Alan Franciscus
Editor
Good news for Hepatitis
C Patients with Cirrhosis
The results of a phase II/III clinical trial of Pegasys for
treating HCV + patients with cirrhosis by Dr. J. Heathcote and others
was reported in the December issue of the New England Journal of
Medicine.
This trial studied the effectiveness of Pegasys (Roche’s Peginterferon
alfa-2a) in treating HCV+ patients with compensated liver cirrhosis for
48 weeks with treatment followed by 24 weeks of follow-up. This study is
particularly important because this patient population is considered a
difficult group to treat with current antiviral medications.
This study measured the sustained virologic response (elimination of HCV
at end of 48-week treatment and 24 week follow-up), and biochemical
response (normalization of alanine aminotransferase (ALT) levels) and
histologic response (improved liver health).
The study enrolled 271 patients worldwide with cirrhosis or bridging
fibrosis and randomized into three treatment arms:
- Interferon (Roferon) - dose: 3 million unit , injected three times
a week - 88 patients.
- Pegylated Interferon (Pegasys) - dose 90 µg, injected once weekly
- 96 patients
- Pegylated Interferon (Pegasys) - dose 180µg, injected once weekly
- 87 patients
| Results |
Arm # 1 |
Arm #2 |
Arm #3 |
| Sustained Virologic Response |
8% |
15% |
30% |
| Sustained Biochemical Response
|
15% |
20% |
34% |
| Histologic Response* |
31% |
44% |
54% |
* 184 patients with biopsies before and after treatment.
Ten percent of the patients in this study discontinued therapy because
of side effects.
Side effects for all three treatment arms were similarly tolerated. It
should be noted that only 56% of study participants were infected with
HCV genotype 1 - the most prevalent genotype in the United States and
the most difficult to treat with interferon.
The authors of this study concluded that Pegasys 180 µg injected once
weekly is significantly more effective than 3 million units of
interferon (Roferon) injected three times a week.
The virologic and histologic response rates of patients in this study
treated with Pegasys 180 µg are very encouraging and will provide new
options for patients with cirrhosis who currently have very few options.
For information on Roche clinical trials, call 866-GO-WINGS.
Quantitative liver function
predicts development of HCV-related cirrhosis
4th April, 2001
Liver 2001;21(1):26-30
Quantitative testing of liver function (QTLF) positively correlates
with progression in hepatitis C virus (HCV) patients who have liver
cirrhosis. A new study reported in the journal Liver by researchers in
Germany has established a significant relationship between QTLF values
and liver classification scoring using Child-Pugh grades, with lower
values reflecting worse liver cirrhosis. QTLF might be a valid indicator
for early chronic hepatitis C related cirrhosis, the researchers
suggest.
C. Herold et al. of the Medical Clinic and Policlinic 1 in Erlangen,
Germany, studied the liver biopsies and QTLF of 86 male and female
patients with chronic hepatitis C related cirrhosis. "QTLF included
aminopyrine breath test (microsomal liver function), galactose
elimination capacity (cytosolic liver function), sorbitol clearance
(liver plasma flow), and indocyanine green clearance (liver perfusion),"
said Herold and associates.
The patients were diagnosed with cirrhosis of Child-Pugh grades A, B,
and C at rates of 55%, 28%, and 17%, respectively. "QTLF showed a steady
decrease from Child-Pugh grade A to grade B and to grade C,"
investigators remarked.
Though metabolic liver function tests showed reduced levels, hepatic
perfusion tests remained within low but normal limits, according to
Herold et al. ("Quantitative testing of liver function in patients with
cirrhosis due to chronic hepatitis C to assess disease severity," Liver,
2001;21(1):26-30).
Cirrhosis patients with Child-Pugh grades B or C had significantly
lower QTLF than healthy volunteers did.
"Since in cirrhosis of grade A, surrogate tests of hepatic perfusion
remained at the lower normal limit, whereas those of metabolic function
were decreased, QTLF may be a tool to predict prognosis or complications
in early cirrhosis due to chronic hepatitis C," researchers concluded.
