Chronic hepatitis C: Interferon may be harmful in re-treatment: “may face an increased risk of dying sooner”

Contact: Jennifer Beal sciencenewsroom@wiley.com 44-012-437-70633 Wiley

People with hepatitis C and chronic liver disease who relapsed or failed to respond to initial treatment are unlikely to improve on interferon retreatment. In fact, they may face an increased risk of dying sooner, and are likely to experience a variety of adverse effects, according to an updated systematic review published in The Cochrane Library.

Hepatitis C affects around 170 million people worldwide. In some cases, infection leads to chronic liver disease, liver failure or liver cancer, eventually resulting in death. Treatment is based on antiviral drugs.

Interferon monotherapy, meaning using interferon alone, is not the first choice of therapy for most clinicians, but it is used in some patients when other drugs cannot be used. Despite costing thousands of dollars to treat one patient for a year, there is currently little evidence that it works. Treatment is considered to have been successful if the virus cannot be detected in a patient’s blood six months after treatment. This outcome is known as sustained viral response (SVR). However, it has never been confirmed that SVR leads to an improvement in the patient’s disease state or their chances of survival.

The authors of the review analysed data from seven trials involving a total of 1,976 patients with chronic hepatitis C liver disease who were being retreated with interferon monotherapy having previously been treated unsuccessfully. When they included all trials in their analysis, the risk of death was no higher for interferon than for placebo or no treatment. However, the researchers also performed a further analysis, leaving out studies that had a high risk of bias and gave less reliable estimates of effect. For example, one of these trials was not blinded, was stopped before the planned number of patients had been enrolled, and did not have all of those who had been enrolled counted in the final analysis. This left the two largest trials, together incorporating 1,676 patients. Focusing only on these trials, the risk of death was significantly higher at 9.4% for interferon retreatment compared to 6.7% for placebo or no treatment.

“It was troubling to see that in those trials providing the most reliable estimates of treatment effects, interferon seemed to increase the risk of death,” said lead researcher Ronald Koretz of Granada Hills in California, US. “Based on these results, interferon monotherapy cannot be recommended for chronic hepatitis C patients who have already failed one course of treatment and are being retreated. Furthermore, patients who are receiving interferon as part of a combination therapy should be informed about this potential adverse effect.”

Interferon treatment did seem to reduce levels of hepatitis C virus in the blood compared to controls, resulting in what would be considered successful treatment or SVR. However, since this response was not associated with an improvement in disease or risk of death, the review suggests that SVR may be inadequate as an indicator of a successful treatment outcome. “Sustained viral response did not suggest that a patient who was destined to develop symptoms or death from hepatitis C was cured, at least in this setting. This tells us that as a treatment outcome it is not universally reliable and needs to be validated before it can be viewed as the goal of any therapy in other clinical scenarios,” said Koretz.

Patients in the treatment group were also more likely to suffer adverse effects. Although the drug did appear to reduce the incidence of nonfatal internal bleeding, the researchers conclude that it is so expensive that it may be hard to justify based on this one small benefit.

HALT-C researchers: Interferon as long-term treatment for hepatitis C not effective

2008 study posted for filing

Contact: LaKisha Ladson
lakisha.ladson@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center

IMAGE:Dr. William M. Lee and other researchers have discovered in a multicenter study that using the drug interferon as a long-term maintenance strategy to slow the progression of liver disease…

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DALLAS – Dec. 4, 2008 – Use of the drug interferon as a long-term maintenance strategy to slow the progression of liver disease associated with the hepatitis C virus is ineffective, UT Southwestern Medical Center researchers and their colleagues from nine other institutions have found in a multicenter study.

Results of the 3½-year study, called the HALT-C (Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis) Trial, appear in today’s issue of The New England Journal of Medicine. The researchers found no difference in the rate of progression of liver disease among patients who received interferon and those who did not.

“It wasn’t that there was an insignificant difference; there was absolutely no difference whatsoever in the progression to cirrhosis and other disease complications,” said Dr. William M. Lee, professor of internal medicine at UT Southwestern and a principal investigator for the study. “It is a negative study but an important one.”

Dr. Lee said physicians should not expect any benefit from the long-term use of interferon by itself in slowing disease progression. By contrast, use of interferon with other drugs such as ribavirin can lead to viral eradication, or complete clearance of hepatitis C virus, a result that will “stop the disease in its tracks,” Dr. Lee said.

Hepatitis C is a viral infection that causes liver inflammation and can progress over many years to cirrhosis, liver cancer, liver failure and death. The disease affects more than 3 million people in the United States and 170 million people worldwide. It is the most common reason for liver transplantation in the U.S.

There is no vaccine to prevent hepatitis C virus infection. The combination of interferon and ribavirin works for about 40 percent to 50 percent of people with the virus, while the other 50 percent to 60 percent of patients will continue to progress to later states of liver disease, Dr. Lee said.

