> The approach is unusual: researchers injected healthy liver cells from a donor into a lymph node in the upper abdomen of the person with liver failure. The idea is that in several months, the cells will multiply and take over the lymph node to form a structure that can perform the blood-filtering duties of the person’s failing liver.
The first treatment was performed on March 25th, so we have several months to see how this will go. Initial recovery looks good. Of course this is huge because we don't have enough livers for everyone that needs one. If we can grow a new one with a little help than that will greatly increase the number of people with failing livers we can help.
Surprisingly little. Most of the liver stand by at idle ready to filter intermittent massive doses of things, such the stuff arriving in your bloodstream after a big meal. This is what makes many liver diseases so evil. A person can live basically free of symptoms for many years as their liver struggles and is progressively damaged by some substance (alcohol). Until one day the amount of remaining functional liver dips slightly below the minimum needed to sustain daily functions. After decades of drinking, over the course of a month a functional alcoholic can go from being a happy drunk to a patient dying in hospital in need of a new liver.
Just do blood tests for liver diseases markers every year. Even if you're not an alcoholic - there's many other diseases that result in similar damage.
For example if you have asthma and especially if you have colitis ulcerosa or crohn's disease - you're at much higher risk of PSC - an autoimmune liver disease which does basically the same thing as decades of drinking.
Readers beware that, like most random testing/imaging, this can lead you down an expensive road with no resolution in sight. Liver markers are frequently elevated, non-symptomatic and with no obvious cause in healthy individuals. It starts with blood tests and progresses to imaging and invasive biopsy.
I suggest finding a good doctor instead and letting them manage the frequency and depth of testing like this. Many chronic liver diseases aren’t curable or even satisfactorily treatable. Losing weight, watching carb intake, and avoiding alcohol are the big preventative measures.
Tangentially, I just found out in a routine test that I have a condition called "gilbert's syndrome" [0]. It's harmless tho. It came from my parents, it seems. My dad died of liver cancer, but I don't know if he was diagnosed with that syndrome and if they were related.
I've got Gilbert's as well - found out about ten years ago during some routine blood work.
The only thing I've noticed is that dehydration hits me a little harder than most people. If I don't drink enough water throughout the day I get fatigued, and if I don't drink enough water after a night out I get pretty gnarly hangovers.
This is just comparing me to my peers though, and might not be due to my Gilbert's at all, but the fact that these things have been linked to Gilbert's in studies means it's possible they're related.
Anyway, staying hydrated never hurts, so thought I'd pass that along in case it helps you too.
What you said makes a lot of sense, I started taking more care of my health in the last 45 days, I took several tests, etc. and then I discovered this condition.
The nutritionist, not yet knowing about Gilbert's syndrome, asked me to drink 2 to 3 liters of water a day and what I noticed was a huge reduction in the sleep I felt during the day. I also realized that caffeine consumption also bothers me and I'm trying to reduce it.
Don't even get me started on the hangover, every time I go out I already know I'm going to have a hellish next day! It's great to know that I'm not the only one and that someone else continues to drink even though they have a "problem" with their liver, so I feel less guilty!
I'm rather unclear about the speed of regrowth. From one source (the web?) It was a matter of years, yet talking to a herpetologist (edit: hepatologist. Blame voice recognition) in a pub, she said it can regrow 80% of itself in a matter of weeks. Assuming a healthy liver, how fast is regrowth?
Assuming a cirrhosed liver , how would that affect regrowth time? TIA.
One of our dogs had days to live by the time we found out he had a congenital defect that caused a fibrous liver. In retrospect some parts of his personality may have been symptoms, but we were wrecked.
They are to an extent. Cirrhosis is permanent. Other conditions such as fatty liver are reversible-ish.
The issue is that the liver is basically fully functional until after you’ve destroyed ~88% of it.
For a tortured analogy it’s a lot like a DB. Most of them time you’re well under your total capacity. Even short spikes in queue length aren’t an issue. But once you hit the tipping point there are cascading failures.
Cirrhosis has been observed to reverse in some individuals. It is still permanent for most patients, and we shouldn’t give people with it false hope, but its reversal isn’t impossible. Most commonly cirrhosis reversal is observed after chronic viral hepatitis is cured by antiviral treatment. There are even a handful of clinical case reports of alcoholic cirrhosis reversing after extended abstinence from alcohol, even though that is a rather rare outcome. I remember reading a case report (sorry can’t find it right now), of a Japanese alcoholic diagnosed with liver cirrhosis, who then was severely disabled by a stroke, and had to be moved to a nursing home. He never drank again because he physically couldn’t drink without nursing staff assistance, and they weren’t going to give him any alcohol. Roughly 20 years later, his cirrhosis had disappeared. Of course, this is a rare outcome (he likely had favourable genetics, plus rarely does an alcoholic find relapse physically impossible), but it shows it can happen.
