Your Pregnancy and Disease of the Liver

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Pregnant women may suffer from liver disease existing prior to pregnancy and may develop new liver diseases that non-pregnant people may also develop. Liver problems occur in approximately 3 percent of pregnancies, and there are a handful of liver problems that strike pregnant women in particular. Notably, these conditions include hyperemesis gravidarum (HG), hemolysis and elevated liver enzymes and low platelets (HELLP) syndrome, acute fatty liver of pregnancy (AFLP), and intrahepatic cholestasis of pregnancy. Occurring during the late second trimester, or any time during the third trimester of pregnancy, ICP also is known as cholestasis of pregnancy, jaundice of pregnancy, obstetric cholestasis, and prurigo gravidarum. The condition features abnormally high flow of bile (a substance produced by the liver that is needed for digestion). This happens because of high levels of the hormone estrogen.

HELLP is a pregnancy complication that sometimes can occur as a further complication of another pregnancy condition, preeclampsia, but the relationship between HELLP and preeclampsia is not totally understood. Preeclampsia features high blood pressure but also dysfunction of organs, particularly the kidney, but it also can be the liver. Thus, preeclampsia and HELLP can overlap, plus HELLP can develop in women who do not have preeclampsia. On the other hand, preeclampsia and HELLP tend to strike mothers-to-be of different age groups, so many researchers consider HELLP and preeclampsia to be separate conditions.

HG features severe nausea and vomiting, weight loss, and disruption of electrolytes, often with dehydration. AFLP, which can occur during the third trimester of pregnancy (usually between 28-40 weeks gestation, especially weeks 35-36), or in a mother soon after delivering a baby, features high concentrations of fat in the mother’s liver. Normally, fat comprises about 5% of the liver’s content, but in AFLP the liver consists of 13-19% fat, and this may be due to problems in the rearrangement and breakdown of molecules called fatty acids coming from the fetus.

Along with symptoms such as nausea, vomiting, abdominal pain, fatigue, headache, and lack of appetite, AFLP can lead to low blood sugar and severely altered states of consciousness or coma. Heartbeat irregularities can happen, as well as bleeding in the gastrointestinal tract and throughout the body. Patients can develop what’s called diabetes insipidus, which means that their blood is getting too diluted, and they are urinating excessively. They also can develop what’s called metabolic acidosis, which means that the pH inside their bodies is too low, a condition that disrupts body chemistry. Multiple organs can be disrupted, including the kidneys, brain, liver, and pancreas. This can lead to kidney failure and/or liver failure, even to the point that the only way to save the patient is with a liver transplant.

HELLP syndrome can develop into further, very severe complications. Once such complication is eclampsia in which, on top of the problems of platelets and organ trouble, the woman suffers seizures. The blood clotting problem connected with platelets can deteriorate into what is called disseminated intravascular coagulation (DIC), plus the kidneys can stop functioning, fluid can accumulate in the lungs and abdomen, clots can block blood vessels in the brain and liver, the retina of the eyes can detach, and there can be bleeding in the brain.

Liver problems occur in approximately 3 percent of pregnancies, and there are a handful of liver problems that strike pregnant women in particular. Notably, these conditions include hyperemesis gravidarum (HG), hemolysis and elevated liver enzymes and low platelets (HELLP) syndrome, acute fatty liver of pregnancy (AFLP), and intrahepatic cholestasis of pregnancy.

Women suffering from HG can develop deficiencies of nutrients such as vitamin B1 (thiamine). This, in turn, can lead to a severe brain condition called Wernicke encephalopathy, featuring tiredness and confusion, dampened reflexes, problems with movement, including movement of the eyes. In very extreme cases, Wernicke encephalopathy can be fatal, if recognized early thiamine deficiency is easily curable. HG also can lead to deficiencies of fat soluble vitamins, such as vitamin K, which is important for blood clotting, so deficiency can lead to bleeding during pregnancy and severe bleeding during labor and delivery. The vomiting may lead to a particular type of acid-base disturbance called metabolic alkalosis, which turn causes or exacerbates a particular electrolyte disturbance called hypokalemia or low potassium. This can lead to muscle damage, kidney problems, and problems with the rhythm of the heart, which also can be fatal. Excessive vomiting and retching furthermore can damage the esophagus, badly enough to cause bleeding and entry of air into tissues and into the chest cavity.

A woman with ICP may experience flu-like symptoms, such as nausea and vomiting as well as abdominal pain and anorexia (lack of appetite). Urine may darken, and it’s possible that a deficiency of vitamin K will develop due to problems absorbing it. If this happens, it can lead to bleeding problems. If the duct that carries bile from the liver becomes obstructed, the woman can develop severe pain and require surgery, but this is very rare.

Because of the decreased pH in the mother’s body in AFLP, the acid-base balance in the fetus can be disrupted as well, putting the life of the fetus at risk until the fetus is delivered. HELLP can cause intrauterine growth restriction, where the fetus does not grow as quickly and as completely as he or she needs to grow, plus the condition can lead to preterm delivery, which itself is connected with numerous complications for the newborn. HELLP and possibly also HG can cause what’s called abruptio placentae or placental abruption, when the placenta detaches from the uterus too early, thereby totally cutting off circulation to the fetus while also causing severe uterine bleeding. Newborns of mothers with HELLP can suffer from neonatal thrombocytopenia (low platelet count resulting in severe bleeding), and respiratory distress syndrome.

HG is associated with increased rates of preterm birth and low birth weight, both of which can lead to physical and mental problems for the baby. Infants born to mothers with HG also may be prone to psychiatric conditions.

ICP is treated effectively with ursodeoxycholic acid (UDCA), which is safe both for the mother and her fetus. The first medication that often is given in cases of HG is a combination of two drugs called doxylamine succinate (an antihistamine) and pyridoxine HCl (vitamin B6), which together are known as Diclegis. The treatment is safe for the baby, but its main use is not for HG but for nausea and vomiting of pregnancy. First line drugs specifically for HG include ondansetron and metoclopramide, while second choice drugs offered to patients who do not improve with one of the other drugs include promethazine, clonidine, and mirtazapine. Corticosteroid medications also have been used in patients with HG, but controversy surrounds whether or not they are effective. With AFLP and HELLP, the baby needs to be delivered early, so medications consist of corticosteroids, particularly betamethasone to accelerate the development of the fetal lungs. Steroids also help the mother with the effects of HELLP. Women with HELLP also need magnesium sulfate to prevent seizures; this also is not harmful to the fetus. The mother also can be given any of a handful of pregnancy-safe blood pressure drugs. The latter must be done with extreme caution, since lowering blood pressure too much can reduce circulation through the placenta, which can harm the fetus.

David Warmflash
Dr. David Warmflash is a science communicator and physician with a research background in astrobiology and space medicine. He has completed research fellowships at NASA Johnson Space Center, the University of Pennsylvania, and Brandeis University. Since 2002, he has been collaborating with The Planetary Society on experiments helping us to understand the effects of deep space radiation on life forms, and since 2011 has worked nearly full time in medical writing and science journalism. His focus area includes the emergence of new biotechnologies and their impact on biomedicine, public health, and society.

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