Human beings and their existence right from their origin are exposed to natural and unnatural challenges. The Antonine Plague in 165AD in the regions of Asia Minor, Egypt, Greece and Italy killed about 5 million people and almost annihilated the Roman Army. The plague of Justinian (541-542 AD) affected the Byzantine Empire and Mediterranean port cities, killing upto 25 million people. This plague killed about a quarter of the population of the Eastern Mediterranean and devastated the city of Constantinople, where at its peak it killed almost 5,000 people per day and resulted in the death of about 40% of the population of the great city. The Black Death (1347-1351) killed about 30% of the European population and about 20 million deaths in Asia. The Spanish flu (also called the 1918 Flu Pandemic) infected more than one-third of the world’s population and killed about 20-50 million people. The 1918 Flu pandemic is considered as India’s worst pandemic.
In India, this Flu was popularly known as Bombay Influenza or Bombay fever with an estimate of 12 million deaths, about 5% of the Indian population. The HIV/AIDS pandemic originated in 1976 and has killed more than 36 million people across the globe since 1981. Currently there are between 31 and 35 million people living with HIV, the vast majority of those are in Sub-Saharan Africa, where 5% of the population is infected, roughly 21 million people. Recently, the health care system across the entire world was under severe pressure to combat the deadly COVID-19 that killed 6.9 million people across the globe. Fortunately, on 5th of May 2023, the COVID-19 emergency committee of World Health Organisation (WHO) met for the 15th time and declared an end to the public health emergency of international concern. While keeping the track of COVID-19 pandemic, the threats and pressures due to other pandemic(s) were largely ignored. The increased incidences of non-communicable diseases such as cardiovascular disease (CVD), various forms of cancers, diabetes, neurological disorders and chronic kidney disease (CKD) are posing a greater challenge to the health of the world.
Within our body, most of the food we eat is broken down into sugar (glucose) and released into the bloodstream. When the sugar (glucose) level goes up, the insulin from the pancreas is released into the bloodstream and helps the glucose to enter into cells for utilisation and conversion into energy. Diabetes is a chronic and long-lasting condition that affects the process of turning food into energy in our body. During diabetes, either the pancreas fails to produce enough insulin (Type I diabetes) or the cells/tissues fail to respond to the insulin (Type II diabetes), resulting in a condition where there is an increased blood sugar (glucose) level in our body. Over a period of time, too much glucose in our bloodstream disturbs cellular homeostasis and can increase the risk towards serious health problems such as heart diseases, kidney diseases, mood disorders, Non alcoholic fatty liver disease (NAFLD), loss of vision, hypertension and different cancers.
The World Health organisation report released on April 05, 2023 provided the estimates of diabetes across the globe. The report says that the number of people with diabetes rose from 108 million in 1980 to 422 million in 2014. In 2021, there were 537 million adults (20-79 years) living with diabetes. The number is expected to be 643 million by 2030 and 783 million by 2045. There were 6.7 million deaths in 2021 due to diabetes. In India, 11.2% of the population is suffering with diabetes. The number in India was 72.9 million in 2017, and by 2045, India will likely have 135 million people with diabetes. All these numbers are at increased risk of developing other major diseases and most commonly Non alcoholic fatty liver disease (NAFLD).
Non alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome. NAFLD represents the spectrum of conditions comprising of simple accumulation of fats in the liver (called as steatosis), inflammation of liver (called as steatohepatitis or Non alcoholic Steatohepatitis/NASH), fibrosis, cirrhosis and end stage liver disease (called as hepatocellular carcinoma). NAFLD has shown a strong and positive correlation with the incidence of diabetes. The prevalence of NAFLD is increasing at the same rate as that of diabetes and showing a uniform trend across the globe with an estimated prevalence of about 25%. The highest NAFLD rates are reported from South America (31%) and the Middle East (32%) followed by Asia (27%), North America (23%) and Europe (24%). The global incidence of an advanced and more severe form of NAFLD, called Non alcoholic steatohepatitis (NASH) ranges between 3% to 5%.
