Gilbert's Syndrome (unconjugated hyperbilirubinemia) and NASH (scientific point of view)

[MINTVCX]

First I have to warn everyone that is about scientific articles and not everyone likes this stuff. Moreover is not approved fact.

Nothing conclusive but below some studies about unconjugated hyperbilirubinemia (like in Gilbert's Syndrome) and some possible protective role for liver. But keep in mind that this is not about situation when high bilirubin level is because of liver damage (and is a sign of bad synthetic function) from my understanding.

GILBERT'S SYNDROME AND NASH: A PROTECTIVE EFFECT OF UNCONJUGATED HYPERBILIRUBINEMIA

"Conclusion: This study shows significantly lower prevalence of unconjugated hyperbilirubinemia in patients with histopathologic evidence of steatohepatitis (NASH) compared to simple steatosis and a normal control group. It is possible that sustained unconjugated hyperbilirubinemia inhibits oxidative stress, inflammation, and hepatic fibrogenesis, preventing NASH. This may have significant therapeutic implications for patients at high risk of developing NASH with medications which elevate unconjugated bilirubin such as probenecid, rifampin, phycobilins, and algal biliverdin metabolites."

livertree.easl.eu/easl/2012...

And also:

" Association between bilirubin and risk of Non-Alcoholic Fatty Liver Disease based on a prospective cohort study"

"Thus, it can be conceivably speculated that bilirubin could be linked to decreased risk of NAFLD, a hepatic manifestation of metabolic syndrome, probably induced by inhibiting oxidative stress."

nature.com/articles/srep31006

"Elevated serum bilirubin levels are inversely associated with nonalcoholic fatty liver disease"

" In conclusion, this study, conducted with a large number of healthy populations, confirmed the inverse relationship between serum bilirubin level and the occurrence of NAFLD. Based on this result, further clinical studies on the disease prevention and treatment by controlling serum bilirubin level will be required in the future.

ncbi.nlm.nih.gov/pmc/articl...

On the other hand no correlation was found here (Chinese population) :

"Genetically Regulated Bilirubin and Risk of Non-alcoholic Fatty Liver Disease: A Mendelian Randomization Study"

"Based on a Mendelian randomization approach, our data suggest that increased bilirubin levels is unlikely a causal factor for a reduced risk of NAFLD."

frontiersin.org/articles/10...

[nash2 Partner]

Interesting question. Hadn't seen that before but could be. There are a lot of things that are beneficial at a low dose but toxic at higher levels. I have Gilbert's myself and it has been a concern for some docs but we apparently don't really know the answer.

Wayne

[MINTVCX in reply to nash2]

Well for sure Gilbert's Syndrome and possible (not conclusive) advantages of slightly high unconjugated bilirubin does not mean the liver is indestructible when we talk about things like HCV, obesity or extensive alcohol use. Interesting if alcohol in let's say small doses can damage liver more than without GS but no scientific studies I think. Most doctors have opinion that GS is neutral to liver. You can be a liver donor with GS (of course if no other liver disease) for example.

Maybe ther is some correlation with GS and relatively normal basic LFT if there is a liver fibrosis for other reasons (fat or alcohol)? If possible bilirubin has something to do with lower ALT, AST level. But this is only my guessing not scientific facts of course. Maybe liver cirrhosis has different course for people with GS? Better prognosis? But I think it would be difficult to find them for study. A lot of questions.

About not only liver I found this, but I think that it was proved that GS have some protective role for heart.

Gilbert's syndrome and the risk of death: a population-based cohort study"

"Conclusions: Mortality rates observed for people with Gilbert's syndrome in the general population are almost half those of people without evidence of Gilbert's syndrome."

pubmed.ncbi.nlm.nih.gov/237...

"Unconjugated hyperbilirubinemia: A blessing in disguise?"

"In conclusion, the demonstration of reduced overall mortality in persons with GS in the study by Horsfall et al. should be of interest to a variety of medical specialists, even though the data are not necessarily conclusive. One hopes that large, prospective, long-term follow-up cohort studies will soon follow to confirm or refute its findings. If these studies confirm the protective effect of GS on the overall risk of death, it would be important to determine the mechanisms underlying this association. Such information may open a vista of newer interventions to improve human health and survival."

onlinelibrary.wiley.com/doi...

[MINTVCX in reply to nash2]

Sorry for private question about you. As I found you use FibroTest (Fibrosure in USA) or something similar (LIVERFASt? ) to check your liver condtion. Because of GS your normal bilirubin level can be twice/triple the upper normal level (but if you have no other problem besides GS sometimes it can be very close to normal). Is your result some kind adjusted because of this fact? When I got mathematic pattern for Fibrotest (Wikipedia) and calculated it the bilirubin level had significant meaning in scoring fibrosis (normal level F2, level found in GS F3).

[nash2 Partner]

GS does complicate things. My bilirubin is above high normal but a lot so I recalculate the test using a normal bilirubin and know that the real answer is somewhere between those two values.

[MINTVCX in reply to nash2]

I know Wikipedia is not the best source but it is from one medical article - > pubmed.ncbi.nlm.nih.gov/255...

"Platelet counts and MPV are decreased in patients with Gilbert's syndrome. The elevated levels of bilirubin and decreasing levels of MPV and CRP in Gilbert's syndrome patients may have an effect on the slowing down of the atherosclerotic process."

en.m.wikipedia.org/wiki/Gil...

Platelet level can also say something about liver condition. And if above is true, with GS they can be decreased... (not sure how much).

I am wonder about AST/ALT level with Gilbert's Syndrome (normal level range). As I remeber when I was 18 years old I was checked AST, ALT during routine blood donation (now in Poland is not performed that time it was). And AST/ALT was above 1 (AST higher than ALT, both normal range below 20). The same was when I was 27 years.

I found some old 1976 article "Liver ultrastructure in Gilbert's syndrome".

Only 9 with GS but 7/9 had also AST/ALT >1 within normal range (all values below 30).

ncbi.nlm.nih.gov/pmc/articl...

[nash2 Partner]

I don't think GS has really had a enough research but it makes sense that multiple chemical processes would be affected in some way given the genetics driving the process. I've never really pursued the question even though I have that diagnosis as I assume that the cirrhosis probably has greater impact.