Initial Presentation of Acute Hepatitis C Virus (HCV) Infection among HIV–Negative and HIV‐Positive Individuals—Experience from 2 Large German Networks on the Study of Acute HCV Infection

To the Editor—With interest we read the article by Matthews et al [1] on the clinical presentation of acute hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-positive and HIV-negative individuals. In particular, the finding that after acquisition of acute HCV infection, HIV-positive individuals were similar with regard to the maximum alanine aminotransferase (ALT) level and clinical presentation, compared with HIV-negative individuals, merits attention. Because of the acquired immunodeficiency, one would expect a less vigorous host-virus interaction among HIV-positive individuals and thus a lessened inflammatory response, with lower maximum ALT levels and less pronounced clinical symptoms or signs. Within the German Network of Competence for Hepatitis (Hep-Net) study group and the German Hepatitis Group, we have prospectively screened 416 patients (259 HIV-negative and 157 HIV-positive) for inclusion into the Acute HCV I, the Acute HCV II, the Acute HCV III [2], or the Acute HCV for HIV-positive individuals clinical trials [3], from 1998 through 2008. The trials were run separately for HIV-negative and HIV-positive patients and differed with respect to the definition of acute HCV infection (table 1). A direct comparison across trials is therefore not possible. However, it is striking that Matthews et al [1] reported a mean maximum ALT level in HIV-negative patients (937 IU/L) within the interquartile range observed in our HIV-negative patients, whereas the reported mean maximum ALT level in HIV-positive patients (981 IU/L) is outside the interquartile range observed in our HIV-positive patients (table 2). Importantly, the inclusion criterion with regard to ALT level was >10 times the upper limit of normal (ULN) in both our trial on HIV-positive patients and the study by Matthews et al [1]. Moreover, in contrast to the findings of Matthews et al [1], in our cohorts HIV-positive patients presented less often with typical symptoms or signs of hepatitis than HIV-negative patients, and the time from estimated infection to the first occurrence of symptoms was longer for HIV-positive patients than for HIV-negative patients. Inclusion criteria of German clinical trials on acute hepatitis C virus (HCV) infection In the study by Matthews et al [1], the characteristics of the HIV-positive population may offer some clues to explain the differences observed. In their study, HIV infection of 93% of the patients was at stage A, according to the United States Centers of Disease Control and Prevention definition [4], whereas in our study population only 29% were at stage A. Moreover, the median CD4 cell count was 614 cells per µL, which is higher than the median CD4 cell count in our cohort (473 cells per µL). In fact, the median CD4 cell count reported by Matthews et al [1] represents just about the upper 75th percentile reported in our cohort. CD4 cell count, however, has been linked to successful immune response against HCV and may be an explanation of the different findings [5]. In addition, more HIV-positive patients in the study by Matthews et al [1] had acquired HCV infection via intravenous drug abuse than in our study (44% vs 1%), which may also contribute to the different presentation. The larger inoculum in the case of intravenous drug abuse might represent a higher antigen exposure to the host, which has been previously shown to influence the natural course of acute HCV infection [6]. Also, the intravenous drug itself, unknown chemical substances used in the preparation of an illicit drug, or simple contamination of the needle with environmental dirt or bacteria may also cause hepatitis. It would be interesting to know whether the mode of transmission had an influence on the clinical presentation in the cohort of Matthews et al [1] and to know whether any differences were observed in the interval between the estimated time of infection and the first occurrence of clinical symptoms. For clinicians and patients, however, it may be important to recognize that for HIV-infected patients, clinical presentation of acute HCV infection may be more subtle than for HIV-negative individuals. This may particularly apply to sexually transmitted acute HCV infection. Therefore, a lack of characteristic symptoms or signs of hepatitis in HIV-positive patients does not rule out acute HCV infection, and further testing for HCV is warranted. Financial support. For Acute HCV I-III studies, the Hep-Net study house founded by the German Federal Ministry of Education and Research (01KI0788 to H.W. and M.C.J.) and Essex Pharma, Germany; for the acute HCV study for HIV-positive patients, the German Network of Competence for HIV/AIDS (01KI0501). Potential conflicts of interest. M.V. has received lecture fees, traveling expenses, and payment of registration fees from Roche, Essex, Tibotec (Johnson & Johnson), Gilead, Glaxo SmithKline, Bristol-Myers Squibb, Merck Sharp & Dohme, Boehringer Ingelheim, and Abbott. A.B. has received lecture fees, traveling expenses, and payment of registration fees from Roche, Essex, Tibotec (Johnson & Johnson), Gilead, Bristol-Myers Squibb, Merck Sharp & Dohme, Boehringer Ingelheim, Pfizer, and Abbott. N.H.G. and M.C.J. have received lecture fees, traveling expenses, and payment of registration fees from Roche, Essex, and Gilead. H.W. has received research grants from Essex, Roche, Bristol-Myers Squibb, and Gilead and consultancy fees, lecture fees, traveling expenses, and payment of registration fees from Roche, Essex, Gilead, Bristol-Myers Squibb, and Novartis. M.P.M. has received research grants from Essex, Roche, Bristol-Myers Squibb, and Gilead and consultancy fees, lecture fees, traveling expenses, and payment of registration fees from Roche, Essex, Gilead, Bristol-Myers Squibb, Tibotec, Vertex, and Novartis. J.K.R. has received unrestricted grants from Essex, Roche, Abbott, and Gilead and consultancy fees, lecture fees, traveling expenses, and payment of registration fees from Roche, Essex, Tibotec (Johnson & Johnson), Gilead, GlaxoSmithKline, Bristol-Myers Squibb, Merck Sharp & Dohme, Boehringer Ingelheim, Vertex, and Abbott. K.D. and J.W.: no conflicts.