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Bugaichuk S, Wilkens V, Horvatits K, Huber S, Lohse AW, Kluwe J, Pischke S, Fründt T. Non-alcoholic fatty liver disease, in contrast to alcoholic liver disease, is associated with lower socio-economic status: results from a German referral center. Ann Hepatol 2025:101926. [PMID: 40383368 DOI: 10.1016/j.aohep.2025.101926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 04/16/2025] [Accepted: 04/26/2025] [Indexed: 05/20/2025]
Abstract
INTRODUCTION AND OBJECTIVES Elevated liver enzymes (ELE) are a common finding in the general population, often caused by undiagnosed chronic liver disease. But little is known to what extent socioeconomic status (SES) influences the occurrence of various liver diseases. MATERIAL AND METHODS Retrospective study of outpatients presenting with ELE. All patients received a structured work-up including abdominal ultrasound and serological testing. SES was assessed for patients from the Hamburg area using the social monitoring database of the Hamburg City Housing Department. SES was rated as high (SES-H), medium (SES-M), and low (SES-L). RESULTS Out of n=859 patients analysed, SES was assessable for n = 310 (53%) patients: SES-H/-M/-L [n; %]: 31 (10%), 223 (72%), 56 (18%). The most prevalent liver diseases were NAFLD (n=125; 40.3%), drug-induced liver injury (n=16; 5.2%) and alcoholic liver disease (ALD, n=13; 4.2%). Prevalence of NAFLD differed significantly between SES-subgroups (SES-H/-M/-L [n; %]: 6 (19%) vs. 88 (39%) vs. 32 (55%); p= .004), the distribution of ALD was similar between the SES subgroups (1(3.2%) vs. 11 (4.9%) vs. 1 (2%); p= .55). Median body mass index (BMI) increased from SES-H to SES-VL (SES-H/-M/-L [kg/m2]: 24.4 vs. 26.2 vs. 28.6; p= .001). CONCLUSIONS NAFLD is the most prevalent liver disease in patients presenting with unexplained ELE, with a significantly higher occurrence in individuals from lower SES groups. Furthermore, BMI increases among patients with lower SES, highlighting the potential role of socioeconomic factors in NAFLD development. These findings underscore the need for targeted public health interventions, particularly in socioeconomically disadvantaged population.
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Affiliation(s)
- Semjon Bugaichuk
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany
| | - Verena Wilkens
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany
| | | | - Samuel Huber
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany
| | - Ansgar W Lohse
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany
| | - Johannes Kluwe
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany; Department of Internal Medicine and Gastroenterology, Amalie Sieveking Hospital, Hamburg, Germany
| | - Sven Pischke
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany
| | - Thorben Fründt
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany.
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Innes H, Buch S, Kendall TJ, Fallowfield JA, Guha IN. Interpreting elevated liver blood test results through a genetic lens: A genome-wide association study. Liver Int 2024; 44:3260-3273. [PMID: 39425533 PMCID: PMC11586890 DOI: 10.1111/liv.16114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 09/10/2024] [Accepted: 09/12/2024] [Indexed: 10/21/2024]
Abstract
BACKGROUND AND AIMS Individuals with genetic polymorphisms in UGT1A1 exhibit bilirubin levels that belie their risk of liver disease (Gilbert's syndrome) but it is not known if this phenomenon extends to other common liver blood tests (LBTs). METHODS A genome-wide association analysis of 10 LBTs was conducted using the UK biobank. Polygenic scores (PGS) were created from discordant loci (e.g. loci associated with the LBT but not associated with cirrhosis morbidity risk). Participants were assigned to a low, intermediate or high PGS for each LBT. A high PGS approximates Gilbert's syndrome (i.e. elevated LBT without an analogous increase in disease risk). The prognostic significance of an 'elevated' LBT-and how this differs by PGS-was assessed through competing risk survival analysis. RESULTS This study included 157 005 and 166 871 participants for the discovery and validation phases, respectively. Elevated LBTs were more prevalent in the high versus low PGS group, yet the 10-year risk of cirrhosis morbidity was comparable. For example, in the low PGS group, 4.3% had an elevated gamma-glutamyltransferase (GGT) and the 10-year risk of cirrhosis morbidity was .45%. Conversely, in the high PGS group, 21.2% had an elevated GGT and the 10-year risk was .38%. Accordingly, the 10-year risk of cirrhosis morbidity for individuals with an elevated GGT was markedly different in the low vs. high group (4.2% vs. 1.2%; p < .001). Similar results were apparent for Fibrosis-4 index, total bilirubin, and platelet count. CONCLUSION Variability in LBTs is influenced by genetic polymorphisms that have a neutral effect on disease risk. These findings have implications for interpreting elevated LBTs in clinical practice.
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Affiliation(s)
- Hamish Innes
- School of Health and Life SciencesGlasgow Caledonian UniversityGlasgowUK
- BBV/STI team, Public Health ScotlandGlasgowUK
- Lifespan and Population HealthUniversity of NottinghamNottinghamUK
| | - Stephan Buch
- Medical Department 1University Hospital DresdenDresdenTUGermany
| | - Timothy J. Kendall
- Centre for Inflammation Research, Institute for Regeneration and RepairUniversity of EdinburghEdinburghUK
- Edinburgh PathologyUniversity of EdinburghEdinburghUK
| | - Jonathan A. Fallowfield
- Centre for Inflammation Research, Institute for Regeneration and RepairUniversity of EdinburghEdinburghUK
| | - Indra Neil Guha
- NIHR Nottingham Biomedical Research CentreNottingham University Hospitals NHS Trust and the University of NottinghamNottinghamUK
- Nottingham Digestive Diseases Centre, School of MedicineUniversity of NottinghamNottinghamUK
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Koc ÖM, Vaes B, Robaeys G, Catalan CF, Aertgeerts B, Nevens F. Clinical audit of quality of care among patients with viral hepatitis in primary care in a low endemic region. Fam Pract 2024; 41:693-701. [PMID: 38887051 DOI: 10.1093/fampra/cmae019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/20/2024] Open
Abstract
BACKGROUND The current hepatitis B (HBV) and hepatitis C virus (HCV) screening practices may fail to detect many infected patients who could benefit from new therapeutic agents to limit progression to cirrhosis and hepatocellular carcinoma. OBJECTIVES This study assessed the test positivity rate and cascade of care of viral hepatitis patients in primary care in a low endemic region as well as the testing policy of abnormal alanine aminotransferase (ALT) level. METHODS This is a retrospective clinical audit among primary health care practices in Flanders, Belgium, assessing patients with an active medical file between 2019 and 2021. RESULTS A total of 84/89 (94.4%) primary health care practices participated representing 621,573 patients of which 1069 patients (0.17%) were registered as having viral hepatitis, not further specified. Detailed information was available from 38 practices representing 243,723/621,573 (39.2%) patients of which 169 (0.07%) were HBsAg positive and 99 (0.04%) anti-HCV positive. A total of 96/134(71.6%) chronic HBV-infected and 31/77(40.3%) chronic HCV-infected patients were referred to a hepatologist. A total of 30,573/621,573(4.9%) patients had an abnormal ALT level, and by at random selection, more detailed information was obtained on 211 patients. Information on high-risk groups was missing in up to 60%. In patients with abnormal ALT level, HBsAg and anti-HCV testing were conducted in 37/211(17.5%) and 25/211(11.8%), respectively. CONCLUSION In a low endemic region, the testing rate and cascade of care of HBV and HCV-infected patients can be improved in primary care, especially in high-risk groups and patients with abnormal ALT levels.
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Affiliation(s)
- Özgür M Koc
- Department of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands
- School of Nutrition and Translational Research in Metabolism (NUTRIM), University Maastricht, Maastricht, the Netherlands
- Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium
| | - Bert Vaes
- Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium
| | - Geert Robaeys
- Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium
| | - Cristian F Catalan
- Biostatistics and Statistical Bioinformatics Centre (L-BioStat), KU Leuven, Leuven, Belgium
| | - Bert Aertgeerts
- Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium
- CEBAM, Belgian Centre for Evidence Based Medicine, Leuven, Belgium
| | - Frederik Nevens
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
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Nobes J, Leith D, Handjiev S, Dillon JF, Dow E. Intelligent Liver Function Testing (iLFT): An Intelligent Laboratory Approach to Identifying Chronic Liver Disease. Diagnostics (Basel) 2024; 14:960. [PMID: 38732374 PMCID: PMC11083526 DOI: 10.3390/diagnostics14090960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 04/29/2024] [Accepted: 05/02/2024] [Indexed: 05/13/2024] Open
Abstract
The intelligent Liver Function Testing (iLFT) pathway is a novel, algorithm-based system which provides automated laboratory investigations and clinical feedback on abnormal liver function test (LFT) results from primary care. iLFT was introduced to NHS Tayside, Scotland, in August 2018 in response to vast numbers of abnormal LFTs, many of which were not appropriately investigated, coupled with rising mortality from chronic liver disease. Here, we outline the development and implementation of the iLFT pathway, considering the implications for the diagnostic laboratories, primary care services and specialist hepatology clinics. Additionally, we describe the utility, outcomes and evolution of iLFT, which was used over 11,000 times in its first three years alone. Finally, we will consider the future of iLFT and propose areas where similar 'intelligent' approaches could be used to add value to laboratory investigations.
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Affiliation(s)
- Jennifer Nobes
- Department of Blood Sciences, NHS Tayside, Ninewells Hospital, Dundee DD1 9SY, UK
- Population Health & Genomics, School of Medicine, University of Dundee, Dundee DD1 9SY, UK
| | - Damien Leith
- Department of Gastroenterology and Hepatology, NHS Tayside, Ninewells Hospital, Dundee DD1 9SY, UK
- Gut Group, School of Medicine, University of Dundee, Dundee DD1 9SY, UK
| | - Sava Handjiev
- Department of Blood Sciences, NHS Tayside, Ninewells Hospital, Dundee DD1 9SY, UK
- Gut Group, School of Medicine, University of Dundee, Dundee DD1 9SY, UK
| | - John F. Dillon
- Department of Gastroenterology and Hepatology, NHS Tayside, Ninewells Hospital, Dundee DD1 9SY, UK
- Gut Group, School of Medicine, University of Dundee, Dundee DD1 9SY, UK
| | - Ellie Dow
- Department of Blood Sciences, NHS Tayside, Ninewells Hospital, Dundee DD1 9SY, UK
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Madorran E, Kocbek Šaherl L, Rakuša M, Munda M. In Vitro Human Liver Model for Toxicity Assessment with Clinical and Preclinical Instrumentation. Pharmaceutics 2024; 16:607. [PMID: 38794269 PMCID: PMC11124512 DOI: 10.3390/pharmaceutics16050607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 04/19/2024] [Accepted: 04/25/2024] [Indexed: 05/26/2024] Open
Abstract
The existing in vitro toxicological models lack translational potential, which makes difficult the application of gathered information to clinical usage. To tackle this issue, we built a model with four different types of primary liver cells: hepatic sinusoidal endothelial cells, hepatic stellate cells, Kupffer cells and hepatocytes. We cultured them in different combinations of composition and volumes of cell medium, hepatocyte proportions of total cells and additions of extracellular matrixes. We added rifampicin (RIF), ibuprofen (IBU) and 5-fluorouracil (5-FU) to this model and observed the microanatomy and physiology changes for a week with preclinical and clinical instruments. Among the different model configurations, we selected the feature combination of the in vitro model that had similar biomarker values to those measured in clinical diagnostics. When we exposed the selected model configuration to RIF, IBU and 5-FU, we observed similar glucose, triglyceride and albumin dynamics as in vivo (from clinical data). Therefore, we have built an in vitro liver model that resembles the liver microenvironment, and we have analysed it with clinical instrumentation to facilitate data translation. Furthermore, during these observations, we found that Kupffer and LSEC cells are suitable candidates for the search for clinical diagnostic markers of liver function.