Key points reported in this study include:
a.. Quantitative testing for liver function (QTLF) values decrease
as scores for Child-Pugh grade increase in HCV patients with cirrhosis
b.. Metabolic liver function tests fall in HCV patients with early
cirrhosis, while hepatic perfusion values remain within normal limits
c.. QTLF values may be a good indicator for progression in patients
with early HCV related liver cirrhosis
Common Hepatitis C Virus Genotype Raises Cirrhotic Decompensation
Risk
06/20/2001
By Anne MacLennan
Type 1b and, to a lesser extent, type 2 are the most common hepatitis C
virus genotypes in European patients with cirrhosis. Furthermore,
although type 1b is not linked with any greater risk for hepatocellular
carcinoma (HCC), it increases by threefold the risk for decompensation
in cirrhosis patients, a European study found.
Study objective was to evaluate distribution and clinical significance
of hepatitis C virus (HCV) genotypes in Europeans with compensated
cirrhosis due to hepatitis C (Child class A) being seen at tertiary
referral centres.
Researchers studied 255 stored serum samples from cirrhotics followed up
for an average of seven years. Genotype-specific primer PCR was used to
determine HCV genotypes. Study inclusion criteria were biopsy-proven
cirrhosis, absence of complications of cirrhosis and exclusion of all
other potential causes of chronic liver disease.
Of the patients, 69 percent had type lb, 19 percent had type 2, 6
percent type 3a, 5 percent type 1a, 0.5 percent type 4 and 0.5 percent
type 5.
Five-year risk by Kaplan-Meier of hepatocellular carcinoma was 6 percent
for patients infected by type 1b and 4 percent for those infected by
non-1b.
Corresponding figures for decompensation were 18 percent (those infected
by type 1b) and 7 percent, and for event-free survival were 79 percent
and 89 percent.
When researchers took baseline clinical and serological features into
account, HCV type 1b did not increase risk for HCC. It did, however,
increase risk for decompensation by a factor of three, and it decreased
event-free survival by a factor of 1.7.
Dr. G. Fattovich of the University of Verona, Verona, Italy, headed this
multicentre study.
Journal of Viral Hepatitis 06/07/2001
New Treatment
Stops Liver Scarring in Mice
Genetic tinkering turns back cirrhosis
By Randy Dotinga
HealthScoutNews Reporter
MONDAY, Oct. 29 (HealthScoutNews) -- When people think of scars, the
first things that usually come to mind are the marks of old injuries on
the skin. But traumatized internal organs can scar too, wreaking havoc
on the inner workings of the body. For several years, scientists have
been trying to find ways to stop and even reverse excessive scarring.
Now, American and British researchers say they are close to figuring out
how to do that for patients with cirrhosis, an often fatal liver disease
characterized by scarring. If successful, the treatment may help
patients with severe burns, cystic fibrosis and other ailments.
The key is reprogramming a protein whose job is to make scarring
happen. "It's a completely different approach, not just another
antibiotic," says Dr. Mario Chojkier, co-author of a new study and
professor of medicine at the University of California at San Diego.
Liver disease and cirrhosis are the 10th leading killer of Americans.
While cirrhosis is closely connected to alcoholism -- an estimated half
of men who drink more than eight drinks a day will develop the ailment
-- it's also caused by hepatitis and other diseases.
As liver disease progresses, toxins poison the organ and cause scar
tissue to build up, blocking blood vessels that travel through it. "It's
like clogging a pipe. It makes the blood flow go backwards, which will
have major consequences. Things that are good or bad for the body can't
be handled accordingly by the liver because the blood can't reach it,"
Chojkier says.
Other problems can develop, like yellowish skin (known as jaundice),
bleeding and liver failure.
While doctors can try to stop the causes of cirrhosis, they haven't
been able to turn back time on scarring. "We have to accept that we
cannot treat everybody. That's why we need alternatives," says Dr.
Adrian Di Bisceglie, medical director of the American Liver Foundation.
That's where the U.S. and U.K researchers come in. Their findings
appear in the Oct. 26 issue of the medical journal Molecular Cell.
By tinkering with the genetics of a protein so that it no longer has
an amino acid that starts an excessive scarring process, they have
changed the way scars develop in mice with liver disease.
