Published online Nov 28, 2017. doi: 10.3748/wjg.v23.i44.7863
Peer-review started: July 28, 2017
First decision: August 30, 2017
Revised: September 25, 2017
Accepted: September 28, 2017
Article in press: September 28, 2017
Published online: November 28, 2017
Processing time: 122 Days and 21.6 Hours
No reliable predictive models exist for hepatocellular carcinoma (HCC) in primary biliary cholangitis (PBC). Aspartate aminotransferase (AST) to platelet ratio index (APRI) not only captures fibrosis/cirrhosis, but also reflects other biologically significant pathways like hepatic necroinflammation or non-cirrhotic portal hypertension. The usefulness of APRI in predicting HCC in PBC remains unknown.
A predictive marker for HCC development in PBC patients will help disease prognostication and streamline the follow-up and HCC surveillance strategy.
To investigate the usefulness of APRI in predicting HCC in PBC.
The authors recruited all PBC patients who had follow-up in the Hepatology Clinic of Queen Mary Hospital (QMH) between January 2000 and October 2015. Patients were followed up every 3 to 6 mo with regular monitoring of platelet count, liver biochemistry, prothrombin time and alpha-fetoprotein level. In the analysis of the risk factors for adverse events, suboptimal response to UDCA was identified by using various treatment response criteria. APRI-r1 in combination with treatment response criteria enables further stratification of PBC patients into low-risk (biochemical response with APRI-r1 ≤ 0.54), intermediate-risk (suboptimal biochemical response with APRI-r1 ≤ 0.54, or biochemical response with APRI-r1 > 0.54) and high-risk (suboptimal biochemical response with APRI-r1 > 0.54) groups of developing adverse outcomes in terms of liver transplantation or death. The Cox proportional hazards model was used to determine the hazard ratio (HR) of HCC with different variables. The Kaplan-Meier method was used to analyze the development of HCC. The performances of various prognostic models were expressed in terms of area under the receiver operating curve (AUROC).
A total of 144 patients were identified. The median age at diagnosis was 57.8 years (interquartile range: 48.7-71.5 years), and 41 (28.5%) had baseline cirrhosis. The median follow-up duration was 6.9 years (range: 1.0-26.3 years), with a total of 1136 patient-years. Twelve patients developed HCC, with an incidence rate of 10.6 cases per 1000 patient-years. The overall 5-, 10- and 15-year probabilities of HCC development were 2.3% [95% confidence interval (CI): 0%-4.8%], 8.4% (95%CI: 1.8%-14.5%) and 21.6% (6.8%-34.1%), respectively. Independent risk factors for HCC development were older age (HR = 1.07), cirrhosis (HR = 4.38) and APRI at 1 year after treatment (APRI-r1) > 0.54 (HR = 3.94). APRI-r1 in combination with treatment response further stratified the risk of HCC development (log rank P < 0.05). The AUROC of APRI-r1 in predicting HCC was 0.77 (95%CI: 0.64-0.88).
APRI-r1 can be used as a predictive marker for HCC development in PBC patients. Combination of APRI-r1 with treatment response can further stratify the HCC risk.
Our study confirmed the usefulness of APRI-r1 in predicting HCC development in PBC patients receiving UDCA. The combination of APRI-r1 with treatment response allowed further stratification of HCC risk. Owing to its non-invasiveness and cost-effectiveness, APRI can be used as a marker to streamline the HCC surveillance protocol in PBC patients. Future multi-center studies with larger sample size are warranted to confirm our findings.