Fat soluble vitamins and function in adults awaiting liver transplantation.

Abbott-Johnson, Winsome (2008). Fat soluble vitamins and function in adults awaiting liver transplantation. PhD Thesis, School of Medicine, The University of Queensland.

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Author Abbott-Johnson, Winsome
Thesis Title Fat soluble vitamins and function in adults awaiting liver transplantation.
School, Centre or Institute School of Medicine
Institution The University of Queensland
Publication date 2008-01
Thesis type PhD Thesis
Supervisor Clague, Alan
Crawford, Darrell
Kerlin, Paul
Subjects 11 Medical and Health Sciences
Formatted abstract
Nutritional assessment in advanced liver disease has focused mainly on protein- calorie malnutrition. Little attention has been devoted to fat soluble vitamins, especially in hepatocellular disease. Deficiencies of these vitamins have the potential to impact on morbidity and mortality.
Chapter 1 describes current knowledge of fat soluble vitamins in liver disease including a) functions of the vitamins and adverse effects of deficiencies and b) reasons for deficiencies (reduced intake, malabsorption and metabolic disturbances).
Preliminary data indicated a high prevalence of vitamin A deficiency in pre-transplant cirrhotic patients. Methods to quantitate the effects of altered vitamin A on the eye (dark adaptation (DA) and electroretinography (ERG)) are discussed.
Chapter 2 describes 107 patients assessed for liver transplantation between July 2000 and October 2002 and compares blood concentrations of fat soluble vitamins between patients with cholestasis and hepatocellular dysfunction.
The prevalence of vitamin A deficiency was 75% (<1.0 µmol/L), vitamin D 66% (<50 nmol/L) and vitamin E 3% (< 12.5 µmol/L). The hepatocellular group had lower concentrations of vitamins A and E compared with the cholestatic group. Vitamin D was lower but did not reach significance. Disease severity was greater in hepatocellular disease. Within hepatocellular disease, vitamin A was lower in alcoholic liver disease (where disease severity was greater) than for hepatitis.
Univariate analysis was used to relate vitamin levels to biochemical indicators of disease severity (albumin, bilirubin), plasma zinc and clinical scores (Child-Pugh score, MELD score). Levels of fat soluble vitamins were directly related to albumin and inversely to bilirubin and the clinical scores. Vitamins A and D were also directly related to plasma zinc. Multivariate analysis was then performed using the univariate predictors and disease aetiology to determine the persistent predictors of fat soluble vitamin levels. The concentrations of the fat soluble vitamins were predicted by disease severity rather than aetiology (hepatocellular or cholestatic). This important conclusion contradicts the common belief that fat soluble vitamin levels are predicted only by cholestasis.
The aim of chapter 3 was to quantitate dark adapted vision impairment from a clinical hepatology perspective using a field instrument (SST-1 Dark Adaptometer) in a cohort of 20 patients (15 M mean age 51 years). Patients were selected on the basis of low serum vitamin A (<0.7 µmol/L) and were compared with 15 healthy age-matched control subjects. The end-point used was the lowest intensity of light seen (DA threshold, which is the commonly-used clinical end-point) after adaptation following exposure to a bright light (bleach). Forty percent of patients had impaired DA seen in both cholestatic and alcoholic liver disease. Perception of impairment of DA was determined by questionnaire in 14 patients. Of these, 8/14 had impairment of DA and most (6/8) were unaware of this impairment. No relationship was found between DA and vitamin A status (retinol, retinol-binding protein) plasma zinc or disease severity. Eight patients received 50,000 IU of aqueous retinyl palmitate intramuscularly and were restudied at one month. By one month post-intervention, plasma vitamin A was not significantly different from pre-intervention. In spite of this, DA improved, with light being detected at half the lowest intensity which could previously be seen.
The under-recognition of impairment of DA in patients was a risk to safety. Because impairment of DA is not predicted by biochemical test and is under-recognised, DA testing offers and important assessment of the visual deficiency. Improved biochemical predictors which better reflect delivery of retinol to the eye are needed. The aqueous form of retinyl palmitate was effective.
Chapters 4 and 5 relate to vision science and examine a novel approach using mathematical DA curve-fitting with the intent of overcoming the limitations of the DA threshold. Chapter 4 describes satisfactory exponential curve-fitting in both control subjects and patients prior to intervention. ERG was performed in a subset of patients.
A strong relationship was found between lag time to see after bleach and DA threshold. Decay was also slower in patients than control subjects. No relationship was found between curve-fit parameters and vitamin A status, zinc or disease severity. Impairment of scotopic ERG was present with significant delay of -24dB implicit time. There was also reduction of amplitudes in some patients.
Differences between patients and control subjects were shown using cure-fitting. The use of curve-fitting strengthens the utility of this field instrument. Delayed -24dB implicit time may be an early indicator of impairment due to vitamin A deficiency.
Chapter 5 studied the response to vitamin A treatment using DA curve-fit parameters and ERG. Significant improvements in DA decay and ERG (scotopic a and b waves and 30 Hz flicker) were shown following intervention. Comparisons between baseline curve-fit parameters and ERG revealed significant interrelationships between a) lag time and scotopic a wave implicit time and b) decay and scotopic amplitudes.
The relationships which were found between curve-fit parameters and scotopic ERG confirmed the utility of these parameters. Improvement of dark adapted vision at one month without change in plasma retinol suggests that tissue availability within the retina may be more important.

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