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Based on presentations from an EASL Satellite Symposium titled: An Update on Ribavirin Analogues: Meeting the Challenge of Anemia in Hepatitis C Treatment Includes: Educational Modules Interactive Case Challenges Speakers' PowerPoint Slides     Treating HCV-infected Patients at High Risk of Anemia Yves Benhamou, MD, PhD Incidence of Anemia Related to HCV Therapy Impact of Anemia Related to HCV Therapy Mechanism of HCV Therapy-related Anemia Management of Anemia Related to HCV Therapy Click here Ribavirin Analogues and Ribavirin-like Molecules: New Directions in Antiviral Therapy Robert G. Gish, MD Ribavirin Ribavirin-Associated Anemia Viramidine: Preclinical and Early Clinical Studies Viramidine: Phase 2 Study Levovirin Merimepodib (VX-497) Click here Two Interactive Case Challenges, by Dr. Raymond T. Chung, MD: Management of a Treatment-Naive Man With HCV Genotype 1 and Advanced Fibrosis Management of Chronic Hepatitis C in a Man With HIV Coinfection Speakers' slides from the live symposium These slide presentations are in Microsoft PowerPoint format. To view the slides in your browser, simply click the 'Download Slides' button. Mac Users: Slides will be downloaded to, and can be accessed from your desktop. You must be logged into the clinicaloptions.com site to view or save the slides.   Treating HCV-infected Patients at High Risk of Anemia Ribavirin Analogues and Ribavirin-like Molecules: New Directions in Antiviral Therapy

This program is available online at:
http://clinicaloptions.com/go/

WARNING:

·         REBETOL monotherapy is not effective for the treatment of chronic hepatitis C virus infection and should not be used alone for this indication.  (See WARNINGS.)

·         The primary toxicity of ribavirin is hemolytic anemia.  The anemia associated with REBETOL therapy may result in worsening of cardiac disease that has lead to fatal and nonfatal myocardial infarctions.  Patients with a history of significant or unstable cardiac disease should not be treated with REBETOL.  (See WARNINGS, ADVERSE REACTIONS, and DOSAGE AND ADMINISTRATION.)

·         Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin.  In addition, ribavirin has a multiple-dose half-life of 12 days, and so it may persist in nonplasma compartments for as long as 6 months.  Therefore, REBETOL therapy is contraindicated in women who are pregnant and in the male partners of women who are pregnant.  Extreme care must be taken to avoid pregnancy during therapy and for 6 months after completion of treatment in both female patients and in female partners of male patients who are taking REBETOL therapy.  At least two reliable forms of effective contraception must be utilized during treatment and during the 6-month post-treatment follow-up period.  (See CONTRAINDICATIONS, WARNINGS, PRECAUTIONS-Information for Patients and Pregnancy Category X.) 

·         Alpha interferons, including PEG-INTRON and INTRON A, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic and infectious disorders.  Patients should be monitored closely with periodic clinical and laboratory evaluations.  Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy.  In many but not all cases these disorders resolve after stopping therapy with PEG-INTRON or INTRON A.  (See WARNINGS, ADVERSE REACTIONS.)

08/01/03
 

Bone damage - more than just nukes involved

.....combination of the anti-hepatitis-C nuke ribavirin with interferon-alpha had an increased risk of developing thinning bones compared to other people with hepatitis C who used interferon only.

TreatmentUpdate 117 - 2001 May; Volume 13 Issue 1
Hosein SR

The Australian study that uncovered a link between high levels of lactic acid and bone damage in PHAs (see previous story) is perhaps not surprising. Last year, researchers in Spain found that people with hepatitis C virus infection (who were HIV negative) who used a combination of the anti-hepatitis-C nuke ribavirin with interferon-alpha had an increased risk of developing thinning bones compared to other people with hepatitis C who used interferon only.

The common link between the HIV positive and HIV negative groups of people is the use of a group of drugs called nukes. These drugs damage the energy-producing parts of a cell, called mitochondria, and appear to cause the liver to produce higher-than-normal levels of lactic acid, or lactate.

