One of the great horrors of Hepatitis C is cirrhosis, when the liver tissue becomes home to an increasing mass of scar tissue. It comes on us slowly, over the years, and it has been greatly feared because most people think it is irreversible but every week now I get messages from people telling me how well their liver has healed once the virus is gone.
So what is cirrhosis?
Essentially cirrhosis is scar tissue formed in the liver as the result of some form of toxin.
Alcohol abuse is one of the commonly known cause of cirrhosis however the battle between the Hep C virus and our own immune system is another cause.
The bad thing about cirrhosis, this scar tissue, is that it provides a place where the Hep C virus ‘hides’ from the medication we take to remove the virus. That is to say because scar tissue does not have blood vessels like normal flesh it is difficult for medication, which is carried in the blood, to penetrate, or saturate, scar tissue so virus that is living in the scarred areas of the liver is harder to reach. This is one reason why people with severe cirrhosis are often given longer treatment periods. This is particularly the case with Hepatitis C Genotype 3, which has proven a true beast to clear,
The other problem with cirrhosis/scar tissue is that this is the area where tumours or cancer is likely to form. The chances of getting liver cancer as part of the Hep C package becomes much higher when a person gets to cirrhosis stage.
How Well the Liver Heals. The level of liver damage/scarring is called Fibrosis and there are several ways of detecting and measuring fibrosis, which include the biopsy, CT scan, Ultrasound scan and Fibroscan.
The common measurement for fibrosis is the ‘F’. So F0 means no fibrosis, F1 a little, F2 more, F3 even more and F4 means a person has cirrhosis.
When I was tested using first Ultrasound, then CT Scan and then the Fibrascan my rating was F3 bordering on F4. In other words I was almost at the cirrhosis stage.
In other words I had a lot of scar tissue in my liver. This combined with my ALT (enzyme) levels of between 600 and 800 told my doctor that I probably had liver cancer or would get it soon.
That is one of the reasons I went to India immediately generic Sofosbuvir became available.
Now the point of all this stuff I have just written is to tell you that now my liver is at F1, in other words my liver has done a LOT of healing.
Of course if this was just about me and my liver it would not be very interesting however over the last 6 months, as more and more people complete their treatments and clear Hep C from their system, more and more people write to me and tell me the same story. Their ‘F’ ratings have dropped and dropped significantly. Lots of people report reaching F1 or even F0 after end of treatment.
So there are two things to take from this story: one is to get treatment as soon as possible so that you do not reach cirrhosis and the other is that once you have cleared the virus how well the liver heals.
The liver is an amazing organ and given half a chance with the removal of the virus and a good healthy life style then the liver will heal itself.
So cheer up if you are F1 or F2 or F3 or F4, once you clear the virus your liver will improve. Just how much it improves will probably depend largely on the life style choices you make post treatment, but given a chance your liver will do its best for you!
22nd November 2016
A Word on the Price of Generic Meds
I received an email today from a lady in India who had recently travelled there to buy generic Harvoni. She had ordered and paid for a 12 weeks supply from a local pharmacy and was waiting for delivery because these meds are not carried in stock by pharmacies in India so they had to be shipped down from Mumbai.
While she was waiting she started to worry.
HOW would she know these were the right medicines and not fakes?
So she wrote to me for advice, which I am always happy to give.
My reply was that there are almost no fake Hep C generics in India. In the 20 months that I have been working with people using Indian generic Hep C medicines I have not come across even one single instance of someone in India buying fake meds.
Fake Hep C meds do exist but I have only come across them in other places, never India. Generally if someone is going to make a counterfiet drug they will make the branded version not the generic version. Why go to all the trouble of making fake lables and fake tablets of a generic drug? If someone is going to go to all that trouble then they will make fake Harvoni or fake Epclusa.
Just like if someone is going to make fake sunglasses they will make fake Raybans and not a fake version of some cheap brand you can already buy at the supermarket for $20.
The reason for this is that the real generics are so cheap anyway in India and no reputable dealer would risk their reputation by supplying fakes.
So that is good news.
The next issue that arose from this lady’s email was price.
She told me that she had paid US$375 per bottle for generic Harvoni.
This price is way too high. For example the normal price generic Harvoni to be shipped from India to the USA, including shipping and various other costs, is generally not more than US$1,100 for 3 bottles (12 weeks treatment). Indeed the price is more often closer to US$1,000.
