that antibodies to HCV envelope glycoproteins may have a We studied the heterogeneity in the E2/NS1 hypervarineutralizing effect, 4,5 and the genetic drift in HVR1 is thought able region 1 of the hepatitis C virus (HCV) genome in to provide HCV with a better chance for adaptation to imrelation to the natural course after infection. The submune pressure. 6,7 jects were composed of 38 chronic hepatitis C carriers Very recently, it has been shown that patients with a hetwho had been followed for 9 to 218 months after the erogenous HCV population are less likely to respond to interonset of non-A, non-B (type C) hepatitis, being tested feron therapy than those with a homogenous HCV populamonthly for serum alanine aminotransferase levels. The tion, [8][9][10] indicating that the HVR1 quasispecies nature may complexity of the sequence heterogeneity was assessed be useful for predicting responses to antiviral therapy, as is by single-strand conformation polymorphism analysis.
the case with HCV replicative levels and genotypes. 11-15 Thus, The quasispecies complexity had no relation to the route the HVR1 quasispecies seem to play an important role in of infection, the time from infection and the duration of persistent HCV infection. aminotransferase elevation after the onset. However, it
At present, factors affecting the development of the HVR1 had a significant relationship with the degree of aminoquasispecies nature in the natural course of chronic HCV transferase elevation in the course of the disease. The infection remain to be worked out. In this study, the degree quasispecies complexity was directly correlated with of complexity of HVR1 quasispecies was assessed in chronic the first peak of serum aminotransferase at the onset (r HCV carriers using single-strand conformation polymor-ร
.48, P รต .01) and the mean aminotransferase levels phism (SSCP) analysis. 10 The results were correlated with during the period of persistent aminotransferase elevathe clinical courses of the patients after infection to study tion (r ร
.58, P รต .01). Twenty-three of the 38 patients factors affecting the HVR1 quasispecies nature. were further followed for 24 months with biweekly alanine transaminase (ALT) tests. Their aminotransferase PATIENTS AND METHODS levels remained within the normal range during followup, and no significant change was seen in the quasispe-Patients. Sixty-two patients had undergone detailed follow-up cies complexity after this asymptomatic period. Howafter the onset of non-A, non-B (type C) hepatitis in a hemodialysis unit. Forty of the 62 patients received no blood transfusion after the ever among the 23 patients, the quasispecies complexity onset and were subjected to the study. The remaining 22 patients, increased in six cases (26%) and decreased in five (22%).
who received blood products during the follow-up, were excluded
A significant direct relation was seen between changes
because possible superinfection with HCV in contaminated blood in the quasispecies complexity and the mean aminoproducts can hamper the analysis of HCV HVR1 derived from initial transferase levels during the asymptomatic period (r ร
infection. The HVR1 quasispecies nature at the end of follow-up could .55, P ร
.01). These findings suggest that the development be estimated using SSCP analysis in 38 of the 40 cases tested. Thus, of the HCV quasispecies nature may be related to the these 38 patients were enrolled in the analysis. They were 17 males severity of the hepatitis in the course of infection. (HEPAand 21 females ranging in age from 36 to 75 years (median age, 55 TOLOGY 1997;25:439-444.) years). The causes of their renal failure were chronic glomerulonephritis (n ร
30), diabetic nephropathy (n ร
4), and polycystic kidney disease (n ร
4). The 38 patients had undergone detailed follow-up Since the genome of hepatitis C virus (HCV) was cloned, 1 for 9 to 218 months (median, 93 months) from the onset of non-A, many studies have revealed the heterogeneity of the HCV non-B (type C) hepatitis until 1993. After the diagnosis of renal genome. As with other RNA viruses, HCV circulates as a disease, they received monthly routine laboratory tests including mixture of genetically different but closely related variants, serum alanine transaminase (ALT) activity. Hepatitis B surface anti- gen was examined every 1 to 3 months. Since serological tests for thus forming quasispecies. This quasispecies nature is most HCV became available in 1990, HCV antibody was also tested every prominent in the hypervariable region 1 (HVR1) found at the 3 to 6 months. These 38 patients showed the onset of non-A, non-B N-terminus of the E2/NS1 region. 2,3 Several studies showed (type C) hepatitis 6 to 108 months (median, 15 months) after their entry to the hemodialysis program. They had no preexisting liver disease and had showed repeatedly normal ALT values for more than 3 years. Elevated ALT activity was first noted, and at least two Abbreviations: HCV, hepatitis C virus; HVR1, hypervariable region 1; SSCP, singleabnormal values were observed in measurements separated by 1 or strand conformation polymorphism; ALT, alanine transaminase; RT-PCR, reverse-tranmore weeks. Hepatotropic viruses other than HCV and nonviral scription polymerase chain reaction; bDNA assay, branched DNA assay; nt, nucleotide causes of hepatocellular injury were excluded by conventional clinical position.