Although both the Australian and Spanish results need to be confirmed by other researchers, it is important to note that there are other factors associated with bone loss. Some of these factors likely play a role in the bone health of PHAs. These factors can include the following:

Medical conditions

• diabetes
• kidney dysfunction
• thyroid dysfunction
• liver damage
• pancreatitis
• less-than-normal levels of testosterone (men)
• less-than-normal levels of estrogen (women)

Nutritional issues

• poor eating habits
• not eating enough calcium and magnesium-rich food
• not getting enough vitamin D

Lifestyle

• excessive bed rest
• no regular weight-lifting exercise

Drugs

• alcohol abuse
• corticosteroid use

Protecting bones

Researchers are not sure about the best way to protect the bones of HAART users. A first step might be to develop a regimen of nutrients that nourish and protect mitochondria:

• vitamins C and E
• L-carnitine
• co-enzyme Q10
• B-complex vitamins

Another step may be to take supplements of bone-building nutrients such as calcium and vitamin D3. To help maintain bone health, the dose of calcium recommended by the American Institute of Medicine for "older adults" is between 1,000 to 1,500 mg per day. The best dose of vitamin D3 for adults with osteoporosis is not clear but is probably somewhere between 400 to 1,000 international units per day. Readers should note that there appear to be factors other than nuke-related bone damage which need further study.

Protease inhibitors and non-nukes

Even though the Australian researchers mentioned in the previous report on lactic acidosis and bones found little or no connection between thinning bones and protease inhibitors (PIs) or non-nukes, other researchers may have found such a link. A research team in the U.S. has found that in lab experiments PIs and non-nukes impair the liver's ability to convert vitamin D to its useful or "activated" form, vitamin D3. Without sufficient amounts of active vitamin D, the body may be unable to absorb and retain enough calcium to build and maintain strong bones.

PIs may also interfere with the growth and development of cells in the bone marrow that eventually turn into bone-building cells.

It is also possible that HAART may upset certain chemical signals, such as TNF, used by both the immune system and bone cells. This can have the effect of unnecessarily prolonging the life of specialized cells whose function is to tear down bones. Further study of the drugs that make up HAART and their impact on bone health needs to be done.

REFERENCES

1. Scribner AN, Troia-Cancio PV, Cox BA, et al. Osteonecrosis in HIV: a case control study. JAIDS 2000;25:19-25.

2. Knobel H, Guelar A, Vallecillo G, et al. Osteopenia in HIV-infected patients: is it the disease or is it the treatment? AIDS 2001;15(6):807-808.

3. Solís-Herruzo JA, Castellano G, Fernández I, et al. Decreased bone mineral density after therapy with alpha interferon in combination with ribavirin for chronic hepatitis. Journal of Hepatology 2000;33:812-817.

4. Chiu KM, Keller ET, Crenshaw TD and Gravenstein S. Carnitine and dehydroepiandrosterone sulfate induce protein synthesis in procine primary osteoblast-like cells. Calcified Tissue International 1999;64:527-533.

5. Varanasi SS, Francis RM, Berger CEM, et al. Mitochondrial DNA deletion associated oxidative stress and severe male osteoporosis. Osteoporosis International 1999;10:143-149.

6. Hagen TM, Ingersoll RT, Lykkesfeldt J, et al. (R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate. Federation of American Societies for Experimental Biology Journal 1999;13:411-418.

7. Leidig-Bruckner G, Hsch S, Dodidou P, et al. Frequency and predictors of osteoporotic fractures after cardiac or liver transplantation: a follow-up study. Lancet 2001;357:342-347.

8. O'Brien KO, Razavi M, Henderson RA, et al. Bone mineral content in girls perinatally ..

Interferon alfa-2a, recombinant = Roferon-A

Central nervous system adverse reactions have been reported in a number of patients. These reactions included decreased mental status, dizziness, impaired memory, agitation, manic behavior and psychotic reactions. More severe obtundation and coma have been rarely observed. Most of these abnormalities were mild and reversible within a few days to 3 weeks upon dose reduction or discontinuation of Roferon-A therapy. Careful periodic neuropsychiatric monitoring of all patients is recommended.

Read Study The Dangers of Interferon