HCV Advocate DDW 2009 Coverage
Updated
·
Liver disease: Better monitoring, better
prognosis
·
Advances being made in the treatment of hepatitis
·
Clinic study links liver disease to cancer
·
Telaprevir Improves HCV Clearance in Resistant
Patients
·
Breath Test Could Help Assess Liver Function
Liver disease: Better monitoring, better prognosis
Health outcomes explored at DDW 2009
"The research being
presented during DDW shows how widespread our efforts are in understanding and
treating liver disease," said Brent Tetri, MD,
DDW is the largest
international gathering of physicians and researchers in the fields of gastroenterology,
hepatology, endoscopy and gastrointestinal surgery.
Text Messaging Reduces Rejection in Pediatric Liver
Transplant Recipients (Abstract #175)
Text messaging may improve compliance
rates in pediatric liver transplant recipients, reduce organ rejection and
provide significant cost savings with medications and hospitalizations,
according to a new study. Children and adolescents who receive liver
transplants often have trouble remembering to take their medication regularly;
in addition to being less vigilant than adults, liver patients also suffer
memory problems. Missing medication is especially dangerous since their bodies
can reject the transplanted liver after only two missed doses of medication.
But because young people are generally technologically savvy, researchers
sought to determine whether sending text messages would result in improved
adherence.
The study looked at 41 young
people who were on average 15 years old and at various stages after receiving a
liver transplant. The MediM AS system from CareSpeak Communications, which
funded the study, was used to decide which time of day patients/or caregivers
preferred to receive a medication reminder via text message, which were then
sent accordingly. To ensure that patients not only received the message but
also took their medication, patients had 15 minutes to send a reply text
confirming intake. If they did not,
To determine the
effectiveness of the text reminders, researchers looked at two factors: the
level of medication in the patient's blood and whether their bodies rejected
the liver transplant. Patients who took medication erratically had a higher
deviation of medication in their blood, compared to patients who took their
medication regularly. In the year prior to the study, 12 of 41 patients
experienced rejection that required hospitalization and treatment because the
patient's body rejected the transplant due to improper medication dosage. But
one year into this study, just two patients suffered rejection of the liver.
Lead investigator Tamir
Miloh, MD, assistant professor in pediatric hepatology and surgery at
Previous studies have looked
at the effectiveness of text reminders, but not on liver patients and not on a
scale of this size.
Dr. Miloh will present these
data on Sunday, May 31 at
The Point of Care 13C Methacetin Breath Test
Accurately Predicts Long Term Prognosis with Chronic Liver Disease: A
Non-Invasive Liver Function Test (Abstract #S1837)
Researchers at the
Previously, prognosis in
patients with chronic liver disease has been determined by using a combination
of blood tests. However, this method is limited to predicting prognosis for up
to three months and may only change after a life threatening complication has
occurred.
Using a test called the
13C-Methacetin breath test, a rapid, non-invasive procedure, investigators were
able to accurately predict the survival of liver disease patients for a period
of up to two years. The test is conducted with the patient drinking a cup of
water containing a dissolved substrate. The device then measures the appearance
of tagged CO2 (the product of the hepatic metabolism of the 13C-Methacetin) in
the exhaled breath; the patient does not do anything except sitting and
breathing normally.
Studying 575 patients with
varying types and degree of liver disease, investigators showed that the breath
test can predict which patients will develop complications that will affect
their prognosis.
"The potential for this
test is tremendous," said
Researchers believe that the
accuracy of the test, and its capacity to assess liver function, makes the
breath test a potentially powerful new tool in predicting prognosis of liver
related complications, prioritizing patients for organ transplantation, and
predicting their ability to survive surgery.
Dr. Lalazar will present
these data on Sunday, May 31 at
Cumulative Incidence and Risk Factors of
Hepatocellular Carcinoma (
There is a significant risk of
developing of liver cancer in patients with nonalcoholic steatohepatitis, or
NASH, according to a study from the Cleveland Clinic. The study also found that
mild alcohol consumption may significantly increase the risk of developing
liver cancer in patients with end stage liver disease.
