Hepatic Disorders During Pregnancy




Key Abbreviations


Acute fatty liver of pregnancy AFLP


Acute intermittent porphyria AIP


Computed tomography CT


Disseminated intravascular coagulation DIC


Endoscopic retrograde cholangiopancreatography ERCP


Esophagogastroduodenoscopy EGD


γ-Glutamyl transpeptidase GGTP


Gastroesophageal reflux disease GERD


Hepatobiliary iminodiacetic acid scan HIDA


Hepatocellular cancer HCC


Hyperemesis gravidarum HG


Intrahepatic cholestasis of pregnancy ICP


Long-chain 3-hydroxyacyl coenzyme A dehydrogenase LCHAD


Magnetic resonance cholangiopancreatography MRCP


Magnetic resonance imaging MRI


Nausea and vomiting of pregnancy NVP


Right upper quadrant RUQ


Total parenteral nutrition TPN


Transjugular intrahepatic portosystemic shunt TIPS


Hepatic, biliary, and pancreatic disorders are relatively uncommon but are not rare during pregnancy. For example, during pregnancy about 3% of women develop serum liver function test abnormalities, and about 1 in 500 develop potentially life-threatening hepatic diseases that endanger fetal viability.


Hepatic, biliary, and pancreatic disorders are often complex and clinically challenging problems during pregnancy. First, the differential diagnosis during pregnancy is extensive and includes both disorders related and unrelated to pregnancy. Second, the clinical presentation and natural history of these disorders may be altered during gestation. Indeed, some disorders—such as intrahepatic cholestasis of pregnancy—are unique to gestation. Third, the diagnostic evaluation may need to be slightly altered because of pregnancy. Nonetheless, almost all radiologic tests can be done judiciously to maintain fetal safety. Fourth, the interests of both the mother and the fetus must be considered in therapeutic decisions. Usually these interests do not conflict, because generally, what is good for the mother is good for the fetus. Sometimes, however, maternal therapy must be modified to substitute alternative but safer therapy because of concerns about drug teratogenicity. Rarely, maternal and fetal interests are diametrically opposed, as in the use of chemotherapy for maternal cancer, a therapy that is potentially life-saving to the mother but dangerous to the fetus. These conflicts raise significant medical, legal, and ethical issues.


Obstetricians, hepatologists, surgeons, and internists should be familiar with hepatic, biliary, and pancreatic disorders that can present in pregnancy and how these conditions affect and are affected by pregnancy. This chapter reviews these conditions with a focus on features unique to pregnancy.




Physiologic Effects of Pregnancy and Assessment of Liver Disease


Abdominal assessment is modified during pregnancy. The expanding gravid uterus can displace abdominal viscera and may conceal an abdominal mass on physical examination. During the first and second trimesters of pregnancy, blood pressure normally declines modestly. A rise in blood pressure during pregnancy may, therefore, portend preeclampsia or eclampsia. Physiologic alterations of laboratory values during pregnancy include mild leukocytosis, physiologic anemia of pregnancy, and electrolyte changes, particularly mild hyponatremia (see Chapter 3 ). The risk of thromboembolic phenomena is increased during pregnancy because of mild hypercoagulopathy from hyperestrogenemia and vascular stasis from vascular compression by the enlarged gravid uterus. The changes in serum glucose levels during pregnancy are complex. Normal pregnancy is characterized by fasting hypoglycemia, postprandial hyperglycemia, and hyperinsulinemia. Meticulous control of the serum glucose level is important in diabetic patients for proper fetal development.


