Trends in indirect liver function marker testing in Wales from 2000 to 2017 and their association with age and sex: an observational study

Objective If non-invasive markers of liver fibrosis were recorded frequently enough in clinical practice, it might be feasible to use them for opportunistic community screening for liver disease. We aimed to determine their current pattern of usage in the national primary care population in Wales.Design Using the Secure Anonymised Information Linkage (SAIL) Databank at Swansea University (2000–2017), we quantified the frequency of common liver blood tests (aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelet count and albumin) used in fibrosis marker algorithms. We examined measurement variation by age and sex.Results During the 18-year study period, there were 2 145 178 adult patients with at least one blood test available for analysis. Over the study period, the percentage of SAIL patients receiving an ALT test in each year increased from 2% to 33%, with platelet count and albumin measurement increasing by a similar factor. AST testing, although initially rising, had decreased to 1% by the end of the study. AST and ALT values varied by age and sex, particularly in males with the upper normal range of ALT values decreasing rapidly from 90 U/L at age 30 to 45 U/L by age 80.Conclusion The reduction in AST testing to only 1% of the adult population limits the use of many non-invasive liver marker algorithms. To enable widespread screening, alternative algorithms for liver fibrosis that do not depend on AST should be developed. Liver fibrosis markers should be modified to include age-specific and sex-specific normal ranges

“Low FIT” Colorectal Cancer: A four-year comparison of the Nottingham “4F” protocol with FIT10 in symptomatic patients.

Aim:To evaluate colorectal cancer outcomes after “low” (sub-threshold) Faecal Immunochemical Test (FIT) results in symptomatic patients tested in primary care.Method:Retrospective audit of 35,289 patients with FIT results, having consulted their general practitioner with lower gastrointestinal symptoms, and subsequent colorectal cancer (CRC) diagnoses. The Rapid Colorectal Cancer Diagnosis pathway was introduced in November 2017 to allow incorporation of FIT into clinical practice. The local “4F” protocol combined FIT results with blood tests and digital rectal examination (DRE): FIT, Full blood count (FBC), Ferritin and Finger.Outcome: Detection rates of CRC, missed CRC and time to diagnosis in local “4F” protocols for patients with a sub-threshold faecal Haemoglobin (fHb) result compared to thresholds of 10 and 20µgHb/g Faeces.Results:A single threshold of 10 µgHb/g Faeces identifies a population in whom the risk of CRC is 0.2% but would have missed 63 (10.5%) of 599 CRCs in this population. The Nottingham “4F” protocol would have missed fewer CRCs (42 of 599 (7%)) despite using a threshold of 20 µgHb/g Faeces for patients with normal blood tests. Subthreshold FIT results in patients subsequently diagnosed with a palpable rectal tumour yielded the longest delays.Conclusion:Combination of FIT with blood results and DRE (“4F”) reduced the risk of missed or delayed diagnosis. Further studies on the impact of such protocols on the diagnostic accuracy of FIT are expected. The value of adding blood tests to FIT may be restricted to specific parts of the fHb result spectrum

‘Low’ faecal immunochemical test (FIT) colorectal cancer: a 4-year comparison of the Nottingham ‘4F’ protocol with FIT10 in symptomatic patients

Aim: The aim of this work was to evaluate colorectal cancer (CRC) outcomes after ‘low’ (sub-threshold) faecal immunochemical test (FIT) results in symptomatic patients tested in primary care. Method: This work comprised a retrospective audit of 35 289 patients with FIT results who had consulted their general practitioner with lower gastrointestinal symptoms and had subsequent CRC diagnoses. The Rapid Colorectal Cancer Diagnosis pathway was introduced in November 2017 to allow incorporation of FIT into clinical practice. The local ‘4F’ protocol combined FIT results with blood tests and digital rectal examination (DRE): FIT, full blood count, ferritin and finger [DRE]. The outcome used was detection rates of CRC, missed CRC and time to diagnosis in local 4F protocols for patients with a subthreshold faecal haemoglobin (fHb) result compared with thresholds of 10 and 20 μg Hb/g faeces. Results: A single threshold of 10 μg Hb/g faeces identifies a population in whom the risk of CRC is 0.2%, but this would have missed 63 (10.5%) of 599 CRCs in this population. The Nottingham 4F protocol would have missed fewer CRCs [42 of 599 (7%)] despite using a threshold of 20 μg Hb/g faeces for patients with normal blood tests. Subthreshold FIT results in patients subsequently diagnosed with a palpable rectal tumour yielded the longest delays in diagnosis. Conclusion: A combination of FIT with blood results and DRE (the 4F protocol) reduced the risk of missed or delayed diagnosis. Further studies on the impact of such protocols on the diagnostic accuracy of FIT are expected. The value of adding blood tests to FIT may be restricted to specific parts of the fHb results spectrum

