Hello folks,
Its a cold snowy day here in Michigan, hope its warmer in your part of the world
Welcome to
HCV rewind, a weekly digest of news, research and a look at today's headlines.
Interferon Free
Published recently online at
Medscape, is a look into the therapeutic options beyond interferon for the treatment of hepatitis C, presented by Catherine AM Stedman.
Current Prospects for Interferon-free Treatment of Hepatitis C in 2012
Published Jan 22 2013 in
Journal of Gastroenterology and Hepatology
Numerous other DAAs are in clinical development, and
phases 2 and 3 trials are evaluating interferon-free combination DAA therapy.
Interferon-free sustained virologic responses have now been
achieved with combinations of asunaprevir and daclatasvir; sofosbuvir and
ribavirin; sofosbuvir and daclatasvir; faldaprevir and BI207127; ABT-450,
ritonovir and ABT-333; ABT-450, ritonovir and ABT-072; miracitabine, danoprevir
and ritonavir; and alisporivir and ribavirin.
Some drugs are
genotype-specific in their activity, whereas others are pan-genotypic, and
differential responses for the genotype 1 subtypes 1a and 1b have emerged with
many DAA combinations. Viral breakthrough and resistance are important
considerations for future trial design. The prospect of
interferon-free combination DAA therapy for hepatitis C virus is now finally
becoming a reality.
Continue reading at
Medscape or here on the
blog.
Updates Telaprevir
Futility rules defined for telaprevir-based HCV therapy
Therapy with telaprevir, peginterferon, and ribavirin should be stopped in both treatment-naive and treatment-experienced patients with hepatitis C virus infection if HCV RNA levels are greater than 1,000 IU/mL at week 4 or 12 of treatment, according to new futility rules developed using phase II and III trial data.
The rules are important for preventing needless drug exposure and to minimize the development of drug-resistant variants in patients with little or no chance of achieving sustained virologic response, reported Dr. Nathalie Adda of Vertex Pharmaceuticals Inc., Cambridge, Mass., and her colleagues.
Continue reading @
GI and HEPATOLOGY News
Pegylated interferon and ribavirin
Reported by
Reuters; About one in six of the estimated 5 million U.S. patients with chronic hepatitis C (HCV) has a contraindication to standard treatment with pegylated interferon and ribavirin, researchers say.
The study published online January 7 in
Alimentary Pharmacology & Therapeutics included 45,690 hepatitis C patients diagnosed between 2004 and 2009, a reported 7,903 or 17.3% were found to have contraindications to therapy. Notably the majority - 6,928, (87.6%) had only one contraindication.
The most common contraindications were bipolar disorders (6.5%), anemia (5.9%), and pregnancy (1.9%). The study concluded, "Clinical assessment of contraindications as relative and/or modifiable should be considered and used to determine if patients could benefit from current pegylated-interferon–containing triple therapy or future pegylated-interferon– or ribavirin-free regimens.
"Dr. Andrew H. Talal from the State University of New York, Buffalo, told Reuters Health by email. "The fact that the majority of the contraindications are reversible or readily treatable was another surprising aspect."
This study was funded in part by Genentech Inc. and F. Hoffmann-La Roche Ltd; some of the authors are employees of Genentech.
Read the article here, or the full text published in
Alimentary Pharmacology & Therapeutics.
In Todays News - Treatment response improved neurocognitive function in patients with chronic HCV
Patients with chronic HCV who responded to treatment with pegylated interferon and ribavirin experienced a subsequent improvement to neurocognitive performance in a recent study.
Continue reading....
Hepatitis C In Elderly Patients
Commentary:
efficacy and safety of ribavirin plus pegylated interferon-alpha in geriatric
patients with chronic hepatitis C
The study of Hu
et
al. from Taiwan
adds evidence on the safety and efficacy of treatment with pegylated
interferon-alpha plus ribavirin (PR) in elderly patients with chronic
hepatitis C virus (HCV) infection.......
Possibly the
development of new all oral HCV therapies with direct-acting antivirals will
become the standard of care in the difficult to treat HCV patients, including
the elderly.
Read more here.....
Research - Hepatitis C Genotypes
New Ways to Study HCV, Genotypes 3 and 4
Posted on
January 21, 2013
by
Kristine Novak, PhD, Science Editor
Researchers can now study replication of Hepatitis C virus genotypes 3 and 4 in cultured cells, described in 2 articles in the January issue of Gastroenterology. These new tools will improve our understanding of how they cause liver disease, and could lead to new treatments.
There are 6 major HCV genotypes. Genotypes 1 and 2 are the most prevalent in North America, Europe, and Japan, and are the most highly studied. However, other genotypes have specific characteristics. Genotype 3a infection can cause hepatic steatosis, and is more resistant to treatment with telaprevir and boceprevir. Genotype 4 is prevalent in the Middle East and many African countries, and is becoming more common in central and northern Europe; it accounts for 93% of HCV infections in Egypt, and 5%–15% of infections in several European countries....
