Marion G. Peters, MD, MBBS and Norah Terrault, MD

NIH Consensus Development Conference on
Management of Hepatitis C: 2002 

Bethesda, Maryland
June 10-12, 2002

Excess alcohol consumption can worsen the course and outcome of chronic hepatitis C. ^(1–3) However, adverse effects of moderate amounts of alcohol intake have not been clearly shown. ⁽⁴⁾ Alcohol use has been reported in some studies to be associated with higher HCV RNA levels and lower responses to therapy. ⁽⁵⁾ Despite a large number of publications on the topic of alcohol and hepatitis C, current evidence from the literature is not adequate to provide clear and definitive recommendations regarding alcohol use in patients with hepatitis C. In the absence of conclusive data, a conservative approach is taken and abstinence is usually recommended.

What Level of Alcohol Intake Is Harmful in Chronic Hepatitis C?

Poynard and coworkers compared liver histology of patients with hepatitis C drinking >50 g per day to that of non-drinkers and found a 34 percent increased rate of progression of fibrosis in heavy drinkers. ⁽¹⁾ Associations between fibrosis progression and lesser amounts of alcohol intake were not significant, but the measurement of alcohol intake was assessed in a uniform, standardized manner. The HCV National Register Steering Group in the UK traced 924 patients who had received an anti-HCV-positive unit of blood for an average of >10 years after transfusion and assessed alcohol intake using validated questionnaires. ⁽⁶⁾ Liver-related deaths were increased among those who drank >20 units per week (approximately 30 g per day) in both patients with hepatitis C and controls.

The Dionysos study analyzed hepatitis virus markers, alcohol intake (assessed by questionnaires of daily and lifetime intake), and clinical and  iochemical evidence for liver disease among 6,917 unselected residents of two Northern Italian cities. ^(3,7) In all, 2.3 percent had HCV RNA and 62 percent drank alcohol, including 21 percent who drank more than 30 g per day. Both control subjects and persons with HCV who drank more than 30 g per day for >10 years had a threefold higher risk of cirrhosis (95 percent CI = 1.2 to 7.4, p<0.01). Intake below 30 g per day did not increase the risk of clinically apparent cirrhosis, but histology was not assessed in most patients. Harris and coworkers analyzed factors associated with cirrhosis among 206 patients who developed hepatitis C after transfusion and were followed for an average of 15 years in addition to a cohort of controls who were transfused but did not develop hepatitis C. ⁽⁸⁾ Among those with hepatitis C, 17 percent developed cirrhosis.

The risk of cirrhosis increased fourfold among those who were also heavy drinkers (>80 g per day). Corrao and Arico analyzed results from two hospital-based, case-control studies of 285 patients with cirrhosis and 417 controls. ⁽⁴⁾ A lifetime daily alcohol intake of >50 g per day was associated with an increased risk of cirrhosis in both HCV-positive and negative subjects. The combination had an additive effect on the risk, and these risks were multiplied (synergism) at very high levels of alcohol intake (>125 g per day). Wiley and coworkers analyzed factors associated with more advanced liver disease in a cohort of 176 patients who underwent liver biopsy for chronic hepatitis C. ⁽²⁾ Alcohol intake of > 80 g daily was associated with a higher rate of cirrhosis (56 percent vs 22 percent) and an increase in the estimated rate of progression of fibrosis.

In a study from Japan, Khan and Yatsuhashi found higher degrees of fibrosis on liver  biopsies from patients with chronic hepatitis C who drank alcohol compared to those who didnot, and this increase was seen with both heavy (>80 g per day) and “moderate” (<80 g per day) alcohol intake. ⁽⁹⁾ Further delineation of effects of lower levels of alcohol intake were not given. Excess alcohol intake can also predispose to the development of liver cancer. (10) Thus, multiple studies have shown that heavy alcohol intake increases the risk of cirrhosis and liver cancer in hepatitis C, but the effects of moderate alcohol intake have not been adequately evaluated.

Are There Gender Differences in Effect of Alcohol on Progression of HCV  Infection?

Chronic hepatitis C is often milder in women, but women may be more sensitive to the adverse effects of alcohol. The Dionysos cohort study found the risk of cirrhosis was twice as high in women as in men with the same alcohol intake. ^(3,7) Wiley et al. found a lower alcohol threshold for development of cirrhosis in women. ⁽²⁾ Thus, women may be at increased risk of alcohol effects on chronic hepatitis C.

