Background and Aims: A deranged metabolic status and alcohol intake may trigger induction and progression of chronic hepatitis C virus (HCV) liver disease. The aim of this study was to evaluate whether dietary composition affects the severity of liver damage and response to therapy in patients with HCV-related chronic hepatitis.
Methods: We enrolled 1,084 patients with biopsy-proven HCV-related chronic hepatitis (432 treated with interferon plus ribavirin) and 2,326 healthy subjects in this prospective study conducted in a university hospital. Dietary habits were recorded in enrolled individuals, and their alcohol consumption was evaluated with a questionnaire (AUDIT). Body mass index, and plasma levels of blood glucose, nitrogen, creatinine, cholesterol, and triglycerides were also measured. All individuals underwent routine liver tests and HCV genotyping.
Results: At study onset, there were no differences in metabolic status or alcohol consumption between patients and controls. About 50% of each group was overweight, and about 60% consumed alcohol. Patients and controls had similar dietary habits. Intake of carbohydrates, lipids and polyunsaturated fatty acids, and alcohol consumption were independent factors of liver damage at histology (logistic regression analysis). Some dietary components (unsaturated fatty acids, iron, zinc, vitamin A, and niacin) and alcohol intake differed significantly (P < 0.05 and P 0.01, respectively; univariate analysis) between responders and nonresponders to interferon therapy. Genotype, age, body mass index, steatosis, and fibrosis were independent predictors of therapy outcome (P < 0.02; multivariate analysis).
Conclusions: The severity of HCV-related chronic hepatitis depends on a variety of factors. Our results show that dietary composition is related to the extent of liver damage. Although traditional risk factors independently affected treatment response, some dietary components were associated with nonresponse to therapy in our patients. This suggests that HCV patients may benefit from instructions regarding their diet.

 

Viral and host factors regulate the progression of chronic hepatitis and the response to therapy in patients with HCV-related chronic hepatitis, which has been termed a metabolic disease.^[1-6] Recent years have seen a surge of interest in complementary food and chemopreventers to treat various liver diseases including cirrhosis.^[7-13] Diet influences body mass index (BMI), iron content in the liver, insulin, enzyme activities, substrate reserves, and metabolic pathways in hepatocytes, and many foods have been reported to exert protective or toxic effects on the liver in animal models and humans.^[14-20] Moreover, imbalanced diets were found to affect the development and progression in a group of patients with nonalcoholic steatohepatitis. However, to our knowledge, there are no data about the relationships between diet and liver damage in patients with HCV-related chronic hepatitis.

We undertook the present prospective study to evaluate the effect of diet on the severity of liver damage and on the response to antiviral therapy in patients with HCV-related chronic hepatitis.

 

Informed written consent was obtained from each subject and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution's human research committee. We prospectively enrolled patients affected by HCV from Southern Italy referred to our Department between 2002 and 2005. Excluded from the study were patients with chronic HBV and HIV infection, decompensated cirrhotics, and patients with such other clinically relevant associated diseases as decompensated diabetes, kidney diseases, pulmonary diseases, collagen diseases, tumors. A total of 1,084 patients with HCV-related chronic hepatitis were enrolled in the study. Of these, 408 patients had well compensated Child A cirrhosis and 432 were naive patients (including chronic hepatitis and Child A cirrhosis) who had undergone antiviral therapy. HCV genotypes were collected before starting antiviral treatment. As a control group, we studied 2,326 apparently healthy blood donors who were negative for HCV antibody and hepatitis B surface antigen (HBsAg), and had normal liver tests.

The 1,084 patients with chronic liver disease underwent a liver biopsy, which was scored according to Ishak et al.. Steatosis was graded as absent (0), mild (<33%, 1), moderate (>33% and ≤66%, 2), or severe (>66%, 3). The subgroup of patients, in whom interferon (IFN) therapy was indicated, received pegylated-IFN + ribavirin and were treated for 48 (in genotype 1-4 patients) or 24 wk (in genotype 2-3 patients) according to current guidelines. The virological response to therapy was assessed by HCV-RNA measurements at baseline, at 12 and 48 wk of treatment, and 24 wk after treatment ended. Based on qualitative HCV-RNA results, the patients were defined either sustained virological responders (SVRs) (no detectable HCV-RNA after 24/48 wk of treatment and 6 months thereafter) or non-responders (NRs) (viral breakthrough, and virological nonresponse, with persistence of HCV-RNA at the end of treatment). Treatment was discontinued in virological nonresponders at week 12 of therapy, based on a positive quantitative HCV-RNA test.

Patients and controls with a BMI between 25 kg/m² (for men) and 24 kg/m² (for women) and 29.9 kg/m² were considered overweight (determined as kg/m², and those with a BMI ≥30 kg/m² were considered obese. Plasma levels of blood glucose, nitrogen, creatinine, cholesterol, triglycerides after 12 h of fasting (routine kits) were measured, and patients and controls underwent routine liver tests. Dietary habits were recorded for all enrolled subjects. For this purpose, we used the Winfood Software 2.0 package (Medimatica s. r. l., Martinsicuro, Italy) program, which has previously been used to assess alimentary history.^[26,27] On the basis of the quantities and qualities of foods consumed, the program elaborates the energy intake and the percentage of macronutrients and micronutrients, and calculates the elements in each food. Proteins are reported as animal and vegetal proteins. Carbohydrates are divided in soluble and amide, lipids in saturated, polyunsaturated, monounsaturated fatty acids, and cholesterol. The complete elaboration of intakes shows the list of diet components, the ratio among components and calories, and the subdivision in breakfast, lunch, and dinner. We recorded the food intake of a complete week, including working days and the weekend. The dietary examination was randomly repeated in a large number of subjects (202 patients and 334 controls, equally distributed in men and women) to evaluate variability. Data collected were similar in all interviews (Concordance: k = 0, 8). The data were compared with the tables of food consumption and recommended dietary intakes of the Italian National Institute of Nutrition and Food Composition Database in Italy.^[28,29]

Alcohol use was evaluated with a standardized precodified questionnaire (complete AUDIT test). We considered as constant a continuous daily alcohol intake in the last 3 yr at least. The quantity of daily alcohol intake was calculated based on a drink that corresponds to about 12 g of pure ethanol.

 

RESPONSE TO IFN. ......Besides the association between gender, age, genotype, and fibrosis, also obesity, some nutrients, and alcohol consumption were significant. At multivariate analysis, age, BMI, steatosis, fibrosis, and HCV genotypes were independent predictors of the outcome to therapy in our HCV-infected patients.