SO she has paid too much. Not a huge amount too much, the real price when buying generic medicines in India for 12 weeks treatment of Sof+_Dac or generic Harvoni should not be more than US$800 and prices around US$700 would be normal.
THE other issue is that whilst one does NOT need a prescription to buy these meds in India it is a very very good idea to get a prescription if you are returning home to where ever you are from carrying a treatment of prescription drugs.
A prescription from a reputable doctor in India will not cost more than $20.
INTERNATIONAL conventions allow a person to carry up to 12 weeks supply of prescription medicines across international borders however many countries will require you to have the prescription to prove that the medicines belong to you.
SO travelling to India to buy meds is a great idea and for people in a lot of places, such as Europe, it is a cheap option, particularly if you include a holiday or getting some dental work done. Indian densits are generally excellent.
But do your homework first.
I am always available to give free advice.
24th November 2016
New Zealand: The Land of the Long White Cloud.
Last week I flew to New Zealand to meet with a group of friends there who included Hep C activists, medical practitioners and also people who have been cured of their Hep C through generic treatment. I had been to New Zealand once before, more than forty years ago, and returning to New Zealand in such circumstances was an amazing journey for me because I was returning to the place where, 42 years earlier, I had gone ‘cold turkey’ to kick my heroin addiction, to kick the habit, which I did not know then, had given me Hepatitis C.
I guess I should share a little of that story.
I grew up around Sydney’s northern beaches and left home when I was 16 because of ongoing conflicts with my father.
That was in 1969.
I hit the road and lived where ever I could. Home was where ever I could find a place to sleep out of the rain. Sometimes it was in a dumped car in the bush or on a friend’s sofa or under a sheet of tin.
For short periods I rented rooms in shared houses but I was a restless soul and never stayed long in one place.
Eventually I drifted deeper and deeper into the drug culture of 1970’s Sydney and ended up becoming addicted to heroin at the age of 19.
Heroin was very available in those days with many tourists simply smuggling a few ounces from Thailand in their underwear or hidden in their luggage when they returned from a few weeks in Asia.
There were no sniffer dogs back then and Customs had not yet realised what was happening in the drug world in Australia.
Like most addicts I began a little low level drug dealing to support my habit and one day in the middle of a deal the police pounced on me. I had a pistol shoved in my face and was told my head would be blown off if I moved.
It turned out that the guy I was doing the deal with was a police informant and I had been set up. Of course I was a small fish and the few capsules of heroin I had on me earned me a fine and suspended sentence however the shock of having the pistol stuck in my face made me realise that the world I was living in was a world that would sooner or later kill me.
So I decided it was time to make a new start.
I had seen friends try to kick their habits and knew how hard it was so I was savvy enough to know that the only way I could have any hope of a new start was to get away from everyone I knew in the drug scene…. So I flew to New Zealand and went cold turkey in my tent camped in a forest near the Bay of Island on the very northern tip of New Zealand.
To cut a long story short I lived in New Zealand for a bit more than one year and stayed clean. I got involved in Tibetan Buddhism and also the martial art of Tai Kwon Do. I was fortunate to meet a Tibetan monk of great wisdom and a Korean Tai Kwon Do master who was equally wise in a different way and, under their guidance, I did a lot of meditation and got very, very fit, mentally and physically.
So after a year I returned to Australia and (not without a struggle) remained clean.
As a result I always considered New Zealand to be my spiritual homeland, the place where I was “born again” and the place where I managed to turn my life around, to step back from the brink of the abyss.
But from then until now I had never returned to New Zealand. A couple of times I almost did but it never happened.
So forty two years later I was back in the place of my rebirth. Not as a young man of 21 just learning about life but as an old man of 63 who had lived and learned.
What a different visit this was. The first time I knew no-one and had to go through a long time of being alone; alone and wrestling with my demons.
This time I was meeting dear friends and angels.
It is one of the wonders of being human in the 21st century that we can build relationships with people thousands of miles away so it was wonderful to finally meeting face to face with people who I have been corresponding with for more than a year. Pivotal to this meeting was my very good friend and Hep C activist Hazel Heal. Hazel lives in Dunedin and kindly organised a wonderful get together at her place.
