Student Number : 0101826W -
M Med dissertation -
School of Clinical Medicine -
Faculty of Health Sciences / Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease with
hepatic histology that resembles alcoholic liver disease. It is a frequent
cause of chronic liver disease and is attracting increasing scientific
attention worldwide. I explored the possibility that increased gastrointestinal
alcohol production may have a role as a “second hit” in the pathogenesis of
NAFLD in study subjects with the metabolic syndrome. In an attempt to
investigate this hypothesis, this study looked at blood, urine and breath
levels of alcohol in patients with the metabolic syndrome versus matched
age and ethnic group healthy controls. Of the twenty study subjects, 80%
had dyslipidaemia, 60% had hypertension and 70% had type 2 diabetes
mellitus. Their mean BMI was 35.1±8.2 kg/m² (mean ± SD, P < 0.0001
versus controls). The serum aminotransferases were significantly elevated
in the study subjects, their ALT levels being 57.4±44.79 U/L versus
17.4±4.60 U/L in the controls (95% CI 18.02 – 61.42, P < 0.001), and their
AST levels 52.5±36.21 U/L versus 23.4±4.86 U/L in the controls (95% CI
11.99 – 46.20, P < 0.01). Seventy five percent of the study group had sonar
features suggestive of fatty liver disease. Two adipocytokines, adiponectin
and leptin, mediators of insulin resistance, an important factor in the development and progression of NAFLD, were also measured. Adiponectin
levels were significantly lower (6875 ng/L versus 15475 ng/L; median
value, P < 0.01), and leptin concentration levels significantly higher (13.56
ng/L versus 3.05 ng/L; median value, P < 0.05) in the study subjects than
in the control group.
Alcohol was detected in 60% of the study subjects, of which 35% tested
positive for ethanol, 55% tested positive for methanol, and 30% tested
positive for both ethanol and methanol. This was a statistically significant
result, as none of the control group tested positive for any of the alcohols.
The ethanol concentration in the study subjects’ blood was 7.14±3.28 mg%
(mean ± SD), in their urine 3.71± 12.87 mg% (mean ± SD) whilst none was
detected in their breath. The methanol concentration in the study subjects’
blood was 16.17±17.95 mg% (mean ± SD), in their urine 6.8± 13.58 mg%
(mean ± SD) while their breath level was 2.05±3.19 mg (mean ± SD).
This study therefore suggests that endogenous alcohol production may be
indeed be involved in the pathogenesis of NAFLD in subjects with the
metabolic syndrome. Not only ethanol but also methanol was detected in
the subjects tested. Endogenous alcohol may therefore be responsible for
the ‘second hit’ theory in the pathogenesis of NAFLD, and it is likely that formaldehyde, the metabolite of methanol may be a more potent toxin of
hepatocyte injury as opposed to acetaldehyde, the metabolite of ethanol.
The most likely source of the alcohol is from intestinal bacterial flora. These
findings provide further insight into the pathogenesis of NALFD,
suggesting other therapeutic alternatives such as the use of antibiotics and
probiotics as a potential treatment strategy for NAFLD.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/2048 |
| Date | 19 February 2007 |
| Creators | Menezes, Colin Nigel |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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