Continue reading....
Today From Medscape
IL28B Polymorphisms Predict Response to Therapy Among Chronic Hepatitis C Patients With HCV Genotype 4
Discussion Only
View full text @ Medscape
This study confirms that SNP near
IL28B strongly predicts virological response to therapy among chronic hepatitis C with HCV-4. Although HCV-4 was initially branded as a 'difficult-to-treat' genotype, recent data, especially from Egypt, where HCV-4 represents >90% of HCV infections,
[14] have suggested SVR rates between 43 and 70%, that is, intermediate between those reported for HCV-1 and HCV-2 or HCV-3.
[14]
Major factors influencing response are Egyptian origin, absence of advanced fibrosis and insulin resistance – measured as homoeostasis model assessment of insulin resistance or homoeostasis model assessment of insulin resistance (HOMA-IR).
[15]
As multivariate analyses have shown that polymorphisms near
IL28B are the strongest predictors of response to therapy among HCV-1, and much less so in HCV-2 and -3,
[3–7] the interest of studying these genetic variants as predictors of response in HCV-4 is obvious. The amount of available data is, however, limited and often gathered on ethnically heterogeneous populations of patients. Three series reported patients monoinfected with HCV: one analysed 102 cases from Austria (97% from Egypt),
[8] another on 103 patients from Milan, Italy (68% from Egypt)
[9] and a third on 82 patients from different ethnic groups (51% Egyptians, 34% Europeans and 13.4% Sub-Saharan Africans).
[10] These studies identified several baseline predictors of SVR in HCV-4: female sex,
[9]rs12979860 CC genotype,
[8–10] Egyptian ethnicity,
[9] low stages of liver fibrosis
[8,9] or low viral load.
[8,10]
In two additional studies on small series of patients (
n = 13 and
n = 23, respectively) coinfected with HCV and HIV
[11,12] suggest that both viremia and low stages of fibrosis predicted response independently of
IL28B SNP, although in the larger study patients with HCV-1 and HCV-4 were pooled together, rendering the analysis difficult. Our present study, the largest to date on patients of homogeneous ancestry (all from Middle East), confirms the strong predictive value of
IL28B genotypes on SVR, and, indeed, predictors of SVR were similar to those previously reported, with the exception of SNP at marker
rs12979860 being replaced by
rs8099917. In our series, in fact, both the absence of advanced fibrosis and polymorphisms near
IL28B were independent predictors of SVR, confirming that algorithms of treatment for HCV-4 should include at least these two variables.
Additional prospective analyses are warranted to ascertain whether on-treatment variables should also be considered, for example, to tailor therapy duration in patients with rapid virological response (RVR). In general, in HCV-monoinfected patients with HCV-4,
IL28B polymorphisms do not seem to predict SVR in patients who have achieved RVR.
[8,9] However,
IL28B genotype may be included in treatment algorithms to tailor therapy among patients who have failed to achieve RVR.
[9] In the study from Milan,
[9] HCV-4 non-RVR patients with CT/TT genotypes at marker
rs12979860 had SVR rates as low as 23%, compared with 75% reached by patients with the CC genotype. These Authors stated that lack of RVR in patients with unfavourable
IL28B genotypes should not be considered as a univocal stopping rule; however, premature therapy termination should be considered in cases with severe treatment side effects, poor motivation or severe comorbidities.
[9] In our study, we could not collect data on RVR.
Thus, also given the small sample size of studies conducted so far, additional prospective studies are warranted to assess the predictive value of
IL28B polymorphisms on the virological response to therapy among HCV-4, possibly assessing the impact of liver fibrosis stage, HOMA-IR score and on-treatment viral response relative to
IL28B genotypes.
Thus,
IL28B polymorphisms are strong predictors of virological response also in chronic hepatitis C with HCV-4, confirming previous reports
[8–12] and extending data on spontaneous eradication.
[15] Interestingly,
IL28B SNP do not seem to predict viral response to therapy among patients with HCV-5 from the same genetic ancestry as the present study.
[16] Whether these polymorphisms may be used to tailor therapy duration in patients with HCV-4 remains to be determined by larger prospective studies.
Free registration required,
full text available here
Do HCV Patients Still Need A Liver Biospy In 2013?
Over at
CCO the age old debate lives on rather hepatitis C patients still need a liver biopsy for assessing liver damage, in the article one physician is satisfied with today's non-invasive methods, Mark S. Sulkowski MD writes; "With interferon-free, all-oral therapies on the near-term horizon, I am increasingly comfortable relying on patient history, physical exam, routine laboratory tests, and liver imaging as well as noninvasive serum markers to obtain a picture of liver health.."
View all links to the article
here, along with a review of imaging technology developed by Mayo to detect liver fibrosis called Magnetic Resonance Elastography, or MRE.