Existing scar tissue may even evaporate, a process called "melting"
by some researchers. "It could get back to normal little by little,"
Chojkier says.
Experiments on humans may come in the next several years. With luck,
the new treatment "could be utilized for the prevention of fibrosis
[scarring] in other organs, like the lungs and kidney and skin and the
brain. We think if it works in one organ, it has a very good chance of
working in another," Chojkier says.
Liver disease experts say the new research is intriguing, but they
caution that successful research in mice doesn't always translate to
human treatments.
The findings are part of a "growing body of information and
excitement" in the medical community about the prospects of stopping and
reversing scarring, says Dr. Scott Friedman, professor of medicine at
Mt. Sinai School of Medicine.
Even without the new research, doctors can do much more for liver
disease patients than in the recent past, Di Bisceglie says. "If you go
back 10 or 15 years ago, we had very few treatments. In the last 10
years, we've seen a lot of developments like liver transplants, which we
do 4,000 to 5,000 times a year in this country. There are treatments
that are increasingly effective."
InterMune Announces
Start of Phase II Trial of Actimmune for the Treatment Of Liver Fibrosis
Actimmune May Become First Anti-fibrotic Therapy for Advanced Liver
Disease BRISBANE, Calif., Jan. 8 /PRNewswire-FirstCall/ -- InterMune,
Inc. (Nasdaq: ITMN - news)
announced today that it has begun enrolling patients in its Phase II
clinical trial of Actimmune® (Interferon gamma-1b) injection for the
treatment of severe liver fibrosis, or cirrhosis, caused by hepatitis C
virus (HCV). The objective of the study, called AEGIS (Anti-fibrotic
Efficacy Gamma Interferon Study), is to evaluate the safety and anti-fibrotic
activity of Actimmune in HCV patients who have failed standard antiviral
therapy.
More than four million people are affected with
HCV in the United States, and current antiviral therapy for HCV
infection is effective in only approximately 50% of patients. Because
treatment is often not effective, continued HCV infection leads to
progressive liver fibrosis or cirrhosis (scarring caused by the
accumulation of tough fibrous proteins). These patients are at an
increased risk of developing life-threatening complications such as
internal bleeding, inability to remove toxins from the blood,
progressive liver failure and death.
``Interferon gamma has been shown to inhibit
activation, proliferation and production of extra-cellular proteins
associated with fibrosis in the hepatic stellate cells -- the key cell
type involved in liver fibrosis,'' said Henry Hsu, MD, Vice President of
Clinical Research at InterMune. ``Preclinical and clinical data have
demonstrated that Interferon gamma may prevent or reverse the
development of cirrhosis. Based on these data, we believe the results of
this trial, which we expect in early 2004, could represent a major
advance in the management of patients with advanced liver disease.''
In the Phase II, multi-center,
placebo-controlled study, 450 patients will be randomized to receive
either placebo, 100 mcg of Actimmune or 200 mcg of Actimmune three times
per week via subcutaneous injection. The study is designed to evaluate
the proportion of patients showing a reduction of one or more points on
the fibrosis staging score (using the Ishak staging system, a standard
clinical measurement in this disease) following treatment with Actimmune,
compared to placebo, for 48 weeks.
``There is a clear unmet medical need in
patients suffering from HCV-related liver fibrosis, as they have few, if
any, effective treatment options,'' said W. Scott Harkonen, M.D.,
President and Chief Executive Officer of InterMune. ``Actimmune is a
promising therapy against this disease, and if demonstrated safe and
effective in this study, could also possibly be used broadly to treat
other forms of liver cirrhosis such as those caused by alcoholism,
metabolic disorders or the hepatitis B virus.''
About Actimmune in Liver Fibrosis
Actimmune is being investigated as a potential
treatment for liver fibrosis based on an emerging body of evidence that
demonstrates the importance of interferon gamma as a cytokine that
modulates the interaction of a downstream protein, transforming growth
factor-beta (TGF-beta), that has been shown to play a critical role in
the pathogenesis of fibrotic diseases. Data from in vitro studies,
studies in animal models of liver fibrosis and studies in humans with
HCV infections and idiopathic pulmonary fibrosis (IPF) support a
potential therapeutic role for Interferon gamma in the inhibition of
fibrosis in the liver and other organs.
