How does long-term alcohol abuse lead to cirrhosis?

Submitted by gnarglgna t3_y1zti2 in askscience

I have seen a figure that displays a pathway of alcoholic liver disease leading to cirrhosis annotated with certain probabilities. On that way the first step is fatty liver. Is fatty liver always a requirement to develop alcoholic fibrosis/cirrhosis? Can a fibrotic/cirrhotic liver lose its fat again and look like a normal one? What are the mechanisms of this pathway?

425

Comments

You must log in or register to comment.

mtx013 t1_is1fohj wrote

More about fatty liver and cirrhosis:

One of liver basic functions is to store energy, one pathway to it is transforming sugar (and ethanol) in fat. Once you fat storage/usage is skewed, the liver keeps producing and storing fat, which leads to chronic inflammation.

Alcohol, hepatitis virus B and C or even your own autoimmune system cause direct inflammation in your liver.

Inflammation, while reversible, leads to cell damage, which cause (1) repair and (2) scars.

(1) chronic inflammation-repairing leads to increased cancer risk.

(2) scars are mostly irreversible and when accumulated, are called cirrhosis.

How much fatty liver you have before developing cirrhosis depends on genetics, amount and speed of liver damage. For reference, when discussing fatty liver disease, we usually divide it between alcoholic and non-alcoholic due to how much more damage alcohol causes.

29

CocktailChemist t1_is1pezd wrote

Replying to [deleted] (#87,080)

Nope, taking breaks during the week is much more important than taking larger blocks off. The damage tends to be something of a positive feedback loop - damage accumulates, which tends to lead to inflammation, which leads to more damage. Having time when the repair mechanisms can work before the inflammation sets in will do a lot more than a big break after that cycle has already been going for a while.

7

Wh0rse t1_is1povb wrote

Replying to mtx013 (#87,005)

Alcohol can't be stored at all, it has to be prefered to be metabolised over all macros because of this. In the presence of ethanol, dietry fat is stored and sugar converted to fat, but ethanols matabolism is to be eventually converted to CO2 and water for elimination.

6

Magurndy t1_is3fsa1 wrote

Fatty liver can restore themselves if you stop drinking or taking medication that’s causing it, or change your diet. However, once it gets to a cirrhotic state it’s scarred and therefore can’t really recover. Most people do have fatty livers in the western world once you are Middle Aged due to diet but it’s treatable. Also liver function tests tend to show damage before the physical signs can be seen on imaging. Cirrhotic livers though can be a ticking time bomb.

4

OneStrongBear t1_is3u05z wrote

In addition to what others have mentioned, chronic heavy ethanol consumption engages three different enzymatic pathways to metabolize the ethanol to acetaldehyde and eventually acetate to be oxidized to ATP.

In light or casual drinkers, their stomach contains alcohol dehydrogenase (ADH) which initiates the breakdown of ethanol to acetaldehyde - note that men have more ADH than women which contributes to their naive tolerance of ethanol and eating food allows more time for your stomach ADH to function. "It's not a myth, folks."

After that is where the dose makes the poison. In the liver we use a hepatic isoform of ADH to break down what the stomach could not, but if the hepatic ADH is overwhelmed we use the microsomal ethanol oxidizing system, or MEOS. The MEOS is our 'overdrive' that helps compensate for heavy alcohol consumption but as a result produces a high degree of free radical byproducts that can lead to cell damage in the liver. Over years of consistent MEOS activity and damage you see the cellular dysfunction characteristic of cirrhosis.

7

S0NNYDL1TE t1_is4mz0e wrote

So my question: is there a relationship between feeling “drunk” and the point where you cause damage to your liver? I drink probably four nights a week to the point of a light buzz, like 4-5 shots of vodka in a Bloody Mary(typical example) I don’t usually feel drunk but is this causing damage or is damage starting once you actually feel drunk?

2

hellbellone t1_is4otlo wrote

In all chronic liver diseases, alcohol intake creates an additional burden on the liver and is an additional factor in its destruction. If the nature of the disease is associated with liver damage and the possible formation of cirrhosis, then alcohol intake significantly activates this process.

3

backwardupsidedown t1_is53ce4 wrote

Alcohol is poisonous to humans, just depends on the dosage. The thing is alcoholism, is the NEED to consume, and the amount is not how we define alcoholism. There is no amount that won’t cause damage to liver, it’s what you drink, how often you drink, and how much you drink. If you drink regularly, high proof liquor eventually it could cause cirrhosis’. Some people drink like fish and never get it, some drink a little over years and get it. There are so many factors involved it is not quantifiable. If you consume excessive( which you are ) amounts eventually over time you will In fact damage your liver, wether you end up with cirrhosis, is something no one can answer. Besides why play with fire, knowing eventually you could get burned. Try other ways to de stress. Alcohol being addictive will only make your life and relationships more difficult as you become dependent.

2

gnarglgna OP t1_is5t7ey wrote

Replying to backwardupsidedown (#92,573)

Yeah, I'm just doing that, not drinking anymore. I would agree that it was definitely too much, too. But besides, I didn't mention my consumption pattern, did I? How do you know? And I was indeed interested in the mechanisms.

3

grumble11 t1_is6qken wrote

Replying to gnarglgna (#94,119)

Three small glasses of wine a day would be 21 units a week. As one example, Canada's existing guidelines at 15 drinks a week max for men and 10 drinks a week max for women before you hit material negative health consequences, and more recent research is likely to update those guidelines as it's been shown that intake at lower levels than 15/10 is still harmful. The newly proposed guidelines are two drinks a week, regardless of gender, noting that women are more impacted by men as you exceed 2/week but that both will experience meaningful statistical harm including meaningful increases in certain cancers (like breast and colon for example).

https://ccsa.ca/sites/default/files/2022-08/CCSA-LRDG-Update-of-Canada%27s-LRDG-Final-report-for-public-consultation-en.pdf

2