The pathogenesis of how the accumulated hepatic fat causes liver damage is a complicated issue.

According to “ 2 or multiple hits hypothesis”, the accumulated hepatic fat in some people causes injury to liver cells (nonalcoholic steatohepatitis or NASH) through direct lipotoxicity from free fatty acids (FFAs), oxidative stress, mitochondrial dysfunction, gut microbiota/LPS, activation of fibrogenesis, etc.

Yes,Long standing NAFLD can cause cirrhosis through inflammatory cascade activation and release of fibrogenic cytokines

NAFLD is becoming one of the major cause of chronic liver diseases, including liver cancer (cellular hepato carcinoma) in the developped countries (where viral hepatitis is efficiently treated). PM

Yes, NAFLD can lead to chronic liver disease. Most chronic liver diseases starts from accumulation of fat within liver tissue

Certainly, the NAFLD is one of the 3 leading causes of chronic liver disease and cirrhosis globally. It is the consequence of the progression of some NAFLD cases to a real hepatitis (NASH) and fibrosis. The incidence and prevalence of NASH are varies among different communities, and also depend on the method used for the diagnosis of liver fibrosis as a consequence of NASH. Liver biopsy remains the gold standard for diagnosis of NASH & degree of fibrosis and inflammation but the indirect, non-invasive methods (biochemical & fibroscan) are usually used to estimate the incidence and prevalence of NASH and its associated fibrosis in general population. The estimated prevalence of NAFLD in general population according to a meta-analysis study is around 25.24% and the prevalence of NASH among NAFLD patients is around 1.5-6.45%. The NASH is a second leading cause of mortality after cardiovascular disease in such patients (Younossi ZM, et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. HEPATOLOGY 2016;64:73-84).

it is actually the first cause of liver cirrhosis in the occidental word after having improved a lo the efficacy af anti-viral treatments for hepatitis C

Right. So how does this fat in isolation damages hepatocyes?

The pathogenesis of how the accumulated hepatic fat causes liver damage is a complicated issue.

According to “ 2 or multiple hits hypothesis”, the accumulated hepatic fat in some people causes injury to liver cells (nonalcoholic steatohepatitis or NASH) through direct lipotoxicity from free fatty acids (FFAs), oxidative stress, mitochondrial dysfunction, gut microbiota/LPS, activation of fibrogenesis, etc.

Thanks a lot Ismail

So this fat is as FFA which causes damages nd further downstream actions.

Regards

Yes , mainly the short chain fatty acids and further cascade downstream with oxidative stress , lipid per-oxidation ,membrane damage

Mechanisms of tissue injury, cell cycle dysfunction, and fibrogenesis are not established in NAFLD. Fat accumulation in the liver occurs for many different reasons, but only a subset develop liver injury/fibrosis/cirrhosis/HCC/etc. Several SNPs have been identified that stratify subgroups with or without injury/etc. and some knockout/knockin animal models appear to support at least some of these observations in human studies. In general, this is a very active area of research these days, and ripe for doing some good applied basic science. Liver injury and consequences associated with liver fat has become a very significant worldwide public health problem, and industry, foundations and government-supported research is mainstream..

Dear Geofffrey

Thanks for highlighting these genetic and sort of epigenetic factors. I also personally believe that different people living in similar environmental conditions behave differently and in the case of NAFLD, i believe there could be genetic predispositions as not all patients are obese and some have just minimal fat deposition.

Yes its a kind of pandemic and possibly becomes a major future problem though incidence of chronic liver disease without hepatitis it is on the rise especially in the west .

Thanks a lot.

Regards

thanks, a couple stats worth considering: fatty liver is common in overweight or hyperlipidemia or diabetes, but only about 15-20% of those with fatty liver have inflammation +/- fibrosis (similair to the histology distribution in persons with sufficient alcohol intake to have steatosis). The other stats to consider are: NAFLD is now the most common primary diagnosis in persons receiving liver transplant in the US; and while most people with Syndrome X or Metabolic Syndrome historically died of CAD or CVA events, these causes are decreasing and liver-associated causes are increasing.

Yes, the nature progression is thought to be from NAFLD to NASH ( inflammation) and then fibrosis to frank cirrhosis and chronic liver disease with its associated complications such as portal hypertension and HCC.

Of course it is, specially in the very developed countries where the metabolic syndrome is more prevalent

Yes, it can. I will follow an interesting discussion and offered answers.

I agree with the opinion of Geeta Kutty

Dear Sikandar Hayat Khan

Maybe the following links will be useful...

Article Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalco...