NASH is one of two stages of
non-alcoholic fatty liver disease, the most common liver disease in the
In a retrospective study of
more than 500 patients with either HCV-cirrhosis (hepatitis C) or
NASH-cirrhosis over a three year period, researchers found that 20 percent of
patients with HCV-cirrhosis and 12.8 percent of patients with NASH-cirrhosis
developed hepatocellular carcinoma (liver cancer). The annual risk for
developing liver cancer in HCV patients is 4 percent per year and that of NASH
patients is 2.6 percent per year. The annual risk for NASH patients was
previously unknown. While the rates are higher for patients with HCV, the risk
of developing liver cancer for NASH patients is significant.
Investigators also sought to
identify modifiable risk factors in effort to potentially reduce the burden of
liver cancer in this patient population. They found that even mild alcohol
consumption may significantly increase the liver cancer risk in patients with
end-stage liver disease.
"This study offers
valuable insight into the care of patients with NASH," said Nizar N. Zein,
MD, chief of hepatology and medical director of liver transplantation at the
Cleveland Clinic. "Not only do we need to adjust the way we follow these
patients, including tracking and preparing for the potential development of
liver cancer, but we may also need to counsel this patient population against
any alcohol intake given its risk."
Dr. Zein will present these
data on Monday, June 1 at
Public Awareness and Attitudes towards Non Alcoholic
Fatty Liver Disease (NAFLD) (Abstract #T1006)
Patient awareness of
non-alcoholic fatty liver disease (NAFLD) and its complications is poor and
must be improved to ensure prevention, detection and treatment of the
condition. NAFLD is the most common cause of abnormal liver enzymes and one of
the most common causes of cirrhosis of the liver in the
Researchers conducted a
survey of 5,000 outpatient adults asking about awareness levels of NAFLD and
its risk factors. Ninety-eight percent of the patients said their physicians
had never talked about NAFLD with them. By contrast, a previous study on
colorectal cancer found that 40 percent were aware of that disease and its risk
factors.
"It is both disturbing
and significant that a surprisingly high number of respondents were uninformed
about this silent but deadly disease," said Sury Anand, MD, chief of
gastroenterology at
The survey also found that 95
percent did not realize that fat in the liver could cause serious health
problems and 80 percent had never heard of cirrhosis. Dr. Anand said prevention
is especially critical since treatment options for NAFLD are limited. Public
awareness of NAFLD must rise to the level of other chronic diseases and
conditions, which can best be achieved with the active participation of primary
care physicians, pediatricians and other providers in counseling their patients
to adopt preventive lifestyle modifications.
He recommends that doctors
encourage patients to maintain healthy weight by having a good balanced diet
and regular exercise to fend off NAFLD in the similar way that patients need to
limit their carbohydrate intake in order to prevent prediabets and diabetes.
The study subjects were all from
Dr. Nan Sandar will present
these data on Tuesday, June 2 at
Advances being made in the treatment of hepatitis
Health outcomes explored at DDW 2009
CHICAGO, IL (June 2, 2009) –
Researchers are making great strides in the development of new treatments for
hepatitis and in confirming the effectiveness of current treatments, according
to several studies being presented at Digestive Disease Week® 2009 (DDW®).
"Only about half of the
patients infected with hepatitis B and C respond to currently used
treatments," said Nicholas J. Shaheen, MD,
Hepatitis is an inflammation
of the liver that usually produces swelling, tenderness and sometimes permanent
damage. Hepatitis B can be spread from mother to child at birth or soon after
and through sexual contact, contaminated blood transfusions and needles.
Hepatitis C, the most common form of viral hepatitis, can be spread through
blood transfusions and contaminated needles, but for a substantial number of
patients, the cause is unknown. Both forms of viral hepatitis may lead to cirrhosis,
or scarring, of the liver.
