Download - CNS and Liver in Pregnancy

CME ONMEDICAL DISORDERS IN PREGNANCY

NERVOUS SYSTEM AND LIVER

Prof. Dr. S Sundar’s Unit

Dr. Deepu Sebin, PG in Internal Medicine

CNS in Pregnancy

Liver

Challenges us with the diagnosisChallenges are both in diagnosis and treatment

Brain and Liver – There are changes with pregnancy , but not much !

Liver in Pregnancy

CVAs and Seizures Pregnancy specific liver diseases

CVA during pregnancy

Pregnancy and the postpartum period are associated with a marked increase in the relative risk and a small increase in the absolute risk of ischemic stroke and intracerebral hemorrhage, with the highest risk during the puerperium.

Most cerebral infarctions associated with pregnancy are due to arterial occlusion, not cerebral venous thrombosis1

Ischemic and hemorrhagic strokes have been reported in roughly equal proportions.

1.Jaigobin and Silver (Stroke, 2000), McGriger etal 2003, NEFh study 1999

Stroke and Pregnancy: Subarachnoid Hemorrhage

Subarachnoid hemorrhage (SAH) is a leading cause of non-obstetric-related maternal death Which is often not identified.

Incidence of SAH from aneurismal rupture in pregnancy ranges from 3 to 11 per 100,000 pregnancies2

50% of all aneurismal ruptures in women below the age of 40 years are pregnancy related3

1. Visscher HC, Visscher RD. Indirect obstetric deaths in the state of Michigan 1960–1968. Am J Obstet Gynecol 1971;109:1187–96.2. Sharshar T, Lamy C, Mas JL. Incidence and causes of strokes associated with pregnancy and puerperium: a study in public hospitals of Ile de France. Stroke 1995;26:930–6.3. Barrett JM, Van Hooydonk JE, Boehm FH. Pregnancy-related rupture of arterial aneurysms. Obstet Gynecol Surv 1982;37:557–66.

Risk Factors Age >35 years Black Ethnicity HTN: Pre-eclampsia and Eclampsia Hypercoagulable state of pregnancy Heart Disease Smoking Diabetes Lupus Sickle Cell Disease Migraine Headache Alcohol and Substance Abuse Caesarean Delivery Fluid and Electrolyte Disorders Thrombophilia Multiple Gestation Greater Parity Postpartum Infection AntiPhospholipid Antibody Syndrome Gestational Trophoblastic Disorder Peripartum cerebral angiopathy

Risk FactorsRisk Factors Age >35 years Black Ethnicity HTN: Pre-eclampsia and Eclampsia Hypercoagulable state of pregnancy Heart Disease Smoking Diabetes Lupus Sickle Cell Disease Migraine Headache Alcohol and Substance Abuse Caesarean Delivery Fluid and Electrolyte Disorders Thrombophilia Multiple Gestation Greater Parity Postpartum Infection AntiPhospholipid Antibody Syndrome Gestational Trophoblastic Disorder Peripatrum Cerebral Angiopathy

Stroke and Pregnancy: Pre-eclampsia and Eclampsia

The proportion of patients with pregnancy-related stroke who have pre-eclampsia or eclampsia is 25-45%1

Proposed mechanisms for increased risk of stroke in pre-eclampsia and eclampsia:2

Endovascular dysfunction Abnormal cerebral autoregulation resulting in higher cerebral

perfusion pressures, which may result in barotrauma and vessel damage

Hemoconcentration due to third spacing of intravascular fluids Activation of the coagulation cascade with micro-thrombi

formation Cerebral hemorrhage is the most common cause of

death in women with eclampsia3

Stroke is the most common cause of death in women with HELLP syndrome4

Women with a history of pre-eclampsia are 60% more likely to have a non-pregnancy-related ischemic stroke5

1. Sharshar T, Lamy C, Mas JL. Incidence and causes of strokes associated with pregnancy and puerperium: a study in public hospitals of Ile de France. Stroke 1995;26:930–6.2. Treadwell SD, Thanvi B, Robinson TG. Stroke in pregnancy and the puerperium. Postgrad Med J of BMJ 2008;84:238-45.3. Okanloma KA, Moodley J. Neurological complications associated with the preeclampsia/eclampsia syndrome. Int J Gynaecol Obstet 2000;71:223–5.4. Isler CM, Rinehart BK, Terrone DA, et al. Maternal mortality associated with HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Am J Obstet Gynecol 1999;181:924–8.5. Brown DW, Dueker N, Jamieson DJ, et al. Preeclampsia and the risk of ischemic stroke among young women. Stroke 2006;37:1055–9.

