Hep C Patients with Normal ALT
Reported by Jules Levin
The subject of whether or not to treat patients with chronic HCV was
discussed at the NIH HCV Consensuc Development Conference June 10-12, 2002.
Several reports of information on this subject follow in this article. Here
is the preliminary draft recommendation from the panel:|
Approximately 30 percent of patients with chronic HCV have normal ALT levels,
another 40 percent have ALT levels less than two times the upper limit of
most of these patients have disease that is histologically mild, some
patients may progress to
advanced fibrosis and cirrhosis. Experts differ on whether to biopsy and
treat these patients.
Numerous factors must be considered in recommending treatment, including
genotype, presence of hepatic fibrosis, patient motivation, symptoms,
severity of comorbid
illness, and the patient's age. SVR rates do not differ in patients with
normal or mildly elevated
ALT when treated with interferon monotherapy. Studies of PEG-interferon with
not been completed in patients with normal ALT levels.
Do patients with normal ALT respond the same to therapy? Prior study found
ALT could elevate during therapy.
Bruce Bacon, MD, St Louis University Division of GI & Hepatology, delivered a
talk on patients with normal ALT at the NIH hearing which including response
& safety of therapy:
CLINICAL AND VIROLOGICAL FEATURES OF CHRONIC HEPATITIS C PATIENTS WITH NORMAL
A large proportion of patients with chronic hepatitis C (CHC) have
persistently normal alanine aminotransferase (ALT) but the clinical and
virological features and natural history of these patients are not well
Stefan Zeuzem et al including Roche reported at the DDW conference in May
2002 on this study.The aim of this study is to characterize the natural
history of normal ALT CHC patients and the evolution of the disease regarding
viremia and ALT. This is a multicenter study evaluating efficacy and safety
of treatment with 40 kDa pegylated interferon alfa-2a and ribavirin in normal
ALT CHC patients is ongoing.
Patients in the control group will be observed untreated for 72 weeks. CHC
infection must be documented by both positive anti-HCV antibody and HCV RNA
PCR tests at least 6 months prior to the study. Persistently normal ALT was
defined by at least 3 determinations equal or below the ULN, minimum 4 weeks
apart, with one value within screening period and another between 6 and 18
months before onset. Liver disease consistent with CHC was confirmed by
biopsy within 36 months before trial.
RESULTS: At the time of this interim analysis 73 patients were randomized to
the control group; 4 withdrew at baseline and 36 have been followed for 24
weeks or more. Demographic features: mean age 41.8 years, male to female
ratio 28:45, mean weight 71 Kg (2.2 lbs per kg). Mode of infection i.v. drug
use 34%, transfusion 20%, other 14%, unknown 32%. 65.8% of patients had
genotype 1. Histological activity (Ishak score): 2 or less for
necroinflammatory changes in 86% of the patients, fibrosis score 3 or less in
90%. Baseline mean and median viral load were 1,286,512 and 789,500 IU/mL,
respectively, and remained stable.
Of 36 patients followed for 24 weeks, ALT stayed within normal limits in 53%.
Of 69 subjects, sporadic ALT elevations of <2x ULN occurred in 33%. One
patient had an isolated 12x ULN ALT flare accompanied by a moderate AST
increase. No significant hematological or biochemical changes were observed.
8 patients presented CHC-related symptoms at onset. Mild adverse events were
reported in 14 subjects.
The authors concluded that normal ALT population has distinct biological and
virological features. According to previous data from studies on abnormal ALT
CHC patients, there are no differences in age, weight and infection source;
however, the male to female ratio is inverted in the normal ALT population.
Genotype distribution is similar, while baseline viremia appears to be lower
in normal ALT patients. Liver disease is also milder. During follow-up,
viremia was stable and ALT values stayed within normal or near normal range.
The majority of the patients remained asymptomatic.