Abnormal Liver Function in Obstetrical Patients (Ludwig, 6/1/2022)

Many thanks to Dr. Alec Ludwig for an excellent presentation about liver and biliary abnormalities in pregnancy. It was jam-packed with good information. 

A recording of his presentation is available HERE. 

My notes:

Remember that what we typically call "liver function tests"  is actually a misnomer. In fact, there is no test that reliably demonstrates the liver's function. Elevation of AST and ALT -- the liver enzymes-- indicates liver injury, not liver dysfunction. Albumin and prothrombin time are factors that are produced by the liver and may be better markers of function. 

In normal pregnancy, you can see elevated alkaline phosphatase (up to 3x normal), as well as elevated cholesterol, triglycerides, and fasting gallbladder volume. Note that many measures we use to evaluate the liver (AST/ALT, T Bili, PTT, liver size, bile acids) don't change in pregnancy.

Hepatocellular injury as measured by elevation in AST/ALT:

• acute viral/toxic hepatitis: AST/ALT 25x upper limit of normal
• ischemic hepatitis: AST/ALT 50x upper limit of normal
• chronic HCV/HBV: slight elevation of AST/ALT (2x normal), rarely greater than 10x normal

Gallstone disease in pregnancy

Gallstone disease is much more prevalent in pregnancy for several reasons. 1) Increased estrogen levels increase cholesterol, thereby supersaturating bile with cholesterol. 2) Progesterone slows contraction of gallbladder, disrupting the excretion of bile acids. AND 3) Increased fasting gallbladder volume.

• acute cholecystitis: blockage of the cystic duct causing inflammation in the gallbladder
• fever, WBC count, can have slightly elevated AST/ALT (if large stone)
• choledocholithiasis: stone in CBD or hepatic duct, causing backup into liver, injury to liver
• definite elevation AST/ALT
• acute cholangitis: can be emergency due to severity of illness
•  Charcot's triad (RUQ pain, jaundice, fever)

Generally treat GB disease in pregnancy with IV antibiotics, surgery if indicated. Laparoscopic cholecystectomy is safe in pregnancy, safest in the second trimester. Should occur within 24-48 hours conservative management. ERCP is also safe in pregnancy; minimize radiation by shielding, fetal monitoring.

Viral Hepatitis (A-E)

• HAV: most common acute hepatitis in general population, but infrequent in pregnancy. 
• Acute infection  (only care about IgM). 
• Generally mild (malaise, HA, fever, jaundice, RUQ pain), supportive treatment. 
• HAV vertical transmission rare but has been documented. Associated with preterm birth, neonatal cholestasis. 
• Breastfeeding okay, HAV vaccine safe in breastfeeding
• HBC: surface Ag used to screen everyone in pregnancy, core Ag, e Ag indicated infectivity/vertical transmission to 80-90% if occurring in the 3rd trimester. 
• Major causes IVDU, sexual intercourse with people w/HBV, vertical transmission. 
• can present with asymptomatic acute phase, can pick up infection even prior to symptoms
• if mom has chronic HBV in pregnancy: need to check viral load, 1 million to 100 million is elevated, may need treatment during pregnancy w/Tenofovir after 28-32 weeks (to prevent vertical transmission)
• Babies born to mothers with HBV needs HB IVIG and first dose of vaccine within 12 hours, don't determine delivery method
• Breastfeeding is safe as long as infant got IVIG and HBV vaccine
• HCV: can be acute and chronic 
• HCV on the rise in the last few years (2009-2019 2x increase of patients with HCV), likely due to IVDU
• vertical transmission 3-5%
• 75% HCV infections are asymptomatic
• ACOG does have some recommendations of Category B meds that could be used to treat HCV in pregnancy to decrease vertical transmission (Ribavirin is teratogenic)
• Vertical transmission increases if co-infection w/HIV, invasive surgical procedure, ROM >6 hours, conflicting data but discourage fetal scalp electrode
• Breastfeeding okay w/HCV
• HDV: coexists with HBV only, anyone with chronic HBV should be tested for HDV. Supportive treatment, monitor symptoms. If treat HBV, clears HDV.
• HEV: can be acute and chronic, based on genotype
• some areas in Mexico, Asia, Africa and South America endemic (travel recommendations not to travel to endemic areas in 2nd and 3rd trimester)
• believed to be water born
• pregnancy women are particularly susceptible to severe liver damage and liver failure, 20-30% mortality
• rare vertical transmission
• breastfeeding okay

