During this 20-25 minute pre-recorded lecture, Dr. Tatyana Kushner discusses the topic of liver disease in pregnancy. This in-depth review will provide an update on this topic for your clinical practice as well as supplement your learning for the ABIM Gastroenterology and Hepatology boards. CME pre-requiste of live Q & A webinar, 8th Annual Mount Sinai Intensive Board Review in Gastroenterology & Hepatology on Oct 13.
Hi everyone. I'm dr christian and I will be discussing liver disease of pregnancy. This is definitely a very testable subject on the boards. I'll try to provide you an overview of the topic in a case based format. So I'll start with case one we have a 29 year old pregnant G. Two P. 0010 female. She's referred to you at 25 weeks of pregnancy because of concern for chronic liver disease. This is her second pregnancy has otherwise been unremarkable and she's only taking a prenatal vitamin on her exam. Her vitals are stable but she does have scattered spider and gliomas across her chest as well as lower extremity edema. Which reminds you of physical findings and patients with cirrhosis. Her labs show mild anemia with the hemoglobin? 10.9 borderline low platelets of 150,000 as well as elevated alkaline phosphate taste. To to 20 and albumin of 3.1 which is on the lower side. So what would be the next best step in management here? Would you work up for cirrhosis prefer to transplant center? Perform an M. R. C. P. For evaluation for biliary disease. Given elevated alkaline phosphate taste or provide reassurance. So the answer years to provide reassurance and this question gets at what is normal and pregnancy. What physical exam findings and blood test changes do you see normally in the context of pregnancy. So it is important to recognize that in pregnancy there's a rise of maternal heart rate and cardiac output and a decrease in S. P. R. And blood pressure. There's also an increased estrogen state which leads to spider angio hmas as well as palmer erythema which we see in our patients with cirrhosis. However the appearance of the size of delivers should be normal and the hepatic absolute blood flow should be normal as well. Finally it is not abnormal at all to see lower extremity edema. This is considered normal in the context of pregnancy in terms of lab work. So in pregnancy A. S. T. A. L. T. Billy Rubin I. N. R. G. T should stay the same unless there's something underlying going on of course that A. F. P. Is elevated as well as the alkaline phosphate tastes more towards the third trimester of pregnancy. Where we see increased placental release of alkaline phosphate taste as well as fetal bone growth, leading to increase bonuses enzyme of alkaline ferocity. So it is normal in pregnancy to see elevated alphas, particularly in the third trimester and then do to him, oh dilution. We see a lower hemoglobin and I'll be money. So very important to remember that any elevation and L. T. A. S. T. Billy Rubin and I in our are abnormal in the context of pregnancy and should be investigated. And when we do the investigation for what could be causing these abnormal liver tests it is very helpful to categorize potential liver disease abnormalities in three main categories. One is chronic liver disease. The second is liver disease unique to pregnancy or liver disease that only occurs in the context of pregnancy. And the last is liver disease which may be coincidental to pregnancy and the work that you do in terms of evaluating abnormal blood test you, it is helpful to think about these three different categories. So for example, when thinking about chronic liver disease, you want to screen them for chronic viral hepatitis hepatitis B and hepatitis C. When you think about liver disease, unique to pregnancy, you think about things like coolest basis of pregnancy and preeclampsia, for which you can send bile acid levels and urinary protein. And when you think about liver disease, coincidental pregnancy or liver diseases that may occur with increased frequency and pregnancy, you think about things like gall stones. In which case you would recommend an ultrasound with Doppler as well as Hepatitis E, which has a more severe course in pregnancy. So you would check hepatitis E and we'll go over all of these in the lecture. So moving on to case two, we have a 28 year old woman. She's on her first pregnancy and she's brought into the emergency room for three days of vomiting. This is week 14 of her first pregnancy and she's had intermittent vomiting throughout The past couple of weeks. She has lost £5 in the past three weeks as a result, Her vitals are okay, although she is take a card with a pulse of 1:18 and uh she doesn't have any writer per quadrant tenderness on her physical exam. Her labs are significant to elevated liver test with A. S. T. Of 98 A. L. T. 1 20. And the other labs are mostly unremarkable, including uh a normal outline foster taste level. The question here is all of the following are true about this condition except this condition should resolve after 18 weeks gestation. This condition typically occurs during the first trimester of pregnancy. This condition leads to cirrhosis and this with with treatment of this condition, there is little risk to the fetus. So the answer here that is not correct is this conduct addition leads to cirrhosis. And of course the condition that we are talking about here is hyperemesis, gravity, air in which we will discuss. So when you think about that category of liver disease specific to