dr. r.taslimi gastroenterologist & hepatologist imam ... · clinical scenario a 32 year-old...
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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