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Liz Highleyman
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In This Issue:
Obesity Has a Negative Impact
on HCV Progression
Hepatocellular Carcinoma on the Rise
Clues about HCV/HBV Coinfection
Obesity
Has a Negative Impact on HCV Progression
Data continues to accumulate
indicating that obesity promotes HCV progression and liver
fibrosis and renders interferon therapy less effective. For
example, Canadian researchers reported in the September issue
of Hepatology that obese patients (body mass index [BMI] greater
than 30 kg/m2) had about an 80% lower chance of a sustained
response to therapy compared with normal or moderately overweight
patients. And in the October issue of Gastroenterology, another
research team reported that hospitalization or death due to
cirrhosis was more likely among obese individuals.
Now, Ke-Qin Hu, MD, from the University
of California at Irvine and colleagues report in the January
2004 issue of the Journal of Hepatology that hepatic steatosis
(fatty liver) is more common in obese or overweight people
and is associated with progression of liver fibrosis. The
authors reviewed medical charts from 324 patients at a U.S.
university medical center and a regional Veterans Administration
medical center. They found that patients who were either obese
(BMI at least 30 kg/m2) or moderately overweight (BMI at least
25 kg/m2) were at higher risk for hepatic steatosis. They
also found that steatosis—especially advanced (grade
II or III) steatosis—was significantly associated with
persistently elevated ALT levels, advanced (stage III or IV)
fibrosis, and higher histological activity index (HAI) scores.
The authors concluded that being overweight or obese is as
an independent risk factor for hepatic steatosis in patients
with chronic HCV, and that steatosis accelerates activity
and progression of chronic hepatitis C.
It is unclear how increased fat accelerates
liver fibrosis, but recent research provides some clues. In
the December 2003 issue of the same journal, Ingrid Hickman
from the University of Queensland in Brisbane and colleagues
measured serum levels of insulin, C-peptide, and leptin (a
hormone produced by fat cells that helps promote normal insulin
activity) in 160 HCV patients and 45 uninfected control subjects
matched for age, sex, and body weight; the HCV patients also
underwent liver biopsies. Consistent with previous research,
patients with HCV genotype 3 had more severe steatosis than
those with genotype 1. Among subjects with either genotype,
overweight patients had significantly more steatosis and higher
insulin and leptin levels. In the overweight HCV patients,
an increase in serum insulin was correlated with increasing
fibrosis, leading the authors to suggest that elevated circulating
insulin “may be a factor responsible for the association
between [body mass index] and fibrosis in patients with HCV.”
Another study in the same issue suggests
that blood glucose abnormalities themselves, rather than excess
body weight, may trigger fibrosis progression. Vlad Ratziu,
MD, from Hôpital Pitié Salpétrière
in Paris and colleagues analyzed 710 patients with chronic
HCV. When analyzing various factors separately, both elevated
serum glucose (blood sugar) and higher BMI were associated
with increased fibrosis. However, in a multivariate analysis
(which corrects for confounding associations), age at infection,
duration of infection, serum glucose, and alcohol intake were
independently associated with increased fibrosis, but body
mass was not. The authors concluded that, “High serum
glucose is an independent co-factor of fibrosis in chronic
hepatitis C with a higher pro-fibrogenic impact than overweight.”
Hepatocellular
Carcinoma on the Rise
Hepatocellular cancinoma is a type of liver cancer than can
occur in people with advanced hepatitis C or B. Because HCV
progresses slowly, many people infected years or even decades
ago are only now coming down with liver cancer and other serious
long-term consequences of chronic hepatitis. In the November
18, 2003 issue of the Annals of Internal Medicine, Hashem
El-Serag, MD, MPH, of the Houston Veterans Affairs Medical
Center and Baylor College of Medicine, and colleagues reported
that hepatocellular carcinoma is increasing rapidly in the
U.S. The authors conducted a retrospective analysis of data
from the National Cancer Institute Surveillance, Epidemiology,
and End Results (SEER) registries, which represent about 10%
of the U.S. population. Between 1975 and 1998, the overall
age-adjusted incidence rate of hepatocellular carcinoma doubled
from 1.4 case per 100,000 persons in 1975–1977 to 3.0
caes per 100,000 persons in 1996–1998. In 1995–1998
alone, the rate increased 25%. Rates rose for men and women,
all ethnic groups, and most age groups over 40, but the increase
was greatest among white men aged 45–54. The authors
concluded that their results likely reflect a true increase
in the incidence of hepatocellular carcinoma, rather than
changes in diagnostic practices or changing demographic features
of the general population. “This is an alarming increase
in a highly lethal cancer,” said Dr. El-Serag. “We
think that hepatitis C virus infections, acquired two to three
decades earlier [e.g., in the 1960s and 1970s], are partially
responsible for this increase in liver cancer.”
Clues about HCV/HBV
Coinfection
While in recent years considerable attention has focused on
HCV/HIV infection, and is increasingly turning to HBV/HIV
coinfection, very little is known about dual infection with
HCV and HBV. However, since the two viruses are spread in
similar ways, it is likely that HCV/HBV coinfection is more
common that generally recognized. In the February issue of
the Journal of Medical Virology (published online in December
2003), Takeshi Tanaka of Tokyo Metropolitan Komagome Hospital
and colleagues reported on the incidence and significance
of low-level HBV infection in patients with HCV-associated
liver disease. The authors collected blood samples from 93
HCV-infected subjects without detectable HBV surface antigen
(HBsAg) and 220 healthy, uninfected volunteers. Using a PCR
test for HBV DNA, they determined that 34.4% of the HCV-infected
patients had HBV genetic material in their blood—despite
having no evidence of HBsAg—compared with just 1.8%
of the uninfected volunteers. The researchers also reported
that hepatocellular carcinoma was more common in HCV/HBV coinfected
patients than in those with HCV alone, and that the hepatitis
C and B viruses were distributed differently in the liver
tissues of coinfected patients than in those with either virus
alone. The results suggest that low-level HBV infection is
common in people with HCV, and points to the need for more
research on this form of coinfection.
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