What Are the Effects of Alcohol Consumption on Treatment of Hepatitis C?

Alcohol can affect the outcome of therapy in decreasing adherence or interfering with the antiviral actions of interferon or combination therapy. Virtually all large trials of therapy of hepatitis C have excluded persons who have a recent history of alcohol abuse, requiring a one- to two-year period of abstinence before therapy is initiated. However, the need for a period of abstinence has never been shown. Among patients treated for hepatitis C, a proportion continued drinking, and the ultimate response rate correlated inversely with the level of alcohol intake during therapy. The mechanism of the decreased response rate in patients drinking alcohol has not been defined. Some studies have shown that alcohol intake is associated with higher levels of HCV RNA ^(1,5) but other studies have not, ^(2,3,10) and the increase in HCV RNA levels with drinking alcohol has been modest. Thus, continued alcohol intake during therapy is likely to adversely affect the response to treatment, and both counseling and monitoring before and during therapy is recommended.

Does Alpha Interferon Therapy Cause Increase in Rate of Relapse Among Persons With a History of Alcohol Abuse or Dependence?

Relapse in alcohol intake during alpha interferon therapy has been reported, but the rate of relapse has not been compared in studies using untreated control patients. Nevertheless, the depression, irritability, and anxiety that occurs in 20–30 percent of patients treated with alpha interferon is likely to be difficult for the patient with a recent history of alcohol dependence and predisposition to relapse.

Conclusions

While the effects of heavy daily alcohol intake on the course of chronic hepatitis C appear to be incontrovertible, lesser amounts of alcohol may not be harmful. On the other hand, abstinence appears to be prudent for the patient with chronic hepatitis C, particularly while receiving a course of alpha interferon or combination therapy. Patients with a history of alcohol abuse or dependence should be asked to be abstinent for a period before starting therapy and need to be supported by professional counseling and monitoring during therapy. Better studies using validated instruments to measure alcohol intake in larger numbers of patients, followed for longer periods and with careful histological documentation, are needed to better define the effects of moderate alcohol intake on chronic hepatitis C and the need for abstinence before and during therapy. At the present time, there is no reason to withhold antiviral therapy of chronic hepatitis C from the patient with a history of alcoholism as long as adequate support can be provided during the period of therapy.

References

1. Poynard T, Bedossa P, Opolon P, for the OBSVIRC, METAVIR, CLINVIR, and DOSVIRC groups. Lancet 1997;349:825–32.

2. Wiley TE, McCarthy M, Breidi L, Layden TJ. Impact of alcohol on the histological and clinical progression of hepatitis C infection. Hepatology 1998;28:805–9.

3. Bellentani S, Pozzato G, Saccoccio G, Crovatto M, Croce LS, Mazzoran L, et al. Clinical course and risk factors of hepatitis C virus related liver disease in the general population: report from the Dionysos study. Gut 1999;44:874–80.

4. Corrao G, Arico S. Independent and combined action of hepatitis C virus infection and alcohol consumption on the risk of symptomatic liver cirrhosis. Hepatology 1998;27:914–9.

5. Loguercio C, Di Pierro M, Di Marino MP, Federico A, Disalvo D, Crafa E, et al. Drinking habits of subjects with hepatitis C virus-related chronic liver disease: prevalence and effect on clinical, virological and pathological aspects. Alcohol Alcohol 2000;35:296–301.

6. Harris HE, Ramsay ME, Andrews N, Eldridge KP. Clinical course of hepatitis C virus during the first decade of infection: cohort study. BMJ 2002;324:1–6. 7. Bellentani S, Saccoccio G, Costa G, Tiribelli C, Manenti F, Sodde M, et al. Drinking habits as cofactors of risk for alcohol induced liver damage. The Dionysos Study Group. Gut 1997;41:845–50.

8. Harris DR, Gonin R, Alter HJ, Wright EC, Buskell ZJ, Hollinger FB, et al. The relationship of acute transfusion-associated hepatitis to the development of cirrhosis in the presence of alcohol abuse. Ann Intern Med 2001;134:120–4.

9. Khan KN, Yatsuhashi H. Effect of alcohol consumption on the progression of hepatitis C virus infection and risk of hepatocellular carcinoma in Japanese patients. Alcohol Alcohol 2000;35:286–95.

10. Donato F, Tagger A, Gelatti U, Parrinello G, Boffetta P, Albertini A, et al. Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am J Epidemiol 2002;155:323–31.
 

Alcohol and Hepatitis C
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