3 research outputs found
Role of microRNA biomarkers to predict complications of gallstones
Gallstones are the most common cause for abdominal pain requiring an emergency
hospital admission. About 5.5 million people in the UK have the condition and over 60,000
cholecystectomies are performed every year. At present there are no specific biomarker tests
that can predict whether an individual patient with gallstones has severe inflammatory,
infective or obstructive complications requiring inpatient management and urgent surgical
intervention; or has symptoms without complications that can be managed as an outpatient or
day-case basis. Building on evidence that microRNA (miRNA) biomarkers can predict acute
cholestatic liver injury, and have been shown to be superior to alanine aminotransferase (ALT),
this study hypothesised that miRNA biomarkers might be used to predict gallstone
complications in emergency surgical patients and help to inform clinical decision-making. The
specific aim of this research is to determine whether microRNA (miR) -122 and miR-210
measured at first presentation to hospital can predict complications of gallstone diseases and
differentiate those patients who require acute inpatient admission.
Patients admitted to the Royal Infirmary of Edinburgh from 3rd September 2014 to
12th May 2015 with a differential diagnosis of gallstone disease on index presentation were
recruited to this study and a blood sample was taken for miRNA analysis in the plasma fraction.
A pilot study was carried out after 6 months of patient recruitment with a third of the samples
collected. miR-122 and -210 were quantified by PCR. All analyses were performed blinded to
the clinical data. Each patient was followed up for a minimum period of one month during
which investigation reports, operation notes and pathology results were obtained.
A total of 232 patients were recruited to the study. Eight-two random samples were
analysed in the pilot study. As the pilot study did not show any significant differences in miR-
210 concentration between different patient groups (P=0.365), the main study only focused on
miR-122 analysis. There was a significant difference in plasma miR-122 concentration
between patients with gallstone (Median: 0.039 [95% CI: 0.027 , 0.059]) and non-gallstone
diseases (Median: 0.011 [95% CI: 0.0079 , 0.015]) (P<0.001); and between uncomplicated
(Median: 0.062 [95% CI: 0.039 , 0.11]) and complicated (Median: 0.030 [95% CI: 0.022 ,
0.047]) gallstone diseases (P=0.040). Plasma miR-122 was significantly lower in patients with
cholecystitis (Median: 0.023 [95% CI: 0.017 , 0.032]) (P=0.006) and significantly higher in
patients with choledocholithiasis (Median: 0.099 [95% CI: 0.054 , 0.17]) (P<0.001). The PPV
and NPV for plasma miR-122 in detecting (a) gallstone diseases were 78.0% and 41.9%
respectively; (b) complicated gallstone diseases were 81.0% and 32.0% respectively; and (c)
choledocholithiasis were 63.0% and 75.9% respectively.
In conclusion, relative miR-122 concentration in plasma at presentation to hospital is
significantly different in patients with complications of gallstone diseases that may require
acute in-patient admission. When these tests are developed for rapid analysis or made suitable
for a near-patient assay platform, and if these findings are validated in an independent cohort,
there exists the potential to substantially reduce emergency hospital admissions by identifying
low risk patients suitable for direct discharge from the Emergency Department and further
management in an outpatient setting