The war against Hep C, that monster from the microrealms, is waged on many fronts - biochemical, behavioural, socio-political and more. On none of these have we claimed victory until the emergence of DAAs.
We may now say, categorically, that the Hep C elimination effort is no longer being held up by drug development. The virus, backed by oceans of time and the heavy hand of evolution, has been beaten down by the club of human science. In the labs and clinics its biochemical back has been broken. Indeed, the DAAs which entered the ring with great fanfare around two years ago are beginning to look old.
AbbVie, makers of the Viekira Pak, have for a long time been running second to Gilead, but their new pangenotypic product Mavyret may put them ahead. Not only have they undercut Gilead’s drugs on price, but the Mavyret regimen takes a flat eight weeks, further diminishing the cost. As of February this year, they had snagged a third of the US Hep C market.
AbbVie has also been the first to retire new generation Hep C meds, announcing that they will cease to produce two formulations containing Ribavirin. (Ribavirin is an older-style anti-viral with severe side-effects which was believed to increase the chances of a cure in certain cirrhotic patients.)
Merck & Co, who had been angling for a niche position with their drug Zepatier, have decided to abandon the HCV field entirely (though not before attempting to sue Gilead for billions over Sovaldi patent issues).
(TGP - I have heard that Merck sales reps are still shilling for Zepatier in Melbourne clinics, so the above info may be limited to the USA.)
Janssen Sciences has also abandoned Hep C as the overall market value shrinks in the aftermath of the of DAA miracle.
Wait. Shrinks? Shrinking? With millions of Hep C patients at large in the world? With the US opioid epidemic ramping that country's transmission rate? I think that by ‘shrinking’ the stock-market analysts are referring to the pool of patients who are wealthy or insured enough to pay massive prices for a course of Hep C drugs.
Interestingly, Gilead and other big drug companies are injecting money into research on Nonalcoholic Steatohepatitis (NASH). Why interesting? I’ll explain.
First off, NASH is a form of NAFLD. That would be Non-Alcoholic Fatty Liver Disease. It refers to a pathological buildup of fat in the liver. If there is also inflammation and damage to liver cells, then it becomes ‘NASH’. Around half of all people with Hep C have some degree of steatosis (fatty liver) and the condition is an important means by which the disease harms the liver, accelerating the progression to cirrhosis and liver cancer.
US researchers have ascertained that, even after the cure, a similar percentage of patients suffer from NAFLD. After treatment, therefore, you can look forward to a lessening of fibrosis and a normalising of inflammation markers (ALT, AST), but your NAFLD may dig in its heels.
The reaction of Big Pharma has been predictable. In stock-market related gossip NASH has become the new Hep C and the list prices of companies are rocketing all over the place on rumours of a new Sovaldi. To quote Seeking Alpha (A US stocks blog) ‘Biotech investors are crazy about NASH. Rarely do borderline efficacious results from a Phase II trial inspire triple digit percentage moves’. Madrigal, Intercept, Galmed. They sound like the kind of nefarious corporate entities who might develop risky life-extension technologies in secret science compounds on unmapped islands. Think Westworld. Or Stranger Things. Or Lost. Or Jurassic Park.
Anyway. It appears that drugs already in development will be able to reduce fat-levels and fibrosis in the livers of affected patients. This is a big deal because there is currently no good treatment for NASH/ NAFLD. Gilead may be able to console itself over its declining revenues by re-treating those they have cured of Hep C with brand-new, appallingly expensive fatty liver medicines. What’s more, there seems to be a correlation between more severe steatosis and a higher body mass index score – meaning richly-insured obesity patients will be bounced into the equation. No wonder Gilead and her sisters are licking their chops over these fatty buildups.
(While on the subject of Gilead, a repurposing of their mega-drug Sovaldi may be underway - as a treatment for, of all things, the Zika virus. Remember the panic caused by Zika (a flavivirus like HCV) when it led to an outbreak of microcephaly (undersized brains) among newborn Brazilian infants in 2015?)
I should note that there is also an AFLD (Alcoholic Fatty Liver Disease). Enthusiastic alcohol consumption exacerbates fatty liver disease. Therefore - as if you did not know - people with Hep C and those who have been cured of Hep C should watch their alcohol intake. As well as their diet. We should exercise too.
This research on NAFLD underlines the importance of ongoing liver monitoring for those who have been cured. Because you can have perfectly normal blood results but still have creeping NAFLD/AFLD, this surveillance may benefit from tests that include ultrasound and FibroScan.
A cure increases the quality and quantity of life, but it’s only been a couple of years since DAAs rode in to slay the beast. The long-term treatment landscape remains unclear, so… basically, take care.
Aside from eating sensibly, exercising and curtailing ones alcohol consumption, what else can those touched by Hep C do to amend their diets for the better?
As usual, there is news on this front and, as usual, it should be taken with a grain of salt. Let’s begin with pot. Pot. What can’t it do?
You would have to be deaf dumb and blind not to have noticed the hype surrounding ‘medical marijuana’. The effects of cannabidiol (CBD) oil in particular have been touted hugely. (CBD is the cannabinoid responsible for the ‘body stone’ as compared to the ‘head stone’ produced by THC-heavy bud.)