Article Modeling the epidemic of nonalcoholic fatty liver disease de...

https://www.ncbi.nlm.nih.gov/pubmed/26707365

Non-alcoholic fatty liver disease (NAFLD) is a very common disorder and refers to a group of conditions where there is accumulation of excess fat in the liver of people who drink little or no alcohol. The most common form of NAFLD is a non serious condition called fatty liver. In fatty liver, fat accumulates in the liver cells. Although having fat in the liver is not normal, by itself it probably does not damage the liver. A small group of people with NAFLD may have a more serious condition named non-alcoholic steatohepatitis (NASH). In NASH, fat accumulation is associated with liver cell inflammation and different degrees of scarring. NASH is a potentially serious condition that may lead to severe liver scarring and cirrhosis. Cirrhosis occurs when the liver sustains substantial damage, and the liver cells are gradually replaced by scar tissue, which results in the inability of the liver to work properly. Some patients who develop cirrhosis may eventually require a liver transplant.

The majority of individuals with NAFLD have no symptoms and a normal examination. Children may exhibit symptoms such as abdominal pain, which may be in the center or the right upper part of the abdomen, and sometimes fatigue. However, other causes of abdominal pain and fatigue should be considered. On physical examination the liver might be slightly enlarged and some children may have patchy, dark discoloration of the skin present (acanthosis nigricans) most commonly over the neck and the under arm area.

Causes of NAFLD/NASH:

NAFLD is part of the metabolic syndrome characterized by diabetes, or pre-diabetes (insulin resistance), being overweight or obese, elevated blood lipids such as cholesterol and triglycerides, as well as high blood pressure. Not all patients have all the manifestations of the metabolic syndrome. Less is known about what causes NASH to develop. Researchers are focusing on several factors that may contribute to the development of NASH. These include:

• Oxidative stress (imbalance between pro-oxidant and anti-oxidant chemicals that lead to liver cell damage)
• Production and release of toxic inflammatory proteins (cytokines) by the patient’s own inflammatory cells, liver cells, or fat cells
• Liver cell necrosis or death, called apoptosis
• Adipose tissue (fat tissue) inflammation and infiltration by white blood cells
• Gut microbiota (intestinal bacteria) which may play a role in liver inflammation

Risk Factors of NAFLD:

NAFLD is a very common disorder affecting and may affect as many as one in three to one in five adults and around one in ten children in the United States. Obesity is thought to be the most common cause of fatty infiltration of the liver. Some experts estimate that about two thirds of obese adults and half of obese children may have fatty liver. About 2 to 5 percent of adult Americans and up to 20 percent of those who are obese may suffer from the more severe condition NASH. The number of children who have NASH is not known. The presence of type 2 diabetes and other conditions associated with insulin resistance, such as polycystic ovarian syndrome are know risk factors for the development of fatty liver and NASH.

Treatment of NAFLD/NASH:

A few studies have suggested that weight loss may be associated with regression of fat within the liver. Therefore, the most important recommendations for people with fatty liver are to lose weight if they are overweight or obese, increase their physical activity, follow a balanced diet and avoid alcohol and unnecessary medications. New evidence suggests that Mediterranean diet (rich in monounsaturated fatty acids) may be more beneficial than low fat diet. Drinking coffee seems to decrease the risk of having fatty liver in large cohort studies. In patients with NASH, the more severe form of NAFLD, these same recommendations may be helpful. It is also important to control diabetes and treat elevated cholesterol levels when appropriate. Development of medications that could treat NAFD and NASH is an area of intense research. Recent trials in adult and children have shown that vitamin E (an anti-oxidant) could help improve NASH in non-diabetic patients. Strategies currently being evaluated by physicians and scientists to decrease the amount of fat/ inflammation in the liver include:

• Weight reduction (diet + exercise, medications, surgery)
• Lipid lowering medications
• Insulin sensitizers (medications)
• Decrease the amount of liver inflammation by administering anti-oxidant medications, anti-apoptotic medications and anti-cytokine medications

Really in developed countries is going to rich the first cause of liver cirrhosis

YES, Luis Rodrigo its on the increase. As we are more and more close to managing infectious causes, here we have this curse of exuberance

NAFLD is a leading cause of liver cirrhosis in the west. In tropical Africa, some studies are putting it as 2nd to viral hepatitis.

Therefore, there is a strong need for collaboration between endocrinologists and gastroenterologist in the curbing of this growing menace

NAFLD is the leading cause of cirrhosis now. Agree with Sikandar Hayat Khan that infectious disease control is better now.

US statistics have shown it to have a rising trend. The mechanism leading from steatotosis to cirrhosis still needs clarification though.

Following

Following

May be.

Fatty liver is the sign of ineffectiveness of liver to bear the load. It perhaps advice us to change food habit and lifestyle.

Most of us do not want to listen the advice and try to depend on medicines.

The condition practically become worse afterwards among some patients which may lead to cirrhosis.

Not only alcoholics, fast food - chemical drink lovers or Viral hepatitis sufferers, but even the village dwellers suffering from chronic Amoebiosis may get cirrhosis of liver.

Thanks.

Following answers.

@ Dr. Sikandar Hayat Khan

The answer to your question is "Yes". Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide, with a prevalence of 25-30% of the general population.

Article NASH‐related cirrhosis: An occult liver disease burden

Very important question that provoked several valuable informative answers by our RG colleagues

Following answers