Intrahepatic cholestasis during pregnancy associated with later liver disease

Association should be further studied to determine cause

A retrospective case-control study of 21,008 women in Finland has found that those with intrahepatic cholestasis of pregnancy (ICP), an itchy skin condition when bile gets backed up in the liver, are significantly more likely to suffer other liver diseases later in life. The study is published in the April 2006 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). Published on behalf of the society by John Wiley & Sons, Inc., the journal is available via Wiley InterScience at http://www.interscience.wiley.com/journal/hepatology.

ICP occurs in one percent of pregnancies, causing intense skin itching and elevated levels of liver enzymes and bile acids. It resolves spontaneously after delivery, but can recur in later pregnancies. The cause of ICP is unknown, though it often runs in families. One theory holds that ICP is caused by the liver's insufficient capacity to metabolize the high amounts of placenta-derived sex steroids during pregnancy.

Because no previous longitudinal studies have assessed subsequent risk of liver and biliary diseases in ICP patients, researchers led by Anne Ropponen, M.D. of the Department of Obstetrics and Gynecology at Helsinki University Central Hospital, designed a cohort study using cases recorded in the Finnish Hospital Discharge Register between 1972 and 2000.

The researchers included 10,504 women with a history of ICP and matched them to controls without ICP based on age at, site of, and time of delivery. They studied a total of 21,008 women, and collected information on their subsequent hospitalizations. Women who had ICP were more likely than the controls to be hospitalized during the study time frame. The researchers noted hospitalizations due to liver diseases and calculated rates, rate ratios and confidence intervals for both ICP cases and controls.

The researchers found statistically significant differences in the incidence of several liver and biliary diseases. Women who had ICP were significantly more likely to later be diagnosed with hepatitis C, non-alcoholic cirrhosis, gallstones, cholecystitis and non-alcoholic pancreatitis. The risk for miscellaneous liver disorders was also higher in women who had ICP, although their risk for alcohol-related liver disorders was not.

Limitations of this study include the use of register data, although the Finnish Hospital Discharge Register includes virtually all inpatient hospital care records, and diagnoses have been shown to be consistent with medical records. Still, disease occurrences that did not lead to inpatient care would not be in the register.

"After all the conservative analyses performed in this study, we conclude that there is an association between ICP and several liver and biliary diseases," the authors report. "The results suggest that in a subgroup of patients, ICP may not only be the self-limiting, spontaneously resolving condition that it has been thought to be, but also an indicator of subsequent, often more serious diseases. To resolve the cause of association we have identified, further studies are clearly indicated."

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Article: "Intrahepatic Cholestasis of Pregnancy as an Indicator of Liver and Biliary Diseases: a Population-Based Study," Anne Ropponen, Reijo Sund, Seija Riikonen, Olavi Ylikorkala, and Kristiina Aittomäki, Hepatology; April 2006 (DOI: 10.1002/hep.21111).


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