In
HIV/HCV-coinfected Patients, Normal ALT Levels Do Not Indicate Reduced Necroinflammation
or Slower Progression to Fibrosis Hepatitis
C virus (HCV) infection is a principal cause of chronic liver disease leading
to cirrhosis and hepatocellular
carcinoma (liver cancer). Elevation
of alanine aminotransferase (ALT)
is widely regarded as an indicator of hepatocellular inflammation and injury in
patients with chronic hepatitis C. In undiagnosed
individuals, persistently elevated ALT levels (PNAL) are considered an indication
to screen for HCV infection. Approximately
30% of HCV-monoinfected patients manifest persistently
normal ALT levels, whereas an additional 40% have mild ALT elevations (less
than 2 times the upper limit of normal). Prior studies have demonstrated that
the natural history of HCV infection is milder in monoinfected patients with normal
ALT levels, as shown by reduced necroinflammation and slower fibrosis
progression, compared with patients with elevated ALT levels.  Several
epidemiologic studies have documented increased hepatic necroinflammation and
accelerated fibrosis in HIV/HCV-coinfected patients compared with HCV-monoinfected
patients. In these studies, mean ALT levels did not differ between patient groups.
A recent study
found that the percentage of patients with normal ALT levels did not differ between
HIV/HCV-coinfected and HCV-monoinfected patients (R K (Sterling et al. J Acquir
Immune Defic Syndr 32; 2004). In
the present study, researchers sought to evaluate whether normal ALT levels identify
HIV/HCV-coinfected patients with reduced necroinflammation and fibrosis as compared
with those with elevated ALT levels. They retrospectively evaluated demographic,
clinical, viral, and histologic parameters obtained from HIV/HCV-coinfected patients
with normal and elevated ALT levels who had undergone a liver biopsy. Because
prior studies have documented milder liver disease in HCV-monoinfected patients
with normal ALT levels, they also evaluated the same parameters in monoinfected
patients with normal and elevated ALT levels. Results
Mean ALT levels and the percentage of patients with normal ALT (?40 U/L) levels
were similar in HIV/HCV-coinfected (mean ± SD, 81.7 ± 56.1 U/L;
21%) and HCV-monoinfected patients (97.3 ± 100.7 U/L; 18%; P = 0.19 and
0.54, respectively).
Coinfected patients, however, had significantly advanced necroinflammation (P'=
0.001) and fibrosis (P = 0.02) compared with monoinfected patients.
The percentage of patients with advanced necroinflammation (grades 3 or 4) was
lower in HCV-monoinfected patients with normal ALT levels compared with those
with elevated ALT (5% vs 20%, respectively).
In contrast, the percentage of coinfected patients with advanced necroinflammation
was similar whether the patient had normal or elevated ALT levels (32% vs 37%,'respectively). |
The
authors conclude, "In coinfected patients, normal ALT levels are not an indicator
of mild necroinflammation and may not portend a more benign disease course." Discussion
and Summary
In HCV-monoinfected patients, persistently elevated ALT
levels are considered a marker of hepatocellular damage, an indication for liver
biopsy, and a consideration for initiation of therapy.
In these patients,
normal ALT levels distinguish a subgroup of patients with a milder course of liver
disease. In these patients, normal ALT levels distinguish a subgroup of patients
with a milder course of liver disease.
In a recent longitudinal study,
HCV-monoinfected patients with normal ALT levels had a relatively benign natural
history; 22.5% of the patients with normal ALT levels had fibrosis progression
compared with 41.5% of the patients with elevated ALT levels over a median of
6.3 years (C K Hui et al. J Hepatol;38; 2003). Other studies have corroborated
these findings in HCV-monoinfected patients.
The findings presented here
provide evidence and comparative histologic data indicating that normal ALT levels
in HIV/HCV-coinfected patients do not predict benign liver histology [emphasis
added-Ed]. Furthermore, this study included a larger sample size, and the investigators
used a rigorous definition of normal ALT levels (?40 U/L).
Although normal
ALT levels distinguished a subgroup of HCV-monoinfected patients with reduced
necroinflammation, the study authors did not observe a significant association
between ALT levels and fibrosis. These findings suggest that the association between
ALT levels and necroinflammation may be stronger than the association between
ALT levels and fibrosis.
In closing, the authors write, "Our findings
suggest that in HIV/HCV-coinfected patients, ALT levels may not provide adequate
information regarding the extent of liver disease. Furthermore, we provide additional
evidence that normal ALT levels are not associated with benign hepatic histology
in HIV/HCV-coinfected patients."
05/12/06 Reference
S
A Gonzalez, R-C Liu, B R Edlin, and others. HIV/Hepatitis C Virus-Coinfected Patients
with Normal Alanine Aminotransferase Levels. Journal of Acquired Immune Deficiency
Syndromes 41(15): 582-589. April 15, 2006.
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