Hope on horizon for patients with Hepatitis C: Sofosbuvir for 99% less comes to india

Wonder Hepatitis C drug almost here.....at 99% reduced price

Hepatitis C is a viral disease that mainly affects the liver and is transmitted parenterally ( through contaminated blood products, syringes etc), vertically (from mother to child in womb) and sexually.

More than 40% of patients infected with the virus develop chronic infection because the body is unable to eliminate the virus from the system.

Progression of chronic hepatitis is usually slow and culminates within 10-20 years of acquiring infection into cirrhosis and chronic liver failure that may be fatal without transplantation. About 4 out of every 100 patients with cirrhosis due to hepatitis C develop cancerous growths (hepatocellular carcinoma) in the liver that significantly reduces their survival. Alcoholism, obesity, diabetes mellitus, immunosuppressive medication and HIV infection are risk factors for early progression of chronic hepatitis to cirrhosis and liver failure.

In the absence of a reliable vaccine, treatment of chronic hepatitis C has so far yielded less than optimal results (40-55% sustained viral response). Silent undetected progression of disease, multiple genotypes of virus and  poor tolerance of patients to medications ( particularly those with cirrhosis) contribute to the poor response.

Inability of cirrhotic patients to tolerate medications and reduced effectiveness results in most patients having detectable virus in blood at time of transplantation. Reinfection of new liver occurs within hours of transplantation and inflammation of graft starts weeks to months after transplantation depending on various factors like viral load, type of liver graft, immunosuppression, age and other factors. Post transplant recurrence of hepatitis C is more difficult to treat due to the presence of immunosuppression and sustained virological response is between 15-50% in various studies. A significant number of patients may need a second graft between 5-25 years after transplantation for recurrence of hepatitis C and cirrhosis.

Treatment of chronic hepatitis C has hinged on mainly two drugs: the antiviral drug Ribavarin (RBV) and the immunobodulator drug Interferon (IFN). Most regimens for treatment of hepatitis B include RBV and IFN (usually in pegylated form). Genotype 1 infection in particular has significantly poor response to PEG-IFN and RBV. Recently it has been identified that those patients that have infection with CC subtype of IL28 gene has double the response when compared to CT or TT genotypes.

Further research into HCV treatment resulted in a new class of molecules called Protease inhibitors that inhibit viral enzymes 
 Bocepravir and Telaprevir were the first generation of protease inhibitors introduced for management of chronic hepatitis in untreated as well as previously treated patients with chronic HCV and compensated cirrhosis. Addition of a protease inhibitor to combination of IFN & RBV significantly increased the sustained viral response rate ( by 15-30%) for difficult to treat genotype 1 patients over IFN&RBV alone except in treatment experienced patients who were null responders. Monotherapy is not recommended because rapid resistance results.

Simepravir (SPV) is a second generation protease inhibitor effective against HCV introduced about a year ago. It is never used a monotherapy. For genotype 1 a patients , SPV in combination with IFN & RBV for both treatment naive and experienced patients with genotype 1 infection. It can also be effective in combination with RBV and Sofosbuvir for patients who cannot tolerate toxic IFN therapy. SPV based triple therapy is a superior alternative to first generation protease inhibitors and is better tolerated. It can also be used as an alternative to Sofosbuvir in combination with a longer course of IFN & RBV. One of the main disadvantages in the high cost .....about 70000 USD ( approximately Rs 43 lakh) for a 12 week course.

Sofosbuvir (SBV) is also a polymerase inhibitor effective against HCV introduced about a year ago. It is effective for all genotypes of HCV but FDA approved only for 1,2,3 &4. It can be used with RBV with or without PEG-IFN and has shown promise in treatment naive, experienced as well as HIV coinfected patients of chronic hepatitis C and compensated cirrhosis. It has high acceptability due to fewer side-effects and interactions, once daily dosing and pan-genotypic activity. For genotypes 2 & 3 an all oral regimen of SBV and RBV is effective. For 1,3,4 & 5 genotypes addition of PEG-IFN is recommended but for those who cannot tolerate IFN, combination of SBV,SMV with or without RBV is showing promise.