About Actimmune
Actimmune is an approved product on the market
for the treatment of two rare congenital diseases, chronic granulomatous
disease (CGD) and severe, malignant osteopetrosis. InterMune is
conducting or planning to conduct multiple Phase II and three Phase III
clinical studies with Actimmune, including a Phase III clinical trial
for the treatment of IPF. The company plans to announce the results of
this trial in November 2002.
InterMune recently reported positive results
from a Phase II clinical trial examining the use of Actimmune in
combination with amphotericin B for the treatment of cryptococcal
meningitis, a difficult-to-treat and life-threatening fungal infection.
The company plans to initiate a Phase III trial of Actimmune for the
treatment of ovarian cancer. Studies are also ongoing with Actimmune for
the treatment of cystic fibrosis and atypical mycobacterial infections.
About InterMune
InterMune is a commercial-stage biotechnology
company dedicated to developing innovative products for the treatment of
serious pulmonary and infectious diseases and cancer. InterMune has
three marketed products, growing product revenues and advanced-stage
clinical programs addressing a range of diseases with attractive
commercial markets. For additional information about InterMune, please
visit www.intermune.com.
Except for the historical information contained
herein, this press release contains certain forward-looking statements
that involve risks and uncertainties, including without limitation
statements indicating that: Interferon gamma may prevent or reverse the
development of cirrhosis and represent a major advance in the management
of patients with advanced liver disease; Actimmune could possibly be
used more broadly to treat other forms of liver cirrhosis; Interferon
gamma may have a potential therapeutic role in inhibiting fibrosis in
the liver and other organs; InterMune expects to complete the liver
fibrosis study early in 2004; InterMune is planning to conduct multiple
Phase II and three Phase III clinical studies with Actimmune, including
a Phase III clinical trial for the treatment of IPF and a Phase III
trial for the treatment of ovarian cancer; and initial results from the
IPF trial are expected in November 2002. All forward-looking statements
and other information included in this press release are based on
information available to InterMune as of the date hereof, and InterMune
assumes no obligation to update any such forward-looking statements or
information. InterMune's actual results could differ materially from
those described in InterMune's forward-looking statements. Factors that
could cause or contribute to such differences include, but are not
limited to those discussed in detail under the heading ``Risk Factors''
and the other risks and factors discussed in InterMune's 8-K report
filed with the SEC on December 21, 2001, and other periodic reports
(i.e., 10-K, 10-KA, 10-Q and 8-K) filed with the SEC, which are
incorporated herein by reference. The risks and other factors that
follow, concerning the forward-looking statements in this press release,
should be considered only in connection with the fully discussed risks
and other factors discussed in detail in the 8-K report and InterMune's
other periodic reports filed with the SEC. InterMune's forward-looking
statements in this press release concerning Actimmune are subject to the
uncertainties and risks associated with the uncertain, lengthy and
expensive drug research and development and regulatory process; budget
constraints; third-party manufacturers; significant competition; and
InterMune's ability to obtain, maintain and enforce patents and other
intellectual property.
SOURCE: InterMune, Inc.
HCV and Estrogen in
Women
This study suggests
that before menopause women with HCV-related cirrhosis may be better
able to protect against developing liver cancer. The study suggests that
this protection is in part due to higher hepatic levels of estrogen
receptors. This suggests to me that hepatic estrogen receptor levels in
pre-menopause may play a role in HCV disease progression or response to
HCV therapy.
ESTROGEN RECEPTOR LEVELS AND LIPID PEROXIDATION IN
HEPATOCELLULAR CARCINOMA WITH HEPATITIS C VIRUS INFECTION.
Ichiro Shimizu,
Toshihiro Omoya, Yajun Zhou, Hiroshi Shibata, Hirohiro Honda, Susumu
Ito, Tokushima Univ Sch of Medicine, Tokushima, Japan.
