The UK‐PBC risk scores: Derivation and validation of a scoring system for long‐term prediction of end‐stage liver disease in primary biliary cholangitis

Abstract

; and the members of the UK-PBC Consortium*The biochemical response to ursodeoxycholic acid (UDCA)-so-called "treatment response"-strongly predicts long-term outcome in primary biliary cholangitis (PBC). Several long-term prognostic models based solely on the treatment response have been developed that are widely used to risk stratify PBC patients and guide their management. However, they do not take other prognostic variables into account, such as the stage of the liver disease. We sought to improve existing long-term prognostic models of PBC using data from the UK-PBC Research Cohort. We performed Cox's proportional hazards regression analysis of diverse explanatory variables in a derivation cohort of 1,916 UDCA-treated participants. We used nonautomatic backward selection to derive the best-fitting Cox model, from which we derived a multivariable fractional polynomial model. We combined linear predictors and baseline survivor functions in equations to score the risk of a liver transplant or liver-related death occurring within 5, 10, or 15 years. We validated these risk scores in an independent cohort of 1,249 UDCA-treated participants. The best-fitting model consisted of the baseline albumin and platelet count, as well as the bilirubin, transaminases, and alkaline phosphatase, after 12 months of UDCA. In the validation cohort, the 5-, 10-, and 15-year risk scores were highly accurate (areas under the curve: >0.90). Conclusions: The prognosis of PBC patients can be accurately evaluated using the UK-PBC risk scores. They may be used to identify high-risk patients for closer monitoring and second-line therapies, as well as low-risk patients who could potentially be followed up in primary care. (HEPATOLOGY 2016;63:930-950) SEE EDITORIAL ON PAGE 697 P rimary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the intrahepatic bile ducts results in cholestasis and progressive fibrosis.(1) Biliary injury may eventually lead to cirrhosis and liver failure-but the rate of disease progression is variable.(2) Across the spectrum, some patients with PBC progress to end-stage liver disease (ESLD) within a few years of diagnosis; some develop cirrhosis that remains well compensated; others (perhaps the majority) do not even develop cirrhosis. In PBC, as in other conditions, accurate prognostication enables management of the disease to be tailored to the patient. This is the basis of precision medicine-and it has clear benefits: patients at higherAbbreviations: AIH, autoimmune hepatitis; ALP, alkaline phosphatase; ALP12, alkaline phosphatase after 12 months of UDCA; AMA, anti-mitochondrial antibody; ANA, anti-nuclear antibodies; ALT, alanine aminotransferase; ALT12, ALT after 12 months of UDCA; AST, aspartate transaminase; AST12, AST after 12 months of UDCA; AUC, area under receiver operating characteristic curve; BIL, bilirubin; BIL12, bilirubin after 12 months of UDCA; CI, confidence interval; CRFs, case record forms; EASL, European Association for the Study of Liver; ESLD, end-stag...

External validation of the United Kingdom‐primary biliary cholangitis risk scores of patients with primary biliary cholangitis treated with ursodeoxycholic acid

“…The UK‐PBC risk scores were calculated using an approach consistent with the original UK‐PBC manuscript (personal communication with Dr. M. Carbone, Department of Health Sciences, School of Medicine and Surgery, University of Milano, Italy, marco.carbone@unimib.it.). Outcomes were defined using the same criteria as those defined in the derivation of the UK‐PBC risk scores4: death from a liver‐related cause (i.e., liver failure, variceal hemorrhage, or hepatocellular carcinoma), liver transplant or serum bilirubin >5.8 mg/dL. For patients with multiple events, only the first to occur was included in the analysis.…”

“…The advent of ursodeoxycholic acid (UDCA) as a treatment for PBC led to development of different binary response criteria (e.g., Barcelona, Paris I, Rotterdam, Paris II, Toronto),3 all predicated on responses after 1 to 2 years of UDCA treatment. More recently, the aspartate aminotransferase to platelet ratio was developed to predict outcome independent of UDCA, and continuous prognostic risk scores were developed by the Global PBC group (GLOBE score) and the United Kingdom‐PBC group (UK‐PBC risk scores) 4, 5. The UK‐PBC risk scores predict the probability of death, liver transplant, or severe hyperbilirubinemia (e.g., bilirubin >5.8 mg/dL) at 5, 10, and 15 years following 1 year of UDCA treatment 4.…”

“…More recently, the aspartate aminotransferase to platelet ratio was developed to predict outcome independent of UDCA, and continuous prognostic risk scores were developed by the Global PBC group (GLOBE score) and the United Kingdom‐PBC group (UK‐PBC risk scores) 4, 5. The UK‐PBC risk scores predict the probability of death, liver transplant, or severe hyperbilirubinemia (e.g., bilirubin >5.8 mg/dL) at 5, 10, and 15 years following 1 year of UDCA treatment 4. These 5‐, 10‐, and 15‐year UK‐PBC risk scores were derived (n = 1,916) and validated (n = 1,249) from patient data collected from a research network of 155 centers across the United Kingdom 4…”

Clinical application of the GLOBE and United Kingdom‐primary biliary cholangitis risk scores in a trial cohort of patients with primary biliary cholangitis

“…They estimate the risk of LT or death (overall death for the GLOBE score and liver‐related death for the UK‐PBC risk score) in patients with PBC at specific time points. Both scores outperformed previous response criteria7, 8, 9, 10, 11, 13, 14 in terms of prognostic utility and could potentially help physicians identify patients at high risk of disease progression and in need of second‐line therapy. They have also been validated in patients not treated with UDCA, strongly suggesting that such scoring systems reflect disease activity and stage expressed by the laboratory investigations, regardless of treatment.…”

“…Two independent research groups, the Global PBC Study Group and the United Kingdom (UK)‐PBC Consortium, developed and externally validated continuous prognostic models (the GLOBE score and UK‐PBC risk score, respectively) that address these limitations 13, 14. These models include the liver biochemistry following treatment with UDCA as well as surrogate measurements of disease stage (e.g., serum albumin and platelet count).…”