Due to the chronic progressive disease characteristics of primary biliary cholangitis (PBC), patients with advanced PBC should not be ignored. Most prognostic score studies have focused on early stage PBC.

To compare the prognostic value of various risk scores in advanced PBC to help PBC patients obtain more monitoring and assessment.

This study considered patients diagnosed with PBC during hospitalization between 2015 and 2021. The clinical stage was primarily middle and late, and patients usually took ursodeoxycholic acid (UDCA) after diagnosis. The discriminatory performance of the scores was assessed with concordance statistics at baseline and after 1 year of UDCA treatment. Telephone follow-up was conducted to analyze the course and disease-associated outcomes. The follow-up deadline was December 31, 2021. We compared the risk score indexes between those patients who reached a composite end point of death or liver transplantation (LT) and those who remained alive at the deadline. The combined performance of prognostic scores in estimating the risk of death or LT after 1 year of UDCA treatment was assessed using Cox regression analyses. Predictive accuracy was evaluated by comparing predicted and actual survival through Kaplan-Meier analyses.

We included 397 patients who were first diagnosed with PBC during hospitalization and received UDCA treatment; most disease stages were advanced. After an average of 6.4 ± 1.4 years of follow-up, 82 patients had died, and 4 patients had undergone LT. After receiving UDCA treatment for 1 year, the score with the best discrimination performance was the Mayo, with a concordance statistic of 0.740 (95% confidence interval: 0.690-0.791). The albumin-bilirubin, GLOBE, and Mayo scores tended to overestimate transplant-free survival. Comparing 7 years of calibration results showed that the Mayo score was the best model.

The Mayo, GLOBE, UK-PBC, and ALBI scores demonstrated comparable discriminating performance for advanced stage PBC. The Mayo score showed optimal discriminatory performance and excellent predictive accuracy.

Primary biliary cholangitis (PBC) is a chronic progressive liver disease that causes the gradual destruction of the intrahepatic small bile ducts[1]. Preclinical PBC may present with specific diagnostic antibodies (anti-mitochondrial antibody, AMA) but remain asymptomatic with normal liver function for over a decade. Approximately 50%-60% are asymptomatic at diagnosis[2]. Ursodeoxycholic acid (UDCA) is the first-line treatment. It increases long-term survival. However, approximately 40% of patients with PBC have incomplete responses, and these patients progress rapidly to the middle and late stages of disease after early diagnosis and treatment[3]. Because of the chronic progressive disease characteristics, PBC patients in the middle and late stages should not be ignored.

Over the past 20 years, several risk-scoring models for PBC have been proposed as tools to estimate the risk of adverse outcomes and to guide management[4]. The most influential scores are GLOBE and UK-PBC, developed for early PBC patients. Recent studies reported that these scores accurately predict outcomes in patients treated with UDCA treatment at various disease stages[5-7]. However, their application to middle and late stage PBC patients remains to be studied. The Mayo score was developed to determine the timing of liver transplantation (LT) in PBC and is now a model for predicting PBC survival[8-10]. The aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) are non-invasive fibrosis scores based on biochemical indicators[11]. All parameters, including aminotransferase, platelets, and age, are associated with PBC outcomes[12,13]. The albumin-bilirubin (ALBI) score was initially developed to assess liver function in hepatocellular carcinoma patients[14]. The total bilirubin (TBil) and albumin in the score are associated with PBC progression, and some studies have used them to predict PBC outcomes[15,16]. There are few studies on the efficacy and differences of the various prognostic scoring systems in PBC patients, especially in patients in advanced stages[17-19].

Some patients with decompensated cirrhosis return to a clinical state consistent with compensated cirrhosis when they undergo appropriate etiological and symptomatic supportive treatment, named the “recompensation phenomenon”[20]. Portal hypertension and systemic inflammation can lead to the progression of decompensated cirrhosis. Recently, studies have been performed on the mechanism and clinical feasibility of reversing decompensation and recompensation in cirrhosis[21-23]. These findings led to updating the stage evaluation concept and an outcomes estimate system for decompensated cirrhosis.

The present study enrolled patients diagnosed with PBC during hospitalization whose disease stages were in the middle and late stages. We compared the effectiveness and differences of various prognostic scoring systems to optimize monitoring, disease evaluation, and timely treatment for advanced stage PBC.

We assessed the PBC-specific scores GLOBE, UK-PBC, and Mayo and compared the ALBI, APRI, and FIB-4 scores. These analyses revealed that the ALBI and Mayo scores showed adequate discriminatory performance and good predictive accuracy at baseline. The Mayo score demonstrated superior discriminatory performance and calibration singly and combined with other risk models, suggesting that this score is the best risk prediction model for predicting liver-related death or LT in PBC patients in the advanced stage. These findings also suggested that the performance of the PBC-specific risk scores was superior to other prognostic scores for advanced PBC.

