Written by George D Henderson.

Fibrosis; prevention and reversal

Hepatic stellate cell activation and proliferation; HSC inhibition, apoptosis, and reversion induced by natural compounds.


The Hepatitis C Handbook by Matthew Dolan is one of the best resources in the subject of Hep C. I was amazed to find, looking up fibrosis in the index, that there is no reference at all to it in the 1997 edition.

Until the last 10 years or so fibrosis was seen purely as an aspect of liver damage that was not really distinct from damage to hepatocytes. In fact, fibrosis, and therefore cirrhosis is an aspect of liver repair mechanisms, albeit one that can lead towards increased damage and loss of function if it is not switched off. The good news is that many strategies have been developed to switch off fibrosis and resorb scarring (for example, in Modern Chinese Medicine the herbal preparation Cpd 861 was able to reverse 4 stages of fibrosis and 2 of cirrhosis in clinical trials) and it seems relatively easy to prevent fibrosis from snowballing in the first place. To understand how this is possible, we must first look at fibrosis as a natural event.

Hepatic Stellate Cells

Damage to the liver, whether by drugs, virus, radiation, or trauma (for example, a biopsy needle) must involve damage to the microcirculation, the tiny blood vessels essential to liver function, as well as to hepatocytes. The microcirculation consists of endothelial cells, called sinusoidal because there are windows in them. This tiny tube, only 2-3 cells in diameter, is surrounded by a space (the Space of Disse) separating it from the hepatocytes. The Space of Disse is inhabited by main two cell types; Kuppfer cells, the macrophage white blood cells that keep it clean, and Hepatic Stellate Cells (HSCs or Ito cells). In health, HSCs have three main functions; they store fats and vitamin A; they produce and degrade matrix (collagen and similar protein fibres), both to restrict the size of particles able to pass in and out of the microcirculation, and perhaps to keep open the Space of Disse; and, HSC also serve as glial cells, similar to the neuroglial caretaker cells in the brain; that is, they respond to many neurotransmitters and neural hormones, and can both break down and produce many such chemicals, interacting with the nerves that transit the liver. This is particularly important as it gives a mechanism as to how moods and emotions can impact on liver function, and vice versa, as well as some psychoactive drugs.

Written by Linda McInnes - Editor/Administrator of AHCS

There are fundraisers for illnesses such as:

• Breast Cancer foundation
• Epilepsy foundation
• Blind welfare Association
• Guide Dogs foundation
• Canteen for kid’s cancer foundation
• Cancer foundation
• Leukaemia foundation
• HIV/AIDS

I could go on and on here listing the different organisations that raise money to help assist people with these illnesses, I have these organisations phone me up to entice me into buying raffle tickets, or to donate money for their cause.
I have even door knocked for the Red Cross Appeal when asked by them one year to help them.

I have seen badges, ribbons and pens etc for sale at every outlet I can think of to support these types of organisations to raise money.
There are retreats for different people with illnesses to go to if they are very ill and need a break, and also the family needing a break.

I have never been approached by phone to give money to any hepatitis C fundraising organisation nor have I seen any ribbons or pens displayed in shops for purchase with proceeds going to aid for people with hepatitis C.

Written by LINDA MCINNES (AHCS)
Editor/Administrator
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Hepatitis C Conference - Brisbane, October 20th - 23rd, 2008

I attended the above conference as a person with Hepatitis C and the Editor/Administrator of the Australian Hepatitis C Support - AHCS Website.  I was sponsored by Roche Pharmaceuticals to attend the conference and I remain deeply grateful for their support.  Roche Products is a world leader in in-vitro diagnostics and medicines in various areas including virology.  In Australia, Roche offers a range of patient support materials, compassionate access to PEGASYS, education programs and is committed to clinical research to optimize patient treatment with PEGASYS.

There were 500 registrants attending the conference and Maroochy, an Australian Aboriginal, sang a 'Welcome to the Country' song to open the conference.

As it was my first conference there were a lot of presentations and I could not attend all of them as they were held in 3 different conference rooms and some intermingled with the other.  Hepatitis B was also a part of the conference and I did not attend any of these sessions as my sole interest is in Hepatitis C.

A few other hepatitis C forum members from the Hep C Australasia and AHCS - Australian Hepatitis C Support websites were also present at the conference, this enabled us to meet each other for the first time and also offer support during the conference.  Online forums are very important for patients with HCV, they can remain anonymous, express their anguish living with this disease and often they are overwhelmed and relieved with the online support, information regarding HCV, treatment and sharing they will find.
The AHCS website/forums provide an assortment of information in relation to Treatment, Health Hubb, Vitamins and Supplements, Information Station, Symptoms News, Alternative Therapy, Latest News and also links to all the other Hepatitis C Councils within Australia.  If a person cannot find any information the team of AHCS will endeavour to search the internet to provide them with answers to their questions or refer them to the appropriate Hepatitis C Council or other internet source.