1. Bushnell CD, Jamison M, James AH. Migraines during pregnancy linked to stroke and vascular diseases: US population based case-control study. BMJ 2009;338:b664.

Stroke and Pregnancy: Migraine

Migraine was thought to be associated with a with a 17-fold increased risk of pregnancy-related stroke1

Large Inpatient Sample (2000-2003):2

Strongest association between migraine and ischemic stroke (OR=30.7)

Intracranial hemorrhage strongly associated with migraine (OR=9.1)

Pre-eclampsia and venous thromboembolism/PE associated with migraine

CVT and SAH were not associated with migraine1. James AH, Bushnell CD, Jamison MG, Myers ER. Incidence and risk factors for stroke in pregnancy and the puerperium. Obstet Gynecol 2005;106:509-16.2. Bushnell CD, Jamison M, James AH. Migraines during pregnancy linked to stroke and vascular diseases: US population based case-control study. BMJ 2009;338:b664.

Stroke and Pregnancy: Migraine

Overlapping pathophysiological mechanisms exists.

Migrainers have increased peripheral and central blood pressure, a decreased diameter and compliance of superficial muscular arteries, and decreased endothelial dilatation response to hyperemia compared to controls1.

Active migraine during pregnancy can be viewed as a marker of vascular diseases, especially ischemic stroke2.

1. Vanmolkot F, Van Bortel L, de Hoon J. Altered arterial function in migraine of recent onset. Neurology 2007;68:1563-70.2. Bushnell CD, Jamison M, James AH. Migraines during pregnancy linked to stroke and vascular diseases: US population based case-control study. BMJ 2009;338:b664.

Increased von Willebrand factor,Factor 8, fibrinogenReduced protein S concentrationsIncreased plasminogen activator inhibitors 1 and 2Platelet aggregation

Barotrauma during deliver due to raised ICP due to straining

Gravid uterus compressing the vessels

Stroke and Pregnancy:Cerebral Vein Thrombosis (CVT)

Occlusion of the dural venous sinuses or cortical veins can result in venous infarction and hemorrhage with associated focal neurological signs and symptoms Impaired absorption of CSF Intracranial HTN Headache, vomiting, papilledema Seizures, coma, death

Risk of CVT is increased in the puerperium due to pregnancy-related hypercoagulability

Incidence rate of 11.6 cases of peripartum CVT per 100,000 deliveries1

1. Lanska DJ, Kryscio RJ. Risk factors for peripartum and postpartum stroke and intracranial venous thrombosis. Stroke 2000;31:1274–82.

Stroke and Pregnancy:Cerebral Vein Thrombosis (CVT)

Treatment is complicated by uncertainty regarding the safety of antithrombotic agents during pregnancy

Low dose aspirin appears to be safe for the fetus after the first trimester

Warfarin may be safe for the fetus after the first 12 weeks, but is not usually recommended during pregnancy because of teratogenic risk

American Heart Association/American Stroke Association recommendations for high-risk thromboembolic complications in pregnancy: Adjusted-dose unfractionated (UFH) heparin throughout

pregnancy with PTT monitoring Adjusted-dose low-molecular-weight heparin (LMWH)

throughout pregnancy with factor Xa monitoring UFH or LMWH until week 13 followed by warfarin until the

middle of the third trimester, when UFH or LMWH is reinstituted until delivery1

1. Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack. Stroke 2006;37:577–617.

