid intake and substitution with medium-chain fatty acids.These dietary approaches appear promising in the short-term, but not the long-term outcome.
43In conclusion Important to diff. AFLP from HELLP Diff. mainly based on lab. + imaging (CT-MRI)Diff. because AFLP needs:Maternal follow-up for recurrenceBaby follow-up for FAOD needing dietary controlNext pregnancies for presymptomatic diagnosis