Hepatitis C and Alcohol : Liver Cancer, Disease Progression

by National Institute of Health

(Page 2 of 3)

Liver Cancer

An Italian survey showed that alcohol intake doubles the risk of hepatocellular carcinoma in HCV-infected patients who drink 41 to 80 g of alcohol per day (between 3.4 and 6.7 drinks) and quadruples the risk for patients who drink more than 80 g of alcohol per day. Other research has shown that HCV-infected patients who drink heavily are more likely to develop liver cancer at a younger age than are those who drink less. For example, Noda and colleagues observed that patients who drank at least 46 g of alcohol daily were diagnosed with hepatocellular carcinoma an average of 26 years after developing transfusion-associated HCV, whereas those who drank less than 46 g per day were diagnosed with cancer an average of 31 years after transfusion. And Kubo and colleagues found that, among HCV-infected patients with hepatocellular carcinoma, heavy drinkers had more advanced tumors and died sooner after diagnosis than did nondrinkers.

Moderate-to-Heavy Drinking and Disease Progression

Most studies have evaluated the effect of extremely heavy drinking on the progression of HCV infection to other liver disease, with little emphasis on the effects of moderate drinking on disease progression. However, some studies have found indications that moderate-to-heavy alcohol consumption also may increase the risk of developing liver fibrosis and cirrhosis in patients infected with HCV.

Ostapowicz and colleagues specified no particular threshold level above which the risk of disease progression increases but found that, among patients with chronic HCV infection, those who had cirrhosis reported higher lifetime and total alcohol consumption than those HCV patients who did not have cirrhosis.

Several other studies have examined the effects of moderate drinking on HCV progression. (In these studies, definitions of moderate drinking differ from current Federal guidelines, which consider moderate drinking to be no more than one drink per day for women, and no more than two drinks per day for men.) Assessing HCV-infected patients who drank less than 40 g of alcohol (3.3 drinks) per day, Westin and colleagues found that patients whose alcohol intake was above the median level (4.8 g of alcohol, or less than one drink per day) showed more liver scarring (fibrosis) than patients whose alcohol consumption was below the median level. Hézode and colleagues also found that the severity of fibrosis in patients with chronic HCV was correlated with the amount of alcohol consumed. Finally, a recent study of 180 patients with untreated chronic hepatitis C confirmed these findings.

Gender and Disease Progression

The data regarding the contribution of gender to the progression of HCV in alcoholics is quite limited. Chronic hepatitis C often is milder in women than in men, but women may be more sensitive than men to the adverse effects of alcohol.

Histologic Features of Chronic Hepatitis C in Alcoholic Patients

As discussed above, there is strong evidence that heavy alcohol consumption and perhaps even moderate consumption - increases the risk that HCV infection will progress to more serious liver disease. In patients infected with HCV, alcohol consumption has a direct effect on liver histology. Specifically, patients with HCV who are drinkers show greater liver necrosis, inflammation, fibrosis, and fatty infiltration than HCV patients who do not drink. Further, alcohol consumption and fatty liver have been shown to act together to increase fibrosis in patients infected with HCV, especially in those who are obese and diabetic.

Mechanisms of Liver Injury in Alcoholic Hepatitis C Infection

Although researchers do not fully understand how alcohol consumption accelerates liver injury in patients with HCV infection, it is likely that several factors are involved. The following mechanisms have been proposed.

Increased replication of HCV in the liver. As illustrated in figure 4, some research (although not all) has found that greater alcohol consumption is related to higher HCV RNA blood concentrations. Moreover, as shown in figure 5, when people infected with HCV who drank more than 10 g of alcohol (about 5.8 drinks) per day abstained from alcohol or substantially reduced their consumption for 4 months before treatment, HCV RNA levels dropped; the decline in serum HCV RNA among subjects who drank less than or equal to 10 g of alcohol per day before abstaining was not statistically significant.

Mutations of the HCV virus (forming what are known as quasi-species). Alcoholics infected with HCV show greater quasi-species complexity than do nonalcoholics with HCV infection. In alcoholic HCV patients, such increased viral complexity might make it difficult for the immune system to control the mutated viruses, leading to progressive injury.

Increased programmed cell death (apoptosis) of liver cells. Apoptotic death of liver cells, which can ultimately lead to liver fibrosis, is increased by alcohol consumption in people with HCV infection.

Higher levels of inflammation and immunoregulatory proteins (specifically, interleukin, tumor necrosis factor, and interferon). In research with mice, Geissler and colleagues noted that chronic alcohol feeding in mice inhibited immune responses (specifically, responses by T-helper cells and cytotoxic T-lymphocytes) that play a pivotal role in removal of HCV from the body.

Viral gene mutations. Fatty liver. Accumulation of fat in the liver is common in patients with HCV. Examining a large group of patients with HCV infection, Serfaty and colleagues found that fibrosis progressed about twice as quickly among drinkers with steatosis as among drinkers without steatosis or nondrinkers with or without steatosis.

Accumulation of excess iron in body tissues (iron overload). Alcohol consumption increases iron stores in the liver, and iron overload seems to contribute to HCV disease progression by inducing fibrosis.

Oxidative stress. Alcohol stimulates the production of reactive oxygen-containing molecules (oxygen radicals). Heavy alcohol use also depletes the body's supply of molecules that normally defend tissues against damage caused by oxygen radicals (antioxidants). This state, known as oxidative stress, may accelerate liver damage in patients with HCV. Depression of the immune system by alcohol.

About the Author

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