LiverHope

Hepatitis C Virus Replication Seen in Patients With Apparent Viral Clearance

NEW YORK (Reuters Health) Nov 07, 2006 - Hepatitis C virus (HCV) can persist and replicate in the livers of patients who have apparently cleared the virus from their blood after antiviral therapy, according to a report in the November 15th issue of Clinical Infectious Diseases.

Previous studies have identified positive-strand HCV RNA in the hepatic tissue of patients with a sustained treatment response. However, it was unclear if viable HCV, capable of replication, was actually present since negative-strand HCV RNA, the viral replicative intermediate, was not detected.

In the present study, Dr. Vicente Carreno and colleagues, from the Foundation for the Study of Viral Hepatitis in Madrid, Spain, tested for positive- and negative-strand HCV RNA in hepatic tissue taken from 20 patients who had shown no serologic evidence of the virus for 35.4 months on average.

Nineteen of the 20 samples contained positive-strand HCV RNA, the report indicates. Moreover, of these 19 samples, 15 had negative-strand HCV RNA also.

Testing of peripheral blood mononuclear cells revealed positive-strand HCV RNA in 13 of 20 samples. Twelve of the 13 samples also contained negative-strand HCV RNA.

The post-treatment liver biopsy specimens of 15 patients still displayed liver necroinflammation, the findings indicate, and fibrosis remained present in seven patients. However, hepatic damage improved in all but two of the patients.

The findings indicate that "these patients did not experience HCV infection clearance, despite apparent clinical disease resolution," the researchers conclude.

They say the possibility of reactivation should be borne in mind if patients undergo chemotherapy or become immunosuppressed, for example. The team cites a case in which HCV reemerged following prednisone therapy, after 8.5 years of negative test results.

Clin Infect Dis 2006;43:1277-1283.

November 7, 2006 (Boston) — Interim results of the Daily-dose consensus Interferon and Ribavirin Efficacy of Combined Therapy (DIRECT) trial were announced here this week at the 57th annual meeting of the American Association for the Study of Liver Diseases (AASLD).

This large, multicenter, randomized trial shows that daily treatment with consensus interferon plus ribavirin has a response rate of between 20% to 25% in patients with hepatitis C virus (HCV) infection who failed to respond to the currently approved pegylated formulation of interferon, usually administered 3 times a week, plus ribavirin.

"Consensus interferon produces constant pharmacologic pressure on HCV. It has good potency, with a shorter activity period.... In vitro studies have shown that it is more potent than interferon alfa-2a and alfa-2b," principal investigator Bruce Bacon, MD, director of the Division of Gastroenterology and Hepatology at St. Louis University School of Medicine and Co-Medical director of the Saint Louis University School of Medicine and Co-Medical director of the Saint Louis University Liver Center in Missouri, told Medscape in an interview.

The DIRECT trial involved more than 500 patients with HCV infection who were nonresponders to standard therapy. The study population included 77% with advanced liver fibrosis.

Patients were randomized to 1 of 2 doses of consensus interferon combined with ribavirin (1.0 - 1.2 g/day). Group 1 received 9 µg/day, group 2 received 15 µg/day and a third group received no treatment, with the intention to randomize patients in the no-treatment group to 1 of the 2 active treatment groups at 6 months if the DIRECT trial showed positive results.

"Interim analysis of the efficacy [of consensus interferon] was about 25% at 48 weeks," Dr. Bacon announced. "Fifteen to twenty percent are showing a sustained viral response, but that data is not in yet.... Some relapse was expected." There was no change in status of patients

randomized to no treatment and they were subsequently randomized to active treatment.

"The incidence and type of adverse events were about the same as with pegylated interferon. About 10% on the 9-µg dose and 15% on the 15-µg dose discontinued treatment," Dr. Bacon said. "But remember, this is fairly intensive therapy.

"These were nonresponders to the current best therapy for HCV," said Dr. Bacon. "The robustness of the failure to respond was good, which is one criticism of treatment response studies."

There has been some regression of fibrosis, which Dr. Bacon is watching with interest. Data on that plus sustained efficacy data should be available in the spring, and will be presented at the annual meeting of the European Association for the Study of the Liver, he said.

Dr. Bacon's study is supported by a grant from Valiant Pharmaceuticals International, and Dr. Bacon has disclosed a financial relationship with Valiant.

Robert Brown, MD, associate professor of medicine at Columbia University Medical Center in New York City and a specialist in digestive and liver diseases, called consensus interferon "consistently intriguing" in an interview with Medscape, "but we need to wait for the sustained efficacy data.