Pregnancy does not affect the liver span. The liver may be pushed cephalad by the gravid uterus, but a liver span greater than 12 cm, when appreciated, remains a valid indicator of hepatomegaly. Spider angiomata and palmar erythema, cutaneous lesions often associated with chronic liver disease, may appear transiently during normal pregnancy without underlying liver disease, presumably because of hyperestrogenemia during pregnancy. During pregnancy, the serum alkaline phosphatase level normally increases mildly as a result of placental synthesis; the serum albumin level also declines, primarily from hemodilution and secondarily from decreased hepatic synthesis. Serum bilirubin levels tend to change little during pregnancy because of the effect of mildly impaired hepatic excretion balanced by the opposing effects of hemodilution and hypoalbuminemia. Serum bile acids tend to mildly increase during gestation because of impaired hepatic transport and biliary secretion. Serum levels of cholesterol, triglycerides, and phospholipids increase moderately during pregnancy as a result of increased hepatic synthesis. The serum aminotransferase levels are largely unaffected by pregnancy. Changes of serum levels of common blood tests during pregnancy are summarized in Box 47-1 (see Appendix I , “Normal Values in Pregnancy”).



Box 47-1

Changes in Routine Laboratory Tests and Liver Function Tests during Pregnancy


Mildly Decreased Serum Levels





  • Sodium



  • Albumin



Moderately Decreased Blood Level





  • Hematocrit: physiologic anemia of pregnancy



Mildly Increased Blood or Serum Levels





  • Leukocyte count



  • Alkaline phosphatase



  • Amylase



Moderately Increased Serum Levels





  • Serum bile acids



  • Cholesterol



  • Triglycerides



Other





  • Glucose level: fasting hypoglycemia, postprandial hyperglycemia






Differential Diagnosis of Hepatobiliary Symptoms and Conditions during Pregnancy


Maternal Jaundice


As in the general population, acute viral hepatitis is the most common cause of jaundice during pregnancy . The differential diagnosis of jaundice during the first and second trimesters of pregnancy also includes drug hepatotoxicity and gallstone disease such as acute cholecystitis, choledocholithiasis, ascending cholangitis, or gallstone pancreatitis. In addition to these disorders, the differential of jaundice during the third trimester includes pregnancy-related causes such as intrahepatic cholestasis of pregnancy; acute fatty liver of pregnancy (AFLP); and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Moderate direct hyperbilirubinemia without jaundice during the third trimester may also be due to preeclampsia, eclampsia, and Budd-Chiari syndrome. Predominantly indirect hyperbilirubinemia during pregnancy is usually due to hemolysis (including the HELLP syndrome) or Gilbert syndrome.


Right Upper Quadrant Abdominal Pain


The differential diagnosis of right upper quadrant (RUQ) abdominal pain is extensive during pregnancy ( Box 47-2 ). In addition to hepatic, biliary, gastrointestinal (GI), and renal disorders that can occur in nonpregnant patients, the differential includes diseases related to pregnancy. In the medical history, the pain intensity, nature, temporal pattern, radiation pattern, exacerbating factors, and alleviating factors help narrow the differential diagnosis. Biliary colic produces a waxing and waning intensity of pain. Acute cholecystitis is associated with RUQ pain and pain referred to the right shoulder. The pain of acute pancreatitis is often boring in quality, located in the abdominal midline, and radiating to the back. Careful physical examination of the abdomen that includes inspection, palpation, and auscultation can further pinpoint the cause of the pain. Laboratory evaluation of significant abdominal pain routinely includes a complete blood count (CBC), serum electrolytes, and liver function tests (LFTs) as well as a leukocyte differential, coagulation profile, and serum lipase determination. In evaluating the laboratory results, gestational changes in normative values, as mentioned earlier, must be considered. Radiologic tests may be extremely helpful diagnostically, but the choice of radiologic imaging is constrained by the pregnancy, as discussed below. RUQ pain and abnormal LFTs in the setting of new-onset hypertension should strongly suggest preeclampsia with hepatic involvement. RUQ pain and abnormal LFTs in the setting of thrombocytopenia and microangiopathic hemolysis, as demonstrated by the presence of schistocytes in a peripheral blood smear, should strongly suggest the HELLP syndrome.