Ken Abrahams from the Hep C Australasia forums gave a presentation informing the 'audience' that forums are important because people with HCV find information and talk about:

• Making transitions and decisions about the future.
• social acceptance, making friends.
• exchanging information.
• Support during difficult times and also celebrations.
• People with HCV need support from other people with HCV treatment experiences.

The presenters used 'case studies' of people with HCV, all of them were about people that had been injecting drug users (IDU), how they coped with living with HCV, disclosure, family, friends, and discrimination.
I was disappointed that there were no case studies of anyone that had acquired the HCV virus from transfusions, violence, tattoos, surgery, transplants or any medical procedures etc to hear of their experience as being 'labelled' as an injecting drug user (IDU) with HCV.

I am aware that most people with HCV became infected through drug use, and this is the reason that they are the ones most focused upon.  In a conversation with a Clinical Nurse at the conference, she expressed her concern that 'violence/fighting' was not more focused upon as being a mode of transmission.

It was also brought to my attention that patients with HCV that commence treatment may be able to access priority housing with the South Australian Housing Trust and this could take up to 6 weeks, which is remarkable considering there may at least be a 12-20 year waiting list depending on which category you fall into.

Schering Plough are providing retreatment options for people with HCV which many patients that have been non-responders or relapsers may now consider and should pursue this with their specialists. This retreatment will be available on the PBS and listed on 1st December 2008. New Ribavirin 1400mg/day will also be available from 1st December 2008.

Proven Predictability

At 12 weeks, the proven predictability of Pegatron will allow the Doctor and the patient to make the right decision whether to continue treatment.

• 37% of all patients treated with Pegatron achieved undetectable HCV-RNA livels at 12 weeks.
• 57% of all patients with undetectable HCV-RNA levels at 12 weeks went on to achieve SVR. For patients with >2log, decline, yet detectable HCV-RNA levels at week 12, the rate of SVR was only 6% and was 0% for patients with <2log, decline.

To achieve the likelihood of success, identifying the right HCV patients for retreatment with Pegatron the following should be taken into consideration:

• Low degree of fibrosis
• Low baseline viral load
• Relapsers
• Genotype 2/3
• Non-pegylated interferon failures

Prior relapsers show a much higher chance of SVR, pateints with low baseline viral load respond better than high viral load patients, higher SVR were observed in patients with lower fibrosis scores and Genotype 2/3 patients responded better than genotype 1 patients.


Charles Gore - President of the World Hepatitis Alliance gave a presentation on his endevour to have May 19th recognised as World Hepatitis Day.  Mr Gore is also involved with the Hepatitis C Trust, London, UK in which he spends a lot of time raising awareness of HCV in the political sector and around the world where he is trying to bring chronic viral hepatitis into the same priority as malaria,TB and HIV/AIDS.
Mr Gore believes 'patients' should run or lead World Hepatitis Day as he believes that Governments will listen to them first.

There is a book to be published in March 2009 called "Hepatitis C: An Expanding Perspective".

Edited by Greg Dore, Meredith Temple-Smith and Andrew Lloyd "... which will be essential reading for anyone working in the area of HCV.  "...In the last 5 years, the number of Australians living with hepatitis C has almost doubled.
Research in recent years has resulted in major developments, not only in the management and treatment of HCV, but also in our understanding of the issues involved in preventing the transmission of HCV.  As more information has become available about this epidemic, policy responses have also been modified...."
Greg Dore, Associate Professor and Head, Viral Hepatitis Clinical Research Program, National Centre in HIV Epidemiology and Clinical Research, University of NSW.
Go to www.ipcommunications.com.au to view more details of the book.


Brian Edlin (Professor of Medicine) discussed 'The Elephant in the Living Room'.

• There are 10-30% per year of IDU excluded from treatment.
• Homeless and underpriveleged are not diagnosed nor treated.
• Drug users dont seek medical help or see doctors.
• It is not ethical to withold treatment from current IDU and the National Institute of Health (NIH) recommends changes.
• Methodone is not a contraindication to hepatitis C treatment.
• Physicians dont know enough about hepatitis C to treat HCV patients.
• Drug and alcohol dependence should be treated.

