Prevalence and incidence of NAFLD

NAFLD has become a major public health concern worldwide, with its prevalence escalating in parallel with the increasing rates of obesity and metabolic syndrome. 

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NAFLD and its subtype, nonalcoholic steatohepatitis (NASH) affect approximately 30% of the adult global population, making it the most common chronic liver disease. The incidence varies across different regions, ethnicities, and age groups, with a higher prevalence observed in Western countries.

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Risk factors: 

Several factors contribute to the development of NAFLD. 

• Obesity (especially abdominal or visceral adiposity)
• Type 2 diabetes 
• Insulin resistance 
• Dyslipidemia (high levels of triglycerides or abnormal levels of cholesterol)
• Hypertension
• Metabolic syndrome (70–90% of patients have NAFLD)
• Obstructive sleep apnea
• Genetic predisposition
• Sedentary lifestyle
• Unhealthy dietary habits
• Cholelithiasis 
• Age (Higher risk with increasing age)

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The mechanisms underlying the development of NAFLD are complex and multifactorial. 

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Insulin resistance and an imbalance in lipid metabolism play crucial roles in the pathogenesis. 

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Excessive intake of fructose, saturated fats, and refined carbohydrates contributes to fat accumulation in the liver.

Oxidative stress, inflammation, and gut microbiota alterations are also implicated in disease progression.

Symptoms: 

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NAFLD is often asymptomatic in the early stages. However, as the disease progresses, some individuals may experience fatigue, malaise, and mild abdominal discomfort. 

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In more advanced stages, it can lead to non-specific signs such as hepatomegaly (enlarged liver), jaundice, and signs of liver dysfunction. Importantly, NAFLD can progress to non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma, which may present with severe symptoms.

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How to diagnose NAFLD/NASH

Accurate diagnosis of NAFLD requires a comprehensive evaluation. Initially, a detailed medical history, physical examination, and assessment of risk factors are crucial. 

Blood tests are performed to assess

• liver enzymes - alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
• lipid profile
• glucose metabolism
• markers of liver inflammation and fibrosis. 

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Imaging techniques like ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) can provide information regarding liver fat content and the presence of complications. 

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Liver biopsy remains the gold standard for definitive diagnosis and assessment of hepatic steatosis, hepatocellular injury, inflammation, and fibrosis, but non-invasive alternatives such as transient elastography and serum biomarkers are gaining importance.

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Elastography is mainly used to check the liver for stiffness. Stiff areas in the liver are a sign of scar tissue (fibrosis) caused by liver disease.

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Ultrasonography is commonly employed as the initial diagnostic modality for hepatic steatosis, providing a qualitative evaluation of liver fat accumulation. It is particularly effective in diagnosing steatosis when more than 33% of hepatocytes are affected.

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However, its reliability diminishes with lesser degrees of fat infiltration. Therefore, the absence of detectable abnormalities on ultrasound does not definitively rule out mild fatty infiltration.

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In patients with abnormal liver functional tests (LFTs), alternative causes of liver disease should be excluded, including alcohol excess, drug-induced liver injury, viral hepatitis, autoimmune liver disease, haemochromatosis, coeliac disease and Wilson’s disease.

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Accurate staging of fibrosis is an essential step in the evaluation of patients with non-alcoholic fatty liver disease (NAFLD) as it helps identify individuals who are at a higher risk of developing liver-related complications. Advancing hepatic fibrosis can lead to hepatocellular dysfunction and portal hypertension, which can be reflected in routine blood tests. 

Parameters such as low albumin levels in liver function tests, thrombocytopenia in the full blood count, and prolonged prothrombin time in the coagulation profile can provide indirect indications of fibrosis severity. 

These  non-invasive tests offer a convenient means to assess fibrotic progression, aiding clinicians in risk stratification and treatment decision-making for patients with NAFLD.

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Evolution

In NAFLD, up to 90% of patients could have a milder form called simple steatosis, which generally has a good prognosis with no significant increase in mortality. 

Around 10-30% of patients develop a more progressive form called non-alcoholic steatohepatitis (NASH), characterized by liver cell injury and inflammation. 

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Among those with NASH, approximately 25-40% will experience ongoing liver fibrosis, leading to cirrhosis in 20-30% of cases.

Cirrhosis resulting from NASH carries a poor long-term outlook. Over a 10-year period, the mortality rate for individuals with Child-Pugh A disease is around 20%, and 45% may experience decompensation within the same timeframe. 

Additionally, individuals with NASH-related cirrhosis face a significant risk of developing hepatocellular carcinoma, a type of liver cancer.

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It is important to recognize the potential progression from simple steatosis to NASH and then to advanced liver fibrosis and cirrhosis, as this can help guide appropriate management and monitoring strategies to improve long-term outcomes for individuals with NAFLD.

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The management of NAFLD

The management of NAFLD  involves lifestyle modifications and treatment of underlying risk factors. 

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Weight loss through a combination of dietary changes and increased physical activity is recommended, aiming for a gradual and sustained reduction in body weight. 

A healthy diet, rich in fruits, vegetables, whole grains, and lean protein sources, should be followed. 

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Pharmacological interventions targeting specific aspects of the disease may be considered 

• insulin sensitizers
• lipid-lowering agents
• antioxidants

Close monitoring of associated comorbidities and regular follow-up with healthcare providers are essential.

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Prevention of NAFLD

Prevention of NAFLD involves adopting a healthy lifestyle from an early age. Maintaining a normal body weight, engaging in regular physical activity, and following a balanced diet are key preventive measures. Limiting the consumption of added sugars, saturated fats, and processed foods is advised.

NAFLD is associated with an elevated risk of extrahepatic disorders, including CVD, diabetes, and other metabolic diseases.

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Conclusions

NAFLD has become a significant burden on healthcare systems worldwide, with its prevalence closely tied to the rise in obesity rates. The pathogenesis of NAFLD involves inflammation, metabolic stress, and fibrosis, and a subset of patients progress to more severe liver conditions such as NASH and cirrhosis. 

Implementing integrated approaches for the prevention and management of NAFLD are essential in reducing the burden of disease and improving overall patient outcomes. 

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