Models with a C-statistic value greater than 0.7 are considered good prognostic models. The Mayo score was the only model consistently reaching this threshold at baseline and 1 year of UDCA treatment. The C-statistic of the Mayo score was greater after patients received UDCA for 1 year, suggesting an increase in discriminatory performance with prolonged UDCA treatment. The next most effective predictive models were the GLOBE, UK-PBC, and ALBI scores, with no significant differences in predicting liver-related death or LT following UDCA treatment for 1 year.

The Mayo score exhibited consistently better discriminative performance than other scores in this PBC patient cohort. The Mayo score is a traditional risk prediction model developed for PBC patients, primarily developed to evaluate untreated PBC patients. However, this study enrolled patients that had undergone UDCA treatment and were in an advanced stage. The Mayo score has previously been linked to transplant-free survival among patients that underwent UDCA treatment, enabling their stratification into low- and high-risk groups based on the original thresholds[29,30]. However, the reliance of this scoring model on ascites, which can be subjective, may limit its clinical applicability.

In this study, the parameter was derived from the results of imaging examinations during hospitalization, and this examination is a routine item of these hospitalized patients. Therefore, the judgment of the parameter of ascites was relatively objective. In theory, the superior discriminatory performance of the Mayo score may be promoted by ascites and prothrombin time, which are the most relevant parameters in late stage PBC; other parameters are TBil and ALB, which also are indicators of significant changes in patients with more advanced stages. Based on these characteristics, the Mayo score may be more applicable for prognosis assessment in advanced stage PBC patients. Our study verified this point, but the actual evidence remains to be further verified in a large population or more studies.

The discriminatory performance of the GLOBE, UK-PBC, and ALBI scores is secondary to the Mayo score. Both the UK-PBC and GLOBE scores were developed as PBC-specific scoring systems and have previously been applied to evaluate the prognosis of early PBC patients. Our cohort was mainly late stage patients, and the results were inferior to the Mayo score. The ALBI score is calculated using two indicators (TBil, ALB), which are validated biomarkers associated with PBC disease progression[31-33]. APRI and FIB-4 scores had inferior discriminatory performance in this study, while the two were liver fibrosis scores based on biochemical indicators. However, this study’s poor performance may be because most patients had cirrhosis without significant differences in the progression of liver fibrosis, which is not applicable to predicting advanced PBC patients.

The different combinations of prognostic models were evaluated for their ability to predict death or LT. The study results showed that GLOBE and UK-PBC were relatively stable, with little change in the C-statistic when other scores were added. Moreover, the univariate and multivariate Cox regression analyses of all predictive models also support this point. The highest C-statistic value increases were observed when the Mayo scores were combined with the other scores. The results demonstrated that the GLOBE and UK-PBC score models have good stability and are applicable for prognosis assessment exclusively. While the APRI and FIB-4 scores were applied to combine with other scores, the best discriminatory performance was combined with the Mayo score.

We chose the ALBI, GLOBE, and Mayo sores for model calibration, which had superior discriminatory performance after UDCA therapy for 1 year, while the UK-PBC model was omitted because it predicts liver-related death and not transplant-free survival[28]. These scores all tended to overestimate the transplant-free survival rate, with better calibration at 1-3 years. The deviation tended to increase yearly after 3 years. In the 1-7-year interval, the deviation of the GLOBE score was the greatest, and the Mayo score was the most minor. In contrast, the best model calibration was the Mayo score. These findings suggested that the Mayo score has the best prediction performance and accuracy for advanced PBC patients.

This study has several limitations. First, we did not have a large study cohort, and the comparison of prognostic scores was calculated at baseline and 1 year later. This limitation indicates the need for verification using large sample sizes and prospective studies. Second, this was a retrospective analysis; some of the included data were missing. We applied predictive mean matching to interpolate the missing values. Third, while the UK-PBC risk score was developed to predict liver-related death and not transplant-free survival (unlike the other score models), the same analyses used the endpoints and indicated similar discriminatory performance. Despite the limitations, the study is significant because of the lack of the comparison of prognostic scores in advanced PBC patients.

The Mayo, GLOBE, UK-PBC, and ALBI scores had excellent prediction performance for death and LT. Mayo scores had the best prediction efficacy in discriminating performance and predicting outcomes. The significance of this study was that it enables advanced PBC patients to be monitored and assessed closely in clinical practice to delay PBC progression.