Dietary Cholesterol Intake Is Associated With Progression of Liver Disease in Patients With Chronic Hepatitis C: Analysis of the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis Trial

Clinical Gastroenterology and Hepatology
Volume 11, Issue 12 , Pages 1661-1666.e3, December 2013

Lei Yu, Chihiro Morishima, George N. Ioannou

published online 28 May 2013.

Abstract

Background & Aims

Little is known about whether dietary cholesterol affects disease progression in patients with chronic hepatitis C virus infection.

Methods

We analyzed data from the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis trial, which included patients with advanced fibrosis and compensated cirrhosis. Cholesterol intake was determined for 608 participants on the basis of responses to food frequency questionnaires, administered at baseline and 1.8 years later. We investigated whether cholesterol intake was associated with clinical progression (death, variceal bleeding, encephalopathy, ascites, peritonitis, Child–Turcotte–Pugh score ≥7, or hepatocellular carcinoma) or histologic progression of disease (an increase in Ishak fibrosis score of 2 or more points in a second liver biopsy compared with the first).

Results

After adjustments for age, sex, race, presence of cirrhosis, body mass index, treatment with peginterferon, lifetime alcohol consumption, smoking, health status, and coffee and macronutrient intake, each higher quartile of cholesterol intake was associated with a 46% increase in the risk of clinical or histologic progression (adjusted hazard ratio [AHR], 1.46; 95% confidence interval [CI], 1.13–1.87; P for the trend = .004). Compared with patients in the lowest quartile of cholesterol intake (32–152 mg/day), those in the 3rd (224–310 mg/day; AHR, 2.83; 95% CI, 1.45–5.51) and 4th quartiles (>310 mg/day; AHR, 2.74; 95% CI, 1.22–6.16) had significantly increased risk of disease progression.

Conclusions

On the basis of analysis of data from the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis trial, higher dietary cholesterol intake is associated with higher risk of disease progression in HCV-infected patients with advanced fibrosis or compensated cirrhosis.

Keywords: Diet, Cholesterol, Hepatitis C, Cirrhosis

Abbreviations used in this paper: AHR, adjusted hazard ratio, BMI, body mass index, CI, confidence interval, CTP, Child–Turcotte–Pugh,FFQ, food frequency questionnaire, HALT-C, Hepatitis C Antiviral Long-term Treatment Against Cirrhosis, HCC, hepatocellular carcinoma,HCV, hepatitis C virus, MTP, microsomal triglyceride transfer protein, TLR, Toll-like receptor

Source

Dietary Cholesterol Intake Is Associated With Progression of Liver Disease in Patients With Chronic Hepatitis C: Analysis of the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis Trial

Clinical Gastroenterology and Hepatology

Article in Press

Lei Yu, Chihiro Morishima, George N. Ioannou,

published online 28 May 2013.
Uncorrected Proof

Abstract

Background & Aims

Little is known about whether dietary cholesterol affects disease progression in patients with chronic hepatitis C virus infection.

Methods

We analyzed data from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis trial, which included patients with advanced fibrosis and compensated cirrhosis. Cholesterol intake was determined for 608 participants on the basis of responses to food frequency questionnaires, administered at baseline and 1.8 years later. We investigated whether cholesterol intake was associated with clinical progression (death, variceal bleeding, encephalopathy, ascites, peritonitis, Child–Turcotte–Pugh score ≥7, or hepatocellular carcinoma) or histologic progression of disease (an increase in Ishak fibrosis score of 2 or more points in a second liver biopsy compared with the first).

Results

After adjustments for age, sex, race, presence of cirrhosis, body mass index, treatment with peginterferon, lifetime alcohol consumption, smoking, health status, and coffee and macronutrient intake, each higher quartile of cholesterol intake was associated with a 46% increase in the risk of clinical or histologic progression (adjusted hazard ratio [AHR], 1.46; 95% confidence interval [CI], 1.13–1.87; P for the trend = .004). Compared with patients in the lowest quartile of cholesterol intake (32–152 mg/day), those in the 3rd (224–310 mg/day; AHR, 2.83; 95% CI, 1.45–5.51) and 4th quartiles (>310 mg/day; AHR, 2.74; 95% CI, 1.22–6.16) had significantly increased risk of disease progression.