pregnancy, that's where we'll start with our overview. You really need to think about these conditions by the trimester in which they occur and that really helps you to categorize, which if any of these conditions can be causing deliver test abnormalities or the symptoms in the first trimester. The main condition that we think of as hyperemesis gravedigger. Um As we move on to the second trimester uh inter hypocritical states of pregnancy as well as pre eclampsia can occur as early second trimester and the third trimester conditions that only occur during pregnancy are acute fatty liver of pregnancy. Pre eclampsia and help syndrome and again with acute fabulous of pregnancy as well as the pre eclampsia help spectrum. They can occur in second trimester and can actually occur uh immediately postpartum. The first conditional discusses hyperemesis, gravity era. So this is a condition that again occurs in the first trimester and up to 2% of all pregnancies And really onset is usually between four and 10 weeks of gestation. And as we have mentioned it resolves largely by 18 weeks of gestation. Clinical presentation is categorized by intractable vomiting, dehydration, ketosis and even weight loss. And it is not unusual to see elevated liver tests in this condition which can reach up to 20 times dr limit of normal. Usually it's the L. T. Nasdr. Elevated and billy Rubin is rarely elevated. The treatment is really supportive. It's not directed in terms of anything liver specific but with treatments such as including I. V. Hydration, anti um medics, vitamins implementation. The condition tends to get better and as the symptoms get better, the liver tests tend to get better as well. Moving onto the next case case three. So we have a 37 year old woman, she's in her second pregnancy and she's 34 weeks gestation. She presents complaining of three weeks of intense itching on her palms and the soles of her feet. The engine keeps her up at night and she also has mild square electorates. She is A and O. Times three and she has no asterix is on blood work. Her billy Rubin is elevator 4.3 here. S. T. N. A. L. T. R. 8 92 and 7 89 quite elevated And she's mildly anemic and her platelets are 200,000. Her bio acid level is 32 and the normal cut off is 10. Another work up. She is found to be immune to hepatitis B. She's hepatitis C negative and an N. A. Was sent as well for evaluation for autoimmune hepatitis and it is not very significantly elevated. And she had a liver ultrasound which is normal. So which is the next best step in her management. So a deliver baby early at 34 weeks. Test for l chad deficiency, perform a liver biopsy starter. So deoxyribonucleic acid transfused platelets with delivery. So the answer here is to start orthodoxy colic acid because this is a case of intra hepatic cola stasis of pregnancy. So what is it? You're a political states of pregnancy. Well, it is a condition that occurs during second or third trimester extremely rare to see it in first trimester and definitely not testable uh As occurring earlier than 2nd trimester. Not very common but it is more common in certain ethnic groups. Uh specifically in some parts of south America and Scandinavian countries. And the risk factors associated with the one important one to recognize is hepatitis C. Having active hepatitis C increases the risk of coal states of pregnancy and there's also seasonal variation in terms of higher uh occurrence of this condition during certain seasons, as well as association with selenium levels and vitamin D. Levels. And there's also a genetic predisposition to this condition. The clinical features are itching or politis on the palms and soles of feet. That's the classic presentation. It's classically worse at night than during the day. And it is important that john doe's can occur. But oftentimes actually these patients really present more with elevated A. S. T. E. N. A. L. T. So even though it's called coalesced Asus of pregnancy, the alkaline facilities and the billy Rubin do not have to be elevated. But the A. S. T. N. A. L. T. Are often elevated. And the way that the diagnosis is made is by checking bile acid levels. So bile acid levels of over 10 are used to help diagnose the condition in regards to associated features of it. So in geopolitical space of pregnancy, the concern with it is that it can lead to poor fetal outcomes. Um and even fetal demise. And that's really the main concern with this condition. Um And in terms of the mom, the mom tends have good outcomes although it is important to counsel pregnant women that if they have cool stasis and one pregnancy. Their increased risk in future pregnancy or even during uh oral contraceptive use due to the hormonal effect. Generally speaking, the symptoms resolve after delivery. The management really the mainstay of treatment that we have is treatment with are so versatile at 10-15 mg per kilogram. And the recommendation also is to deliver the infant soon after fetal maturity. And generally speaking, the guidelines recommend delivery at 37 weeks. So if you're diagnosed with coal states of pregnancy, the recommendation is to induce delivery at 37 weeks as opposed to going to full term 40 weeks If their speed, signs of fetal distress, um you can deliver even sooner than the 37 weeks. I also wanted to draw you your attention to some more recent data about cole stasis of pregnancy. So there were two studies published in the Lancet, both in 2019 evaluating the aspect of coal states pregnancy of