Stroke and Pregnancy:Postpartum Cerebral Angiopathy

Postpartum cerebral angiopathy (PCA) is a cerebral vasoconstriction syndrome

Also known as eclamptic vasospasm or Call-Fleming syndrome

Exact pathophysiology unknown Symptoms usually occur in late pregnancy or

early puerperium, and may be associated with pre-eclampsia or eclampsia1,2

Recurrent thunderclap headache Focal neurological deficits (transient or permanent) Photosensitvity Vomiting Altered level of consciousness Seizures

1. Treadwell SD, Thanvi B, Robinson TG. Stroke in pregnancy and the puerperium. Postgrad Med J of BMJ 2008;84:238-245.2. Singhal AB, Kimberly WT, Schaefer PW, Hedley-Whyte ET. Case 8-2009: A 36-year-old woman with headache, hypertension and seizure 2 weeks post partum N Engl J Med 2009;360:1126-37.


Radiological features Multifocal segmental narrowing of the cerebral arteries Reversibility and resolution of narrowing within 3 months Vasogenic edema Border-zone ischemic strokes

Cerebrospinal Fluid Usually normal (Differentiates PCA from SAH)

Pathology May be necessary to distinguish PCA from vasculitis Early hypertensive vascular changes and subendothelial

thickening have been described1

No pathological changes specific to PCA have been described Treatment

Calcium channel blockers (IV, PO or intra-arterial) Corticosteroids

1. Singhal AB, Kimberly WT, Schaefer PW, Hedley-Whyte ET. Case 8-2009: A 36-year-old woman with headache, hypertension and seizure 2 weeks post partum N Engl J Med 2009;360:1126-37.


1. Singhal AB, Kimberly WT, Schaefer PW, Hedley-Whyte ET. Case 8-2009: A 36-year-old woman with headache, hypertension and seizure 2 weeks post partum N Engl J Med 2009;360:1126-37.

STROKE AND PREGNANCY

Diagnostic Imaging

Natural background exposure in a costal area is ~300 mrad per year.

Maximum estimated fetal absorbed dose of ionizing radiation is

50 mrad for a head CT

Stroke and Pregnancy: Ionizing Radiation

Estimated increase in lifetime risk of developing cancer after fetal exposure form a head CT is 0.07%4

Analysis suggests that pregnant women exposed to less than 5000 mrad have no additional risk to the fetus4

There is no direct evidence that fetal exposure to ionizing radiation used in diagnostic imaging causes cancer or birth defects

MRI does not involve ionizing radiation Any long-term effects are yet to be determined

1. Hart D, Hillier MC, Wall BF, et al. Doses to patients from medical x-ray examinations in the UK – 1995 review. Chilton: NRPB-R289, 1996.

2. Osei EK, Faulkner K. Fetal doses from radiological examinations. Br J Radiol 1999;72:773–80.3. NRPB. Diagnostic medical exposures: exposure to ionizing radiation of pregnant women. Doc NRPB

1993;4:5–14.4. Treadwell SD, Thanvi B, Robinson TG. Stroke in pregnancy and the puerperium. Postgrad Med J of BMJ

2008;84:238-245.

Seizure Disorder and Pregnancy

How Bad are AEDs ?

All Anti Epileptic drugs have teratogenic effects

Lack of conclusive data on the comparative teratogenicity of different AEDs.

A possible exception is valproate. Early results from pregnancy registries and most recent cohort studies suggest a trend toward higher teratogenicity with valproate than with other AEDs

•Seizures cause fetal bradycadia and fetal hypoxia•Seizure cause considerable increase in maternal mortality

•Anti epileptic drugs•All can have

harmful effects for fetus

1.Know epileptic patient, planning for a pregnancy

Does She even Need AED ?

Polytherapy to Monotherapy Therapy

Taper to Lowest Possible Dose

Replace Valproate

Add Folate 4 mg, Vitamin K in third trimester

Adequate Sleep

Plan conception after 6 months

Use barrier contraception

2.A pregnant epileptic patient

Does She even Need AED ?