In India, the prevalence of NAFLD is relatively lower (9%), however the urban areas mimic the western prevalence, with varying rates between 16% to 32%. The risk of developing NAFLD and its progression to NASH is strongly increased by the presence of Type II diabetes. The prevalence of NAFLD in patients having Type II diabetes is 59% with adverse outcomes such as increased mortality rates due to cirrhosis. Quite interestingly, the prevalence of NASH in Type II diabetes patients is about 20%. Moreover, the prevalence of advanced liver fibrosis in Type II diabetes patients is 5%-7%. A study published in Indian Journal of Gastroenterology suggests that NAFLD is an important cause of unexplained rise in cirrhosis and hepatocellular carcinoma (Liver cancer). Further the study suggests that hypertension (high blood pressure) is a common feature associated with NAFLD and is present in approximately 50% of Indian patients with NAFLD. In the United States, the hospitalization rate due to NAFLD-related liver cirrhosis has increased by 10.6% annually, from 13.4 per 100,000 hospitalizations to 32.1 per 100,000 hospitalizations. The hospitalization for NAFLD-related liver cancer showed an 8% increase in annual rate.
What is Non alcoholic Fatty liver Disease?
Basically, there are two types of fatty liver diseases. One is called Alcoholic Fatty liver disease (AFLD), where alcohol intake is the primary cause. The other one is called Non alcoholic fatty liver disease (NAFLD), where diet and sedentary lifestyle are among the major causes. NAFLD is a condition where excess fat is stored in the liver of the patients who consume little or no alcohol. It is absolutely normal for any tissue to contain some amount of fat. However, the amount of fat in every tissue has its own limit. For example, Adipose tissue stores huge amounts of fat and acts as energy reservoirs of our body. But other tissues such as pancreas, gall bladder and kidney store very little amount of fat. If fat exceeds a certain limit in these extra-adipose tissues, it induces a condition called Lipotoxicity (toxicity induced by fat). In the case of the liver, if the fat content is more than 5%-10% of the normal weight of the liver, then this condition is called hepatic steatosis or simply fatty liver. If this fatty liver persists, it leads to the activation of inflammatory signals and induces inflammation of the liver, and then this condition is relatively severe and is called Non alcoholic steatohepatitis (NASH).
Analysis and detection of Fatty liver Disease:
The detection of fatty liver disease is generally done by Ultrasonography (USG, commonly called as ultrasound) and in most of the cases it is accidental detection. According to my personal observation, most of the people are being recommended USG for some other reason, but there they discover fatty liver. In most common languages we have three grades of fatty liver. Grade I, Grade II and Grade III depending upon the fat content in the liver. Grade I fatty liver is defined as by the presence of >5% (5-30) of fat in the liver. Grade II is defined as the presence of >30% (30-60) of fat in the liver. And above 60%, the condition is called Grade III. Among these grades, Grade I is not a critical condition and is the most common form of fatty liver in the general population. Grade I fatty liver can sometimes be transient, meaning occurring in some individuals at some point of time when an individual assumes a sedentary lifestyle for some time. During this period, a person may develop fat in the liver, which is burned once a person starts to exercise or do some physical work. One should not worry with Grade I fatty liver as it is an easily treatable condition. Grade II fatty liver is a little bit problematic as it may need proper medication, but treatable. The problem becomes worse if Grade II fatty liver progresses to Grade III fatty liver, where an individual accumulates large fat depots in its liver and these fat depots start getting oxidised which results in inflammation.
It is this inflammation that serves as a precursor to its advanced form commonly called as NASH. This NASH may progress to more dreaded forms such as fibrosis, cirrhosis and end stage hepatocellular carcinoma (Liver Cancer). Not only the content of the fat, but the quality of fat is very important in defining the disease outcome in NAFLD. So utmost care is needed to know about liver fat content as well as quality. The most commonly used technique to know about the fat in the liver is Ultrasonography. However, Ultrasonography is a very insensitive technique in determining the fat within soft tissue such as the liver. A more advanced technique such as MRI should be employed in determining the fatty liver condition in patients.