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Affiliation(s)
- Eneko Madorran
- Faculty of Medicine, Institute of Anatomy, Histology and Embryology, University of Maribor, Taborska Ulica 8, 2000 Maribor, Slovenia; (L.K.Š.); (M.R.); (M.M.)
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Al Harthi T, Whiting P, Watson J. Liver function tests in patients with hypertension in primary care: a prospective cohort study. BJGP Open 2024; 8:BJGPO.2023.0082. [PMID: 37726171 PMCID: PMC11169983 DOI: 10.3399/bjgpo.2023.0082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 08/30/2023] [Accepted: 09/13/2023] [Indexed: 09/21/2023] Open
Abstract
BACKGROUND Liver function tests (LFTs) are frequently used to monitor patients with hypertension in UK primary care. Evidence is lacking on whether testing improves outcomes. AIM To estimate the diagnostic accuracy of LFTs in patients with hypertension and determine downstream consequences of testing. DESIGN & SETTING Prospective study using the Clinical Practice Research Datalink (CPRD). METHOD In total, 30 000 patients with hypertension who had LFTs in 2015 were randomly selected from CPRD. The diagnostic accuracy measures for eight LFT analytes and an overall LFT panel were calculated against the reference standard of liver disease. Rates of consultations, blood tests, and referrals within 6 months following testing were measured. RESULTS The 1-year incidence of liver disease in patients with hypertension was 0.5% (95% confidence interval [CI] = 0.4% to 0.6%). Sensitivity and specificity of an LFT panel were modest: 61.3% (95% CI = 53.1% to 69.0%) and 73.8% (95% CI = 73.1% to 74.3%), respectively. The positive predictive value (PPV) of the eight individual LFT analytes were low ranging from 0.2% to 8.9%. Among patients who did not develop liver disease, mean number of consultations, referrals, and tests were higher in the 6 months following false-positives at 10.5, 0.7 and 29.8, respectively, compared with true-negatives: 8.6, 0.6, and 19.8. CONCLUSION PPVs of LFTs in primary care were low, with high rates of false-positive results and increased rates of subsequent consultations, referrals, and blood testing. Avoiding LFTs for routine monitoring could potentially reduce patients' anxiety, GP workload, and healthcare costs.
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Affiliation(s)
- Thuraiya Al Harthi
- Research Department, The Royal Hospital, Ministry of Health, Muscat, Oman
| | - Penny Whiting
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Jessica Watson
- Centre for Academic Primary Care, Bristol Medical School, University of Bristol, Bristol, UK
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Gandhi P, Latifi N. Mild Transaminase Elevation With Rapid Diagnostic Escalation: A Teachable Moment. JAMA Intern Med 2023; 183:1152-1153. [PMID: 37578790 DOI: 10.1001/jamainternmed.2023.3884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/15/2023]
Abstract
This Teachable Moment describes a 33-year-old woman with decreasing transaminase levels on repeated testing and ultrasonography showing fatty infiltration.
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Affiliation(s)
- Priyal Gandhi
- Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Niloofar Latifi
- Division of Hospital Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Schreiner AD, Zhang J, Moran WP, Koch DG, Livingston S, Bays C, Marsden J, Mauldin PD, Gebregziabher M. Real-World Primary Care Data Comparing ALT and FIB-4 in Predicting Future Severe Liver Disease Outcomes. J Gen Intern Med 2023; 38:2453-2460. [PMID: 36814048 PMCID: PMC10465412 DOI: 10.1007/s11606-023-08093-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 02/08/2023] [Indexed: 02/24/2023]
Abstract
BACKGROUND Alanine aminotransferase (ALT) has long provided a cue for chronic liver disease (CLD) diagnostic evaluation, but the Fibrosis-4 Index (FIB-4), a serologic score used for predicting advanced fibrosis risk in CLD, may provide an alternative signal. OBJECTIVE Compare the predictive performance of FIB-4 with ALT for severe liver disease (SLD) events while adjusting for potential confounders. DESIGN Retrospective cohort study of primary care electronic health record data from 2012 to 2021. PATIENTS Adult primary care patients with at least two sets of ALT and other lab values necessary for calculating two unique FIB-4 scores, excluding those patients with an SLD prior to their index FIB-4 value. MAIN MEASURES The occurrence of an SLD event, a composite of cirrhosis, hepatocellular carcinoma, and liver transplantation, was the outcome of interest. Categories of ALT elevation and FIB-4 advanced fibrosis risk were the primary predictor variables. Multivariable logistic regression models were developed to evaluate the association of FIB-4 and ALT with SLD, and the areas under the curve (AUC) for each model were compared. KEY RESULTS The cohort of 20,828 patients included 14% with an abnormal index ALT (≥40 IU/L) and 8% with a high-risk index FIB-4 (≥2.67). During the study period, 667 (3%) patients suffered an SLD event. Adjusted multivariable logistic regression models demonstrated an association between high-risk FIB-4 (OR 19.34; 95%CI 15.50-24.13), persistently high-risk FIB-4 (OR 23.85; 95%CI 18.24-31.17), abnormal ALT (OR 7.07; 95%CI 5.81-8.59), and persistently abnormal ALT (OR 7.58; 95%CI 5.97-9.62) with SLD outcomes. The AUC of the index FIB-4 (0.847, p < 0.001) and combined FIB-4 (0.849, p < 0.001) adjusted models exceeded the index ALT adjusted model (0.815). CONCLUSIONS High-risk FIB-4 scores demonstrated superior performance compared to abnormal ALT in predicting future SLD outcomes.
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Affiliation(s)
| | - Jingwen Zhang
- Medical University of South Carolina, Charleston, SC, USA
| | | | - David G Koch
- Medical University of South Carolina, Charleston, SC, USA
| | | | - Chloe Bays
- Medical University of South Carolina, Charleston, SC, USA
| | - Justin Marsden
- Medical University of South Carolina, Charleston, SC, USA
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Rowe IA. Understanding the risks and benefits of policy action in NAFLD. J Hepatol 2023; 79:22-24. [PMID: 37023965 DOI: 10.1016/j.jhep.2023.03.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 03/21/2023] [Accepted: 03/26/2023] [Indexed: 04/08/2023]
Affiliation(s)
- Ian A Rowe
- Leeds Institute for Data Analytics, St. James's University Hospital, University of Leeds, Leeds, United Kingdom.
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Brindley JH, Abeysekera K, Hood G, Jennings S, Moore J, Hickman M, Alazawi W. Feasibility and acceptability of a primary care liver fibrosis testing pathway centred on the diabetes annual review: PRELUDE1 prospective cohort study protocol. BMJ Open 2023; 13:e066493. [PMID: 37208139 DOI: 10.1136/bmjopen-2022-066493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/21/2023] Open
Abstract
INTRODUCTION Non-alcoholic fatty liver disease is the most common chronic liver disease worldwide affecting 20%-25% in the USA and Europe with a 60%-80% lifetime prevalence for people with type 2 diabetes (T2D). Fibrosis has repeatedly been demonstrated to be the major determinant of liver disease morbidity and mortality and there is currently no routine screening for liver fibrosis in at-risk T2D population. METHODS AND ANALYSIS This 12-month prospective cohort study of automated fibrosis testing uses the fibrosis-4 score (FIB-4) in patients with T2D linked to the investigation of hospital-based versus community-based second-tier transient elastography (TE) testing. We plan to include >5000 participants across 10 General Practitioner (GP) practices in East London and Bristol. This will determine the rate of undiagnosed significant liver fibrosis in a T2D population, the feasibility of two-tier liver fibrosis screening using FIB-4 at the diabetes annual review and subsequent TE delivered either in the community or secondary care settings. This will include an intention-to-treat analysis for all those invited to attend for diabetes annual review. A qualitative substudy regarding the acceptability of the fibrosis screening pathway will comprise semistructured interviews/focus groups with primary care staff (GPs and practice nurses), and patients taking part in the wider study. ETHICS AND DISSEMINATION This study received a favourable opinion from the Cambridge East research ethics committee. The results of this study will be disseminated in peer-reviewed scientific journals, conference presentations and local diabetes lay panel meetings. TRIAL REGISTRATION NUMBER ISRCTN14585543.
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Affiliation(s)
| | - Kushala Abeysekera
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Gill Hood
- Barts Liver Centre, Queen Mary University of London, London, UK
| | - Stacey Jennings
- Wolfson Institute of Population Health, Queen Mary University of London, London, UK
| | - John Moore
- Barts Liver Centre, Queen Mary University of London, London, UK
| | - Matthew Hickman
- Bristol Population Health Science Institute, University of Bristol, Bristol, UK
| | - William Alazawi
- Barts Liver Centre, Queen Mary University of London, London, UK
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Kim RG, Khalili M. Undiagnosed abnormal alanine transaminase levels in vulnerable populations: Impact of sex, race/ethnicity, and body mass. Obes Sci Pract 2023; 9:190-199. [PMID: 37034566 PMCID: PMC10073815 DOI: 10.1002/osp4.634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 07/27/2022] [Accepted: 08/15/2022] [Indexed: 11/07/2022] Open
Abstract
Background Liver disease is a leading cause of death in the United States and is often initially detected incidentally on lab tests ordered by general practitioners. Alanine transaminase (ALT), a marker of liver inflammation, is commonly ordered and may be abnormal in the setting of elevated body mass index, diabetes and dyslipidemia. Data regarding ALT testing within vulnerable populations are limited. Therefore, the prevalence of ALT testing and abnormal ALT in the absence of known chronic liver disease (CLD) among a safety-net population were assessed and factors associated with these outcomes were identified. Methods In this retrospective longitudinal study of 92,997 patients seen between 01/2017-01/2019 within San Francisco's Safety-Net Healthcare System, electronic medical records were used to abstract data back to 04/1997. Descriptive analyses and multivariable modeling were performed. Results Overall, 59,323 (69%) without known CLD received an ALT test. Age, Black race, Latinx ethnicity, and metabolic factors were associated with higher odds of ALT testing, (p < 0.01). Among those with an abnormal ALT (44%) without known CLD: median age 53 years, 41% male, 19% White, 11% Black, 40% Latinx, 29% Asian/Pacific Islander (API), and 84% overweight/obese. On multivariable analysis, female sex (OR 2.7), Latinx ethnicity (OR 2.6), API race (OR 1.3), overweight/obesity (OR 1.8, OR 2.6), and dyslipidemia (OR 1.3) were associated with abnormal ALT, (p ≤ 0.001). Conclusions In the absence of known CLD, women, Latinx, API and persons with excess body weight were associated with greater odds of abnormal ALT. Future longitudinal studies are needed to confirm these differences and to determine if adequate work up for CLD is performed for abnormal ALT levels among at-risk populations.