Cardiovascular disease, cancer and mortality among people with type 2 diabetes and alcoholic or non-alcoholic fatty liver disease hospital admission

OBJECTIVE: To describe associations between alcoholic fatty liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD) hospital admission and cardiovascular disease (CVD), cancer, and mortality in people with T2DM. RESEARCH DESIGN AND METHODS: We performed a retrospective cohort study using linked population-based routine data from the diabetes register, hospital, cancer and death records for people aged 40-89 years, diagnosed with T2DM in Scotland 2004-2013 who had one or more hospital admission records. Liver disease and outcomes were identified using International Classification of Diseases codes. We estimated hazard ratios from Cox proportional hazards models, adjusted for key risk factors (aHRs). RESULTS: There were 134,368 people with T2DM (1707 with ALD and 1452 with NAFLD) with mean follow-up of 4.3 years for CVD and 4.7 years for mortality. Among people with ALD, NAFLD or without liver disease hospital records respectively there were: 378, 320 and 21,873 CVD events, 268, 176 and 15,101 cancers and 724, 221 and 16,203 deaths. For ALD and NAFLD respectively, aHRs (95% CIs) compared to the group with no record of liver disease were: 1.59 (1.43, 1.76) and 1.70 (1.52, 1.90), for CVD; 40.3 (28.8, 56.5) and 19.12(11.71 31.2), for hepatocellular cancer (HCC); 1.28 (1.12, 1.47) and 1.10 (0.94, 1.29) for non-HCC cancer; 4.86 (4.50, 5.24) and 1.60 (1.40, 1.83) for all-cause mortality. CONCLUSIONS: Hospital records of ALD or NAFLD are associated, to varying degrees, with increased risk of CVD, cancer and mortality in people with T2DM

Sociodemographic Variations in the Uptake of Faecal Immunochemical Tests in Primary Care

Background: Faecal Immunochemical Testing (FIT) usage for symptomatic patients is increasing, but variations in use by sociodemographics are unknown. We introduced FIT for symptomatic patients in November 2017. Aim: Identify whether demographics, ethnicity or social deprivation affect FIT return in symptomatic patients. Design and Setting: FIT was introduced as a triage tool in Primary Care and was mandated for all colorectal referrals (except rectal bleeding/mass) to secondary care. FIT was used, alongside full blood count and ferritin, to stratify colorectal cancer risk. Method: All referrals November 2017-December 2021 were retrospectively reviewed. Sociodemographic factors affecting FIT return were analysed by multivariate logistic regression. Results: 35,289 patients returned their index FIT (90.7%), 3631 (9.3%) did not. On multivariate analysis, males were less likely to return FIT (OR 1.11, 95%CI 1.03-1.19). Patients over 65 were more likely to return FIT (OR 0.78 for non-return, 95%CI 0.72-0.83). Unreturned FIT was more than doubled in the most compared to the least deprived (OR 2.20, 95%CI 1.99-2.43). Patients from Asian (OR 1.82, 95%CI 1.58-2.10), Black (OR 1.21, 95%CI 0.98-1.49) and Mixed/Other ethnic groups (OR 1.29, 95%CI 1.05-1.59) were more likely to not return FIT compared to White ethnicity. 599 colorectal cancers were detected (1.5%), 561 in those who returned a first FIT request, 38 in those who did not. Conclusion: FIT return in those suspected of having colorectal cancer varies by gender, age, ethnicity, and socioeconomic deprivation. Strategies to mitigate effects on FIT return and colorectal cancer detection should be considered as FIT usage expands