Conclusions

On the basis of analysis of data from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis trial, higher dietary cholesterol intake is associated with higher risk of disease progression in HCV-infected patients with advanced fibrosis or compensated cirrhosis.

Keywords: Diet, Cholesterol, Hepatitis C, Cirrhosis

Abbreviations used in this paper: AHR, adjusted hazard ratio, BMI, body mass index, CI, confidence interval, CTP, Child–Turcotte–Pugh, FFQ, food frequency questionnaire, HALT-C trial, Hepatitis C Antiviral Long-term Treatment Against Cirrhosis trial, HCC, hepatocellular carcinoma, HCV, hepatitis C virus, MTP, microsomal triglyceride transfer protein, TLR, toll-like receptor

Source

Cholesterol and chronic hepatitis C virus infection

Hepatol Res. 2011 Jun 17. doi: 10.1111/j.1872-034X.2011.00838.x. [Epub ahead of print]

Honda A, Matsuzaki Y.

Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan.

Abstract

Cholesterol is an essential molecule for the life cycle of the hepatitis C virus (HCV). This review focuses on the roles of cholesterol in HCV infection and introduces HCV events related to cholesterol metabolism and applications for cholesterol metabolism as a therapeutic target. HCV appears to alter host lipid metabolism into its preferable state, which is clinically recognized as steatosis and hypocholesterolemia. While hepatic fatty acid and triglyceride syntheses are upregulated in chronic hepatitis C patients, no direct evidence of increased hepatic de novo cholesterol biosynthesis has been obtained. Impaired VLDL secretion from hepatocytes is suggested to increase intracellular cholesterol concentrations, which may lead to hypocholesterolemia. Clinically, lower serum cholesterol levels are associated with lower rates of sustained virological responses (SVR) to pegylated-interferon plus ribavirin therapy, but the reason remains unclear. Clinical trials targeting HMG-CoA reductase, the rate-limiting enzyme in the cholesterol biosynthetic pathway, are being conducted using statins. Anti-HCV actions by statins appear to be caused by the inhibition of geranylgeranyl pyrophosphate synthesis rather than their cholesterol lowering effects. Other compounds that block various steps of cholesterol metabolic pathways have also been studied to develop new strategies for the complete eradication of this virus.

© 2011 The Japan Society of Hepatology.

Source

Serum lipids and their associations with viral levels and liver disease severity in a treatment-naïve chronic hepatitis C type 1-infected cohort

J Viral Hepat. 2010 Nov 10. doi: 10.1111/j.1365-2893.2010.01394.x. [Epub ahead of print]

Ramcharran D, Wahed AS, Conjeevaram HS, Evans RW, Wang T, Belle SH, Yee LJ.

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA Division of Gastroenterology, School of Medicine, University of Michigan, Ann Arbor, MI, USA Department of Infectious Disease and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA Division of Infectious Diseases, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Abstract

Summary.  In patients with chronic hepatitis C virus (HCV) infection, steatosis and fibrosis have been shown to be inversely associated with total cholesterol (TC) and low-density lipoprotein cholesterol. Steatosis and fibrosis have also been found to be associated with triglyceride (TG) levels; though, the direction of the relationship is inconsistent across studies. The objective of this study was to assess whether viral level and histological factors are associated with the serum lipid profile in a treatment-naïve cohort with chronic HCV genotype 1 infection. Participants were from the prospective Study of Viral Resistance to Antiviral Therapy (Virahep-C). Fasting lipid profiles were analysed for 160 African Americans and 170 Caucasian Americans. Linear regression was used to evaluate associations of each lipid with viral load and liver disease. TG levels were significantly and directly associated with HCV levels (P = 0.0034) and steatosis (P < 0.0001). Other lipid parameters were significantly lower in those with fibrosis [HDLc (P = 0.001) and TC levels (P = 0.004)] than in those without fibrosis. In patients with HCV genotype 1 infection, more severe liver disease was associated with lower lipid levels, with the exception of TG levels that were directly related to steatosis. The direct relationship between viral load and TG levels is consistent with proposed the mechanisms of very low density lipoprotein/HCV particle secretion. In contrast, the direct relationship between TG level and steatosis is inconsistent with posited mechanisms of HCV-induced steatosis, a possible reflection of HCV genotype 1 infection and a metabolic aetiology of steatosis.

© 2010 Blackwell Publishing Ltd.

Source