DDW is the largest
international gathering of physicians and researchers in the fields of
gastroenterology, hepatology, endoscopy and gastrointestinal surgery.
Tenofovir Disoproxil Fumarate (TDF) Versus
Emtricitabine Plus TDF (FTC/TDF) for Treatment of Chronic Hepatitis B (
Two year follow-up data from
this ongoing trial demonstrate that hepatitis B (HBV) patients with persistent
viremia (presence of virus of blood) while receiving adefovir dipivoxil (
At week 96, HBV
"These data expand upon
the safety and efficacy findings from the TDF hepatitis B pivotal trials,"
said David Oldach, MD, director of clinical research at Gilead Sciences, Inc.
"Tenofovir disoproxil fumarate has demonstrated consistent efficacy across
a broad range of chronic hepatitis B patients, including patients with
preexisting resistance mutations or prior suboptimal response to adefovir
dipivoxil, patients with cirrhosis, and patients with any of the major HBV
genotypes. An additional very promising finding in the registrational trial
among HBeAg positive patients has been hepatitis B surface antigen loss, occurring
in 3 percent of TDF recipients in one year and 6 percent in two years
time."
Continued Dr. Oldach,
"The data to be presented review outcomes from the first two years of a
three and a half year study. While we cannot predict future treatment outcomes,
we hope and expect that the participants will continue to receive durable
benefit from this therapy."
Dr. Oldach will present these
data on Monday, June 1 at
The Long Term Effects of Interferon Based (IFNTx)
Therapy on Hepatic Histology in Patients with Chronic Hepatitis C Virus.
Results of a Five Year Prospective Evaluation on Fibrosis Progression and
Fibrosis Regression (Abstract #7)
Interferon or peginterferon
with or without ribavirin (IFNTx) should be the standard treatment for patients
with hepatitis C (HCV), according to a study presented by researchers from the
"The use of interferon
or peginterferon for the treatment of patients with hepatitis C can have a
dramatic improvement on the histology of the disease, including the
disappearance of cirrhosis," summarized Richard Sterling, MD, MSc,
Professor of Medicine,
Researchers conducted a
longitudinal cohort study to evaluate the use of IFNTx on liver histology in
patients with chronic HCV. Seven hundred and fifty five patients underwent
liver biopsy and received a single course of IFNTx or no treatment. Of these
patients, 230 were followed for five years without additional treatment (41
patients declined treatment and 189 received IFNTx without obtaining sustained
virologic response) before undergoing a repeat liver biopsy. An additional 102
patients who received IFNTx and obtained sustained virologic response (
There were no significant
differences in worsening of inflammation or fibrosis scores between those who
did not undergo treatment or did not have an
Dr. Mitchell Shiffman will
present these data on Sunday, May 31 at
For the first time,
researchers have shown that patients with hepatitis C (HCV) genotype 1 who do
not respond to standard treatment can obtain a sustained virologic response
using a combination regimen of telaprevir (T) plus peginterferon-alfa-2a (P) ±
ribavirin (R). About 70 percent of patients who had relapsed on previous HCV
treatment experienced sustained virologic response and about 40 percent of
patients who previously had not responded to treatments experienced sustained
virologic response. Patients who had not responded to previous treatments
needed to undergo 48 weeks of treatment with T/PR. The sustained virologic
response rate was significantly higher in all treatment groups receiving T/PR
regimens compared with those receiving placebo plus PR48.
"This is a very
important and unique trial," said Adrian M. Di Bisceglie MD, FACP,
chairman of the department of internal medicine and chief of hepatology at the
Saint Louis University School of Medicine, and lead investigator of the study.
"Since a large majority of hepatitis C patients do not experience a
sustained response to current treatments, it is necessary to identify new drugs
and treatment regimens to help better the chances of patients clearing the
disease from their systems. The results of this trial bring us closer to
understanding how to do that."