Helen Blacklaws (Clinical Nurse), Interferon and ribavirin therapy for chronic hepatitis C: Family Impact Study.
The outcomes were:  

• Support from family and friends was very important.
• Anger and irritability, and always apologising.
• Hard on the family but understood.
• The patient experiences 'Loss of role', self image, and no normality in life.
• Financial - loss of money, couldnt work
• Witnessing families distress
• Secrecy, rejection, stigma, discrimination.
• Brought the families closer together and their resilience and coping was remarkable.
• There are negatives and positives for the patients and their families.
• Isolation

Pre-treatment education should be more focused and coping strategies further explored in order to better prepare patients and families for their forthcoming experience.


Max Hopwood (National Centre in HIV Social Science) is doing a new study called: Post-treatment
outcomes study: psychosocial impacts following completion of hepatitis C treatment - ongoing.

There needs to be a program for the end of treatment where patients can seek advice, referrals and support for re-orientation to work etc.
Interview participants reported a variety of sustained physical and psychological after-effects from treatment for HCV.  some after-effects were described as severe and debilitating, had persisted many months following treatment completion and impacted substantially on quality of life.
This paper:

• provides social-contextual information in relation to the impact of persistant neurotoxicity on risk practices for re-infection with HCV.  
• explores the impact of SVR (ie:cure) and treatment failure, e.g., on employment, personal relationships and emotional and social functioning;
• describes individual perceptions of improvement or deterioration in health and quality of life after treatment.

Carla Treloar (National Centre in HIV Social research, University NSW, Centre for Womens studies & Gender research, School of Political and Social Inquiry, Monash University, discussed Hepatitis C treatment in pharmacotherapy services: increasing treatment uptake needs a critical review.

In Australia there are 2,000 - 3,000 people treated each year for HCV and this needs to be 6,000.
To attract the IDU patients planning is underway for non-specialist services such as Opiate Maintenance Therapy (OPT) Clinics.

One way to increase HCV treatment access and uptake may be to provide this treatment through existing Alcohol and other Drug Services (AOD).
Many people with HCV are treated different and experience discrimination from Doctors, Nurses, Hospitals and Health Care Workers which may be a barrier to HCV treatment. (L. Brener et al 2007).

"...HCV patients are treated differently by Health Care Workers, and the attitude of health care workers has an impact on treatment outcomes in AOD treatment facilities. - is this the perception that people with HCV have or does it happen?..."


Magdalena Harris (National Centre in HIV Social Research: Safe to Drink? - Alcohol and Hepatitis C Study.

• Patients with HCV find it hard to stop drinking due to social pressure.

• They think if ALT levels are normal, then its OK to drink.

• Some may also become 'closet' drinkers from pressure not to drink.

"...There is a need for those working in the hepatitis C field to be mindful of the meaning and function that alcohol has for people with hepatitis C and, if possible, provide information on less harmful alternatives..."
Some patients have been advised to smoke cannabis to relieve the symptoms of HCV and treatment.


N Leembruggen et al - Is reduction of hazardous alcohol intake maintained post therapy in hepatitis C patients?

"...Excessive alcohol consumption exacerbates liver disease in patients with hepatitis C and decreases response to pegylated interferon and ribavirin therapy.
People with HCV tend to decrease alcohol intake rapidly in preparation for treatment and maintain this during therapy.  However, there is a cohort of patients who resume risky drinking habits post therapy and may be at an increased risk of cirrhosis, hepatocellular carcinoma and liver failure.  Further research in a long-term alcohol intake and risk factors for relapse is recommended...."


MW Douglas et al: Hepatitis C virus core protein affects insulin signalling in a genotype-specific manner.

....."We have shown that chronic infection with the hepatitis C virus, particularly genotype 1 infection, is specifically associated with insulin resistance.  More importantly in HCV-infected patients, insulin resistance predicts faster progression to cirrhosis and hepatocellular carcinoma, and predicts a poor response to antiviral therapy.  The mechanisms for the development of insulin resistance in HCV infection are unclear, though this information is vital to better understand disease pathogenesis and progression and to devise novel therapies.."
(M Douglas et al).

The future direction is to test drugs to reduce insuling resistance so that treatment works.

I would encourage everyone infected with HCV to be tested for Insulin Resistance, especially before commencing treatment to enable your chances of SVR to be in the higher odds category.  Eating a healthy diet and exercising, no smoking tobacco or drinking alcohol will improve your chances of SVR. (L. McInnes).

Below is an excerpt from the book written by James Lovelock - 'The Revenge of Gaia', whilst reading this I came across a theory of why some viral diseases, such as hepatitis C and B cause cancer through chronic inflammation of the liver.  This book is a 'must read' for every human living on this planet, that has concerns about the future of Earth and our own lives in the very near future.  In this book Mr James Lovelock advises that Nuclear Energy is the only way to go, and may be the only way for us to survive and slow down Global Warming.  We have been confused and given deadly information by the media that we are all scared to even contemplate Nuclear Energy, well its time to change these views, and the only way for you to understand all this is to read this book as I have.