Box 47-2

Differential Diagnosis of Right Upper Quadrant Abdominal Pain during Pregnancy


Hepatic Disorders





  • Hepatitis



  • Hepatic vascular engorgement



  • Hepatic hematoma



  • Hepatic malignancy



Biliary Tract Disease





  • Biliary colic



  • Choledocholithiasis



  • Cholangitis



  • Cholecystitis



Diseases Related to Pregnancy





  • Preeclampsia or eclampsia



  • Hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome



  • Acute fatty liver of pregnancy



  • Hepatic hemorrhage or rupture



Renal Disorders





  • Pyelonephritis



  • Nephrolithiasis



Gastrointestinal Disorders





  • Peptic ulcer disease



  • Perforated duodenal ulcer



Other Conditions





  • Rib fracture



  • Shingles



Referred Pain From Another Disease





  • Pneumonia



  • Pulmonary embolus or infarct



  • Pleural effusion



  • Radiculopathy



  • Inferior wall myocardial infarction



  • Colon cancer




Occasionally, the pregnancy is not known by the patient or is not revealed to the physician, particularly in early pregnancy, when physical findings are absent. The physician should be vigilant for possible pregnancy in a fertile woman with abdominal pain, particularly in the setting of missed menses, because pregnancy affects the differential diagnosis, clinical evaluation, and mode of therapy. Pregnancy tests should be performed early in the evaluation of acute abdominal pain in a fertile woman.


Nausea and Vomiting


Nausea and vomiting may be ubiquitous during pregnancy, and nausea and vomiting of pregnancy (NVP) is the most common cause (see Chapter 6 ). It typically begins at about 6 weeks and abates at about 18 weeks and is caused by the physiologic effects of the pregnancy without demonstrable mucosal or mural disease. Hyperemesis gravidarum (HG) is a serious and potentially life-threatening form of NVP associated with loss of more than 5% of the pregravid weight. HG is a diagnosis of exclusion, based on nausea and vomiting that occur early in pregnancy and that gradually resolve during the middle second trimester and unassociated with other symptoms. The differential diagnosis of nausea and vomiting during pregnancy also includes hepatic and pancreatobiliary diseases such as pancreatitis, viral hepatitis, symptomatic cholelithiasis, acute cholecystitis, AFLP, and occasionally intrahepatic cholestasis of pregnancy. GI causes include gastroesophageal reflux disease (GERD), peptic ulcer disease, viral gastroenteritis, appendicitis, gastroparesis diabeticorum, and GI obstruction. Other causes include adnexal torsion, pyelonephritis, urolithiasis, and Addison disease (glucocorticoid deficiency).


Pruritus


The differential diagnosis of pruritus during pregnancy includes intrahepatic cholestasis of pregnancy, cholestatic viral hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis, and mechanical choledochal obstruction from benign or malignant strictures. Pruritus sometimes occurs physiologically during pregnancy; this pruritus is typically mild, localized, unassociated with other symptoms, and unassociated with abnormal liver function tests (see Chapter 50 ). Important clues that pruritus may be due to the intrahepatic cholestasis of pregnancy include pruritus that begins during the third trimester of pregnancy with no history of chronic liver disease, absence of abdominal pain, pruritus that affects mostly the hands and feet, and only mild to moderately elevated serum transaminase and bilirubin levels.


Hepatic Lesions


Hepatic lesions identified on abdominal imaging studies are classified as cystic or solid. The differential of cystic hepatic lesions includes simple hepatic cysts, hepatic cysts associated with polycystic kidney disease, Caroli disease (a rare inherited disorder characterized by dilation of the intrahepatic bile ducts), bacterial abscesses, amebic abscesses, intraparenchymal hemorrhage, hemangiomas, echinococcal cysts, and rarely hepatic malignancies. The differential of a solid hepatic mass includes hepatic adenoma, focal nodular hyperplasia, hepatocellular carcinoma, and hepatic metastases.


Ascites


Hepatic causes of ascites during pregnancy include cirrhosis, AFLP, Budd-Chiari syndrome, portal vein thrombosis, hepatic fibrosis, and hepatocellular carcinoma. Other causes of ascites during pregnancy include ovarian cancer, abdominal tubercu­losis, cardiac failure, protein-losing nephropathy, and severe protein malnutrition (kwashiorkor).


