Association of a cumulative liver damage index and thrombocytopenia with advanced liver disease - utility in a case finding approach

Introduction

Chronic liver disease remains challenging with many patients referred late in their disease course. The Somerset Liver Improvement Project developed a unique case-finding tool that uses longitudinal analysis of blood test results from 0.5 million patients to identify cohorts at risk. We previously reported using a novel Cumulative Liver Damage Index (CLDI – integral of liver enzyme over time) to predict liver disease. In this current study we looked at the distribution of CLDI-ALT among patients with thrombocytopenia. We hypothesized that a) high CLDI-ALT/low platelets is an indicator of advanced liver disease; b) there were significant delays in diagnosis and c) using these markers in the case finding tool will enable risk stratification and earlier diagnosis.

Methods

Blood test results from 2005 to 2020 were analysed in the database and filtered to show patients with platelet count <100 x10⁹/l, a marker of advanced liver disease. Patients with evidence of acute hepatitis (ALT>1000) were excluded as were those with a non-liver cause of low platelets. The distribution of CLDI-ALT was defined for this population. Using this marker the c100 highest risk men and women were identified. Cases were individually reviewed to determine the aetiology of liver disease and evidence of referral delay.

Results

Increasing CLDI reduces cohort size exponentially (figure 1: male: R²=0.93, p <10^-5; female R² = 0.87, p<10^-4). A threshold of CLDI-ALT of 305,000 and 235,000 yielded 107 men and 102 women respectively. Insufficient data in clinical systems were available for 12 patients, and a further 13 had no clear indication of chronic pathology. of the remainder, 67% (men) and 66% (women) had definite chronic liver disease. 32% of male and 19% of female liver patients were deceased as of 2022. 41% had alcohol related liver disease. The remainder were distributed among other chronic liver disease diagnoses. Where referral pathways were clear 50% of men and 49% of women had a delay in referral of at least 1 year (median delay 47.5 months [men] and 96 months [women]).

Conclusions

CLDI-ALT combined with low platelets can be used to risk stratify populations for advanced liver disease. It is likely that lowering the threshold of CLDI-ALT will identify patients with earlier disease. The distribution of diagnoses confirms the relative specificity of this risk stratification tool for liver disease (as previously published). Further work within the Somerset Liver Improvement Project is underway to identify undiagnosed patients using these markers in order to identify them for treatment. Figure 1: Cohort size with increasing CLDI-ALT