Other viral hepatitis: HSV hepatitis (rare but high mortality), CMV hepatitis (also rare, more common in organ transplant pts): most common hearing loss

Cirrhosis in Pregnancy: it is more difficult to get pregnant if cirrhotic (due to secondary amenorrhea), but can still get pregnant. High risk for bleeds, aneurysms and acute on chronic liver failure. Need variceal screening DURING pregnancy. Increased mortality with pregnancy (should calculate MELD, do HCC screening even during pregnancy). Can use beta blockers (e.g. propranolol) but can cause some side effects to baby. Octreotide okay. Mode of delivery unclear, should be individualized.

Autoimmune hepatitis in pregnancy generally improve during the 2nd trimester BUT can flare post partum.

Hyperemesis Gravidarum: 50-60% of patients hospitalized with hyperemesis demonstrate some abnormal liver tests: hyper bilirubin, elevated AST/ALT. Generally don't get fever, jaundice. 

Cholestasis of Pregnancy (ICP) is the most common liver disorder unique to pregnancy. Generally presents as pruritis without a rash. Even though palms and soles are most common places, can be in other places as well. May see abnormalities in AST/ALT. Increased serum bile acids confirm a diagnosis (>10=cholestasis dx, >100=severe, should be induced after 36 weeks, earlier other indications).

• Elevated ALT 30x normal, elevated conjugated bilirubin
• generally not jaundiced
• start antenatal testing right away
• treatments (all grade C): ursodiol improved labs and symptoms but no data that improves still birth. Other treatments: Hydroxyzine, cholestyramine
• Some data on PO vitamin K (evolving evidence)
• Can progress: 2-5x risk of progression to preE, if bile acids >40

Pre-Eclampsia is diagnosed by blood pressure criteria: SBP >140, DBP >90, 2 x, 20 minutes apart after 20 weeks AND either proteinuria (>0.3 microalbumin/creatinine ratio) OR lab abnormalities (platelets <100K, SCr>1.1 or double baseline, impaired liver tests (2x normal). Symptoms-based diagnosis is NOT recommended. Antenatal testing twice weekly. Deliver at 37 weeks

Pre-E with severe features: 

• BP >160/110 (2x, 4 hours apart) OR
•  thrombocytopenia, elevated SCr or liver test abnormalities (regardless of BP)
• Antenatal testing daily, deliver at 34 weeks

HELLP syndrome is considered a complication of PreE even though 15% of patients don't have elevated BP or proteinuria. 10-20% of women with severe PreE progress to HELLP. Diagnosed with signs of hemolysis (LDH>600, platelets <100, AST/ALT 2x normal).  High mortality. Can lead to hepatic rupture/hematoma, placental abruption, acute renal failure, etc. Treatment is magnesium sulfate, treat BP and delivery. Hepatic hematoma and rupture (stretching of Gleason's capsule) -- pts often have severe RUQ pain. 

Acute Fatty Liver of Pregnancy has a lot of similarities with HELLP, Severe PreE and acute fatty liver. Originates from genetic defect in fetus and a susceptible mother. Presents with n/v, pain, jaundice, fever. Generally don't present with elevated BP. Swansea criteria to make diagnosis. Can add ammonia, uric acid to help classify. Imaging may demonstrate hypoechoic liver with lots of fatty deposits.