Independent and combined action of hepatitis C virus infection and alcohol consumption on the risk of symptomatic liver cirrhosis

Abstract

Although alcohol intake and hepatitis C virus (HCV) infection are the major determinants of liver cirrhosis (LC) in Western countries, the joint effect of these two factors on LC risk has not yet been adequately studied. We used data from two hospital-based case-control studies performed in Italy. Cases were 285 cirrhotic patients admitted for the first time to district hospitals for liver decompensation. Controls were 417 patients admitted during the same period, and in the same hospitals as the cases, for acute diseases unrelated to alcohol. Alcohol consumption was expressed as lifetime daily alcohol intake (LDAI). Serum HCV antibodies (anti-HCV) were detected using a secondgeneration test and recombinant immunoblotting assay. We found a dose-effect relationship between LDAI and the risk of LC in both anti-HCV-negative and -positive subjects. Considering the extreme LDAI categories (LDAI ‫؍‬ 0 g, lifetime teetotalers, and LDAI ‫؍‬ 175 g), the LC odds ratios increased from 1.0 (reference category) to 15.0 (95% CI, 7.1-31.7) and from 9.2 (95% CI, 2.0-43.2) to 147.2 (95% CI, 42.1-514.3) in anti-HCV-negative and -positive patients respectively. The interaction between LDAI and HCV showed an additive structure for LDAI F50 g/day and a multiplicative structure for consumption G125 g/day. Alcohol intake and HCV infection are independent risk factors for symptomatic liver cirrhosis, each being sufficient to induce the disease. In subjects with high alcohol intake, the coexistence of HCV infection multiplies the alcohol-associated risk of cirrhosis. In subjects with low alcohol intake, other factors could be involved. (HEPATOLOGY 1998;27:914-919.)Alcohol intake represents the main determinant of liver cirrhosis in Italy 1,2 and other Western countries. 3 Evidence in this respect has been given by ecological, 3-5 prevalence, 6-9 case-control, 10-15 and cohort 16,17 studies. However, several observations suggest that other factors should interact with alcohol consumption in causing liver damage. [18][19][20] In alcoholics, liver histology is normal in 5% to 25% of biopsies and 18% of autopsy findings, 21 and cirrhosis develops at a low yearly incidence rate of around 2%. 16 Thus, only 10% to 25% of alcoholics will suffer from cirrhosis during their life. 22 Among these interacting factors, the role of chronic infection with hepatitis B virus is still debated. [23][24][25][26] Similarly, despite the initial suggestion that chronic infection with hepatitis C virus (HCV) may multiplicatively interact with alcohol intake in determining cirrhosis, 27 recent evidence suggests that these two factors act independently. 28 The aim of the present study was to assess, using a case-control design, the risk of developing liver cirrhosis associated with alcohol intake, HCV infection, and the combined action of these factors. PATIENTS AND METHODS Selection of Cases and Controls.We used the data from two hospitalbased case-control studies performed with the same design in two different periods and in two different Italian areas.The desi...

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“…Similar to other studies evaluating the factors associated with severe fibrosis, we found that duration of moderate to heavy alcohol use was an independent predictor of moderate to severe fibrosis (2,21,28,29). Definitions of "heavy" alcohol use vary across different studies and not all studies use gender-specific cut-offs.…”

Impact of aging on the development of hepatocellular carcinoma in patients with posttransfusion chronic hepatitis C

“…There is solid evidence that excessive alcohol intake is a risk factor for the progression of liver disease caused by HCV. 17,18 The current study data appear to support that view.…”

Southern Europe as an example of interaction between various environmental factors: a systematic review of the epidemiologic evidence

“…Other case-control studies carried out in South Europe have demonstrated a dose-effect relationship of increased risk for both cirrhosis and HCC with increasing alcohol intake, when also adjusting for HBV and HCV infection (Corrao et al, 1993(Corrao et al, , 1997Bellentani et al, 1994;Corrao and Arico`, 1998;Kuper et al, 2000a). On the same line, two meta-analyses conducted by Corrao et al (1998aCorrao et al ( , 2004 on the risk of cirrhosis and of various neoplasms, including liver cancer, show a continuous curve of increasing risk of disease with increasing alcohol intake.…”

“…Some Italian studies on the aetiology of cirrhosis confirm the hypothesis of a synergism between alcohol intake and HCV or HBV infection (Corrao and Arico`, 1998). In agreement with these findings, in a French study among subjects with HCV infection, age at infection and duration of infection were associated linearly with fibrosis stage, both associations being modified by alcohol intake: patients who consumed 50 g/day or more of alcohol had a higher fibrosis Table 4 Interaction between HBV or HCV infection and heavy alcohol intake (>60 g/day of ethanol for at least 10 years) in the Brescia HCC case-control study (Donato et al, 2002, data Figure 2 Odds ratio for HCC according to alcohol intake and the presence of HBV or HCV, obtained by fitting spline regression models that included age and residence as covariates, hepatitis B surface antigen and HCV RNA in the Brescia HCC study.…”