INTRODUCTION:

Hepatitis C is an inflammation of the liver caused by an infection with the hepatitis C virus. The virus is transmitted mostly via direct contact with contaminated blood or blood products. At-risk groups are primarily drug abusers who share needles with others. Around 170 million people worldwide suffer from chronic hepatitis C, and in Austria these numbers are between 40,000 and 80,000.

Fig-1

New therapy

A new combination therapy allows chronic hepatitis C to be treated in a manner that is less aggressive yet equally efficient.

This is the result of a current study, led by primary author Peter Ferenci from the University Department of Internal Medicine III at the MedUni Vienna, which has been published in the highly New England Journal of Medicine. "This is a revolutionary breakthrough in the treatment of this disease and represents a huge improvement in the quality of life of those affected," says the Vienna hepatologist. Ferenci and a global group of scientists were able to demonstrate using 419 test subjects with chronic hepatitis C that the combined use of the protease inhibitor ABT-450r, the NS5A inhibitor Ombitasvir and the non-nucleoside polymerase inhibitor Dasubavir yields significantly higher cure outcomes than the previous therapy which involves Ribavarin and the hormone interferon (mostly in combination with a protease inhibitor). These therapies also had considerable side effects. The test subjects in these current "PEARL" studies were all in the early stages of the disease, i.e. before liver cirrhosis had developed.

Twelve weeks of treatment: almost a 100-percent cure rate- Says Ferenci: "After just twelve weeks, we had achieved an almost 100-percent cure rate with this new, side-effect-free therapy." The therapy involves three tablets -- two in the morning and one in the evening. Until now, patients with hepatitis C had to take Ribavirin and the hormone interferon for up to 18 months, and the side effects were considerable. With the new combination therapy, which is also free of interferon, this additional therapy is not required.^1,2

TABLE-1 Combination Antiviral Therapy for Hepatitis C

Generic Name	Brand Name
Peg interferon alfa-2a and ribavirin	Peg interferon
Peg interferon alfa-2b and Ribavirin	Peg intron /Rebetol Combo Pack

Fig-2

Mechanism of action-

Peg interferon— Peg interferon’s are chemically modified derivatives of interferon Alfa Peg interferon Alfa is available in two forms: peg interferon alfa-2a and peg interferon alfa-2b. Peg interferon alfa-2a consists of the covalent attachment of a 40-kD branched PEG chain to interferon alfa-2a; peg interferon alfa-2b consists of the covalent attachment of a 12-kD PEG linear chain to interferon alfa-2b. The two drugs differ pharmacokinetically in that peg interferon alfa-2a has a mean terminal half-life of approximately 80 hours, whereas the half-life of peg interferon alfa-2b is approximately 40 hours. The mechanism of action of interferon, a naturally produced protein, is not completely understood. This cytokine is thought to facilitate viral clearance partly by inducing cells infected with virus to manufacture antiviral proteins that disrupt viral replication processes and to function through more indirect immunomodulatory and anti inflammatory mechanisms.^4.5,6,7,8

RIBAVIRIN is a nucleoside analog which has a broad spectrum of antiviral activity. It inhibits the replication of RNA viruses in cell culture. Ribavirin is an old broad-spectrum antiviral that is highly effective when used in combination with interferon-α and also as part of triple therapies containing new inhibitors of the hepatitis C virus (HCV) non-structural (NS)3/4 protease or HCV NS5B polymerase for the treatment of patients with chronic hepatitis C. Ribavirin appears to decrease hepatitis C virus infectivity in a dose-dependent manner. Its mode of action is not completely understood, but several mechanisms may be involved:

· Depletion of intracellular triphosphate pools through direct inhibition of inosine monophosphate dehydrogenase

· Inhibition of the 5'-cap structure of viral mRNA

· Inhibition of the viral-dependent RNA polymerases

· Altering the balance between proinflammatory (Th1-like) and antiinflammatory (Th2-like) cytokines

· Inducing mutations into viral RNA

· Potentiating interferon action

Results from a recent Cochrane systemic review and meta analysis in which 72 clinical trials with a total of 9991 patients were included showed meaningfully that treatment with Ribavirin plus interferon-α, as compared with interferon-α alone, significantly reduced morbidity plus mortality and significantly improved sustained viral clearance in treatment-naive patients, virological relapsers and non-responders. Combination therapy also significantly improved liver histological response. In patients with advanced fibrosis, SVR to antiviral therapy has been shown to reduce liver-related morbidity and mortality.^{6, 7, 8}

An additional two drugs (telaprevir and boceprevir) have also been recommended as treatment options for use in combination with peg interferon–Ribavirin in people who have the type 1 hepatitis C virus.

