Obesity Is Found To Increase The Risk Of Liver Cancer.

Metabolic disorders, particularly obesity increases the risk of a number of cancers, e.g. colon, mammary, pancreas and liver.

The primary functions of the liver are metabolism and detoxification. Nutrients from the gut are metabolised in the liver involving the insulin regulated PI3K/PTEN pathway. Wnt/β-catenin signalling also plays important role in regulating the metabolic and detoxicating functions of the liver as it regulates liver structure and zonation. Following a diet containing high fat, sugar, cholesterol, or alcohol, activation of these signals results steatosis. The consequence cell death due to steatosis and loss of liver structure leads to inflammatory cell infiltration. Inflammatory mediators produced due to liver inflammation propagate any genotoxic events as they induce the proliferation of tumour initiating cells that carry mutations of TERT, CTNNB1, TP53 and to a lesser extent PTEN and MYC as well as others. The Wnt/β-catenin, PI3K/PTEN and MAPK signaling pathways as well as cytokine and chemokine are all implicated in the proliferation of the tumour cells and play roles in propagating the initial mutagenic events.

To prevent the risk of liver cancer, it is critical to focus on prevention of liver disease.

What to Know About Fatty Liver 

Fatty liver is also known as hepatic steatosis. It happens when fat builds up in the liver. Having small amounts of fat in your liver is normal, but too much can become a health problem. Your liver is the second-largest organ in your body. It helps process nutrients from food and drinks, and filters harmful substances from your blood. Too much fat in your liver can cause liver inflammation, which can damage your liver and create scarring. In severe cases, this scarring can lead to liver failure. When fatty liver develops in someone who drinks a lot of alcohol, it’s known as alcoholic fatty liver disease (AFLD). In someone who doesn’t drink a lot of alcohol, it’s known as nonalcoholic fatty liver disease (NAFLD).

What are the symptoms of fatty liver?

Fatty liver can progress through four stages:

1. Simple fatty liver. There’s a buildup of excess fat in the liver. Simple fatty liver is largely harmless if it doesn’t progress.
2. Steatohepatitis. In addition to excess fat, there’s also inflammation in the liver.
3. Fibrosis. Persistent inflammation in the liver has now caused scarring. However, the liver can still generally function normally.
4  Cirrhosis. Scarring of the liver has become widespread, impairing the liver’s ability to function. This is the most severe stage and is irreversible.

Both AFLD and NAFLD present similarly. However, in many cases, fatty liver causes no noticeable symptoms. But you may feel tired, or experience discomfort or pain in the upper right side of your abdomen.

Some people with fatty liver disease develop complications, including liver scarring. Liver scarring is known as liver fibrosis. If you develop severe liver fibrosis, it’s known as cirrhosis, a potentially life threatening condition that can cause liver failure. The liver damage due to cirrhosis is permanent. That’s why it’s so important to prevent it from developing in the first place.

Nonalcoholic fatty liver disease (NAFLD)

Nonalcoholic fatty liver disease (NAFLD) is when fat builds up in the liver of people who don’t drink a lot of alcohol. If you have excess fat in your liver and no history of heavy alcohol use, you may receive a diagnosis of NAFLD. If there’s no inflammation or other complications, the condition is known as simple NAFLD.

Alcoholic fatty liver disease (AFLD)

Drinking a lot of alcohol damages the liver. Alcoholic fatty liver disease (AFLD) is the earliest stage of alcohol-related liver disease. If there’s no inflammation or other complications, the condition is known as simple alcoholic fatty liver. Alcoholic steatohepatitis (ASH) is a type of AFLD. It’s when a buildup of excess fat in the liver is accompanied by inflammation, which is also known as alcoholic hepatitis.

What are the causes of fatty liver disease?
In fatty liver disease, excess fat is stored in liver cells, where it accumulates. A variety of factors can cause this fat buildup.

Drinking too much alcohol can cause AFLD. Heavy alcohol use can alter certain metabolic processes in the liver. Some of these metabolic products can combine with fatty acids, leading to the formation of types of fat that can accumulate in the liver.

In people who don’t drink a lot of alcohol, the cause of fatty liver disease is less clear. For these people, it’s possible their body produces too much fat or doesn’t metabolise fat efficiently enough.

One or more of the following factors may play a role in people who don’t consume much alcohol and develop fatty liver disease:

obesity
type 2 diabetes
insulin resistance
high levels of fat, especially triglycerides, in the blood
metabolic syndrome

Reference:

Thibaut R, Gage MC, Pineda-Torra I, Chabrier G, Venteclef N, Alzaid F. Liver macrophages and inflammation in physiology and physiopathology of non-alcoholic fatty liver disease. FEBS J. 2022 Jun;289(11):3024-3057. doi: 10.1111/febs.15877. Epub 2021 May 2. PMID: 33860630; PMCID: PMC9290065.