'Authors Quote' -

Within each of the billions of cells that make up our bodies are tiny inclusions called mitochondria; these are the power stations of our cells.  Inside these tiny particles, fuel from the food we have eaten reacts with the oxygen that we have breathed in.
The output of energy from the mitochondria is a flood of molecule-sized rechargeagble batteries, adenosine triphosphate (ATP) molecules, each able to power for an instant our muscles and our brains, so that we can walk and run and think.
When discharged, these molecular batteries are recharged again at the mitochondrial power houses.  For our bodies, with their billions of tiny mitochondria, the danger comes from the accidental leak of combustion products.
As oxygen reacts with the food products, unintended pollutants are formed.
These include the oxygen molecule with a negative charge called the superoxide ion, the hydroxyl radical and other highly reactive molecular species.
These destructive molecules escape from the mitochondria as toxic pollutants and also arise accidentally anywhere in the body where oxygen can react unchecked.
The omnipresence of oxygen in our bodies also greatly enhances the damage done by radiation and chemical poisons.  The fiercely reactive radical products of oxidation will attack almost any other molecule they encounter, and this is how they damage intrictate orderly internal assembly of our cells.
Almost all of this damage is repaired by an evolved set of enzymes and systems - which we could look on as the security services of oxygen-breathing life.
But inevitably some damage is done to the genetic chemicals of our cells, like DNA, which are the programs and procedures for building new cells.  Wonderfully, the damage to DNA is also repaired and there is a continuous check of its integrity.

In the course of a lifetime, unavoidably, a few of the billions of these comprehensive checks fail.
From the failures to repair oxygen damage, new cells are born, with fatal or near fatal disorders.
Most of the damaged cells commit cellular suicide using a death pill that every cell possesses called a capsase.
When this is activated it sets in course an orderly progression to dissolution.  It is a miraculous process called apoptosis.  Just imagine if each one of us, on concluding that he or she was so much more harmful than useful, began to take ourselves apart in so perfect a way that a tidy, orderly heap of spare parts for future human use was left.
Sometimes, the damage done to DNA by the products of oxidation disables one of the genes that sets the instructions for cellular suicide, and when this happens a maverick cell is born and grows unchecked.  Then, after several more potentially adverse changes, a fully unrestrained cancer cell is born.  It grows and invades and eventually may kill the animal that spawned it.
This is no more than an imprecise sketch of carcinogenesis.  We still lack knowledge of the finer details, but it is enough to show how the life-giving power of oxygen has a dark side.  By the time we reach the biblical allotted span of seventy years, 30% of us will have died of cancer, and for almost all of those deaths, breathing oxygen will have been the main cause.

Natural Nuclear radiation coming from cosmic rays and from the radioactive elements in the soil, the air and our homes, can and does cause cancer, and it does so because it is energetic enough to split the abundant molecules of water in the living cell and liberate those same free radicals that come from oxidative metabolism.
Other natural and man-made sources of cancer act like radiation, but none of them, apart from smoking cigarettes and too much sunburn, add significantly to the 30% who die from breathing oxygen.
Inflammation, as the name suggests, is a burning sensation and it is always accompanied by increased oxidation in the inflamed tissue and by an increased rate of cellular reproduction.
Not surprisingly, it is associated with cancer.
This is probably why some viral diseases, such as hepatitis C and B, cause cancer through chronic inflammation of the liver.
Few of us are aware that the oxygen of the air is the dominant carcinogen of our environment, but multitudes are convinced by the untruth that most cancers are an avoidable consequence of environmental pollution and there is an unceasing torrent of articles that sustain this false belief.

References:

James Lovelock - 'The Revenge of Gaia'

James Lovelock is the author of more than 200 scientific papers and the originator of the Gaia Hypothsisis (now Gaia Theory).  He has written three books on the subject: Gaia: A New Look at Life on Earth, The Ages of Gaia and Gaia: The Practical Science of Planetary Medicine,  as well as an autobiography, Homage to Gaia.

He has been a Fellow of the Royal Society since 1974.  Since 1961 he has worked as a wholly independent scientist but retained links with universities in the UK and USA, and since 1994 has been an Honorary Visiting Fellow of Green College, University of Oxford.

He has been described as 'one of the great thinkers of our time' (New Scientist) and 'one of the environmental movement's most influential figures' (Observer).

In 2003 he was a Companion of Honour by Her Majesty the Queen, and in September 2005 Prospect magazine named him as one of the world's top 100 global intellectuals.