| Back
to News Review
Liz Highleyman
To download pdf version click here
In This Issue:
Leptin
and Fibrosis
Patients with Cirrhosis Benefit from Treatment
Pegylated Interferon Improves Liver Health
Thymosin-alpha 1
Liver Disease Research Funding
Leptin
and Fibrosis
In recent years there has
been considerable interest in leptin, a hormone produced by
fat cells that helps regulate appetite and promote normal
insulin activity. Leptin leads to weight loss in obese mice,
and is under study as a treatment for lipodystrophy (abnormal
body fat distribution) in people with HIV. Leptin also appears
to play a role in liver fibrosis. In the January 2004 issue
of the Journal of Viral Hepatitis, Dr. Thierry Piche
and colleagues from Nice, France, studied the association
between leptin levels and fibrosis in patients with chronic
HCV. They compared 77 HCV-infected patients and 22 uninfected
control subjects; 65 of the patients had minimal to moderate
(stage F0-F2) fibrosis and 12 had severe (stage F3-F4) fibrosis.
Overall, leptin levels were higher in the HCV-infected patients
compared with the uninfected controls; in addition, leptin
levels were higher in women than in men among both patients
and controls. Higher leptin levels were observed in patients
with fibrosis and steatosis (fatty liver), and elevated leptin
was linked to higher body mass index (BMI) and blood sugar
levels. The authors concluded that, “the severity of
liver fibrosis is associated with serum leptin,” and
suggested that TNF-alpha (a cytokine, or chemical messenger,
produced by immune cells) may be a possible mediating mechanism.
In related research, Dr. Piche and colleagues reported in
2002 that high leptin levels were associated with greater
fatigue in people with chronic HCV.
Back to top
Patients
with Cirrhosis Benefit from Treatment
Several recent journal articles have looked at various aspects
of HCV treatment. In a study published last fall in the November/December
2003 issue of the Journal of Clinical Gastroenterology,
Dr. Jenny Heathcote from Toronto presented an overview of
treatment of HCV patients with cirrhosis. Patients with compensated
cirrhosis (the liver is damaged but can still carry out most
of its normal functions) can benefit from interferon therapy.
Even in this difficult-to-treat population, about 43% achieve
a sustained virological response (SVR) with pegylated interferon
plus ribavirin. Those who achieve an SVR have decreased fibrosis
progression, and some show improvements in liver damage; sustained
responders also appear to be at less risk for hepatocellular
carcinoma (liver cancer). Even some patients who do not achieve
an SVR may still experience histological (tissue health) improvement.
Although patients with cirrhosis may be more likely to experience
treatment side effects, they “have a high chance of
dying from progressive liver disease,” concluded Dr.
Heathcote, and thus “have the most to gain from successful
antiviral therapy.” However, treatment of patients with
decompensated cirrhosis remains potentially dangerous, and
should only be undertaken in the context of a clinical trial.
Back to top
Pegylated
Interferon Improves Liver Health
In the February 2004 issue of Hepatology, Dr. Calogero
Cammà from Palermo, Italy, and colleagues reported
on a meta-analysis of data from three randomized clinical
trials that included a total of 1,013 previously untreated
chronic HCV patients, looking at the effect of treatment on
liver histology. All patients had paired pre- and post-treatment
liver biopsies. Knodell scores were compared before and after
treatment; histological improvement was defined as a decrease
of a least one point in the fibrosis score or at least two
points in the histological (necroinflammatory) activity score
between the two biopsies.
As expected interferon (Pegasys) monotherapy was more effective
than standard interferon monotherapy (33.4% vs 17.6%). After
24-48 weeks of therapy, pegylated interferon improved liver
tissue health the most in patients who achieved a sustained
virological response, and to a lesser extent in relapsers.
Among those with an SVR, about 81% had reduced necroinflammatory
(cell inflammation and death) activity and about 33% had improved
fibrosis; the rate of fibrosis improvement in the nearly 200
participants with cirrhosis was about the same as in those
with less advanced liver damage. However, among nonresponders,
the researchers found that therapy produced “negligible
changes in necroinflammation and no significant change in
fibrosis.” This result conflicts those of some previous
research. Dr. Cammà and colleagues suggested that the
scoring method used in their study might better reflect actual
changes in liver tissue health.
The authors also found that improved liver histology was more
likely in those who experienced an early virological response
at 12 weeks, in those with higher pre-treatment ALT levels,
and in obese patients (body mass index over 30). “[I]mpressive
improvements in terms of fibrosis can be achieved in patients
with SVRs and, to a lesser degree, in patients with recurrent
disease,” the authors concluded, but “[n]o significant
changes were observed in nonresponders.”
Back to top
Thymosin-alpha
1
In the January 2004 issue of the Journal of Viral Hepatology,
Dr. Pietro Andreone and colleagues from Bologna, Italy, reported
that combination therapy with standard interferon plus thymosin-alpha
1 was initially more effective than interferon alone in chronic
HCV patients being treated for the first time. In this study,
22 patients received the combination, while 19 received interferon
monotherapy. After six months of therapy, the end-of-treatment
response rate was higher in the patients receiving thymosin-alpha
1, but after six months of follow-up, the sustained response
rate was the same in both groups. Limitations of this study
include the short treatment duration (genotype 1 HCV is usually
treated for 12 months) and the use of standard interferon
rather than the more effective pegylated interferon. However,
the results suggest that thymosin-alpha 1 might contribute
to treatment effectiveness if added to the best available
therapy.
Back to top
Liver Disease
Research Funding
Finally, also in the February 2004 Hepatology, Dr.
Jay Hoofnagle of the National Institute of Diabetes and Digestive
and Kidney Diseases gave an overview of federal liver disease
research funding. According to Dr. Hoofnagle, funding for
liver disease research accounts for about 1.4% of the total
National Institutes of Health (NIH) budget, spread among 16
of 27 NIH institutes and centers. During the past five years,
liver disease research funding more than doubled, reaching
about $377 million in 2003; total NIH funding doubles during
this period. Among the 1,646 grants funded in 2002 (the last
year for which complete data is available), the largest number
were for viral hepatitis and liver cancer (477 and 418, respectively).
Nearly 60% of the viral hepatitis grants were for HCV, and
almost 20% were for HBV.
Back to top
Back to News Review |