In the PROVE3 study, 453
patients were randomized to receive T/PR for12 weeks followed by PR for 12
weeks (T12/PR24); T/PR for 24 weeks followed by PR for 24 weeks (T24/PR48); T/P
for 24 weeks (T24/P24); or placebo/PR for 24 weeks, then PR for 24 weeks. Of
the participants, 235 (52 percent) completed their assigned treatments. Many of
the patients included in the intent-to-treat analysis had baseline
characteristics know to be associated with poor response to treatment,
including 196 (43 percent) with cirrhosis or bridging fibrosis, 418 (92
percent) with baseline serum HCV RNA ≥ 800,000 IU/mL, and 40 (9 percent)
were African American.
The general safety profile of
T12/PR24 compared with T24/PR28 was similar to that observed in treatment naïve
patients. Patients in the T12/PR24 or T24/PR48 group experienced greater
frequency of fatigue, nausea, headache, rash, pruritus, diarrhea, anemia,
insomnia, fever, hair loss and chills thank those treated with placebo followed
by PR48. Of those patients discontinuing treatment due to adverse events, 11
(10 percent) were in the T12/PR24 group, 29 (25 percent) were in the T24/PR48
group, 10 (9 percent) were in the T24/P24 and five (4 percent) were in the
placebo plus RP48 group.
"We are continuing to
study these treatment combinations in a phase
Approximately 80 percent of
HCV patients in the
This study was funded by
Vertex Pharmaceuticals.
Dr. Di Bisceglie will present
these data on Tuesday, June 2 at
Digestive Disease Week® 2009 (DDW®) is the largest
international gathering of physicians, researchers and academics in the fields
of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.
Jointly sponsored by the American Association for the Study of Liver Diseases
(AASLD), the American Gastroenterological Association (
Clinic study links liver disease to cancer
Angela Townsend/Plain Dealer Reporter
People who suffer from the most
serious form of nonalcoholic fatty liver disease have a significant risk of
developing liver cancer, researchers at the Cleveland Clinic have found.
The findings were presented
Monday at Digestive Disease Week in
Nonalcoholic fatty liver
disease is the most common liver disease in the
The disease is so named
because of the accumulation of fat in the liver -- without an excessive amount
of alcohol as the cause. The liver also becomes inflamed and scarred.
Researchers looked at
patients with the most serious form of the disease, nonalcoholic
steatohepatitis, or NASH. About 20 percent of patients with NASH go on to
develop cirrhosis of the liver. (Cirrhosis of the liver is also caused by
alcohol abuse -- which accounts for most cirrhosis cases -- and other
conditions such as hepatitis B and C.)
"We suspected that
having cirrhosis from fatty liver disease would lead to liver cancer, but that
wasn't defined before," said Dr. Nizar Zein, the Clinic's chief of
hepatology and medical director of liver transplantation.
The research was conducted by
Mustafa Ascha, a student at Case Western Reserve University for whom Zein
serves as a mentor.
It wasn't until the 1980s
that much was known about fatty liver disease. And until recently, alcohol was
blamed as the sole cause.
Cirrhosis of the liver causes
hepatocellular carcinoma, the most common form of liver cancer and the fifth
most common cancer worldwide.
The Clinic study followed 510
patients with liver cirrhosis from 2003 to 2006. About 38 percent (195)
suffered from NASH. The other 62 percent had hepatitis C.
The two goals were to see if
patients would develop liver cancer, and if that risk could be quantified.
The answers were
"yes" and "yes."
Nearly 13 percent of the NASH
patients developed cancer over the course of the study.
Per year, 2.6 percent of the
patients developed liver cancer. If that pattern holds true, more than
one-fourth (27 percent) will develop liver cancer after 10 years, Zein said.
In comparison, about 20
percent of the hepatitis patients developed liver cancer, at an annual rate of
4 percent per year.
But a diagnosis of liver cancer
isn't necessarily an automatic death sentence. Found early, it can be treated,
Zein said.
Those at highest risk for
liver cancer are older people and people who drink alcohol, even in small
quantities.
Zein said he counsels fatty
liver disease patients to avoid alcohol completely, but added the opinion is
not "universal."
