Rebecca Harris

Prevalence of clinically significant liver disease within the general population, as defined by non-invasive markers of liver fibrosis: a systematic review

As of 2016, there is no evidence-based pathway to stratify the risk of chronic liver disease in a general population setting. Non-invasive tests of liver fibrosis might provide a mechanism for earlier diagnosis. These tests have been extensively validated in the hospital setting but their performance in a general population setting is unclear. We did a systematic review of non-invasive tests used to stratify patients at risk of clinically significant liver disease in a general population setting and report the prevalence of chronic liver disease as defined by these tests. We systematically searched Embase, MEDLINE, Web of Science, reference lists from the original studies identified, and recent conference proceedings. All study designs were considered. 19 studies were identified, in which 11 non-invasive tests were used. Only transient elastography and FibroTest were compared with histological endpoints. The prevalence of liver fibrosis varied between 0·7% and 25·7%. More focused stratification for advanced liver fibrosis (0·9-2·0%) or cirrhosis (0·1-1·7%) narrowed the estimates of prevalence. Investigators from studies targeting patients with risk factors of liver disease, such as non-alcoholic fatty liver disease, hazardous alcohol use, or type 2 diabetes, reported higher prevalence of advanced liver fibrosis (0-27·9%) and cirrhosis (2·4-4·0%) than those in the general population. Validated non-invasive tests for liver fibrosis consistently detected otherwise unrecognised liver disease in the general population. Reliance on abnormal liver function tests will miss most patients with significant liver injury. New pathways to stratify chronic liver disease, with the use of non-invasive markers of liver fibrosis, are needed in the general population setting.

Prevalence and natural history of histologically proven chronic liver disease in a longitudinal cohort of patients with type 1 diabetes

Although a higher prevalence of raised liver enzymes and altered echotexture on ultrasound have been reported in patients with type 1 diabetes mellitus (T1DM), the histological spectrum and natural history of chronic liver disease (CLD) in T1DM is unknown. We investigated the prevalence and outcome of histologically proven CLD in a longitudinal cohort of patients with T1DM. We identified patients who have had liver biopsy from a computerized database (DIAMOND; Hicom Technology, Brookwood, UK) containing longitudinal data for over 95% of type 1 diabetes patients from an overall catchment population of 700,000 people. Gender‐matched patients with oral hypoglycemic‐treated (T2OH) and insulin‐treated type 2 diabetes (T2IN) who had liver biopsy formed two comparative cohorts. We collated clinical and histological data, as well as long‐term outcomes of all three groups, and compared T1DM cirrhosis incidence to UK general population data. Of 4,644 patients with T1DM, 57 (1.2%) underwent liver biopsy. Of these, 53.1% of patients had steatosis, 20.4% had nonalcoholic steatohepatitis, and 73.5% had fibrosis on index liver biopsy. Cirrhosis was diagnosed in 14 patients (24.6%) during follow‐up. T1DM with age under 55 years had an odds ratio of 1.875 (95% confidence interval: 0.936‐3.757) for cirrhosis incidence, compared to the general population. Longitudinal liver‐related outcomes were similar comparing the T1DM cohort and respective type 2 diabetes cohorts—when adjusted for important confounders, diabetic cohort type did not predict altered risk of incident cirrhosis or portal hypertension. Conclusion: Type 1 diabetes is associated with a previously unrecognized burden of CLD and its complications. (Hepatology 2014;60:158–168)

Economic evaluation of a community-based diagnostic pathway to stratify adults for non-alcoholic fatty liver disease: a Markov model informed by a feasibility study