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Affiliation(s)
- Rebecca G. Kim
- Department of MedicineDivision of Gastroenterology and HepatologyUniversity of California, San FranciscoSan FranciscoCaliforniaUSA
- Division of Gastroenterology and HepatologyZuckerberg San Francisco GeneralSan FranciscoCaliforniaUSA
| | - Mandana Khalili
- Department of MedicineDivision of Gastroenterology and HepatologyUniversity of California, San FranciscoSan FranciscoCaliforniaUSA
- Division of Gastroenterology and HepatologyZuckerberg San Francisco GeneralSan FranciscoCaliforniaUSA
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12
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Schreiner AD, Moran WP, Zhang J, Livingston S, Marsden J, Mauldin PD, Koch D, Gebregziabher M. The Association of Fibrosis-4 Index Scores with Severe Liver Outcomes in Primary Care. J Gen Intern Med 2022; 37:3266-3274. [PMID: 35048297 PMCID: PMC9550951 DOI: 10.1007/s11606-021-07341-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 12/15/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND The Fibrosis-4 Index (FIB-4)non-invasively assesses fibrosis risk in chronic liver disease (CLD), but underdiagnosis limits FIB-4's application in primary care. OBJECTIVE To evaluate the association of FIB-4 risk with hazard of severe liver outcomes in primary care patients with and without diagnosed CLD. DESIGN Retrospective cohort study of primary care data from 2007 to 2018. PARTICIPANTS Adult patients with qualifying aminotransferase and platelet count results were included and a single FIB-4 score was calculated for each patient using the first of these values. Patients with a CLD diagnosis or outcome prior to their FIB-4 score were excluded. MEASURES FIB-4 advanced fibrosis risk categorization (low, indeterminate, and high) was the primary predictor variable. Patients were followed from FIB-4 score to a severe liver outcome, a composite of cirrhosis, liver transplantation, and hepatocellular carcinoma. We analyzed the association of FIB-4 risk categories with hazard risk of a severe liver outcome using stratified Cox regression models, stratifying patients by known CLD. KEY RESULTS A total of 20,556 patients were followed for a mean 2,978 days (SD 1,201 days), and 4% of patients experienced a severe liver outcome. Of patients with low-, indeterminate-, and high-risk FIB-4 scores, 2%, 4%, and 20% suffered a severe liver outcome, respectively. In the overall adjusted model, high-risk FIB-4 scores were associated with hazard of severe liver disease (HR 6.64; 95% CI 5.58-7.90). High-risk FIB-4 scores were associated with severe liver outcomes for patients with known NAFLD (HR 7.32; 95% CI 3.44-15.58), other liver disease (HR 11.39; 95% CI 8.53-15.20), and no known CLD (HR 4.05; 95% CI 3.10-5.28). CONCLUSIONS High-risk FIB-4 scores were strongly associated with risk of severe liver outcomes in patients with and without known CLD. Comprehensive FIB-4 application in primary care may signal silently advancing liver fibrosis.
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Affiliation(s)
- Andrew D Schreiner
- Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA.
| | - William P Moran
- Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA
| | - Jingwen Zhang
- Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA
| | - Sherry Livingston
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, 29425, USA
| | - Justin Marsden
- Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA
| | - Patrick D Mauldin
- Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA
| | - David Koch
- Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA
| | - Mulugeta Gebregziabher
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, 29425, USA
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Scutt P, Ban L, Card T, Crooks CJ, Guha N, West J, Morling JR. Liver blood marker testing in UK primary care: a UK wide cohort study, 2004-2016. BMJ Open 2022; 12:e058967. [PMID: 36167394 PMCID: PMC9516205 DOI: 10.1136/bmjopen-2021-058967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 03/17/2022] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVE We aimed to determine (1) the temporal trends of liver enzyme testing in UK general practice and (2) how these vary among different subgroups at risk of chronic liver disease (CLD). DESIGN Retrospective cohort study. SETTING UK primary care database (Clinical Practice Research Datalink (CPRD)), 2004-2016. PARTICIPANTS Patients aged 18 years or over, registered in the CPRD from 1 January 2004 to 31 December 2016. OUTCOME MEASURES The frequency of testing recorded within the study period in general practice was calculated for: alanine aminotransferase (ALT); aspartate aminotransferase (AST); gamma glutamyl transferase (GGT); alkaline phosphatase (ALP); bilirubin and platelets. Analyses were conducted in subgroups of patients at high risk of developing liver disease. RESULTS The study cohort included 2 912 066 individuals with median follow-up of 3.2 years. The proportion of patients with at least one measurement for ALT, ALP, bilirubin or platelet test gradually increased over the course of the study period and fell for AST and GGT. By 2016, the proportion of the population receiving one of more tests in that year was: platelet count 28.0%, ALP 26.2%, bilirubin 25.6%, ALT 23.7%, GGT 5.1% and AST 2.2%. Those patients with risk factors for CLD had higher proportions receiving liver marker assessments than those without risk factors. CONCLUSIONS The striking finding that AST is now only measured in a fraction of the population has significant implications for routine guidance which frequently expects it. A more nuanced approach where non-invasive markers are targeted towards individuals with risk factors for CLD may be a solution.
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Affiliation(s)
- Polly Scutt
- Lifespan and Population Health, University of Nottingham, Nottingham, UK
| | - Lu Ban
- Lifespan and Population Health, University of Nottingham, Nottingham, UK
- European Office, Evidera, London, UK
| | - Tim Card
- Lifespan and Population Health, University of Nottingham, Nottingham, UK
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - Colin John Crooks
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre (NDDC), School of Medicine, University of Nottingham, Nottingham, UK
| | - Neil Guha
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre (NDDC), School of Medicine, University of Nottingham, Nottingham, UK
| | - Joe West
- Lifespan and Population Health, University of Nottingham, Nottingham, UK
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - Joanne R Morling
- Lifespan and Population Health, University of Nottingham, Nottingham, UK
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
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14
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Ramakrishnan A, Velmurugan G, Somasundaram A, Mohanraj S, Vasudevan D, Vijayaragavan P, Nightingale P, Swaminathan K, Neuberger J. Prevalence of abnormal liver tests and liver fibrosis among rural adults in low and middle-income country: A cross-sectional study. EClinicalMedicine 2022; 51:101553. [PMID: 35860452 PMCID: PMC9289630 DOI: 10.1016/j.eclinm.2022.101553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 06/08/2022] [Accepted: 06/21/2022] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND Liver disease is the only major chronic disease and mortality is increasing. Earlier detection of liver fibrosis can reduce progression to cirrhosis and hepatocellular carcinoma. Many studies have reported an increased prevalence in liver fibrosis among adults in urban regions but there are few data in physically active rural populations without attributable metabolic risk factors. This aim of this study is to investigate the prevalence of abnormal liver functions tests (LFTs) and liver fibrosis among adults in a rural population. METHODS This cross-sectional study included observations from KMCH-NNCD-II (2017) study (n = 907) from a farming village, Nallampatti, located in South India. We assessed lifestyle (occupation, tobacco use and alcohol consumption using AUDIT-C questionnaire), markers for metabolic diseases (obesity, hypertension, diabetes, hypercholesterolemia), LFTs and markers for hepatitis viruses B and C. 901 participants had transient elastography to assess fibrosis. Participants with abnormal LFTs and significant liver fibrosis (F2-F4) underwent additional liver screening (caeruloplasmin, iron studies and autoimmune hepatitis panel). Multiple logistic regression analyses were performed to understand the association of liver fibrosis with lifestyle and metabolic risk factors after adjustment for co-variates. FINDINGS Significant liver fibrosis (F2-F4) was observed in 14.4%, and cirrhosis in 0.8%. There was an association of liver fibrosis with abnormal LFTs but no association between alcohol consumption, viral hepatitis, hepatic liver screening and liver fibrosis. Among metabolic risk factors, no association was observed for hypertension and hypercholesterolemia but diabetes [OR - 3.206 (95% CI: 1.792 - 5.736)], obesity [1.987 (1.341 - 2.944)] and metabolic syndrome [2.539 (1.680 - 3.836)] showed association with significant liver fibrosis (F2-F4) after adjustment for confounding factors. INTERPRETATION Our results suggest that the prevalence of liver fibrosis in rural population is similar to urban counterparts. The association of metabolic risk factors with liver fibrosis in physically active rural population warrants further investigations in future studies. FUNDING This study is funded by KMCH Research Foundation, India.
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Affiliation(s)
- Arulraj Ramakrishnan
- KMCH Research Foundation, Kovai Medical Center and Hospital, Coimbatore 641 014, Tamil Nadu, India
- Liver Unit, Kovai Medical Center and Hospital, Coimbatore 641 014, Tamil Nadu, India
| | - Ganesan Velmurugan
- KMCH Research Foundation, Kovai Medical Center and Hospital, Coimbatore 641 014, Tamil Nadu, India
| | - Aravindh Somasundaram
- Liver Unit, Kovai Medical Center and Hospital, Coimbatore 641 014, Tamil Nadu, India
| | - Sundaresan Mohanraj
- KMCH Research Foundation, Kovai Medical Center and Hospital, Coimbatore 641 014, Tamil Nadu, India
| | - Dinakaran Vasudevan
- KMCH Research Foundation, Kovai Medical Center and Hospital, Coimbatore 641 014, Tamil Nadu, India
| | - Paari Vijayaragavan
- Liver Unit, Kovai Medical Center and Hospital, Coimbatore 641 014, Tamil Nadu, India
| | - Peter Nightingale
- Statistician, University Hospital Birmingham, Birmingham, B15 2TH United Kingdom
| | - Krishnan Swaminathan
- KMCH Research Foundation, Kovai Medical Center and Hospital, Coimbatore 641 014, Tamil Nadu, India
| | - James Neuberger
- Liver Unit, University Hospital Birmingham, Birmingham, B15 2TH United Kingdom
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15
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Abeysekera KWM, Macpherson I, Glyn-Owen K, McPherson S, Parker R, Harris R, Yeoman A, Rowe IA, Dillon JF. Community pathways for the early detection and risk stratification of chronic liver disease: a narrative systematic review. Lancet Gastroenterol Hepatol 2022; 7:770-780. [PMID: 35525248 DOI: 10.1016/s2468-1253(22)00020-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 01/24/2022] [Accepted: 01/25/2022] [Indexed: 02/07/2023]
Abstract
Patients with chronic liver disease are often diagnosed during an index presentation to hospital with decompensated cirrhosis or liver-related events, and these presentations are associated with high mortality. However, there is often a long asymptomatic phase, in which there is an opportunity for earlier diagnosis and interventions to prevent progression to advanced disease. Therefore, strategies for early diagnosis and interventions (including behavioural changes and pharmacological treatments) that prevent patients progressing to cirrhosis and its associated complications probably have substantial benefits for patients and health-care services. Many community pathways have been generated. Some pathways focus on abnormal liver function tests as a starting point to diagnose liver disease. Other pathways target groups at greater risk of chronic liver disease-particularly people with harmful alcohol consumption, type 2 diabetes, and obesity. This systematic review summarises the existing strategies available for the early detection or risk stratification of liver disease, focusing primarily on alcohol-related liver disease and non-alcoholic fatty liver disease. Conducting randomised clinical trials that compare different strategies will be essential to elucidate which pathways are acceptable to patients, feasible, provide high diagnostic accuracy for the detection of liver disease, improve liver-related outcomes, and are most cost-effective at the population level.
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Affiliation(s)
| | - Iain Macpherson
- Division of Clinical and Molecular Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
| | - Kate Glyn-Owen
- School of Primary Care, Population Science and Medical Education (PPM), Faculty of Medicine, University of Southampton, University Hospital Southampton, UK
| | - Stuart McPherson
- Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, UK
| | - Richard Parker
- Leeds Liver Unit, St James's University Hospital, Leeds, UK
| | - Rebecca Harris
- National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Andrew Yeoman
- Aneurin Bevan University Health Board, Hepatology, Newport, UK
| | - Ian A Rowe
- Leeds Liver Unit, St James's University Hospital, Leeds, UK; Leeds Institute for Medical Research, University of Leeds, Leeds, UK
| | - John F Dillon
- Division of Clinical and Molecular Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
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16
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Liver function tests in primary care provide a key opportunity to diagnose and engage patients with hepatitis C. Epidemiol Infect 2022; 150:e133. [PMID: 35757860 PMCID: PMC9306009 DOI: 10.1017/s0950268822000978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Since the advent of direct-acting antiviral therapy, the elimination of hepatitis c virus (HCV) as a public health concern is now possible. However, identification of those who remain undiagnosed, and re-engagement of those who are diagnosed but remain untreated, will be essential to achieve this. We examined the extent of HCV infection among individuals undergoing liver function tests (LFT) in primary care. Residual biochemistry samples for 6007 patients, who had venous blood collected in primary care for LFT between July 2016 and January 2017, were tested for HCV antibody. Through data linkage to national and sentinel HCV surveillance databases, we also examined the extent of diagnosed infection, attendance at specialist service and HCV treatment for those found to be HCV positive. Overall HCV antibody prevalence was 4.0% and highest for males (5.0%), those aged 37–50 years (6.2%), and with an ALT result of 70 or greater (7.1%). Of those testing positive, 68.9% had been diagnosed with HCV in the past, 84.9% before the study period. Most (92.5%) of those diagnosed with chronic infection had attended specialist liver services and while 67.7% had ever been treated only 38% had successfully cleared infection. More than half of HCV-positive people required assessment, and potentially treatment, for their HCV infection but were not engaged with services during the study period. LFT in primary care are a key opportunity to diagnose, re-diagnose and re-engage patients with HCV infection and highlight the importance of GPs in efforts to eliminate HCV as a public health concern.
