Pregnancy and The Liver

The issues surrounding pregnancy and the liver are many. This section will address several of these issues, including how pregnancy may affect the liver and the general health of a woman with preexistent chronic liver disease. Another issue covered is what impact chronic liver disease may have on the fetus. This section will also discuss some liver diseases that may occur in pregnant women with no prior history of liver disease.

Pregnancy in Women With Preexistent Chronic Liver Disease

Most women with liver disease can become pregnant, have uncomplicated pregnancies, and go on to give birth to healthy babies. However, in some circumstances, liver disease may adversely affect pregnancy and childbirth. The following pages discuss pregnancy in women with preexistent chronic liver diseases, including de compensated cirrhosis, chronic hepatitis B and C, autoimmune hepatitis, and others.

Decompensated Cirrhosis and Pregnancy

Cirrhosis is often associated with amenorrhea (lack of menses) and infertility. Consequently, women with cirrhosis—especially decompensated cirrhosis—may have difficulty conceiving. As a result of their advanced liver disease, women with decompensated cirrhosis who do conceive have an increased risk of serious complications during pregnancy.

Approximately 15 to 20 percent of these women suffer spontaneous abortion (miscarriage). Also, there is an increased risk for premature childbirth or stillbirth. Furthermore, women with decompensated cirrhosis are at an increased risk for the development of liver failure during pregnancy, although it is unknown how often this occurs.

Bleeding from esophageal varices is probably the biggest pregnancy-related health risk for women with decompensated cirrhosis. Variceal bleeding is most common during the second trimester, occurring in approximately 20 to 45 percent of women with portal hypertension. Ten percent of the time, women with decompensated cirrhosis experience variceal bleeding during labor and immediately after childbirth.

Death of the mother from uncontrollable variceal hemorrhage occurs approximately 10 to 18 percent of the time during the course of pregnancy. Depending on the trimester, the baby may nevertheless have chance for survival. Women with decompensated cirrhosis who are thinking about becoming pregnant should undergo an upper endoscopy, which can assess the presence and degree of esophageal varices.

If a woman has esophageal varices, she should be placed on a beta-blocker, such as propanolol (Inderal). It should be kept in mind that beta-blockers may pose risks to a fetus, including a slow heart rate and potential growth retardation. Such risks must be weighed against the potential benefit to be gained by preventing bleeding from esophageal varices. Women who have previously bled from esophageal varices are advised to refrain from becoming pregnant.

For these women, if pregnancy is still desired despite the high risks, it is recommended that a transjugular intrahepatic portosystemic shunt (TIPS) or other shunt procedure be considered before pregnancy occurs—as this may decrease the risk of bleeding from esophageal varices. It has been noted that for pregnant women with chronic liver disease, those with alcoholic cirrhosis appear to have the worst prognosis. Those with primary biliary cirrhosis appear to have the best prognosis.

Despite the increased risk of complications, many women with decompensated cirrhosis successfully proceed through pregnancy and childbirth without any complications. It is important for these women to be monitored regularly by a liver specialist and to choose an obstetrician who has experience with high-risk pregnancies.

Fetuses should be very closely monitored during pregnancy. If there are signs of fetal distress or if bilirubin levels become very high in the mother, early delivery should be considered. Infants born alive generally do very well.

Chronic Hepatitis B and Pregnancy

Women with chronic hepatitis B generally do quite well during pregnancy, providing that they have not progressed to decompensated cirrhosis. Although it has been reported, a flare-up of hepatitis B during pregnancy is very uncommon.

Transmission of the hepatitis B virus (HBV) to the fetus during pregnancy is rare. The placenta is usually an efficient barrier to transmission of HBV to the fetus. However, approximately 15 percent of the time, transmission transplacentaly (through the placenta occurs, apparently in cases where the placenta has leaked blood into the fetus (for example, during a in a pregnancy in jeopardy of a miscarriage).

However, prenatal transmission (transmission from mother to infant during childbirth) is very common, occurring in more than 90 percent of the cases if the mother is HBeAg and/or HBV DNA positive. In fact, transmission to the fetus at childbirth accounts for approximately 40 percent of the world’s chronic carriers in endemic areas (such as Asia and Africa).

The incidence of transmission is similar regardless of whether delivery is by Cesarean section or by vaginal delivery. Newborn infants are usually asymptomatic (without symptoms). Some will eventually develop symptoms, whereas others will not.

Universal vaccination of all newborns whose mothers are HBsAg positive, with both the hepatitis B immune globulin (HBIG) shot and the hepatitis B vaccine within 24 hours of birth is now mandatory (see page xx for a discussion of vaccinations). In fact, universal screening of pregnant women for HBsAg is now standard practice.