Objectives To assess the long-term cost-effectiveness of a risk stratification pathway, compared with standard care, for detecting non-alcoholic fatty liver disease (NAFLD) in primary care. Setting Primary care general practices in England. Participants Adults who have been identified in primary care to have a risk factor for developing NAFLD, that is, type 2 diabetes without a history of excessive alcohol use. Intervention A community-based pathway, which uses transient elastography and hepatologists to stratify patients at risk of NAFLD, has been implemented and demonstrated to be feasible (NCT02037867). Earlier identification could mean earlier treatments, referral to specialist and enrolment into surveillance programmes. Design The impact of earlier detection and treatment with the risk stratification pathway on progression to later stages of liver disease was examined using decision modelling with Markov chains to estimate lifetime health and economic effects of the two comparators. Data sources Data from a prospective cross-sectional feasibility study indicating risk stratification pathway and standard care diagnostic accuracies were combined with a Markov model that comprised the following states: no/mild liver disease, significant liver disease, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, liver transplant and death. The model data were chosen from up-to-date UK sources, published literature and an expert panel. Outcome measure An incremental cost-effectiveness ratio (ICER) indicating cost per quality-adjusted life year (QALY) of the risk stratification pathway compared with standard care was estimated. Results The risk stratification pathway was more effective than standard care and costs £2138 per QALY gained. The ICER was most sensitive to estimates of the rate of fibrosis progression and the effect of treatment on reducing this, and ranged from −£1895 to £7032/QALY. The risk stratification pathway demonstrated an 85% probability of cost-effectiveness at the UK willingness-to-pay threshold of £20 000/QALY. Conclusions Implementation of a community-based risk stratification pathway is likely to be cost-effective. Trial registration number NCT02037867, ClinicalTrials.gov.

The XL probe: A luxury or a necessity? Risk stratification in an obese community cohort using transient elastography:

Background Transient elastography is a non-invasive tool which can stratify patients at risk of chronic liver disease. However, a raised body mass index has been independently associated with a failed or unreliable examination. Objective The purpose of this study was to analyse the performance of two probes (M/XL) on a portable transient elastography device within an obese community population. Method The method involved a prospective study with recruitment from a primary care practice. Patients identified with a risk factor for chronic liver disease were invited to a community-based risk stratification pathway for transient elastography readings with both probes. A threshold of ≥8.0 kPa defined elevated liver stiffness. Results A total of 477 patients attended the pathway. Of the patients, 21% had no valid measurements with the M probe. There was a significant difference between the probes in the proportion achieving ≥10 valid readings (M versus XL probe: 66.2% versus 90.2%; p ≤ 0.001) and in their reliability (M versus XL probe: 77.4% versus 98.5%; p = 0.028). Unreliable readings with the M probe increased as the body mass index increased. The XL probe re-stratified 5.2% of patients to have a normal reading. Conclusion The XL probe on a portable device significantly improves the applicability of transient elastography within a community-based risk stratification pathway.

OC-032 Type 2 Diabetes and Obesity will Drive the Burden of Liver Cirrhosis in the Next Two Decades: Abstract OC-032 Table 1

