Noninvasive Biomarkers Show Promise for Risk Stratification in Primary Biliary Cholangitis

Risk stratification scores based on noninvasive laboratory tests offer a safe, cost-effective method for predicting disease progression and the risk for complications in patients with primary biliary cholangitis (PBC), according to a series of studies presented at The Liver Meeting 2025 in Washington, D.C. 

Patients with PBC are at risk for cirrhosis and liver failure, especially in the absence of adequate treatment. While liver biopsy is the gold standard for assessing and staging liver disease, this modality is invasive and carries a risk for complications, particularly hemorrhage. The GLOBE score is a validated risk prediction tool for assessing response to therapy and the risk for disease progression in patients with PBC, with a higher GLOBE score indicating a worse prognosis. The score is calculated using a formula that includes the patient’s age, bilirubin, alkaline phosphatase (ALP), albumin, and platelet count. 

A retrospective study presented in a poster session at The Liver Meeting showed that pretreatment GLOBE scores accurately predicted histological cirrhosis as well as disease prognosis in patients with PBC. The analysis included 183 patients with PBC, with a median age of 58 years, who underwent liver biopsy. In assessing the diagnostic performance of the GLOBE score, the authors found that the pretreatment score significantly increased with histological stage, from 0.25 in patients with Scheuer stage 1 disease to 2.11 in those with Scheuer stage 4 disease. 

The investigators also assessed the association between the pretreatment GLOBE scores and transplant-free survival rates. Patients with a pretreatment GLOBE score < 1.27 had significantly longer transplant-free survival than those with a score of 1.27 or higher. The 10-year cumulative transplant-free survival rate was 94.6% in patients with a pretreatment GLOBE score < 1.27, compared to 45.6% in untreated patients with a score of 1.27 or higher. 

“The pretreatment GLOBE score was significantly associated with baseline histological cirrhosis, and the identified cutoff value [of 1.27] was predictive of prognosis in PBC patients,” the authors concluded. “These findings suggest that the pretreatment GLOBE score may serve as a useful noninvasive test for assessing liver cirrhosis and prognosis in patients with PBC.”

In a separate retrospective analysis of 427 patients diagnosed with PBC at four hospitals in Japan, the researchers assessed the predictive value of elevated serum IgM levels for liver-related events in PBC alongside other clinical and pathological parameters. Liver biopsy results were available in 273 of the included patients. Because the normal values of IgM vary by sex, the authors used the IgM/upper limit of normal (ULN) ratio as a variable. 

The analysis showed that patients with an IgM/ULN ratio ≥1 had a significantly higher incidence of liver-related events than those with an IgM/ULN ratio <1 (18.4% vs. 13.2%) at 10 years. Liver-related events were defined as the occurrence of ascites, gastroesophageal varices, hepatic encephalopathy, and hepatocellular carcinoma. 

“Serum IgM/ULN [ratio] is a simple biomarker predicting liver-related events in PBC, even at early stages,” lead author Taiki Okumura, MD, from the Shinshu University School of Medicine, in Matsumoto, Japan, noted. Okumura and co-authors found that serum IgM levels were independent predictors of liver-related events even in patients with early clinical and histologic stages of disease, staged according to the albumin-bilirubin scoring system and the Nakanuma staging system.