Highlights from
Digestive Disease Week

May 20-23, 2001
Atlanta, Georgia

Predictive Value of Alt Levels On Histological Findings In Chronic Hepatitis C: A European Collaborative Study

This study of 4,000 patients shows that patients with 1 single ALT normal value may have fibrosis score of 2 to 4 (42%; 9% cirrhosis), and 12% of patients with persistently normal ALT had fibrosis score of 2.

A number of studies have shown that ALT does not necessarily predict liver disease. A patient can have moderate or advanced disease and have a normal ALT. Biopsy is the most reliable way to evaluate the stage of liver disease. The purpose of this study presented at DDW May 2001 was to study the predictive value of ALT levels on the stage of liver disease. 4700 patients were evaluated. In group A patients (using 1 single ALT value) 13% with normal ALT had fibrosis score of 0, 46% had fibrosis score of 1, 23% score of 2, 9% score of 3 and 9% score of 4 (cirrhosis). 8% with elevated ALT had 0 fibrosis score, 35% with elevated ALT had score of 1, 23% score of 2, 17% score of 3, and 15% score of 4. So, 87% with normal ALT had score of 1 or greater, and 91% with elevated ALT has score of 1 or greater.

In group 2 patients (normal ALT means persistently normal), 34% with normal ALT had fibrosis score of 0, 51% had score of 1 fibrosis, 12% score of 2, while 0 had score of 3 and only 1.5% had fibrosis 4. Of patients with elevated ALT, 0.7% had score of 0, 24% had 0 score, 50% had F2, 17% had F3, and 8% had F4. So, 65% with normal ALT had F1 or greater and 99% with elevated ALT had F1 or greater.

The authors concluded 2/3 of patients with persistently normal ALT had significant fibrosis (F1 or greater). They suggest patients with elevated ALT are candidates for HCV therapy. And, biopsy is most warranted for patients with persistently normal ALT in order to identify the 1/3 who don’t have fibrosis (some of whom have cirrhosis) and can defer therapy, and to identify the 2/3 who may require therapy.

(editorial note: Since HIV accelerates HCV progression, coinfected patients with normal ALT are at least as likely as patients infected with HCV alone to have FI or greater, so this study suggests coinfected patients with normal ALT should all get liver biopsy).

Pierre Pradat, Hotel-Dieu, Lyon France; Thierry Poynard, Hosp Pitie Salpetriere, Paris France; Alfredo Alberti, Univ di Padova, Padova Italy; Juan I. Esteban, Hosp Gen Vall d'Hebron, Barcelona Spain; Patrick Marcellin, Hosp Beaujon, Paris France; Ola Weiland, Huddinge Hosp, Huddinge Sweden; Salvatore Badalamenti, Schering-Plough, Kenilworth, NJ; Christian Trepo, Hotel-Dieu, Lyon France

Objective: To study the predictive value of ALT levels on histological findings in HCV patients included in a large European database.

Methods: Data on HCV RNA(+) patients were collected from six European Centers located in Barcelona (Spain), Huddinge (Sweden), Lyon (France), Padova (Italy), and Paris (2 Centers, France). ALT values were collected at the time of biopsy and 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% (F1: 35%, F2: 24%, F3: 17%, F4: 16%) against 87% among patients with normal ALT levels (F1: 46%, F2: 23%, F3: 9%, F4: 9%). The positive predictive value (PPV) of ALT for being at least F1 within group A is therefore 92% whereas the negative predictive value (NPV) is only 13%. Within group B, the percentage of cases with at least F1 among patients with elevated ALT reaches 99% (F1: 24%, F2: 50%, F3: 17%, F4: 8%). It is interesting to observe that among patients with "persistently normal" ALT values, still 65% have at least F1 (F1: 52%, F2: 12%, F4: 1.5%). In group B, the PPV reaches 99% whereas the NPV is 35%.

Conclusions: 1. Almost all HCV RNA(+) patients with elevated ALT present different degrees of fibrosis ( F1). 2. However, the low NPV of ALT indicates that an important proportion of patients with "persistently normal" ALT also show histological signs of fibrosis, some of them even cirrhosis. Finally, for evidence-based medical management, this 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.


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