Dr. R.Taslimi

Gastroenterologist & Hepatologist

Imam Khomaini Hospital

TUMS

Clinical scenario A 32 year-old woman gravida 1 para 0 with a singleton

gestation at 34 weeks of gestation is admitted to the hospital with a:

Three-day history of nausea and vomiting, malaise, abdominal pain and jaundice

Her blood pressure is mildly elevated

PR = 112/min

Serum aminotransferases range between 200 to 500 int. unit/L

ALP = 1200 (180-370)

Serum glucose = 64 mg/dl

T.bili = 4.2 & D.bili = 2.3

WBC = 15800/µl

Hb = 8.8 gr/dl , MCV = 76 fl (80-92)

PLT = 78000/µl

PT = 27 s , INR = 3.1

PTT = 65 s

Urinalysis shows trace protein

Hepatitis serologies were sent, but are unavailable.

Ultrasound revealed :

normal liver (size & echogenicity) and spleen.

No fatty change in liver.

Intrahepatic bile ducts and CBD was normal.

Mild ascitic fluid

Normal fetus

What is your D.DX ?

HEELP

Pre-eclampsia

But the most probable diagnosis is Acute Fatty Liver of Pregnancy

Elevated liver enzyme in pregnancy 1) Is there underlying chronic liver disease?

2)New onset in pregnancy

Chronic liver disease consideration Albumin and total protein (decreased from the

first trimester)

Alkaline phophatase levels (increased in second and third trimester) but gamma GT slightly decreased in pregnancy

New onset liver disease in pregnancy

1) Pregnancy-related physiologic changes: Cholelithiasis, Thrombotic diseases (such as Budd-Chiari

syndrome)

2) Not related to pregnancy but can initially present during pregnancy: Acute viral hepatitis, AIH, Drug-induced hepatic injury,

malignancy

3) Conditions specific to pregnancy

Conditions specific to pregnancy1)Hyperemesis gravidarum should be considered in the

differential diagnosis of abnormal liver tests presenting in the first trimester

2) Cholestasis of pregnancy should be considered in the differential diagnosis of abnormal liver tests presenting initially in the second trimester

3) HELLP and AFLP and Pre-eclampsiashould be considered in the differential diagnosis of abnormal liver tests in the second half of pregnancy, usually in the third trimester

Patients with acute fatty liver of pregnancy have true hepatic dysfunction, and may, or may not, have signs of pre-eclampsia and HELLP syndrome

AFLP (PATHOGENESIS)

Microvesicular fatty infiltration of hepatocytes

Incidence of 1 in 7000

Multiple gestations and possibly in women who are underweight

long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency

The LCHAD catalyzes the third step in the beta-oxidation of fatty acids in mitochondria

The accumulation of long-chain 3-hydroxyacyl metabolites produced by the fetus or placenta is toxic to the liver

12 women with AFLP, 8 had evidence of being heterozygous for LCHAD.

These 8 women had 9 pregnancies complicated by fatty liver; 7 of these pregnancies were also associated with preeclampsia and HELLP (compromised beta-oxidation function)

7 of the 9 offspring were proven or presumed to be homozygous deficient .The other two offspring had heterozygous LCHAD.

One series focused on three families with children presenting with sudden unexplained death or hypoglycemia and elevated liver enzymes (Reye-like syndrome).

In all families, the mothers had AFLP

Three children who were studied had mutations in both alleles for LCHAD

CLINICAL MANIFESTATIONS Nausea or vomiting (approximately 75 percent of patients) Abdominal pain (particularly epigastric, 50 percent) Malaise, anorexia, and fever Jaundice About one-half of patients have signs of preeclampsia at

presentation or at some time during the course of illness Infection occurred Major intra-abdominal bleeding, some of whom required

surgery Transient polyuria and polydipsia due to central diabetes

insipidus Rare patients develop pancreatitis, which can be severe.

LFT ranging from modest values up to 500 int. unit/L.

Serum bilirubin levels are also usually elevated

Acute kidney injury and hyperuricemia are often present

DIAGNOSIS The diagnosis of acute fatty liver of pregnancy is

usually made clinically

There is a large clinical overlap between acute fatty liver of pregnancy and HELLP syndrome, and it may be difficult, even impossible, to differentiate them

However, evidence of hepatic insufficiency such as hypoglycemia or encephalopathy and abnormalities in coagulation studies is more consistent with acute fatty liver of pregnancy

Liver biopsy

TREATMENT AND COURSE Combination of maternal stabilization and prompt

delivery of the fetus, regardless of gestational age.

Maternal stabilization requires:

glucose infusion

reversal of coagulopathy (eg, administration of fresh frozen plasma, cryoprecipitate, packed red blood cells and platelets), as needed.

Most laboratory values normalized within 7 to 10 days after delivery

A transient worsening of liver and renal functions and coagulopathy may be observed during the first few days after delivery followed by a definitive improvement

In most severe cases, mostly when diagnosis has been delayed, there may be many more days of illness requiring maximal supportive management in an intensive care unit, including mechanical ventilation because of coma, dialysis for acute renal failure, parenteral nutrition because of associated pancreatitis, or even surgery to treat bleeding from a preceding cesarean section.

57 patients withAFLP, one woman required a liver transplant and one woman died

There were seven deaths among 67 infants

In a second report with 51 women with acute fatty liver of pregnancy, there were two maternal deaths (4 percent), and the stillbirth rate was 120 per 1000 births

RECURRENCE Acute fatty liver of pregnancy can recur in subsequent

pregnancies, even if the search of long-chain 3-hydroxyacyl CoA dehydrogenase deficiency mutation is negative