Non-alcoholic fatty liver disease (NAFLD) ranges in severity from steatosis to non-alcoholic
steatohepatitis with a potential for progression to cirrhosis and hepatocellular cancer,
making NAFLD a serious public health problem. This study aimed to determine if amount
of fat (total, macrovesicular and microvesicular) accumulated in the liver during
steatosis is linked to increased SREBP-2 expression and to the subsequent clinical
outcomes of the patients.
Annotated liver tissues were provided by the Grosshadern Hospital Tissue Bank. Briefly,
patients were matched by BMI, age and gender. Liver sections were examined and classified
according to the percentage of fat; control (no fat), low fat (less than 30% fat)
and high fat (more than 30% fat). Relative SREBP-2 gene expression was then measured
and follow-ups were done to document the clinical outcomes of the patients.
The high fat group had significantly higher relative SREBP-2 mRNA levels compared
to controls and the low fat group by 3.0- and 2.4-fold respectively. It was also found
that relative SREBP-2 mRNA levels were positively correlated to percent total fat
and macrovesicular fat (P<0.01), but not to microvesicular fat (P>0.01). However,
it appears that the accumulation of fat is not linked to rate and severity of complications
from liver resections, hospitalisation time, blood loss, surgery duration, disease
recurrence, metastasis to other organs and long-term survival (P>0.05).
In conclusion, fat and in particular macrovesicular fat accumulation is linked to
relative SREBP-2 expression. Thus, SREBP-2, an enzyme of cholesterol metabolism, can
potentially be used as a marker for staging steatosis. Knowing the fat accumulation
in a timely fashion by PCR is important since livers with high macrovesicular fat
exhibit high rates of graft dysfunction when transplanted. Further, it appears that
fat accumulation at this early stage of NAFLD does not appear to be linked to the
clinical outcomes investigated.
NAFLD - Steatosis - clinical outcome - tissue bank
