Reply to: “AST/platelet ratio index associates with progression to hepatic failure and correlates with histological fibrosis stage in Japanese patients with primary biliary cirrhosis”
Authors: Palak J. Trivedi, Tony Bruns, Ka-Kit Li, Gideon M. Hirschfield
Journal: Journal of Hepatology (2014)

We read with interest the letter by Joshita and colleagues regarding our original article [[1]Trivedi P.J. Bruns T. Cheung A. Li K.-K. Kittler C. Kumagi T. et al.Optimising risk stratification in primary biliary cirrhosis: AST/platelet ratio index predicts outcome independent of ursodeoxycholic acid response.J Hepatol. 2014; 60: 1249-1258Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar]. In taking the time to present their important Japanese data [[2]Joshita S. Umemura T. Ota M. Tanaka E. AST/platelet ratio index associates with progression to hepatic failure and correlates with histological fibrosis stage in Japanese patients with primary biliary cirrhosis.J Hepatol. 2014; 61: 1443-1445Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar], the authors provide further independent validation of the AST/platelet ratio (APRI) in the risk stratification of patients with primary biliary cirrhosis (PBC). As the authors surmise, the demography of our cohorts was varied but was not representative of all populations globally, and the robustness of any observation – even if simple and low cost as in this case – is in validation more so than in discovery. PBC is not a benign, homogeneous autoimmune liver disease; and although present disease nomenclature needs improvement, the current sole therapy – ursodeoxycholic acid (UDCA) – still leaves a substantial cohort of individuals at risk from life-threatening progressive disease and impaired quality of life. Risk stratification is therefore of value to identify individuals with PBC who will benefit from new treatments and as illustrated herein, APRI at baseline or reapplied 1-year following therapy (APRI-r1) represents an additive tool in identifying those patients at risk of adverse clinical outcome with high accuracy. Joshita et al. also report good correlation between APRI and disease stage; [[2]Joshita S. Umemura T. Ota M. Tanaka E. AST/platelet ratio index associates with progression to hepatic failure and correlates with histological fibrosis stage in Japanese patients with primary biliary cirrhosis.J Hepatol. 2014; 61: 1443-1445Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar] however, it is apparent in both studies that a significant proportion of patients have an APRI >0.54 despite histological evidence of early stage (I-II) disease. Moreover, in our study we were able to show that in those without objective evidence of cirrhosis APRI retains independent predictive value, thus supporting APRI/APRI-r1 as a prognostic, clinically meaningful utility beyond application as a surrogate for liver fibrosis. The ability to reliably predict outcome in patients with PBC is beneficial for patient counselling, timing of diagnostic procedures, and therapeutic intervention. In this regard, prospective evaluation of APRI-r1 in terms of additive value to existing UDCA response criteria is of clear importance; particularly given the potential use of surrogate end points in the development of new treatments in PBC [3Lammers W.J. Van Buuren H. Pares A. et al.Defining optimal laboratory response criteria in UDCA treated primary biliary cirrhosis. Results of an international multicenter long-term follow-up study.Hepatology. 2013; 58: 36A-91ACrossref Google Scholar, 4Trivedi P.J. Hirschfield G.M. Treatment of autoimmune liver disease: current and future therapeutic options.Ther Adv Chronic Dis. 2013; 4: 119-141Crossref PubMed Scopus (39) Google Scholar, 5Silveira M.G. Brunt E.M. Heathcote J. Gores G.J. Lindor K.D. Mayo M.J. American Association for the Study of Liver Diseases endpoints conference: design and endpoints for clinical trials in primary biliary cirrhosis.Hepatology. 2010; 52: 349-359Crossref PubMed Scopus (63) Google Scholar]. Our observations alongside those of Joshita et al., further substantiate the role stratification could play, not just in clinical practice but also in clinical trial design. Hence, future therapeutic trials in PBC should consciously consider inclusion criteria beyond classic response criteria, and such stratifiers may include additional tools such as liver elastography and APRI-r1. Finally, as is evident from our studies, in the pursuit of optimal management for a rare disease such as PBC, methodologically robust, internationally representative, numerically well-powered cohorts are essential in order to allow investigators to make clear replicated observations about disease nature, course and intervention. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. AST/platelet ratio index associates with progression to hepatic failure and correlates with histological fibrosis stage in Japanese patients with primary biliary cirrhosisJournal of HepatologyVol. 61Issue 6PreviewWe read with great interest the study by Trivedi, Bruns and colleagues [1] on the association between the AST/platelet ratio index (APRI) and long-term transplant-free survival in patients with primary biliary cirrhosis (PBC). The authors demonstrated that elevated APRI (>0.54) at diagnosis and/or 1 year afterward (APRI-1y) was significantly associated with a future risk of adverse events independently and additively of the ursodeoxycholic acid (UDCA) therapy response, using a deviation cohort from the Elizabeth Hospital, Birmingham (UK), and a validation cohort from the Toronto Center for Liver Diseases (Canada) and the Jena University Hospital (Germany). Full-Text PDF Open AccessOptimising risk stratification in primary biliary cirrhosis: AST/platelet ratio index predicts outcome independent of ursodeoxycholic acid responseJournal of HepatologyVol. 60Issue 6PreviewOutcomes in primary biliary cirrhosis (PBC) can be predicted by biochemical response to ursodeoxycholic acid (UDCA). Such stratification inadequately captures cirrhosis/portal hypertension, recognised factors associated with adverse events. Full-Text PDF