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.

Drinking coffee slows progression of liver disease in chronic hepatitis C sufferers

2009 study posted for filing

Contact: Dawn Peters
medicalnews@wiley.com
781-388-8408
Wiley-Blackwell

Patients with chronic hepatitis C and advanced liver disease who drink three or more cups of coffee per day have a 53% lower risk of liver disease progression than non-coffee drinkers according to a new study led by Neal Freedman, Ph.D., MPH, from the National Cancer Institute (NCI). The study found that patients with hepatitis C-related bridging fibrosis or cirrhosis who did not respond to standard disease treatment benefited from increased coffee intake. An effect on liver disease was not observed in patients who drank black or green tea. Findings of the study appear in the November issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases.

Hepatitis C virus (HCV) infects approximately 2.2% of the world’s population with more than 3 million Americans infected. The Centers for Disease Control and Prevention (CDC) cites HCV as the leading cause of liver transplantation in the U.S. and accounts for 8,000 to 10,000 deaths in the country annually. Globally, the World Health Organization (WHO) estimates 3 to 4 million persons contract HCV each year with 70% becoming chronic cases that can lead to cirrhosis of the liver and liver cancer.

This study included 766 participants enrolled in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial who had hepatitis C-related bridging fibrosis or cirrhosis and failed to respond to standard treatment of the anti-viral drugs peginterferon and ribavirin. At the onset of the study, HALT-C patients were asked to report their typical frequency of coffee intake and portion size over the past year, using 9 frequency categories ranging from ‘never’ to ‘every day’ and 4 categories of portion size (1 cup, 2 cups, 3-4 cups, and 5+ cups). A similar question was asked for black and green tea intake. “This study is the first to address the association between liver disease progression related to hepatitis C and coffee intake,” stated Dr. Freedman.

Participants were seen every 3 months during the 3.8-year study period to assess clinical outcomes which included: ascites (abnormal accumulation of fluid in the abdomen), prognosis of chronic liver disease, death related to liver disease, hepatic encephalopathy (brain and nervous system damage), hepatocellular carcinoma (liver cancer), spontaneous bacterial peritonitis, variceal hemorrhage, or increase in fibrosis. Liver biopsies were also taken at 1.5 and 3.5 five years to determine the progression of liver disease.

Results showed that participants who drank 3 or more cups of coffee per day had a relative risk of .47 for reaching one of the clinical outcomes. Researchers did not observe any association between tea intake and liver disease progression, though tea consumption was low in the study. “Given the large number of people affected by HCV it is important to identify modifiable risk factors associated with the progression of liver disease,” said Dr. Freedman. “Although we cannot rule out a possible role for other factors that go along with drinking coffee, results from our study suggest that patients with high coffee intake had a lower risk of disease progression.” Results from this study should not be generalized to healthier populations cautioned the authors.

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For the preceding study you may also contact:
NCI Office of Media Relations
301-496-6641
ncipressofficers@mail.nih.gov

Article: “Coffee Intake Is Associated with Lower Rates of Liver Disease Progression in Chronic Hepatitis C,” Neal D. Freedman, James E. Everhart, Karen L. Lindsay , Marc G. Ghany, Teresa M. Curto, Mitchell L. Shiffman, William M. Lee, Anna S. Lok, Adrian M. Di Bisceglie, Herbert L. Bonkovsky, John C. Hoefs, Jules L. Dienstag, Chihiro Morishima, Christian C. Abnet, Rashmi Sinha1, and the HALT-C Trial Group. Hepatology; Published Online: July 13, 2009 (DOI: 10.1002/hep.23162); Print Issue Date: November 2009. http://www3.interscience.wiley.com/journal/122511224/abstract

Media Advisory

What: The 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)

Founded in 1950, AASLD is the leading organization of scientists and healthcare professionals committed to preventing and curing liver disease. AASLD has grown into an international society responsible for all aspects of hepatology, and the annual meeting attracts 7,500 physicians, surgeons, researchers, and allied health professionals from around the world.

The Liver Meeting® is the premier meeting in the science and practice of hepatology, including the latest findings on new drugs, novel treatments, and the results from pilot and multicenter studies.

When: October 31 – November 3, 2009

Where : Hynes Convention Center
900 Boylston Street
Boston, Massachusetts

Contact: Please contact Ann Tracy at 703-299-9766 or atracy@aasld.org to obtain a press pass for this event

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… Click here for more information.

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.

