How lifestyle choices & genetics drive alarming surge in fatty liver disease – Firstpost

Fatty liver disease is a growing concern in India with factors such as insulin resistance, metabolic syndrome and genetic predispositions playing key roles in its development. The disease progresses from simple fat accumulation in the liver to severe conditions like cirrhosis and liver cancer if left untreated.

In India, lifestyle factors like sedentary behaviour and poor diet, along with genetic variations, contribute significantly to the disease’s prevalence. NAFLD (Nonalcoholic Fatty Liver Disease) impacts approximately 20% of non-obese individuals in India, contrasting with its usual association with obesity in Western populations. We spoke with Dr. Nishant Nagpal, Director of Gastroenterology at Fortis Hospital (Noida) to delve deeper into the issue.

What are the primary causes of Nonalcoholic Fatty Liver Disease (NAFLD), and how does it differ from Nonalcoholic Steatohepatitis (NASH)?

Dr. Nishant Nagpal: The primary causes of NAFLD include insulin resistance, which leads to increased glucose and lipid accumulation in liver cells. Other contributing factors are metabolic syndrome and conditions like obesity, hypertension, dyslipidemia, and genetic predispositions such as certain genetic mutations (e.g., PNPLA3) that affect liver fat metabolism. Environmental factors like a sedentary lifestyle, unhealthy diet and exposure to toxins also play a role. NAFLD is a spectrum ranging from simple steatosis (fat accumulation in liver cells) to the more aggressive NASH, which is characterised by inflammation and liver cell damage.

How does FLD progress from simple steatosis to more severe conditions like cirrhosis or hepatocellular carcinoma?

Dr. Nagpal: FLD progresses in stages. It starts with simple steatosis, where excess fat accumulates in liver cells. This can advance to Nonalcoholic Steatohepatitis (NASH), which involves inflammation and liver damage. Over time, the condition can lead to fibrosis (scarring) as collagen is deposited in the liver. If left untreated, it can progress to cirrhosis, characterised by advanced scarring and liver dysfunction and in some cases, hepatocellular carcinoma, which is liver cancer.

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What lifestyle and genetic factors contribute most to the development of FLD in Indian patients?

Dr. Nagpal: In Indian patients, a sedentary lifestyle significantly contributes to insulin resistance and obesity, which are major risk factors for FLD. Unhealthy diets high in sugar, salt, and saturated fats exacerbate the problem. Central obesity which is common in the Indian population increases the risk of insulin resistance and certain genetic mutations such as PNPLA3 and TM6SF2, further predispose people to the disease.

What are the most common symptoms of fatty liver disease, and at what stage do these typically manifest?

Dr. Nagpal: The most common symptoms of fatty liver disease include fatigue which is related to liver dysfunction and inflammation and abdominal discomfort often felt as pain or tenderness in the upper right abdomen. Patients may experience weight loss in advanced stages due to decreased appetite and malabsorption as well as jaundice, which causes yellowing of the skin and eyes.

What diagnostic tools or tests do you recommend for assessing the severity of NAFLD or NASH in patients?

Dr. Nagpal: Several diagnostic tools are used to assess the severity of NAFLD or NASH. Liver function tests (LFTs) help monitor liver enzyme levels. Ultrasound can detect liver fat and fibrosis, while FibroScan is used to measure liver stiffness, which is indicative of fibrosis. MRI helps evaluate liver fat and inflammation. For a definitive diagnosis and staging, a liver biopsy may be required.

Can you elaborate on the link between fatty liver disease and metabolic conditions like diabetes, hypertension, and obesity?

Dr. Nagpal: The link between fatty liver disease and metabolic conditions lies in shared risk factors such as insulin resistance, obesity and physical inactivity. These conditions often involve common pathophysiological mechanisms, including inflammation, oxidative stress and metabolic dysfunction which increase the risk of FLD and its progression.

Why do some patients develop FLD even without obesity, especially in India where 20% of non-obese individuals are affected?

Dr. Nagpal: Non-obese individuals can develop FLD due to genetic predispositions, such as familial NAFLD. In some cases, these individuals may have sarcopenic obesity, where there is low muscle mass despite excess body fat. Also, metabolic dysfunction, including insulin resistance and dyslipidemia, can occur independently of obesity and contribute to the development of FLD.

What are the current treatment strategies for managing NAFLD and NASH, given the absence of targeted drugs?

Dr. Nagpal: The current treatment strategies focus on lifestyle modifications such as improving diet, increasing physical activity and achieving weight loss. Managing comorbidities like diabetes, hypertension, and dyslipidemia is also essential. Emerging therapies, including GLP-1 receptor agonists and FXR agonists, are being studied for their potential in treating NAFLD and NASH.

What lifestyle or dietary changes have proven most effective in reversing or managing fatty liver disease?

Dr. Nagpal: Adopting a Mediterranean diet, which emphasises whole grains, fruits, vegetables, and healthy fats has proven effective in managing FLD. Increased physical activity, including aerobic exercise and strength training, also plays a key role. Weight loss of 5-10% of body weight can significantly improve liver health.

How can patient compliance with lifestyle modifications be improved in the context of fatty liver disease?

Dr. Nagpal: Patient compliance can be improved through education, where patients are made to understand the consequences of NAFLD. Personalized counselling and tailored lifestyle advice based on individual needs can further help. Regular follow-ups to monitor progress and adjust treatment strategies are also crucial for maintaining long-term compliance.

What are some India-specific challenges in diagnosing and managing fatty liver disease, given the different phenotypes in the Indian population?

Dr. Nagpal: One of the main challenges in India is the diverse range of phenotypes, which leads to varying clinical presentations and risk factors. There is also limited awareness of the disease among patients, healthcare providers, and the general public. Inadequate healthcare infrastructure in some regions also limits access to diagnostic and treatment facilities.

How can the InFLiMeN initiative help improve the understanding and management of metabolic liver diseases in India?

Dr. Nagpal: The Indo-French Liver and Metabolic Disease Network (InFLiMeN) aims to address key issues related to a common metabolic liver disorder, non-alcoholic fatty liver disease through research on NAFLD pathogenesis, diagnosis and treatment. It also focuses on education, offering training to healthcare providers and patients, and fostering collaboration among researchers, clinicians and policymakers to address the growing burden of liver diseases in India.