Introduction Over the past 30 years excessive alcohol consumption has been identified as the predominant risk factor underlying the striking rise in standardised mortality rates from liver disease in the UK. However, with the increasing incidence of type 2 diabetes and obesity within the general population, the risk factor profile associated with cirrhosis may change. Aim To estimate the prevalence of clinically significant chronic liver disease amongst adults in a primary care population and identify the impact of different risk factors. Methods Asymptomatic adult patients from a primary care practice covering a population of 4600 in inner city Leicester were screened for risk factors including (1) a diagnosis of type 2 diabetes (2) a raised body mass index (BMI) of ≥27.3 kg/m2 and (3) hazardous alcohol use. All of those with one or more of risk factors were invited to undergo a liver stiffness measurement using transient elastography (TE). A TE threshold of ≥8 kPa was used to make a diagnosis of clinically significant liver disease.1 Results Of the 1320 patients identified with risk factors, 705 underwent TE and 82 had an increased liver stiffness measurement of ≥8 kPa (Table 1). Of those patients with hazardous alcohol use as the only risk factor, 3.5 [95% CI 0.73–9.8]% had raised liver stiffness when compared to 7.9 [95% CI 2.9–16.4]% of patients with type 2 diabetes or 8.6% [95% CI 6–11.9]% with a raised BMI. Overall 16/82 (19.5%) patients had hazardous alcohol use (with or without type 2 diabetes and a raised BMI) as a risk factor for an elevated liver stiffness measurment compared to 66/82 (80.5%) with type 2 diabetes and/or a raised BMI (without hazardous alcohol use).Abstract OC-032 Table 1 Risk factor Total number of patients undergoing TE Number of patients with clinically significant liver disease (%) BMI ≥ 27.3 394 34 (8.6) Type 2 diabetes 76 6 (7.9) Hazardous alcohol use 86 3 (3.5) Type 2 Diabetes + BMI ≥ 27.3 77 26 (22.8) Type 2 Diabetes + Hazardous alcohol use 9 1 (11.1) Hazardous alcohol use + BMI ≥ 27.3 54 8 (14.8) All 3 risk factors 9 4 (44.4) Total 705 82 (11.6) Conclusion In the primary care population that was screened for major risk factors of chronic liver disease, a raised BMI and type 2 diabetes accounted for over 80% of those with clinically significant chronic liver disease. Population based interventions are urgently required to address obesity and type 2 diabetes which are likely to contribute to the burden of cirrhosis in the next decade. Reference 1 Roulot D, et al. Transient elastography as a screening tool for liver fibrosis and cirrhosis in a community-based population aged over 45 years. Gut 2011;60(7):977–84. Disclosure of Interest None Declared

PTU-026 Prevalence of liver histological abnormalities in type 1 diabetes and the long term consequences

Introduction Patients with type 1 diabetes have a higher prevalence of raised liver enzymes than the general population. Ultrasound diagnosis of non-alcoholic fatty liver disease has been reported to be common in type 1 diabetes despite associated insulin deficiency rather than insulin resistance. However, the histological spectrum of liver disease in type 1 diabetes and the natural history of chronic liver disease in this cohort is unknown. We describe the histological findings of patients with type 1 diabetes who had liver biopsy in a tertiary referral centre, and their long-term clinical outcome. Methods The DIAMOND database, which contains longitudinal data for over 95% of type 1 diabetes patients from an overall catchment population of 750 000 in Nottingham, was crossmatched with the clinical pathology database to identify those who had undergone liver biopsy. Case notes were reviewed to obtain follow-up data, and identify liver and non-liver related outcomes. Results Out of 2800 patients with Type 1 Diabetes, 57 patients underwent a total of 82 liver biopsies. Common indications for biopsy were abnormal liver enzymes (28 patients), malignancy (8), Hepatitis C staging (7) and clinical evidence of cirrhosis (3). On index biopsy, 86% had significant histological abnormalities (Abstract PTU-026 figure 1) and 10 patients (17.5%) had cirrhosis. During a total follow-up of 336.4 patient years (median 5.6 years), a further four patients developed cirrhosis, giving a cirrhosis prevalence of at least 500 per 100 000 population—this compares with an estimated UK cirrhosis prevalence of 76.3 per 100 000 population.1 Portal hypertensive sequelae occurred in 11 patients (78.6%) with cirrhosis and hepatocellular carcinoma in three patients. 22 patients (38.6%) died during follow-up. Crude death rate was 6539 per 100 000 person years, compared with national Type 1 Diabetes data2 of 1878 per 100 000 person years.Abstract PTU-026 Figure 1 Index liver biopsy diagnoses. Conclusion Type 1 Diabetes is associated with significant liver histology abnormalities and a higher than expected occurrence of cirrhosis, portal hypertension and mortality. These findings have implications for long-term management of patients with Type 1 Diabetes. Competing interests None declared. References 1. Fleming KM, Aithal GP, Solaymani-Dodaran M, et al. Incidence and prevalence of cirrhosis in the United Kingdom, 1992-2001: a general population-based study. J Hepatol 2008;49:732–8. 2. NHS IC. National Diabetes Audit Mortality Analysis 2007-2008. NHS IC, 2011.