GI in Pregnancy: GI in Pregnancy: Preexisting Liver Disease

0:00Welcome to Board Pearls. This is episode five of six of the GI in Pregnancy chapter, in the Special Populations and Acute or Supportive Care module. This episode is the woman who brings her liver disease into pregnancy. The first patient has autoimmune hepatitis and is planning a pregnancy. Her case shows why autoimmune hepatitis often quiets during pregnancy and flares afterward, which immunosuppressant must stop before conception and why azathioprine is allowed, and how the same principle carries over to primary biliary cholangitis, PBC, primary sclerosing cholangitis, PSC, and Wilson disease. The second patient is pregnant with compensated cirrhosis. Her case shows how risk is judged in cirrhosis, why portal pressure climbs as pregnancy advances, which beta blocker and which vasoactive drug are avoided, and, if her disease someday leads to transplant, when a recipient can safely conceive.

0:53Here's the first patient. A thirty-two-year-old woman has autoimmune hepatitis, well controlled for three years on prednisone five milligrams and mycophenolate, with normal liver tests. She and her partner want to try for a baby this year.

1:08She has autoimmune hepatitis in remission, an immune-mediated hepatitis, and pregnancy will change the immune activity that drives it. Pregnancy shifts immunity toward a Th2-dominant, tolerant state, with cellular immunity returning abruptly after delivery, and it also changes the liver's synthetic and metabolic demands and how drugs are handled. Autoimmune hepatitis often quiets during pregnancy, but the return of cellular immunity after delivery causes flares in thirty to fifty percent. The disease can still flare during pregnancy, in up to a fifth of patients, and flares around delivery carry an eleven percent risk of maternal death or transplant. So her immunosuppression continues through pregnancy, and withdrawing it isn't appropriate.

1:51One of her two drugs has to change before she conceives. Mycophenolate is strictly contraindicated in pregnancy. It inhibits inosine monophosphate dehydrogenase, blocking the guanosine nucleotide synthesis that fetal cell division depends on, and its Food and Drug Administration, FDA, black-box warning lists cleft lip and palate and distal limb, heart, esophageal, and kidney anomalies. It requires a six-month washout before conception, and men taking it avoid fathering children for ninety days after stopping.

2:22Her replacement is azathioprine, continued with her prednisone through pregnancy. Azathioprine carried the old category D letter, and letter categories were retired from labels in twenty fifteen. It's acceptable because the fetal liver lacks inosine triphosphate pyrophosphatase, the enzyme needed to make its active 6-thioguanine metabolite, so the fetus sees little active drug, and clinical experience supports its safety. Older literature suggested a small first-trimester cleft palate signal with prednisone, but recent cohorts show no increased risk. So she switches from mycophenolate to azathioprine under her hepatologist, confirms she stays in remission, and starts trying six months after her last mycophenolate dose.

3:05Her monitoring follows the timing of her flare risk. Liver enzymes are checked each trimester, then every two to four weeks for the first six months after delivery, because that's when flares are most likely.

3:17The principle her case shows, keeping the disease controlled with drugs that are safe for the fetus, applies to the other chronic liver diseases a woman can bring into pregnancy. In primary biliary cholangitis, about a third of diagnoses are made during pregnancy, because the itching prompts investigation. Total bile acids are checked as a baseline in the first trimester, so that a later rise can be told apart from intrahepatic cholestasis of pregnancy, from episode three, which would change the delivery plan. Ursodeoxycholic acid, UDCA, continues, because it's hydrophilic, displaces the toxic hydrophobic bile acids, and improves canalicular transport, with extensive safety experience in pregnancy. Obeticholic acid and fibrates aren't recommended, because their safety data in pregnancy are limited.

4:04Itching may worsen during pregnancy and is treated with cholestyramine, rifampin, or S-adenosyl-L-methionine. Cholestasis impairs absorption of fat-soluble vitamins, so vitamin K is monitored and given parenterally when deficient. Flares after delivery occur in sixty to seventy percent of women with PBC, so follow-up continues after the birth, as it does in autoimmune hepatitis.

4:29In primary sclerosing cholangitis, care in pregnancy is supportive: itch is treated with cholestyramine or rifampin, fat-soluble vitamins are replaced, and surveillance for cholangiocarcinoma and dominant strictures continues, including routine surveillance imaging. Endoscopic retrograde cholangiopancreatography, ERCP, is reserved for cholangitis or for a dominant stricture with progressive cholestasis or jaundice, and it's done in the second trimester when feasible, with limited fluoroscopy and lead shielding.

5:00In Wilson disease, the rule is never to stop therapy, because stopping can precipitate acute liver failure, so a woman asking whether to stop her chelator for her baby is told that stopping is the danger. Zinc continues if the disease is well controlled. Chelator doses are lowered by twenty-five to fifty percent in the third trimester, typically to about five hundred milligrams a day, to support wound healing and the fetus's copper needs. Trientine chelates iron too, so iron needs may rise. Copper-containing prenatal vitamins and copper intrauterine devices, IUDs, are avoided, and a levonorgestrel IUD is the preferred long-acting contraceptive. Untreated Wilson disease itself causes infertility and miscarriage, and breastfeeding on D-penicillamine isn't recommended.