Potential Cause(s) of NAFLD:
There is limited understanding of how fatty liver progresses to cirrhosis and liver cancer. But there are certain possibilities that are considered as potential causes or related to the development of NAFLD and NASH. These include: sedentary lifestyle, diet rich in saturated fatty acids, overweight or obesity, high blood sugar, Insulin resistance (where cells fail to take up sugar in response to Insulin). These combined appear to promote the deposition of fat in the liver. Moreover, the detailed discussion regarding the biological mechanisms and signalling pathways involved in NAFLD development is beyond the scope of this article.
Risk Factors for Non alcoholic Fatty liver Disease:
A risk factor is defined as an attribute or a characteristic that increases the chances of the occurrence of a condition or a disease. NAFLD mostly occurs in the middle age, although children and adults are also affected. Currently, the researchers across the globe have not identified the exact cause, however many risk factors for the development of NAFLD and NASH have been identified. The most common and the major risk factors for NAFLD/NASH development are:
1. Obesity and overweight.
2. Type II diabetes or prediabetes.
3. Abnormal levels of fats in your blood, which may include high levels of triglycerides, high levels of bad cholesterol (LDL) or low levels of good cholesterol (HDL).
4. Metabolic syndrome: This is a spectrum of conditions linked to being overweight or obese and makes you more likely to get fatty liver disease, Type II disease and heart disease.
5. Other risk factors include polycystic ovary syndrome (PCOS), hypertension, underactive thyroid (hypothyroidism), underactive pituitary gland (hypopituitarism), some viral infections such as hepatitis C, taking certain medications such as Glucocorticoids and synthetic estrogens.
Symptoms of NAFLD and NASH:
NAFLD generally produces no signs or symptoms. Even if there is any symptom, it includes fatigue and pain or discomfort or irritation in the upper right abdomen. NASH and advanced fibrosis may produce some symptoms. These include: Abdominal swelling (Ascites), enlarged blood vessels just beneath the skin surface, enlarged spleen, red palms and yellowing of the skin and eyes (jaundice).
Management and Treatment of NAFLD/NASH:
There is no FDA approved drug for fatty liver disease available in the market. However, there are various pharmacological means that are presently being employed for the management of NAFLD. It is important to note that numerous studies over the last decade showed that calorie restriction and regular work out could improve the functioning of the liver in patients with NAFLD. Further lifestyle interventions are as effective (or sometimes more) as drugs and it has been shown that physical exercise potentiates the benefits in the management of NAFLD. For detailed management and treatment of NAFLD, please consult a Doctor.
Precautions needed to improve or avoid NAFLD
With your doctor’s help, there are many ways to control your fatty liver disease. These include: Weight loss by reducing the calories you consume and increase your physical activity, choose a healthy diet that is rich in fruits, vegetables and whole grains (remember to keep counts of calories you consume), diet rich in antioxidants such as Vitamin E and C, Exercise (be more active), lower your cholesterol and follow your doctor.
Take home message
NAFLD and its advanced form NASH are emerging at a greater rate than expected with secular trends across the globe. Diabetes, obesity, overweight, high lipid levels, consistent increased blood sugar and sedentary lifestyle are the potential risk factors and possible causes of NAFLD. However, the good news is that fatty liver disease can be controlled and reversed with smart changes to your lifestyle. It is very essential to be aware of the risk factors associated with fatty liver disease and take steps to lessen your chances of getting it, or keep it from progressing if you have been diagnosed with the disease. Consult your Doctor for regular advice.
Need for population based (epidemiological) study in our state Jammu & Kashmir. In this connection, researchers working in academics and clinics need to play a leading role. This will help us to understand the disease in a better way in our society. Once we understand the problem, together we will find a solution.
The author is Assistant Professor Department of Biochemistry at Government Degree College, Sopore
Research Interests: Cell and Molecular Biology of Lipotoxicity in NAFLD.
DISCLAIMER: The views and opinions expressed in this article are the personal opinions of the author.
The facts, analysis, assumptions and perspective appearing in the article do not reflect the views of GK.