Robert Cramb

Cardiovascular morbidity and mortality after orthotopic liver transplantation

BACKGROUND Hyperlipidemia and hypertension have been reported in liver allograft recipients and contribute to an increased risk of ischemic heart disease (IHD) after orthotopic liver transplantation (OLT). The aims of the study were (1) to determine the prevalence of risk factors for IHD in these patients and (2) to compare the observed incidence of cardiovascular events and related mortality in allograft recipients with a matched population. METHODS One hundred ten consecutive adults (50 male) who attended for review after OLT (median follow-up 3.9 years; range 0.1-17.9) were assessed for cardiovascular risk factors using current blood pressure, diabetic status, and smoking history and measurements of total cholesterol, high-density lipoprotein cholesterol, and triglyceride concentrations. Cardiovascular events and cardiovascular mortality data were collected from the prospective database of all adult liver allograft recipients and compared to matched data from myocardial infarction registries and Office for National Statistics data, respectively. RESULTS Raised serum cholesterol (>5.0 mmol/L) was found in 48 (44%) patients (18 male), and systolic hypertension (>140 mmHg) was found in 69 (63%) patients (27 male). The relative risk of ischemic cardiac events was 3.07 (95% [confidence interval] CI, 1.98-4.53) and the relative risk for cardiovascular deaths was 2.56 (95% CI, 1.52-4.05) in allograft recipients compared to an age-matched population without transplants. CONCLUSIONS Liver allograft recipients have a greater risk of cardiovascular deaths and ischemic events than an age- and sex-matched population. The prevalence of raised cholesterol concentrations in patients after OLT is similar to those in previous reports. Moderate hypertension and hyperlipidemia may be more detrimental in patients after OLT compared to non-transplant patients without these risk factors.

Presence and severity of non-alcoholic fatty liver disease in a large prospective primary care cohort.

BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) is a common cause of abnormal LFTs in primary care, but there are no data defining its contribution nor reporting the range of NAFLD severity in this setting. This study seeks to calculate the range of disease severity of NAFLD in a primary care setting. METHODS Adult patients with incidental abnormal LFTs, in the absence of a previous history, or current symptoms/signs of liver disease were prospectively recruited from eight primary care practices in Birmingham. NAFLD was diagnosed as fatty liver on ultrasound, negative serological liver aetiology screen, and alcohol consumption ≤30 and ≤20 g/day in males and females, respectively. The NAFLD Fibrosis Score (NFS) was calculated to determine the presence or absence of advanced liver fibrosis in subjects identified with NAFLD. RESULTS Data from 1118 adult patients were analysed. The cause of abnormal LFTs was identified in 55% (614/1118) of subjects, with NAFLD (26.4%; 295/1118) and alcohol excess (25.3%; 282/1118) accounting for the majority. A high NFS (>0.676) suggesting the presence of advanced liver fibrosis was found in 7.6% of NAFLD subjects, whereas 57.2% of NAFLD patients had a low NFS (<-1.455) allowing advanced fibrosis to be confidently excluded. CONCLUSIONS NAFLD is the commonest cause of incidental LFT abnormalities in primary care (26.4%), of whom 7.6% have advanced fibrosis as calculated by the NFS. This study is the first of its kind to highlight the burden of NAFLD in primary care and provide data on disease severity in this setting.

Guidelines on the management of abnormal liver blood tests

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.

Comparison of IFCC-calibrated HbA1c from laboratory and point of care testing systems