The origin of the sex-associated differences in the
progression of hepatitisC virus (HCV)-infected liver disease remains to
be elucidated. This study was performed to assess possible risks of
menopause and hepatic estrogen receptor (ER) levels for the development
of hepatocellular carcinoma (HCC). Methods: One thousand and thirty-two
consecutive HCC-patients with HCV-related cirrhosis were divided into
two groups, based on the menopause-related age of 55 years. Liver
tissues were obtained undergoing surgical resection of HCC and
metastatic liver tumor. Results: The HCC subjects <55 years of age had a
significantly lower female proportion (17.5%) than the subjects > 50
years of age (30.1%). Univariate analysis showed that HCV-related
cirrhotic patients who developed HCC were more likely to have low
hepatic levels of ER and copper-zinc superoxide dismutase (CuZn-SOD)
protein, and a high hepatic level of a lipid peroxidation product,
malondialdehyde(MDA). Logistic regression identified older age than 55
years of age (odds ratio [OR]: 7.4, 95% confidence interval [CI]:
2.8-19.1), male gender (OR: 3.5, 95% CI: 1.3-10.2), a decreased ER level
(OR: 21.7, 95% CI: 8.8-55.7), and an increased MDA (OR: 8.3, 95% CI:
2.8-24.0) as the variables independently associated with the development
of HCC in HCV-infected patients with cirrhosis. The study also suggested
that menopause in women led to a lowering of hepatic ER levels.
Conclusions: These findings suggest that increased lipid peroxidation
and impaired SOD function in the liver may be associated with decreased
hepatic ER levels in HCV-infected patients with cirrhosis and HCC, and
that HCV-related cirrhotic women before menopause might have the ability
to protect against developing HCC via hepatic ER.
Peginterferon alfa-2a in Chronic
HCV & Cirrhosis or Bridging Fibrosis
New England Journal of Medicine, December 2000
http://www.natap.org/2000/dec/peginterferon_alfa-2a121300.htm
Pegasys (Pegylated Interferon
alfa-2a) in Patients with Chronic HCV
I just returned from the ACTG meeting in Wash DC where we discussed
coinfection and the need to increase the focus on research addressing
key unanswered questions. These are some key questions affecting
coinfected persons: how do HIV meds affect HCV, does HIV impair response
to HCV and HCV therapy, will coinfected persons respond as well to HCV
therapy, when is the best time to start HCV therapy, how much does CD4
count & CD4 nadir affect response to HCV therapy, how does the virology
of coinfection affect either disease, does ribivarin interaction reduce
AZT/d4T effectiveness, can persons be treated effectively with HAART &
HCV therapy simultaneously, how difficult will adherence be & can we
build a support system for coinfected people taking HCV therapy. Another
key question is who will treat HCV in coinfected patients: are ID docs
prepared to meet this challenge, or will hepatologists have to work
closely, perhaps together in clinic settings, with HIV treaters. The
ACTG has agreed to increase their focus on coinfection research. As you
know its estimated that 30% of HIV-infected individuals have HCV, and
for persons infected with HIV thru IVDU the HCV infection rate is
estimated to be 60-90%.
In the December New England Journall of Medicine, there are two reports
on studies in HCV with Pegasys, the Roche version of pegylated
interferon. These reports contain the fully published data sets of
information that was first reported at previous conferences.
The first
PDF is the report of a study first reported at last Spring's
EASL Conference (European Ass for the Study of Liver Diseases) in
Amsterdam. The data was reported on the NATAP web site and those reports
can be found in the Conference Reports section on the web site. In this
study 39% receiving Pegasys achieved a sustained virologic response
compared to 19% for those receiving interferon alone (6 MU induction
regimen pared down to 3 MU 3 times per week).
The second
PDF is the published study on Pegasys in patients with
cirrhosis or bridging fibrosis which found a 30% sustained virologic
response to Pegasys. Bear in mind the standard of care for HCV is
interferon + ribivarin. It is expected that response rates will improve
when pegylated interferon is used with ribivarin. So far, we have not
seen large scale study results from Pegasys+ribivarin, but at recent
AASLD conference Peg Intron+ribivarin results were reported and show
that ribivarin can be combined with pegylated IFN and does produce
improved results compared to pegylated IFN alone. Ongoing studies are
looking at Pegasys+ribivarin.