This news release is available on our World Wide Web home page at http://www.utsouthwestern.edu/home/news/index.html

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

Regular marijuana use increases risk of hepatitis C-related liver damage

Contact: Aimee Frank media@gastro.org 301-941-2620 American Gastroenterological Association

Bethesda, MD (Jan. 28, 2008) – Patients with chronic hepatitis C (HCV) infection should not use marijuana (cannabis) daily, according to a study published in Clinical Gastroenterology and Hepatology, the official journal of the American Gastroenterological Association (AGA) Institute. Researchers found that HCV patients who used cannabis daily were at significantly higher risk of moderate to severe liver fibrosis, or tissue scarring. Additionally, patients with moderate to heavy alcohol use combined with regular cannabis use experienced an even greater risk of liver fibrosis. The recommendation to avoid cannabis is especially important in patients who are coinfected with HCV/HIV since the progression of fibrosis is already greater in these patients.

“Hepatitis C is a major public health concern and the number of patients developing complications of chronic disease is on the rise,” according to Norah Terrault, MD, MPH, from the University of California, San Francisco and lead investigator of the study. “It is essential that we identify risk factors that can be modified to prevent and/or lessen the progression of HCV to fibrosis, cirrhosis and even liver cancer. These complications of chronic HCV infection will significantly contribute to the overall burden of liver disease in the U.S. and will continue to increase in the next decade.”

This is the first study that evaluates the relationship between alcohol and cannabis use in patients with HCV and those coinfected with HCV/HIV. It is of great importance to disease management that physicians understand the factors influencing HCV disease severity, especially those that are potentially modifiable. The use and abuse of both alcohol and marijuana together is not an uncommon behavior. Also, individuals who are moderate and heavy users of alcohol may use cannabis as a substitute to reduce their alcohol intake, especially after receiving a diagnosis like HCV, which affects their liver.

Researchers found a significant association between daily versus non-daily cannabis use and moderate to severe fibrosis when reviewing this factor alone. Other factors contributing to increased fibrosis included age at enrollment, lifetime duration of alcohol use, lifetime duration of moderate to heavy alcohol use and necroinflammatory score (stage of fibrosis). In reviewing combined factors, there was a strong (nearly 7-fold higher risk) and independent relationship between daily cannabis use and moderate to severe fibrosis. Gender, race, body mass index, HCV viral load and genotype, HIV coinfection, source of HCV infection, and biopsy length were not significantly associated with moderate to severe fibrosis.

Of the 328 patients screened for the study, 204 patients were included in the analysis. The baseline characteristics of those included in the study were similar to those excluded with the exception of daily cannabis use (13.7 percent of those studied used cannabis daily versus 6.45 percent of those not included). Patients who used cannabis daily had a significantly lower body mass index than non-daily users (25.2 versus 26.4), were more likely to be using medically prescribed cannabis (57.1 percent versus 8.79 percent), and more likely to have HIV coinfection (39.3 percent versus 18.2 percent).

The prevalence of cannabis use amongst adults in the U.S. is estimated to be almost 4 percent. Regular use has increased in certain population subgroups, including those aged 18 to 29.

Hepatitis is an inflammation of the liver. Hepatitis C is the most common form of hepatitis and infects nearly 4 million people in the U.S., with an estimated 150,000 new cases diagnosed each year. While it can be spread through blood transfusions and contaminated needles, for a substantial number of patients, the cause is unknown. This form of viral hepatitis may lead to cirrhosis, or scarring, of the liver. Coinfection of hepatitis C in patients who are HIV positive is common; about one quarter of patients infected with HIV are infected with hepatitis C. The majority of these patients, 50 to 90 percent, were infected through injection drug use. Hepatitis C ranks with alcohol abuse as the most common cause of chronic liver disease and leads to about 1,000 liver transplants yearly in the U.S.

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About the AGA Institute

The American Gastroenterological Association (AGA) is dedicated to the mission of advancing the science and practice of gastroenterology. Founded in 1897, the AGA is one of the oldest medical-specialty societies in the United States. Comprised of two non-profit organizations—the AGA and the AGA Institute—our more than 16,000 members include physicians and scientists who research, diagnose and treat disorders of the gastrointestinal tract and liver. The AGA, a 501(c6) organization, administers all membership and public policy activities, while the AGA Institute, a 501(c3) organization, runs the organization’s practice, research and educational programs. On a monthly basis, the AGA Institute publishes two highly respected journals, Gastroenterology and Clinical Gastroenterology and Hepatology. The organization’s annual meeting is Digestive Disease Week®, which is held each May and is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. For more information, please visit www.gastro.org.

About Clinical Gastroenterology and Hepatology

The mission of Clinical Gastroenterology and Hepatology is to provide readers with a broad spectrum of themes in clinical gastroenterology and hepatology. This monthly peer-reviewed journal includes original articles as well as scholarly reviews, with the goal that all articles published will be immediately relevant to the practice of gastroenterology and hepatology. For more information, visit

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