Polytherapy to Monotherapy Therapy

Taper to Lowest Possible Dose,

Replace Valproate

Add Folate 4 mg. Vitamin K in 3rd trimester

Adquate Sleep

Plan conception after 6 months

Use barrier contraception

Beware of Possble dilution Consider plams drug level monitoring

if possible

3.A patient with a seizure in pregnancy or delivery or postpartum

Emergency

Consider MasulfIF:>20 wks of pregnancy or postpartumSeizure not controlled with IV AED & Sedation

Any Features of Preeclampsia in current or previous pregnancy ?

No Yes

* The initial diagnosis of preeclampsia may be postpartum

Suspect CVA/CVT/CNS infection

Manage as similar to non pregnant seizure

Magnesium SulphateDiazepamLorazepam if not resolving

Magnesium Sulphate

A observations drug in the past, Now a evidence based drug.

Magnesium's mechanism of action as an anticonvulsant in preeclampsia/eclampsia is not clearly understood.

Some possibilities include vasodilatation of the cerebral vasculature, inhibition of platelet aggregation, protection of endothelial cells from damage by free

radicals, prevention of calcium ion entry into ischemic cells, decreasing the release of acetylcholine at motor

end plates within the neuromuscular junction as a competitive antagonist to the glutamate N-

methyl-D-aspartate receptor (which is epileptogenic)

Magnesium Sulpahte is an Anti Eplileptic Drug,which is has its maximum effect when the seizures are due to Eclampsia

A tonic-clonic seizure occurs during labor in 1 to 2% of women with epilepsy, and another 1 to 2% 24hrs after delivery. It is therefore essential to maintain a plasma AED level known to protect against seizures during the third trimester and during delivery and postpartum.

Doses must not be missed during the period of labor.

Liver in a Normal Pregnancy

In Normal Pregnancy Physical – Palmar Erythema, Spider

Naevi Pathologically essential normal except

for increased Endoplasmic Reticulum.

Liver Flow is same ( Excess blood because of the increased Cardiac Output is shunted out to the placenta)

Normal Pregnancy

Viral Hepatitis

H. Gravidarum

IHCP HEELP AFLP

S .Bilurubin Slightly down

AST Normal

ALT Normal

ALP 3x in 3rd timester

GGT Normal

S. Bile Acid Normal

PT, INR Normal

S.Ammonia Normal

Total Count Normal

Platelets Normal

RBS Normal

S.Creatine Normal

LDH Normal

DIC No

Preexisting Liver Diseases

Liver diseases coincidental with but not induced by pregnancy

Liver Disease Induced by Pregnancy

Preexistent liver diseases

Portal hypertension, cirrhosis, primary biliary cirrhosis Pregnancy is difficult, Treating bleeding esophageal varices

with nonselective beta-blockers, band ligation, and octreotide is safe and effective during pregnancy.

Ursodeoxycholic acid to be continued in PBC Autoimmune hepatitis

Corticosteroids Flare ups common

Wilson disease Zinc is the agent of choice. D Pencillamin, trientere to

be used in minimum possible dose

Chronic infection with hepatitis B or hepatitis C virus Doesn’t need active therapy in Pregnancy

Liver diseases coincidental with but not induced by pregnancy

Acute viral hepatitis and other viral infections

Alcohol-related diseases

Gallstone disease

Budd-Chiari syndrome

Viral Hepatits in PregnancyWhats Different ? Findings usually include fever, nausea, right

upper quadrant pain, and markedly elevated transaminases (usually above 1000 IU/L)

Hepatitis A The course of hepatitis A during pregnancy is

generally similar to that in nonpregnant patients

Increased risk for premature labor However, hospitalization may be indicated,

specially during the last trimester and in the presence of severe anorexia, nausea, and vomiting.

Hepatitis B Acute infection with hepatitis B during pregnancy is not associated with increased mortality or teratogenicity.

Treatement with Lamivudine seems to decrease the transmission, however therapy during pregnancy is not indicated as of now. We can WAIT.

The risk of transmission is highest in mothers who are HBeAg - positive at the time of delivery

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

Hepatitis C The rate of vertical transmission of hepatitis C is less

than 5%. Hepatitis E

During pregnancy, HEV can cause fulminant hepatitis and can be a Medical Emergency. There is a significant mortality rate of 16-20% in pregnant women with acute HEV infection.