Therefore Sofosbuvir is considered a breakthrough wonder drug for HCV currently and is expected to figure in more and more regimens for HCV. The prohibitive cost of 84000 USD ( 55 lakh INR) has been the main deterrent in greater availability and application of the drug even among insured patients in the western world. The greatest benefit of SBV seems to be in genotype 1 patients which accounts for more than 60% patients in the USA. SBV monotherapy was effective in more than 70% patients in achieving SVR while in combination with IFN & RBV the SVAR rate was more than 90% even among null-responders.

In India the prevalence of HCV is between 3-5 % of the population with 20-25% of patients with chronic liver disease being due to HCV infection. Genotype 3 is the commonest in India (66%) while Genotype 1 is less common (13%). 

Reduction of SBV costs by nearly 99% to USD 900 ( 55000 Rs)  for 12 weeks by the company, is therefore a hugely welcome step to liver physicians caring for patients with HCV infection, particularly null-responders, relapsers or patients with genotype 1 and those who cannot tolerate IFN therapy. Though still out of reach of many patients in India, it will be an option for insured or reimbursed patients who could have more effective treatment to prevent the development of cirrhosis or liver cancer or requirement of liver transplantation in the future.

World Organ Donation Day....Be an organ donor, wipe tears from many a eye

We make a living by what we get, but we make a life by what we GIVE

One donor can save as many as 9 lives

If you had the ability to save 9 lives...wouldn't you?

 After brain-death, organs like heart, lungs, intestines, pancreas, liver and kidneys as well as tissues like cornea of the eye, blood vessels, bones, tendons can be donated to save or improve the lives of many others. Immediately after the heart has stopped beating in certain situations the kidneys and liver can be rapidly harvested and used for transplantation. However beyond a few minutes after the heart stops beating,only  tissues can  be used for donation.

In India, donation after heart stops beating (donation after cardiac death ) has not yet been introduced for multiple reasons. The law allows organ retrieval from brain dead (but heart beating) donors and living related donors.

There is a massive shortage of donor organs in India
Organ donation rate in India is among the lowest in the world standing at 0.08 donations per million deaths as compared to 10-30 per million deaths seen in most parts of the western world. A single organ donor can provide a liver, two kidneys, intestine, pancreas, heart, two lungs that can potentially save the lives of nine others who are suffering from failure of their own organs. In addition sight of two blind persons can be restored. Tissues such as bone, tendons and skin from a single donor can be used to restore function and improve life of several people. As a result of this, the nearly 70 lakh Indian patients with corneal blindness, 3 lakh with dialysis dependent renal failure and 1 lakh with advanced liver disease need nothing short of a miracle to happen in order to get a cornea, kidney or liver from a brain dead (deceased donor). 

Major hurdles in organ donation
Legal
Social
Procedural

Legal hurdles
The Human Organ Transplant Act passed by parliament in 1995 has been passed by most state assemblies. The law has performed commendably in streamlining the process of organ donation, brain death declaration and significantly reducing if not eliminating the ghastly organ trade. However certain well-meaning but probably ill conceived rules have inadvertently prevented organ donation from really taking off. The recently introduced amendments would probably help increase the facilitation when they are in effect.
Prominent among the hurdles are:
For organ harvesting to be performed the hospital where the donor is must only be a transplant center or a registered non-transplant retrieval centre

Brain death declaration required certification by four doctors one of whom must be a neurologist or neurosurgeon

The person in charge of the body (next of kin) has to consent for donation to proceed even if it overrules the brain-dead persons expressed living intention in the form or donor card or living will.

This excludes a large number of hospitals with ICUs and potentially brain dead donors from offering organs for donation. As a result less than 10% potential organ donors in India end up donating organs as opposed to more than 25% in the rest of the world.

