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To the Editor:

We read with great interest the article of Kronenberger et al.1 evaluating viral kinetics in patients with chronic hepatitis C and normal or elevated alanine aminotransferase (ALT) levels. The main conclusions of this study were that viral kinetics did not differ between the two groups of patients, although those with elevated GGT levels showed reduced efficacy of blocking virus production and lower infected cell loss.

Although this study did accurately compare virological, demographic, and histological features between patients with normal and elevated ALT levels, fewer data are given about the differences among those with normal ALT. Indeed, patients with normal ALT might be stratified into three different groups: patients with persistently “low-normal” (updated healthy) ALT levels; patients with “high-normal” ALT levels, and subjects with normal ALT but occasional ALT flares.2, 3 Two recent prospective studies4, 5 have shown that many subjects referred to as hepatitis C virus (HCV) carriers with persistently normal ALT (PNALT) could have ALT flare-ups during the follow-up, thus proving that even prolonged observation periods might not be adequate to distinguish patients with persistent or transient ALT normality. It has been suggested that at least two different subsets of HCV carriers exist: patients with wide temporal ALT fluctuations, who could be within the normal range for several months, and true “biochemically silent” carriers, who show persistently normal ALT values.6 Although it is not clear whether these subgroups have different natural history and disease progression, liver histological activity was found to be significantly more marked among subjects with ALT flare-ups during the follow-up than in those with PNALT, and progression of fibrosis seems to accelerate after ALT flare-ups.3

Thus, we wonder if significant differences in viral kinetic were found between the 6 patients with “healthy” updated ALT levels and the 14 patients with “high-normal” ALT, and between the 5 patients with ALT flares and the 15 with PNALT. Indeed, it would be very interesting to understand whether ALT flare-ups among HCV carriers with PNALT might be due to viral factors (e.g., lower efficacy of blocking virus production/lower infected cell loss) or to nonviral factors (steatosis, drugs, alcohol).

Finally, as to the patients with elevated GGT levels, we ask whether liver steatosis has been ruled out as a possible cause of GGT elevation. In particular, we wonder if significant differences were found in terms of presence and severity of steatosis between the 5 patients with PNALT and elevated GGT, and the 15 subjects with both normal ALT and GGT levels.

References

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  • 1
    Kronenberger B, Herrmann E, Micol F, von Wagner M, Zeuzem S. Viral kinetics during antiviral therapy in patients with chronic hepatitis C and persistently normal ALT levels. HEPATOLOGY 2004; 40: 14421449.
  • 2
    Puoti C, Guido M, Mangia A, Persico M, Prati D. Clinical management of HCV carriers with normal aminotransferase levels. Dig Liver Dis 2003; 35: 362369.
  • 3
    Puoti C. HCV carriers with persistently normal aminotransferase levels: normal does not always mean healthy. J Hepatol 2003; 38: 529532.
  • 4
    Martinot-Peignoux M, Boyer N, Cazals-Hatem D, Bach-Nga P, Gervais A, Le Breton A, et al. Perspective study of anti-hepatitis C virus-positive patients with persistently normal serum ALT with or without detectable serum HCV RNA. HEPATOLOGY 2001; 34: 10001005.
  • 5
    Puoti C, Castellacci R, Montagnese F, Zaltron S, Stornaiuolo GF, Bergami N, et al. Histological and virological features and follow-up of Hepatitis C Virus carriers with normal aminotransferase levels: The Italian Prospective Study of The Asymptomatic C Carriers (ISACC). J Hepatol 2002; 37: 117123.
  • 6
    Puoti C, Magrini A, Stati T, Rigato P, Montagnese F, Rossi P, et al. Clinical, histological and virological features of hepatitis C virus carriers with persistently normal aminotransferase levels. HEPATOLOGY 1997; 26: 13931398.

Claudio Puoti*, Lia Bellis*, Roberto Castellacci*, Fabrizio Montagnese*, * Department of Gastroenterology and Internal Medicine, Genzano Hospital, Rome, Italy.