This
liver graphic shows prominent dark brown/red discoloration on cut section because
of excessive iron storage.
Two
recent studies examined the influence of iron accumulation in the liver on the
development of fibrosis and response to therapy in patients with chronic hepatitis
C.
Study
1
The
first study, published in the November 29, 2006 electronic edition of Gut,
evaluated the role of HFE, ferroportin, and beta-globin gene mutations in promoting
hepatic iron accumulation and fibrosis in patients with chronic HCV infection.
The investigators
performed genetic analyses together with the assessment of hepatic iron content
and liver histology in 100 patients with biopsy-proven chronic hepatitis C, without
HIV or HBV coinfection.
Results
Among the patients analyzed, 12 were heterozygous (carried 2 different gene variants)
for various beta-globin gene mutations (e.g., 39C-T, IVS1.1G-A, IVS1.6T-C).
29 subjects carried HFE gene mutations (C282Y, H63D and S65C).
1 additional patient was heterozygous for both HFE (H63D) and beta-globin (39C-T)
variants.
58 subjects had wild-type (non-mutated) alleles of both genes.
Hepatic iron concentration and hepatic stainable iron were significantly higher
in patients carrying beta-globin mutations than in those with HFE mutations or
wild-type alleles (P < 0.05).
Multivariate analysis confirmed that the presence of beta-globin gene mutations
was independently associated with both hepatic iron concentration (P = 0.008)
and hepatic stainable iron (OR 6.11; P = 0.009).
Moderate to severe fibrosis or cirrhosis (Ishak score > 2) was observed in
48 of the 100 patients.
Logistic regression demonstrated that patient age (OR 1.05; P < 0.005) and
beta-globin mutations (OR 4.99; P = 0.025) were independent predictors of fibrosis
severity.
"Heterozygosis
for beta-globin mutations is a novel risk factor for both hepatic iron accumulation
and the progression to fibrosis in chronic hepatitis C patients," the authors
concluded.
Study
2
In
the second study, described in the November 2006 issue of Gastroenterology, investigators
assessed the influence of HFE mutations and serum and hepatic measures of iron
accumulation on baseline features and response to re-treatment with interferon-based
therapy in patients with advanced chronic hepatitis C (Ishak score > 2) in
the HALT-C trial.
A
total of 1051 subjects (out of 1145) agreed to be tested for HFE mutations (C282Y,
H63D, and S65C). Hepatic iron concentrations were measured in 144 liver biopsy
specimens.
Results
35% of patients analyzed carried at least 1 HFE gene mutation.
There were no significant differences in the prevalence of HFE gene mutations
among subjects with fibrosis (35.5%) versus cirrhosis (32.9%).
33% of subjects achieved an end-of-treatment response and 16% achieved sustained
virological response (SVR).
Patients with HFE mutations - in particular H63D - had a higher end-of-treatment
response rate compared to individuals lacking these mutations (40% vs 29%; P =
0.0078).
The same held true for SVR rates (20% vs 14%; P = 0.009).
In
conclusion, the authors wrote, "Although HFE mutations (especially the most
frequent H63D mutation) are associated with increased iron loading, they are also
associated with increased sustained virologic responses in U.S. patients with
advanced chronic hepatitis C."
Further
research is needed to explain how HFE mutations might promote improved response
to therapy.
12/12/06
References
M
Sartori, S Andorno, M Pagliarulo, and others. Heterozygous beta-globin gene mutations
as a risk factor for iron accumulation and liver fibrosis in chronic hepatitis
C. Gut. November 29, 2006 [Epub ahead of print].
H
L Bonkovsky, D Naishadham, R W Lambrecht, and others. Roles of iron and HFE mutations
on severity and response to therapy during retreatment of advanced chronic hepatitis
C. Gastroenterology 131(5): 1440-1451. November 2006.
Among the patients analyzed, 12 were heterozygous (carried 2 different gene variants)
for various beta-globin gene mutations (e.g., 39C-T, IVS1.1G-A, IVS1.6T-C).