In addition to interferon and ribavirin, new drug agents such as protease and polymerase inhibitors are being used in clinical studies at UT Southwestern to improve rates of virus eradication. Food and Drug Administration approval of these agents is likely to be three years away, Dr. Lee said.

In the HALT-C Trial, conducted between August 2000 and June 2007, 1,050 people with hepatitis C who did not respond to initial antiviral treatment were assigned randomly to either a group that received treatment with a type of interferon called peginterferon or to a group that did not. About 120 patients were enrolled at UT Southwestern.

Participants were monitored every three months and underwent liver scans and biopsies at specified intervals through the study period. Researchers found that although the level of hepatitis C virus in blood and certain enzymes in the liver decreased significantly with treatment, there was not a significant difference in ultimate clinical outcome.

“Currently, we use interferon only to clear the virus,” said Dr. Lee. “If you cannot clear the virus with treatment, the idea that struggling long term through the side effects of interferon is somehow going to help you rid yourself of cirrhosis is just not plausible any longer.”

Some patients cannot tolerate the side effects of the different types of interferon medication, which can cause extreme flu-like symptoms, such as fever, chills, fatigue, depression, muscle aches, chest pain, difficulty breathing, nausea, vomiting, and weight and hair loss.

 

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Other researchers from UT Southwestern involved in the study were Dr. Thomas Rogers, professor of pathology, and Dr. Peter Malet, professor of internal medicine.

Also involved in the study were researchers from Saint Louis University School of Medicine; Virginia Commonwealth University Medical Center; University of Colorado School of Medicine; University of Southern California; National Institute of Diabetes and Digestive and Kidney Diseases; University of Michigan Medical Center; University of Connecticut Health Center; University of California, Irvine, and VA Long Beach Healthcare System; and University of Washington.

The study was funded by the National Institutes of Health. Pharmaceutical manufacturer Hoffman-LaRoche, through an agreement with the NIH, also provided funding.

Dr. Lee has received consulting fees from Eli Lilly, Fibrogen and Astra Zeneca, and grant support from Hoffmann-LaRoche, Schering-Plough, Vertex Pharmaceuticals, GlaxoSmithKline, Siemens, Globelmmune and Bristol-Myers Squibb.

Visit http://www.utsouthwestern.edu/digestive to learn more about UT Southwestern’s clinical services in digestive disorders, including liver diseases.

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Dr. William M. Lee — http://www.utsouthwestern.edu/findfac/professional/0,2356,14217,00.html

Interferon does not slow or stop hepatitis C from worsening, study finds

 

 

Interferon does not slow or halt the progression of chronic hepatitis C and advanced liver disease in patients who haven’t responded to previous attempts to eradicate the disease, a national study in which the Saint Louis University School of Medicine participated has found.

 

Patients in the trial who were treated with interferon did experience a significant decrease in viral levels and liver inflammation, but the trial unequivocally demonstrated that treatment with long-term pegylated interferon – also called peginterferon – does not prevent the worsening of liver disease in patients who’ve failed prior treatments

 

“The results are this study are very clear – long-term therapy with peginterferon for those with chronic hepatitis C is not effective in preventing progression of liver disease for patients who did not respond to an initial course of treatment,” said Adrian Di Bisceglie, M.D., professor of internal medicine at Saint Louis University School of Medicine and chairman of the trial’s steering committee.

Results of the study were reported by Di Bisceglie at the annual meeting of the American Association for the Study of Liver Disease in Boston this week.

 

The randomized, multi-site study involved 1,050 patients with chronic hepatitis C who’d failed prior treatments to eradicate the infection. All had advanced liver fibrosis – a gradual scarring of the liver that puts patients at risk for progressive liver disease.

 

At the end of the study, while patients treated with interferon did have significantly lower blood levels of the hepatitis C virus and less liver inflammation, 34.1 percent of them had experienced one or more of the following outcomes: excess fluid in the abdomen; brain and nervous system damage; cirrhosis (for those who did not have it initially); liver cancer; or death. Of patients in the control group, 33.8 percent experienced one or more of the outcomes.

* Requested Repost

Hepatitis A and or B Gives greater chance to recover from Hep C..Plus Morphine increases HCV Replication

Contact: Lixin Zhu wjg@wjgnet.com 86-108-538-1892 World Journal of Gastroenterology

Who will recover spontaneously from hepatitis C virus infection

More than 3% of world population is infected with hepatitis C virus (HCV). The outcome of HCV infections is either self recovery or chronic hepatitis, and many of the chronic infections will develop into liver cirrhosis or liver cancer. Since there is no cure for chronic hepatitis C, nor is there any approved vaccine for this virus, hepatitis C is currently a major health problem worldwide.

