1. www.alcoholandhealth.org1 Journal Club Alcohol and Health: Current Evidence January-February 2006

2. www.alcoholandhealth.org2 Featured Article Alcohol has no effect on hepatitis C virus replication: a meta-analysis Anand BS, et al. Gut. 2005;54:1468-1472.

3. www.alcoholandhealth.org3 Study Objective To examine whether… alcohol stimulates replication of the hepatitis C virus (HCV)

4. www.alcoholandhealth.org4 Study Design Systematic review and meta-analysis of 14 studies that assessed the association between alcohol use and hepatitis C virus replication

5. www.alcoholandhealth.org5 Users’ Guides for How to Use Review Articles Are the results of the study valid? What are the results? Will the results help me in caring for my patients?

6. www.alcoholandhealth.org6 Are the Results of the Study Valid? Did the overview address a focused clinical question? Were the criteria used to select articles for inclusion appropriate? Is it unlikely that important, relevant studies were missed? Was the validity of the included studies appraised? Were assessments of studies reproducible? Were the results similar from study to study?

7. www.alcoholandhealth.org7 Did the overview address a focused clinical question? Yes. –The question was whether alcohol consumption influences HCV viral levels.

8. www.alcoholandhealth.org8 Were the criteria used to select articles for inclusion appropriate? The most valid study design to assess the effect of alcohol on HCV viral levels is a randomized trial. –However, given ethical and feasibility concerns, these studies are not likely common. Researchers included studies of humans that reported current alcohol consumption and HCV viral titres (and the methods of measurement).

9. www.alcoholandhealth.org9 Is it unlikely that important, relevant studies were missed?  Yes.  The search strategy included…  studies since 1989 when the virus was first described,  studies identified in major databases,  abstracts, and  non-English language articles.

10. www.alcoholandhealth.org10 Was the validity of the included studies appraised? The authors did not report the validity or quality of the individual studies. They did note that some studies did not report viral titres.

11. www.alcoholandhealth.org11 Were assessments of studies reproducible? No information was provided on... –who assessed the studies or –whether the assessments were reproducible.

12. www.alcoholandhealth.org12 Were the results similar from study to study? Study results were heterogeneous.

13. www.alcoholandhealth.org13 What Are the Results?  What are the overall results of the review?  How precise were the results?

14. www.alcoholandhealth.org14 What are the overall results of the review? 3 of 9 studies showed significantly higher hepatitis C viral levels in heavy drinkers (defined variably) than in nondrinkers. However, this difference was no longer significant when data from all 9 studies were combined.

15. www.alcoholandhealth.org15 What are the overall results of the review (continued)? Hepatitis C viral levels did not increase significantly as alcohol use increased, based on combined data from 4 studies of nondrinkers and moderate and heavy drinkers. In 5 small studies (59 subjects total), HCV titres were measured in the same subjects before and after abstinence. –In 2 studies, titres decreased with abstinence. –In 2 studies, titres decreased with abstinence in about half of subjects. –In the remaining study, titres did not change with abstinence.

16. www.alcoholandhealth.org16 How precise were the results? The confidence interval (CI) around the effect size of alcohol use on HCV levels was –0.31 to +1.17. The CI included no effect, a positive effect, and a negative effect.

17. www.alcoholandhealth.org17 Will the Results Help Me in Caring for My Patients? Can the results be applied to my patient care? Were all clinically important outcomes considered?

18. www.alcoholandhealth.org18 Can the results be applied to my patient care? It is not clear whether the results can be applied in practice. The study question remains unanswered because of… –methodological limitations of some of the studies, –small samples, and –a wide confidence interval around the main finding. A consistent effect of alcohol on HCV viral levels was not detected, but it was also not excluded.

19. www.alcoholandhealth.org19 Were all clinically important outcomes considered? Increased HCV viral levels are one possible effect of alcohol on hepatitis C infection. More important outcomes of interest include a range of markers of disease progression, such as hepatic failure and death.