"I don't see consensus interferon as a first-line agent," Dr. Brown commented, "particularly because of its inconvenience, requiring daily injections. In addition, you would end up overtreating hepatitis C patients who may respond to pegylated interferon. That's why you need to give patients about 12 weeks to show a response to peg-interferon.... You can even predict response as early as 4 to 6 weeks in some nonresponders. You could switch to consensus interferon then, or may be able to switch over to another peg-interferon.

"What is another enormously exciting class of drugs [for the treatment of HCV] are the new protease inhibitors," Dr. Brown said. "The investigational agent VX-950 is one of these."

A study of VX-950 (Telaprevir, Vertex Pharmaceuticals, Inc) added to pegylated interferon-alfa-2a and ribavirin after 28 days of the 2-drug regimen, showed "a rapid and substantial antiviral effect," according to John G. McHutchison, MD, professor of medicine and director of

gastroenterology and hepatology research at Duke University in Durham, North Carolina. He and his colleagues in the multicenter trial of VX-950 studied the triple-drug regimen in 12 treatment-naive patients infected with HCV genotype 1.

The 3-drug regimen was well-tolerated and similar to that seen with pegylated interferon and ribavirin alone.

All patients had undetectable viral levels after 28 days of treatment. In 2 patients, levels were undetectable within 8 days of adding the protease inhibitor.

Twelve weeks after completion of VX-950 treatment, 11 patients continued to have undetectable viral levels.

Dr. McHutchison has disclosed a financial relationship with Vertex Pharmaceuticals, which funded the study.

Eugene R. Schiff, MD, professor of medicine and chief of the Division of Hepatology at the University of Miami in Florida, said the findings "equate to a cure of HCV. Unlike hepatitis B, HCV is not incorporated in the cell's DNA, so you can get a cure."

"With these results, you will see many more patients come for treatment," Dr. Schiff told Medscape. "At a maximum, only about 10% are being treated now."

Dr. Schiff receives funding from Pfizer Ltd for research in the field of HCV treatment.

"The protease inhibitors could revolutionize the treatment of HCV. The next 2 years...are going to bring a lot of change," Dr. Brown asserted.

TUESDAY, Oct. 31, 2006 (HealthDay News) -- A new drug called eltrombopag may enable certain hepatitis C patients to take antiviral medications they previously could not use to fight the disease, researchers say.

Hepatitis C patients with cirrhosis and abnormally low platelet levels -- a disorder called thrombocytopenia --

can't take two standard medications, ribavirin and pegylated interferon. These drugs, which are commonly used to fight hepatitis C infection, cause platelet levels to decrease even further.

However, eltrombopag works by stimulating cells in the bone marrow to produce more platelets, said the study's principal investigator Dr. John McHutchison, a liver specialist and professor of medicine at Duke University.

"Eltrombopag increases platelet levels to the point where patients with thrombocytopenia can be effectively treated with the antiviral therapies. If the promising results we've seen so far in these early clinical trials are borne out in future larger scale registration trials, we will be able to potentially treat many more patients for whom there are currently no options," McHutchison said in a prepared statement.

The Phase II trial included 74 hepatitis C patients with thrombocytopenia who were placed in one of four groups: three groups received eltrombopag at doses of 30 milligrams, 50 milligrams or 75 milligrams. Patients in the fourth group received a placebo.

"We found that 95 percent of the patients who received the highest dose of the new drug responded with increased levels of platelets, and 91 percent of those patients were then able to start antiviral therapy with pegylated interferon and ribavirin," McHutchison said. "After 12 weeks, 61 percent of these patients were still able to maintain antiviral therapy."

The study also found that platelet levels in 75 percent of the patients taking the lower doses of eltrombopag

increased enough to allow them to begin antiviral therapy. Of those, 53 percent of the patients taking the 50 milligram dose and 36 percent of those taking the 30 milligram dose were able to complete 12 weeks of antiviral treatment.

The study was expected to be presented Monday at the annual meeting of the American Association for Liver Disease, in Boston.

A laboratory study published this summer showed that HMG-CoA reductase inhibitors -- better known as statins -- were active against hepatitis C virus (HCV), especially when combined with interferon. However, there is some concern that statins, which are prescribed to treat elevated cholesterol, can cause liver toxicity.