The Clinic is one of only a
few institutions that have followed a large population of people with the
disease. To date, the Clinic's study is the largest, Zein said.
Measuring the cancer risk not
only will raise awareness about the dangers of nonalcoholic fatty liver
disease, but also will help physicians decide how often people with the disease
should be screened for cancer, Zein said.
Telaprevir Improves HCV Clearance in Resistant Patients
By Todd Neale, Staff
Writer, MedPage Today
Reviewed by Dori F. Zaleznik, MD; Associate Clinical
Professor of Medicine,
Dorothy Caputo, MA, RN, BC-
CHICAGO, June 3 -- The
investigational protease inhibitor telaprevir, added to standard hepatitis C
(HCV) treatment, produced a sustained virologic response in about half of
patients who had previously failed with conventional therapy, a phase IIb trial
showed.
Patients who received
telaprevir, peginterferon, and ribavirin had higher response rates than those
who received peginterferon and ribavirin alone, the current standard treatment,
according to Adrian Di Bisceglie, M.D., of
The group of patients
who received telaprevir and peginterferon, but not ribavirin had less of a
benefit than those who received all three drugs, he reported at Digestive
Disease Week here.
Because there is no
existing standard of care for patients who fail to respond to standard
treatment for HCV, he said, "I personally believe this . . . represents a
new paradigm for how we will treat nonresponders in the future."
About three million
people in the
Conducted at 53
centers, the PROVE3 (Protease Inhibition for Viral Evaluation) study follows the
PROVE1 and PROVE2 studies, which evaluated the effect of telaprevir in
treatment-naive patients. (See EASL: Telaprevir Shows Promise of Shortened
Hepatitis C Therapy and AASLD: Telaprevir Yields Good Response in Combo Therapy
for HCV)
PROVE3 involved 453
patients with HCV genotype 1, the most common in the
The patients were
randomized to four treatment arms with varying duration of treatment with
telaprevir, peginterferon, and ribavirin:
·
12 weeks of all
three drugs followed by 12 weeks of standard treatment
·
24 weeks of all
three drugs followed by 24 weeks of standard treatment
·
24 weeks of
telaprevir and peginterferon, but no ribavirin
·
24 weeks of
placebo plus standard treatment followed by 24 weeks of standard treatment
(control)
The median age of the
patients was 51 and about two-thirds were male. All four groups were
well-matched according to baseline characteristics.
The primary endpoint
was sustained virologic response 24 weeks after the end of each treatment
regimen.
All three telaprevir
groups were superior to placebo in the percentage of patients who had a
sustained virologic response at follow-up:
·
51% in patients
who received 12 weeks of telaprevir (P<0.001)
·
52% in those who
received telaprevir for 24 weeks along with standard treatment (P<0.001)
·
23% in those who
did not receive ribavirin (P=0.035)
·
14% in the
controls
Similar benefits were
seen at four weeks, indicating a rapid virologic response, and immediately at
the end of treatment.
Some patients relapsed
between the end of treatment and the follow-up, 24 weeks later. The relapse
rates were 30% and 13% in the two groups that received telaprevir plus standard
treatment and 53% in both the group that did not receive ribavirin and the
controls.
Notably, almost 40% of
patients who had not responded to treatment at all before the study showed a
sustained virologic response at follow-up in the two groups that received all
three drugs (P<0.001 for both). That compared with only 9% of the controls.
Response rates of 69%
and 76% were seen among prior relapsers (P<0.001 for both), with the higher
rate occurring in those who received 48 weeks of standard treatment in addition
to 24 weeks of telaprevir.
There was no difference
in response rates between patients with and without cirrhosis.
"It appears that
telaprevir is able to overcome this and other traditional poor response
factors," Dr. Di Bisceglie said.
The most common adverse
events in groups receiving telaprevir were fatigue, nausea, headache, rash,
itching, anemia, and gastrointestinal side effects, only some of which were
severe enough to result in discontinuation.