Abstract
Background. Covalent attachment of a 40-kd branched-chain polyethylene
glycol moiety to interferon alfa-2a results in a compound (peginterferon
alfa-2a) that has sustained absorption, a slower rate of clearance, and
a longer half-life than unmodified interferon alfa-2a. We compared the
clinical effects of a regimen of peginterferon alfa-2a with those of a
regimen of interferon alfa-2a in the initial treatment of patients with
chronic hepatitis C.
Methods
We randomly assigned 531 patients with chronic hepatitis C to
receive either 180 µg of peginterferon alfa-2a subcutaneously once per
week for 48 weeks (267 patients) or 6 million units of interferon
alfa-2a subcutaneously three times per week for 12 weeks, followed by 3
million units three times per week for 36 weeks (264 patients). All the
patients were assessed at week 72 for a sustained virologic response,
defined as an undetectable level of hepatitis C virus RNA (<100 copies
per milliliter).
Results
In the peginterferon group, 223 of the 267 patients completed treatment
and 206 completed follow-up. In the interferon group, 161 of the 264
patients completed treatment and 154 completed follow-up. In an
intention-to-treat analysis in which patients who missed the examination
at the end of treatment or follow-up were considered not to have had a
response at that point, peginterferon alfa-2a was associated with a
higher rate of virologic response than was interferon alfa-2a at week 48
(69 percent vs. 28 percent, P=0.001) and at week 72 (39 percent vs. 19
percent, P=0.001). Sustained normalization of serum alanine
aminotransferase concentrations at week 72 was also more common in the
peginterferon group than in the interferon group (45 percent vs. 25
percent, P=0.001). The two groups were similar with respect to the
frequency and severity of adverse events, which were typical of those
associated with interferon alfa.
Conclusions
In patients with chronic hepatitis C, a regimen of peginterferon alfa-2a
given once weekly is more effective than a regimen of interferon alfa-2a
given three times weekly. (N Engl J Med 2000;343:1666-72.)
A few interesting points raised by study investigators:
Interferon is an essential component of the treatment of chronic
hepatitis C virus (HCV) infection. However, treatment with interferon
alone is generally associated with a sustained virologic response in
fewer than 20 percent of patients. (1,2,3) A 48-week combination regimen
of interferon alfa and ribavirin is associated with a sustained
virologic response in 38 to 43 percent of patients. (4,5)
One of the reasons for the marginal response to interferon is its short
half-life (approximately eight hours (6)), which leads to wide
fluctuations in the plasma concentrations of the drug during the
treatment period. Studies of viral kinetics indicate that HCV has a high
rate of turnover and an in vivo half-life of only a few hours. (7,8)
Among patients treated with interferon alfa three times weekly, an
intermittent increase in viral load can be observed on treatment-free
days. (9) Covalent attachment of a 40-kd branched-chain polyethylene
glycol moiety to interferon alfa-2a produces peginterferon alfa-2a, a
compound that has sustained absorption, a slower rate of clearance, and
a longer half-life than
unmodified interferon alfa. (10,11) The sustained high concentrations of
peginterferon alfa-2a in plasma (12) maintain an antiviral effect on HCV
and make possible once-weekly administration. We compared the efficacy
and safety of peginterferon alfa-2a administered once per week with the
efficacy and safety of interferon alfa-2a administered three times per
week for 48 weeks.
A discordance between the virologic and the biochemical responses at
week 48 was observed in more of the patients assigned to receive
peginterferon alfa-2a than of those assigned to receive unmodified
interferon. Patients who had a virologic response at week 48 but who did
not have a normal serum alanine aminotransferase concentration at this
time had a better histologic response at week 72 than did the entire
study cohort or the subgroup of patients who had both a virologic and a
biochemical response at week 48.
This finding indicates that
peginterferon alfa-2a was not associated with long-term adverse effects
on the liver. In addition, patients who had a virologic response but not
a biochemical response at week 48 had better overall rates of virologic
and biochemical responses at week 72 than patients who had both a
virologic and a biochemical response at week 48. The reason for the
better response in this subgroup of patients is not known, but it may be
associated with a more pronounced immune response in the host and with
the elimination of reservoirs of infected cells in these patients.