This prevents transmission of HBV from the infected mother to the infant approximately 80-90 percent of the time. New mothers are advised to avoid breast-feeding if they are infectious, even though this mode of transmission is not considered very likely. Of course, if the mother has bleeding nipples the risk of transmission increases.

Treatment of pregnant women who have actively infectious chronic hepatitis B should be delayed until after childbirth because the medications used to treat this disease are teratogenic—capable of causing birth defects.

Chronic Hepatitis C and Pregnancy

Women with chronic hepatitis C usually have uneventful pregnancies, provided that the liver disease is stable and the pregnant women has not progressed to decompensated cirrhosis. As a general rule, a stable liver equals a safe pregnancy. Transmission of the hepatitis C virus (HCV) to the newborn is very uncommon, occurring between 4-7 percent of the time.

The likelihood of transmission is increased if the human immunodeficiency virus (HIV)—the virus that causes AIDS, is present. It has been demonstrated that in cases where a women is HIV-positive, aggressively treating the HIV prior to pregnancy greatly reduces the risk of transmitting HCV to the infant.

The risk of transmitting HCV may also be increased by the presence of a high HCV viral loads (for example greater than 2 million viral RNA copies per mL) in the third trimester or at the time of childbirth. However, some studies have shown that transmission of HCV to the newborn does not occur regardless of the mother’s HCV viral load. Invasive procedures such as amniocentesis and the use of fetal-blood monitoring via scalp vein catheter should be avoided as they entail a risk of spreading HCV to the fetus.

A complicated delivery with prolonged rupture of the membranes (greater than 6 hours) has also been associated with an increased risk of transmission to the infant. Some experts believe that delivery by Cesarean section (C- section) may reduce the risk of transmission of HCV to the newborn. However, there is currently not enough evidence of this to warrant routinely recommending C-section over vaginal delivery.

It is not necessary to test infants for the presence of the HCV Ab during their first 18 months of life. Due to passive transfer of this antibody from the mother during childbirth, HCV antibodies will usually be present in the newborn during this time. However, this in no way indicates that the infant has hepatitis C. In fact, in most cases, HCV Ab disappears in infants after six months.

Transmission is determined by a positive HCV Ab in the infant at greater than 18 months of age and/or a detectable HCVRNA level tested after the infant is 2 months of age and confirmed at least twice additionally at intervals of 3 to 4 months apart. HCV can be detected in breast milk (colostrum), however, breast-feeding has not been associated with the transmission of HCV and is considered safe, unless nipples are traumatized, cracked or bleeding.

Infants appear to have a high rate of spontaneous remission of HCV. In one study, up to 75 percent of children cleared HCV spontaneously by two years of age. Thus, it appears that children are more likely to spontaneously clear HCV than adults, however, more data is needed before this conclusion can be definitively be drawn.

Treatment of pregnant women with hepatitis C should be delayed until after they have given birth. This is because ribavirin, a medication used in the treatment of hepatitis C, has been shown to be teratogenic (capable of causing birth defects). Interferon, another medication for hepatitis C, may also be teratogenic.

Autoimmune Hepatitis and Pregnancy

In many cases, severe autoimmune hepatitis causes women to stop menstruating, and as a result, these women cannot become pregnant. However, when treated with corticosteroids and azathioprine, menstrual cycles usually return to normal and pregnancy can be achieved. Women with AIH generally have successful pregnancies and deliveries.

Flare-ups of AIH may occur during pregnancy, although such occurrences are usually rare due to the immunosuppressive effects of pregnancy. In fact, some women have even experienced a remission of AIH during pregnancy. To further minimize the chance of an AIH flare-up, a pregnant woman should remain on therapy during pregnancy. At low dosages, both prednisone and azathioprine have been demonstrated to be safe for use during pregnancy.

However, as a precaution, it is probably wise to discontinue using azathioprine as soon as pregnancy is discovered as some studies have found this medication to be teratogenic. Furthermore, if contemplating pregnancy, one should probably discontinue azathioprine approximately six months before conceiving.

Urodeoxycholic acid and cholestyramine, two other medications often used in the treatment of AIH are considered safe during pregnancy. For women with AIH, there are a few instances in which pregnancy should be delayed at least one year because a poor outcome is likely.

These situations include an AIH flare-up, any liver-related complication, such as variceal bleeding, or the recent withdrawal of prednisone.

Although rare, stillbirths and premature labor have been reported among women with AIH. Conservative management during pregnancy, which should include fluid and sodium restriction and the elimination of all unnecessary medications, enhances the likelihood of a successful outcome for both the mother and her unborn baby.

Alcoholic Liver Disease and Pregnancy

Women with alcoholic liver disease  are often infertile. Women with ALD who do become pregnant and continue to drink alcohol during pregnancy put their infants at high risk for a number of abnormalities. These abnormalities are collectively referred to as the fetal-alcohol syndrome.