2013-Guide to Clinical Trials for People with Hepatitis C
This month
TAG published an insightful second edition guide to hepatitis C clinical trials, written by Tracy Swan and Matt Sharp.
Of Interest
A Study of
TMC435 in Combination With PSI-7977 (GS7977) in Chronic Hepatitis C Genotype
1-Infected Prior Null Responders To Peginterferon/Ribavirin Therapy or HCV
Treatment-Naive Patients
Hepatitis C - 8 Clinical Trials For: Sofosbuvir (GS-7977)
Hepatocellular carcinoma (HCC)
This week in an analysis of HALT-C data, investigating the surveillance of liver cancer in academic centers published by the
American Journal of Gastroenterology, reported only 20% of hepatocellular carcinoma (HCC), was found at a very early stage.
The primary goal of the HALT-C Trial was to determine if ongoing therapy with pegylated interferon monotherapy could suppress the Hepatitis C virus and slow disease progression, including the development of liver cancer in patients who were not able to achieve SVR using pegylated interferon and ribavirin.
Full text is available
here
Liver Cirrhosis
When the Spleen Gets Tough, the Varices Get Going
Published in Gastroenterology -
Volume 144, Issue 1, January
2013
In this era of personalized medicine, it is necessary to stratify different risk
groups among patients with cirrhosis. As recently proposed, a revised staging of
cirrhosis should start with its main classification of compensated and
decompensated cirrhosis, 2 separate entities with different prognostic
significance. Decompensated cirrhosis is defined by the
presence of complications that are mostly secondary to portal hypertension:
Ascites, variceal hemorrhage, and/or hepatic encephalopathy. Compensated
cirrhosis would in turn be composed of 2 substages: Without varices or with
varices. These 2 substages of compensated cirrhosis also have different
prognostic significance; patients without varices have a significantly better
survival than those with varices....
Full text available here...
Liver Cirrhosis - Poor Sleep, Depression and Anxiety
Published January 22 2013 online at BMC Gastroenterology;
Studies have shown psychological distress in patients with cirrhosis, yet no studies have evaluated the laboratory and physiologic correlates of psychological symptoms in cirrhosis. This study therefore measured both biochemistry data and heart rate variability
HRV analysis, and aimed to identify the physiologic correlates of depression, anxiety, and poor sleep in cirrhosis. The found; increased serum AST and abnormal autonomic nervous activities by HRV analysis were associated with psychological distress in cirrhosis. Because AST is an important mediator of inflammatory process, further research is needed to delineate the role of inflammation in the cirrhosis comorbid with depression.
Download
PDF here
Of Interest - Hepatitis C and Sleep
by Lucinda Porter, RN
Big Pharma
BMS-986094 Lawsuit
We heard more on the lawsuit involving 15 patients who were tragically hurt - one died- during the company-sponsored clinical trials of the hepatitis C drug BMS-986094. On Thursday
The Wall Street Journal reported that Bristol-Myers Squibb agreed to pay $80 million to 15 patients who were harmed during the clinical trials.
Read the story @
WSJ
HCV Transmission - The Tattoo
Reuters Reports - Hepatitis C linked to ink
(Reuters Health) - Researchers are hoping that people will do some research about where to get a tattoo, after a study found a link between body art and hepatitis C.The new study found that people with the virus were almost four times more likely to report having a tattoo, even when other major risk factors were taken into account, co-author Dr. Fritz Francois of New York University Langone Medical Center told Reuters Health.
Although the study could not prove a direct cause and effect, "Tattooing in and of itself may pose a risk for this disease that can lay dormant for many, many years," Francois said.
The abstract is available
here, the article
here.
Related @ Healio.com/Hepatology
If tattoos came with ‘fine print’ warnings…
Hepatitis C risk increases for anyone who gets one or more tattoos.
Read more.
HCV Transmission In A Clinical Setting
A Second New York hospital warns of potential HIV, hepatitis C or hepatitis B infection
A second western New York hospital is notifying patients that they may have been exposed to HIV, hepatitis B or hepatitis C through the improper sharing of insulin pens, hospital officials said Thursday.
Olean General Hospital was mailing letters to 1,915 patients who received insulin at the hospital from November 2009 through last week, advising them to call to arrange for blood testing. The risk of infection is very low, hospital officials said, but they wanted patients to be aware of the possibility.
Hospital officials said the action follows an internal review conducted after the Veterans Affairs hospital in Buffalo discovered more than 700 patients may have been exposed to blood-borne pathogens over a two-year period when multi-use pens intended for use by a single patient may have been used on more than one person.
“Interviews with nursing staff indicated that the practice of using one patient’s insulin pen for other patients may have occurred on some patients,” said Timothy Finan, president and chief executive of Upper Allegheny Health System, the parent company of the Olean hospital
Continue reading......
