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Liz Highleyman
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In This Issue: Hepatitis C
Liver Steatosis
Body Weight and Liver Disease
HCV Rates Among Veterans
Liver
Steatosis
Steatosis, or fatty liver, is a type of progressive
liver damage sometimes seen in people with hepatitis C, especially
those with genotype 3. Three recent articles shed further
light on the condition.
In the March 2004 issue of Gut,
L. Castera and colleagues from France reported on the relationship
between steatosis and HCV clearance after antiviral treatment.
The study included 151 subjects who had paired (before and
after treatment) liver biopsies (37 with HCV genotype 3; 114
with non-3 genotypes). None were obese or heavy alcohol users.
Twenty-five patients (16.5%) achieved a sustained virological
response (SVR). Post-treatment biopsies showed improved steatosis
in 36% of subjects, worsened steatosis in 13%, and stable
steatosis in 51%. Steatosis improvement was seen significantly
more often in patients who achieved SVR (64%) compared with
nonresponders (31%). The responder/nonresponder difference
was significant in patients with genotype 3 (91% versus 19%),
but not in those with non-3 genotypes (43% versus 34%). Among
the 25 subjects who achieved SVR, steatosis improvement occurred
significantly more often in genotype 3 patients (91%) than
in those with other genotypes (43%). Among the nonresponders,
steatosis improvement did not differ by genotype. In a multivariate
analysis, improved steatosis was independently associated
with SVR, initial steatosis severity, genotype 3 HCV, and
body mass index of 25 or greater (a BMI over 25 is considered
“overweight,” and a BMI over 30 is considered
“obese”). In conclusion, patients with genotype
3 HCV who achieved SVR showed significant improvement in steatosis,
suggesting that genotype is an important factor in steatosis
pathogenesis.
In the same issue of Gut, L. Rubbia-Brandt
and a group of international colleagues confirmed that genotype
affects steatosis. The researchers performed a multivariable
logistic regression analysis on data from 755 patients with
chronic hepatitis C, 178 of whom had genotype 3. Liver biopsies
revealed that 315 had steatosis and 605 had fibrosis (of whom
187 had progressed to cirrhosis). In this study, steatosis
was independently associated with presence of fibrosis, genotype
3 HCV, ongoing heavy alcohol use, and older age. Fibrosis
was independently associated with presence of steatosis, past
heavy alcohol use, Metavir activity score (degree of liver
damage), older age, and body mass index, but not with genotype.
When patients were separated based on genotype, steatosis
was associated with ongoing heavy alcohol use and older age
only in people with non-3 genotypes, and was associated with
Metavir score only in genotype 3 patients. Similarly, fibrosis
was associated with steatosis only in those with genotype
3, and was only associated with past heavy alcohol use in
those with non-3 genotypes. The researchers concluded that
“steatosis influences chronic hepatitis C progression
in a genotype specific way,” and suggested that patients
with genotype 3 HCV and histologically confirmed steatosis
should receive antiviral treatment.
Finally, in the March 2004 issue of the Journal of Hepatology,
Heather Patton and colleagues from the Scripps Clinic reported
on the impact of steatosis on liver disease progression and
treatment response in patients with chronic hepatitis C. The
researchers evaluated liver biopsies from 574 patients, and
found that steatosis severity was associated with body mass
index, HCV genotype 3, older age, and longer duration of infection.
Among those with genotype 3, higher HCV viral load was associated
with more severe steatosis. In people with genotype 1, fibrosis
with associated with steatosis severity. Also in the genotype
1 group, patients with less severe pre-treatment steatosis
were more likely to achieve SVR. Indeed, genotype 1 patients
who achieved an early virological response were more likely
to have grade 0 (minimal or no) steatosis compared with early
nonresponders. As in Castera’s study, steatosis improved
markedly in genotype 3 patients who achieved SVR. The researchers
concluded that “steatosis is an important cofactor in
hepatitis C as it is associated with fibrosis and reduces
the likelihood of achieving early and sustained virologic
response in genotype 1 infected patients.”
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Body Weight
and Liver Disease
In the March 2004 issue of Hepatology, Saverio Stranges from
the State University of New York at Buffalo and colleagues
looked at the association between body weight, body fat distribution,
and liver enzyme levels. Recent research has shown that in
addition to increasing the risk of insulin resistance and
cardiovascular disease, abdominal (or central) fat accumulation
is also a risk factor for liver steatosis. The researchers
analyzed data from 2,074 subjects without known liver disease.
Using multiple linear regression models, they found that abdominal
fat accumulation was a better predictor of elevated ALT and
GGT (two liver enzymes) than body mass index in both men and
women. The authors concluded that central fat accumulation
(that is, having a “pot belly,” or an “apple”
versus a “pear” shape) is associated with elevated
liver enzyme levels independent of body weight, and suggest
this may be due to unrecognized steatosis.
In the March 2004 issue of Gut, I. Hickman and colleagues
from Australia reported that modest weight loss and increased
physical activity led to decreased ALT, improved fasting insulin
levels, and better quality of life in overweight patients
with chronic liver disease. The study looked at 31 participants
who completed a 15-month diet and exercise program. At the
end of the program, 21 patients (68%) achieved and maintained
a reduction in body weight. ALT improvements were correlated
with the amount of weight lost. Among patients who maintained
their weight loss at 15 months, ALT levels remained significantly
below baseline values, while those who regained their lost
weight had ALT levels similar to baseline. These results are
not surprising, since obesity is associated with steatosis
and fibrosis progression in people with chronic hepatitis
C and other types of liver disease. Those who lost weight
also had improved fasting serum insulin levels and reported
a significantly better quality of life. The researchers concluded
that “[t]reatment of overweight patients should form
an important component of the management of those with chronic
liver disease.”
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HCV Rates
Among Veterans
In the March 2004 issue of the Journal
of Clinical Gastroenterology, Kevin Sloan and colleagues
confirmed that hepatitis C prevalence is higher among U.S.
veterans in the Northwest compared with the population as
a whole. It is estimated that among the general population,
about 1.8% are infected with HCV. Past studies of veterans
have found prevalence rates between 1.7% and 3.5%. In this
study, researchers conducted a retrospective review of medical
records from nearly 38,000 patients tested for HCV between
October 1994 and December 2000 at eight Veterans Administration
Medical Centers in the Northwest Network. Based on their results,
the authors estimated that 11.4% of veterans in the region
are HCV positive, with a lower bound of 4.0% and an upper
bound of 19.5%. This rate is higher than the 8-10% seen in
a national sample of all veterans who received blood tests
throughout the Veterans Healthcare Administration on a single
day in 1999. However, the researchers noted that changes in
testing practices (that is, increased testing of a broader
range of patients) makes it difficult to make comparisons
with rates from past studies.
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