Although several virus-and host-related predictive factors for the response to interferon alfa (IFN-␣) have been defined in patients with chronic hepatitis C, no pretreatment parameter can definitely predict the response to antiviral treatment. Assessment of the initial response by quantification of serum hepatitis C virus RNA before and 4 weeks after initiation of therapy may be a clinically applicable and reliable parameter to predict long-term response. Therefore, the aims of the present study were to test the predictive value of a decline in HCV RNA of at least 3 log in the first 4 weeks of treatment (⌬HCV RNA) in patients treated with 3 ؋ 10 6 units of recombinant IFN-␣2a (rIFN␣2a) three times per week subcutaneously and to compare ⌬HCV RNA with other established predictive factors, such as HCV genotype and pretreatment viremia. Serum HCV RNA was measured by a validated quantitative reverse transcription-polymerase chain reaction (RT-PCR). Geno/ subtyping of HCV was performed by direct sequencing of the nonstructural (NS) 5B region of PCR-amplified isolates and subsequent phylogenetic analysis. Stable HCV RNA levels (⌬HCV RNA I 1 log) within the first 4 weeks of IFN-␣ treatment were present in 42 of 70 patients. A decline in HCV RNA levels between 1 to 3 log and more than 3 log was observed in 9 (13%) and 19 patients (27%), respectively. In 21 of 70 patients (30%), HCV RNA was not detectable at the end of 12 months' treatment. Three of 26 patients (11%) with a pretreatment viremia of I10 6 copies/mL (all HCV subtype 3a) and 6 of 44 patients (14%) with a pretreatment viremia of G10 6 copies/mL (HCV subtypes 1b, 2a, 2c, 3a [two patients], and 4) achieved a virological sustained response to interferon-␣2a treatment. All patients with a virological sustained response had an initial ⌬HCV RNA of more than 3 log. In a stepwise discriminant-function analysis, the initial ⌬HCV RNA was confirmed as the strongest predictor of virological sustained response (P F .0001). In conclusion, the data of the present study suggest that IFN-␣ treatment can be terminated after 4 weeks in patients with a decrease in HCV RNA levels of less than 3 log, when apparent HCV eradication is considered the therapeutic target. The predictive value of ⌬HCV RNA clearly exceeds the significance of HCV genotype and pretreatment viremia as predictors of successful

Nucleotide sequence analysis of hepatitis C virusHepatitis C virus (HCV) infection often progresses to (HCV) strains showed substantial variability leading to chronic hepatitis, cirrhosis, and possibly hepatocellular carcia classification into several genotypes and subtypes. The noma. [1][2][3] Using phylogenetic analysis of the viral 5-noncoding data correlating HCV genotypes and subtypes with hep-region, a classification of HCV strains into six major types atitis C viremia levels, demographic characteristics of (HCV-1 to -6) has been introduced. Analysis of the more varipatients (age, mode of transmission, duration of infec-able coding regions of the viral genome (core, envelope, nontion), and severity of liver disease are conflicting. The structural [NS]-3, and NS-5) indicated that major genotypes interpretation of several studies is further complicated are composed of two or more distinct subtypes, termed 1a, because the molecular methods used lacked specificity 1b, 2a etc. 4,5 The geographic distribution of HCV genomes for genotyping/subtyping and underestimated viremia differs considerably. In Europe and the United States, sublevels, especially in patients infected with HCV geno-types HCV-1a and -1b, HCV-2a and -2b, and HCV-3a are types 2 and 3. In the present study we investigated 97 most abundant, whereas in Japan HCV subtypes 1a and 3a consecutive patients with chronic hepatitis C using mo-are virtually nonexistent. Type 4 genotypes are common in lecular ''gold standard'' methods. HCV subtyping was patients from Northern Africa and the Middle East, and types performed by sequence and phylogenetic analysis of the 5 and 6 have been identified in serum samples obtained from nonstructural (NS)-5 region and serum HCV-RNA con-South Africa and Hong Kong, respectively. Sequence analysis centration was assessed by a validated genotype-inde-of HCV isolates from Vietnamese blood donors revealed addipendent quantitative reverse-transcription-polymerase tional major genetic groups (HCV-7, -8, and -9).6-8 chain reaction assay using an internal RNA standard.Several 9-12 but not all studies 13,14 have indicated a correlaPatients infected with subtypes HCV-1b, HCV-2a-c, and tion between HCV genotypes/subtypes and serum HCV-RNA HCV-4 were older than patients infected with HCV-1a concentrations. The data associating HCV genotypes/suband HCV-3a. Serum HCV-RNA levels ranged from 1.5 1 types and/or hepatitis C viremia levels with demographic, 10 4 to 1.0 1 10 8 copies/mL with no significant differences biochemical, or histological characteristics of chronically inbetween median serum HCV-RNA concentrations in pa-fected patients are conflicting. [15][16][17][18][19][20][21][22][23][24][25][26] These issues are further tients infected with different genotypes/subtypes. Al-complicated by recent evaluations showing that common gethough patients infected with HCV-1b were older, no notyping methods lack specificity 12,27 and that quantification biochemical or histological evidence was obtained that systems underestimate high virem...

A high prevalence of hepatitis C virus (HCV) infection has been reported in hemodialysis patients. Main risk factors for transmission are previous blood transfusions and possibly nosocomial infections within the dialytic environment. In the present study 224 hemodialysis patients from the same department were tested for the presence of anti-HCV antibodies and HCV-RNA. The presence of anti-HCV in hemodialysis patients was correlated with a history of more than 10 blood transfusions (P = 0.001) and with a duration of hemodialysis treatment for more than 10 years (P = 0.001). The issue of possible patient-to-patient infection was addressed by sequence analysis of all HCV-RNA positive hemodialysis patients (N = 14) together with a control panel of HCV isolates from 56 unrelated non-hemodialysis patients with hepatitis C from the same geographical area. Subsequent phylogenetic analysis of nucleotide sequences obtained from the 5'-noncoding region and the nonstructural NS-5 region of the HCV genome revealed that only two hemodialysis patients were infected by a highly related HCV isolate. The remaining HCV-RNA positive hemodialysis patients including those without previous blood transfusions were all infected by phylogenetically-distant HCV isolates, providing evidence against a nosocomial transmission route. The data of the present study show that molecular epidemiological techniques are important to investigate the issue of nosocomial infection. In our hemodialysis unit patient-to-patient infection appears uncommon and draws attention towards other possible (such as, blood products such as human serum albumin, immunoglobulins) or even yet unrecognized transmission routes.

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