The dosing regimen
involving 24 weeks of all three drugs, followed by 24 weeks of peginterferon
and ribavirin, is currently being evaluated in a phase
Dr. Di Bisceglie said
FDA approval for telaprevir is about two years away. Telaprevir and a similar
drug, boceprevir, appear to be the closest to approval.
Patients with
significant liver disease should receive treatment with peginterferon and
ribavirin right away, he said, but patients who have previously failed a course
of treatment might think about waiting for these drugs to hit the market.
"These drugs are
coming and not that far away, and it may be better to be waiting with our
nonresponders for better treatment," he said.
The study was supported
by Tibotec and Vertex Pharmaceuticals, co-developers of telaprevir.
Dr. Di Bisceglie
reported no conflicts of interest.
Primary source: Digestive Disease Week
Source reference:
Di Bisceglie A, et al
"
HIV-HCV Coinfected and HCV Monoinfected Patients with Genotype 2-3 Respond Equally Well to 24 Weeks of Pegylated Interferon plus Ribavirin
http://www.hivandhepatitis.com
Liz Highleyman
Standard therapy for
chronic hepatitis C virus (HCV) infection in HIV negative people is 24 weeks of
pegylated interferon plus weight-adjusted ribavirin for those with HCV
genotypes 2 or 3, and 48 weeks for those with harder-to-treat genotypes 1 or 4.
Current guidelines indicate
that HIV positive patients should receive combination anti-HCV therapy for 48
weeks regardless of HCV genotype. But coinfected individuals with genotypes 2
or 3 can achieve good outcomes with the shorter 24-week course, according to
data presented at the annual Digestive Disease Week (DDW 2009) meeting this
week in
Jean-Jacques Gonvers
and colleagues from
The study included 85
HCV monoinfected participants (38 with genotypes 1, 4, or 5; 47 with genotypes
2 or 3) and 47 HIV-HCV coinfected patients (23 with genotypes 1, 4, or 5; 24 with
genotypes 2 or 3). About 60% of the coinfected participants were on HAART.
Patients with genotypes
1, 4, or 5 were treated for 48 weeks with 180 mcg/week pegylated interferon
alfa-2a (Pegasys) plus 1000-1200 mg/day ribavirin, with doses adjusted according
to body weight. Patients with genotypes 2 or 3 received the same dose of
Pegasys plus 800 mg/day ribavirin (regardless of weight) for 24 weeks.
Results
·
In an
intention-to-treat analysis of participants with genotypes 1, 4, or 5, the
·
Looking at
patients with genotypes 2 or 3, 70% of HCV monoinfected patients and 67% of
HIV-HCV coinfected patients achieved
·
Undetectable HCV
RNA at week 4 -- known as rapid virological response (RVR) -- had a positive
predictive value (PPV) for
o
.78 for HCV
monoinfected patients with genotypes 1, 4, or 5;
o
.81 for HCV
monoinfected patients with genotypes 2 or 3;
o
.76 for HIV-HCV
coinfected patients with genotypes 2 or 3.
·
22 patients (36%)
with genotypes 1, 4, or 5 did not complete the study for various reasons (lack
of response at week 12, withdrawal of consent, adverse events, death) compared with
12 patients (17%) with genotypes 2 or 3.
These findings led the
researchers to conclude, "Genotypes 2 and 3 predict the likelihood of
"In coinfected patients
with genotypes 2 and 3, a 6-month treatment has the same efficacy as in
monoinfected patients," they continued. "Undetectable HCV RNA at week
4 has a good positive predictive value of
Finally, they
recommended, "Aggressive treatment of adverse effects to avoid withdrawal
or treatment stop is crucial."
Centre Hospitalier Universitaire Vaudois and
University of Lausanne, Lausanne, Switzerland; University of Basle, Basle,
Switzerland; University of Zurich, Zurich, Switzerland; Hospital of La Chaux-de-Fonds,
La Chaux-de-Fonds, Switzerland; Hospital of Lugano, Lugano, Switzerland;
Private Practice, Winthertur, Switzerland.
