BOSTON, MA -- November 3, 2004 -- It is possible to significantly increase sustained viral responses (SVR) and reduce relapse rates in patients with hepatitis C virus (HCV) infection by extending the duration of treatment with pegylated interferon alfa-2a (Pegasys) plus ribavirin (Copegus), according to the results of a large, randomized, multicenter trial.

This drug combination is currently approved for 48 weeks of treatment, but viral kinetic and pilot studies suggest that longer treatment might increase SVR in

patients who do not have a rapid decrease in HCV RNA after the start of treatment, said José Sanchez-Tapias, senior consultant, Liver Unit, Hospital Clínico i Provincial, University of Barcelona, Barcelona, Spain.

He presented the findings here on November 1st at the 55th Annual Meeting of the American Association for the Study of Liver Diseases.

The study involved 517 patients with HCV infection treated at 13 centers in Spain. After 4 weeks of treatment with the combination of pegylated interferon 180 mcg/week and ribavirin 800 mg/day, 326 patients did not have a rapid virologic response and were randomized to either 48 weeks or 72 weeks of treatment with the same combination. They were followed for an additional 24 weeks post-treatment.

The SVR rate after 72 weeks of treatment was 45% and 32% after 48 weeks, a significant difference. There was also a significant difference in relapse rates in the two groups, 13% and 48%.

The two groups had similar types and incidence of adverse events, Dr. Sanchez-Tapias said. The most frequent were asthenia, headache, and fever. Serious adverse events were seen in 5% in the 48-week treatment and 8% in the 72-week treatment. The proportion of patients who withdrew due to adverse events or laboratory abnormalities was also similar between the two groups.

"This opens up a new way to cure more patients with chronic HCV infection," said Dr. Sanchez-Tapias. "Extending therapy to 72 weeks does not increase the number or severity of adverse events."

The next research step is to see the effect of higher doses of interferon in this prolonged therapy for those patients who did not respond, he said. "We hope to learn how to individualize therapy by identifying those who are likely to have a high probability of a sustained response," Dr. Sanchez-Tapias said.

[Presentation title: "Longer Treatment Duration with Peginterferon Alfa-2a (40KD) (Pegasys) and Ribavirin (Copegus) in Naïve Patients with Chronic Hepatitis C and Detectable HCV RNA by Week 4 of Therapy: Final Results of the Randomized, Multicenter Teravic-4 Study." Abstract 126]

Doctor's Guide Publishing Limited

AASLD: Drug Combination May Become New Treatment Paradigm for Hepatitis C Virus

By Mark L. Fuerst

BOSTON, MA -- November 3, 2004 -- The combination of a novel, oral polymerase inhibitor and pegylated interferon, may become the new treatment paradigm for hepatitis C virus (HCV) infections, according to results of an interim analysis presented here on November 1st at the 55th Annual Meeting of the American Association for the Study of Liver Diseases.

This new combination "may offer improved efficacy outcomes, especially for HCV patients who are nonresponders or have failed to clear the virus with standard therapy," said Nezam Afdhal, associate professor of medicine at Harvard University.

During his presentation, Dr. Afdhal said that the polymerase inhibitor, NM 283, is the first in a new class of designer drugs that specifically block a step in HCV viral replication. Unlike existing therapies, which are administered by injection, NM 283 is taken orally and appears to have fewer adverse effects than existing agents, Dr. Afdhal said.

He presented data from an ongoing, phase 2, clinical study that evaluated the combination of NM 283 and pegylated interferon. The trial includes 30 treatment-naïve patients with compensated chronic HCV infections. They received NM 283 in escalating daily doses of 400-, 600-, and 800-mg, alone or in combination with pegylated interferon 1.0 mcg/kg subcutaneously on days 8, 15, and 22. At day 8 they reached the 800-mg dose of NM 283.

Dr. Afdhal presented results from an interim analysis of 19 patients, 12 in the combination arm and 7 in the NM283 alone arm. He said that 75% of patients treated with the combination experienced early virologic response. An early virologic response was correlated with an improved chance of sustained viral clearance, he said.

Patients receiving the combination therapy achieved a mean 2.7 log viral load reduction through week 4, representing a 99.8% reduction in HCV RNA. Dr. Afdhal said that this result is consistent with preclinical data that

suggested a synergistic antiviral effect for the combination of NM 283 plus interferon-alfa.

Dr. Afdhal said the safety of the combination therapy was "satisfactory, with typical side effects expected with interferon, and a high compliance rate [more than 90%]."

"This is the first agent in the class to be effective, it has a good safety profile, and is additive with interferon. It's the start of a new paradigm for treating HCV infection," Dr. Afdhal said.

