High Rate of Infection with Hepatitis C Virus Genotype 4 in a District of Galicia, Spain

It is estimated that 170 million individuals are infected with hepatitis C virus (HCV) worldwide (6). The genetic heterogeneity of the virus has revealed six major genotypes. Most of the information on treatment of chronic hepatitis C comes from genotypes 1, 2, and 3, the predominant strains in the United States and Europe. Genotype 4 is more prevalent in Africa and the Middle East and has been frequently associated with evolution to cirrhosis and a poor response to conventional alpha interferon-based regimens (2, 8). The aim of this study is to evaluate epidemiological factors, liver histology, and response to combination therapy with interferon and ribavirin of a series of patients infected with genotype 4. From a total of 350 patients with hepatitis C referred to our Liver Unit from January 1999 to June 2004, 33 patients infected with genotype 4 (9.4%) were identified. Information about their demographics, mode of transmission, and laboratory data was collected. The date of transmission of infection was established by the year of first use of drugs in the case of intravenous drug use and snorting of cocaine and the year of the transfusion, surgery, or tattoo for the remaining forms of transmission. Serum HCV RNA levels were quantified by reverse transcription-PCR assay (Amplicor Monitor HCV 2.0; Roche). HCV genotyping was carried out using a line probe assay (INNO-LIPA HCV II; Innogenetics, Ghent, Belgium). Liver histology was available for 25 patients, and the histological fibrosis stage was assessed according to the score of Scheuer. Thirteen patients were treated with alpha-2b interferon and ribavirin in combination at standard doses. Six were treated with pegylated interferon and ribavirin. HCV RNA was assessed at baseline and at 3, 12, and 18 months after starting treatment. Sustained virologic response was defined as negative HCV RNA 6 months after treatment was stopped. The baseline demographics, liver histology, and biochemical data from these patients are summarized in Table ​Table1.1. All the patients were natives of Galicia and denied having traveled to areas of endemicity. A risk factor for exposure to HCV was noted for most of the patients (90.9%), and the main route of infection was intravenous drug use. The estimated mean age at the moment of infection was 22.4 ± 9.8 years. TABLE 1. Characteristics of genotype 4 patients The baseline HCV RNA level was above 2 × 106 copies/ml in nine cases. Most of the patients had mild to moderate liver disease on biopsy. Only one patient had cirrhosis by clinical, endoscopic, and ultrasonographic criteria. Mixed-genotype HCV infection was not detected in this population. Twelve patients have completed 12 months of therapy. Only one patient discontinued therapy because of side effects. Ten of the patients who completed treatment were considered sustained responders, whereas one was a nonresponder and one relapsed. Overall, 10 of the 13 patients who initiated therapy (76.9%) had a sustained response. Six of them were treated with pegylated interferon and four with standard interferon in combination with ribavirin. Patients with pretreatment HCV-RNA levels lower than 2 × 106 copies/ml had a significantly higher rate of sustained virologic response than patients with a higher viral load (P = 0.03), whereas the liver fibrosis score did not affect the response. The rate of 9.4% for this genotype in our area is noteworthy for a Western country, though it has been found in other districts of northern and southern Spain, in the latter with an even higher frequency (4, 3). Epidemiological and clinical characteristics found in this series differ from those for African and Middle Eastern countries. All patients were white, and, as expected in the Occidental world, the predominant mode of acquisition of the infection was intravenous drug use in almost two-thirds of the cases. This is in agreement with reports from other Western countries. In contrast, a high proportion of HCV infection from an unknown source was observed in Egypt, a country with one of the highest prevalences of genotype 4, and in Kuwait (2). An iatrogenic route was suggested by a study in Egypt, with a major role for parenteral antischistosomal therapy in the spread of HCV (1). The histological stage assessment reflects mild to moderate liver disease. On the other hand, studies with African and Middle Eastern populations suggest a frequent association with cirrhosis and a rapid fibrosis progression rate following liver transplantation (5, 7). Although this genotype was previously categorized as difficult to treat, our results are in accordance with the more recent trials that suggest a response intermediate between those of genotype 1 and non-1 genotypes. In conclusion, the prevalence of genotype 4 in our area is high in comparison with that for other Western countries. The majority of patients acquired the infection through intravenous drug use and had a histological assessment of mild to moderate liver disease.