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17
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Hodgson SH, Iveson P, Larwood J, Roche S, Morrison H, Cosgrove C, Galiza E, Ikram S, Lemm N, Mehdipour S, Owens D, Pacurar M, Schumacher M, Shaw RH, Faust SN, Heath PT, Pollard AJ, Emary KRW, Pollock KM, Lazarus R. Incidental findings in UK healthy volunteers screened for a COVID-19 vaccine trial. Clin Transl Sci 2022; 15:524-534. [PMID: 34670021 PMCID: PMC8652599 DOI: 10.1111/cts.13170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 08/29/2021] [Accepted: 09/13/2021] [Indexed: 11/29/2022] Open
Abstract
The safety of novel therapeutics and vaccines are typically assessed in early phase clinical trials involving "healthy volunteers." Abnormalities in such individuals can be difficult to interpret and may indicate previously unrecognized medical conditions. The frequency of incidental findings (IFs) in healthy volunteers who attend for clinical trial screening is unclear. To assess this, we retrospectively analyzed data for 1838 "healthy volunteers" screened for enrolment in a UK multicenter, phase I/II severe acute respiratory syndrome-coronavirus 2 (SARS-COV-2) vaccine trial. Participants were predominantly White (89.7%, 1640/1828) with a median age of 34 years (interquartile range [IQR] = 27-44). There were 27.7% of participants (510/1838) who had at least one IF detected. The likelihood of identifying evidence of a potential, new blood-borne virus infection was low (1 in 238 participants) compared with identification of an elevated alanine transaminase (ALT; 1 in 17 participants). A large proportion of participants described social habits that could impact negatively on their health; 21% consumed alcohol in excess, 10% were current smokers, 11% described recreational drug use, and only 48% had body weight in the ideal range. Our data demonstrate that screening prior to enrollment in early phase clinical trials identifies a range of IFs, which should inform discussion during the consent process. Greater clarity is needed to ensure an appropriate balance is struck between early identification of medical problems and avoidance of exclusion of volunteers due to spurious or physiological abnormalities. Debate should inform the role of the trial physician in highlighting and advising about unhealthy social habits.
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Affiliation(s)
- Susanne H. Hodgson
- Centre for Clinical Vaccinology and Tropical MedicineThe Jenner InstituteUniversity of OxfordOxfordUK
| | - Poppy Iveson
- The University of Oxford Clinical Medical SchoolUniversity of OxfordOxfordUK
| | - Jessica Larwood
- The University of Oxford Clinical Medical SchoolUniversity of OxfordOxfordUK
| | - Sophie Roche
- The University of Oxford Clinical Medical SchoolUniversity of OxfordOxfordUK
| | - Hazel Morrison
- Centre for Clinical Vaccinology and Tropical MedicineThe Jenner InstituteUniversity of OxfordOxfordUK
| | | | - Eva Galiza
- Vaccine InstituteSt George’s University of LondonLondonUK
| | - Sabina Ikram
- Vaccine InstituteSt George’s University of LondonLondonUK
| | | | | | - Daniel Owens
- NIHR Southampton Clinical Research Facility and NIHR Southampton Biomedical Research CentreUniversity Hospital Southampton NHS Foundation TrustFaculty of Medicine and Institute for Life SciencesUniversity of SouthamptonSouthamptonUK
| | - Mihaela Pacurar
- NIHR Southampton Clinical Research Facility and NIHR Southampton Biomedical Research CentreUniversity Hospital Southampton NHS Foundation TrustFaculty of Medicine and Institute for Life SciencesUniversity of SouthamptonSouthamptonUK
| | | | - Robert H. Shaw
- Oxford Vaccine GroupDepartment of PaediatricsCentre for Clinical Vaccinology and Tropical MedicineNIHR Oxford Biomedical Research CentreUniversity of OxfordOxfordUK
| | - Saul N. Faust
- NIHR Southampton Clinical Research Facility and NIHR Southampton Biomedical Research CentreUniversity Hospital Southampton NHS Foundation TrustFaculty of Medicine and Institute for Life SciencesUniversity of SouthamptonSouthamptonUK
| | - Paul T. Heath
- Vaccine InstituteSt George’s University of LondonLondonUK
| | - Andrew J. Pollard
- Oxford Vaccine GroupDepartment of PaediatricsCentre for Clinical Vaccinology and Tropical MedicineNIHR Oxford Biomedical Research CentreUniversity of OxfordOxfordUK
| | - Katherine R. W. Emary
- Oxford Vaccine GroupDepartment of PaediatricsCentre for Clinical Vaccinology and Tropical MedicineNIHR Oxford Biomedical Research CentreUniversity of OxfordOxfordUK
| | | | - Rajeka Lazarus
- University Hospitals Bristol and Weston NHS Foundation TrustBristolUK
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18
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Karlsen TH, Sheron N, Zelber-Sagi S, Carrieri P, Dusheiko G, Bugianesi E, Pryke R, Hutchinson SJ, Sangro B, Martin NK, Cecchini M, Dirac MA, Belloni A, Serra-Burriel M, Ponsioen CY, Sheena B, Lerouge A, Devaux M, Scott N, Hellard M, Verkade HJ, Sturm E, Marchesini G, Yki-Järvinen H, Byrne CD, Targher G, Tur-Sinai A, Barrett D, Ninburg M, Reic T, Taylor A, Rhodes T, Treloar C, Petersen C, Schramm C, Flisiak R, Simonova MY, Pares A, Johnson P, Cucchetti A, Graupera I, Lionis C, Pose E, Fabrellas N, Ma AT, Mendive JM, Mazzaferro V, Rutter H, Cortez-Pinto H, Kelly D, Burton R, Lazarus JV, Ginès P, Buti M, Newsome PN, Burra P, Manns MP. The EASL-Lancet Liver Commission: protecting the next generation of Europeans against liver disease complications and premature mortality. Lancet 2022; 399:61-116. [PMID: 34863359 DOI: 10.1016/s0140-6736(21)01701-3] [Citation(s) in RCA: 351] [Impact Index Per Article: 117.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 07/10/2021] [Accepted: 07/15/2021] [Indexed: 02/07/2023]
Affiliation(s)
- Tom H Karlsen
- Department of Transplantation Medicine and Research Institute for Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, Norway.
| | - Nick Sheron
- Institute of Hepatology, Foundation for Liver Research, Kings College London, London, UK
| | - Shira Zelber-Sagi
- School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel; Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Patrizia Carrieri
- Aix-Marseille University, Inserm, Institut de recherche pour le développement, Sciences Economiques et Sociales de la Santé et Traitement de l'Information Médicale (SESSTIM), ISSPAM, Marseille, France
| | - Geoffrey Dusheiko
- School of Medicine, University College London, London, UK; Kings College Hospital, London, UK
| | - Elisabetta Bugianesi
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, Torino, Italy
| | | | - Sharon J Hutchinson
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Clinical and Protecting Health Directorate, Public Health Scotland, Glasgow, UK
| | - Bruno Sangro
- Liver Unit, Clinica Universidad de Navarra-IDISNA and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Pamplona, Spain
| | - Natasha K Martin
- Division of Infectious Diseases and Global Public Health, University of California San Diego, San Diego, CA, USA; Population Health Sciences, University of Bristol, Bristol, UK
| | - Michele Cecchini
- Health Division, Organisation for Economic Co-operation and Development, Paris, France
| | - Mae Ashworth Dirac
- Department of Health Metrics Sciences, University of Washington, Seattle, WA, USA; Department of Family Medicine, University of Washington, Seattle, WA, USA; Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
| | - Annalisa Belloni
- Health Economics and Modelling Division, Public Health England, London, UK
| | - Miquel Serra-Burriel
- Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland
| | - Cyriel Y Ponsioen
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam University Medical Centers, Amsterdam, Netherlands
| | - Brittney Sheena
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
| | - Alienor Lerouge
- Health Division, Organisation for Economic Co-operation and Development, Paris, France
| | - Marion Devaux
- Health Division, Organisation for Economic Co-operation and Development, Paris, France
| | - Nick Scott
- Disease Elimination Program, Burnet Institute, Melbourne, VIC, Australia
| | - Margaret Hellard
- Disease Elimination Program, Burnet Institute, Melbourne, VIC, Australia; Department of Infectious Diseases, Alfred Hospital, Melbourne, VIC, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia; Doherty Institute and School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia
| | - Henkjan J Verkade
- Paediatric Gastroenterology and Hepatology, Department of Paediatrics, University Medical Centre Groningen, University of Groningen, Netherlands; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
| | - Ekkehard Sturm
- Division of Paediatric Gastroenterology and Hepatology, University Children's Hospital Tübingen, Tübingen, Germany; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
| | | | | | - Chris D Byrne
- Department of Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK; Southampton National Institute for Health Research, Biomedical Research Centre, University Hospital Southampton and Southampton General Hospital, Southampton, UK
| | - Giovanni Targher
- Department of Medicine, Section of Endocrinology, Diabetes, and Metabolism, University of Verona, Verona, Italy
| | - Aviad Tur-Sinai
- Department of Health Systems Management, The Max Stern Yezreel Valley College, Yezreel Valley, Israel
| | - Damon Barrett
- School of Public Health and Community Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | | | - Tatjana Reic
- European Liver Patients Organization, Brussels, Belgium; Croatian Society for Liver Diseases-Hepatos, Split, Croatia
| | | | - Tim Rhodes
- London School of Hygiene & Tropical Medicine, London, UK
| | - Carla Treloar
- Centre for Social Research in Health, University of New South Wales, Sydney, NSW, Australia
| | - Claus Petersen
- Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany
| | - Christoph Schramm
- Martin Zeitz Center for Rare Diseases, Hamburg Center for Translational Immunology (HCTI), and First Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Poland
| | - Marieta Y Simonova
- Department of Gastroenterology, HPB Surgery and Transplantation, Clinic of Gastroentrology, Military Medical Academy, Sofia, Bulgaria
| | - Albert Pares
- Liver Unit, Hospital Clinic of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; CIBEREHD, Madrid, Spain
| | - Philip Johnson
- Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences-DIMEC, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Isabel Graupera
- Liver Unit, Hospital Clinic of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; CIBEREHD, Madrid, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Spain
| | - Christos Lionis
- Clinic of Social and Family Medicine, Medical School, University of Crete, Heraklion, Greece
| | - Elisa Pose
- Liver Unit, Hospital Clinic of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Spain
| | - Núria Fabrellas
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; CIBEREHD, Madrid, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Spain
| | - Ann T Ma
- Liver Unit, Hospital Clinic of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Juan M Mendive
- Prevention and Health Promotion Research Network (redIAPP), Institute of Health Carlos III, Madrid, Spain; La Mina Health Centre, Catalan Institute of Health (ICS), Barcelona, Spain
| | - Vincenzo Mazzaferro
- HPB Surgery and Liver Transplantation, Istituto Nazionale Tumori IRCCS Foundation (INT), Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Harry Rutter
- Department of Social and Policy Sciences, University of Bath, Bath, UK
| | - Helena Cortez-Pinto
- Clínica Universitária de Gastrenterologia and Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Deirdre Kelly
- Liver Unit, Birmingham Women's and Children's Hospital and University of Birmingham, UK
| | - Robyn Burton
- Alcohol, Drugs, Tobacco and Justice Division, Public Health England, London, UK
| | - Jeffrey V Lazarus
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, Barcelona, Spain
| | - Pere Ginès
- Liver Unit, Hospital Clinic of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; CIBEREHD, Madrid, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Spain
| | - Maria Buti
- CIBEREHD del Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Hospital Universitario Valle Hebron, Barcelona, Spain
| | - Philip N Newsome
- National Institute for Health Research Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK
| | - Patrizia Burra
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
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19
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Yeoman AD. Novel Approaches to Detect Significant Liver Disease in the General Population. Clin Liver Dis (Hoboken) 2021; 18:99-103. [PMID: 34584677 PMCID: PMC8450484 DOI: 10.1002/cld.1097] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 11/17/2020] [Accepted: 12/22/2020] [Indexed: 02/04/2023] Open
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20
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Subhani M, Sheth A, Ahmad B, Ryder S. How to interpret and manage abnormal liver blood test results in older people. Br J Hosp Med (Lond) 2021; 82:1-8. [PMID: 34431345 DOI: 10.12968/hmed.2021.0114] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Ageing impairs liver function and reduces the liver's regenerative capacity. With the predicted increase in the older population, the burden of liver disease will proportionally rise in this age group. Elevated levels of liver enzymes in an otherwise asymptomatic older individual (≥65 years) are a common observation and positively associated with the metabolic syndrome, whereas a decline in albumin levels is linked with a rise in all-cause and liver-specific mortality. Deranged liver function tests do not always indicate liver disease, nor do normal liver function tests exclude liver disease. Therefore, clinicians need to consider individual patient risk factors during the assessment of abnormal liver function tests. This article discusses various liver function tests, their pathophysiology, and the approach to interpret and manage common abnormalities in liver function test results and liver disease in the older population.