Infants suffering from fetal-alcohol syndrome may be born with enlarged, scarred livers and elevated transaminase levels. It thus appears that alcohol intake during pregnancy may cause chronic liver disease in the newborn.

Other abnormalities often found in these newborns include mental retardation, delayed maturity and growth, and defects in the skull, face, and brain. It is extremely important for all women, especially those with ALD, to avoid alcohol during pregnancy.

Primary Biliary Cirrhosis and Pregnancy

Women with primary biliary cirrhosis generally have uneventful pregnancies and deliveries. However, some studies have noted a greater-than-average incidence of stillbirths, spontaneous abortions (miscarriage), and worsening liver function among these women.

These events more commonly occurred in women with advanced liver disease. Pruritus can worsen during pregnancy and may be successfully and safely treated with cholestyramine. On the other hand, pruritus sometimes improves during pregnancy. Ursodeoxy cholic acid, which is used to treat PBC, is generally considered to be safe during pregnancy.

Liver Tumors and Pregnancy

Most liver tumors found in women who are of childbearing age are benign (noncancerous). These tumors include hepatic adenomas, focal nodular hyperplasia, and hemangiomas. They may enlarge and rupture when exposed to high levels of estrogen, which can occur during pregnancy.

Fortunately, such complications during pregnancy are very rare. If rupture does occur, immediate surgery is required, which may put the fetus at risk. Thus, if these tumors are large (greater than 5 cm) and symptomatic, surgical resection should be considered prior to becoming pregnant.

Liver Transplantation and Pregnancy

After liver transplantation, approximately 90 percent of premenopausal women regain menstruation within one year, and menstruation may return as early as 6 weeks from the date of transplant. Thus, despite having undergone a liver transplant, women may become pregnant and can successfully complete their pregnancies.

However, it is advis able that they wait at least one year and preferably at least two years from the time of transplantation before becoming pregnant. Immunosuppressive medications should be continued during pregnancy as there is little risk that they will adversely affect the fetus.

Blood levels of immunosuppressive drugs, especially cyclosporine should be monitored carefully due to potential changes in drug metabolism during pregnancy. In general, there is an increased incidence of premature delivery and low infant birth-weight among women who have undergone liver transplantation.

Women who become pregnant after liver transplantation must be carefully ob served by a liver specialist, as well as by an obstetrician who specializes in high-risk pregnancies. Approximately 70 percent of pregnancies result in live and healthy births. Rarely, liver transplantation needs to be performed during pregnancy.

This usually results in miscarriage.

Liver Diseases That May Develop During Pregnancy

During pregnancy, liver disease can develop in a women who did not have anything wrong with her liver before becoming pregnant The following pages discuss the liver diseases that most commonly occur during pregnancy—viral hepatitis and drug-induced hepatitis—in otherwise healthy women.

Gallstones commonly occur during pregnancy, and women with certain liver diseases (such as PBC) have an increased risk of developing gallstones. Further more, due to the gallbladder’s close proximity to the liver (see Figure 1.1 on page xx), the presence of gallstones often mimics liver disease by causing elevations in LFTs. Therefore, gallstones will also be discussed in this section.

Viral Hepatitis and Pregnancy

When viral hepatitis occurs during pregnancy, it is no different from viral hepatitis as it occurs in nonpregnant women—with the exception of pregnant women infected with the hepatitis E virus (HEV). Viral hepatitis is the most common cause of jaundice occurring during pregnancy. Other causes of jaundice can include medications and gallstones. Read on to learn more about how the different types of viral hepatitis affect pregnancy.

Hepatitis A. Hepatitis A has been reported to occur in approximately 1 out of 1,000 pregnancies. The course of the infection is not affected by pregnancy. Therefore, pregnant women infected with the hepatitis A virus (HAV) do not become any sicker than HAV-infected nonpregnant women.

However, if HAV is contracted during the third trimester, there may be an increased risk of premature labor, although this is uncommon. Transmission of HAV to the newborn may occur, but is rare. HAV, when transmitted from mother to newborn, has not been shown to increase the risk of miscarriage or fetal abnormalities.

In cases where a pregnant woman has been exposed to the hepatitis A virus it is safe for newborns and pregnant women to receive immune globulin injections for hepatitis A as well as the hepatitis A vaccine (see page xx),

Hepatitis B. Acute hepatitis B has been reported to occur in approximately 1- 2 out of every 1,000 pregnancies. The course of the infection is not affected by pregnancy. Transmission of the hepatitis B virus (HBV) to the newborn commonly occurs during childbirth when the baby passes through the birth canal.

This happens approximately 10 to 20 percent of the time, in cases where the mother is HBsAg positive and HBV DNA negative during the third trimester. However, if the mother is both HBeAg and HBV DNA positive during the third trimester, the incidence of transmission increases to over 90 percent.