Neonatal Cholestasis


Neonatal cholestasis is characterized by conjugated hyperbilirubinemia, pale stools, and dark urine. The differential includes neonatal prematurity; anatomic anomalies such as biliary atresia; infections such as cytomegalovirus or toxoplasmosis; and metabolic defects such as cystic fibrosis, alpha 1antitrypsin deficiency, or bile acid synthetic defects. Neonates frequently have unconjugated (indirect) hyperbilirubinemia or physiologic jaundice due to increased production and decreased clearance of bilirubin. The bilirubin may peak at 7 mg/dL several days after birth but rapidly normalizes within about 1 week thereafter. Unconjugated neonatal hyperbilirubinemia may also be due to hemolysis, sepsis, or Gilbert syndrome.




Abdominal Imaging during Pregnancy


Fetal safety during diagnostic imaging is a concern for pregnant patients. Ultrasonography is considered safe and is the preferred abdominal imaging modality during pregnancy. Unfortunately, the test sensitivity depends on operator technique, patient cooperation, and patient anatomy. For example, test sensitivity is decreased by abdominal fat and intestinal gas. No reported harmful effects result from magnetic resonance imaging (MRI) during pregnancy , but few data are available on safety during the first trimester or with use of gadolinium. However, gadolinium has not been associated with adverse fetal outcomes in a number of individual case reports or in limited case series . MRI is preferable to computed tomography (CT) scanning during pregnancy to avoid ionizing radiation, but gadolinium administration should be avoided during MRI in the first trimester. Rapid-sequence MRI is preferable to conventional MRI because of briefer exposures.


Radiation can cause fetal mortality, growth restriction, chromosomal mutations, and neurologic abnormalities that include mental retardation, and they increase the risk of childhood leukemia (see Chapter 8 ). Radiation dosage is the most important risk factor, but fetal age at exposure is also important. Fetal mortality is greatest from radiation exposure during the first 2 weeks after conception, and the risk of neurologic malformations is greatest during the first trimester, when organogenesis occurs. The patient should undergo counseling before diagnostic roentgenography. Exposure to more than 15 rads during the second and third trimesters or more than 5 rads during the first trimester should prompt consideration of termination of pregnancy. Diagnostic studies with high radiation exposure, such as abdominal CT, typically expose the fetus to less than 1 rad and should therefore be considered when indicated . The physician ordering a roentgenographic study can consult with a medical physicist to estimate the fetal exposure. Fetal radiation exposure should be minimized by shielding the abdomen above the uterus and using narrow collimation and rapid-sequence studies. When performing abdominal CT scans with contrast, precontrast films can be reduced or eliminated to reduce radiation exposure.




Therapeutic Endoscopy during Pregnancy


Therapeutic Endoscopic Retrograde Cholangiopancreatography


Choledocholithiasis usually requires urgent therapy because of potentially life-threatening ascending cholangitis or gallstone pancreatitis. Symptomatic choledocholithiasis is best managed by therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in the nonpregnant patient to avoid complex biliary surgery during cholecystectomy. In experienced hands, therapeutic ERCP in the general population has acceptable morbidity of about 5% and low mortality of about 0.5%. Therapeutic ERCP is theoretically more attractive than biliary surgery for choledocholithiasis during pregnancy because surgery entails a significant risk of fetal loss. Aside from maternal risks, therapeutic ERCP during pregnancy entails theoretic risks to the fetus from induction of premature labor, medication and radiation teratogenicity, placental abruption or fetal trauma during endoscopic intubation, cardiac arrhythmias, systemic hypotension, and transient hypoxia.