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Affiliation(s)
- Mohsan Subhani
- Nottingham Digestive Diseases Biomedical Research Centre, School of Medicine, University of Nottingham, Nottingham, UK.,NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Abhishek Sheth
- Nottingham Digestive Diseases Biomedical Research Centre, School of Medicine, University of Nottingham, Nottingham, UK.,NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Bilal Ahmad
- Department of Gastroenterology, Wrexham Maelor Hospital, Wrexham, UK
| | - Stephen Ryder
- Nottingham Digestive Diseases Biomedical Research Centre, School of Medicine, University of Nottingham, Nottingham, UK
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21
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Surana P, Hercun J, Takyar V, Kleiner DE, Heller T, Koh C. Platelet count as a screening tool for compensated cirrhosis in chronic viral hepatitis. World J Gastrointest Pathophysiol 2021; 12:40-50. [PMID: 34084591 PMCID: PMC8160599 DOI: 10.4291/wjgp.v12.i3.40] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 02/25/2021] [Accepted: 03/31/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Simple tools for clinicians to identify cirrhosis in patients with chronic viral hepatitis are medically necessary for treatment initiation, hepatocellular cancer screening and additional medical management.
AIM To determine whether platelets or other laboratory markers can be used as a simple method to identify the development of cirrhosis.
METHODS Clinical, biochemical and histologic laboratory data from treatment naive chronic viral hepatitis B (HBV), C (HCV), and D (HDV) patients at the NIH Clinical Center from 1985-2019 were collected and subjects were randomly divided into training and validation cohorts. Laboratory markers were tested for their ability to identify cirrhosis (Ishak ≥ 5) using receiver operating characteristic curves and an optimal cut-off was calculated within the training cohort. The final cut-off was tested within the validation cohort.
RESULTS Overall, 1027 subjects (HCV = 701, HBV = 240 and HDV = 86), 66% male, with mean (standard deviation) age of 45 (11) years were evaluated. Within the training cohort (n = 715), platelets performed the best at identifying cirrhosis compared to other laboratory markers [Area Under the Receiver Operating Characteristics curve (AUROC) = 0.86 (0.82-0.90)] and sensitivity 77%, specificity 83%, positive predictive value 44%, and negative predictive value 95%. All other tested markers had AUROCs ≤ 0.77. The optimal platelet cut-off for detecting cirrhosis in the training cohort was 143 × 109/L and it performed equally well in the validation cohort (n = 312) [AUROC = 0.85 (0.76-0.94)].
CONCLUSION The use of platelet counts should be considered to identify cirrhosis and ensure optimal care and management of patients with chronic viral hepatitis.
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Affiliation(s)
- Pallavi Surana
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, United States
| | - Julian Hercun
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, United States
| | - Varun Takyar
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, United States
| | - David E Kleiner
- Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, United States
| | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, United States
| | - Christopher Koh
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, United States
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23
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Agarwal R. Aging Liver and Interpretation of Liver Tests. GERIATRIC GASTROENTEROLOGY 2021:1329-1352. [DOI: 10.1007/978-3-030-30192-7_49] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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24
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Keerl C, Bernsmeier C. [Elevated liver function tests - as incidental finding in general practice]. Ther Umsch 2020; 77:371-378. [PMID: 33054645 DOI: 10.1024/0040-5930/a001206] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Elevated liver function tests - as incidental finding in general practice Abstract. In general practice, elevated liver function tests are found in 25 % of patients presenting with unspecific symptoms or during a routine health checkup. Approximately 2.5 % of the general population are expected to show elevated values. Conversely, liver disease can present without abnormal liver function tests. Liver disease is not only frequent but may also imply a significant mortality. Worldwide its prevalence is steadily rising, and liver disease has become the fifth leading cause of death. Responsible for the rapidly increasing prevalence are primarily non-alcoholic fatty liver disease (NAFLD), alcohol-related liver disease (ARLD) and viral hepatitis. Due to the large range of possible differential diagnoses and the coexistence of aetiologies liver diseases represent a diagnostic challenge with important prognostic implication. In case of elevated liver function, a detailed medical history and a thorough clinical examination should be performed first. This allows narrowing down possible causes to the few most likely differential diagnoses. Subsequently, depending on the level of elevated liver function and the clinical presentation as hepatitis or cholestasis, screening tests for differential liver diseases are performed. Laboratory diagnostics and obligatory ultrasound scan can be supplemented by non-invasive methods (e. g. elastography, MRI / MRCP / CT) and in selected cases invasive methods (liver biopsy, ERCP). In the following article we delineate the diagnostic approach to elevated liver function tests using algorithms.
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Affiliation(s)
- Claudia Keerl
- Gastroenterologie und Hepatologie, Clarunis Universitäres Bauchzentrum Basel, St. Claraspital und Universitätsspital Basel.,Claudia Keerl und Christine Bernsmeier haben in gleichem Masse zum Manuskript beigetragen
| | - Christine Bernsmeier
- Gastroenterologie und Hepatologie, Clarunis Universitäres Bauchzentrum Basel, St. Claraspital und Universitätsspital Basel.,Claudia Keerl und Christine Bernsmeier haben in gleichem Masse zum Manuskript beigetragen
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25
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Thiagarajan P, Chalmers J, Guha IN, James MW. Detecting chronic liver disease: are liver function tests the solution? Br J Hosp Med (Lond) 2020; 81:1-8. [PMID: 32097065 DOI: 10.12968/hmed.2019.0308] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
By 2020, chronic liver disease will have eclipsed ischaemic heart disease as the leading cause of working life years lost in the UK. As mortality from chronic liver disease continues to rise, the landscape of aetiology has shifted from infectious to non-communicable causes. In parallel with the growing prevalence of obesity and type 2 diabetes, non-alcoholic fatty liver disease is estimated to affect 25% of the UK adult population. Simultaneously, escalating alcohol consumption has fuelled public health and economic concerns regarding its widespread impact on working-age adults. Given that chronic liver disease remains clinically silent until its advanced stages, there is an urgent unmet need to identify affected individuals earlier in the disease process, enabling targeted intervention strategies which may improve prognosis. Robust epidemiological data have shown that liver fibrosis is the strongest predictor of clinically meaningful outcomes, including decompensation, liver cancer and overall mortality. Detecting fibrosis among at-risk individuals, in a manner that is reproducible, non-invasive, safe and cost effective, has become a major challenge of our time. This article addresses the pitfalls of the standard panel of liver function tests, discusses other non-invasive biomarkers and reviews imaging technologies which may revolutionise community-based diagnosis and stratification of chronic liver disease.
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Affiliation(s)
- Prarthana Thiagarajan
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK.,University of Nottingham, Nottingham, UK.,Nottingham Digestive Diseases Centre, Nottingham, UK
| | - Jane Chalmers
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK.,University of Nottingham, Nottingham, UK.,Nottingham Digestive Diseases Centre, Nottingham, UK
| | - Indra N Guha
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK.,University of Nottingham, Nottingham, UK.,Nottingham Digestive Diseases Centre, Nottingham, UK
| | - Martin W James
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK.,University of Nottingham, Nottingham, UK.,Nottingham Digestive Diseases Centre, Nottingham, UK
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26
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Schreiner AD, Bian J, Zhang J, Haulsee ZM, Marsden J, Durkalski-Mauldin V, Mauldin PD, Moran WP, Rockey DC. The Association of Abnormal Liver Tests with Hepatitis C Testing in Primary Care. Am J Med 2020; 133:214-221.e1. [PMID: 31369723 PMCID: PMC6980508 DOI: 10.1016/j.amjmed.2019.07.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 06/27/2019] [Accepted: 07/01/2019] [Indexed: 12/25/2022]
Abstract
BACKGROUND As hepatitis C virus birth cohort (1945-1965) screening in primary care improves, testing patterns in response to persistently abnormal liver tests are less well known. METHODS This retrospective cohort study of a patient-centered medical home between 2007 and 2016 evaluates the association of abnormal liver chemistries and other clinical and demographic factors with hepatitis C antibody (HCV Ab) testing in patients with persistently abnormal liver tests. Patients with at least 2 consecutive abnormal liver tests were categorized by the clinical pattern of liver chemistry abnormality, including cholestatic, hepatocellular, and mixed patterns. The primary outcomes were: 1) completed HCV Ab tests; and 2) positive HCV Ab results for those patients tested. RESULTS Of 4512 patients with consecutive abnormal liver tests, only 730 (16%) underwent HCV Ab testing within 1 year of the second abnormality; 81/730 (11%) had HCV Ab detected. A logistic regression model revealed that mixed (odds ratio [OR] 2.20; 95% confidence interval [CI], 1.72-2.82) and hepatocellular (OR 1.43; 95% CI, 1.15-1.79) patterns of liver test abnormality, female sex, and alcohol and tobacco abuse were associated with higher odds of HCV Ab testing. Hepatocellular (OR 7.51; 95% CI, 2.18-25.94) and mixed patterns (OR 5.88; 95% CI, 1.64-21.15) of liver test abnormalities, male sex, Medicaid enrollment, and drug and tobacco abuse had higher odds of positive HCV Ab results. CONCLUSIONS There is opportunity to improve hepatitis C diagnostic testing in patients with consecutively elevated liver tests, and hepatocellular and mixed patterns of abnormality should prompt primary care providers to action.
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Affiliation(s)
- Andrew D Schreiner
- Department of Medicine, Medical University of South Carolina, Charleston, SC.
| | - John Bian
- Department of Medicine, Medical University of South Carolina, Charleston, SC
| | - Jingwen Zhang
- Department of Medicine, Medical University of South Carolina, Charleston, SC
| | - Z Merle Haulsee
- Department of Medicine, Medical University of South Carolina, Charleston, SC
| | - Justin Marsden
- Department of Medicine, Medical University of South Carolina, Charleston, SC
| | | | - Patrick D Mauldin
- Department of Medicine, Medical University of South Carolina, Charleston, SC
| | - William P Moran
- Department of Medicine, Medical University of South Carolina, Charleston, SC
| | - Don C Rockey
- Department of Medicine, Medical University of South Carolina, Charleston, SC
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Li W, Homer K, Hull S, Boomla K, Robson J, Alazawi W. Obesity Predicts Liver Function Testing and Abnormal Liver Results. Obesity (Silver Spring) 2020; 28:132-138. [PMID: 31804018 DOI: 10.1002/oby.22669] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Accepted: 09/06/2019] [Indexed: 01/15/2023]
Abstract
OBJECTIVE Abnormal liver function tests in children and young people (CYP) predict a greater burden of liver disease in adulthood, especially in the context of obesity. This study aimed to determine whether obesity and metabolic risk factors predict liver function testing and abnormal liver test results in CYP. METHODS This was a retrospective cross-sectional population study using electronic health care records from 257,746 CYP aged 10 to 25 years who were registered with 170 contiguous general practices in London, UK. Demographic and clinical data were extracted, including serum alanine aminotransferase (ALT) tests between 2015 and 2017. BMI category thresholds were adjusted according to age group and ethnicity. RESULTS Fourteen percent of CYP had ALT measured, of whom 5.4% had abnormal results; 36.3% had BMI indicating overweight or obesity. Nonalcoholic fatty liver disease was the most common liver diagnosis. Multivariate analyses demonstrated that overweight or obesity was an independent predictor of ALT testing in young people (ages 18-25) but not in children (ages 10-17) and of abnormal test results in all CYP, irrespective of ALT threshold. CONCLUSIONS Overweight and obesity are predictors of liver testing (not in children) and abnormal test results, irrespective of ALT threshold. Given the rising prevalence of metabolic dysfunction, a coordinated strategy is needed for liver testing and interpreting results in this young population.