treatment versatile as well as association with adverse pregnancy outcomes. So the first study that I want to draw your attention to is called the pitches study and it was a multi center study conducted in europe where her saddle versus placebo was evaluated a woman with close stasis of pregnancy to determine whether there is any beneficial effect of versatile on adverse fatal outcomes. And what you see here is that in terms of the outcome of uh negative fetal outcomes uh as well as preterm delivery, as well as requirement for nicu admission for the fetus. There was no difference between patients who were treated with their saddle versus patients who were treated with placebo. So although this is a relatively new study, the study, um question whether ursa dial is actually beneficial specifically in terms of improving fetal outcomes as well as pregnancy outcomes. I would still say that the standard of care is still to use our saddle, but and I don't think that the boards would would question that. But it is important to be aware that in the future we may need to look for other treatments that actually do have a more significant favorable outcome on on both fetal outcomes as well as preterm delivery. And then this is another study that was published in the Lancet last year and it looked at different cutoffs of bile acid levels in terms of predicting their main outcome of interest, which was still birth of the fetus as well as looking at preventing another outcome which is spontaneous preterm birth. And what they found is that bile acids over 100 which is the red line here are significantly associated with stillbirth of fetuses. But by lower bile acid cutoffs were not associated with negative fetal outcomes. So it is important to recognize that Cut off of bile acids of over a 100 as opposed to bile acids over 10 or any lower cut off as the cut off that is associated with negative fetal outcomes. Uh they did also see that bile acids over 40 were associated with increased risk of spontaneous preterm birth. So, if you're going to keep two numbers in mind, it's that 40 number and 100 number and the bile acid. Over 100 are really the patients that we are most concerned about. All right. Moving on to case four. So you have a 34 year old women. She presents the emergency room, she's 32 weeks gestation to her first pregnancy and has been uncomplicated so far. She reports that she's had loose stool over the past 24 hours and her husband noted that she also has become progressively more tired and sleepy on her vital. She's a bit tachycardic. She's also febrile and her blood pressure is mildly elevated. On physical exam she does appear drowsy. She does not have asterix as though she has some square electorates and appears jaundice. She has some palmer erythema and she does have some right upper quadrant tenderness as well as lower extremity edema on her blood work. You see that her platelets are quite low at 6 2000. Her white blood cell count is 10 point to her. I. N. R. Is elevated at 2.9. Her glucose is on the lowest side of 59. Her billy Rubin is elevated at 3.1 S. T. And LT, both elevated as well and alkaline. Foster taste. 3 72. The patient is admitted to the ICU for further monitoring blood cultures and urine cultures are sent as well as liver diseases. Work up with viral hepatitis labs and her head ct shows mild cerebral oedema. What would be the most appropriate management for this patient. So a urgent fetal delivery be administered corticosteroids. See administer said, I'll deliver biopsy e list for a liver transplant. F. I've antibiotics and continue monitoring an ICU pending the result of the above studies. So the answer here is urgent fetal delivery and this is a condition of acute fatty liver of pregnancy, which will discuss. So when we think about the late pregnancy syndromes, we have acute fatty liver of pregnancy help syndrome and the preeclampsia spectrum, and these are probably the most feared liver related complications of pregnancy. When we think about acute fatty liver disease of pregnancy, this is a condition that again occurs during late pregnancy and on biopsy findings of these patients if he were to perform a biopsy, which is not recommended. Um But you would see micro vesicular theater Asus as opposed to macro vesicular osteoporosis. You see it in this figure. This is micro vesicular theater doses and the little inset. That's what we would normally think about as macro vesicular theater Asus. And our patients with fatty liver disease. For example, many of the patients with acute fatty liver pregnancy are characterized by an inherited enzyme deficiency in mitochondrial beta oxidation, where the mother is a hetero side and the fetus is a homo psycho. And what happens is that the deficiency of this enzyme, the l chad enzyme leads to accumulation of the long chain three hydroxy castle metabolites produced by the fetus and the placenta. And when these metabolites accumulate, they are directly toxic to maternal liver and that leads to acute fatty liver of pregnancy. It's also important that this this syndrome is mostly classified with clinical features and not all cases of acute fatty liver of pregnancy have this enzyme deficiency associated with it. It occurs mostly during third trimester or early postpartum. Unfortunately it is a very rare condition, very rare to see this in clinical practice although it is a very feared complication of pregnancy. The risk factors for Q fatty liver pregnancy interestingly include low