A diet high in cholesterol appears more harmful to the
liver, and is more strongly linked to liver-related death and liver
transplantation, in women with hepatitis C and advanced fibrosis but not in
men, according to an analysis of a large hepatitis C treatment trial published in
the British Journal of Nutrition.
A diet rich in cholesterol has been shown to cause liver
damage including fibrosis in animal studies in the absence of HCV infection,
and furthermore, mouse studies have shown that HCV increases levels of free
cholesterol and the accumulation of cholesterol in liver cells.
The findings come from the HALT-C study, a large study which
assessed the impact of low-dose treatment with pegylated interferon on the
progression of liver disease in people without hepatitis C who had failed to
respond to previous treatment with pegylated interferon and ribavirin. The
study found that low-dose interferon treatment had no impact on the rate of
liver disease progression.
The analysis published in the January 28 edition of the British Journal of Nutrition analyses
the data of 657 patients who
completed two questionnaires on dietary intake, at baseline and during the
study, who were followed for a mean of 4.7 years. Twenty-nine per cent of the
study population were women.
The impact of dietary intake of cholesterol on liver disease
was calculated in two ways, by comparing those with cholesterol above and below
150 mg per 1000 calories of energy intake per day, and by comparing quartiles
of cholesterol intake per 1000 calories of energy intake. In the study
population the average energy intake was 1827 calories a day, and the average
cholesterol consumption was 220mg a day. In the lowest quartile cholesterol
intake was 143mg day; in the highest quartile it was 307mg a day. (300mg a
cholesterol a day is the equivalent of consuming one large egg and 140mg of
meat a day.)
Unsurprisingly, high cholesterol intake was associated with
higher body mass index, higher fasting glucose and a higher prevalence of
diabetes. It was not associated with higher serum cholesterol, and it was
associated with only one laboratory marker of liver damage, baseline ALT.
Cholesterol intake was significantly associated in women
with the risk of liver-related death and of undergoing a liver transplant
during the follow-up period, but not in men. In women, each quartile of higher
cholesterol intake was associated with an 83% increase in the risk of
liver-related death or transplant (adjusted hazard ration 1.83, 95% confidence
interval 1.12-2.99), regardless of baseline liver disease status.
When comparing cholesterol intake above and below US dietary
guidelines, women with a cholesterol intake above the recommended level of
300mg a day had a fourfold increased risk of liver-related death or
transplantation compared to those women who had a lower cholesterol intake.
There was no significant difference in either of these outcomes when
cholesterol intake was assessed in men.
There was no difference between women with advanced fibrosis
or cirrhosis, but the risk was much higher for post-menopausal women than for
pre-menopausal women (AHR 5.51, 95% CI 1.42-21.3), although the confidence
intervals of this estimate were very wide. The risk was also strengthened in
women with higher levels of physical activity (AHR 2.93, 95% CI 1.116-7.35),
although the confidence intervals of this estimate were also very wide.
The authors speculate that the underlying mechanism for any
sex-related effect is hormonal, but say that more work is needed to establish
how cholesterol intake might affect women with hepatitis C differently from
The researchers say these findings are important for women
who have not yet started treatment and for those who are waiting for treatment
due to rationing or the high cost of treatment, and also for women who have
been cured of hepatitis C but who remain at risk of developing hepatocellular
carcinoma (liver cancer) due to advanced fibrosis. However, they say that a
dietary intervention trial is needed to test whether reducing cholesterol
intake could slow the progression of liver damage in women with advanced