A literature review of about 350 cases of ERCP during pregnancy noted three larger studies that encompassed over 100 patients in total and numerous small case series or individual case reports. Almost all pregnant patients in all these studies required therapeutic intervention, mostly for choledocholithiasis. The outcome after ERCP was favorable in the three larger studies in terms of maternal health, maintenance of pregnancy, and eventual fetal outcome. Complications included maternal pancreatitis in 5% to 16%, one spontaneous abortion 3 months after ERCP, one neonatal demise 26 hours after delivery, and a prematurity rate of 8%. These relatively favorable results were confirmed in the review of the rest of the approximately 350 cases. Although the individual studies were generally flawed because of small study size, retrospective design, and limited follow-up after delivery, the consistency of the favorable results across so many studies argues forcefully that ERCP is justifiable during pregnancy for appropriate indications and contemplated therapeutic intervention . These results have been further confirmed in additional individual studies and literature reviews. In particular, therapeutic ERCP can be performed during pregnancy to help avoid complex biliary surgery or to postpone cholecystectomy until after parturition. Special precautions to minimize fetal risks from ERCP during pregnancy include consideration for consultation with a neonatologist, radiation physicist, and anesthesiologist before ERCP; referral to a tertiary medical center for management by a team of experts; lead shielding of the mother’s abdomen except for the region of the proximal pancreas and biliary tree; use of a modern fluoroscope to minimize radiation leakage; avoidance of spot radiographs for documentation because they require considerable radiation energy; and, if possible, delay ERCP until the second trimester to reduce radiation teratogenicity.


Endoscopic Variceal Sclerotherapy or Banding


Pregnancy appears to increase the risk of variceal bleeding from portal hypertension because of the gestational increase in plasma volume. Endoscopic ligation (banding) or sclerotherapy are particularly attractive therapies for variceal bleeding during pregnancy because the alternative of trans­jugular intrahepatic portosystemic shunt (TIPS) requires radiation, and the surgical alternatives can cause fetal loss. Esophagogastroduodenoscopy (EGD) can be performed during pregnancy with relatively low fetal risks and should certainly be considered when strongly indicated, such as for acute upper GI hemorrhage. Endoscopic banding and sclerotherapy raise concerns beyond that of diagnostic EGD from the additional procedure time, the typically severe underlying maternal illness, and the therapy itself. Variceal banding is preferred over sclerotherapy in the general (nonpregnant) population. Scant clinical data exist on variceal banding during pregnancy and comprise one small case series and individual case reports. These data suggest relatively favorable maternal and fetal outcomes after variceal banding compared with the poor prognosis in untreated patients. More clinical data exist on sclerotherapy during pregnancy. In one clinical series, 10 patients underwent a mean of three endoscopic sclerotherapy sessions during pregnancy, five for active variceal bleeding and five for prophylaxis. Hemostasis was achieved in all actively bleeding patients. One patient suffered a complication from sclerotherapy of an esophageal stricture, which was successfully treated using perioral esophageal dilators. All patients had a normal vaginal delivery at term. Nine other patients successfully underwent endoscopic sclerotherapy for actively or recently bleeding esophageal varices with delivery of healthy infants in all cases. One study reported less favorable pregnancy outcomes after endoscopic sclerotherapy, attributable to the underlying maternal disease. Four of seventeen pregnant patients undergoing endoscopic sclerotherapy for variceal bleeding due to noncirrhotic portal hypertension had adverse pregnancy outcomes of stillbirth or neonatal death. Still, the available data should justify endoscopic therapy during pregnancy for actively bleeding esophageal varices, after informed consent, because of poor outcomes with the alternative available therapies.


Team Approach and Informed Consent


A team approach with consultation and referral helps optimize the management of complex diseases during pregnancy that affect both the mother and the fetus and that require disparate areas of expertise. The obstetrician may consult with the hepatologist regarding timing of delivery in patients with obstetric-related hepatic disease. The gastroenterologist contemplating therapeutic ERCP for symptomatic choledocholithiasis may consult with the obstetrician about the optimal procedure timing and with the anesthesiologist about analgesia during endoscopy. The internist may discuss with the radiologist the benefits versus risks of radiologic tests, and the radiologist may in turn consult with a physicist about methods to monitor and reduce fetal radiation exposure. Complex hepatic problems during pregnancy are best handled at a tertiary hospital with the requisite experience and expertise.


The patient should be informed about the consequences to both herself and her fetus of diagnostic tests and therapy and should be actively involved in medical decisions. The patient makes the decision under the vigilant guidance of the experts and with input from her partner, family, and friends. When an intervention, such as roentgenographic tests, entails significant potential fetal risk, a signed, witnessed, and informed consent is recommended even though this intervention would be routine and would not require consent in a nonpregnant patient.