Faecal immunochemical testing and blood tests for prioritization of urgent colorectal cancer referrals in symptomatic patients: a 2-year evaluation

BackgroundA novel pathway incorporating faecal immunochemical testing (FIT) for rapid colorectal cancer diagnosis (RCCD) was introduced in 2017. This paper reports on the service evaluation after 2 years of pathway implementation.MethodsThe RCCD protocol was based on FIT, blood results and symptoms to stratify adult patients in primary care. Two-week-wait (2WW) investigation was indicated for patients with rectal bleeding, rectal mass and faecal haemoglobin (fHb) level of 10 µg Hb/g faeces or above or 4 µg Hb/g faeces or more in the presence of anaemia, low ferritin or thrombocytosis, in all other symptom groups. Patients with 100 µg Hb/g faeces or above had expedited investigation . A retrospective audit of colorectal cancer detected between 2017 and 2019 was conducted, fHb thresholds were reviewed and critically assessed for cancer diagnoses.ResultsIn 2 years, 14788 FIT tests were dispatched with 13361 (90.4 per cent) completed returns. Overall, fHb was less than 4 µg Hb/g faeces in 9208 results (68.9 per cent), 4–9.9 µg Hb/g in 1583 (11.8 per cent), 10–99.9 µg Hb/g in 1850 (13.8 per cent) and 100 µg Hb/g faeces or above in 720 (5.4 per cent). During follow-up (median 10.4 months), 227 colorectal cancers were diagnosed. The cancer detection rate was 0.1 per cent in patients with fHb below 4 µg Hb/g faeces, 0.6 per cent in those with fHb 4–9.9 µg Hb/g faeces, 3.3 per cent for fHb 10–99.9 µg Hb/g faeces and 20.7 per cent for fHb 100 µg Hb/g faeces or above. The detection rate in the cohort with 10–19.9 µg Hb/g faeces was 1.4 per cent, below the National Institute for Health and Care Excellence threshold for urgent referral. The colorectal cancer rate in patients with fHb below 20 µg Hb/g faeces was less than 0.3 per cent.ConclusionUse of FIT to "rule out" urgent referral from primary care misses a small number of cases. The threshold for referral may be adjusted with blood results to improve stratification

Choice of faecal immunochemical test matters: Comparison of OC-Sensor and HM-JACKarc, in the assessment of patients at high risk of colorectal cancer

Objectives: Currently NICE recommends the use of faecal immunochemical test (FIT) at faecal haemoglobin concentrations (f-Hb) of 10 μg Hb/g faeces to stratify for colorectal cancer (CRC) risk in symptomatic populations. This f-Hb cut-off is advised across all analysers, despite the fact that a direct comparison of analyser performance, in a clinical setting, has not been performed.Methods: Two specimen collection devices (OC-Sensor, OC-S; HM-JACKarc, HM-J) were sent to 914 consecutive individuals referred for follow up due to their increased risk of CRC. Agreement of f-Hb around cut-offs of 4, 10 and 150 µg Hb/g faeces and CRC detection rates were assessed. Two OC-S devices were sent to a further 114 individuals, for within test comparisons.Results: 732 (80.1%) individuals correctly completed and returned two different FIT devices, with 38 (5.2%) CRCs detected. Median f-Hb for individuals diagnosed with and without CRC were 258.5 and 1.8 µg Hb/g faeces for OC-S and 318.1 and 1.0 µg Hb/g faeces for HM-J respectively.Correlation of f-Hb results between OC-S/HM-J over the full range was rho=0.74, p[less than]0.001. Using a f-Hb of 4μg Hb/g faeces for both tests found an agreement of 88.1%, at 10μg Hb/g faeces 91.7% and at 150μg Hb/g faeces 96.3%.114 individuals completed and returned two OC-S devices; correlation across the full range was rho=0.98, p[less than]0.001.Conclusion: We found large variations in f-Hb when different FIT devices were used, but a smaller variation when the same FIT device was used. Our data suggest that analyser-specific f-Hb cut-offs are applied with regard to clinical decision making, especially at lower f-Hb