The really amazing thing about this get together was that (I believe) every single person attending it had once had Hep C, but was now cured. That was certainly a first for me because in Australia there is not really any such close knit Hep C community (that I am aware of).
Hazel and I shared the common experience of being the first people in our respective countries to “come out” publicly about having Hep C and treating the disease with generics. Hazel had seen a news story about what I was doing in Australia and was that that moment about to sell her house to fund the treatment of her Hepatitis C with Harvoni. When she read about the generic option she treated with generics and now both has her home and her health. She is cured.
Hazel was also brave enough to go public with her story and this started the chain reaction in New Zealand that my media work had done in Australia.
Many people with Hep C in New Zealand began generic treatment. As in Australia there was great resistance to generics by the mainstream medical ‘Establishment’ and it was hard for New Zealanders to find a doctor who would write a prescription. But then as more and more results came through more doctors began to write prescriptions.
The flow of generics into NZ also put pressure on Big Pharma to reduce prices and the New Zealand government was able to negotiate a deal with Abbvie to make the VPak available through their health system at a very good price.
Of course the VPak is quite a good option for people with Genotype 1 but not so good for other genotypes so in New Zealand now many doctors actually tell their patients to go the generic route. This has all happened in less than 12 months and again shows how if a few brave people will make a stand and get some media attention is it possible to make positive changes happen very quickly.
Anyway back to my friends and the party.
We had the party at Hazel’s home (the one she would have had to have sold if not for generics) and I was honoured to be given a traditional Maori welcome and the most wonderful gift of a Maori ponamau, which is a pendant hand carved from New Zealand jade intended to be worn as a protection from negative forces. What was really special about this gift was that it was carved especially for me and included features that represented myself, my wife and my three sons. I was deeply moved and honoured to receive this gift and also the wonderful friendship of all the people I met in Dunedin.
9th December 2016
Fake and Counterfeit Hep C Medicines: Fear Based Propaganda.
Of the many emails I get every day asking about buying generic Hepatitis C medicines one of the frequently repeated questions is:
“How do I know that these meds are not fake?”
Along with this question is usually a comment about having read an article about fake or counterfeit medicines coming out of India.
So I thought I should re-visit this topic and just explain a couple of basic points.
Firstly I have been involved in helping people buy generic Hepatitis C medicines since May 2015, when they first became available from India.
In that time I have helped many thousands of people to buy generic Hep C meds from India and in that time I have never heard of even one person who has purchased fake or counterfeit generic Hep C medicine from India, not one.
Now having said that I will also say that I have heard of counterfeit Hep C meds being sold, but not from India and not counterfeit generic Hep C meds.
Let me explain why.
To set up the production of counterfeit medicines is not a simple thing.
First you need a pill press that will produce an exact replica of the pill you are counterfeiting, with identical imprint and shape and colour etc.
Next you have to have the same bottle, the same label, the same box, the same user’s instruction sheet and so on.
Of course all of these things can be done but it involves time and expense. So if a person is going to make counterfeit Hep C meds they are not going to make counterfeit generic meds they are going to make counterfeits of the expensive brand versions of the medicines. They will make counterfeit Harvoni, counterfeit Daklinza, counterfeit Epclusa and so on.
You ask why?
Because the cost of making a counterfeit bottle of Harvoni is exactly the same as making a counterfeit generic. So why counterfeit a product that sells for $1,000 when for exactly the same expense you can counterfeit a product that sells for $84,000!
That is why people make counterfeit RayBan sunglasses but do not make counterfeit versions of cheap brands of sunglasses that you can buy at a discount store.
If you are going to make counterfeit money then you make a fake $20 note not a fake $1 note because the cost of making the fake is the same.
So people making counterfeit drugs do not make counterfeit versions of the cheapest drugs on the market, generics, they make counterfeits of the most expensive.
It is that simple.
So why is there such a thing in everyone’s mind about buying fake Indian generic Hep C treatment? Even when there is not even one actual example of it every happening?
Simply because this is one of the ways that Big Pharma tries to deter people from using generic Hep C medicines.
It is a fear campaign. It is well organised with press releases and continual rumour mongering. Big Pharma has huge resources and teams of people dedicated to manipulating the media, creating fake news and public opinions. Big Pharma is expert at creating and spreading rumours about counterfeit generic Hep C medicines coming out of India. They pay people to do it.