A quick scan of the net will tell you that CBD will ease or even cure various cancers, epilepsy, irritable bowel syndrome, schizophrenia, rheumatoid arthritis, MS, lupus and any number of other auto-immune conditions. It is said to help with anxiety, inflammation, pain, sleep and appetite issues and is, predictably, an anti-oxidant.
But what about Hep C and the liver?
According to Hep Mag (to which I give a solid nod as an interesting, reliable and useful publication) a French team has ‘found that regular pot use is associated with a lower risk’ of fatty liver among those with HCV (and HIV) – even when figures are controlled for body weight and other risk factors. ‘Does this mean,’ continues Hep Mag, ‘that everyone with HIV and HCV should fire up the bong or bake a bunch of brownies?’
Predictably, chief researcher Patrizia Carrieri suggests that her results should be ‘interpreted with caution.’ She stresses the importance of lifestyle factors – exercise, diet, alcohol consumption – and reminds us that the smoking of anything is a risk to the health. Although the results point in an interesting direction, she says, science is yet to determine whether there is an actual causal relationship between pot use and FLD.
It has been suggested that cannabinoids can ease the symptoms of Hep C by reducing liver inflammation, and twelve or more states in the USA offer pot as such a treatment. Unfortunately, thus far, studies only show that ‘using medical marijuana to treat the liver does not make the liver worse.’ Just over a year ago, Jamaican(!) scientists hinted that they may be close to developing a CBD-based drug with true antiviral activities which could provide a cheaper alternative to DAAs.
Of course, as a rational thinker and proud sceptic, I have been champing at the bit for months in my search for CBD oil. (I remember doing the same for Prozac when it first arrived on the radar.) Lots of people, at home and in the office, claimed to have leads on acquiring the semi-legal substance, but nothing panned out. A few weeks ago, I finally acquired some (I won’t say how) and, though I can’t give you results on any fatty liver disease I may or may not have, I must say that I have been sleeping well, feeling okay generally, and have had no episodes of anxiety.
I’m going for a stronger dose next time. But that’s just me.
What else is good for Hep C, or in the aftermath of Hep C? Maybe green tea. And Zinc. What’s bad? Olive and avocado oils. Maybe.
First the good news. Scientists at the Mayo clinic, using mouse models, have observed that an antioxidant extract of green tea ‘Theaphenon E’ ‘prevented liver tumours from forming and lowered the number and size of such tumors’. I won’t go any deeper here, but it is interesting research and there are reasons to believe that it could scale up for humans. A cautious head-researcher suggests that taking the extract ‘at least couldn’t hurt’ – though Hep Mag warns that such nutritional supplements are poorly regulated and therefore not wholly trustworthy. Might drinking actual green tea be a solution?
As for zinc… well it’s complex and involves proteins called Metallothioneins (MTs). MTs have numerous functions but are principally known for binding metals like zinc within cells. Hep C is known to affect the expression of these MTs, exciting it in the acute phase, suppressing it in the chronic. (Chronic Hep C is also known to deplete zinc levels in the blood.) Western Australian scientists have been digging into this pile with the idea that MTs may have an actual anti-viral effect. They conclude that zinc (with the help of MTs) does indeed inhibit HCV replication and that ‘zinc supplementation could be a low-cost and safe addition to current therapies.’ The take-away? Get treated and you won’t have to worry about zinc supplementation.
I consumed kilograms and kilograms of blueberries when I had Hep C. This was thanks to Japanese scientists and the results they achieved with blueberry extract and petri-dishes. Who knows if it had an effect? Sadly, one rarely hears of these kind of studies beyond the initial hoo-ha.
Now the bad news.
American mice have suffered further to teach us about our livers. This time, strangely, the research involves the possible long-term harmful effects of monounsaturated oils – the so-called ‘good oils’ derived from such things as avocados and olives. It may be that ‘bad-oils’ – i.e. saturated animal fats – are less likely than thought to cause Fatty Liver Disease (see above).
Groups of mice were fed a variety of high-fat diets. While all grew obese and most showed symptoms of FLD, researchers were surprised to find that those on a ‘starchy monounsaturated fat diet had by far the most severe disease, accumulating 40 percent more liver fat than the mice on the other … diets’. More research is clearly indicated, but the authors of the study do suggest that we ought to enjoy vegetable oils like avocado and olive in moderation. I would go on to say that fad-diets can be dangerous, and that variety in itself is a good basis for any diet.
As usual with these newsy posts, I have to stop myself going on forever. But before I finish, I'd like to mention a couple more things.
There is fabulous news – reports of which are coming from many sources – that DAAs are causing a boost in organ transplantation. Lungs, kidneys and other organs from Hep C positive cadavers are increasingly been used - after which the recipient is cured with DAAs. Liver transplant waiting lists around the world have been significantly reduced since the new treatments became available. And yes, livers actually infected with HCV have been used in transplantation.
Also, I have been fascinated lately by behavioural studies on gender disparity in Hep C infection. Figures suggest that women who inject drugs ‘are about 39% more likely to become infected with hepatitis C virus than men who inject’. The reasons for this are various and slippery, and I’m curious to look into it a little more. I’m interested in the assumption (true or not) that women are more likely to share needles in a social setting - as well as the darker side, involving masculine control and the likelihood of females 'going second'. Perhaps I’ll look into it more thoroughly in the future.
The Golden Phaeton