Indication:

Combination antiviral therapy is prescribed for people who have ongoing (chronic) hepatitis C infection. It may be given to people who have never had treatment or when interferon alone has failed to control the disease.

Side effects:

All medicines have side effects. But many people don't feel the side effects, or they are able to deal with them. Consult doctor about the side effects of each medicine you take. Side effects are also listed in the information that comes with medicine.

Following are side-effects-

Trouble breathing, Swelling of your face, lips, tongue, or throat, Hives, Fatigue, headache, muscle and joint aches, fever, or chills, Nausea, loss of appetite, or weight loss, Irritability, insomnia, or confusion, Depression, Thyroid problems, Hair loss or skin rash, Low levels of red cells, white cells, and platelets in your blood.

Here are some important things to think about:

· Usually the benefits of the medicine are more important than any minor side effects.

· Side effects may go away after you take the medicine for a while.

· If side effects still bother you and you wonder if you should keep taking the medicine, call doctor.

· He or she may be able to lower your dose or change your medicine.

· Do not suddenly quit taking your medicine unless your doctor tells you to.

Special consideration-

· The specialist will order blood tests to check your liver enzyme levels and to see whether the virus is still present.

· Peg interferon and other interferon’s may be given without Ribavirin if you have anemia or heart or kidney problems.

· Periodic liver function tests and a liver biopsy every 3 to 5 years.

· In case of significant liver damage, antiviral therapy may slow the progression of liver damage or make liver cancer less likely.

· In case of obesity or have poorly controlled diabetes, there is a need to delay treatment until the weight or blood sugar under is control.

In children:

Only a few clinical trials have tested antiviral medicines in children. The results suggest that they work about as well in children as in adults. Combination therapy using interferon and Ribavirin is now approved by the U.S. Food and Drug Administration for use in children ages 3 to 17 years.

For women:

Do not use this medicine if you are pregnant or planning to get pregnant.

CHECKUPS-Follow-up care is a key part of treatment and safety. One have to be sure to make and go to all appointments, and call doctor if there is any problem.

ACKNOWLEDGEMENT:

At very outset, I would like to thank almighty for his presence. My sincere thanks goes to all participants of my study. lastly and most importantly I am grateful to everybody who was important to successful realization of thesis.

Conflict of interest:

There is no conflict of interest.

Funding source:

Self financed

REFERENCES:

1. Peter Ferenci et al. ABT-450/r–Ombitasvir and Dasabuvir with or without Ribavirin for HCV. New England Journal of Medicine, 2014; 140504060027001 DOI: 10.1056/NEJMoa1402338

2. Brok J, Gluud LL, Gluud C. Effects of adding ribavirin to interferon to treat chronic hepatitis C infection: a systematic review and meta-analysis of randomized trials. Arch Intern Med 2005; 165: 2206-12.

3. Veldt BJ, Heathcote EJ, Wedemeyer H, et al. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Ann Intern Med 2007; 147: 677-84.

4. Perry CM, Jarvis B. Peginterferon-α-2a (40kD): a review of its use in the management of chronic hepatitis C. Drugs 2001;61:2263-88.

5. Wang C, Pflugheber J, Sumpter R Jr, et al. Alfa interferon induces distinct translational control programs to suppress hepatitis C virus RNA replication. J Virol 2003;77:3898-912.

6. Roberts MJ, Bentley MD, Harris JM. Chemistry for peptide and protein PEGylation. Adv Drug Deliv Rev 2002;54:459-76.

7. Bailon P, Palleroni A, Schaffer CA, et al. Rational design of a potent, long-lasting form of interferon: a 40 kDa branched polyethylene glycol-conjugated interferon α-2a for the treatment of hepatitis C. Bioconjug Chem 2001;12:195-202.

8. Wang Y-S, Youngster S, Bausch J, Zhang R, McNemar C, Wyss DF. Identification of the major positional isomer of pegylated interferon alfa-2b. Biochemistry 2000;39:10634-40.

9. Sidwell RW, Huffman JH, Khare GP, Allen LB, Witkowski JT, Robins RK. Broad-spectrum antiviral activity of virazole: 1-beta-d-ribofuranosyl-1,2,4-triazole-3-carboxamide. Science 1972; 177: 705-6.

10. Poynard T, Marcellin P, Lee SS, et al. Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT). Lancet 1998; 352: 1426-32.

11. Mchutchison JG, Gordon SC, Schiff ER, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med 1998; 339: 1485-92

Received on 21.05.2014 Modified on 25.06.2014

Research J. Pharm. and Tech. 7(10): Oct. 2014 Page 1190-1192