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The impact of chronic liver disease on the endo- crine system has been of great interest to both endocrinologists and hepatologists, as multiple abnormalities in sex hormone metabolism have been reported. In addition, a number of clinical manifestation of liver disease have been reported to be the result of these, including amenorrhoea, impotency, gynaecomastia, and spider angiomata
There is probably no greater demand on the female endocrine system than the establishment and maintenance of pregnancy. In this regard, the disease autoimmune hepatitis is of particular interest as it predominantly impacts women, and at a relatively younger age, compared with many other forms of chronic liver disease. In addition, these patients often have cirrhosis by the time a diagnosis is made.
The majority of patients respond well to immunosuppressive drugs but most women with autoimmune hepatitis require maintenance immunosuppression for a sustained benefit. It has long been believed that women with autoimmune hepatitis have difficulty conceiving and maintaining pregnancy. Moreover, it has been reported previously that obstetric outcomes can be poor, with a relatively high incidence of toxaemia, premature delivery, and low birth weight.
In this issue of Gut, Heneghan and colleagues1 from the Institute of Liver Studies at King's College Hospital report the outcomes of 35 pregnancies in 18 women with autoimmune hepatitis (see page 97). This currently represents the largest reported series of pregnancies in women with autoimmune hepatitis. The report represents all known pregnancies in the autoimmune hepatitis population at King's College over a 15 year period.
The study is important in that it debunks the myth that pregnancy rarely occurs in women with autoimmune hepatitis or that there is a marked increase in the risk of fetal loss. From these 35 pregnancies, there were 31 live births. More than one third of patients had a diagnosis of cirrhosis that was made prior to conception. Two patients experienced, what has been previously reported, autoimmune hepatitis beginning during pregnancy. There were flares in disease activity in four pregnancies, and in another four patients within three months of delivery. The one disturbing fact was that there were two deaths, one of which occurred during pregnancy and one shortly after pregnancy.
The immunosuppressive agents used to control autoimmune hepatitis, azathioprine and corticosteroids, have been associated with concerns about potential birth defects. However, only two of 31 children developed birth defects that might be attributable to autoimmune hepatitis or its treatment. One child was delivered prematurely and had severe disabilities, which likely reflected the premature delivery. Another child had Perthe's disease.
Women with autoimmune hepatitis of childbearing age and physicians who care for them must interpret this study as good news. I suspect there has been a longstanding admonition to these women that they should avoid pregnancy based on previously reported studies. Clearly, this study demonstrates that women with autoimmune hepatitis can become pregnant and can carry successful pregnancies to term with the expectation of delivering a normal baby.
There are however several caveats. Firstly, their disease needs to be monitored closely during this period because of the possibility of flare during pregnancy. Secondly, those with cirrhosis may experience complications of portal hypertension, such as variceal bleeding. Again, this needs to be monitored closely. Finally, it goes without saying that such patients need to be managed by physicians with real expertise in managing this disease. The group at King's College has extensive experience with this disease, and whether their excellent results will be obtained in the greater community at large remains to be determined. None the less, there are many liver centres throughout the world that are more than adequately equipped to manage these challenging patients. It is clear that these patients should be maintained during their pregnancy on immunosuppressive drugs at the lowest dose possible to maintain remission. Hence in addition to expert obstetrical management, our young female patients with autoimmune hepatitis can be expected to have families. This is truly important to young women with this disease who, with current therapies, can have longstanding periods of remission and a favourable natural history. Moreover, even for those women who fail therapy, liver transplantation is now an excellent alternative, such that these women should fully expect to not only raise their own families but see their children raise families as well.
See article on page 97
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