Twenty to fifty percent of HCV infected patients recovers spontaneously. The hepatitis C patients and their relatives like to know if his/her infection would fall into the category for self recovery.

A research article to be published on August 21 in the World Journal of Gastroenterology addresses this question. The research team led by Dr. Mihm from Georg-August-Universität spent more than 8 years working with a cohort of 67 patients who spontaneously recovered from HCV infection. In addition to these, the researchers included a similar number of patients with chronic HCV infection. Large sample size allowed these investigators to obtain results with great statistical significance, and to draw very reliable conclusions.

One conclusion reported by the investigators is, patients who self recovered usually have lower levels of HCV antibody. Thus patients with lower HCV antibody titer may have a brighter clinical outcome. However, for a practical standard to be established to define a low HCV antibody titer, more effort is needed by investigators in the future.

Another interesting conclusion reached by these investigators is, co-infection by hepatitis B virus (HBV) is associated with a higher possibility of self recovery. The investigators suggested that the infection of HBV interferes with the HCV replication, which would finally lead to virus eradiacation.. HCV patients co-infected by hepatitis A virus also have a better chance of self recovery, possibly by a similar mechanism.

Active iv drug users are less likely to self recover, for a couple of reasons: 1, they have a higher incidence of re-infection; 2, drugs have been shown to inhibit the expression of antiviral cytokines such as IFN- and IFN-; 3, HCV replication has been shown to be enhanced both by morphine use and morphine withdrawal.

Several different genotypes of HCV were discovered. The HCV genotype studied by Dr. Milm¡¯s group is type 1b, which is the prevalent genotype in Germany, and in China.

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* Reposted on Request

Widely prescribed MS treatment may not slow progression of disease: VCH-UBC research

Researchers with the UBC Hospital MS Clinic and Brain Research Centre at Vancouver Coastal Health and the University of British Columbia have published important data in the Journal of the American Medical Association (JAMA) about the impact of a common drug therapy on the progression of multiple sclerosis for people with the relapsing‑remitting form of the disease.

The study, led by Drs. Helen Tremlett, Afsaneh Shirani, Joel Oger and others, shows no strong evidence that a group of drugs, beta interferons (β-IFNs),  prescribed to treat MS had a measurable impact on the long-term disability progression of the disease.

The team examined the linked health records of 2656 BC patients between 1985 – 2008 in a retrospective cohort study, which means data from already collected sources were linked together in an anonymized form and studied. Data sources included the BC Ministry of Health, PharmaNet and the BC Multiple Sclerosis (BCMS) database, facilitated by Population Data BC.

The study population included patients with MS who were treated with beta interferons (β-IFNs), the most widely used treatment for relapsing‑remitting MS, as well as untreated MS patients. The research team discovered that administration of β-IFN was not associated with a significant change in the progression of disability.

These findings will be of interest to MS patients with this form of the disease, but researchers are quick to point out that this is just one measure of these disease modifying drugs and there is still potentially significant benefit to patients.

“What this study provides is additional information to patients and clinicians about the longer term effect of this class of drugs,” says corresponding author, Dr. Helen Tremlett (PhD), who also holds the Canada Research Chair in Neuroepidemiology and Multiple Sclerosis at UBC. “We know that this class of drugs is very helpful in reducing relapses, which can be important to patients. We do not recommend that patients stop taking these medications, but these findings provide evidence, allowing more realistic expectations as to the anticipated benefits associated with drug treatment from the disability perspective.”

“It is still possible that some patients gain long-term benefit from β-IFNs. We are currently working toward identifying who those potential treatment responders might be,” says Dr Afsaneh Shirani, who is the first author of the paper and a post-doctoral research fellow in the UBC Faculty of Medicine and Brain Research Centre at UBC and VCH Research Institute. “Our study also encourages the investigation of novel treatments for MS,” she adds.

“In addition, this study suggests that linked data from health administrative databases have enormous potential for research applications, despite all the challenges of record linkage” says Dr Shirani.

Relapsing-remitting MS is characterized by relapses or “flare-ups” during which time new symptoms can appear or old ones can resurface or worsen. The relapses are followed by periods of remission during which time the person can fully or partially recover. Relapsing-remitting MS is the most common form of MS affecting around 85% of MS patients in Canada.

“In clinical trial situations, it has been quite evident for years that patients receiving β-IFN treatment have reduced frequency of relapses as well as reduced frequency of new lesions seen on MRI,” says Dr. Joel Oger, who is also a neurologist with the UBC Hospital MS Clinic. “This study following a large number of patients for a long time in “real life situation” does not show an association of the β-IFNs with long term disability and tends to confirm a more modern way of understanding MS: relapses may not be responsible for long term disability in all patients and another mechanism might be at work as well.”

The research team is preparing for future studies further examining this and other classes of disease modifying drugs. The hope is that the research will ultimately lead to an individualized approach to the treatment of MS.