Hepatic Dysfunction During Pregnancy Ayman Mokhtar Kamaly, MD Professor of Anesthesiology [email protected].

Hepatic Dysfunction During Pregnancy

Ayman Mokhtar Kamaly, MD

Professor of Anesthesiology

[email protected]

• Most pregnant women are young & healthy.

• Liver disease is a rare complication of pregnancy, but when it occurs it may be so dramatic & in a tragic fashion for both mother & infant.

• Abnormal liver tests occur in 3%-5% of pregnancies, with many potential causes:

Coincidental toPregnancy

Underlying ChronicLiver Disease

Diseases Unique toPregnancy

Viral hepatitis Chronic hepatitis B or C Hyperemesis gravidarum

Gallstones Autoimmune hepatitis Intrahepatic cholestasis ofpregnancy

Drugs 1ry sclerosing cholangitis Preeclampsia

Sepsis Wilson disease HELLP syndrome

Budd-Chiari* 1ry biliary cirrhosis (rare) Acute fatty liver ofpregnancy

Cirrhosis (uncommon)

Normal liver in pregnancy

• Physiological changes in pregnancy:

– 40% increase in plasma volume,– Increase in CO & HR (peaks at 32 wks),– Hepatic Bl flow remains the same or even

decreases (35% of CO in non-pregnant Vs 28% in pregnants).

Abnormal LFT During Pregnancy ‘normal for pregnancy’

• AST• ALT• GGT• BIL

20% ↓

• ALP• Triglycerides• Cholesterol• Transferrin• α1, α2 globulins

↑

• Alb• Urea• Uric acid

↓

(I) Liver Diseases Unique to Pregnancy

• Occurs in 0.3% of pregnancies (1st trimester),

• Sever enough to indicate IV hydration,

• Risk factors: – Hyperthyroidism,– Molar pregnancy,– Pre-existing DM, – Multiple pregnancies.

1) Hyperemesis Gravidarum (HG)

• LFT:o Mild ↑ Bil (< 4mg%), related to malnutrition & impaired excretion of Bil.o ALP ↑ twice N.o AST/ALT ↑ 20-fold

• Biopsy: Histological normal.

• Management: Rehydration, nutrition, antiemetics (± steroids).

• 3rd trimester disease (25-30 wks),• ↑ bile acid [BA] (due to defective biliary transport) & Pruritus• Etiology:– Hormonal: Sex hormones have known cholestatic

effects

– Genetic: Certain ethnic groups (gene associated ICP)

– Exogenous: seasonal, geographical, selenium

deficiency

2) Intrahepatic Cholestasis of Pregnancy (ICP)

Clinical Features and Diagnosis:• Pruritus: – Affects all parts of the body, – Worse @ night, – Severe cases→ patient may be suicidal.

• Obstructive Jaundice: – 2-4 wks post pruritus (20-60% of pts.),– Pale stools & dark urine, – Diarrhea or steatorrhea,– Sudden fetal death, (due to ↑ fetal levels of BA).

• Labs (= Biliary obst):

– ↑ Bil. (< 5 mg%)

– ↑ ALP x 4

– ↑ ALT/AST: 2-10 fold

– ↑ B.A. (most specific): 10-100 fold.

Management:

• Symptomatic therapy for mother + close monitoring & early delivery for the fetus.

• Urso-deoxy-cholic acid (UDCA), 10-15 mg/kg (ttt of choice, completely safe)

• Dexamethasone (12 mg/day for 1 wk) has the advantage of promoting fetal lung maturity

• Cholestyramine, 10-12 g/day,

• Prophylactic Vitamin K.

Outcome of pts. with ICP:• Pruritus & liver dysfunction resolve immediately

after delivery.• 45-70% recurrence in subsequent preg. or with

oral contraceptives.• More liable to: –Gallstones,–Cholecystitis,–Hepatitis C, –Nonalcoholic pancreatitis,–Nonalcoholic cirrhosis.

• Triad (hypertension + edema + proteinuria), • 5-10% of pregnancies in the 3rd trimester.• Liver involvement, always indicates severe

preeclampsia.Etiology:• Placental hypoperfusion, with alteration of vasomotor

tone, initiation of the coagulation cascade.• Nitric oxide has role, (upregulation of NO-synthase in

normal pregnancy)• Imbalance of prostacyclin (PGI2) : thromboxane ratio

increase systemic resistance.

3) Preeclampsia and Eclampsia

Hepatic Involvement:• Abnormal LFT in 20–30% of pts due to VC of

hepatic vascular bed.• ALP (which is often elevated in pregnancy),

may be further ↑,• Transaminases: 10-20 fold ↑,• Bilirubin < 5 mg%,

• Complications: Subcapsular hematoma & rupture, infarction,

& fulminant failure.

Acute Hepatic Hemorrhage of the Rt Lobe with a Subcapsular Hematoma.

Extensive necrosis throughout the Rt lobe with patchy necrosis in the Lt lobe

Autopsy of a eclamptic woman shows multiple regions of hepatic infarction (pale zones).

• Unfortunately; No specific therapy for the hepatic involvement of preeclampsia,

• It is only significant as an indicator of severity & need for immediate delivery to avoid eclampsia, hepatic rupture, or necrosis.

• HELLP is a complication of severe preeclampsia in 2-12% of cases (Hemolysis, Elevated Liver tests, & Low Platelet).

