Reported by Jules Levin

ALT Levels (liver enzymes) Can Be Normal But Liver Disease Can Be Advanced:

When ALT was normal in study reported below, Normal liver was found in 17% of the patients; 34% had minimal CH, 44% mild CH, 4% moderate-severe CH, and 1 % had cirrhosis.

Previous small studies have shown that a person could have normal ALT with moderate to severe liver fibrosis. Presented at EASL are these two additional studies showing the same finding. Unfortuneately, it is still thought by some that if ALT is normal liver disease must be ok. This appears not to be true. It does not appear that you can conclude liver disease is minimal if ALT is normal. This is a particular concern in HCV/HIV coinfection because HCV may progress more quickly in coinfected persons. So, if ALT is normal in coinfected person and you conclude liver disease is minimal the patient may progress to more advanced HCV more quickly.

PREDICTIVE VALUE OF ALT LEVELS ON HISTOLOGICAL FINDINGS IN CHRONIC HEPATITIS C: A EUROPEAN COLLABORATIVE STUDY
     P. Pradat, T. Poynard, A. Alberti, J. I. Esteban, P. Marcellin, O. Weiland, S. Badalamenti, C. Trepo Hepatology, Hotel-Dieu, Lyon, France

Objective :
To study the predictive value of ALT levels on histological findings in HCV patients.

Methods :
Data on HCV RNA(+) patients were collected from six European Centers. ALT values were collected at the time of biopsy before any treatment. In a subset of patients, normal ALT values were defined as normal at serial testing during at least 6 months. Histological results were given using the METAVIR scoring system.

Results:
Data on 4728 patients were collected. In 3861 of them, ALT was assessed from a single value (group A) whereas in the remaining 867 patients, a normal ALT value meant "persistently" normal (group B). Within group A, the percentage of cases with at least F1 among patients with elevated ALT is about 92% against 87% among patients with normal ALT levels. Within group B, the percentage of cases with at least F1 among patients with elevated ALT reaches 99%. Among patients with "persistently normal" ALT values, still 65% have at least F1.

Conclusions :
1. Almost all HCV RNA(+) patients with elevated ALT present different degrees of fibrosis (>=F1).

2. However, an important proportion of patients with "persistently normal" ALT also show histological signs of fibrosis, some of them even cirrhosis. This study suggests that patients with HCV RNA(+) and elevated ALT are a priori candidates for antiviral therapy. It also suggests that a significant proportion of cases with normal ALT may also benefit and that paradoxically, it is for them that liver biopsy may be most warranted.

HCV CARRIERS WITH NORMAL ALT: HEALTHY PEOPLE OR PATIENTS WITH CHRONIC HEPATITIS ? THE ITALIAN STUDY OF THE ASYMPTOMATIC C CARRIERS (ISACC)
     C. Puoti, M. Puoti, E. Minola, G. Gaeta, R. Castellacci , F. Montagnese, T. Zaltron, G. Stornaiuolo, M. Pace, C. Lo Iacono, N. Bergami; Liver Unit, Genzano, Rome, Infectious Disease, Brescia, Infectious Disease, Bergamo, Infectious Disease, II University, Naples, Italy

Study design:
In order to define the clinical and histological profile of HCV carriers with persistently normal ALT levels (PNAL), a multicentric study was started in 1997. 4 Italian Centers have participated in this study. HCV carriers were defined by HCV RNA by PCR and normal ALT in at least 4 different occasions 3 months apart over a 12-month period. Subjects with ALT flare-ups during the follow-up were excluded from this study.

Results:
691 subjects entered the study. The majority of them were females (72%), did not report symptoms (82%) and had a high prevalence of history of blood exposure (67%). 27% of the patients had had previous HBV infection. An overall prevalence of genotype non-1 was found (1a 14%, 1b 28%, 2 52%, others 6%). Liver biopsy was performed in 159 patients. Normal liver was found in 17% of the patients; 34% had minimal CH, 44% mild CH, 4% moderate-severe CH, and 1 % had cirrhosis.

Conclusions:
Many HCV carriers with PNAL have significantly liver damage. Although in the majority of them histological damage is mild, the possibility of severe liver damage cannot be ruled out. This multicentric study contributes to highlight the danger of any false sense of security given by PNAL in HCV carriers.