Pancreatobiliary Disease


Acute Pancreatitis


Acute pancreatitis occurs in about 1 per 3000 pregnancies, most commonly during the third trimester. Gallstones cause about 70% of cases because alcoholism is relatively uncommon during pregnancy . The risk of cholesterol stones is increased during pregnancy because of increased cholesterol secretion into bile. Other causes include drugs, abdominal surgery, trauma, hyperlipidemia, hyperparathyroidism, vasculitis, and infections such as mumps or mononucleosis. The risk of pancreatitis from hyperlipidemia is increased during pregnancy because of the significant elevation of triglyceride levels during late pregnancy. Some cases are idiopathic.


The clinical presentation, diagnostic tests, and treatment of pancreatobiliary disorders during pregnancy are summarized in Table 47-1 . Pregnancy does not significantly alter the clinical presentation of acute pancreatitis . Epigastric pain is the most common symptom. The pain commonly radiates to the back, and nausea, emesis, and pyrexia frequently occur. Signs include midabdominal tenderness, abdominal guarding, hypoactive bowel sounds, abdominal distension, and increased tympany. Severe cases are associated with shock and pancreatic ascites. Turner sign, bruising of the flanks, or Cullen sign, superficial edema and bruising around the umbilicus, suggest retroperitoneal bleeding.



TABLE 47-1

CLINICAL PRESENTATION AND TREATMENT DURING PREGNANCY OF COMMON PANCREATIC DISORDERS MINIMALLY AFFECTED BY PREGNANCY
























DISEASE OR DISORDER SYMPTOMS AND SIGNS LABORATORY FINDINGS TREATMENT
Acute pancreatitis Epigastric pain radiating to back, nausea and vomiting, pyrexia; abdominal tenderness, guarding, distension Increased serum lipase, leukocytosis; abdominal ultrasound can reveal pancreatomegaly, peripancreatic inflammation, inhomogeneous pancreas Discontinue oral intake; provide aggressive IV hydration, analgesia, and nasojejunal feeding or TPN for a prolonged bout of pancreatitis
Acute cholecystitis Epigastric or RUQ pain, nausea and vomiting, tachycardia, Murphy sign Leukocytosis, variably, mildly elevated LFTs; abdominal ultrasound shows a thickened gallbladder wall, pericholecystic fluid, gallstones in gallbladder Discontinue oral intake; provide IV hydration, analgesia, and antibiotics; cholecystectomy can be performed during pregnancy, most safely during the second trimester
Choledocholithiasis with ascending cholangitis RUQ pain, pyrexia, jaundice (Charcot triad); epigastric tenderness Leukocytosis, jaundice, variably elevated other LFTs; abdominal ultrasound shows dilated choledochus, possible gallstones in gallbladder; ERCP reveals dilated choledochus, choledocholithiasis Discontinue oral intake; provide IV hydration, antibiotics; ERCP with sphincterotomy may be performed during pregnancy to address choledocholithiasis

ERCP, endoscopic retrograde cholangiopancreatography; IV, intravenous; LFTs, liver function tests; RUQ, right upper quadrant; TPN, total parenteral nutrition.