But the truth is that they are rumours and have no basis in truth.
As I mentioned previously I have not come across even one instance of fake generic Hep C meds coming out of India.
How do I know?
Because people report their results to me every day and the results all show that there is not one person who has used fake meds to do their treatment. Yes there are some people who have relapsed after treatment and there are some people who have been “slow responders” but these results are statistically the same as the results from people who have done treatment using the brand versions like Sovaldi, Harvoni and Daklinza.
So in my experience there are no fake India generic Hep C meds however there are other scams. There are people who will charge too much, people who will take your money and then not deliver, or deliver less than promised. Normal online shopping type scams, common on the internet. Such scams as these are avoided simply by using suppliers who have a known track record. There are now many forums on Facebook and the Web where advice about suppliers is available. If these, and common sense, are used then there will be no problem.
So there is no need to worry about the “Counterfeit Meds” myth, the only thing you need to be concerned about is the integrity of your supplier.
18th December 2016
The Importance of Not Delaying Treatment
One of the most fantastic things about doing this work that I, assisting people access affordable Hep C treatment, is when someone writes to me and tells me they are cured and their liver is healing itself.
Unfortunately this does not happen for everyone. Below is a story sent to me a while back from Pete, an Australian guy who was in that first wave of people accessing generics. He had G3 and was a non-responder to treatment with Sof+Riba but refused to give up and tried again with Sof+Dac.
Please read his story, it is a story of courage and resilience and an amazing refusal to be defeated.
Pete’s Story: Fighting Back
It’s difficult to say when I contracted Hep C, most likely in the late 1970’s when I briefly experimented with IV opiates ( when I say brief I mean three times, and I didn’t even like their effects, but hey it only takes one infected shot ).
Or it could have been when I was traveling through Indonesia in the early 1970’s where I contracted a couple infections that required injections of antibiotics. One of those was given by friends who were I.V. drug users. Another injection of antibiotics was by Catholic nuns in a Leper Hospice. And then there was that tattoo as the last possibility.
Hepatitis C was unknown back in the 1970’s and 80’s, and it wasn’t until an acute onset with nausea, extreme fatigue and jaundice in 1996 that I was diagnosed with non A or B hepatitis. The doctor that diagnosed me really wasn’t up to speed, as Hep C was actually discovered in 1989; he couldn’t wait to get rid of me and offered no help or advice.
So I battled the transition from acute to chronic for a couple of years, until the amount of sick leave I had to take led to early retirement.
During that time I did suffer from some stupid discrimination from people who knew I had Hep C. Stuff like a group who wouldn’t use the plates and cutlery from the cafeteria that I ate in. Seriously dumb arseholes. But that said, the vast majority of my workmates and management were very supportive.
I did consult with specialists in the public system who offered nothing but invasive tests, so with the support of my new GP (who I have now been with for over twenty years now) I monitored and managed the monster, which turned out to be Genotype 3… the hardest dragon to slay.
Then in 2007 a routine ultrasound scan revealed cirrhosis, so it was back to another specialist who convinced me to undergo the interferon + ribavirin combo therapy. Needless to say it failed and gave me terrible side effects including pancytopenia which left me zero red blood cells and platelets. Interferon therapy caused me so much damage with no benefits.
(Pancytopenia is a deficiency of all types of blood cells, including white blood cells, red blood cells, and platelets. It occurs when your body cannot produce enough blood cells because the bone marrow stem cells that form blood cells do not function normally.)
With not more treatment options but with the support of my GP I did the best I could to manage my disease with many complimentary therapies and dietary and herbal supplements.
Then along came a T.V. current affairs show that my Mum saw and alerted me to. There was an interview with a gentleman named Greg Jefferys, who was assisting people from all over the world to legally obtain the latest, (normally) outrageously expensive but very effective hep c drugs, from licensed generic manufacturers overseas at an affordable cost.
The T.V. show explained that Greg was a Hep C sufferer himself and had undertaken a trip to India to access the new treatment, which was successful in clearing the virus from him. To his great credit he teamed up with other good souls and put in enormous effort to make the treatments available to others in need without the need to travel abroad.
After little research I found out how to contact Greg and he organised my meds without fuss or hesitation, or any great effort on my part. He provides remarkable support for Hep C sufferers around the world, and gets a huge thank you from us all.
