Routine blood tests may help diagnose liver disease in pregnancy: Study

Noninvasive scores for liver scarring seen to help detect ICP earlier

Written by Michela Luciano, PhD |

A dropper squirting blood is shown next to four half-filled vials.

Noninvasive scores originally developed to assess liver scarring may help diagnose pregnant women who have intrahepatic cholestasis of pregnancy (ICP), the most common pregnancy-specific liver disease, a new study shows.

Researchers found that three blood test-based scores — the aminotransferase-to-platelet ratio index (APRI), Fibrosis-4 (FIB-4), and Fibrosis-5 (FIB-5) — were elevated in women with ICP relative to those without the condition, which can increase the risk of complications for both mothers and their unborn babies.

Further analysis showed that APRI, and to a lesser extent FIB-5, performed comparably to traditional liver enzyme tests in distinguishing women with ICP from those without the condition.

“These indices may provide clinicians with additional information when evaluating [liver] dysfunction” in ICP and “could support early recognition and structured clinical monitoring in clinical practice,” the researchers wrote. The team added that further testing of these potential markers “are warranted to further validate their clinical utility.”

The study, “Diagnostic utility of APRI, FIB-4, and FIB-5 in intrahepatic cholestasis of pregnancy: A retrospective case-control study,” was published in the journal Gynecology & Obstretrics.

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Cholestasis occurs when bile, a digestive fluid produced by the liver, does not flow properly into the intestines. This causes bile acids, the main component of bile, to build up in the liver, which can damage the organ, and also leak into the bloodstream, leading to symptoms such as intense itching.

ICP is a form of cholestasis that develops during pregnancy, usually in the second or third trimester.

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While ICP typically resolves after childbirth, it can lead to complications such as preterm birth, meaning the baby is delivered before 37 weeks of pregnancy. Women with ICP are more likely to have gestational diabetes and preeclampsia, marked by sudden high blood pressure and organ dysfunction, and their babies may have low birth weights and signs of reduced oxygen blood levels, according to a previous study.

Diagnosis mainly relies on measuring bile acids in the blood, given that direct assessments of liver damage would require a biopsy, an invasive procedure not suitable during pregnancy.

As a result, noninvasive markers of ICP have been developed, but the condition is still sometimes underdiagnosed or diagnosed late. This has prompted interest in finding better tools to assess liver function and predict liver damage.

APRI, FIB-4, and FIB-5 are noninvasive scores based on routine blood tests that combine different measures of liver function into a single value to assess liver health.

The APRI score considers levels of aspartate aminotransferase (AST), a liver enzyme, and the number of platelets, the cell fragments that help the blood clot. The FIB-4 score is calculated through a formula that includes age, platelet counts, and levels of AST and alanine aminotransferase (ALT), another liver enzyme. The FIB-5 score involves a formula based on platelet counts, AST and ALT levels, and levels of albumin, a protein produced in the liver.

Although originally developed to evaluate liver scarring, or fibrosis, in chronic liver diseases, these three scores may also reflect liver stress and dysfunction, the researchers noted.

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2 scores found to best distinguish women with, without ICP

To investigate their diagnostic potential in ICP, a team of researchers in Turkey retrospectively analyzed data from 217 pregnant women who delivered their babies at a single center in Istanbul between September 2018 and February 2024. Of these, 105 were diagnosed with ICP and 112 had uncomplicated pregnancies and served as controls.

The two groups were similar in age (mean 29.1 vs. 30.4). However, preterm birth was significantly more frequent in the ICP group (48.6% vs. 32.1%), as was the need for the baby to be admitted to the neonatal intensive care unit, typically called the NICU (29.5% vs 3.6%).

Women with ICP also had significantly higher blood levels of AST and ALT, indicating liver injury. Blood albumin levels were significantly lower in the ICP group, suggesting impaired production by the liver.

APRI, FIB-4, and FIB-5 were also significantly higher in women with ICP, further supporting the presence of liver damage, the data showed.

Diagnostic potential was assessed with a statistical tool called area under the curve (AUC), with scores ranging from zero to one; the higher the AUC value, the better the ability to discriminate people with a given disease from those without.

Levels of ALT and AST showed each the strongest ability to distinguish women with ICP from those without the condition, with AUC values of 0.95 and 0.93, respectively, according to the researcehrs. APRI performed nearly as well, demonstrating similarly high diagnostic potential (AUC of 0.90).

FIB-5 showed moderate discriminative potential (AUC of 0.72), while FIB-4 performed poorly (AUC of 0.59), suggesting limited usefulness as a standalone diagnostic marker, the team.

Overall, this study showed that using these scores may help in detecting potential liver disease in pregnant women, the researchers noted.

“These findings support the utility of non-invasive fibrosis markers — particularly APRI and FIB- 5 — as adjunctive tools in identifying ICP,” the team wrote. “Their performance is comparable to classical [liver] enzymes, and they may serve as surrogate markers when bile acid testing is unavailable.”