Alcohol Potentiates Hepatitis C Virus Replicon Expression

Abstract

H epatitis C virus (HCV) is responsible for the vast majority of cases of transfusion-associated and community-acquired non-A, non-B hepatitis 1,2 and infects an estimated 170 million people worldwide. 3 The seroprevalence of anti-HCV antibody in the United States has been estimated at 1.8%, which corresponds to approximately 4 million people. 4 HCV is the leading cause of chronic viral hepatitis in the United States, 5 and HCV-infected individuals are the major recipients of liver transplantation. HCV, first molecularly cloned in 1989, 1 is a positive-strand RNA virus of the flavivirus family with a genome size of ϳ10 kb, which encodes a number of structural (core, E1, E2, and p7) and nonstructural (NS2, NS3, NS4A, NS4B, NS5A and NS5B) proteins. 6 HCV has at least 6 distinct but related genotypes with more than 50 subtypes, and genotype 1 is the most common in the United States, Europe, and most parts of Asia. HCV typically escapes clearance by the host's immune system and leads to the establishment of a persistent infection in approximately 70% of infected individuals. 7 The consequences of a subset of patients with chronic HCV infection are cirrhosis, liver failure, and hepatocellular carcinoma. 8,9 Treatment of HCV with interferon alfa (IFN-␣) and ribavirin is associated with a sustained response rate of less than 50%. 7,10,11 These limited therapeutic efficacies and the absence of an effective HCV vaccine underscore the importance of research on factors that enhance HCV infection and compromise IFN-␣-based therapy.Alcohol is the most commonly used and abused drug in the United States. Alcohol abuse significantly affects morbidity and mortality from infectious diseases. 12 Alcohol consumption accelerates liver damage, diminishes therapeutic response to IFN-␣, and increases the rate of hepatocellular carcinoma in patients with chronic HCV

Hepatitis C Virus Inhibits Intracellular Interferon Alpha Expression in Human Hepatic Cell Lines *

“…These cells were maintained in DulbeccoЈs Modified EagleЈs Medium (DMEM) (Gibco-BRL, Grand Island, NY) as previously described. 20 For all experiments, functionally endotoxin-free media and reagents were used. All cell cultures were checked for mycoplasma contamination by MycoAlert Mycoplasma Detection Kit (Cambrex).…”

“…Luciferase activities in cell lysates were quantified using a Luciferase Assay System (Promega) and a TD-20/20 Luminometer (Turner Designs, Inc., Sunnyvale, CA). 20 The results were presented as relative light units (RLU) normalized by the total proteins in the cell lysates. For IFN-␣ promoter-luciferase reporter experiments, the transfection was performed in 24-well plates, in which each well contained 10 5 cells in 1 mL DMEM.…”

“…The total proteins (ϳ50 g) were extracted from the cells, quantitated, and subjected to Western blot assay as described. 20 For immunofluorescent evaluation of HCV NS5A protein, Huh7 cells transfected with the plasmid containing HCV NS5A gene were cultured on glass coverslips (12 mm) in a 24-well plate for 48 hours. The cells were fixed with 75% ice-cold acetone and then pretreated with a blocking solution for 30 minutes.…”

Prevalence and Risk Factors Associated with Various Types of Diseases in Sikkim

“…Excess of liver fats can cause cirrhosis to liver failure. Risk factors for obesity include behavioural components which include exercise and weight control measures, social components which includes food choices and eating patterns in different cultural groups [18]. In our study two parameters vegetarian and non-vegetarian diet (at least 3 meals in a week) were investigated and it was found that diet especially non vegetarian diet could be a risk factor for various diseases as the relative risk value is greater than 1 however more data is required as this value is not statistically significant except for dermal diseases which is >0.05 does not play a significant role in diseases considered.…”

Prevalence of Hepatitis C in alcoholic liver disease.

“…HCV also increases COX-2 expression; thus, this common pathway can amplify liver damage. Furthermore, toxic effects of alcohol on mitochondrial function may inhibit cellular regeneration in the live 13,14 , and HCV core proteins can also cause mitochondrial damage through free oxygen radical generation 15 .Incrased viral replication: Some in vitro hepatocyte studies have demonstrated an increase in HCV replication with alcohol exposure 16,17 , although this effect has not been demonstrated clearly in humans. Indeed, a meta-analysis performed in 2005 reported no increase in HCV RNA levels in the blood of patients with chronic alcohol consumption 18 .…”