My wonderful GP who had supported my unorthodox treatment suggested I was well overdue for an ultrasound, but I don’t always take her advice, and this was one of those occasions. So without the ultrasound I went on the ribavirin and Sofosbuvir twelve week treatment, but nothing happened, there was no change in my bloods, just some unpleasant side effects from the ribavirin.
By this time Daclatasvir had appeared, which combined with Sofosbuvir was considered the answer for G3. Once again Greg steered me in the right direction. Unfortunately adding the Sofosbuvir + Daclatasvir gave the same result, nothing!
By this time my doctor and I both knew something was very wrong so I finally had that ultrasound she had suggested I pre-treatment. The results were bad, and a follow up CT scan confirmed multiple hepatocellular carcinomas, end stage cirrhosis, portal hypertension, and several other bad things.
An appointment with the liver specialist in preparation for palliative care caused a glimmer of hope, as he thought my general health ticked all the boxes to make me eligible for consideration for a transplant. Unfortunately the team at Princess Alexandra Hospital in Brisbane felt my cancer was too advanced for a good outcome. Once again we were shattered, but to his credit my liver specialist sent me off to the oncologist, confident that there were procedures that could buy me some time, even though there was no chance of a cure.
My oncologist sent me off to the interventional radiologist for a TACE ( transarterial chemoembolization) procedure, whereby chemotherapy drugs and tiny particles the size of a grain of sand are delivered directly to the tumor via a catheter through the hepatic artery. This method reduces side effects and allows for stronger doses, the tiny particles block the blood supply that feeds the tumour and also keeps the chemo in contact with the tumour for the maximum time. After a couple of weeks recovery life is pretty well back to normal, maybe even a bit better than before. A follow up CT scan after a couple of months will reveal the effectiveness of the treatment.
After all this waffle my message to anyone afflicted with this nasty super virus we call Hep C is short and simple, get treatment ASAP. Find a good GP get a referral to a specialist. Get every relevant test and scan, and find out about the state of your liver. Then get treatment, the earlier the better.
If this sounds too straightforward, it may well be. Finding caring competent medical practitioners is not always easy, even some so called support sites can be compromised. So it’s up to yourself to become educated and informed, knowledge is power. Your wellbeing is ultimately your responsibility. All this from someone who has made too many mistakes too many times, some of us are slow learners, or maybe just lazy.
I’m a classic example of what happens when you wait too long for treatment, in my case in spite of Greg’s assistance with obtaining the meds before they became readily available the damage was already done. The journey through life is a short one, but when you get a death sentence there is a sense of devastation. Don’t get me wrong it’s a miracle I’ve survived almost four decades of Hep C and despite some monumental mistakes, life has been remarkably good to me.
Living is still good, with new experiences and stuff to learn and you never know how strong you are until being strong is your only choice.
Postscript; I just received the scan results of my two months post TACE treatment, the three out of four tumours that my interventional radiologist blasted have gone, while this is not a cure, it does buy me more time, and I feel better than I have in a long time. Thank you Dr Letitia De Villiers for your skill, judgment and caring.
1st January 2017
Hepatitis C Tests and Test Results: An Overview
Over the past year or so I have exchanged emails with many hundreds of people asking me to explain what their tests results mean. Usually this is because their doctor or specialist has not bothered to take the time to give this explanation or has explained things in such technical terms that the patient has not understood what was being said.
Of course not all doctors do this and I am sure the majority of doctors give a good explanation to their patients however the numbers of people who do not understand what their Hepatitis C test results actually mean is high enough to concern me.
For this reason I am writing this little guide in the hope that it will be of use to some people in understanding what Hepatitis C tests there are and what they mean.
Hepatitis C virus (HCV) tests are blood tests that look for the genetic material (RNA) of the Hepatitis C virus OR for the antibodies the body’s immune system makes to try to remove HCV.
The Hepatitis C Antibody Test
The HCV antibody test is usually the first test done when a doctor suspects a patient has Hepatitis C; it is a cheap and simple test. This test looks for the antibodies that your immune system makes to try to kill the Hep C virus. If this test shows that you do have Hepatitis C antibodies present in your blood it means that at some time you have had a hepatitis C infection; it does not mean that you are now infected.
The facts are that over 20% of people (more than 1 in 5) who are infected by the Hepatitis C virus will clear the virus with their own immune system. If you are a woman then the self-healing rate is actually closer to 30%. These people will always carry the Hep C antibodies but are no longer infected.