Newborns infected with HBV usually have no symptoms, although they typically develop either chronic hepatitis B or become chronic carriers of the virus. Therefore, any newborn whose mother is HBsAg positive should receive the hepatitis B immune globulin shot (HBIG) and the hepatitis B vaccination (see page 385).

For women exposed to HBV during pregnancy, the immune globulin shot and the hepatitis B vaccination—both of which have been shown to be safe and effective for pregnant women—should be obtained.

Hepatitis C. It is unknown how often pregnant women contract acute hepatitis C. However, it is believed that the course of infection of hepatitis C is not affected by pregnancy, and that hepatitis C does not adversely affect the outcome of pregnancy.

Therefore, pregnant women who become infected with the hepatitis C virus (HCV) do not become any sicker from this virus than nonpregnant women do.

The risk of transmission of HCV to the newborn is extremely low. However, this risk increases when there is coinfection with HIV. The risk may also increase when there are high viral loads of HCV, although some studies dispute this. However, even for those women, the risk of transmission of HCV to the newborn is estimated to be less than 10 percent.

Unfortunately, there is no protective vaccination available.

Hepatitis D. Acute hepatitis D infects only people who have hepatitis B. Trans mission of the hepatitis delta virus (HDV) to the newborn during pregnancy and/or childbirth is exceedingly uncommon. Delta hepatitis is preventable by administration of the hepatitis B vaccine.

Hepatitis E. Hepatitis E occurs most commonly in Third World countries and is very rare in the United States. This virus has a very severe course in pregnant women. Therefore, pregnant women are advised not to travel to Third World countries.

Hepatitis E results in fulminant hepatitis in approximately 20 percent of pregnant women. In fact, approximately 20 percent of women who acquire this virus during the third trimester of pregnancy die as a result.

Hepatitis E also increases the incidence of fetal complications and fetal death. Currently, here is no antiviral medication for hepatitis E and there is no vaccine available to prevent hepatitis E, – however, one is undergoing testing.

Drug-Induced (Medication-Induced) Liver Disease

If a woman with normal liver function before pregnancy develops liver-related abnormalities during pregnancy, drug-induced liver disease should be suspected. However, drug-induced liver disease is no more common in pregnant women than it is in nonpregnant women.

Medications that are commonly associated with liver abnormalities during pregnancy include the following: the antibiotic erythromycin estolate, the thyroid medication propylthiouracil, the anesthetic halothane, and the antipsychotic medication chlorpromazine.

Pregnant women are advised to use alternatives to these medications whenever possible. (The topic of drug-induced liver disease is discussed in more detail on page xx).

Gallstones

Being of the female gender and pregnancy are both risk factors for the development of gallstones. Thus, gallbladder disease is common during pregnancy. Furthermore, women with certain liver diseases, such as PBC, have an increased risk for the development of gallstones.

The incidence of gallstones ranges from approximately 3 to 12 percent in pregnant women. Its likelihood increases ( within this range) during the second and third trimesters and also increases as the number of times a women has been pregnant increases. Approximately 65 percent of women with gallstones have no symptoms.

In fact, the presence of gallstones is usually discovered during a pelvic sonogram done during a routine evaluation of the pregnancy. In cases where gallstones are asymptomatic, no treatment is necessary. In fact, in 13 to 28 percent of women, gallstones disappear within a year after childbirth.

People who suffer from pain due to gallstones, a condition known as biliary colic, typically have abdominal or right upper quadrant pain radiating to their right shoulders or backs. The pain usually lasts about three hours per episode. The pain often occurs after a meal has been consumed and is sometimes associated with nausea and vomiting.

During pregnancy, symptoms typically worsen as childbirth nears. LFTs are often elevated and may mimic LFT elevations that can occur with hepatitis or with other liver diseases. It is important to keep in mind the frequency with which gallstones can occur during pregnancy. In this way, gallstone-caused LFT elevations will not be erroneously attributed to hepatitis of liver disease.

If gallbladder disease becomes complicated by infection or inflammation of the pancreas (gallstone pancreatitis), surgery is necessary. The surgery will involve removing the entire gallbladder containing the gallstones. It is safest to perform this surgery during either the second trimester or after childbirth.

Gallbladder surgery during the first trimester is associated with spontaneous abortions (miscarriage), whereas gallbladder surgery during the third trimester is associated with premature labor. Removal of the gallbladder and gallstones can be safely performed during pregnancy using a technique known as laparoscopic gallbladder surgery.

This involves the insertion of a laparoscope into the umbilicus to remove the gallbladder. This technique allows the patient to avoid the large incision and long hospital stay required of open gallbladder surgery is avoided.