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Wednesday, January 23, 2008

Liver Diseases & Pregnancy

During pregnancy, there are significant normal physiologic changes in liver function studies. These include:

1. A decrease in both the total protein as well albumin.
2. An elevation of the liver dependent clotting factors such as fibrinogen.
3. In addition, there are elevations in the transport proteins produced in the liver such as
ceruloplasmin, transferrin, and sex steroid binding globulin.
4. The alkaline phosphatase will be elevated 2 - 4 times normal.
5. Of note is the fact that the transaminase levels should remain normal during pregnancy. This
has tremendous importance when evaluating the possibility of liver disease in pregnancy.
6. In addition, the bilirubin should stay normal.

However, there are also certain liver conditions that may cause complications in pregnancy. These include:

Hepatitis

The most common liver disease encountered during pregnancy is that of hepatitis. This is no different than in the non - pregnant individual. In some areas around the world such as India, it remains the most common cause of maternal death during pregnancy. It has also been appreciated that the finding of a mother who is a carrier for hepatitis places her foetus at risk in later life of developing both chronic hepatitis and cancer of the liver. It has become accepted clinical practice to screen all patients with a hepatitis surface antigen as a part of their regular parental laboratory work. The diagnosis, evaluation and treatment of hepatitis during pregnancy is no different than in non - pregnant individual.

Cholestatis of Pregnancy
Cholestatis of pregnancy is a condition of unknown cause. It usually arises late in the third trimester of pregnancy. The primary symptom associated with it is extreme itchiness. There may also be mild jaundice (yellowing of the skin due to excess bilirubin). The laboratory evaluation in such patients reveals tremendous increase in alkaline phosphatase to 7-10 times above normal. If the serum bile acids were assayed, it would be found that they are between 10 and 100 times normal. It is this extreme evaluation of bile acids, which is felt to cause the generalized purities. Liver biopsies which have been performed in such patients show simple biliary status without disruption of the hepatocellular architecture.

These changes are completely reversible and return to normal after the pregnancy ends. Cholestatis of pregnancy has no adverse effect on pregnancy and the cure of the problem is the delivery of the foetus, attempts at using ion exchange resins such as cholestyramine to try to lower the serum bile acids have been uniformly unsuccessful due to the tremendous elevation in these bile acids.

Acute Fatty Liver of Pregnancy
A more serious liver disease encountered during pregnancy is that of acute fatty liver. This too, is a condition of unknown cause. It is an extremely rare condition affecting less than 1 in 10,000 patients.

The symptoms are that of a rather sudden onset in the last four weeks of pregnancy of rapidly deepening jaundice, somnolence, and in short order, coma, bleeding dyathosis, and hepatorenal failure. The usual time course form onset of symptoms to hepatorenal failure is approximately 2 weeks. The maternal mortality rate from acute fatty liver of pregnancy approaches 30%. Some similarities to this condition with Reye's syndrome have been suggested. However, there is enough variation in the symptoms and the pathology that such an association is suspect.

The diagnosis of acute fatty liver of pregnancy is usually made upon liver biopsy. The biopsy shows an intense infiltration of all the hepatocytes by fat with a marked disruption of the hepatic architecture. The liver transaminase will be markedly elevated. The alkaline phosphatase will be slightly elevated. The bilirubin is significantly elevated.

It has been recognized as of late that the rapid delivery of the baby will improve the maternal mortality. It has been this understanding which has lead to the improvement in the survival rates from such a condition. There is one case in the literature where, despite the delivery of the baby, it was felt that the disease process had not been reversed and the patient underwent successful liver transplant. There are several cases reported where patients who have survived acute fatty liver of pregnancy have subsequently had an uneventful pregnancy. It has been suggested that there is no increased risk of recurrence. However, the number of such patients is small and it seems premature to advise the margin of safety in subsequent pregnancies.

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