maternal B. M. I. Male fetus and advanced maternal age. Clinical presentation includes signs and symptoms of liver failure as well as systemic disease which can include gi bleeding, D. I. C. Acute pancreatitis. And the labs associated with it are labs that you would see an acute liver failure which includes elevated I. Nr elevated ammonia levels and of course elevated L. T. A. S. T. And what is sometimes helpful for the diagnosis of this condition is the Swansea criteria which is listed here and basically when the patient meets six or more of these criteria which includes um symptoms, laboratory findings and physical exam findings listed here then uh they're consistent with having Swansea a criteria. The management for this condition is immediate delivery and usually after delivery. The patient improves all the liver transplant may be needed if they are not delivered soon enough and they do not improve. Moving on to the next case, we have a 39 year old woman, she's at week 35 of her second pregnancy. She's a little bit hypertensive and she's noted to have mild palmer demon spider ngoma. Her abdomen demonstrates gravity uterus consistently the 35 week pregnancy. But she does have mild right upper quadrant tenderness and she has a demon to her knees bilaterally on her exam on her blood work. Rather, her billy Rubin is slightly elevated S. T. And LT are also elevated. Um And then her platelets are on the low side and she does have three plus urinary protein which of the following is the most appropriate diagnosis here. And the answer is preeclampsia. And that's really because of the protein urea in urine, her lower extremity edema as well as the lowest platelets. So preeclampsia eclampsia. So we see this in 5-10% of all pregnancies and occurs in second or third trimester. Um And it is the most common cause of liver tenderness and abnormal liver test in terms of the pregnancy specific conditions. Risk factors are advanced maternal age, pre existing hypertension, pre existing diabetes and the clinical presentation is that try out of high blood pressure oedema and protein urea, although Dema is no longer a required component of the diagnosis If it progresses eclampsia is characterized by seizures or altered mental status. And the laboratory features include elevated L. T. N. A. S. T. Which can go up to 10 to 20. Um Full at times the upper limit of normal. And then the end spectrum of this condition is something called help which stands for him. Also elevated liver enzymes and low platelets. And this presentation there is often right upper quadrant pain, nausea, vomiting, fatigue, malaise. Um there's also some classification systems that you see in this green box here that are helpful for the diagnosis and main features are that you have elevated LDH over 600 platelets under 100 and elevated esteem. And these are helpful in clinical practice to try to help diagnose help and also distinguished from other conditions such as acute fatty liver of pregnancy or straightforward preeclampsia. I'm glad work. You'll see thrown beside a penny elevator at L. D. H. And on smear you'll see shift the sites and a potential complication of this is hip, attic infarction or rupture which we see in the C. T. Scan showed here which is associated with significant maternal morbidity and as well as mortality. So this is a dreaded complication of this condition. And again the management for this similarly to acute fatty liver of pregnancy is really immediate delivery supportive iCU care. All right. Moving on to case # six We have a 23 year old woman who is 18 weeks pregnant. Her pregnancy so far has been on remarkable. She's presenting for recurrent right upper quadrant abdominal pain and low grade fevers on the ultrasound, she's found to have gallbladder wall thickening and perry polycystic fluid. Which of the following is true. Um This diagnosis is unique to first trimester of pregnancy. It should be managed with early surgical intervention, emergent delivery is indicated for fetal safety, laproscopic ALs hysterectomy is contra indicated. So this should be managed with early surgical intervention because this is called cystitis. So this is bringing us to the topic of liver disease coincidental to pregnancy which includes the conditions here including gallstone disease. But chiari due to the hyper quiet global state and pregnancy as well as uh HSV. Hepatitis A hepatitis E. So moving on to biliary disease. So, cool with ISIS is common in pregnancy and that's related to the hormonal state which affects the production of gall stones and sludge as well as decreased gallbladder motility. E. R. C. P. Can be performed for strong indications in a tertiary center and closest ectomy if needed is best performed in the second trimester and laproscopic. AlS that suspect me if needed is considered safe viral. Hepatitis is the most common cause of jaundice in pregnancy in the United States and uh in the concept pregnancy. That is important to think about hepatitis A which can occur acutely. Um although vertical transmission is low and hepatitis E which has a more severe course during pregnancy associated with increased maternal mortality and high rate of intra uterine death but fortunately is very rare and generally speaking, the treatment is supportive. It is also important to remember to check for HSV when doing a liver diseases, elevated liver test work up because this again is very important to recognize in pregnancy and if associated with significant liver injury