Sunday, March 25, 2018

Hepatitis C - Silent Killer or Innocent Bystander?

For a few decades, I did not treat patients with Hepatitis C (HCV) infection, despite aggressive marketing by the pharmaceutical companies and cheerleading by academics.  I was an iconoclast as most of my gastroenterology colleagues were HCV treatment enthusiasts. They argued that if the virus could be eradicated, that there was evidence that these patients could avoid some horrendous HCV complications, such as cirrhosis, liver failure and cancer of the liver.

I’m certainly against cancer and liver destruction, but I have thought that the evidence that HCV patients who vanquished the virus would be saved from these fates was somewhat murky.  Treatment proponents would argue that the medical evidence for thes claims is solid, but I wonder to what extent their favorable bias toward treatment influenced their judgment.  We physicians know that a doctor or a drug company will seize on  particularly studies that supports their views.  Studies that challenge their beliefs may be criticized for 'study design flaws' and other defects.  I am generalizing here, but we all know how we tend to pursue confirmation bias, seeking out sources and opinions that support what we already think. This is not quite a pursuit of the truth.

Additionally, there is a well-known phenomenon called publication bias when favorable treatment results are more likely to be published than negative treatment results.  In other words, a study that shows a drug is effective is more likely to be published than a study that shows a failed result. This means that physicians like me who read medical journals may receive an over optimistic view of drugs because of this cherry picking.

In my 30 years of practice, I have never had any of my untreated HCV patients develop any measurable deterioration of their liver status.   In fact, nearly all of them were asymptomatic and felt
entirely well. 

Illustration of the liver created 100 years ago.

Consider these facts:
  • Most patients with HCV are not ill.
  • HCV is not easily transmissible to other individuals.  It is spread via contaminated blood, such as with sharing IV needles.
  • The majority of HCV patients will never develop liver cancer or liver failure.
  • The majority oF HCV patient have had the infection for decades and remain well.
  • Until recently, HCV medications had very limited efficacy and had numerous complications.
Like all of you, I harbor my own biases.  I am a very conservative practitioner, as readers know well.  I am never among the first to jump aboard the New Treatment Train.

Until groundbreaking HCV treatment emerged in recent years, I had been unable to convince myself, let alone my patients, that they should accept a complex medical regimen that included injections, that didn’t work well and would make them feel sick.   

While my academic colleagues would have accused me of nihilism, not a single HCV patient in my practice has seemingly progressed.  (Of course, my academic friends would claim that many of my patients may have 'silently progressed' even though they still feel well.)   There is always a medical argument a physician can wield to justify his or her recommendation or belief.

I'm not claiming that my view here is the only legitimate one.  I do suggest that it deserves to be heard.

In an upcoming post, I will share why I have jumped, with some reluctance, into the HCV treatment arena. 


Anonymous said...

If you didn't want to treat HC because you felt the science was poor, that is nothing to be ashamed about. Or to even be defensive over. Or instance, if a Neurologist or ER doc did not want to give tPA for eligible people with an acute ischemic stroke, the science would probably back them up. For some reason that has become the standard of care despite 12 negative trials vs. 2, maybe 3 positive ones. One wonders how tPA passed the FDC approval process!!!?!

However if you were a lone wolf in your field, or if HC treatment was recommended in the GI practice guidelines but you simply didn't think it was necessary, then that would be a big problem. About how many active HC patients do you follow? 30? 50?

I don't know much about HC. You use words like "most don't progress" instead of percentages. I'll tell ya, as a 42 yo person if I had HC and had even a 5% lifetime chance of developing debilitating cirrhosis or metastatic liver cancer, and there was a treatment out there that was more or less safe and effective, I would want it (unless it was cost prohibitive).

If you are elderly and develop atrial fibrillation, your yearly chance of developing an acute stroke is between 2.5 - 5%. Being on warfarin reduces that to 1%. Same with the newer anticoagulstion drugs. They all come with some rather significant potential harms. Were the treatments for HC that you used to eschew also potentially dangerous?

Michael Kirsch, M.D. said...

Thanks for your comment. Yes, there were some serious side effect potential with prior HCV medicines. More commonly, they just made patients feel ill. The rough percentages of what I was taught is that no more than 20% of HCV will progress, although please recognize that experts may disagree on this or favor studies that mirror their own beliefs. My personally belief is that most HCV patients who are treated would likely never have suffered from advanced HCV disease. Keep in mind that HCV is not easily transmitted, so there is not a good argument to treat folks to reduce spreading the illness, such as occurs with influenza. As for your wanting to be treated personally, even if you felt well and faced low risk of progression, I assume your decision is influenced if you are not personally paying for the medicine. Although the cost has come down, a year or so ago, the cost of a standard regimen was $1,000 a pill. I'll leave the math to you for a 12 week course.

Anonymous said...

Of course my decision to be treated is influenced by whether I have to pay for the medicine.

There are people out there that are smarter than me and you who can calculate, using statistical models, the cost of treating something like asymptomatic HCV. If your life expectancy is 40 years and there is a 5% chance of contracting debilitating cirrhosis or liver cancer, then there is a price point where it's cheaper to treat everyone now than the cost of treatment for the few who get cirrhosis or liver cancer. I wonder if the FDA considers these costs when approving a medicine.

Anonymous said...

Imagine if you are on the FDA and you are asked to approve a medicine for cancer that increased yours life expectancy by 5 months. Total treatment costs $50,000. Is this a worthwhile outcome to justify tax payers footing the bill?

That is a difficult question and potentially full of controversy. We need drug companies and other institutions (like major academic research centers) to discover new treatments, but they also need to be cost effective.

Michael Kirsch, M.D. said...

My understanding is that the FDA considers safety and efficacy, not cost. I do not think that there is consensus on the risks that an asymptomatic individual with HCV will develop complications over time. No one knows which patient will progress, but it is still true that most will not. Because of this uncertainty, it is difficult for me to endorse global treatment.

Anonymous said...

I work in a corrections environment and we come upon the Hep C question all the time. My impression is similar in that I tell my patients that most people with Hep C feel well and will do well for their entire lives, but that about 20% may go on to develop serious liver disease. Currently, our strategy is to treat the ones with identified liver disease beyond a certain point. The rest we watch and wait. The cost of the first few DAAs was quite high, approaching or exceeding $100K per course of treatment. Recently, there has come a regimen which is about a third of the cost, and I suspect this will put a downward pressure on the others.

Michael Kirsch, M.D. said...

@anonymous, appreciate the comment. Enthusiasts of treating everyone defend the practice by stating correctly that we have no surefire way of determining which HCV patient is destined to progress. Therefore, they advocate using a wide net. I have a different philosophy.

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