Optimising risk stratification in primary biliary cirrhosis: AST/platelet ratio index predicts outcome independent of ursodeoxycholic acid response

Trivedi, Palak; Bruns, Tony; Cheung, Angela; Li, Ka-Kit; Kittler, Clemens; Kumagi, Teru; Shah, Husnain; Corbett, Christopher; Al-Harthy, Nadya; Acarsu, U.; Coltescu, Catalina; Tripathi, Dhiraj; Stallmach, Andreas; Neuberger, James; Janssen, Harry L.A.; Hirschfield, Gideon M.

doi:10.1016/j.jhep.2014.01.029

Cited by 120 publications

(124 citation statements)

References 20 publications

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“…In PBC patients without AIH features, the risk factors were consistent with published studies [34,41,42], but IgG levels were not considered as risk factors, unlike another study in Chinese patients [43]. For those patients with AIH features, the predictive role of AST was unexpected.…”

Section: Discussionsupporting

confidence: 73%

The Natural History and Prognosis of Primary Biliary Cirrhosis with Clinical Features of Autoimmune Hepatitis

Yang

Wang

et al. 2015

Clinic Rev Allerg Immunol

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Although a variant of primary biliary cirrhosis (PBC) characterized by features of autoimmune hepatitis (AIH) has been recognized for many years, few studies with ample numbers of patients have focused on its natural history. This study aimed to clarify the natural history, prognosis, and response to therapy in a cohort of patients with PBC with AIH features. We retrospectively analyzed 277 PBC patients without AIH features and 46 PBC patients with AIH features seen between September 2004 and April 2014. The 5-year adverse outcome-free survival of PBC patients with AIH features was 58% compared to 81% in PBC patients without AIH features. Multivariate analysis in the patients with AIH features indicated that total bilirubin ≥ 2.70× the upper limit of normal predicted a poor prognosis (p = 0.008, relative risk 8.39, 95% confidence interval (CI) 1.73, 40.73). Combination therapy with ursodeoxycholic acid (UDCA) and immunosuppression provided better short-term responses in PBC patients with AIH features, defined by multiple criteria. Higher aspartate aminotransferase (AST) level at accession suggested better prognosis for PBC patients with AIH features while worse prognosis for PBC patients without AIH features. PBC patients with AIH features differ from those without AIH features in terms of natural history, prognostic indicators, and response to therapy.

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Section: Discussionsupporting

confidence: 73%

The Natural History and Prognosis of Primary Biliary Cirrhosis with Clinical Features of Autoimmune Hepatitis

Yang

Wang

et al. 2015

Clinic Rev Allerg Immunol

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“…However, we identified a subgroup of participants for whom the current weight-adjusted dose of UDCA was available (n 5 1,253). In this subgroup, the median dose of UDCA was 12 mg/kg/day (interquartile range [IQR]: [9][10][11][12][13][14]. This is lower than the recommended dose of UDCA (13-15 mg/kg/day), albeit comparable to the median dose reported by Lammers et al (13) in their study of 4,845 PBC patients from leading academic centers across the globe.…”

Section: Explanatory Variablesmentioning

confidence: 54%

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

et al. 2015

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; 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...

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“…Treatment benefit is best highlighted by applying biochemical stratification to therapy,3 5–9 and up to two-thirds of patients have an improved transplant-free/overall survival in this regard. However, there is a paucity of data with regard to biochemical response and modification of cancer risk in PBC 10 11.…”

Section: Introductionmentioning

confidence: 99%

Stratification of hepatocellular carcinoma risk in primary biliary cirrhosis: a multicentre international study

Trivedi

Lammers

Buuren

et al. 2015

Gut

148

106

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Optimising risk stratification in primary biliary cirrhosis: AST/platelet ratio index predicts outcome independent of ursodeoxycholic acid response

Cited by 120 publications

References 20 publications

The Natural History and Prognosis of Primary Biliary Cirrhosis with Clinical Features of Autoimmune Hepatitis

The Natural History and Prognosis of Primary Biliary Cirrhosis with Clinical Features of Autoimmune Hepatitis

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

Stratification of hepatocellular carcinoma risk in primary biliary cirrhosis: a multicentre international study

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