5:50Now the second patient. A thirty-five-year-old woman has well-compensated cirrhosis from autoimmune hepatitis, with a Model for End-Stage Liver Disease, MELD, score of nine. She's fourteen weeks pregnant and has never had an endoscopy.

6:05Her cirrhosis is compensated, and successful pregnancy is possible in well-compensated cirrhosis, so her risk is judged before her plan is made. Decompensated cirrhosis calls for careful counseling, because hypothalamic-pituitary dysfunction causes amenorrhea and infertility, although pregnancy can still occur. A MELD above ten predicts decompensation during pregnancy with about eighty-three percent sensitivity and specificity, and complications occur in roughly ten percent of women above that threshold. Her MELD of nine is reassuring.

6:37Her main risk is variceal bleeding, and it rises as her pregnancy advances. Plasma volume expansion late in pregnancy raises portal pressure further, so variceal bleeding risk climbs, especially in the second trimester and around delivery, reaching twenty to twenty-five percent in women with existing varices, and maternal mortality from variceal hemorrhage is ten to eighteen percent. That's why varices are screened for within twelve months of conception, or with upper endoscopy early in the second trimester if that was missed. Never scoped and now fourteen weeks pregnant, she has her endoscopy now, and it shows large varices.

7:11Her large varices are treated with options that are safe in pregnancy. Large varices get a non-selective beta blocker or band ligation, and propranolol is preferred over nadolol, because nadolol's long half-life causes fetal bradycardia and low birth weight. If she bleeds, she's treated with band ligation, octreotide, and ceftriaxone prophylaxis. Vasopressin is avoided, because it activates V1 receptors on the myometrium, causing uterine contractions and preterm labor. She starts propranolol, and her varices go into her delivery plan, because the peripartum period carries the highest risk.

7:46Her cirrhosis brings two other sources of bleeding into that plan. A splenic artery aneurysm is present in about two point six percent of pregnancies in cirrhosis, and its rupture is often fatal, so ultrasound screening during pregnancy is appropriate. Aneurysms larger than two centimeters carry the highest risk, although half of the ruptures in pregnancy involve smaller ones. Postpartum hemorrhage occurs in seven to ten percent. So she delivers at a tertiary center, with a plan that covers bleeding from varices, the splenic artery, and the uterus.

8:19If her cirrhosis eventually leads to a liver transplant, pregnancy afterward has its own rules. Pregnancy is delayed at least a year after transplant or after a rejection episode, until graft function is stable on maintenance therapy. Menstruation returns within ten months in ninety percent of recipients, so fertility often returns before pregnancy is safe, and a recipient eight months out with regular periods needs contraception and a conversation about waiting.

8:45During a post-transplant pregnancy, tacrolimus, cyclosporine, prednisone, and azathioprine continue, with trough levels checked every two to four weeks, because plasma volume expansion lowers calcineurin inhibitor levels and doses need adjusting, and unnoticed falling levels could let the graft reject. Sirolimus and everolimus are avoided because limited data show a miscarriage signal of about thirty-one percent, and mycophenolate is switched to azathioprine before conception, as in the first patient. Gestational diabetes, in about ten percent, and hypertensive disorders, in twenty-two to seventy-three percent, are common, so co-management with maternal-fetal medicine and high-risk obstetrics is standard.

9:25Here are the traps the boards set in these patients. Stopping autoimmune hepatitis therapy during pregnancy. Conceiving on mycophenolate, or without a six-month washout. Avoiding azathioprine because of its old letter category. Relaxing monitoring after delivery, when flares peak. Stopping UDCA in PBC, or using obeticholic acid. Stopping Wilson therapy, or forgetting to lower chelator doses late in pregnancy. Skipping variceal screening in cirrhosis. Choosing nadolol over propranolol. Giving vasopressin for variceal bleeding. Forgetting to screen the splenic artery. And conceiving within a year of transplant, or on an mTOR inhibitor.

10:09So, start to finish. Autoimmune hepatitis therapy continues through pregnancy with prednisone and azathioprine, mycophenolate stops six months before conception, and postpartum flares are expected, with liver tests every two to four weeks for six months after delivery. In PBC, UDCA continues and baseline bile acids are checked early. Wilson therapy is never stopped, but chelator doses are lowered late in pregnancy.

10:33In cirrhosis, varices are screened within a year of conception or early in the second trimester, large varices get propranolol or banding, vasopressin is avoided, the splenic artery is screened, and delivery is at a tertiary center. After liver transplant, pregnancy waits at least a year, tacrolimus levels are checked every two to four weeks, and mycophenolate and mTOR inhibitors are avoided.

10:57Episode six, the last of the chapter, is inflammatory bowel disease and pregnancy after bariatric surgery.

11:04For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode five of six of chapter thirty-five, and I'll see you in the next one.