Abstract
Among patients with chronic hepatitis C virus (HCV) infection, serum alanine aminotransferase (ALT) rarely increases above 500 IU/L. We examined the clinical and virological features of untreated patients with serum ALT ≥ 500 IU/L. One thousand seven hundred and sixty adult patients with chronic HCV infection were followed‐up. Among these patients, 22 developed ALT flare‐up (M:F = 13:9, median age, 50.5 years). We evaluated liver function tests, genotype, and viral titer in these patients and 44 randomly selected age‐ and sex‐matched control without ALT flare‐up. In four patients with ALT flare‐up, we examined changes in viral loads and sequential changes in amino acid sequences of the core region, hypervariable region 1 (HVR1), and interferon sensitivity determining region (ISDR) before and after ALT flare‐up. Multivariate analysis identified genotype 2 as the only significant determinant of ALT flare‐up. ALT flare‐up occurred in three of four patients without increase in viral load. Several alterations in amino acids were noted in HVR1 before and within 6 months of ALT flare‐up. One or two alterations in the core region and many alterations in HVR1 were noted after ALT flare‐up in some patients. Genotype 2 is an important factor for ALT flare‐up. However, we could not directly relate ALT flare‐up to these alterations in amino acids of the core region, HVR1, and ISDR. J. Med. Virol. 75:240–248, 2005. © 2004 Wiley‐Liss, Inc.