Fulminant hepatitis due to hepatitis E may resemble liver failure from acute fatty liver of pregnancy, hepatic infarction in the syndrome of hemolysis, elevated liver enzymes and low platelets (HELLP), or herpes simplex hepatitis

Treatemnt is largely Supportive.

Normal Pregnancy

Viral Hepatitis

H. Gravidarum

IHCP HEELP AFLP


< or >5

AST Normal >1000

ALT Noraml >1000


Raised in choleststic ph

S. Bile Acid Normal Nl or raised

PT, INR Normal Normal

S.Ammonia Normal Normal

Total Count Normal Normal

Platelets Normal Normal

RBS Normal Normal

S.Creatine Normal Normal

LDH Normal Normal

DIC No No

Liver diseases induced by pregnancy

First trimester Hyperemesis gravidarum

Second and third trimesters Intrahepatic cholestasis of pregnancy

Preeclampsia, eclampsia, and the HELLP syndrome

Acute fatty liver of pregnancy

Hyperemesis Gravidarum

Clinicaly In First trimester Severe, persistent nausea and vomiting Mild jaundice, pruritis. Can also Present with hypovolemia, dehydration,ketosis

& electrolyte imbalance

50% have increased LFTs (2-3x normal) seen 1-3 weeks after onset. Enzymes elevated may be upto 1000. Bilurubin elevates in severe cases

Resolves rapidly with cessation of emesis. Negligible mortality .

Normal Pregnancy

Viral Hepatitis

H. Gravidarum

IHCP HEELP AFLP


< or >5 <5

AST Normal >1000 <500

ALT Noraml >1000 <500



Normal

S. Bile Acid Normal Nl or raised Normal

PT, INR Normal Normal Normal

S.Ammonia Normal Normal Normal

Total Count Normal Normal Normal

Platelets Normal Normal Normal

RBS Normal Normal Normal

S.Creatine Normal Normal Normal

LDH Normal Normal Normal

DIC No No No

Intrahepatic Cholestasis of Pregnancy Incidence of 1 in 1,000-10,000

pregnancies Seems to have a seasonal variation,

peaking in November Second and third trimester of pregnancy

Pathogenesis

Cause is unknown Evidence suggests both genetic and

hormonal factors play a role Genetic

The ABCB4 (adenosine triphosphate-binding cassette, subfamily B, member 4) , especially in a subtype of progressive familial intrahepatic cholestasis called PFIC3

Hormonal Estrogen Progesteron

Clinical Manifestations

A pregnant lady in her 2nd or 3rd trimester With pruritus more in palms, soles and

face Troubled more at night With excoriations due to scrathing May have excoriations due to scratching She also gives a h/o of similar itching

during previous pregnacny And the fetus died inutero at that time !


~2 weeks after start of symptoms, jaundice develop in 50%

Accounts for 20-25% of cases of jaundice during pregnancy.

Jaundice is usually mild, but persists until delivery.

Symptoms usually abate about 2 days after delivery.

Lab Investigations

ALP increases 5-10 fold

Serum total bile acids Serum total bile acid concentrations increase

in ICP, and may be the first or only laboratory abnormality

Total bilirubin mildly increased

AST, ALT may increase mild to >1,000 U/L

Lab Investigations

GGT normal or slightly elevated

Coagulation factors INR

usually normal may be increased scondary to Vitamin K

deficiency due to cholestasis or due to the use of bile acid sequestrants.

USG to rule out obstructive causes

Normal Pregnancy

Viral Hepatitis

H. Gravidarum

IHCP HEELP AFLP


< or >5 <5 <5 , direct

AST Normal >1000 <500 <300

ALT Noraml >1000 <500 <300



Normal Elevated

S. Bile Acid Normal Nl or raised Normal Raised

PT, INR Normal Normal Normal Can be elevate

S.Ammonia Normal Normal Normal Normal

Total Count Normal Normal Normal Normal

Platelets Normal Normal Normal Normal

RBS Normal Normal Normal Normal

S.Creatine Normal Normal Normal Normal

LDH Normal Normal Normal Normal

DIC No No No No

Treatement Ursodeoxycholic acid 500 mg twice a day Vitamin K Cholestyramine Benadryl, hydroxyzine and other

antihistamines may help only slightly Antihistamines may aggravate respiratory

difficulties in preterm babies

Early delivery if fetal lung maturity is attained

The maternal prognosis in ICP is good. Affected women generally have no hepatic sequelae