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Affiliation(s)
- Wenhao Li
- Barts Liver Centre, Blizard Institute, Queen Mary University of London, London, UK
| | - Kate Homer
- Centre of Primary Care and Public Health, Queen Mary University of London, London, UK
| | - Sally Hull
- Centre of Primary Care and Public Health, Queen Mary University of London, London, UK
| | - Kambiz Boomla
- Centre of Primary Care and Public Health, Queen Mary University of London, London, UK
| | - John Robson
- Centre of Primary Care and Public Health, Queen Mary University of London, London, UK
| | - William Alazawi
- Barts Liver Centre, Blizard Institute, Queen Mary University of London, London, UK
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28
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Schreiner AD, Bian J, Zhang J, Kirkland EB, Heincelman ME, Schumann SO, Mauldin PD, Moran WP, Rockey DC. When Do Clinicians Follow-up Abnormal Liver Tests in Primary Care? Am J Med Sci 2019; 358:127-133. [PMID: 31331450 DOI: 10.1016/j.amjms.2019.04.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Revised: 01/23/2019] [Accepted: 04/17/2019] [Indexed: 11/30/2022]
Abstract
BACKGROUND Many guidelines addressing the approach to abnormal liver chemistries, including bilirubin, transaminases and alkaline phosphatase, recommend repeating the tests. However, when clinicians repeat testing is unknown. MATERIAL AND METHODS This retrospective study followed adult patients with abnormal liver chemistries in a patient-centered medical home (PCMH) from 2007 to 2016. All PCMH patients possessing at least 1 abnormal liver test (total bilirubin, aminotransferases and alkaline phosphatase) were included. Patients were followed from the index abnormal liver chemistry until the next liver test result, or the end of the study period. The primary predictor variable of interest was the number of abnormal chemistries (out of 4) on index testing. Demographic and clinical variables served as other potential predictors of outcome. A Cox proportional hazards model was applied to investigate associations between the predictor variables and the time to repeat liver chemistry testing. RESULTS Of 9,545 patients with at least 2 PCMH visits and 1 liver test abnormality, 6,489 (68%) obtained repeat testing within 1 year, and 80% of patients had follow-up tests within 2 years. Patients with multiple abnormal liver tests and those with higher degrees of abnormality were associated with shorter time to repeat testing. CONCLUSIONS A large proportion of patients with abnormal liver tests still lack repeat testing at 1 year. The number of liver abnormal liver tests and degree of elevation were inversely associated with the time to repeat testing.
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Affiliation(s)
- Andrew D Schreiner
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina.
| | - John Bian
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina
| | - Jingwen Zhang
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina
| | - Elizabeth B Kirkland
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina
| | - Marc E Heincelman
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina
| | - Samuel O Schumann
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina
| | - Patrick D Mauldin
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina
| | - William P Moran
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina
| | - Don C Rockey
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina
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Härmälä S, O’Brien A, Parisinos CA, Direk K, Shallcross L, Hayward A. Development and validation of a prediction model to estimate the risk of liver cirrhosis in primary care patients with abnormal liver blood test results: protocol for an electronic health record study in Clinical Practice Research Datalink. Diagn Progn Res 2019; 3:10. [PMID: 31143841 PMCID: PMC6532213 DOI: 10.1186/s41512-019-0056-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Accepted: 03/29/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Driven by alcohol consumption and obesity, the prevalence of non-viral liver disease in the UK is increasing. Due to its silent and slow nature, the progression of liver disease is currently unpredictable and challenging to monitor. The latest National Institute for Health Care Excellence cirrhosis guidelines call for a validated risk tool that would allow general practitioners to identify patients that are at high risk of developing cirrhosis. METHODS Using linked electronic health records from the Clinical Practice Research Datalink (a database of > 10 million patients in England), we aim to develop and validate a prediction model to estimate 2-, 5- and 10-year risk of cirrhosis. The model will provide individualised cirrhosis risk predictions for adult primary care patients, free from underlying liver disease or viral hepatitis infection, whose liver blood test results come back abnormal. We will externally validate the model in patients from 30 further Clinical Practice Research Datalink general practices in England. DISCUSSION The prediction model will provide estimates of cirrhosis risk in primary care patients with abnormal liver blood test results to guide referral to secondary care, to identify patients who are in serious need of preventative health interventions and to help reassure patients at low risk of cirrhosis in the long term.
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Affiliation(s)
- Suvi Härmälä
- 0000000121901201grid.83440.3bInstitute of Health Informatics, University College London, 222 Euston Road, London, NW1 2DA UK
| | - Alastair O’Brien
- 0000000121901201grid.83440.3bDivision of Medicine, University College London, Rayne Building, 5 University Street, London, WC1E 6JJ UK
| | - Constantinos A. Parisinos
- 0000000121901201grid.83440.3bInstitute of Health Informatics, University College London, 222 Euston Road, London, NW1 2DA UK
| | - Kenan Direk
- 0000000121901201grid.83440.3bInstitute of Health Informatics, University College London, 222 Euston Road, London, NW1 2DA UK
| | - Laura Shallcross
- 0000000121901201grid.83440.3bInstitute of Health Informatics, University College London, 222 Euston Road, London, NW1 2DA UK
| | - Andrew Hayward
- 0000000121901201grid.83440.3bInstitute of Epidemiology and Health Care, University College London, 1-19 Torrington Place, London, WC1E 7HB UK
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GPs' experiences and perceptions of early detection of liver disease: a qualitative study in primary care. Br J Gen Pract 2018; 68:e743-e749. [PMID: 30249611 DOI: 10.3399/bjgp18x699377] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Accepted: 05/31/2018] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The incidence of liver disease is increasing in the UK and primary care is a key setting where improvement in the detection and management of liver disease is required. Little is known about GPs' understanding and confidence in detecting liver disease. AIM To explore GPs' experiences of liver disease with a focus on early detection and interpretation of liver function tests (LFTs). DESIGN AND SETTING A qualitative study employing semi-structured interviews of a purposive sample of GPs from five UK primary care study sites. METHOD Telephone and face-to-face interviews of GPs were undertaken. Data were analysed thematically, using a constant comparative approach. RESULTS From a total of 25 GP interviews (N = 25), four themes were identified from the data: test-requesting behaviour, confidence and challenges in diagnosing disease, access to specialist tests, and guidance and education. Participants' descriptions of how they request and interpret LFTs varied widely. Concern over missing diagnoses was a common reason for requesting blood tests; patients with mildly abnormal LFTs and those at risk of non-alcoholic fatty liver disease (NAFLD) were a particular cause of concern. GPs saw themselves as generalists, with a reluctance to take on specialist investigations. Guidelines promoted confidence for some clinicians, but others felt that liver disease was too complex to be amenable to simple instructions. Most felt that they did not have access to relevant, focused education on liver disease. CONCLUSION Liver disease is not perceived as a priority in primary care. If GPs are to take on a greater role in identification and management of liver disease, support is needed to promote awareness, knowledge, and confidence.
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Miller MH, Fraser A, Leggett G, MacGilchrist A, Gibson G, Orr J, Forrest EH, Dow E, Bartlett W, Weatherburn C, Laurell A, Grant K, Scott K, Neville R, Dillon JF. Development and validation of diagnostic triage criteria for liver disease from a minimum data set enabling the 'intelligent LFT' pathway for the automated assessment of deranged liver enzymes. Frontline Gastroenterol 2018; 9:175-182. [PMID: 30046420 PMCID: PMC6056084 DOI: 10.1136/flgastro-2017-100909] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Revised: 12/22/2017] [Accepted: 01/14/2018] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Liver function tests (LFTs) are commonly abnormal; most patients with 'incidental' abnormal LFTs are not investigated appropriately and for those who are, current care pathways are geared to find an explanation for the abnormality by a lengthy process of investigation and exclusion, with costs to the patient and to the health service. OBJECTIVE To validate an intelligent automatable analysis tool (iLFT) for abnormal liver enzymes, which diagnoses common liver conditions, provides fibrosis stage and recommends management. DESIGN A retrospective case note review from three tertiary referral liver centres, with application of the iLFT algorithm and comparison with the clinician's final opinion as gold standard. RESULTS The iLFT algorithm in 91.3% of cases would have correctly recommended referral or management in primary care. In the majority of the rest of the cases, iLFT failed safe and recommended referral even when the final clinical diagnosis could have been managed in primary care. Diagnostic accuracy was achieved in 82.4% of cases, consistent with the fail-safe design of the algorithm. Two cases would have remained in primary care as per the algorithm outcome, however on clinical review had features of advanced fibrosis. CONCLUSION iLFT analysis of abnormal liver enzymes offers a safe and robust method of risk stratifying patients to the most appropriate care pathway as well as providing reliable diagnostic information based on a single blood draw, without repeated contacts with health services. Offers the possibility of high quality investigation and diagnosis to all patients rather than a tiny minority.
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Affiliation(s)
- Michael Hugh Miller
- Gut Group, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
| | - Andrew Fraser
- NHS Grampian, Aberdeen Royal Infirmary, Aberdeen, UK
| | | | | | - George Gibson
- NHS Greater Glasgow and Clyde, Glasgow Royal Infirmary, Glasgow, UK
| | - James Orr
- NHS Greater Glasgow and Clyde, Glasgow Royal Infirmary, Glasgow, UK
| | - Ewan H Forrest
- NHS Greater Glasgow and Clyde, Glasgow Royal Infirmary, Glasgow, UK
| | - Ellie Dow
- NHS Tayside, Ninewells Hospital and Medical School, Dundee, UK
| | | | | | - Axel Laurell
- Gut Group, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
| | - Kirsty Grant
- Gut Group, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
| | - Kathryn Scott
- Department of Gastroenterology, University of Dundee, Dundee, UK
| | - Ronald Neville
- NHS Tayside, Ninewells Hospital and Medical School, Dundee, UK
| | - John F Dillon
- Gut Group, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
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Abstract
PURPOSE OF REVIEW Liver blood tests, including bilirubin, aminotransferases, and alkaline phosphatase, are among the most commonly encountered tests in medicine. With roles including the investigation of symptoms, medication monitoring, assessment of chronic disease, and routine assessment, these tests serve many purposes and result in abnormality in up to 40% of patients. RECENT FINDINGS The toll of liver disease continues to rise and abnormal liver tests offer an opportunity to identify hepatic disease early, when treatment is most effective and before patients suffer the potential downstream consequences of cirrhosis, portal hypertension, and hepatocellular carcinoma. By utilizing diagnostic strategies including detailed history gathering, alcohol use assessment, recognition of metabolic syndrome, and identifying patterns of liver test abnormalities, clinicians can develop a systematic approach to address abnormal liver tests. For these reasons, developing an evidence-based, systematic approach to handling abnormal liver tests is critically important. SUMMARY This review seeks to synthesize key elements of the best evidence, presently available guidelines, and expert opinion in drafting a strategy to aid clinicians and patients in the timely and accurate diagnosis of liver disease for the adult asymptomatic patient with abnormal liver tests.
