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Intravenous drug use (IVDU) remains a major means of hepatitis C virus (HCV) transmission. In this study, 101 drug users were studied prospectively after cessation of IVDU. Of these, 75.8% were anti-HCV positive, and 71.4% had elevated levels of alanine aminotransferase. These levels decreased significantly within 1 month of IVDU cessation (p 0.02). Liver biopsies showed minimal or mild fibrosis in 32 (71%) of 45 subjects, and severe fibrosis in two (4.4%) subjects. Anti-HCV-positive intravenous drug users in this study presented with mild liver disease and variable stages of disease progression. Biochemical disease activity might be affected by IVDU.
Following the introduction of blood donor screening for hepatitis C virus (HCV) infection, intravenous drug use (IVDU) remains the major mode of HCV transmission in developed countries . Anti-HCV prevalence in Germany is c. 1% in blood donors  and 70–80% in intravenous drug (IVD) users . Currently, there are c. 150 000 HCV-infected IVD users in Germany, and the number is increasing by c. 10 000 each year . Little is known about the natural course of HCV infection in IVD users. In patients with post-transfusion HCV infection, histopathological alterations appear to be more severe . The present study aimed to provide prospective data on anti-HCV prevalence and viraemia in a group of recently injecting IVD users, and to correlate these with data regarding alanine aminotransferase (ALT) levels and histopathogical changes.
The study followed a group of 101 consecutive drug users (91 IVDU; ten non-IVDU) from an in-patient clinic for drug addicts in Freiburg, Germany, between January 1997 and July 1998. The mean follow-up period was 8 months (range 2–18 months). After informed written consent was obtained, each patient was interviewed by means of a standardised questionnaire to obtain the data listed in Table 1. All participants had consumed drugs until 2–3 weeks before entering the clinic. Screening for continued alcohol or drug consumption was performed through blood and urine tests. Patients continuing to use drugs or alcohol were excluded from the study and discharged from the clinic.
Table 1. Clinical and serological data of patients in the study group
| ||Total drug users n = 101||IVD users n = 91||Non-IVD users n = 10|
|Age, years (mean ± SD)||27.3 ± 5.1|| || |
|Women||16 (15.8%)|| || |
|Duration of IVDU||NA||5.6 ± 4.4||NA|
| Jaundice||30 (29.7%)||30 (33.0%)||0|
| Blood transfusions||2 (2.0%)||2 (2.2%)||0|
| Tattoos||64 (64.6%)||61 (67.0%)||3 (30.0%)|
|Anti-HIV1-positive||2 (2.0%)a||2 (2.2%)||0|
|Anti-HAV-positive||30 (29.7%)||27 (29.7%)||3 (30.0%)|
|Anti-HBc-positive||43 (42.6%)||42 (46.2%)||1 (10.0%)|
|HBsAg-positive||4 (4.0%)b||4 (4.4%)||0|
|Anti-HCV-positive||70 (69.3%)c||69 (75.8%)||1 (10%)|
All subjects were tested for HCV, hepatitis B virus (HBV), hepatitis A virus (HAV) and human immunodeficiency virus (HIV). Sera were tested for the presence of anti-HCV with a fourth-generation anti-HCV assay (Monolisa; Sanofi Diagnostics Pasteur, Marnes-la-Coquette, France) and a recombinant immunoblot assay (Recomblot; Mikrogen, Martinsried, Germany). A commercially available ELISA was used to detect anti-HAV, anti-HBV core (HBc) antigen, HBV surface antigen (HBsAg) and anti-HIV (Sorin Biomedica Diagnostics, Saluggia Vercelli, Italy). Serum samples of 70 anti-HCV-positive subjects were tested for HCV RNA with the Amplicor PCR assay (Hoffman La Roche, Basel, Switzerland).
Results of matched ALT tests at 1, 6 and 14 weeks were available for 41 patients. Liver biopsies were obtained from 45 anti-HCV positive subjects with elevated ALT levels. One of the patients was positive for HBsAg. The histomorphological grading and staging was based on the classification system of Hytiroglou et al.. Descriptive statistics were obtained for all numerical (mean ± standard deviation) and categorical (relative frequencies) variables (SPSS software; SPSS Inc., Chicago, IL, USA). Statistical significance was evaluated by the Student t-test for paired numerical variables and the chi-square test for categorical variables, with p < 0.05 considered to be significant.
Table 1 summarises the clinical and serological findings in the study population. None of the individuals had jaundice or hepatomegaly. Of the 101 subjects, 70 were anti-HCV-positive, and three also had HBsAg. Anti-HCV positivity correlated with the duration of IVDU; thus 31 (66%) of 47 subjects who had been IVD users for < 4 years, and 18 (95%) of 19 subjects who had been IVD users for > 8 years, were anti-HCV-positive. The mean viral load was 3.7 × 106 RNA-equivalents/mL. Genotype 3 was most frequent (47.3%), followed by genotypes 1a (30.5%) and 1b (11.1%). More than one genotype was found in five patients. ALT levels were elevated in 52 (57.2%) of 91 IVD users, but were normal in all ten non-IVD users. Of 67 anti-HCV-positive/HBsAg-negative subjects, 47 (70%) had increased ALT levels. These ALT levels decreased significantly after follow-up periods of 6 and 14 weeks (mean ALT 34.8 ± 14.4 vs. 26.5 ± 11.4 U/L; p 0.02). The histological activity index was stage 0 in two patients (4.4%), stage 1 in 34 (74%) and stage 2 in ten (22.2%). Minimal-to-mild fibrosis (stage 0/1) was present in 32 (71%) patients, moderate fibrosis (stage 2) in 13 (29%), and severe fibrosis in two (4.4%), with one of the last-mentioned patients being HBsAg-positive. Liver cirrhosis was not found. Neither the histological activity index nor the extent of fibrosis correlated with ALT levels after 6 weeks or the duration of IVDU.
Persistent HCV infection may be present in up to 98% of IVD users, and is associated with duration of drug use [1,3,7–9]. Despite this high prevalence, only two prospective studies that compare histopathological and biochemical findings in these patients have been published [10,11]. In the present series, the prevalence of HCV was 70% and correlated with the duration of IVDU.
Elevated ALT levels are used to select HCV-infected patients for liver biopsy and treatment. However, they are poor indicators of the extent of liver cell damage in post-transfusion HCV infection . In the present study, 17% of anti-HCV-negative IVD users had elevated ALT levels at initial evaluation, while 13% of anti-HCV-positive subjects had normal results. ALT levels did not correlate with histopathological grade and stage, although previous studies showed positive and negative correlations [10,11,13]. Interestingly, ALT levels decreased significantly within 6 weeks after discontinuation of parenteral drug use, but no further decrease occurred thereafter. As a consequence, elevated ALT levels in recent IVD users, and even histopathological alterations, might reflect not only HCV infection, but also non-specific changes secondary to toxic substances injected with drugs, or concomitant viral or bacterial infections. This should be taken into account when interpreting liver histology or liver function tests in active IVD users.
Histopathological liver changes in anti-HCV-positive IVD users are generally mild and highly variable [5,10,14,15]. The duration of IVDU in the present study did not correlate with histopathological grade and stage, reflecting inter-individual variability in disease progression.
In conclusion, the present study found that anti-HCV-positive IVD users usually present with mild liver disease. Active IVD use may cause increases in serum ALT levels independent of HCV infection, and might also affect histopathological findings. Additional follow-up data on the time course of HCV-related liver disease in IVD users, including sequential biopsies, are needed to characterise the progression of the disease and to identify prognostic factors.