Non-invasive risk scores do not reliably identify future cirrhosis or hepatocellular carcinoma in Type 2 diabetes: The Edinburgh type 2 diabetes study.

Sheila M Grecian,Joanne R Morling,Brian M Frier,Nicola N Zammitt,Rebecca M Reynolds,Mark W J Strachan,Peter C Hayes,Stela Mclachlan,Stephen Glancy,Patrick K A Kearns,Neil I Guha,Rachel M Williamson,Jackie F Price,Jonathan A Fallowfield

doi:10.1111/liv.14590

Abstract

The incidence of cirrhosis and hepatocellular carcinoma (HCC) is increased in Type 2 diabetes, primarily secondary to non-alcoholic fatty liver disease (NAFLD). European guidelines recommend screening for NAFLD in Type 2 diabetes. American guidelines, while not advocating a screening protocol, suggest using non-invasive markers of fibrosis for risk-stratification and guiding onward referral. To test the ability of individual fibrosis scores and the European screening algorithm to predict 11-year incident cirrhosis/HCC in an asymptomatic community cohort of older people with Type 2 diabetes. The Edinburgh Type 2 Diabetes Study investigated men and women with Type 2 diabetes (n = 1066, aged 60-75 at baseline). Liver markers were measured at baseline and year 1; steatosis and fibrosis markers were calculated according to independently published calculations. During 11 years of follow-up, cases of cirrhosis and HCC were identified. Forty-three out of 1059 participants with no baseline cirrhosis/HCC developed incident disease. All scores were significantly associated with incident liver disease by odds ratio (P < .05). The ability of the risk-stratification tools to accurately identify those who developed incident cirrhosis/HCC was poor with low-positive predictive values (5-46%) and high false-negative and -positive rates (up to 60% and 77%) respectively. When fibrosis risk scores were used in conjunction with the European algorithm, they performed modestly better than when applied in isolation. In a cohort with a moderately low incidence of cirrhosis/HCC, existing risk scores did not reliably identify participants at high risk. Better prediction models for cirrhosis/HCC in people with Type 2 diabetes are required.

Highlights

People with Type 2 diabetes have a higher incidence of cirrhosis and hepatocellular carcinoma (HCC) than the general population.[1,2,3] The commonest cause of liver disease in Type 2 diabetes is non-alcoholic fatty liver disease (NAFLD) with estimates of prevalence from 40% to 70%.4-7It would be valuable to identify those at high risk of developing cirrhosis/HCC because NAFLD is potentially reversible by weight loss, and it would direct screening and early treatment for varices and HCC, while promoting intensive management of increased cardiovascular risk.[8,9]A significant problem in creating appropriate risk assessment tools for NAFLD is that no consistent risk factors for progressive disease have been identified
Several groups have developed non-invasive risk scoring models to identify those with fibrosis (including the Fibrosis 4 Index (FIB-4), the NALFD Fibrosis Score (NFS), aspartate aminotransferase (AST):alanine aminotransferase (ALT) ratio, the AST to Platelet Ratio Index (APRI) and the Enhanced Liver Fibrosis test (ELF)).[12,13,14,15,16]
One study of the EASL-EASD-EASO referral algorithm reported that around one third of people routinely attending a diabetes clinic would fulfil the criteria for hepatology referral; the incidence of subsequent cirrhosis and HCC in that cohort was not reported.[24]

Summary

Conclusions

In a cohort with a moderately low incidence of cirrhosis/HCC, existing risk scores did not reliably identify participants at high risk. Better prediction models for cirrhosis/HCC in people with Type 2 diabetes are required. KEYWORDS cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease, risk prediction, screening, type 2 Diabetes

| INTRODUCTION

| METHODS

Findings

| DISCUSSION