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Schreiner AD, Moran WP, Zhang J, Kirkland EB, Heincelman ME, Schumann Iii SO, Mauldin PD, Rockey DC. Evaluation of liver test abnormalities in a patient-centered medical home: do liver test patterns matter? J Investig Med 2018; 66:1118-1123. [PMID: 29941546 DOI: 10.1136/jim-2018-000788] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/29/2018] [Indexed: 11/03/2022]
Abstract
Abnormal liver tests are extremely common in clinical practice, present with varying patterns and degrees of elevation, and can signal liver injury from a variety of causes. Responding to these abnormalities requires complex medical decision-making and merits investigation in primary care. This retrospective study investigates the association of patterns of liver test abnormality with follow-up in primary care. Using administrative data, this study includes patients with abnormal liver tests seen between 2007 and 2016 in a patient-centered medical home. Liver tests examined include serum bilirubin, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Patients entered the cohort on the first liver test elevation. The outcome examined was completion of repeat testing, and the proportions of patients without follow-up were compared by patterns of index abnormality. 9545 patients met the inclusion criteria. Of these, 6155 (64.5%) possessed one liver test abnormality and 3390 (35.5%) possessed multiple abnormalities on index testing. Overall 1119 (11.7%) patients did not have repeat testing performed during the study period. A greater proportion of patients with lone abnormalities lacked repeat testing compared with those patients with multiple abnormalities. Differences in repeat testing appeared when comparing clinical patterns of abnormality, with higher proportions of follow-up in patients with testing suggestive of cholestasis. Over 11% of patients with abnormal liver tests did not undergo repeat testing during the study period. Repeat testing occurred more often in patients with multiple abnormalities and in clinical patterns suggestive of cholestasis. This study highlights a potential opportunity to improve quality of care.
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Affiliation(s)
- Andrew D Schreiner
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| | - William P Moran
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Jingwen Zhang
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Elizabeth B Kirkland
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Marc E Heincelman
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Samuel O Schumann Iii
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Patrick D Mauldin
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Don C Rockey
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
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34
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Schreiner AD, Mauldin PD, Moran WP, Durkalski-Mauldin V, Zhang J, Schumann SO, Heincelman ME, Marsden J, Rockey DC. Assessing the Burden of Abnormal LFTs and the Role of the Electronic Health Record: A Retrospective Study. Am J Med Sci 2018; 355:537-543. [PMID: 29673744 DOI: 10.1016/j.amjms.2018.02.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Revised: 12/14/2017] [Accepted: 02/07/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Primary care clinicians encounter abnormal liver function tests (LFTs) frequently. This study assesses the prevalence of abnormal LFTs and patient follow-up patterns in response. METHODS This is a retrospective study from 2007-2016 of adult patients with abnormal LFTs seen in an internal medicine clinic. The proportion of patients with follow-up testing and the time (in days) to repeat LFTs were the primary outcomes measured. Results were evaluated before and after the implementation of the institution's electronic health record (EHR). RESULTS This study identified a period prevalence for abnormal LFTs of 39%. Of these, 9,545 unique patients met inclusion criteria, with 8,415 patients (88.2%) possessing follow-up LFTs and no significant difference in the proportion of patients receiving follow-up by degree of initial abnormality. Median time to follow-up in mild abnormalities (1-2 times normal) was 138 days, compared to 21 days for severe abnormalities (>4 times normal, P < 0.0001). Reduced time to repeat testing across all spectrums of abnormality was observed following EHR implementation, but proportions of missing follow-up did not improve. A multivariable logistic regression model identified younger age, poverty, living over 50 miles from clinic, recent cohort entry and a lower magnitude of abnormality as predictors for missing repeat LFT testing (area under the curve = 0.838 [95% CI: 0.827-0.849]). CONCLUSIONS Abnormal LFTs were detected in 39% of all patients seen. The degree of LFT abnormality did not influence rates of follow-up testing, but does appear to play a role in the timing of repeat testing, when obtained. Follow-up rates did not improve with EHR implementation.
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Affiliation(s)
- Andrew D Schreiner
- Departments of Medicine and Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina.
| | - Patrick D Mauldin
- Departments of Medicine and Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina
| | - William P Moran
- Departments of Medicine and Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina
| | - Valerie Durkalski-Mauldin
- Departments of Medicine and Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina
| | - Jingwen Zhang
- Departments of Medicine and Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina
| | - Samuel O Schumann
- Departments of Medicine and Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina
| | - Marc E Heincelman
- Departments of Medicine and Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina
| | - Justin Marsden
- Departments of Medicine and Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina
| | - Don C Rockey
- Departments of Medicine and Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina
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Omabe M, Omabe KN, Igwe D, John OC, Uchenna SK, Elom S. Xenobiotics-Induced Liver Damage Is Biochemically Abrogated by Treatment with Lipophilic Extracts of <i>Moringa oleifera in Vivo</i>. Health (London) 2018. [DOI: 10.4236/health.2018.103025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Newsome PN, Cramb R, Davison SM, Dillon JF, Foulerton M, Godfrey EM, Hall R, Harrower U, Hudson M, Langford A, Mackie A, Mitchell-Thain R, Sennett K, Sheron NC, Verne J, Walmsley M, Yeoman A. Guidelines on the management of abnormal liver blood tests. Gut 2018; 67:6-19. [PMID: 29122851 PMCID: PMC5754852 DOI: 10.1136/gutjnl-2017-314924] [Citation(s) in RCA: 332] [Impact Index Per Article: 47.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 10/06/2017] [Accepted: 10/15/2017] [Indexed: 12/13/2022]
Abstract
These updated guidelines on the management of abnormal liver blood tests have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the liver section of the BSG. The original guidelines, which this document supersedes, were written in 2000 and have undergone extensive revision by members of the Guidelines Development Group (GDG). The GDG comprises representatives from patient/carer groups (British Liver Trust, Liver4life, PBC Foundation and PSC Support), elected members of the BSG liver section (including representatives from Scotland and Wales), British Association for the Study of the Liver (BASL), Specialist Advisory Committee in Clinical Biochemistry/Royal College of Pathology and Association for Clinical Biochemistry, British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN), Public Health England (implementation and screening), Royal College of General Practice, British Society of Gastrointestinal and Abdominal Radiologists (BSGAR) and Society of Acute Medicine. The quality of evidence and grading of recommendations was appraised using the AGREE II tool. These guidelines deal specifically with the management of abnormal liver blood tests in children and adults in both primary and secondary care under the following subheadings: (1) What constitutes an abnormal liver blood test? (2) What constitutes a standard liver blood test panel? (3) When should liver blood tests be checked? (4) Does the extent and duration of abnormal liver blood tests determine subsequent investigation? (5) Response to abnormal liver blood tests. They are not designed to deal with the management of the underlying liver disease.
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Affiliation(s)
- Philip N Newsome
- National Institute for Health Research (NIHR), Birmingham Biomedical Research Centre and Centre for Liver Research, University of Birmingham, Birmingham, UK,Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Rob Cramb
- National Institute for Health Research (NIHR), Birmingham Biomedical Research Centre and Centre for Liver Research, University of Birmingham, Birmingham, UK
| | - Suzanne M Davison
- Leeds Children’s Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - John F Dillon
- Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, UK
| | | | - Edmund M Godfrey
- Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | | | | | - Mark Hudson
- Regional Liver and Transplant Unit, Freeman Hospital, Newcastle Upon Tyne, UK,Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK
| | | | | | | | - Karen Sennett
- Killick Street Health Centre, London, UK,NHS Islington Clinical Commissioning Group, London, UK
| | - Nicholas C Sheron
- Clinical and Experimental Science, Faculty of Medicine, University of Southampton, Southampton, UK
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Reducing liver function tests for statin monitoring: an observational comparison of two clinical commissioning groups. Br J Gen Pract 2017; 67:e194-e200. [PMID: 28137784 DOI: 10.3399/bjgp17x689365] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Accepted: 09/25/2016] [Indexed: 01/24/2023] Open
Abstract
BACKGROUND Current liver function testing for statin monitoring is largely unnecessary and costly. Statins do not cause liver disease. Both reduction in test frequency and use of a single alanine transaminase (ALT) rather than a full seven analyte liver function test (LFT) array would reduce cost and may benefit patients. AIM To assess LFT testing in relation to statin use and evaluate an intervention to reduce full-array LFTs ordered by GPs for statin monitoring. DESIGN AND SETTING Two-year cross-sectional time series in two east London clinical commissioning groups (CCGs) with 650 000 patients. One CCG received the intervention; the other did not. METHOD The intervention comprised local guidance on LFTs for statin monitoring and access to a single ALT rather than full LFT array. RESULTS Of the total population, 17.6% were on statins, accounting for 43.2% of total LFTs. In the population without liver disease, liver function tests were 3.6 times higher for those on statins compared with those who were not. Following intervention there was a significant reduction in the full LFT array per 1000 people on statins, from 70.3 (95% confidence interval [CI] = 66.3 to 74.6) in the pre-intervention year, to 58.1 (95% CI = 55.5 to 60.7) in the post-intervention year (P<0.001). In the final month, March 2016, the rate was 53.2, a 24.3% reduction on the pre-intervention rate. CONCLUSION This simple and generalisable intervention, enabling ordering of a single ALT combined with information recommending prudent rather than periodic testing, reduced full LFT testing by 24.3% in people on statins. This is likely to have patient benefit at reduced cost.
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Patient perspectives on test result communication in primary care: a qualitative study. Br J Gen Pract 2016; 65:e133-40. [PMID: 25733434 DOI: 10.3399/bjgp15x683929] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022] Open
Abstract
BACKGROUND Although the number of blood tests ordered in primary care continues to increase, efficient systems for the communication of blood test results to patients are lacking. This is a concern in terms of both patient safety and patient satisfaction. AIM To gain an understanding of patient perspectives on organisational and technological aspects of current and prospective systems for communicating laboratory test results in primary care, and the influences that impact patients' preferred methods for receiving results. DESIGN AND SETTING Qualitative study using patient focus groups in four primary care practices in Birmingham, UK. METHOD The primary care practices were purposively selected to ensure they varied in size, socioeconomic environment, and the default pathways they used to communicate test results. A total of 26 patients from the four practices who had had a recent blood test were recruited. Over a 6 month period in 2011, six, 1-hour focus groups were conducted at the four practices involved in the study. RESULTS Patients expressed a preference for receiving results from the ordering GP or a clinically qualified member of staff. Suggestions for refining current systems included improved access to phlebotomy appointments, better management of patient telephone calls, and a clear, accessible protocol for the communication of results. CONCLUSION Despite the testing and result communication process being a core activity in primary care, it was found that practices could improve their service in a number of areas. Patients described frequent delays and inconsistency in both the level of information and the method of communication, as well as dissatisfaction with non-clinical staff relaying results. Patient preferences for result communication based on their experience of current systems have produced practical suggestions to improve processes.
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Abstract
BACKGROUND Liver disease is a major cause of morbidity and mortality worldwide. Large numbers of liver function tests (LFTs) are performed in primary care, with abnormal liver biochemistry a common finding. Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. Metabolic syndrome, common in people from South Asia, is an important risk factor for NAFLD. AIM It is hypothesised that a large gap exists between numbers of patients with abnormal LFTs and those with recorded liver diagnoses, and that NAFLD is more common among adults of South Asian ethnic groups. DESIGN AND SETTING A cross-sectional study of 690,683 adults in coterminous general practices in a region with high ethnic diversity. METHOD Data were extracted on LFTs, liver disease, and process of care measures from computerised primary care medical records. RESULTS LFTs were performed on 218,032 patients, of whom 31 627 had elevated serum transaminases. The prevalence of abnormal LFTs was highest among individuals of Bangladeshi ethnicity. Of the patients with abnormal LFTs, 88.4% did not have a coded liver diagnosis. NAFLD was the most frequently recorded liver disease and was most common among Bangladeshi patients. In a multivariate analysis, independent risk factors for NAFLD included Bangladeshi ethnicity, diabetes, raised BMI, hypertension, and hypercholesterolaemia. CONCLUSION Abnormal LFTs are common in the population, but are underinvestigated and often remain undiagnosed. Bangladeshi ethnicity is an important independent risk factor for NAFLD.