Prevention of cirrhosis is the
best measure against hepatocellular cancer
Lakartidningen 1999 Jan 27;96(4):338-41
Kaczynski J Overlakare, medicinska kliniken, Sahlgrenska Universitetss,
jukhuset/Ostra, Goteborg.
The prevalence of adult cirrhosis in Western countries is estimated to
be about 3-5 per cent. Hepatocellular carcinoma (HCC), the predominant
type of primary liver cancer, is associated with cirrhosis in a majority
of cases. The estimated annual incidence of cancer associated with
cirrhosis is 1-11 per cent. All cirrhosis may be complicated by cancer,
but the cancer risk is reported to be highest in cases of hepatitis B (HBV)
or C (HCV) infection, or haemochromatosis. In two Swedish studies,
comprising a total of 605 patients with HCC, cirrhosis was present in
about 70 per cent. The most common causes of cirrhosis were alcohol
abuse and chronic HCV infection, and there was not a single case of
chronic HBV infection. Most patients presented with cancer but no
history of cirrhosis. In HCC, prognosis is usually very poor, and the
results of screening for HCC in cirrhosis patients have been
disappointing. Thus, prevention of cirrhosis (e.g., by reducing alcohol
consumption), treatment of chronic HCV infection and, in certain cases,
vaccination against HBV, is an approach likely to have the greatest
impact on the incidence of HCC.
Liver Scarring Not
Always Permanent
Study shows surgery reverses cirrhosis in some patients
By Adam Marcus
HealthScout Reporter
THURSDAY, Feb. 8 (HealthScout) -- Scars built up by chronic insults
to the liver can disappear over time with surgery, says a new study from
French researchers.
Patients with extensive liver damage who had their bile ducts
unblocked showed far less scarring in the years following the procedure,
the scientists say.
The findings, which appear in this week's issue of The New England
Journal of Medicine, could be especially important for people with
hepatitis C, a liver-eroding virus that may infect as many as 4 million
Americans. Of those, 20 percent to 40 percent will suffer serious liver
scarring, or cirrhosis.
Liver scarring was long believed to be irreversible. Once damaged by
alcohol or infection, a transplant was the only way to reach full
recovery.
But mounting evidence suggests the liver can indeed regenerate itself
after the offending problem is eliminated.
In the latest work, researchers at Beaujon Hospital in Clichy
followed 11 men with severe liver scarring from chronic pancreatitis, an
inflammation that ultimately blocked their bile ducts.
Doctors surgically drained the bile ducts in all of the patients, but
blockages returned in two. Of the remaining nine, liver tissue samples,
taken an average of 2.5 years later, showed the organ was less scarred
in six of the patients while two had significant improvement. In the
three others, the damage didn't worsen.
The study didn't include a control group of patients who weren't
treated, so it's not clear if the men might have improved on their own.
Still, the researchers write, the results show cirrhosis "may regress"
after duct drainage.
Dr. Scott Friedman, a liver expert and co-author of an editorial
accompanying the study, says the French work "is one of the better
studies that really indicate in a careful way that when the inciting
stimulus is removed, the scarring can decrease. The accumulation of scar
is not as irreversible as previously believed."
While the French scientists only looked at cirrhosis linked to
pancreatic inflammation, liver scarring is the same regardless of its
cause, Friedman says. So the findings could also apply to alcohol abuse,
hepatitis C and hepatitis B, he says.
Researchers must now identify why scarring occurs more rapidly in
some patients than others, and why some livers rebound more quickly,
Friedman says.
But not every expert was impressed with the French report.
Dr. Mitchell Schiffman, a liver specialist at the Medical College of
Virginia in Richmond, says the reversibility of liver scarring is common
knowledge in the field, and he was skeptical about the relevance of the
latest findings.
"It doesn't mean that cirrhosis is reversible. Some studies show that
cirrhosis disappeared, but I'm not sure how many people believed it,"
Schiffman says.
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