Gilbert’s Syndrome and cancer treatment

[Rock_Robster]

Hi all, a bit of a cancer-adjacent issue, but thought I’d share my experience and also see if the group mind has any advice for me.

Throughout my 4+ years of treatment (including a lot of liver-directed therapy), my bilirubin levels have never really been an issue. However over the past 6 months or so my total bilirubin has shot up rapidly; sitting around 30-40 mg/dL (1.7 - 2.2 mmol/L in US units), and in the last month has doubled to 60 mg/dL (3.3 mmol/L). Normal upper limit is 20 mg/DL (around 1.2 mmol/L). The thing is - all other liver markers are perfect (no enzyme elevation), there is no concern around obstructive/drainage disorders on liver imaging, and I have no symptoms of hyperbilirubinemia. I don’t have a gallbladder, so presume no risk of gallstones. Because of this, 3 oncologists have separately now concluded that I probably have Gilbert’s Syndrome (and my GP/PCP agrees).

Although it’s a bit strange that it only started to show recently, apparently Gilbert’s symptoms can be brought on by periods of physical stress or injury - eg cancer treatment. It seems to be a fairly common genetic condition (5-10% of males), and generally mild and asymptomatic. The only relevancy raised so far for my cancer treatment is, (1) dosage of irinotecan would need to be adjusted down for my diminished clearance rate, and (2) I would likely need to get an exemption from upper t-bili limits on clinical trials due to Gilbert’s Syndrome (apparently that’s usually recognised by investigators). Otherwise provided my other liver enzymes are fine and I’m asymptomatic, my oncologist(s) are not concerned. It may well be that Gilbert’s is the least of my problems.

However… like everything I’m conscious there’s a lot I don’t know, so interested if folk have any other experiences with this, or recommendations on how to manage.

Thanks,
Rob

[beach sunrise]

Never heard of Gilberts Syndrome. I will have to ask my ND about that.
When my bilirubin started to rise it was because my common bile duct was inflammed inside and outside for some reason and RBC's were affected by it also. We got it straightened out with hepogennesis, bilberry and a gallbladder supplement.

[Rock_Robster]

Thanks beach sunrise - any insights welcome! I’ve picked up RP’s earlier suggestion of taurine supplementation to help with bili clearance.

[beach sunrise]

Good deal, thats great!
The compound supplement I took had taurine.

[rp1954]

Hi all, a bit of a cancer-adjacent issue, but thought I’d share my experience and also see if the group mind has any advice for me.

My advice is to show all your blood work to more interested, capable, specialized people.
The whole enchilada can take on additional meaning and detail - continued whole dataset (extended) analysis is what we had to do to get ahead and respond in real time. Normal clinical practices are inherently 1 to 9 months more retrospective in different aspects.

The thing is - all other liver markers are perfect (no enzyme elevation), there is no concern around obstructive/drainage disorders on liver imaging, and I have no symptoms of hyperbilirubinemia.

I'm not sure what you call perfect.
The thing I found in the literature is that a lot of panels, especially in combination in particular "eras", can take on whole new meanings with colorectal cancer with quite different lab ranges.
For some panels, that's ca 0.5 - 1 * upper limit of the normal lab range becomes an early warning (2nd edit)

Most oncologists weren't that specialized, weren't reading their own literature, and couldn't be bothered. If it was important, NCCN, their oncology society or the sales reps would tell them. I try to bite my tongue and not be too critical because we had several advantages they don't have.

Because of this, 3 oncologists have separately now concluded that I probably have Gilbert’s Syndrome (and my GP/PCP agrees).

[shrug]"You're a pallative patient between scans with no immediate distress or approved indications, and we'll see you next time/month."

Although it’s a bit strange that it only started to show recently, apparently Gilbert’s symptoms can be brought on by periods of physical stress or injury - eg cancer treatment. It seems to be a fairly common genetic condition (5-10% of males), and generally mild and asymptomatic. The only relevancy raised so far for my cancer treatment is, (1) dosage of irinotecan would need to be adjusted down for my diminished clearance rate, and (2) I would likely need to get an exemption from upper t-bili limits on clinical trials due to Gilbert’s Syndrome (apparently that’s usually recognised by investigators).

You may be limiting your options to the std/conventional box several ways.

[Rock_Robster]

I agree RP it does seem like the conventional view is to dismiss this based on asymptomatic and palliative patient. I’ll definitely be looking into it more.

Just so I’m clear on the inference - your suggestion is this might not be Gilbert’s but potentially something more sinister? It’s a relatively easy blood test to confirm Gilbert’s, so perhaps that’s worthwhile having done.