This is why there is a lot of hope that some of the liver disease drugs currently in the clinical pipeline may be able to reverse cirrhosis (and if not them, maybe their future successors). However, current trials are focusing on fibrosis not cirrhosis. And they run into the difficulty that what counts as cirrhosis seems reasonably clear in everyday clinical practice, but how to reliably detect its existence/progression/improvement/reversal to a clinical trial standard of certainty is difficult and a matter of dispute
(No I don’t have cirrhosis, as far as anyone knows, but my aunt had it-albeit asymptomatic, it was only discovered on autopsy after she suddenly and unexpectedly died from a cardiac arrest while asleep one night-which is actually very common, majority of people with liver disease die from heart disease before the liver disease kills them, or even causes any observable symptoms-but I do have intermittent hypochondria, and in some of my past hypochondriac episodes I have become rather obsessed with reading papers on this and related topics.)
Patients with cirrhosis have significant scarring of the liver that disrupts the normal liver architecture. When liver cell regenerate on this abnormal scaffolding it forms regenerative nodules surrounded by scar tissue that prevents then from doing their normal filtering.
> Hufford says there’s reason to think that the organs won’t grow indefinitely in the lymph nodes. The mini organs rely on chemical distress signals from the failing liver to grow; once the new organs have stabilized blood filtering, they will stop growing because that distress signal disappears, he says. But it’s not yet clear precisely how large the mini-livers will become in humans, he adds.
Well that looks promising, hopefully they stay as mini-livers.
I immediately imagined people with much larger liver masses in their necks and got to wondering how safe it would be. Is there risk of impingement on things like arteries or the spine were they to continue to grow? What's the margin of safety between how big they're expected to get and how big would be dangerous? (I know nearly nothing about any of the systems involved, so I won't be surprised if these end up being comically naïve questions. I just still wonder!)
Almost all human cells are programmed to remain in a specific place and to commit suicide if they discover they're misplaced. This way when things go a little bit wrong and a few cells are somewhere they shouldn't they just die, and there are more where those came from.
The lymph system's own cells deliberately lack this programming, they're part of the immune system and are supposed to wander about on their own. But these liver cells presumably don't think they're actually lymph cells, so they aren't entitled to just wander off.
I was thinking mini-kidneys, mini-hearts? The latter might involve difficult coordination, but maybe that's not necessary if you've got individual hearts running at lower blood pressure.
It all just reminds me of Neal Asher's stories, where creatures build nano factories in their bodies as and when needed, including local fusion "nodes".
I think there's a lot of parts in the brain that involve day to day coordinations that could be moved out. Fine motor control stuff in the cerebellum probably wouldn't hurt if it's closer to the muscles, but the cerebrum might be harder to split up and scatter because of latency and bandwidth. On the other hand, we could go from dual core in the cranium to multicore distributed - like octop(uses|i) have one brain per arm and I believe another to rule them all.
Does anyone know if they could use the patient’s own liver cells instead of a donor’s? Is every cell in the dying liver so unhealthy that they couldn’t harvest any?
This is my thought too. How many cells are actually need to do this. If it's just a few, surely if a patients kidney is in 80% bad shape, then they can take a few cells from the 20% good and do this?
I guess if there is a genetic problem with the patients own liver, then it would make sense to use another persons cells.
Ahh just read the last paragraph:
> If the liver trial is successful, Gouon-Evans says, it would be worth investigating whether a person’s own stem cells could be used to generate the cells that seed the lymph nodes. This technique could create personalized cells that capture the diversity of cells in the liver and don’t require immunosuppressive drugs, she says.
This was my question too, so thanks for doing the legwork. Wondering (in complete ignorance of this general topic) why they didn't jump straight to that approach, though...
edit: I guess maybe if you start with a healthy liver, the variable of whether the liver disease in question could affect the viability of transplanted cells is taken out of question? Presumably the immune response/immunosuppressant stuff is better characterized.
That last paragraph is different though, it’s using stem cells to make liver cells, not using the patients liver cells directly..
I have no idea why not, but my wife does a lot of work growing different cell types from stem cells, and my understanding is that that’s still like.. they think they are making cell types a, b or c, but it’s a lot of uncertainty. What they really do is convert the stem cells into cells that express m various markers/pass various tests that the “real” cell type also express.. but it’s really hard to know that it’s actually a 1-1 match.
Just yesterday she was lamenting they were making astrocyte cells, and many of the cells in the colony instead became.. something else, unclear what, maybe not even a cell type that exists in humans normally?
Either way: using healthy liver cells from a healthy liver would be a way to ensure you actually really have liver cells, and not something that just sorta duck-types as one
inside a lymph node is the very last place i would expect a transplant.
they are teaming with immune cells that should be hostile to an inter-species transplant. there are no red blood cells for oxygen, just lymph fluid. how would it recruit blood vessels to grow? it would be painful; swollen glands.
Years ago, someone noticed that hepatocytes injected into a mouse's abdomen would migrate into the lymph nodes and start making liver cells. I don't even know why they were doing that in the first place, but all this research follows from that observation.
This is covered in the article. As I understand it, the liver grows in response to chemicals in the blood which it also filters. So it will stop growing when it's large enough to filter all the markers.
The first treatment was performed on March 25th, so we have several months to see how this will go. Initial recovery looks good. Of course this is huge because we don't have enough livers for everyone that needs one. If we can grow a new one with a little help than that will greatly increase the number of people with failing livers we can help.