Liver Health - Don’t Double Up on Acetaminophen
You have flu symptoms, so you've been getting some relief for the past two
days by taking a cough and flu medicine every few hours. Late in the day, you
have a headache and you think about grabbing a couple of acetaminophen tablets
to treat the pain.
Stop right there.
What you may not realize is that more than 600 medications, both prescription
and over-the-counter (OTC), contain the active ingredient acetaminophen to help
relieve pain and reduce fever. Taken carefully and correctly, these medicines
can be safe and effective. But taking too much acetaminophen can lead to severe
liver damage.
Acetaminophen is a common medication for relieving mild to moderate pain from
headaches, muscle aches, menstrual periods, colds and sore throats, toothaches,
backaches and to reduce fever. It is also used in combination medicines, which
have more than one active ingredient to treat more than one symptom.
'Tis Cold and Flu Season
The National Institutes of Health (NIH) says that Americans catch one billion
colds per year and as many as 20% of Americans get the flu. Moreover, 7 in 10
Americans use OTC medicines to treat cold, cough and flu symptoms.
Fathia Gibril, M.D., M.HSc., a supervisory medical officer at the Food and
Drug Administration (FDA), explains that consumers looking for relief from a
cold or the flu may not know that acetaminophen comes in combination with many
other medications used to treat those symptoms. "So if you're taking more than
one medicine at a time," she says, "you may be putting yourself at risk for
liver damage."
Symptoms of acetaminophen overdose may take many days to appear, and even
when they become apparent, they may mimic flu or cold symptoms. The current
maximum recommended adult dose of acetaminophen is 4,000 milligrams per day, To
avoid exceeding that dose:
- don't take more than one OTC product containing acetaminophen,
- don't take a prescription and an OTC product containing acetaminophen, and
- don't exceed the recommended dose on any product containing
acetaminophen.
"When you're at the store deciding which product to buy, check the 'Drug
Facts' label of OTC cold, cough and flu products before using two or more
products at the same time," Gibril says. If you’re still not sure which to buy,
ask the pharmacist for advice.
Rely on Health Care Experts
Acetaminophen is used in many commonly prescribed medications in combination
with pain relievers such as codeine, oxycodone and hydrocodone. As of January
2011, FDA reported that overdoses from prescription medicines containing
acetaminophen accounted for nearly half of all cases of acetaminophen-related
liver injury in the U.S. When your health care professionals prescribe a drug,
be sure to ask if it contains this active ingredient, and also to inform them of
all other medicines (prescription and OTC) and supplements you take.
Even if you still have fever or pain, it's important not to take more than
directed on the prescription or package label, notes FDA supervisory medical
officer Sharon Hertz, M.D. But be careful, the word "acetaminophen" is not
always spelled out in full on the container's prescription label. Abbreviations
such as APAP, Acetaminoph, Acetaminop, Acetamin, or Acetam may be used
instead.
When buying OTC products, Hertz suggests you make it a habit of telling the
pharmacist what other medications and supplements you’re taking and asking if
taking acetaminophen in addition is safe.
When the medicine is intended for children, the "Directions" section of the
Drug Facts label tells you if the medicine is right for your child and how much
to give. If a dose for your child's weight or age is not listed on the label and
you can't tell how much to give, ask your pharmacist or doctor what to do.
If you're planning to use a medication containing acetaminophen, you should
tell your health care professional if you have or have ever have had liver
disease.
Acetaminophen and alcohol may not be a good mix, either, Hertz says. If you
drink three or more alcoholic drinks a day, be sure to talk to your health care
professional before you use a medicine containing acetaminophen.
January 24, 2013
Related - Hepatitis C and Tylenol
Written by
Lucinda Porter, RN
The most common question I am asked by hepatitis C patients, “Is Tylenol (acetaminophen or paracetamol as it is called in other countries) safe for the liver? The answer is, “Yes, if taken as directed.”
Read the full article @
http://lucindaporterrn.com/blog/
Liver Health - Binge Drinking
Binge drinking will exacerbate liver injury, especially if comorbid conditions such as obesity, Hepatitis C, or HIV infection exist.
Alcoholic liver disease (ALD) is characterized by a fatty liver, hepatitis, fibrosis, and cirrhosis. Binge drinking is on the rise worldwide, and is particularly common in the U.S. A review of studies addressing the effects of binge drinking on the liver underscores the complex interactions among various immune, signaling pathways, epigenetic, and metabolic responses of the liver to binge drinking.
"Therefore, people should not binge drink, especially on an empty stomach, and if they are chronic heavy drinkers, binge drinking will exacerbate liver injury, especially if comorbid conditions such as obesity, Hepatitis C, or HIV infection exist."
Continue reading....
Heavy Alcohol Use Increases Liver Cancer Risk for People with Hepatitis B
Hepatitis B patients with liver cirrhosis who consumed large amounts of alcohol were more likely to develop hepatocellular carcinoma than people who drank less, according to a report in the December 6, 2012, online edition of the Journal of Hepatology .