can be associated with significant mortality. So it's important to recognize it and start a cycle of your early. Now moving on to case seven. So we have a 27 year old woman, she's 26 weeks pregnant and is referred by her O. B. G. Y. N. For a history of hepatitis B. Her liver tests are normal, her surface antigens positive and her e antigen is positive for HPV. D. N. A. Is one million. In addition to hepatitis B immunoglobulin and vaccination of the internet birth which of the following reduces mother to child transmission. And the answer here is that we need to treat the mother with Tenofovir now and that's because her viral load is very high. So with hepatitis B vertical transmission generally occurs during the delivery. So there's no role for uh C. Section to lower the risk of transmission. High viral load increases the risk of mother's child transmission. And if the viral load is over 200,000 during the third trimester, then the patient should get 10ofovir in order to lower the risk of transmission infant. Of all hepatitis B positive mothers regardless of viral load, should receive hepatitis B immunoglobulin and vaccine with the first dose being within 12 hours of birth in order to prevent transmission. And then it is important to check the infant for Post that vaccines neurologic testing at 9-18 months to make sure that they are hepatitis B negative and responded to the vaccine. Hepatitis B breast feeding is not contraindicated because there's a very a minimal risk of transmission. Alright case 8 35 year old woman, week 30 of her first pregnancy referred by her primary care provider and she's a former injection drug user on her blood work evaluation. She's noted to have Hepatitis C. With hepatitis C. Antibody positive and elevated viral load. So which of the following should be recommended Begin treatment with tapestry depicts fear uh right now begin treatment with faster blood spatter sphere and ribavirin. Plan on having a C. Section. Or recommend to avoid prolonged rupture of membranes. The answer is recommend to avoid prolonged rupture of membranes because we want to decrease the risk of hepatitis C transmission to the baby and prolonged rupture of membranes has been associated with increased risk of transmission. So for hepatitis C in pregnancy it is important to recognize that currently most major societies recommend universal screening during pregnancy and this is relatively new as of this year. So the U. S. P. S. T. F. S. L. D. As well as the C. D. C. Recommends screening all women for hepatitis C during pregnancy. No longer. Just risk based screening, vertical transmission of hepatitis C. is and around 5%. But if Patients are contacted with HIV that risk is higher. So probably closer 10-12%. So when evaluating for transmission that infants should be tested at 18 months of age for hepatitis C antibody, there are certain risk factors for increased transmission which include again co infection with HIV as well as certain pregnancy management issues which include prolonged rupture membranes, invasive fetal monitoring. There is no effect of delivery type whether you have vaginal or C. Section in terms of prevention of transmission and breastfeeding. Similarly to hepatitis B should not be discouraged. Uh I'm getting to the end here. The next topic is I wanted to mention very quickly of hepatic masses or lesions, the one to look out for us in paddock adenoma. So these are accelerated and growth in high estrogen states. So patients who have a greater than five centimeter hepatic adenoma should be referred for potential reception prior to pregnancy because they're at increased risk of hemorrhage and ruptured during pregnancy. That does not apply to other liberal lesions such as human gliomas and F. N. H. Is okay and then portal hypertension during pregnancy. Just a few words here. So generally speaking women with cirrhosis and portal hypertension have lower fertility and therefore are not as likely to be pregnant but can become pregnant of course and they are associated with increased pregnancy complications. The main thing that we worry about with patients with portal hypertension is increase plasma blood volume, which can increase the risk of various still bleeding. So the recommendation is to screen for various is uh before pregnancy as well as during second trimester to address them prior to increase blood volume and increased risk of bleeding. Finally end with pregnancy. Post liver transplantation. Generally speaking, it's recommended to delay pregnancy for at least a year after liver transplant when immune suppression regimen is stable. Um and in patients who do perceive pregnancy post liver transplantation there is increased risk of maternal and fetal complications. Um also important to know that most immunosuppressive regimens actually can be taken during pregnancy, but self stepped or micro phenolic michael Fennelly should uh is strictly contraindicated. Alright, so to conclude here, liver disease during pregnancy can be specific to pregnancy, chronic or coincidental to pregnancy. It's important to think of these three different categories when evaluating patients who present. For example, with elevated liver tests, the timing of when the liver disease occurs can help to determine the ideology for help and acute fatty liver of pregnancy, emergent delivery is really the treatment and important to think about mother to child transmission in patients with hepatitis A hepatitis B. Hepatitis C. Good luck on the boards