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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:
Normal ALT
Approximately 30 percent of patients with chronic HCV have normal ALT levels, and another 40 percent have ALT levels less than two times the upper limit of normal. Although 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 favorable 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 ribavirin have 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:
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 defined.
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.
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