They identified 174 patients seen between 2000 and 2004 who had chronic hepatitis C and were prescribed a statin. They also assembled 2 control cohorts: 129 patients with chronic hepatitis C who were not on statins, and 116 patients without HCV who were taking statins. Individuals with HBV or HIV coinfection were excluded. Baseline liver function tests -- including levels of the liver enzymes ALT and AST -- were recorded prior to statin initiation and at 3-9 month intervals over 2 years.

· Most patients were men (97%) and Caucasian (74%), with a mean age of 59.6 years and a mean body mass index (BMI) of 29.2.

· Statins discontinued due to increased liver enzymes was not more likely in patients with hepatitis C than in HCV negative individuals (8 total discontinuations; 4% vs 0.9%; P = non-significant).

· However, statins were discontinued for any reason more frequently in the group with hepatitis C (17.8% vs 8.6%; P < 0.05).

· Although mean baseline ALT and AST levels were significantly different between the 3 groups, the mean and maximum changes in liver enzyme levels from baseline were not significantly different.

"We found that patients with chronic HCV who were taking statins were not more likely to develop significant elevations in aminotransferases than control patients," the researchers concluded. "The results of our study indicate that statins can be safely used in the majority of patients in whom hyperlipidemia and chronic HCV coexist."

V Krishna, M Mann, R Yen, and others. Effect of Statin Use in Patients with Chronic HCV. 57th AASLD. Boston, MA. October 27-31, 2006. Abstract 894.

Helen Clark has announced that she will be retiring from her position as President of the LiverHope Support and Education Group. She has worked the past 8 years non-stop towards helping patients and educating the public about Hepatitis C. Helen worked locally as well as nationally towards awareness and funding for this insidious disease. She has been featured in many publications and videos towards this cause. She has spent many hours on the phone counseling and has made countless trips to doctor’s visits with patients and held many hands during biopsies as well as walked on Washington to visit with Congress and the Senate to push for funding.

Helen will leave the organization on January 1, 2007 and she will be greatly missed by everyone.

Bruce Clark, Helen’s husband and our Treasurer will also be retiring and we wish him well too.

Rich Murray and Carol Forcier will be joining the LiverHope organization January 1, 2007 and will be a great addition to our family. Many of you know this engaged (and engaging) couple and I hope you will welcome them as our new group leaders.

Pat Buchanan will remain with the organization and welcomes the addition of Rich and Carol.

Please attend our next meeting on December 12^th to wish Helen and Bruce farewell and to welcome Rich and Carol. Please bring a snack or dessert to share.

A HeXus Carol (A Hepatitis Christmas Carol Parody): Based on The Twelve Days of Christmas

Hair falling-out, Some memory loss, Two bruised thighs, and Anemia and no energy.

Hives and a rash, Hair falling-out, Some memory loss, Two bruised thighs, and Anemia and no energy.

Seven months cold-sweating, Six months of flaking, Hives and a rash, Hair falling-out, Some memory loss, Two bruised thighs, and Anemia and no energy.

Eight months of ranting, Seven months cold-sweating, Six months of flaking, Hives and a rash, Hair falling-out, Some memory loss, Two bruised thighs, and Anemia and no energy.

Nine months of raving, Eight months of ranting, Seven months cold-sweating, Six months of flaking, Hives and a rash, Hair falling-out, Some memory loss, Two bruised thighs, and Anemia and no energy.

Ten months of leaking, Nine months of raving, Eight months of ranting, Seven months cold-sweating, Six months of flaking, Hives and a rash, Hair falling-out, Some memory loss, Two bruised thighs, and Anemia and no energy.

Eleven months of griping, Ten months of leaking, Nine months of raving, Eight months of ranting, Seven months cold-sweating, Six months of flaking, Hives and a rash, Hair falling-out, Some memory loss, Two bruised thighs, and Anemia and no energy.

Twelve months of migraines, Eleven months of griping, Ten months of leaking, Nine months of raving, Eight months of ranting, Seven months cold-sweating, Six months of flaking, Hives and a rash, Hair falling-out, Some memory loss, Two bruised thighs, and Anemia and no energy.

Tests for remission, Some facial rash, Hair growing back, Some memory found, Two white thighs, and the hope of a recovery.

LiverHope Support Group

Helen Clark & Pat Buchanan

Co-Facilitators

16807 Canterbury Drive

Minnetonka, MN 55345-2621

Voicemail: (763) 780-0108

Email: info@liverhope.com

Website: www.liverhope.com

Helen: helen@liverhope.com

Pat: patb@liverhope.com