Virological
and Histological Features and Predictors of Fibrosis in Hepatitis B Patients with
Persistently Normal ALT
Alanine
aminotransferase (ALT) is a liver enzyme released into the bloodstream during
liver inflammation. Traditionally, elevated ALT has been used as a marker of liver
damage and need for treatment in patients with chronic
hepatitis B virus (HBV) infection. Several studies, however, have shown that
considerable liver disease progression may occur in people with persistently normal
ALT levels.
Study
1
In
a study reported in the May 2008 issue of Gastroenterology, Indian researchers
looked at virological and histological features of chronic hepatitis B patients
with persistently normal ALT.
The analysis included 1387 hepatitis B surface
antigen (HBsAg) positive asymptomatic patients. Among the 189 participants with
persistently normal ALT, 73 were hepatitis B "e" antigen (HBeAg) positive
and 116 were HBeAg negative. Among the 1198 individuals with persistently or intermittently
elevated ALT, 530 were HBeAg positive and 668 were HBeAg negative. Participants
were followed for at least 1 year.
Results
•
Among the HBeAg positive patients, 60.3% with persistently normal ALT and 73.8%
with elevated ALT had a baseline HBV DNA level > 5 log copies/mL (P
= 0.018).
•
Among HBeAg negative patients, the corresponding percentages were 35.5% and 76.0%,
respectively (P < 0.001).
•
In the HBeAg positive group, 40.2% with persistently normal ALT and 65.5% with
elevated ALT had at least moderate fibrosis (> stage 2) (P < 0.001).
•
In the HBeAg negative group, the percentages were 13.8% and 63.9%, respectively
(P < 0.001).
•
Approximately 21% of HBeAg negative patients with persistently normal ALT and
HBV DNA < 5 log copies/mL nevertheless had histologically active liver disease
(defined as histological activity index > 3 and/or fibrosis stage >
2).
Based
on these findings, the study authors concluded, "A fair proportion of patients
with chronic HBV infection with persistently normal ALT have HBV DNA >
5 log copies/mL and significant histologic fibrosis."
They added that
use of ALT and HBV DNA levels without resorting to liver biopsy to define an 'inactive
carrier state' in HBeAg negative individuals with persistently normal ALT "may
miss histologically significant disease in a proportion of patients."
Study
2
In
a related study published in the August 2008 Journal of Clinical Gastroenterology,
Chia Wang and colleagues examined the prevalence and correlates of significant
liver fibrosis in patients with so-called
"immunotolerant" hepatitis B.
As
background, the authors noted that adults with chronic HBV infection acquired
early in life -- as is common throughout much of Asia -- often have immunotolerant
hepatitis B, characterized by normal ALT but high HBV DNA.
The
investigators conducted a cross-sectional study of 28 hepatitis B patients in
a tertiary care setting with positive HBeAg, serum HBV DNA titers > 10 copies/mL,
and persistently normal ALT. Liver biopsies
were reviewed by a single blinded pathologist. The prevalence of significant (stage
2) fibrosis was determined using both the hospital-defined upper limit of normal
for ALT and 2 other more stringent criteria.
Results
•
The prevalence of stage 2 fibrosis was 32% using the hospital-defined criteria
and 13% using the most stringent definition of normal serum ALT.
•
The negative predictive values of these criteria were 68% and 88%, respectively.
•
The following factors were independently associated with stage 2 fibrosis on liver
biopsy:
•
Age greater than 30 years (P = 0.035);
•
Grade 2 liver inflammation (P = 0.005);
•
Lower serum HBV DNA (mean 7.45 vs 8.42 log10 copies/mL; P<0.001).
In
conclusion, the study authors wrote, "These results highlight the need to
use stringent definitions of normal serum ALT when making clinical decisions for
patients with chronic hepatitis B."
"Older
age and lower serum HBV DNA level predict significant hepatic fibrosis on biopsy,"
they added. "Our findings may guide decisions regarding liver biopsy among
patients with immunotolerant hepatitis B."
7/29/08
References
M
Kumar, SK Sarin, S Hissar, and others. Virologic and histologic features of chronic
hepatitis B virus-infected asymptomatic patients with persistently normal ALT.
Gastroenterology 134(5): 1376-1384. May 2008. (Abstract)
CC
Wang, LY Lim, H Deubner, and others. Factors predictive of significant hepatic
fibrosis in adults with chronic hepatitis B and normal serum ALT. Journal of Clinical
Gastroenterology 42(7): 820-826. August 2008. (Abstract)
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