Read more @
HIV and Hepatitis
In Todays News - Liver Health
DGNews
FDA: Significant Liver Injury Associated With Use of Tolvaptan
ROCKVILLE, Md -- January 25, 2013 -- The US Food and Drug Administration (FDA) and Otsuka pharmaceuticals are notifying healthcare professionals of significant liver injury associated with the use of tolvaptan (Samsca).
In a double-blind, 3-year, placebo-controlled trial in about 1,400 patients with autosomal dominant polycystic kidney disease (ADPKD) and its open-label extension trial, 3 patients treated with the drug developed significant increases in serum alanine aminotransferase (ALT) with concomitant, clinically significant increases in serum total bilirubin.
In the trials the maximum daily dose of tolvaptan administered (90 mg in the morning and 30 mg in the afternoon) was higher than the maximum 60 mg daily dose approved for the treatment of hyponatremia.
Most of the liver enzyme abnormalities were observed during the first 18 months of therapy. Following discontinuation of treatment, all 3 patients improved.
An external panel of liver experts assessed these 3 cases as being either probably or highly likely to be caused by tolvaptan.
These findings indicate that tolvaptan has the potential to cause irreversible and potentially fatal liver injury.
These data are not adequate to exclude the possibility that patients receiving tolvaptan for its indicated use of clinically significant hypervolemic and euvolemic hyponatremia are at a potential increased risk for irreversible and potentially fatal liver injury.
Tolvaptan is a selective vasopressin V2-receptor antagonist indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia. Tolvaptan is not approved for the treatment of ADPKD.
Recommendations for Healthcare Professionals:
· Healthcare providers should perform liver tests promptly in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice.
· If hepatic injury is suspected, tolvaptan should be promptly discontinued, appropriate treatment should be instituted, and investigations should be performed to determine probable cause.
· Tolvaptan should not be re-initiated in patients unless the cause for the observed liver injury is definitively established to be unrelated to treatment with Samsca.
Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of this product to the FDA's MedWatch Safety Information and Adverse Event Reporting
Program:
· Complete and submit the report Online:
https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm
http://www.fda.gov/Safety/HowToReport/DownloadForms/default.htm
Forms or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178
SOURCE: US Food and Drug Administration
Published Today - In The Current Issue Of GI & Hepatology News
AASLD - Ribavirin induced anemia
BY N E I L OSTERWEIL
IMNG Medical News
BOSTON
Cirrhotic patients have similar hepatitis C virus SVRs when treated with either ribavirin dose reduction or erythropoietin
Anemia developed significantly more often among patients with hepatitis C virus infection and compensated cirrhosis than among noncirrhotic patients during triple therapy in a randomized, open-label trial of treatment-naive patients, but
in most instances the anemia was effectively treated.
In an anemia management subanalysis of a study comparing sustained
virologic response (SVR) rates
in cirrhotic and noncirrhotic patients
treated with boceprevir (Victrelis),
pegylated interferon alfa-2b (Peg-Intron),
and ribavirin (RBV), 57% of
patients with cirrhosis and anemia
treated with a ribavirin dose reduction
had an SVR, compared with 64%
of those treated with erythropoietin.
Among noncirrhotic patients with
anemia, the respective SVR rates
were 73% and 72%. None of the differences
between those treated with
a RBV dose reduction or erythropoietin
was significant in cirrhotic and
noncirrhotic patients, Dr. Eric J.
Lawitz, AGAF, reported at the annual
meeting of the American Association
for the Study of Liver Diseases.
ª
Sustained viral responses are comparable
in cirrhotic patients when
anemia is managed by ribavirin dose
reduction or erythropoietin,º said Dr.
Lawitz, medical director and principal
investigator at Alamo Medical Research
in San Antonio.
He also noted that ribavirin dose
reductions should be the initial strategy
for managing anemia, followed,
if necessary, by erythropoietin.
In the trial, 687 treatment-naive
patients with hepatitis C virus
(HCV) infections were treated for 4
weeks with pegylated interferon
(PEG-IFN) alfa-2b and RBV, then 24
or 44 weeks of boceprevir added in.
Baseline hemoglobin (Hb) levels
ranged from 12 g/dL to 15 g/dL for
women, and from 13 g/dL to 15
g/dL for men.
Patients with Hb approaching 10
g/dL or less (tested from baseline
through week 48) were randomized
to either ribavirin dose reduction
(249 patients) in 200-mg increments
(first increment of 400 mg for initial
1,400-mg daily doses) at the investigators'
discretion, or to erythropoietin
(251 patients) at 40,000 U/week,
modifiable to 20,000 U/week or
60,000 U/week at the investigator's
discretion.
The remaining patients received
anemia prophylaxis but were
not randomized.
