In patients with chronic hepatitis C, alcohol consumption has been proposed as a risk factor for the progression of liver disease; however, evidence for this remains conflicting. Two hundred thirty-four anti-hepatitis C virus (HCV)positive patients who had a liver biopsy performed within the past 24 months were studied. Demographic data and information on risk factors were recorded. A detailed lifetime alcohol consumption history was obtained. Viral studies included HCV viral titer and HCV genotype. Mean age (Ψ SEM) of the group was 40.8 Ψ 0.7 years. One hundred sixty-six (71%) were male. A risk factor for HCV infection was found in 195 patients (86%). Genotype distribution was: 1b: 22%; 1a: 15%; 1(nonsubtypable): 15%; 3a: 34%; and 2: 7%. Fifty (21%) patients had cirrhosis. Patients with cirrhosis were older (51.6 Ψ 1.8 years) than those with chronic hepatitis (37.6 Ψ 0.6 years; P β«Ψβ¬ .0001), were infected at an older age (25.9 Ψ 2.0 vs. 20.9 Ψ 0.6 years; P β«Ψβ¬ .001), and had a longer duration of infection (20.5 Ψ 1.3 vs. 16.2 Ψ 0.5 years; P β«Ψβ¬ .0008). Patients with cirrhosis had a greater total lifetime alcohol consumption (288,765 Ψ 58,115 g) than those with chronic hepatitis (189,941 Ψ 15,453 g; P β«Ψβ¬ .018). Cirrhotic patients also had greater total alcohol consumption during the period of infection with HCV (240,962 Ψ 63,756 g vs. 146,510 Ψ 12,862 g; P β«Ψβ¬ .02). On multivariate analysis, subject age and total alcohol consumption were independently associated with the presence of cirrhosis. Total lifetime alcohol consumption is a risk factor for the progression of liver disease caused by HCV. (HEPATOLOGY 1998;27:1730-1735.) After exposure to hepatitis C virus (HCV), over 70% of persons will fail to clear the infection and become chronic carriers. These individuals develop chronic hepatitis of varying severity. Progression to cirrhosis has been reported in approximately 20% of infected persons. Many questions remain unanswered regarding the natural history of HCV infection. While greater age and duration of infection are associated with more severe disease, 5 it remains unclear which other factors may predispose to the development of cirrhosis. Some investigators have found more severe liver disease in persons infected with genotype 1b than in those infected with other genotypes. More recently, it has been suggested that genotype may be a surrogate for the duration of disease rather than an independent factor influencing disease progression. Earlier investigators concluded that HCV viral load may predispose to more severe disease. This has not been confirmed in more recent studies. Greater diversity of HCV quasispecies, 12 coinfection with hepatitis B virus, 13 and hepatic iron stores 14,15 have also been examined; however, no firm conclusions can be reached.
Excessive alcohol use has also been proposed as a factor that influences the progression of HCV infection. Its significance, however, especially that of ''moderate drinking,'' remains unclear. While some investigators have reported excessive alcohol use to be associated with the development of more significant liver disease or cirrhosis, 16,17 these findings are not supported by the work of others. Retrospective analysis of alcohol consumption is very difficult and timeconsuming. Populations used in previous studies have often been small and not comparable. Methods employed in assessing alcohol consumption have often been inadequate and included the examination of intake over short periods of time, such as during the 12 months before diagnosis or over a period of 5 years. Other investigators classified subjects into heavy or light drinkers according to differing criteria (40-60 g/d) without indication of the period of time over which this was assessed. None of the studies have performed a detailed assessment of lifetime alcohol consumption, which is necessary to accurately examine the relationship between alcohol intake and the progression of liver disease.
The aims of this study were to: 1) examine the association between alcohol use and the severity of liver disease by performing a detailed assessment of lifetime alcohol consumption; and 2) identify other factors related to the development of cirrhosis in a large group of Australian patients with chronic HCV infection.
PATIENTS AND METHODS
Patients. Patients were recruited from those referred to liver clinics at St. Vincent' s Hospital (SVH), Melbourne, Australia. Since January 1990, approximately 1,300 patients with HCV have been assessed at SVH. Fifty percent of the referrals have been from general practitioners, while others have been from the Red Cross Blood Bank (identified through routine blood donor screening) (29%), other specialists (14%), and SVH outpatients (7%). Patients who had a liver biopsy performed between January 1992 and December 1996 were asked to participate in the study. Liver biopsies were performed on those individuals who had alanine transaminase (ALT) elevated more than 1.5 times the upper limit of normal and were being Abbreviations: HCV, hepatitis C virus; SVH, St. Vincent' s Hospital; ALT, alanine aminotransferase; IDU, injecting drug use; PCR, polymerase chain reaction.