Social
The social, cultural and religious issues are myriad. 

Despite most religions teachings
 having no major objections to organ donation, most families decline donation on religious grounds based on misconceptions that a person without organs will not be allowed in heaven or a person who is not buried or cremated with all organs will be reborn without those organs.

Religious teachings & organ donation

Steeped in  traditions and illiteracy, many sections of society find it difficult to accept that their loved one whose heart is still beating is actually not with them anymore. Added to this dangerous mix is a motley crew of community elders, village panchayats and ill informed practitioners of traditional medicine who parochially impose their views on the family of the brain-dead patient offering unrealistic hopes that their patient will miraculously recover from his irreversible coma. This often creates anger and a trust deficit between the brain-dead persons family and counselors who are perceived to be in pursuit of profit at the expense of the life of their loved one.

All the above however pales in front of the rank indifference and apathy shown by medical professionals towards the entire process of organ donation. In the absence of motivation from being a part of a transplant center, a majority of medical professions continue to manage patients with irreversible coma without broaching the subject of organ donation or a reluctant to discuss the issue with patient family citing fears of angry backlash from family members.An equal number of medical professionals themselves harbor numerous misconceptions and misgivings regarding organ donation. The medical education in India until recently had no inclusion of organ donation and brain death in its curriculum. 

Procedural 
 In a survey it was estimated that there has been a 51% increase in unnatural deaths in the decade 2002-2012. Nearly 32.6 accidental occur in India per 100,000 population. In 2012-2013 there were nearly 4,00,000 accidental deaths of which more than 94% were unnatural. nearly 42% of these occur following rail or road traffic accidents. Out of all accidental deaths, approximately 10-15% are due to irreversible injury to brain. Therefor at current estimates, there are between 30000-40000 potential candidates for donation after brain death amongst accidental deaths annually. However less than 500 donations happen across the country in any given year.

Ignoring the legal and social hurdles for a moment, this has not only a lot to do with poor trauma and transport services for maintaining these victims till they reach hospital but also to red-tapism, tedious and laborious paperwork and alarming apathy on part of investigating officers, forensic experts and other agencies in allowing organ donation to proceed in the brain dead individual is a victim in a crime or accident scene.

All is not lost...through tireless campaigning by several individuals, organisations and agencies of governments who have awakened albeit belatedly to the issue, the organ donation rate has nearly quadrupled over the last 10 years. There is a lot of distance to be covered. At a mere 1-2 donations per million deaths, this country can meet its transplant needs so that nobody with organ failure has to die waiting for an organ.

The medical fraternity should lead by example by pledging their organs and encouraging their friends and family to register to be donors. 

At my center, to commemorate World Organ Donation Day, we took a pledge to donate all our usable organs after our death and to work to encourage our friends and family towards registering themselves as organ donors.

"We, the doctors and staff of Continental Hospital, on the occasion of World Organ Donation Day, hereby unconditionally pledge to donate all our usable organs and tissues following our death to save the lives of others. We take this pledge in the presence of the almighty and our soul as our witnesses.

We also swear to work towards educating our families and friends about organ donation and also to encourage them to be organ donors and give the gift of life to others after they are gone"

Organ donation logo

Pledge board signing

 
I invite and urge all readers to join this movement with a poem I penned sometime ago

Your body is but a shrine
That envelops your soul
A gift from your maker
To help discharge your earthly role

When it's time and end is nigh
Your soul readies to depart
The body, it's shell
Free from your essence
Is but a wilted flower
Devoid of fragrance

Consigned to flames or ceremonially buried
To tune of hymns, chants and litanies varied
Into wasteful ashes or earth shall return
All precious body parts turn by turn
Many a heart, kidneys and liver
In needy others which could still deliver



Arise, its never too early to make the choice
Gift your organs after you've left
Save many lives that remain bereft
Wipe tears from many a eye
That's the only way to leave this world on a high!