Acute pancreatitis is diagnosed by finding typical abnormalities in two of the following three parameters: (1) clinical presentation, (2) laboratory tests, or (3) radiologic examinations. Typical symptoms of pancreatitis include epigastric or RUQ pain and nausea and vomiting. Serum lipase is a reliable marker of acute pancreatitis during pregnancy because the lipase level is unchanged during normal pregnancy. The serum amylase level is a less specific marker of pancreatitis because it mildly rises during late pregnancy, and it can rise due to diabetic ketoacidosis, renal failure, bowel perforation, or bowel obstruction. Hypertriglyceridemia can falsely lower the serum amylase level in pancreatitis, but the lipase level remains elevated. A serum alanine aminotransferase level more than three times the upper limit of normal strongly suggests biliary pancreatitis. Abdominal ultrasonography is useful in gauging pancreatic inflammation in thin patients with mild to moderate acute pancreatitis, but CT scanning is better at delineating areas of pancreatic necrosis in patients with severe pancreatitis. Abdominal CT is, however, generally discouraged during pregnancy because of potential teratogenicity. Abdominal ultrasonography is also useful to detect cholelithiasis and bile duct dilatation, but endoscopic ultrasonography is required to reliably detect choledocholithiasis. Because of fetal risks from ionizing radiation with ERCP, magnetic resonance cholangiopancreatography (MRCP) is preferable to ERCP as a diagnostic study to visualize the common bile duct during pregnancy, unless endoscopic therapy is contemplated. Acute pancreatitis during pregnancy is often mild and usually responds to medical therapy that includes intravenous (IV) fluid administration, gastric acid suppression, analgesia, sometimes nasogastric suction, and discontinuation of oral intake . Meperidine is the traditional choice for analgesia because it does not cause contraction of the sphincter of Oddi. Short-term administration of meperidine appears to be relatively safe during pregnancy. Pancreatitis complicated by a pancreatic phlegmon, abscess, sepsis, or hemorrhage necessitates antibiotic therapy, total parenteral nutrition (TPN), and possible radiologic aspiration or surgical debridement with patient monitoring in an intensive care unit (ICU). Large and persistent pancreatic pseudocysts require endoscopic or radiologic drainage or surgery. Endoscopic sphincterotomy can be performed for gallstone pancreatitis during pregnancy with minimal fetal radiation exposure. Pregnancy should not delay these therapies. Laparoscopic cholecystectomy can be utilized during pregnancy and is best performed during the second trimester after organogenesis has occurred and before the growing gravid uterus interferes with visualization of the laparoscopic field. Maternal mortality is low in uncomplicated pancreatitis but exceeds 10% in complicated pancreatitis. Fetal outcome is generally good for mild to moderate pancreatitis but can be poor with severe pancreatitis. However, moderately severe pancreatitis is occasionally associated with fetal death during the first trimester and is associated with premature labor in the third trimester. Nutritional requirements for TPN for severe pancreatitis should include the extra nutritional requirements of the gravida.


Cholelithiasis and Cholecystitis


Pregnancy promotes bile lithogenicity and sludge formation because estrogen increases cholesterol synthesis, and progesterone impairs gallbladder motility. In large population surveys using abdominal ultrasonography, 12% of pregnant women in Chile had cholelithiasis, and 8% of pregnant women in the United States had cholelithiasis or biliary sludge detected by abdominal ultrasonography. Most gallstones are asymptomatic during pregnancy, although symptoms of gallstone disease during pregnancy are the same as those in other patients. The usual initial symptom is biliary colic, pain located in the epigastrium or RUQ that may radiate to the back or shoulders. The pain typically increases over several hours then plateaus and subsides over several hours. It can occur spontaneously or can be induced by eating a fatty meal. Diaphoresis, nausea, and emesis are common. Physical examination is unremarkable, other than occasional RUQ tenderness. About two thirds of patients with biliary colic will experience recurrent attacks during the ensuing 2 years.


More severe complications of cholelithiasis include cholecystitis, choledocholithiasis, jaundice, ascending cholangitis, hepatic abscess, and gallstone pancreatitis. Pregnancy does not increase the frequency or severity of these complications. Acute cholecystitis is a chemical inflammation usually caused by cystic duct obstruction by a gallstone. It is the third most common nonobstetric surgical emergency during pregnancy with an incidence of about 4 cases per 10,000 pregnancies. As in biliary colic, the pain is located in the epigastrium and RUQ, but the pain is usually more severe, prolonged, and associated with other clinical findings that include nausea, emesis, pyrexia, tachycardia, right-sided subcostal tenderness, Murphy sign, and leukocytosis. A positive Murphy sign is increased discomfort or inspiratory arrest (a catching of the breath) during deep inspiration when the examiner palpates the gallbladder fossa just beneath the liver edge. Serum biochemical parameters of liver function and serum levels of amylase may be mildly abnormal. Ultrasound is very helpful in diagnosing acute cholecystitis during pregnancy , and it may demonstrate cholelithiasis. Findings compatible with acute cholecystitis include gallbladder wall thickening, pericholecystic fluid, and a positive sonographic Murphy sign in which inspiratory arrest is elicited by pressing the ultrasound transducer probe against the gallbladder fossa during inspiration. Cholescintigraphy with 99mTc hepatobiliary iminodiacetic acid (HIDA) scan is sometimes used to confirm acute cholecystitis in nonpregnant patients, but it is rarely required during pregnancy even though it is believed to be relatively safe to the fetus when strongly indicated. Jaundice suggests choledocholithiasis, and pronounced hyperamylasemia suggests gallstone pancreatitis.