Recurrence can occur In contrast to the favorable prognosis for

mothers, ICP carries significant risk for the fetus. The main complications are fetal prematurity, meconium stained amniotic fluid, intrauterine demise, and an increased risk for neonatal respiratory distress syndrome

HELLP SYNDROME

HELLP SYNDROME

The HELLP syndrome is a multi-system disease variant of severe preeclampsia that is characterized by microangiopathic hemolytic anemia (MAH), hepatic dysfunction (hepatic necrosis), thrombocytopenia (platelet count, <100,000/ mm3), and, in the syndrome’s most severe form, DIC.

HELLP Syndrome

Third trimester Incidence of 0.17-0.85% Occurs in 20-25% of women with

preeclampsia 20% with HELLP have no HTN or proteinuria ? Imbalance between vasoconstrictive and

vasodilative forces causing endothelial dysfunction and platelet aggregation

HELLP Syndrome

Presentation: Mean age – 25 years RUQ pain 70-90% Nausea, vomiting common Headache 25% Visual changes 15-30% Generalized edema 50-67% Ascites 8-10%

HELLP Syndrome

Lab Abnormalities Low haptoglobin level in 95% Bilirubin elevation 47-62% Low platelets 50% AST/ALT elevation (3x above normal)

Normal Pregnancy

Viral Hepatitis

H. Gravidarum

IHCP HEELP AFLP


< or >5 <5 <5 , direct <5

AST Normal >1000 <500 <300 >500

ALT Noraml >1000 <500 <300 >500



Normal Elevated Normal

S. Bile Acid Normal Nl or raised Normal Raised Normal


May be elevat

S.Ammonia Normal Normal Normal Normal Normal

Total Count Normal Normal Normal Normal Normal

Platelets Normal Normal Normal Normal Low

RBS Normal Normal Normal Normal Normal

S.Creatine Normal Normal Normal Normal Usually Nl

LDH Normal Normal Normal Normal Raised

DIC No No No No Can Occur

HELLP Syndrome

Maternal complications DIC 4-38% Placental abruption 10-16% Acute renal failure 1-8% Severe ascites 5-8% Pulmonary edema 2-10% ARDS 1% Hepatic infarction / rupture 1%

HELLP Syndrome

Management Complete bed rest Corticosteroids beneficial Supportive therapy

Coagulopathy correction Ventillatory Support Dialysis Platelet transfusion

Maternal mortality 8% Fetal mortality 8-37%

Treatement - HELLP

Removal of the chorionic villi by delivery is the only defenitive therapy

Severe maternal an indication for prompt delivery regardless of gestational age.

For pregnancies ≥ 34 weeks of gestation, delivery rather than expectant

For pregnancies less than 34 weeks of gestation in which maternal and fetal status is reassuring, delivery after a course of glucocorticoids to accelerate fetal pulmonary maturity rather than expectant management or prompt delivery.

For gestations less than 30 to 32 weeks with an unfavorable cervix, cesarean delivery to avoid a potentially long induction

Treatement - HELLP

Correct coagulopathy if DIC is present IV magnesium sulfate to prevent seizures Provide treatment for severe hypertension

to prevent stroke Platelet transfusion Consider Dexamthasone Onset of DIC = immediate delivery Be aware of the possiblity of subscapsular

hematoma and rupture Keep Blood ready Surgical Interventions

Acute Fatty Liver of Pregnancy

Acute Fatty Liver of Pregnancy

Acute Yellow atrophy of liver Characterized by microvesicular fatty

infiltration of hepatocytes, is a disorder which is unique to human pregnancy.

True MEDICAL and OBSTRETICAL Emergency

1 in 7000 to 1 in 20,000 deliveries It is more common with multiple gestations

and possibly in women who are underweight.