[Presentation title: "Final Phase I/II Trial Results for NM283, a New Polymerase Inhibitor for Hepatitis C: Antiviral Efficacy and Tolerance in Patients with HCV-1 Infection, Including Previous Interferon Failures." Abstract LB03]

Doctor's Guide Publishing Limited

AASLD – Cognitive Impairment in Patients With Chronic Hepatitis C

Presentation Time: 10/31/2004

Author Block:

Doron Levi Zamir, Barzilai Hospital, Ashkelon, Israel; Simion Kerzman, Anima Scan, Ashdod, Israel; Steven Melnik, Ehud Melzer, Kaplan Hospital, Rehovot, Israel; Vaneli Maguli, Zoya Aladjem, Ron Milo, Zoya Aladjem, Barzilai Hospital, Ashkelon, Israel.

Abstract Body:

Background: Cognitive deficit was reported in hepatic cirrhosis even in early stages. Recent publications demonstrated cognitive impairment in patients with chronic HCV hepatitis even before the development of cirrhosis.

Aims: to check whether there is cognitive impairment in patients with chronic HCV hepatitis and to find the type of cognitive impairment.

Methods: A group of 28 patients with active chronic hepatitis C all planned for treatment with PEG interferon + Ribavirin was evaluated. Patients with impaired Mini Mental State Examination or with major depression were excluded previously. Ten volunteers with the same demographic parameters were chosen as a control group. Both groups underwent a computerized neuropsychological assessment “CogScan” which included 15 psychologic tests: Finger Tapping Test

(FTT), Inspection time (IT), Motion Perception Test (MPT), Simple Reaction Time (SRT), Choice Reaction Time, Immediate and Delayed Memory for Pictures, Words and Faces, Stroop test, Time-Accuracy Tradeoff test (TATT), Digit Symbol Substitution Test (DSST), and Continuous Performance test (CPT). Statistical analysis was performed using t-test for Equality of Means. Probability was estimated (p value<0.05).

Results: The patients with hepatitis C were found to be cognitively impaired in all subtests, except sustained attention (CPT) versus control subjects. Most impairments were subtests of motor output, selective attention (Stroop test, accuracy), working memory and pair-associated learning (DSST test).

Conclusions: Patients with chronic HCV hepatitis have significant impairment in all stages of information processing. Deficits in performance on tests of selective attention, working memory and learning ability suggests an impairment in fronto-subcortical circuits, especially in anterior cingulate girus. These functions have major importance in everyday activity, quality of life and driving skills. The correlation between severity of disease and degree of cognitive impairment may necessitate further investigation.

(Presentation title: “Information Processing Deficits In Patients With Chronic Hepatitis C” Abstract 523)

AASLD: Treatment for Mental and Physical Fatigue in Hepatitis C Patients

By Maria Bishop

BOSTON, MA -- November 3, 2004 -- Patients with hepatitis C virus (HCV) rank both mental and physical fatigue as their primary complaint, according to research reported here on November 1st at the 55th Annual Meeting of the American Society for Liver Diseases.

In addition, a second study presented here on October 30th showed that there is a possibility that ondansetron (Zofran) might be an effective treatment for that complaint.

Zofran has been shown to be effective in patients with chronic fatigue syndrome and in chronic liver disease, prompting researchers to investigate its uses in patients

with chronic HCV, noted Albert Tran, MD, professor of hepatogastroenterology, Archet Hospital 2, Nice, France.

In a randomized, placebo-controlled, double blind trial, the Dr. Tran's team enrolled 36 patients with for whom fatigue was the predominant symptom, scoring more than 4 out of 0-10 on a visual analog scale (VAS).

Patients were treated with oral ondansetron 4 mg twice daily or placebo for 1 month, followed by 4 weeks of observation. Fatigue and depression were measured on day 0, 15, 30 and 60 using the Fatigue Impact Scale and Beck Depression Inventory, a validated self-report questionnaire.

Compared to placebo, ondansetron was shown to significantly reduce fatigue, with 30% improvement at day 15, day 30 and day 60. Ondansetron also significantly reduced fatigue at day 15 and day 60 compared to placebo; the difference reached statistical significance at day 30.

These observations support the concept that fatigue involves serotoninergic pathways, and even though Dr. Tran noted that ondansetron is too expensive yet to be indicated for this purpose, such data may encourage further evaluation of the alteration of central serotoninergic neurotransmission to combat fatigue in chronic liver disease.

[Presentation title: "Effect of Ondansetron, a 5-HT3 Receptor Antagonist, on Fatigue in Chronic Hepatitis C: a Randomized Double Blind Placebo Controlled Study." Abstract 354]

The Long-term Benefit of Estrogen Exposure on the Progression of Liver Fibrosis in Women Infected with Hepatitis C

Female sex is a protective factor for the progression of fibrosis in patients with chronic hepatitis C virus (HCV) infection. Experimental data suggest that estrogens may have an antifibrotic effect.

The objective of this study in Paris, France was to evaluate the influence of past pregnancies, oral contraceptives, menopause, and hormone replacement therapy (HRT) on liver fibrosis progression in HCV-infected women.

Four hundred seventy-two HCV-infected women received a survey regarding prior pregnancies, menopause, and the use of oral contraceptives and HRT.

The impact of these variables on liver fibrosis and its progression were evaluated using multivariate analyses considering all putative confounding factors.