If the Hb level dropped to 8.5
g/dL, patients could receive the other
treatment as a secondary intervention,
and patients with Hb 7.5 g/dL
were discontinued from all study
drugs.
Primary efficacy measures for all
patients (cirrhotic and noncirrhotic)
in each anemia strategy group were
identical, with 82% having an end-oftreatment
response, 71% having an
SVR, and 10% experiencing relapse.
Among cirrhotic vs. noncirrhotic
patients, rates were 68% vs. 76% for
end-of-treatment response , 55% vs.
64% for SVR, and 18% vs. 11% for relapse.
Patients with cirrhosis were significantly
more likely to require a secondary
anemia intervention (44% vs.
26%, P = .009).
Among noncirrhotic patients (but
not cirrhotic patients), a secondary
anemia intervention was associated
with a greater likelihood of SVR
(80% vs. 70% for only one intervention,
P = .05).
Serious adverse events occurred in
20% of cirrhotic patients and 12% of
noncirrhotic patients, but only one
study death occurred. The noncirrhotic
patient died of a cardiac arrest,
which was considered to be unrelated
to therapy.
Treatment-emergent adverse
events occurred in 3% of patients
with cirrhosis and 2% of those without
cirrhosis.
Drug discontinuation for adverse
events occurred in 17% of cirrhotic
patients, and 16% of noncirrhotic patients, according to Dr. Lawitz.
Cirrhotic patients were more likely
to have Hb concentrations ranging
from 6.5 to 8.0 g/dL than were noncirrhotic
patients, but no patient in
either group had an Hb concentration
below 6.5 g/dL.
Neutrophil counts in the range of
500-749/mm3 occurred in 24% of cirrhotic
patients and 27% of noncirrhotic
patients, and counts below
500/mm3 were seen in 20% and 12%.
Platelet counts from 25,000 to
49,999/mm3 occurred in 22% of cirrhotic
patients and 2% of noncirrhotic
patients.
Counts below
25,000/mm3 were seen in 3% vs. less
than 1%, respectively. Transfusion
rates were similar between the
groups.
AASLD - New interferon speeds HCV virologic responses
BY N E I L OSTERWEIL
IMNG
Medical News
BOSTON
Call it interferon 3.0. An
investigational form of the immunomodulator,
known as interferon-
lambda, appeared to be effective
against chronic hepatitis C virus infections,
but had fewer side effects
than interferon alfa, in two separate
clinical trials.
In a phase IIb study, ribavirin plus
pegylated interferon-lambda-1a (IFNL/
RBV) was comparable in efficacy
to ribavirin plus pegylated interferon
alfa-2a (PEG-IFN/RBV) in treatment-
naive patients with hepatitis C
(HCV) genotype 1 or 4 viral infections,
Dr. Andrew J. Muir reported at
the annual meeting of the American
Association for the Study of Liver
Diseases.
The improved tolerability, together
with a faster time to virologic response,
supports the further
assessment of lambda-based, directacting
antiviral combination regimens
in patients chronically infected
with HCV genotypes 1 or 4,º said Dr.
Muir, clinical director of hepatology
in the department of medicine at
Duke University Medical Center,
Durham, N.C.
In a separate small study also presented
at the meeting, IFN-L/RBV,
combined with a direct-acting antiviral
agent, yielded high rates of sustained
virologic response (SVR) in
Japanese patients with HCV genotype
1b infections, said Dr. Namiki
Izumi of Musashino Red Cross Hospital
in Tokyo.
IFN-L is a type III interferon with
strong antiviral activity but a restricted
receptor distribution that is reputed to
give the drug a better tolerability profile
than the alfa interferons currently
in widespread clinical use.
Comparing New and Old IFNs
In the EMERGE phase IIb study, Dr.
Muir and his colleagues randomized
527 noncirrhotic, treatment-naive
adults with HCV genotypes 1-4 on a
1:1:1:1 basis to either PEG-IFN 180
mcg weekly plus daily ribavirin or
IFN-L at dose levels of 120, 180, or
240 mcg weekly plus daily ribavirin.
Because of safety issues, patients
with genotypes 1 and 4 assigned to
receive the 240-mcg dose of IFN-L
had their dose reduced to 180 mcg
at study week 12, and this dose level
was subsequently chosen for phase
III trials.
Dr. Muir reported results
through 72 weeks of follow-up for
407 patients with genotypes 1 or 4
treated for 48 weeks. Approximately
60% of patients in each of the four
treatment arms completed treatment
and follow-up.
IFN-L at the 180-mcg dose was associated
with significantly more
rapid virologic responses at week 4
(RVR4 14.7% vs. 5.8%) and complete
early virologic responses at week 12
(55.9% vs. 36.9%) than was PEG-IFN
(P less than .05 for each comparison).
However, there were no significant
differences in response rates at either
the end of treatment or in SVR24 at
last follow-up, and relapse rates were
similar between the groups.