Acute fatty liver of pregnancy most frequently complicates the third trimester and is commonly associated (or complicated ) with preeclampsia (50 to 100 percent).

Acute fatty liver of pregnancy is similar histologically and clinically to Reye's syndrome and Jamaican vomiting sickness, both diseases of microvesicular fatty infiltrationRiely CA. Hepatic disease in pregnancy. Am J Med 1994;96(1A):18S-22S

3. Samuels P, Cohen AW. Pregnancies complicated by liver disease and liver dysfunction. Obstet Gynecol Clin North Am 1992;19:745-63


The duration of prodromal symptoms and signs is variable

Often presents with nausea and vomiting, followed by severe abdominal pain and headache


The right upper quadrant is generally tender, but the liver is not enlarged to palpation

Within a few days, jaundice appears, and the patient becomes somnolent and eventually comatose

Hematemesis and spontaneous bleeding result when the patient develops hypoprothrombinemia and DIC

Vomiting 80

Abdominal pain 52

Jaundice 93

Encephalopathy 87

Polydipsia 80

Pruritus 60

Ascitis 47


Oliguria, metabolic acidosis, and eventually anuria occur in approximately 50 percent of patients

Diabetes insipidus may also accompany the disease, but may not manifest itself until postpartum

These patients may respond to dDAVP after delivery


If the disease is allowed to progress, labor begins and the patient delivers a stillborn infant

Uteroplacental insufficiency may be the cause of fetal distress and fetal death in these patients.


During the immediate postpartum period, the mother becomes febrile, comatose and, without therapy, dies within a few days

DIC, renal failure, profound hypoglycemia, and occasionally pancreatitis are the most often cited immediate causes of death

Pathogenesis

• A genetic component has been suggested

• Recent research suggests that AFLP is associated with a ln mutation in the long-chain 3-hydroxy

acyl-coenzyme A dehydrogenase (LCHAD), a fatty acid β oxidation enzyme.

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

•Matern D, Hart P, Murtha AP, Vockley J, Gregersen N, Millington DS, et al. Acute fatty liver of pregnancy associated with short-chain acyl- coenzyme A dehydrogenase deficiency. J Pediatr 2001;138:585-8. [76]. Brackett JC, Sims HF, Rinaldo P, et al. Two alpha subunit donor splice site mutations cause

human trifunctional protein deficiency. J Clin Invest 1995;95:2076-82.

Normal Pregnancy

Viral Hepatitis

H. Gravidarum

IHCP HEELP AFLP


< or >5 <5 <5 , direct <5 <5

AST Normal >1000 <500 <300 >500 <500

ALT Noraml >1000 <500 <300 >500 <500



Normal Elevated Normal Normal

S. Bile Acid Normal Nl or raised Normal Raised Normal Normal


May be elevat

Elevated

S.Ammonia Normal Normal Normal Normal Normal Elevated

Total Count Normal Normal Normal Normal Normal High

Platelets Normal Normal Normal Normal Low Low

RBS Normal Normal Normal Normal Normal Low

S.Creatine Normal Normal Normal Normal Usually Nl Can be raised

LDH Normal Normal Normal Normal Raised Raised or normal

DIC No No No No Can Occur Yes

There is a large clinical overlap between AFLP and HELLP syndrome and it may be difficult, even impossible, to differentiate them. However, evidence of hepatic insufficiency such as hypoglycemia or encephalopathy are suggestive of AFLP.

Imaging tests are primarily used to exclude other diagnoses, such as an hepatic infarct or hematoma

Liver Biopsy in AFLP

Liver biopsy is diagnostic, showing the characteristic picture which is the microvesicular fatty infiltration of the hepatocytes. The fat droplets surround centrally located nuclei, giving the cytoplasm a foamy appearance.

The primary treatment of acute fatty liver of pregnancy is prompt delivery

Treat complication Correct coagulation Correct Platelets Mechanical Ventilation in Coma, Respiratory

distress Electrolytes Dialysis in Renal Failure Parentral Nutrition in Pancreatitis

Can Recurr in subsequens pregnancies

Thank you