If you have been treated for Hep C and cleared the virus you will also always carry the Hep C antibodies. As with people who have ‘self-cleared’ you will have those antibodies in your blood for the rest of your life.
These antibodies have been made by your own body and have nothing to do with whether or not the virus is still present.
It has been very disturbing for me to realise how many doctors do not know this simple fact and I have answered emails from many people whose were very distressed because their doctor has told them that they have Hep C based solely on the results of the antibody test.
Of course the up side of this is that when I suggest that they get the next stage of testing and they discover that they do not have Hep C they are greatly relieved, often “dancing on the moon”.
The Liver Function Test
After the Hep C antibody test there are several options for which testing path to follow.
Because RNA, or genetic testing, for the Hep C virus is relatively expensive at about US$250 per test, for many people in the world this may be more than one month’s wages and impossible to afford so if money is an issue a Liver Function Test is an option to consider.
The Liver Function Test is a relatively cheap test that looks at various enzymes that the liver produces. If the liver is being damaged by the Hepatitis C virus there are certain ‘marker’ enzymes that indicate liver damage. The main ones are called ALT, AST, ALP and GGT. If these enzymes are significantly above normal levels AND you have Hep C antibodies then there is a very high chance that you have Hepatitis C and further testing for viral load and genotype, or just starting treatment, could be considered.
If money is a problem some people do decide simply to go ahead and start treatment with a generic Hepatitis C medicine that is effective against all genotypes of Hep C, such as Darvoni (Sofosbuvir 400 mg + Daclatasvir 60 mg). Because the cost of Darvoni is less than US$800 delivered it makes good sense to avoid spending between US$300 and US$500 on further testing if you can clear the virus for only $800.
However if it is possible then doing the next round of testing to discover viral load and genotype is ideal.
The Quantitative HCV RNA test
The quantitative HCV RNA test measures the amount, or number, of hepatitis C virus in the blood. The result will be an exact number, such as “1,378,980 IU/L.” Many people refer to the quantitative measurement as the Hepatitis C “viral load”… the load of virus a patient is carrying.
The viral load measurement does not tell anything about the severity of a patient’s liver disease or the degree of fibrosis (liver scarring). For that information, the patient would need a liver fibrosis scan (Fibroscan).
If a quantitative HCV RNA test result is reported in a form such as “<615 IU/L,” (under 615) this means that the quantitative test used cannot measure the hepatitis C virus below that number. It may mean that there is no detectable HCV RNA in the patient at all, but it may also mean that the level of virus is just too low for the test to pick it up. A qualitative test should then be performed to see if there is any detectable hepatitis C virus at all.
The Qualitative Hepatitis C RNA Test
The Qualitative HCV RNA test uses either a process called PCR or a process called TMA. Either type of qualitative test will report whether the hepatitis C virus is present in the bloodstream or not. The result is reported as either “detected” or “not detected.”
If a qualitative RNA test is positive (detected), then it is confirmed that the patient has Hepatitis C DNA in their blood. The “qualitative” test is more accurate than the “quantitative” test because qualitative tests are able to detect very low levels of the virus.
So there are four test options for Hep C.
The Hepatitis C Antibody Test (AB or Ab Test).
The Hepatitis C Quantitative Test or Viral Load Test
The Hepatitis C Qualitative Test or PCR Test.
The Liver Function Test (LFT) does not test for Hep C but in combination with the Antibody Test is a good indicator of chronic or acute Hepatitis C.
As with all testing the RNA based tests are not infallible and it does appear that very small amounts of “dead” Hepatitis C genetic material can survive in the patient’s blood for some time after the virus has actually been cleared.
This is somewhat controversial however I have seen a number of cases where people have been tested at end of treatment and come up clear and then tested at 4 weeks after end of treatment and been given a reading of around 100 or 400 or 1,000 and then tested again in another 4 weeks and come up clear again.
I call this effect a ‘shadow’ and I don’t know what it means other than a lot of people have had this experience and thought that they had relapsed only to find that they had not relapsed. It is an area that needs more research.
Please note that I am not a medical doctor and the advice I am giving is based on my own personal observation and communications with people who have Hepatitis C. How Well the Liver Heals therfore depends upon many different factors.