Chapter 18: Hepatic Disease Associated with Pregnancy

Question 1

Hepatic diseases may occur in women with chronic liver disease who become pregnant, or they
may develop during pregnancy in women who were not affected by liver disease.

Abnormal liver
tests occur in 3% to 5% of pregnancies. [68]

Question 2

What is the most common cause of jaundice in pregnancy?

Answer 2

Viral hepatitis (HAV, HBV, HCV, and even HBV +
HDV)

While these women require careful
clinical management, pregnancy does not specifically alter the course of the liver disease.

The one exception is HEV infection, which, for unknown reasons, runs a more severe course in
pregnant patients, with fatality rates of 10% to 20%.

Question 3

Viral hepatitis (HAV, HBV, HCV, and even HBV +
HDV) is the most common cause of jaundice in pregnancy.

While these women require careful
clinical management, pregnancy does not specifically alter the course of the liver disease.

The
one exception is what?

Answer 3

HEV infection,

which, for unknown reasons, runs a more severe course in
pregnant patients, with fatality rates of 10% to 20%.

Question 4

A very small subgroup of pregnant women (0.1%) develops hepatic complications directly
attributable to pregnancy: what are these complications?

Answer 4

• preeclampsia and eclampsia,
• acute fatty liver of pregnancy, and
• intrahepatic cholestasis of pregnancy.

NOTE: In extreme cases of the first two conditions, the outcome is fatal.

Question 5

Preeclampsia affects 3% to 5% of pregnancies and is characterized by what?

Answer 5

• maternal hypertension,
• proteinuria,
• peripheral edema,
• coagulation abnormalities, and
• varying degrees of disseminated intravascular coagulation ( Chapter 22 ).

Question 6

What is eclampsia?

Answer 6

When hyper-reflexia and convulsions occur the

condition is called eclampsia and may be life-threatening.

Question 7

What is HELLP syndrome?

Answer 7

Alternatively, subclinical hepatic
disease may be the primary manifestation of preeclampsia, as part of a syndrome of _hemolysis,
elevated liver enzymes, and low platelets_, dubbed the HELLP syndrome.

Question 8

What is the morphology of the affected liver in preeclampsia?

Answer 8

The affected liver in preeclampsia is normal in size, firm, and pale, with small red patches due to hemorrhage.

Occasionally, yellow or white patches of ischemic infarction
can be seen.

Question 9

What is the microscopic morphology of the affected liver in preeclampsia?

Answer 9

Microscopically,

the periportal sinusoids contain fibrin deposits with
hemorrhage into the space of Disse, leading to periportal hepatocellular coagulative
necrosis.

Blood under pressure may coalesce and expand to form a hepatic hematoma;
dissection of blood under Glisson’s capsule may lead to catastrophic hepatic rupture ( Fig. 18-42 ).

Question 10

Patients with hepatic involvement in preeclampsia may show modest to severe elevation of what lab findings?

Answer 10

serum aminotransferases and mild elevation of serum bilirubin.

Hepatic
dysfunction sufficient to cause a coagulopathy signifies far-advanced and potentially lethal disease.

Question 11

What is the definitive treatment for preeclampsia?

Answer 11

. Definitive treatment in severe cases requires termination of the pregnancy.

In mild cases patients may be managed conservatively.

Women who survive mild or severe
preeclampsia recover without sequelae.

Question 12

Answer 12

FIGURE 18-42 Eclampsia. Subcapsular hematoma dissecting under Glisson’s capsule in a
fatal case of eclampsia.

Question 13

What is AFLP?

Answer 13

ACUTE FATTY LIVER OF PREGNANCY (AFLP)

AFLP presents with a spectrum ranging from modest or even subclinical hepatic dysfunction
(evidenced by elevated serum aminotransferase levels) to hepatic failure, coma, and death

. It is a rare disease affecting 1 in 13,000 deliveries. Affected women present in the latter half of
pregnancy, usually in thethird trimester.

Symptoms are directly attributable to incipient hepatic
failure, including bleeding, nausea and vomiting, jaundice, and coma. In 20% to 40% of cases
the presenting symptoms may be those of coexistent preeclampsia.

Question 14

The diagnosis of acute fatty liver of pregnancy rests on biopsy identification of the what?

Answer 14

characteristic microvesicular fatty transformation of hepatocytes.

In severe cases there may
be lobular disarray with hepatocyte dropout, reticulin collapse, and portal tract inflammation,
making distinction from viral hepatitis difficult. Diagnosis depends on

• (1) a high index of suspicion and
• (2) confirmation of microvesicular steatosis using special stains for fat (oil-red-O or Sudan black) on frozen tissue sections; electron microscopy may also be used to
  demonstrate the steatosis.

Question 15

What is the clinical course of AFLP?

Answer 15

While this condition most commonly runs a mild course, women with AFLP can progress within
days to hepatic failure and death.

Question 16

What is the primary treatment for AFLP

Answer 16

• *termination of the
  pregnancy. **

Question 17

What is the pathogenesis of AFLP?

Answer 17

The pathogenesis of this disease is unknown, but mitochondrial dysfunction has
been implicated.

In a subset of patients, both mother and father carry a heterozygous deficiency in mitochondrial long-chain 3-hydroxyacyl coenzyme A (CoA) dehydrogenase.

The
homozygous-deficient fetuses fare well during pregnancy but cause hepatic dysfunction in the
mother, because long-chain 3-hydroxylacyl metabolites produced by the fetus or placenta are
washed away into the maternal circulation and cause hepatic toxicity.

This is a rare instance of
the fetus causing metabolic disease in the mother.

Question 18

What is the onset of INTRAHEPATIC CHOLESTASIS OF PREGNANCY?

Answer 18

The onset of pruritus in the third trimester, followed by darkening of the urine and occasionally
light stools and jaundice, heralds thedevelopment of this enigmatic syndrome.

Question 19

What are the laboratory results in INTRAHEPATIC CHOLESTASIS OF PREGNANCY?

Answer 19

• Serum bilirubin (mostly conjugated) rarely exceeds 5 mg/dL;
• alkaline phosphatase may be slightly elevated.

Question 20

What is revealed in the biopsy of INTRAHEPATIC CHOLESTASIS OF PREGNANCY?

Answer 20

Liver biopsy reveals mild cholestasis without necrosis.

Question 21

What is pathogenesis of INTRAHEPATIC CHOLESTASIS OF PREGNANCY?

Answer 21

The altered hormonal state of pregnancy
seems to combine with biliary defects in the secretion of bile salts or sulfated progesterone
metabolites to engender cholestasis.

Although this is generally a benign condition, the mother is at risk for gallstones and malabsorption, and the incidence of fetal distress, stillbirths, and
prematurity is modestly increased.

Perhaps most importantly, the pruritus can be extremely distressing for the pregnant mother.

Question 22

END

Hepatic Disease Associated with Pregnancy