High cholesterol diet more harmful to the liver for women with hepatitis C than men

Keith Alcorn
17 February 2016

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 men.

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 fibrosis.


Yu L, Morishima C, Ioannou G. Sex differences in liver-related mortality and transplantation associated with dietary cholesterol in chronic hepatitis C virus infection. British Journal of Nutrition 115: 193-201, 2016.