The Post-Treatment Landscape - Glorious but with Pitfalls
DAAs have been around for long enough now for us to get a decent view of the post-treatment landscape.
There’ve been some very positive findings. But also, some scary ones.
I’ll begin with the good news.
A review of successfully treated patients, who were yet to develop any significant fibrosis, has shown a very low rate of subsequent liver-related issues in the three years post-treatment. This is further evidence that the sooner treatment is embarked upon the better. It seems that, if you halt the virus soon enough, the liver has a chance to fully rejuvenate. As for those who have progressed to cirrhosis, Hep C treatment has significantly reduced the number of hospitalisations.
Regarding diabetes 2, for which Hep C seems to be something of a risk factor, long term studies are showing that a cure reduces the likelihood of developing the disorder by a factor of three, regardless of any other risk factors (i.e. a high Body Mass Index).
Another long-term study, cla
iming to be the first of its kind, makes a strong case that the cure substantially lifts a subject’s general quality of life - as described by their general health, vitality, and ‘physical symptoms, such as pain’. In the medical game this is referred to as HRQL (Health-Related Quality of Life). Also addressed were issues such as ‘social-functioning, emotional roles and mental health.’ According to this research, most subjects improved to a level comparable to the general population.
Hmmn. Wish I could include myself in this happy, happy group. But maybe things will improve…
Thing is, it’s easy for some of us, myself included, to assume that curing Hep C automatically cures the liver. Am
id the excitement of defeating the disease, it’s a forgivable mistake to make – but a risky one. Certainly, the liver has a near-magical ability to heal itself, but there are limits - particularly after what may have been decades of inflammation.
A recent blog post from the magazine ‘Hep’ put the issue into stark relief, guiding our attention to some ‘unsettling’ research that may not be getting the attention it deserves amid the general atmosphere of celebration and optimism.
It makes me feel queasy even thinking about this, but here I go ...
Common sense (and a good swathe of evidence) tells us that the risks of contracting HCC (hepatocellular carcinoma – the most common form of liver cancer) decrease once the liver has been cleansed of HCV.
Subjects who have not progressed to cirrhosis have traditionally been considered more or less exempt from risk of the disease, particularly after successful treatment.
Until now, it seems...
A recent study titled 'Increase in Hepatocellular Carcinoma in Hepatitis C Patients Without Cirrhosis' (by Sanath K. Allampati and colleagues) has analysed data associated with 2328 patients with HCC. They discovered that ‘liver cancer rates were trending consistently higher. Further, this increase was more pronounced in the non-cirrhotic group, increasing from under 10% to nearly 22%.’
The researchers expressed concern that patients cured of Hep C may be at a higher risk of developing HCC than previously believed. The results may be of particular significance to non-cirrhotic or near-cirrhotic patients who may have abandoned any surveillance of their liver health after being cured of Hep C.
The take-away here, I would suggest, is to take your follow-ups seriously, particularly if your FibroScan or biopsy results have ever been on the high end.
But, even if the worst comes true, more than a little hope remains. For example, BMS (Bristol-Myers Squibb) has developed a drug called Opdivo which, in more than half a group of 262, caused tumours to either shrink or stabilise in size. Who knows? Perhaps the mages of pharmacology are on the way to repeating the Hep C miracle with HCC?
Speaking of miracles, aspirin never ceases to amaze. It has been discovered that, among people with Hep B, those on daily aspirin therapy are half as likely to develop HCC as those who are not. I don’t know if this has any relevance to HCV - and it’s probably irresponsible of me to suggest that it has – but it may be worth keeping an eye on any future aspirin research.
Hold on though, I haven’t entirely finished with the nasty stuff.
Researchers in Washington DC examined 101 subjects who had successfully completed treatment. They all showed significant improvements in fibrosis and liver enzyme levels - which ordinarily would indicate a liver well on its way to good health. Unfortunately, they discovered worrisome levels of steatosis or fatty liver disease - a condition which can be associated with Hep C and which would be expected to improve after successful treatment.
The researchers warned that clinicians should be vigilant for signs of post treatment NAFLD (Non-Alcoholic Fatty Liver Disease) an illness not commonly monitored in those cured. On a quick reading, the subjects of this study did seem on the high-risk end for developing such a condition (Average age: 60, 90% with diabetes) but, regardless, this does seem to give us further reason to keep an eye on our livers post-treatment.
The authors also made it clear that in no way were they suggesting that DAAs themselves were responsible for the worrying results. Indeed, these new longer-term studies do appear to confirm the safety of the drugs, placing any concerns directly on the liver itself and its natural response to the elimination of the virus.
However, if you have - or have ever had - Hep B, you may want to take heed of a box warning instated by America’s FDA (Food & Drug Administration). Though the evidence is scant, the agency has erred on the side of caution, informing DAA customers of the slim chance that their Hep B may intensify or reactivate after taking the drugs.
DAAs may have a near clean bill of health, but not so their predecessors – primarily alpha interferon and ribavirin. These drugs are horrible to take and there seems to be some suggestive evidence of negative effects down the track - though I should stress that nothing conclusive has been proven.
Interferon-Alpha (most often injected in its PEGylated form) has been accused of sparking auto-immune conditions like psoriasis, rheumatoid arthritis and lupus. It is commonly linked with thyroid dysfunction, and is most often associated with major depression and other psychiatric issues. A friend of mine who is being treated for early onset dementia has no doubt in his mind that interferon is to blame. Ribavirin, which can inhibit the body’s ability to absorb oxygen, has its own suite of long-term issues, but, again, there is nothing known for certain. All I can suggest is that - if you were unlucky enough to have been treated with these ghastly substances - you should perhaps widen your medical surveillance to include the kind of nasties with which they have been correlated.
Thank the heavens for DAAs is all I say. They’ve saved the day, and what’s more, there is better to come. It seems that the incredible cure-rate of the current crop is about to be eclipsed by even more potent molecules that are effective over as short a period as six to eight weeks.
An example is Vosevi, Gilead Science’s latest offering. It comes as single pill taken once daily containing sofosbuvir, velpatasvir and a new substance named voxilaprevir LINK. The first two drugs comprised Gilead’s pangenotypic blockbuster Epclusa, the third adds power to the punch. Though it is intended as a salvage drug for those who have failed previous DAA treatment, Vosevi could likely serve as a stand alone compound with a cure rate over 99%. And, though a twelve-week regimen is suggested, it is possible that it only requires two thirds of that time to get the job done.
So, on the whole, thus far, the post-treatment landscape looks pretty rosy. There’s every chance that a great many of those treated will never be bothered by their livers again - but there’s a caveat. Many of us will also need to keep a weather eye out for the well-being of our precious livers. Sadly, we will always be that little bit more likely than the average citizen to succumb to cancer, cirrhosis or, apparently, Non-Alcoholic Fatty Liver Disease.
Remember those changes you may have instigated while you still had the disease? – avoiding alcohol, maintaining good hydration, getting enough sleep, managing stress and keeping a healthy diet? Well they might be worth continuing with, just in case.
The Golden Phaeton.