Adverse events of any grade were
similar among the groups, except for
lower percentages of myalgia (5.9%
for IFN-L vs. 33.0% for PEG-IFN),
pyrexia (7.8% vs. 33%, respectively),
chills (3.9% vs. 21.4%), and arthralgia
(5.9% vs. 20.4%).
Treatment-emergent liver abnormalities
included alanine aminotransferase
(ALT) 5 to 10 times the
upper limit of normal in 2.9% of
patients on IFN-L, compared with
4.9% for those on PEG-IFN.
In contrast,
total bilirubin levels 2.6 to 5
times the upper limit of normal
were seen in 5% vs. 3.9%, respectively.
In both the 120-mcg and 180-
mcg IFN-L groups and the PEG-IFN
group, 1% of patients required dose
reductions due to liver-related lab
abnormalities. In all, 2.9% of patients
of IFN-L discontinued the
drug for liver abnormalities, compared
with 1.9% for PEG-IFN.
High SVR With Lambda and Direct-
Acting Antivirals
In the D-LITE study, Dr. Izumi and
her colleagues compared IFN-L/RBV
in combination with either daclatasvir,
an investigational viral
NS5A replication complex inhibitor,
or asunaprevir, an investigational NS3
protease inhibitor, with each group
including a placebo for the alternate
direct-acting antiviral agent. (For example,
patients receiving IFN-L/RBV
and daclatasvir also received an
asunaprevir placebo.)
In addition, the
trial contained a substudy arm with
patients assigned to PEG-IFN/RBV
with daclatasvir and asunaprevir
placebos; Dr. Izumi reported only on
the IFN-L arms.
All patients in the IFN-L groups
were treated for 24 weeks, at which
point those patients who did not have
a protocol-defined response (PDR)
were given an additional 24 weeks of
treatment.
A PDR was defined as an
HCV RNA level at week 4 below the
lower limit of quantification (less
than 25 IU/mL) and undetectable
HCV RNA at 12 weeks.
In the daclatasvir group, eight of
eight patients had a PDR, compared
with five of six in the asunaprevir
arm. The single patient without a response
in the latter arm discontinued
therapy for an adverse event during
week 3.
All eight patients in the daclatasvir
arm and the five remaining patients
in the asunaprevir arm had week 4
and week 12 sustained virologic responses
(SVR4 and SVR12).
Grade 3 or 4 adverse events occurred
in one of eight patients on
daclatasvir, and in four of five on
asunaprevir.
There were no grade 3
or 4 lab abnormalities among patients
on daclatasvir. In the
asunaprevir group, there was one
case of hemoglobin abnormalities,
three with elevated ALT, four with
elevated aspartate aminotransferase,
and one with elevated total bilirubin.
The authors concluded that the
combination of IFN-L/RBV and daclatasvir
had the best safety profile,
and that the data support further investigation
of the combination in patients
with HCV genotype 1b.
Both the EMERGE IIb and DLITE
studies were supported by
Bristol-Myers Squibb.
Dr. Muir reported
receiving grant and research
support and serving on advisory
committees or review panels for the
company.
Dr. Izumi reported receiving
speaking and teaching fees from
the company.
AASLD - Triple therapy has poor safety in cirrhotic hepatitis C
BY N E I L OSTERWEIL
IMNG
Medical News
BOSTON
In patients with chronic
hepatitis C virus infections and compensated
cirrhosis, a combination of a
direct-acting antiviral agent, pegylated
interferon, and ribavirin produced
high on-treatment virologic response
rates, but at the cost of significantly
increased toxicities in an interim
analysis of a French multicenter trial.
Although the efficacy of direct-acting
antiviral regimens involving the
protease inhibitors telaprevir (Incivek)
and boceprevir (Victrelis) combined
with pegylated interferonalfa-2a or -2b in combination with
ribavirin (PEG-IFN/RBV) in cirrhotic
nonresponders to prior therapy was
good, their safety was ª poor,º said
Dr. Christophe Hézode of Hôpital
Henri Mondor, Créteil, France.
Virologic response at 16 weeks in a
per-protocol analysis was 92% with
telaprevir and 77% with boceprevir.
However, there were increased
rates of serious adverse events and
more difficult-to-manage anemia
than in phase III trials for telaprevir
and boceprevir, which included only
a few patients with cirrhosis, Dr. Hézode
said at the annual meeting of
the American Association for the
Study of Liver Diseases.
In treatment-experienced cirrhotic
patients with platelet counts of
100,000/mm3 or serum albumin levels
below 35 g/L, clinicians should treat
on a case-by-case basis because of the
high risk for severe complications, Dr.
Hézode said. Cirrhotic experienced
patients without predictors of severe
complications should be treated, but
carefully monitored, he added.