When you say this may have limited my options to conventional treatment in ‘several ways’, are you referring to beyond qualifying for clinical trials?

Thanks,
Rob

[rp1954]

Just so I’m clear on the inference - your suggestion is this might not be Gilbert’s but potentially something more sinister? It’s a relatively easy blood test to confirm Gilbert’s, so perhaps that’s worthwhile having done.

My view is that they aren't sure, or are not discussing possibilities because they have no indicated action items "today".
This can lock you into std trajectories when it is still technically possible to maneuver, beyond std.
e.g. if it's chemo damage or if it's early signs of met activity, they won't act very often or very much from their limited menu, so to them there's nothing to discuss.
Vs with my wife we could fine tune or make changes each blood test to try to improve measurements, improve actual results and anticancer activity.
In your shoes, I'd probably do whatever Gilbert's Syndrome test(s) and sharpen up on the expanded blood testing, maybe add a ctDNA.

When you say this may have limited my options to conventional treatment in ‘several ways’, are you referring to beyond qualifying for clinical trials?

First, your comments show you're not breaking out of the box from conventional data analysis of the data you do have, and hence impairs your ability to improve your own follow up. I know it's not easy and it's not likely to be one stop shopping. Beyond a certain point, digging the papers out is a time intensive option. Asking for help is faster.
Second the more detail you present on the forum can better attract others' experiences, data comparisons, and opportunities otherwise likely missed.
Third, being better informed can help you actively find and qualify for trials, or running your own.

[roadrunner]

Rob: IMO your exchange with rp1954 is an interesting—and perhaps strategically material—discussion. My concern is something you said above, namely, that “it’s a bit strange that [the possible Gilbert’s Syndrome] only started to show recently, apparently Gilbert’s symptoms can be brought on by periods of physical stress or injury—e.g., cancer treatment.”

You’ve had a very substantial amount of treatment, including surgeries and serious non-surgical therapeutic interventions, over the last few years. And I assume that you’ve had innumerable bilirubin tests/hepatic enzyme panels. Yet this seems (from your account) to be novel. So the “strange” aspect appears two-fold: Not only did the (potential) Gilbert’s symptoms fail to appear before generally, but they don’t seem to have been a concomitant phenomenon to your many cancer treatment stresses. To me, that is potentially significant. I would *at least* discuss that specific issue with the oncologists providing the diagnosis. Also, your point about the “simple” test is a good one: wouldn’t it make sense to find out?

My sense is that while you are realistic about the challenges you face, you are doing everything reasonably productive to gain time, and perhaps even eventual victory over your disease. While—with respect—I don’t share all of rp1954’s negative perspectives on SOC/conventional oncologists, I agree with his view that they (IMO by the nature of their job, including the volume of diverse patients that they see) can bring in unacknowledged/undisclosed perspectives to consultations that are divergent from ours as patients—particularly from highly informed and engaged patients like you. Here, I’d say this—going solely on your personality and perspectives evinced on this forum: If there’s a simple test for this syndrome, wouldn’t it be better to know? I believe you might wish to explore other explanations, and perhaps therapeutic options, if it is not present.

[Rock_Robster]

Thanks for the perspective all, indeed getting the test now seems a no-brainer, and I’ll organise it.

Also need to keep in mind that even if I am Gilbert+, that doesn’t automatically mean that’s the reason for high bilirubin.

ctDNA is a good suggestion now too, given my other data is a bit patchy.

Cheers,
Rob

[rp1954]

My sense is that while you are realistic about the challenges you face, you are doing everything reasonably productive to gain time, and perhaps even eventual victory over your disease

The major aspect of gaining victory over palliative treatment is to have biologically plausible plans to bridge the gaps in std medicine to convert to a curable, -ed patient and then treat it like a major project where you have to complete all the steps of the project. Preferably each step has good historical examples . Often important answers do remain obscure for various (common) reasons.

With my wife, improved measurement and interpretation were foundational to any path forward, especially multiple steps beyond the std of care box. Once we had identified technical components and project steps, the medical obstructions were really psychological, social, economic in nature rather than true technical show stoppers.

Basically, once something is available somewhere in the world or even doable, it shifts to more to psychological, social and economic dimensions, much of it in the medical systems rather than patients.
Many of the unused or under utilized techs are more favorably done at home.

Time and timing also become bigger considerations with more advanced metastatic disease. My view of incurable and too late for cure is structurally different in a situation where delay can be a very deadly form of denial.