Alcohol and hepatitis C

Abstract

Infection with the hepatitis C virus (HCV) has become a leading cause of scarring of the liver (i.e., fibrosis) and cirrhosis in the United States. HCV-related cirrhosis (with its associated complications, such as liver cancer) is a major cause of death, although it develops slowly and occurs only in approximately one-third of HCV-infected patients. Alcohol can exacerbate HCV infection and the associated liver damage by causing oxidative stress and promoting fibrosis, thereby accelerating disease progression to cirrhosis. Furthermore, alcohol may exacerbate the side-effects associated with current antiviral treatment of HCV infection and impair the body's immune defense against the virus. Of the HCV-infected people who do not consume alcohol, only a minority progresses to severe liver disease and requires antiviral treatment. Because alcohol potentiates the fibrosis- and cancer-inducing actions of HCV, alcoholics are particularly vulnerable to HCV infection and most in need of treatment.

Figure 1

The progression of hepatitis C (HCV) infection and the proportion of initially infected patients who develop each disease stage. Approximately two-thirds of the people suffering an acute infection experience a relativity benign disease course; that is, the infection resolves on its own, does not progress, or responds to antiviral treatment. Conversely, approximately one-third of people infected with HCV develop cirrhosis, and many later die of complications from the cirrhosis (i.e., decompensated cirrhosis) or from liver cancer (i.e., hepatocellular carcinoma [HCC]). The proportions shown here provide only a general indication of how this disease progresses. The actual prognosis may vary strikingly in each patient, depending on numerous factors, including the patient’s genetic makeup; gender; age at onset of the infection; presence or absence of antiviral treatment; and, especially, concomitant alcohol use. These factors also affect the duration of disease progression, which, from the onset of the infection to the end-stages of disease, may last from 10 to 30 years.

Figure 2

Relationship between hepatitis C virus (HCV) levels in the blood and self-reported alcohol consumption (SRAC) (in grams of alcohol per week*) during a typical week in the month preceding the HCV measurement. Greater alcohol consumption was associated with higher virus levels in the blood. *One standard drink (i.e., 12 fluid ounces of beer, 5 fluid ounces of wine, or 1.5 fluid ounces of distilled spirits) contains approximately 14 grams (0.5 ounces) of pure alcohol. NOTE: Statistical significance: r = 0.26, p<0.0001. SOURCE: Pessione et al. 1998, with permission.

Figure 3

The beneficial and toxic roles of CYP2E1, an enzyme involved in the breakdown of alcohol in the liver that acts in conjunction with another compound (i.e., nicotinamide adenine dinucleotide phosphate or NADPH). CYP2E1 typically helps process compounds that are normally present in the body (e.g., fatty acids and ketones), and breaks down potentially toxic foreign substances (i.e., xenobiotics), including alcohol. Enhanced CYP2E1 activity, however, also results in the increased generation of harmful byproducts (e.g., acetaldehyde from alcohol) and other toxins, such as free radicals (e.g., superoxide [O₂^•] and hydroxyl [OH^•]) that can cause liver injury by promoting excessive breakdown of fat molecules (i.e., lipid peroxidation). SOURCE: Lieber 1999a, with permission.

Figure 4

Relationship between mean self-reported alcohol consumption (SRAC) prior to the diagnosis of hepatits C virus (HCV) infection (expressed in grams per week*) and the severity of fibrosis (i.e., scarring of liver tissue, which indicates an early stage of liver disease). The severity of fibrosis was assessed using the Knodell index, which measures changes in the tissue’s structure and chemical composition (i.e., histological changes). The data show that greater alcohol consumption was associated with more severe fibrosis (i.e., greater liver damage) by the time the HCV infection was diagnosed, and therefore with more rapid disease progression. *One standard drink (i.e., 12 fluid ounces of beer, 5 fluid ounces of wine, or 1.5 fluid ounces of distilled spirits) contains approximately 14 grams (0.5 ounces) of pure alcohol. NOTE: Statistical significance: p<0.02 (univariate analysis). SOURCE: Pessione et al. 1998, with permission.