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A. Types of Liver/GI Disease

  1. Cholestatic Disease
    1. Pruritis (often severe) and jaundice are prominent
    2. Abdominal pain does not usually occur
    3. Hyperemesis Gravidarum
    4. Intrahepatic cholestasis of pregnancy
    5. Primary biliary cirrhosis
    6. Gallstones may occur as well (usually with severe pain)
  2. Hepatocellular Disease
    1. Characterized mainly by abdominal pain (epigastrium and/or right upper quadrant)
    2. Jaundice may follow but pruritis is uncommon
    3. Acute viral hepatitis - particularly Hepatitis E, other hepatitis viruses, herpes simplex
    4. Acute Fatty Liver of Pregnancy (AFLP)
    5. Preeclampsia / Eclampsia
    6. HELLP Syndrome - occurs in ~10% of persons with preeclampsia
    7. Budd-Chiari Syndrome - hepatic vein thrombosis, very uncommon
  3. Pospartum coma due to Bartonella infection has been described [3]

B. Hyperemesis Gravidarum

  1. Nausea and vomiting usually in first (or second) trimester
  2. May be severe leading to dehydration and malnutrition
  3. <1% of pregnancies in USA
  4. Liver Changes
    1. In severe hyperemesis, ~50% of patients have aminotransferase elevations
    2. Alkaline phosphatase levels may be 2X normal
    3. Hyperbilirubinemia <4mg/dL may be present (~50% conjugated fraction)
    4. Liver biopsy shows normal picture or has fatty changes
  5. Wernicke Encephalopathy - due to thiamine deficiency
  6. Severe cases may require hospitalization
    1. Intravenous fluids
    2. Vitamin and mineral supplementation
    3. Hyperalimentation may be required
  7. Acupuncture appears to be effective in some patients [2]
  8. May lead to reduced neonatal birth rates

C. Intrahepatic Cholestasis of Pregnancy

  1. Main symptom is pruritis (with hyperbilirubinemia)
  2. Occurs in third (or second) trimester
  3. <0.2% of pregnancies in USA
  4. Symptoms of pruritis and jaundice persist until after delivery
  5. Increased risk in patients with mutations of the phospholipid translocator MDR3 [5]
  6. Bilirubin <6mg/dL, ALT <300U/L, pale stool, dark urine
  7. Liver biopsy shows cholestasis without inflammation
  8. Increased risk of prematurity and stillbirth
  9. Cholestyramine 10-12gm/day to relieve pruritis (consider ursodiol as well)
  10. Vitamin K prophylaxis recommended to reduce bleeding risk

D. Acute Fatty Liver of Pregnancy (AFLP)

  1. Estimated occurrance 1:13,000 deliveries in USA
  2. Usually occurs at ~36 weeks gestation (always third trimester)
  3. Causes
    1. AFLP has some overlap with HELLP syndrome
    2. Abnormal fetal long chain fatty oxidation has been implicated
    3. Fetal deficiency in long chain 3-hydroxyacyl-CoA dehydrogenase (HACDH) causes AFLP [5] and may play a role in HELLP [5]
    4. AFLP is stronlgy linked to E474Q alteration in HACDH
    5. All women with HELLP and AFLP (and their partners) should be screened as carriers [5,6]
    6. Newborns with pregnancies complicated with AFLP should be screened [6]
    7. Unclear if HACDH deficiency is etiologic in HELLP syndrome
  4. Main symptoms (third trimester)
    1. Nausea and vomiting ~70%
    2. Pain in RUQ or epigastrium ~65%
    3. Malaise and anorexia
    4. Jaundice common (usually without pruritis)
    5. Untreated disease has very high (>70%) mortality rate
    6. This is due to fulminant hepatic failure, DIC and coma
  5. Accumalation of microvesicular fat within hepatocytes
  6. Laboratory Values
    1. ALT <500U/L
    2. Reduced glucose (due to poor hepatic synthesis) - may be profound
    3. Hyperbilirubinemia
    4. Ammonia elevation late in disease
    5. Small liver size on ultrasonography
    6. Elevated white blood cell count (>15K/µL)
    7. Reduced albumin value (usually <3.0gm/dL)
  7. Ultrasonography
    1. Useful to rule out Budd-Chiari Syndrome (hepatic vein thrombosis)
    2. May not be helpful in ruling out HELLP syndrome
  8. DIC may be present in up to 70% of cases
  9. Pregnancy should be terminated promptly when AFLP is present

E. HELLP Syndrome

  1. Components of Syndrome
    1. Hemolysis - micrangiopathic, intravascular
    2. Elevated Liver enzymes - AST and ALT (alkaline phosphatase may be normal)
    3. Low Platelets
  2. Complication of severe preeclampsia (~30% of severe preeclampsia cases)
  3. Two thirds of cases occur at 27-36 weeks; one third after delivery
  4. Some cases of HELPP may be caused by fetal deficiency in HACDH [5] but this is not clear [6]
  5. Symptoms
    1. Malaise ~90%
    2. Abdominal pain ~80%
    3. Weight gain (edema) ~60%
    4. Nausea / Vomiting ~40%
    5. Headache 30% (may be related to hypertension)
    6. Jaundice 5%
  6. Laboratory abnormalities peak 1-2 days post-partum
    1. Hemolysis - elevated lactate dehydrogenase and bilirubin
    2. AST and ALT 2-10X normal
    3. Platelets <100K/µL
  7. Treatment
    1. Delivery is critical to maternal and fetal well-being
    2. Supportive care following delivery is crucial
    3. For <34 weeks gestation, give magnesium sulfate and glucocorticoids
    4. Delivery may be postponed for 24-48 hours in these cases with intensive monitoring
    5. Plasmapheresis may improve platelet counts in patients refractory after delivery
  8. Complications
    1. Disseminated intravascular coagulopathy (DIC)
    2. Abruptio placentae
    3. Renal Failure
    4. Pulmonary Edema
    5. Fetal Loss - perinatal mortality of infant ~35%
    6. Increased risk of recurrence in subsequent pregnancies

References

  1. Knox TA and Olans LB. 1996. NEJM. 335(2):569
  2. NIH Consensus Statement on Acupuncture. 1998. JAMA. 280(17):1518 abstract
  3. McCormack G, Fenelon LE, Sheehan K, McCormick PA. 1998. Lancet. 351(9117):1700 abstract
  4. Jacquemin E, Creteil D, Manouvrier S, et al. 1999. Lancet. 353(9148):210 abstract
  5. Ibdah JA, Bennett MJ, Rinaldo P, et al. 1999. NEJM. 340(22):1723 abstract
  6. Yang Z, Yamada J, Zhao Y, et al. 2002. JAMA. 288(17):2163 abstract