Chronic hepatitis C in patients with persistently normal alanine transaminase levels.
OBJECTIVE
Many patients with chronic hepatitis C virus (HCV) have persistently normal serum alanine transaminase (ALT) levels. We compared characteristics of chronic hepatitis C patients with patients with normal and elevated ALT levels using data from 3 randomized phase III trials of peginterferon alfa-2a (40 kDa).


METHODS
The characteristics of 480 patients with normal ALT values (on >or=3 occasions without any increases in ALT level over a 6- to 18-month period) and 1993 patients with elevated ALT levels were compared. Sixty-eight of the 480 patients with normal ALT levels were randomized to no treatment and monitored for 72 weeks.


RESULTS
More patients with normal ALT levels than patients with elevated ALT levels were women (59% vs 32%; P<.01). The serum HCV RNA titer was significantly lower in patients with normal ALT levels (P<.01 vs in patients with elevated ALT levels). Patients with normal ALT levels had significantly lower inflammation and fibrosis scores on liver biopsy examination than patients with elevated ALT levels, but almost two-thirds had portal fibrosis and 10% had bridging fibrosis. No correlation between baseline ALT activity, HCV RNA level, and liver histology was observed in patients with normal ALT levels. During the 72-week follow-up period, ALT activity elevated above the upper limit of normal in 53% of the untreated patients with normal levels of ALT. None became HCV RNA undetectable.


CONCLUSIONS
Chronic hepatitis C patients with normal ALT levels should be evaluated in a similar manner as patients with elevated ALT levels because they are at risk for developing significant liver disease. The decision to treat with peginterferon alfa and ribavirin should be based on multiple factors, rather than on ALT levels alone.
Shiffman
Mitchell L
ML
Virginia Commonwealth University Medical Center, Richmond, Virginia 23298, USA, and Hospital General de Valencia, Spain. mshiffma@vcu.edu
Diago
Moisés
M
Tran
Albert
A
Pockros
Paul
P
Reindollar
Robert
R
Prati
Daniele
D
Rodríguez-Torres
Maribel
M
Lardelli
Pilar
P
Blotner
Steven
S
Zeuzem
Stefan
S
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood* / Q000378:metabolism; D000998:Antiviral Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D017326:Clinical Trials, Phase III as Topic; D004279:DNA, Viral / Q000032:analysis; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011336:Probability; D016032:Randomized Controlled Trials as Topic; D012016:Reference Values; D012720:Severity of Illness Index
D000998:Antiviral Agents; D004279:DNA, Viral; D000410:Alanine Transaminase