Most cases of biliary colic and some cases of very mild acute cholecystitis can be managed conservatively with close observation, expectant management, and deferral of surgery to the immediate postpartum period. However, most patients with recurrent biliary colic or acute cholecystitis undergo cholecystectomy. Preoperative management includes discontinuing oral intake and then administering IV fluids, analgesia, and usually antibiotics. Ampicillin, cephalosporins, and clindamycin are relatively safe antibiotics during pregnancy. Cholecystectomy is best performed during the second trimester; cholecystectomy during the first trimester is occasionally associated with fetal loss, and cholecystectomy during the third trimester may be associated with premature labor. Cholecystectomy has become increasingly accepted during the first and third trimesters because of improved surgical outcomes, although tocolysis may be necessary during cholecystectomy performed in the third trimester. Intraoperative cholangiography is only performed during pregnancy for strong indications to avoid radiation teratogenicity. Laparoscopic cholecystectomy is safe during pregnancy and is best performed during the second trimester. Both maternal and fetal mortality from acute cholecystitis is less than 2.5% during pregnancy.


Choledocholithiasis


Symptomatic choledocholithiasis is uncommon during pregnancy. Choledocholithiasis can produce gallstone pancreatitis manifested by pyrexia, nausea, and severe abdominal pain or ascending cholangitis manifested by pyrexia, RUQ pain, and jaundice (Charcot triad). Endoscopic ultrasound is relatively safe in pregnancy and is sensitive in detecting choledocholithiasis. Patients with choledocholithiasis and gallstone pancreatitis should undergo ERCP and sphincterotomy with stone extraction, as previously described. Pancreatography can be avoided to minimize fetal radiation exposure. These patients then usually undergo cholecystectomy postpartum but can, if necessary, undergo cholecystectomy antepartum, especially during the second trimester, with acceptable maternal and fetal risks. Cholecystectomy can be performed by laparoscopic, rather than open, techniques during the first or second trimester of pregnancy.


Choledochal Cysts


Choledochal cysts are rare. They typically produce a diagnostic triad of abdominal pain, jaundice, and a palpable abdominal mass in nonpregnant patients. Choledochal cysts are classified into types 1 through 4, depending upon which segment of the biliary tree is dilated. Choledochal cysts can initially present during pregnancy, which can exacerbate the abdominal pain and increase the jaundice because of choledochal compression by the enlarged gravid uterus. However, pregnancy can mask the palpable abdominal mass because of the size of the uterus. Severe pain suggests cyst rupture or concomitant pancreatitis. A choledochal cyst is often diagnosed by abdominal ultrasound, although cholangiography is sometimes required. MRI is preferred over abdominal CT or diagnostic ERCP for determining the anatomy. Surgical management is generally recommended for symptomatic choledocholithiasis because of the risk of recurrent cholangitis and malignant degeneration. The standard surgery is cystectomy, cholecystectomy, and reconstitution of biliary-intestinal flow by either a Roux-en-Y hepaticojejunostomy or choledochojejunostomy. Medical management, including antibiotics and temporary percutaneous or endoscopic drainage, may sometimes suffice until delivery.

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Mar 31, 2019 | Posted by in OBSTETRICS | Comments Off on Hepatic Disorders During Pregnancy
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