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Chronic hepatitis C and 'normal' ALT levels: Treat the disease not the test
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Journal of Hepatology Sept 2005
Claudio Puotiemail address, Lia Bellis, Francesca Martellino, Riccardo Guarisco, Orlando Dell' Unto, Laura Durola, Alessandra Galossi
Department of Hepatology and Internal Medicine, Marino General Hospital, Via XXIV Maggio, 00047 Marino, Rome, Italy
To the Editor:
We read with interest the comprehensive review by Dr Alberti [1], in which he notes that few studies have assessed the natural course of liver disease in patients with chronic hepatitis C and persistently 'normal' alanine aminotransferase (PNALT) levels. We would like to contribute to what is known of the natural history of this entity by describing our ongoing experience with four couples that we first encountered between 1992 and 1995 [2]. Each partner was infected with the same genotype of the hepatitis C virus (HCV) and in each couple one partner had elevated ALT levels and the other had PNALT levels. In each couple, the spouse with 'normal' ALT levels had more severe liver disease as determined by liver biopsy, but only patients with elevated ALT were eligible for antiviral therapy according to treatment guidelines. All of the patients have been seen in our clinic approximately every six months and ALT activity has been determined every three-to-four months for the past 10-12 years. Repeat liver biopsies have been offered to the untreated partners with 'normal' ALT activity.
HCV RNA has been detectable in serum during follow-up in all patients with PNALT levels, none of whom have experienced an ALT 'flare' at any time. Progressive liver damage has been documented in three of the four individuals with PNALT levels. Indeed, one woman with PNALT is awaiting liver transplantation. Two further patients have experienced significant progression of fibrosis. Serial biopsies reveal progression from F0 to F3 during a decade of watchful waiting in one individual and from F2 to F4 in another. The fourth individual with PNALT levels has been stable with no evidence of disease progression according to a biopsy performed 5 years after presentation.
All of the patients with elevated ALT levels were treated with antiviral therapy and HCV was eradicated in three of these four individuals. The fourth patient has not experienced progression of fibrosis despite persistence of HCV RNA in serum and ongoing elevation of serum ALT levels.
Since we published our original observations regarding these patients [2], there have been major advances in antiviral treatment for chronic hepatitis C. With the current treatment of choice, pegylated interferon plus ribavirin, it is possible to cure more than 50% of patients with PNALT levels [3].
In our previous report, we questioned whether we should be treating the disease (HCV infection, liver damage) or the test (serum ALT) [2]. The results of follow-up in these patients provide a clear answer to this question. Evidence from this and other series [4] shows that patients with persistently 'normal' ALT levels are at risk of progressive liver damage and 'watchful waiting' does not result in clearance of HCV from serum. We agree with Dr Alberti that there is no absolute correlation between serum ALT levels and liver disease activity and conclude that treatment decisions in patients with chronic hepatitis C should be based on a global evaluation of the patient, rather than the results of a laboratory test.
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