• Key abnormalities: – V.C, platelet activation & consumption,– Thromboxane : Prostacyclin ratio alteration,– Activation of complement & coagulation cascade

causing microangiopathic hemolytic anemia,– elevated liver enzymes with periportal and hepatic

necrosis.

4) HELLP Syndrome

Clinical Features & Diagnosis

• There are no distinguished clinical features from preeclampsia (upper abdominal pain, nausea & vomiting, headache, edema, hypertension, and proteinuria).

• Diagnosis requires the all 3 laboratory criteria: (1) Hemolysis (↑ indirect bil.),

(2) ↑ Transaminases (10-20 fold + bil. < 5 mg%),

(3) Thrombocytopenia (<150000).

Mississippi Class System:• Class 1: Platelets < 50000

• Class 2: Platelets 50-100000

• Class 3: Platelets 100-150000 + Hemolysis + ↑liver enzymes (LDH>600)

Tennessee System• Complete syndrome:

AST &/or ALT > 40Platelets <100000

LDH > 600 IU/L AST > 70

• Incomplete syndrome:

Any 1 or 2 of the above

Classification of HELLP:

Thrombotic disorders• Thrombotic thrombocytopaenic purpura,• Hemolytic uremic syndrome,• Sepsis & DIC,• Drug-induced hemolytic anemias.

Consumptive disorders• Acute fatty liver of pregnancy,• Sepsis and DIC,• Hemorrhage.

Others• Connective tissue disease,• SLE,• Antiphospholipid syndrome,• Procoagulant disorders.

Differential Diagnoses of HELLP

• Hospitalization for stabilization (hypertension & DIC, seizure prophylaxis, fetal monitoring),

• Delivery is the only definitive therapy (< 34 wk → steroids for lung & plt),

• Outcome @ < 34 wk is better when steroids (dexamethasone, which cross the placenta) are used for 24-48 hr (main benefit is lung maturity & platelet count).

Management:

Complications of HELLP

• DIC, ARF, eclampsia, pulm edema, ARDS,

• Indications for liver transplantation are very limited (persisting bleeding from a hepatic hematoma or hepatic rupture or liver failure - necrosis).

• Hepatic hemorrhage or rupture due to exogenous trauma (abdominal palpation, convulsions, emesis & unnecessary transportation)

Lt lobe Large subcapsular hematoma. Rt lobe has widespread necrosis a (heterogeneous, hypodense appearance), with “sparing” of Lt lobe.

• Rare fatal complication of preg. (3rd trimester).

• ChCh: microvesicular fatty infiltration → encephalopathy & hepatic failure with up to 10% mortality.

• Etiology: Enzyme mutation (mitochondria fatty acid oxidation)

• 20% of babies for mothers with AFLP are +ve for the enzyme .

5) Acute Fatty Liver of Pregnancy (AFLP)

Clinical Features and Diagnosis

• 40%-50% of pts with AFLP are in their 1st preg, with twin.

• Presentation: vary from asymptomatic, nonspecific symptoms, to fulminant liver failure.

• Transaminases : 300-500, Bil. < 5 mg%• Presumptive diagnosis is made on compatible

clinical and lab features.

• Definitive diagnosis is histological.

AFLP: Diffuse fatty infiltration (A): (low power), (B):(high power)

• Immediate termination of pregnancy,

• Vaginal Vs CS according to INR (< 1.5) & plt (> 50000),

Outcome: • before 1980, both maternal & fetal mortality

were 85%,

• With advance of supportive care, mortality went down to 7-18%.

Management:

(II) Liver Diseases Occurring Coincidentally ina Pregnant Patient

• 40% of jaundice in pregnant women in USA.

• Hepatitis A, B, C, D, E, Herpes, CMV, Epstein-Barr viruses.

• Management of pt with acute viral hepatitis is supportive,

• Viral hepatitis is NOT an indication for termination of pregnancy, caesarean section, or discouragement for breastfeeding

1) Viral Hepati ti s

• Pregnants with -ve HBV antibodies, & @ high risk (e.g., +ve partner) can be vaccinated safely with little fetal risk.

• HBV transmission is NOT transplacental, but only during delivery.

• HCV mother to infant transmission is only 1-5%.

• Cholesterol secretion ↑ in the 2nd & 3rd trimesters > bile acids & phospholipids, → to supersaturated bile,

• Surgery is indicated when not responding to conservative measure (1st trimester (risk of abortion), & in 3rd trimester (risk of prematurity) ideally: Laproscopic .

• ERCP for impacted CBD stone (fluoroscopy minimization)

2) Gallstones & Biliary Disease

(III) The Pregnant Patient with Chronic Liver Disease

• In HCV, aminotransferases may fall & viral RNA ↑ during pregnancy.

• Unfortunately, the optimal management of pregnancy with cirrhosis and portal hypertension in the modern era of obstetrics is undefined.

• Most patients with advanced cirrhosis are amenorrheic & infertile due to hypothalamic -pituitary dysfunction.

• B-blocker is indicated for Pts with large varices, despite fetal effects,

• Acute variceal bleeding is managed endoscopically (as in non-preg), however; Vasopressin is contraindicated.

• In Pts with known large varices, avoidance of CS is recommended to avoid ↑ in portal pressure.

Conclusion