Hepatitis C is more severe in drug users with human immunode®ciency virus infection R. Romeo, 1 M. G. Rumi, 1 M. F. Donato, 1 M. A. Cargnel, 2 P. Vigano Á, 2 M. Mondelli, 3 B. Cesana 4 and M. Colombo 1 1 Department of Internal Medicine, IRCCS, Ospedale Maggiore, University of Milan, 2 Institute of Infectious Diseases, L. Sacco Hospital, Milan, 3 Institute of Infectious Diseases, University of Pavia and 4 Epidemiologic Unit, Ospedale Maggiore, Milan, Italy Received June 1999; accepted for publication November 1999 INTRODUCTION Drug users with chronic hepatitis C are frequently co-in- fected with human immunode®ciency virus-1 (HIV-1). Although biological interaction between the two viruses in the same patients may modify the course of hepatitis C virus (HCV) infection [1,2], it is still not clear whether HIV-1 aggravates the natural history of hepatitis C. In a pilot study, all three patients infected with HIV-1 developed non-A, non- B-related cirrhosis in a 3-year period, compared to only eight of 94 (8%; 95% CI 4±16%) non-HIV-1 infected patients with chronic non-A, non-B hepatitis [3]. The time between acquisition of HCV infection and development of cirrhosis was shorter in Spanish drug users co-infected with HIV/HCV than in patients infected with HCV alone [4,5]. In another study [6], the risk of developing HCV-related cirrhosis in HIV-infected drug users was 3.5 times that of HIV-negative HCV carriers. Serum levels of HCV RNA and the risk of liver failure were higher in HIV/HCV co-infected haemophilic patients with low CD4 counts than in similar patients not infected with HIV, or in HIV-positive patients with normal CD4 counts [7,8], suggesting that the HIV-1-related immunode®ciency had promoted HCV pathogenicity. These ®ndings, however, were not con®rmed in a large study of 224 male homosexuals with acquired immune de®ciency syndrome (AIDS), which found that HCV co-infection did not adversely in¯uence survival; clinically evident liver disease was rare and none of the patients co-infected with HCV/HIV died of liver failure [9]. A prospective study of infected drug users might provide a convincing answer as to whether the natural history of hepatitis C is modi®ed by HIV-1, but this is hardly feasible in terms of patients' compliance. Hence, to obtain further information on the interaction between HCV and HIV-1 in drug users, we conducted a multicentre observational study in 163 drug addicts in whom the severity of HCV-related liver disease had been established histologically. Abbreviations: CH, chronic hepatitis; HCV, hepatitis C virus, HIV, human immunode®ciency virus. Correspondence: Massimo Colombo, Department of Internal Medicine, University of Milan, Via Pace 9, 20122 Milan, Italy. Journal of Viral Hepatitis, 2000, 7, 297±301 Ó 2000 Blackwell Science Ltd SUMMARY. Drug users with chronic hepatitis C virus (HCV) infection are frequently co-infected with human immun- ode®ciency virus-1 (HIV-1), but it is still not clear whether HIV-1 worsens the natural history of hepatitis C. To inves- tigate this, we conducted a multicentre observational study in 163 drug addicts with histologically documented hepatitis C, 92 of whom were also infected with HIV-1: 25 (27%) were CDC stage II, 53 (58%) were CDC stage III and 14 (15%) were CDC stage IV. Eighty-eight (54%) patients had chronic hepatitis (CH) with minimal activity, 28 (17%) had CH with moderate activity, 40 (25%) had CH with severe activity and seven (4%) had active cirrhosis. Twenty-one HIV-negative patients and 15 HIV-positive patients admitted to alcohol abuse (29% vs 16%, P  0.0665). Liver disease was more severe in HIV-positive patients than in HIV-negative ones (P  0.0198): 34 HIV-positive patients and 13 HIV negat- ives had severe CH and cirrhosis. These two severe liver diseases were seen more often in HIV-positive patients with a history of alcohol abuse than in HIV-negative patients (10 out of 16 vs seven out of 21). Age, alcohol abuse and dis- tribution of the histological categories of liver disease were statistically different in HIV-infected and HIV-uninfected patients. Multivariate analysis showed that age, alcohol abuse and serum antibodies to HIV were independently associated with severe CH or cirrhosis. Thus, HIV may enhance the risk of severe liver disease in drug users with hepatitis C, independently of the degree of immune dys- function. Alcohol abuse may contribute independently, aggravating the cause of HCV-dependent liver disease. Keywords: alcohol abuse, chronic hepatitis C, drug addiction, human immunode®ciency virus.