Dr. Hézode and his coauthors in
the French Cohort of Therapeutic
Failure and Resistances in Patients
Treated With a Protease Inhibitor(telaprevir or boceprevir), Pegylated
Interferon, and Ribavirin (CUPIC) trial
studied two cohorts of patients
with chronic hepatitis C virus (HCV)
infections, and compensated cirrhosis
(Child Pugh class A) who had relapsed
or had only a partial response
to prior therapy, with partial response
defined as at least a 2 log10 decline
in HCV RNA but failure to
clear virus by week 24.
He presented data on 497 patients
who had completed 16 weeks of therapy
on one of two regimens. In one
cohort, 292 patients received 12 weeks
of telaprevir 750 mg every 8 hours,
and PEG-IFN alfa-2a (Pegasys) 180
mcg/wk with ribavirin 1,000-1,200
mg/day, followed by PEG-IFN/RBV
through 48 weeks. In the second cohort,
patients received a 4-week initiation
phase with PEG-IFN alfa-2b
(PegIntron) and ribavirin, followed by
44 weeks of boceprevir 800 mg every
8 hours, PEG-IFN 1.5 mcg/kg per wk,
and ribavirin 800-1,400 mg/day.
At week 16, 45% of patients on
telaprevir had had at least one serious
adverse event, with 14.7% ending
therapy because of a serious side effect.
In all, 22.6% discontinued therapy,
and there were five deaths: from
septicemia, septic shock, pneumopathy,
endocarditis, and bleeding
esophageal varices.
Other complications
in this group included grade 3or 4 infections in 6.5%, grade 3 or 4
hepatic decompensation in 2%, grade
3/4 asthenia in 5.5%, and renal failure
in 1.7%.
Hematologic adverse
events included anemia of grade 2 or
greater in 30.4%, erythropoietin use
in 53.8%, blood transfusion in 16.1%,
and ribavirin dose reduction in 13%.
In addition, 2.7% of patients had
grade 3 or 4 neutropenia, and 1.7%
had grade 3 or 4 thrombocytopenia.
In the boceprevir group, 32.7% had
at least one serious adverse event,
26.3% discontinued prematurely, and
7.3% discontinued because of serious
events.
The cause of one death was
pneumopathy. Grade 3 or 4 adverse
events involved infections in 2.4%,
hepatic decompensation in 2.9%, and
asthenia in 5.8%.
Hematologic events
included grade 2 or greater anemia in
27.8%, erythropoietin use in 46.3%,
blood transfusion in 6.3%, and ribavirin
dose reduction in 10.7%.
Grade 3 or 4 neutropenia was seen
in 4.4%, and grade 3 or 4 thrombocytopenia
in 5.4%.
Two patients (1%) in
this cohort received thrombopoietin.
In a multivariate analysis, significant
baseline predictors of severe
complications (death, severe infection,
hepatic decompensation) included
platelet counts of 100,000/mm3 or
lower (odds ratio, 3.11; P = .0098)
and a serum albumin level below 35
g/L (OR, 6.33; P less than .0001).
Source
The Current Issue Of
GI & Hepatology News
(VOL. 7 NO. 1 JANUARY 2013): Download
PDF Or View
Interactive Version
GI & Hepatology News is the official newspaper of
the AGA Institute and provides the gastroenterologist with timely and relevant
news and commentary about clinical developments and about the impact of
health-care policy.
The newspaper is led by an
internationally renowned board of editors.
Personal HCV Experiences
An Interview with Alan Franciscus of the Hepatitis C Support Project (Part 1)
There is a very good argument to be made that Alan Franciscus is the most
significant trailblazer in his work for hepatitis C awareness and advocacy
movement in the United States. Since the existence of hepatitis C as a distinct
virus was not even proven until 1989, the movement has been in existence for
only about twenty odd years, and it has been far from a powerful entity in terms
of public awareness and reach. In fact, a good deal of what has been
accomplished has been accomplished by Alan Franciscus. And the man doesn’t even
have a Wikipedia page.
Read the interview at
Hepatitis Connect
Addicition
Christopher Kennedy Lawford who unknowingly contracted hepatitis C during his years of drug use, also wrote Healing Hepatitis C in 2009, here is his video.
In The News - Christopher Kennedy Lawford brings his story of recovery and redemption to Pasadena
By
Carl Kozlowski 01/23/2013
Growing up in a world of showbiz and political privilege as the son of movie star Peter Lawford and the nephew of President John F. Kennedy, Christopher Kennedy Lawford couldn’t have imagined that alcohol and drug addiction would eventually cost him his share of the family fortune and very nearly his life.
Boston—Enthusiasm is growing for the various interferon (IFN)-free therapies on the horizon for patients with hepatitis C virus (HCV) infection. At the recent annual meeting of the American Association for the Study of Liver Diseases (AASLD), The Liver Meeting 2012, four of the six late-breaking abstracts and a slew of other studies discussed new oral regimens that can be used to achieve high rates of sustained virologic response (SVR) in a variety of HCV patient cohorts, including null responders.