Reference
JJ Gonvers, MH Heim, M
Cavassini, and others. In HIV-HCV Co-Infected Patients with HCV Genotype 2 or 3
Infection a 6-Month Treatment with Peginterferon Alpha Plus Ribavirin Has the
Same Efficacy As in Mono-Infected Patients. Digestive Disease Week (DDW 2009).
Breath Test Could Help Assess Liver Function
By Todd Neale, Staff
Writer, MedPage Today
Reviewed by Zalman S.
Agus, MD; Emeritus Professor
University
of
Patients divided into
high, medium, and low-risk groups according to the breath test had two-year
survival rates of 98.9%, 89.7%, and 73%, respectively, Gadi Lalazar, M.D., of
The test might be able
to add predictive value to the Model for End-Stage Liver Disease (MELD), he
said.
Among patients with
relatively high MELD scores of 17 and 18, a one-point increase in the breath
test score was associated with a 30% higher risk of death.
The new test could be
used to assess prognosis from the earliest stages of liver disease to
cirrhosis, to help doctors determine whether a cirrhotic patient has enough
liver function to undergo a surgical procedure, to prioritize patients for
liver transplantation, and perhaps to decide when patients need to start
therapy for chronic viral hepatitis, Dr. Lalazar said.
Brent Tetri, M.D., of Saint
Louis University, a moderator at the press briefing where the findings were
presented, said, "The liver does so many hundreds of different things, it
would be very nice to have a good, simple test where we can just assign a
number to how a liver's functioning."
Although MELD is able
to predict prognosis in chronic liver disease, it is based on several blood
tests and only estimates three-month risk.
In addition, patients
with similar MELD scores will sometimes have different disease courses -- some
will decompensate and die and others will not, according to Dr. Lalazar.
And often, the MELD
score will only rise after a complication has occurred, at which point it's too
late to prepare the patient for transplantation, he said.
So Dr. Lalazar and his
colleagues assessed the predictive ability of the 13C-methacetin breath test.
Here's how it works:
The patient drinks a solution containing methacetin, which is exclusively
metabolized by the liver. He then sits and breathes normally. A nasal cannula
measures exhaled carbon dioxide tagged with 13C for 15 minutes.
The changes in the
amount of 13C exhaled allow the researchers to assess liver function.
The researchers gave
the test to 575 patients with chronic liver disease of different etiologies. About
two-thirds were the result of hepatitis C. More than a third (36.3%) were cirrhotic.
After two years, 25
patients had died from both liver-related and non-liver-related causes.
A survival model was
constructed containing age, percent dose of methacetin recovered at 15 minutes
(
The model significantly
predicted survival (P<0.0001) such that those with high scores had a
two-year survival rate of 98.9%. Those with medium scores had a survival rate
of 90%, and those with low scores had a survival rate of 73%.
In cirrhotic patients
the test was also discriminatory with survival rates of 97%, 85% and 70% at 24
months respectively (P=0.0171).
Dr. Lalazar and
colleagues found that the addition of the scores from the breath test helped
predict mortality risk even within MELD categories.
Further research is
needed, however, before determining whether patients flagged for increased risk
by breath test should be get priority in treatment.
That the variability
between breath tests in a single patient was about
11%, a consistency rate which Dr. Tetri called "pretty good."
There were no
tolerability issues, according to Dr. Lalazar.
The study was supported
in part by Exalenz Bioscience, which developed the breath test. One of the
study authors is the medical director for the company.
Dr. Lalazar reported no
conflicts of interest.
Dr. Tetri reported
serving on advisory committees or review panels for Amylin Pharmaceuticals,
Gilead Sciences, and Vertex Pharmaceuticals.
Source reference:
Lalazar G, et al
"The point of care 13C methacetin breath test accurately predicts
long-term prognosis in patients with chronic liver disease: a non-invasive
liver function test" DDW 2009; Abstract S1837.