Non-Alcoholic Fatty Liver Disease as the Marker of a Lifestyle that Shortens Life Span

If you are overweight, then you will suffer a faster pace of aging, more age-related disease, greater lifetime medical costs, and an earlier death. The more excess weight and the longer that weight is held, the worse the outcome. In at least one sense, being overweight literally accelerates aging, increasing the pace at which harmful senescent cells accumulate in the body. These errant cells secrete signals that produce chronic inflammation, but this isn't the only way in which visceral fat tissue causes unresolved, chronic inflammation, an unwanted overactivation of the immune system that disrupts metabolism and speeds the progression of age-related disease. Fat cells produce signals that mimic those of infected cells, and DNA fragments released from dying fat cells produce a similar outcome.

Whenever one looks at the relationship between mortality and metabolic diseases - such as non-alcoholic fatty liver disease, today's topic - that are usually the product of being overweight, then one is looking at a proxy measure of the progression of mechanisms by which visceral fat tissue accelerates aging. Today's research materials note that even mild non-alcoholic fatty liver disease is linked to increased mortality. This is because the most common cause of mild non-alcoholic fatty liver disease is for an individual to be meaningfully overweight, carrying excessive visceral fat tissue that disrupts metabolism and harms future prospects.

Even mild fatty liver disease is linked to increased mortality

Non-alcoholic fatty liver disease, NAFLD, is often caused by obesity and affects nearly one in four adults in Europe and the US. Earlier research has demonstrated an increased risk of death in patients with NAFLD. Now, researchers show that mortality increases with disease severity, but even mild fatty liver disease is linked to higher mortality. The researchers matched 10,568 individuals with biopsy-confirmed NAFLD to general population controls through Sweden's comprehensive, nationwide registers. They found that all stages of NAFLD were associated with excess mortality risk, even early stages of disease. This risk was driven primarily by deaths from cancer (excluding liver cancer) and cirrhosis, while the risks of cardiovascular mortality or hepatocellular carcinoma (HCC) mortality were relatively modest.

Patients with NAFLD had a 93 percent increased risk of all-cause mortality, but the numbers varied with disease severity. The risk increased progressively from the mildest form of NAFLD (simple steatosis), to non-fibrotic steatohepatitis (NASH), to non-cirrhotic fibrosis, and to severe NAFLD with liver cirrhosis.

Even mild fatty liver disease is linked to increased mortality

This nationwide, matched cohort study included all individuals in Sweden with biopsy-confirmed NAFLD (1966 to 2017; n=10,568). NAFLD was categorised as simple steatosis, non-fibrotic steatohepatitis (NASH), non-cirrhotic fibrosis and cirrhosis. Using Cox regression, we estimated multivariable-adjusted hazard ratios (aHRs).

Over a median of 14.2 years, 4,338 NAFLD patients died. Compared with controls, NAFLD patients had significantly increased overall mortality (aHR=1.93). Compared with controls, significant excess mortality risk was observed with simple steatosis (aHR=1.71), non-fibrotic NASH (aHR=2.14), non-cirrhotic fibrosis (aHR=2.44) and cirrhosis (aHR=3.79). This dose-dependent gradient was similar when simple steatosis was the reference. The excess mortality associated with NAFLD was primarily from extrahepatic cancer (aHR=2.16), followed by cirrhosis (aHR=18.15), cardiovascular disease (aHR=1.35) and hepatocellular carcinoma (HCC) (aHR=11.12).

In conclusion, all NAFLD histological stages were associated with significantly increased overall mortality, and this risk increased progressively with worsening NAFLD histology. Most of this excess mortality was from extrahepatic cancer and cirrhosis, while in contrast, the contributions of cardiovascular disease and HCC were modest.

Comments

How many here drink alcohol? I don't.

Posted by: Gekki at October 20th, 2020 4:44 PM

I have a few drinks occasionally. Much less than before, though. But even close to the 10% in drinking water for that mouse study which showed that constant alcohol use increases murine lifespan... Everything should be in moderation.

Posted by: Cuberat at October 20th, 2020 8:35 PM

I have a non-alcoholic slightly fatty liver at 10% body fat. I had another scan recently and the doctor said it's likely due to diet soda drinks.

Posted by: Gareth Turner at October 21st, 2020 3:19 AM

@Gareth Turner
fasting can reduce the fat content around the liver. In fact , the first things to be scavenged is the glycogen within the liver (usually takes 3 days of water fast or running a marathon) . After that the liver slowly will switch to ketosys and start consuming surrounding fats. Doesn't reverse aging but helps with such conditions...

Posted by: cuberat at October 21st, 2020 7:04 AM

Thank for that cuberat. I might add that's it's fasting, not dieting that properly removes visceral fat. Older people can diet and look way too thin but still have that protruding belly.
According to this study, fasting- for even 24 hours - removes both subcutaneous (good) fat and visceral fat. The good news is that upon reseeding most of the sub fat comes back while less of the visceral does. Do it often enough and you gradually "eat up" your visceral fat while preserving important sub fat.
https://www.nature.com/articles/ncomms11533

Posted by: august33 at October 21st, 2020 9:00 PM

There's a more extreme version for faster results. I find it easier to tolerate it than a weekly 24h fast. Here's my protocol.
On day 0 take laxative or food that has such effects to clean/relieve the intestines. Do 2-3 days dry fast. It is surprising but up to 3 days it is easier to tolerate than water fast. It seems to force the body to switch to ketosis much faster. Then from day 4 to day 7 switch to water fast. The most important part is breaking the fast. I use 2 days to drink freshly extracted beat and carrot juice. Start slowly. On the day 3 start eating a bit of veggies. On Day 4 gradually introduce yogurt (plain) and fruits. Day 5 and 6 can bread and nuts(unsalted). On day 7 slowly start retuning to the normal target diet. This is actually the hardest part not to start overeating. Take probiotics and bacteria pills. Try exercising. In two weeks after breaking the fast do an ultrasound of your liver.

Before trying my protocol do a few 24 and 48 hours water fasts to see how you tolerate it, gain some experience and train your body.
Disclaimer: If you are underweight be extremely careful. Medication and dry fast cannot be combined since the effects change drastically. Fasting and insulin , metformin and be other medications that lower the blood sugar can be combined only in clinical settings under medical supervision with frequent monitoring and be ready to break the fast at any moment.

I personally believe that fasting after a course of senolytics gives a compound effect. However, I have no scientific proof.

Posted by: Cuberat at October 21st, 2020 10:34 PM

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