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Hepatitis B and C prevalence in Portugal: disparity between the general population and high-risk groups. Eur J Gastroenterol Hepatol 2016; 28:640-4. [PMID: 26866523 DOI: 10.1097/meg.0000000000000608] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIMS The prevalence of anti-HCV and HBsAg in Portugal has been shown to be elevated in high-risk groups, such as intravenous drug-users and incarcerated individuals. However, in the general population, prevalence remains largely unknown. The aims of this study were to estimate the prevalence of anti-HCV and HBsAg in the general Portuguese population and identify associated risk factors. MATERIALS AND METHODS We carried out a nationwide, population-based cross-sectional study of adults resident in mainland Portugal. Serology for HBsAg, anti-HBc, anti-HBs, and anti-HCV was performed. Anti-HCV-positive individuals were tested for HCV RNA by PCR. RESULTS Of 1685 participants, 50.6% were men, mean age 50.2±18.3 years. In terms of hepatitis C, the prevalence of anti-HCV was 0.54% [95% confidence interval (CI): 0.2-0.9] and 0.12% (95% CI: 0.0-0.3) were viremic, with peak prevalence among individuals 35-64 years of age (0.8%), men (0.8%), and individuals from Lisbon and Tagus Valley region (1.9%).In terms of hepatitis B, the estimated prevalence of HBsAg was 1.45% (95% CI: 0.9-2.0). A higher prevalence was found in individuals who were 35-64 years old (2.2%), in men (2.5%), and in the Northern region (2.6%).The presence of positive serological markers of hepatitis C virus and hepatitis B virus infection did not correlate with elevated aminotransferases, race, place of birth, and alcohol consumption. CONCLUSION These results suggest a low endemicity for both hepatitis B and hepatitis C in the general population, in contrast to a very high prevalence in risk groups, thus suggesting that targeted screening to high-risk groups may be more cost-effective than general population screening.
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Litchfield I, Bentham L, Hill A, McManus RJ, Lilford R, Greenfield S. Routine failures in the process for blood testing and the communication of results to patients in primary care in the UK: a qualitative exploration of patient and provider perspectives. BMJ Qual Saf 2015; 24:681-90. [PMID: 26251507 PMCID: PMC4680130 DOI: 10.1136/bmjqs-2014-003690] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2014] [Accepted: 06/18/2015] [Indexed: 11/04/2022]
Abstract
BACKGROUND The testing and result communication process in primary care is complex. Its successful completion relies on the coordinated efforts of a range of staff in primary care and external settings working together with patients. Despite the importance of diagnostic testing in provision of care, this complexity renders the process vulnerable in the face of increasing demand, stretched resources and a lack of supporting guidance. METHODS We conducted a series of focus groups with patients and staff across four primary care practices using process-improvement strategies to identify and understand areas where either unnecessary delay is introduced, or the process may fail entirely. We then worked with both patients and staff to arrive at practical strategies to improve the current system. RESULTS A total of six areas across the process were identified where improvements could be introduced. These were: (1) delay in phlebotomy, (2) lack of a fail-safe to ensure blood tests are returned to practices and patients, (3) difficulties in accessing results by telephone, (4) role of non-clinical staff in communicating results, (5) routine communication of normal results and (6) lack of a protocol for result communication. CONCLUSIONS A number of potential failures in testing and communicating results to patients were identified, and some specific ideas for improving existing systems emerged. These included same-day phlebotomy sessions, use of modern technology methods to proactively communicate routine results and targeted training for receptionists handling sensitive data. There remains an urgent need for further work to test these and other potential solutions.
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Affiliation(s)
- Ian Litchfield
- School of Health and Population Sciences, Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Louise Bentham
- School of Health and Population Sciences, Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Ann Hill
- Department of Transformation, Worcestershire Acute Hospitals, Worcestershire, UK
| | - Richard J McManus
- Nuffield Department Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Richard Lilford
- Health Sciences, Warwick Medical School, University of Warwick, Coventry, UK
| | - Sheila Greenfield
- School of Health and Population Sciences, Medical and Dental Sciences, University of Birmingham, Birmingham, UK
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Badrick T, Turner P. Review and Recommendations for the Component Tests in the Liver Function Test Profile. Indian J Clin Biochem 2015; 31:21-9. [PMID: 26855484 DOI: 10.1007/s12291-015-0493-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2015] [Accepted: 03/21/2015] [Indexed: 01/01/2023]
Abstract
Pathology laboratories group some tests that they perform on their high throughput biochemistry analysers into profiles of tests that are associated with different organs (e.g. liver function tests-LFT). The components of these profiles are historic and often vary between different laboratories. This can lead to confusion and begs the question of what should be in a particular profile. In community medicine profiles may be used as screening tests but some of the components of the profiles may have low sensitivity and specificity and may produce both false positives and negatives. The LFT may include components which are poor liver function tests but are sensitive to fatty liver and hence elevations may cause unnecessary concern. Harmonisation of clinical chemistry reference intervals and units is occurring now so it is time to consider a similar process for components of a profile. A proposed list of analytes to be performed in the LFT profile is given.
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Affiliation(s)
- Tony Badrick
- Faculty of Health Sciences and Medicine, Bond University, Robina, Australia ; Royal College of Pathologists of Australasia Quality Assurance Programs, St Leonards, Sydney, Australia
| | - Peter Turner
- Faculty of Health Sciences and Medicine, Bond University, Robina, Australia
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A systematic review of the prevalence of mildly abnormal liver function tests and associated health outcomes. Eur J Gastroenterol Hepatol 2015; 27:1-7. [PMID: 25380394 DOI: 10.1097/meg.0000000000000233] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Liver function tests (LFTs) are commonly performed to investigate asymptomatic individuals or those with nonspecific symptoms. Understanding the prevalence of mildly abnormal LFTs in the general population and the prevalence of liver disease following abnormal LFTs has important implications for the planning of care pathways and the provision of healthcare services. A systematic review of the literature on the prevalence of abnormal LFTs in the general population and their respective health outcomes was conducted. A total of 37 studies reporting data on the prevalence of abnormal LFTs (published between 2000 and 2014) were identified from online database searches or were manually selected from article bibliographies. The prevalence of mildly abnormal LFTs, with one or more abnormal constituents in the LFT, was high at 10-21.7%. The prevalence of severe liver disease within cohorts with abnormal LFTs is relatively low (<5%), and a large proportion of abnormal LFTs remains unexplained. Among individuals with unexplained abnormal LFTs, risk factors include obesity and insulin resistance. Common aetiologies for abnormal LFTs were non-alcohol-related fatty liver disease (NAFLD), followed by alcohol use and viral infections. In addition, normal LFTs do not rule out liver disease. The prevalence of abnormal LFTs depends on the definition and population but is likely to be between 10 and 20% in the general population. Abnormal LFTs are associated with a range of health outcomes but are not necessarily strongly diagnostic of severe liver pathology. Important areas of future research include further studies on the prevalence and predictive ability of LFTs in large, population-representative samples.
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Williams R, Aspinall R, Bellis M, Camps-Walsh G, Cramp M, Dhawan A, Ferguson J, Forton D, Foster G, Gilmore I, Hickman M, Hudson M, Kelly D, Langford A, Lombard M, Longworth L, Martin N, Moriarty K, Newsome P, O'Grady J, Pryke R, Rutter H, Ryder S, Sheron N, Smith T. Addressing liver disease in the UK: a blueprint for attaining excellence in health care and reducing premature mortality from lifestyle issues of excess consumption of alcohol, obesity, and viral hepatitis. Lancet 2014; 384:1953-97. [PMID: 25433429 DOI: 10.1016/s0140-6736(14)61838-9] [Citation(s) in RCA: 444] [Impact Index Per Article: 40.4] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Litchfield IJ, Bentham LM, Lilford RJ, Greenfield SM. Test result communication in primary care: clinical and office staff perspectives. Fam Pract 2014; 31:592-7. [PMID: 25070182 PMCID: PMC4169669 DOI: 10.1093/fampra/cmu041] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE To understand how the results of laboratory tests are communicated to patients in primary care and perceptions on how the process may be improved. DESIGN Qualitative study employing staff focus groups. SETTING Four UK primary care practices. PARTICIPANTS Staff involved in the communication of test results. FINDINGS Five main themes emerged from the data: (i) the default method for communicating results differed between practices; (ii) clinical impact of results and patient characteristics such as anxiety level or health literacy influenced methods by which patients received their test result; (iii) which staff member had responsibility for the task was frequently unclear; (iv) barriers to communicating results existed, including there being no system or failsafe in place to determine whether results were returned to a practice or patient; (v) staff envisaged problems with a variety of test result communication methods discussed, including use of modern technologies, such as SMS messaging or online access. CONCLUSIONS Communication of test results is a complex yet core primary care activity necessitating flexibility by both patients and staff. Dealing with the results from increasing numbers of tests is resource intensive and pressure on practice staff can be eased by greater utilization of electronic communication. Current systems appear vulnerable with no routine method of tracing delayed or missing results. Instead, practices only become aware of missing results following queries from patients. The creation of a test communication protocol for dissemination among patients and staff would help ensure both groups are aware of their roles and responsibilities.
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Affiliation(s)
- Ian J Litchfield
- Health and Population Sciences, University of Birmingham, Edgbaston, UK.
| | - Louise M Bentham
- Health and Population Sciences, University of Birmingham, Edgbaston, UK
| | - Richard J Lilford
- Health and Population Sciences, University of Birmingham, Edgbaston, UK
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Affiliation(s)
- Naveed Sattar
- BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK
| | - Ewan Forrest
- Department of Gastroenterology, Glasgow Royal Infirmary, Glasgow, UK
| | - David Preiss
- BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK
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Lilford RJ, Bentham LM, Armstrong MJ, Neuberger J, Girling AJ. What is the best strategy for investigating abnormal liver function tests in primary care? Implications from a prospective study. BMJ Open 2013; 3:e003099. [PMID: 23794594 PMCID: PMC3686167 DOI: 10.1136/bmjopen-2013-003099] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2013] [Accepted: 05/13/2013] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVE Evaluation of predictive value of liver function tests (LFTs) for the detection of liver-related disease in primary care. DESIGN A prospective observational study. SETTING 11 UK primary care practices. PARTICIPANTS Patients (n=1290) with an abnormal eight-panel LFT (but no previously diagnosed liver disease). MAIN OUTCOME MEASURES Patients were investigated by recording clinical features, and repeating LFTs, specific tests for individual liver diseases, and abdominal ultrasound scan. Patients were characterised as having: hepatocellular disease; biliary disease; tumours of the hepato-biliary system and none of the above. The relationship between LFT results and disease categories was evaluated by stepwise regression and logistic discrimination, with adjustment for demographic and clinical factors. True and False Positives generated by all possible LFT combinations were compared with a view towards optimising the choice of analytes in the routine LFT panel. RESULTS Regression methods showed that alanine aminotransferase (ALT) was associated with hepatocellular disease (32 patients), while alkaline phosphatase (ALP) was associated with biliary disease (12 patients) and tumours of the hepatobiliary system (9 patients). A restricted panel of ALT and ALP was an efficient choice of analytes, comparing favourably with the complete panel of eight analytes, provided that 48 False Positives can be tolerated to obtain one additional True Positive. Repeating a complete panel in response to an abnormal reading is not the optimal strategy. CONCLUSIONS The LFT panel can be restricted to ALT and ALP when the purpose of testing is to exclude liver disease in primary care.
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Affiliation(s)
- Richard J Lilford
- School of Health and Population Sciences, University of Birmingham, Edgbaston, Birmingham, UK
| | - Louise M Bentham
- School of Health and Population Sciences, University of Birmingham, Edgbaston, Birmingham, UK
| | - Matthew J Armstrong
- Centre for Liver Research and NIHR Biomedical Research Unit, University of Birmingham, Edgbaston, Birmingham, UK
| | - James Neuberger
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Alan J Girling
- School of Health and Population Sciences, University of Birmingham, Edgbaston, Birmingham, UK
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