Treatment of primary biliary cholangitis (PBC) with obeticholic acid may reduce gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) levels below the thresholds that predict negative clinical outcomes, according to a recently published study in the medical journal Hepatology.
GGT and ALP are molecules called enzymes that help speed up chemical reactions throughout the body. They can be found in many cells, but especially in the cells that make up the liver. When liver cells get damaged or die, GGT and ALP are released into the bloodstream.
“A recent study from the Global PBC study group has shown that GGT ≥ 3.2×upper limit of normal and ALP ≥ 1.5×upper limit of normal increases the risk of liver transplantation or death in patients with PBC; GGT also increases the prognostic value of ALP,” the researchers wrote.
Obeticholic acid is a potent medication used in the treatment of PBC. It received accelerated approval from the US Food and Drug Administration (FDA) in 2016 based on positive results of the POISE study.
Read more about PBC prognosis
In order to analyze the effect of obeticholic acid on the levels of GGT and ALP, the researchers performed a sub-analysis of the POISE study. In this study, patients with PBC were randomly assigned to groups receiving either obeticholic acid or placebo for 12 months.
During the study, neither the doctors nor patients knew who was receiving the experimental drug. After the 12-month study period, participants kept receiving obeticholic acid for another five years. The results demonstrated the high efficacy and safety of the drug. The level of GGT lower than the 3.2×upper limit of normal and the ALP level lower than the 1.5×upper limit of normal was considered a positive treatment response.
According to the sub-analysis, the proportion of patients treated with obeticholic acid who responded well to treatment significantly increased over time compared with those treated with placebo. Patients who received the highest dose of obeticholic acid, 10 mg, showed the highest reduction in their GGT and ALP levels.
Among those who received five to 10 mg of obeticholic acid, 17% had a meaningful decrease in the level of biomarkers after nine and 12 months of treatment. In the group treated with 10 mg of obeticholic acid, the highest number of responders was observed after nine months (32%), followed by 12 months (26%).
One patient treated with placebo had a notable decrease in GGT and ALP levels after six and nine months of treatment. In the five-year extension period, the proportion of patients who responded to obeticholic acid treatment increased from 16% (after three months) to 38% (after 51 months of extension). At 60 months of the extension period, the rate of responders was 37%.