Two hundred one women completed the survey (43% response rate), 157 of whom had an estimated date of HCV infection (96 postmenopausal women, 96 women with previous pregnancies, and 105 women with past use of oral contraceptives).

Through multivariate analyses, the estimated rate of fibrosis progression was higher in postmenopausal and nulliparous women and was associated with greater histological activity.

Prior use of oral contraceptives had no significant influence.

Among postmenopausal women, the estimated rate of fibrosis progression was lower in women who received HRT compared with untreated patients and was similar to that of premenopausal women.

The French authors conclude, “Menopause appears to be associated with accelerated liver fibrosis progression in HCV-infected women, an effect that may be prevented by HRT.”

“Pregnancies may have a beneficial impact on the long-term progression of liver fibrosis.”

Reference

V Di Martino and others. Progression of liver fibrosis in women infected with hepatitis C: Long-term benefit of estrogen exposure. Hepatology 40(6): 1426-1433. December 2004.

Initial Results Reported in Clinical Study of Herbal Product Honso® Sho-saiko-to (H09) for Hepatitis C Non-responders

Phoenix, AZ (PRWEB) December 1, 2004 -- A Japanese herbal product, Sho-saiko-to (H09), is under a clinical phase II trial by Memorial Sloan-Kettering Cancer Center to determine its effect on hepatitis C patients. The preliminary results of the trial have been reported at the 1st Annual Society of Integrative Oncology Conference in

New York on November 18th, 2004. The testing herbal product, Honso® Sho-saiko-to (H09), is manufactured and supplied by Honso Pharmaceutical Co., Ltd. headquartered in Nagoya Japan and branched in Phoenix, Arizona.

Chronic hepatitis C is associated with significant morbidity (liver cirrhosis and hepatocellular carcinoma) and mortality. Current treatment is based on interferon and ribavirin. However, treatment options are limited for patients who are not candidates for interferon-based therapy. This study is entitled "Sho-saiko-to for Patients with Chronic Hepatitis C Who Are Intolerant to Or Have Contraindication to Interferon-Based Therapy: A Phase II Study". Sho-saiko-to has been demonstrated in anti-fibrotic effect by inhibition of lipid peroxidation in hepatocytes and stellate cells in animal studies. It has also been shown to reduce aminotransferase levels and the incidence of hepatocellular carcinoma in hepatitis and liver cirrhosis patients.

According to the design of the clinical trial, 31 patients will receive Sho-saiko-to (H09) granules at 2.5 grams three times daily for 52 weeks. Ten patients have completed the treatment and the preliminary results have been reported. No serious adverse events have been attributed to Sho-saiko-to (H09) among all patients who enrolled in the trial.

Among the 10 patients who completed the study, reductions in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were observed in 8 patients, and reduction of viral load was observed in 4 out of 7 detectable patients. This suggests anti-inflammatory and anti-viral activity. Liver biopsy response is defined as decrease in Knodell score of 2 points or more after the treatment in a blind fashion by an expert pathologist. The histologic responses were observed in 2 of the 10 patients who completed the study. This suggests anti-fibrotic effect in chronic hepatitis C patients.

Japanese herbal medicine also known as Kampo is part of the East Asian Chinese medicine tradition. Kampo is fundamentally a clinical system based on the classical medical literature dating back to the Han Dynasty in ancient China. In Japan today, fully 75% of physicians use at least some of the traditional Kampo formulas. In the US, Sho-saiko-to (H09) is available in granules through health professionals and in tablet as Liver Kampo to consumers.

The Splashes Of Life

A Sioux Indian story…

My grandfather took me to the fish pond on the farm when I was about seven, and he told me to throw a stone into the water. He told me to watch the circles created by the stone. Then he asked me to think of myself as that stone person.

"You may create lots of splashes in your life but the waves that come from those splashes will disturb the peace of all your fellow creatures," he said.

"Remember that you are responsible for what you put in your circle and that circle will also touch many other circles. You will need to live in a way that allows the good that comes from your circle to send the peace of that goodness to others. The splash that comes from anger or jealousy will send those feelings to other circles. You are responsible for both."

That was the first time I realized each person creates the inner peace or discord that flows out into the world. We cannot create world peace if we are riddled with inner conflict, hatred, doubt, or anger. We radiate the feelings and thoughts that we hold inside, whether we speak them or not. Whatever is splashing around inside of us is spilling out into the world, creating beauty or discord with all other circles of life.

Remember the eternal wisdom:

WHATEVER YOU FOCUS ON EXPANDS...

~Author Unknown~

LiverHope Support Group

Helen Clark & Pat Buchanan

Co-Facilitators

16807 Canterbury Drive

Minnetonka, MN 55345-2621

Voicemail: (763) 780-0108

Email: info@liverhope.com

Fax: (763) 566-0589

Website: www.liverhope.com

Helen: (952) 933-0932 – helen@liverhope.com

Pat: (763) 566-3839 – pat@liverhope.com