OBJECTIVE WHO, IDF and ADA recommend HbA(1c) ≥6.5% (48 mmol/mol) for diagnosis of diabetes with pre-diabetes 6.0% (42 mmol/mol) [WHO] or 5.7% (39 mmol/mol) [ADA] to 6.4% (47 mmol/mol). We have compared HbA(1c) from several methods for research relating glycaemic markers. RESEARCH DESIGN AND METHODS HbA1c was measured in EDTA blood from 128 patients with diabetes on IE HPLC analysers (Bio-Rad Variant II NU, Menarini HA8160 and Tosoh G8), point of care systems, POCT, (A1cNow+ disposable cartridges and DCA 2000(®)+ analyser), affinity chromatography (Primus Ultra2) and the IFCC secondary reference method (Menarini HA8160 calibrated using IFCC SRM protocol). RESULTS Median (IQ range) on IFCC SRM was 7.5% (6.8-8.4) (58(51-68) mmol/mol) HbA(1c) with minimum 5.3%(34 mmol/mol)/maximum 11.9%(107 mmol/mol). There were positive offsets between IFCC SRM and Bio-Rad Variant II NU, mean difference (1SD), +0.33%(0.17) (+3.6(1.9) mmol/mol), r(2)=0.984, p<0.001 and Tosoh G8, +0.22%(0.20) (2.4(2.2) mmol/mol), r(2)=0.976, p<0.001 with a very small negative difference -0.04%(0.11) (-0.4(1.2) mmol/mol), r(2)=0.992, p<0.001 for Menarini HA8160. POCT methods were less precise with negative offsets for DCA 2000(®)+ analyser -0.13%(0.28) (-1.4(3.1) mmol/mol), r(2)=0.955, p<0.001 and A1cNow+ cartridges -0.70%(0.67) (-7.7(7.3) mmol/mol), r(2)=0.699, p<0.001 (n=113). Positive biases for Tosoh and Bio-Rad (compared with IFCC SRM) have been eliminated by subsequent revision of calibration. CONCLUSIONS Small differences observed between IFCC-calibrated and NGSP certified methods across a wide HbA(1c) range were confirmed by quality control and external quality assurance. As these offsets affect estimates of diabetes prevalence, the analyser (and calibrator) employed should be considered when evaluating diagnostic data.

Comparison of Potassium ISFETs with the Radiometer KNA1 and the Corning 902 Ion Selective Electrode Analysers for Whole Blood Potassium Ion Estimation

Evaluation of the performance of potassium ion sensitive field effect transistors (K+ ISFETs), developed by Thorn EMI in a form suitable for mass production and for incorporation in ‘near the patient’ analysers, showed only very small constant and proportional biases against the Radiometer KNA1 and the Corning 902 for whole blood potassium ion estimation. Between batch imprecision tests with whole blood showed the K+ ISFET was comparable in performance to the Corning 902 but inferior to the Radiometer KNA1. The evaluation demonstrated that ISFET manufacturing technology has now reached a stage of development at which ISFETs should be considered seriously for use in clinical chemical analysers.

Advanced non-alcoholic fatty liver disease and adipose tissue fibrosis in patients with Alström syndrome.

Alström syndrome (AS) is a recessive monogenic syndrome characterized by obesity, extreme insulin resistance and multi‐organ fibrosis. Despite phenotypically being high risk of non‐alcoholic fatty liver disease (NAFLD), there is a lack of data on the extent of fibrosis in the liver and its close links to adipose in patients with AS. Our aim was to characterize the hepatic and adipose phenotype in patients with AS.

Clinical Evaluation of Sodium Ion Selective Field Effect Transistors for Whole Blood Assay

Sodium ion selective field effect transistors (ISFETs) were evaluated for their performance in measurement of sodium ions in whole blood for ‘near patient’ analysis in operating theatres and intensive care units. Performance was evaluated in comparison with a standard clinical laboratory sodium/potassium ion analyser (Radiometer KNA1) and with sodium and potassium assays using flame photometry on the plasma from each whole blood specimen. The imprecisions (coefficients of variation) of three ISFETs for sodium ion assay were 1·08, 1·56 and 1·10%, respectively. Robust bivariate linear regression (reweighted least squares preceded by least median of squares) of the ISFET versus KNA1 sodium ion activity yielded a regression coefficient of 1·08 and an intercept of −18·2 mM. The influence of potassium, protein and lipid on the measurement of sodium ions by both ISFETs and the KNA1 was assessed using robust multiple regression (also based on reweighted least squares preceded by least median of squares). In the regression versus flame photometry, protein was found to be more influential for the KNA1 (glass sodium ion selective electrode) than for the ISFET. Potassium had no influence on assays using the ISFET, but had a weak negative influence on assays using the KNA1. Two ISFETs lasted for more than 200 assays each demonstrating their robustness in the assay of whole blood.

Whole blood electrolyte assay using ChemPro 500 : a comparison of assay performance with standard laboratory instruments

The ChemPro 500‘near‐the‐patient’analyser, with ChemPro‘Ion Profile’sensor cards, was evalutated for the assay of pH, Ca2+, K+ and Na+ in whole blood samples from patients in the intensive care unit or during surgery for heart or major blood vessel disease, or for liver transplantation. Imprecisions estimated from replicate whole blood measurements were much greater for all four ions than even the least stringent of the generally accepted analytical goals, and much greater than those estimated using quality assurance materials. Comparisons of assayed values with those obtained using standard laboratory instruments showed significant constant and proportional biases. The performance of the ChemPro 500 with the Ion Profile cards gave us no confidence in recommending their use to anaesthetists and intensivists.