Fatty Liver Disease
Disease Details
Family Health Simplified
- Description
- Fatty liver disease is a condition characterized by the accumulation of excess fat in liver cells, which can lead to liver inflammation and damage over time.
- Type
- Fatty liver disease can be classified into two main types: non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD). The disease is not directly inherited through a specific pattern of genetic transmission. However, genetic factors can influence an individual's susceptibility to developing fatty liver disease, particularly NAFLD. Variants in certain genes, such as PNPLA3 and TM6SF2, have been associated with an increased risk of NAFLD.
- Signs And Symptoms
- Often there are no or few symptoms. Occasionally there may be tiredness or pain in the upper right side of the abdomen.
- Prognosis
- Fatty liver disease prognosis varies depending on the type (non-alcoholic fatty liver disease (NAFLD) or alcoholic fatty liver disease (AFLD)) and the stage of the disease. In many cases, early-stage fatty liver disease is reversible with lifestyle changes such as diet modification, weight loss, and abstaining from alcohol. However, if left untreated, it can progress to more severe liver conditions such as non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, or liver cancer, which carry more serious health risks and a poorer prognosis. Early detection and management are key to improving outcomes.
- Onset
- Fatty liver disease, also known as hepatic steatosis, can have an insidious onset, often developing over years without causing noticeable symptoms. It can be broadly classified into alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD). Risk factors influencing the onset include excessive alcohol consumption (for AFLD), obesity, type 2 diabetes, metabolic syndrome, and high cholesterol (for NAFLD). In many cases, it is detected incidentally during imaging studies or elevated liver enzyme tests done for other reasons.
- Prevalence
- The prevalence of fatty liver disease (NAFLD) varies but is estimated to affect approximately 25-30% of the global population.
- Epidemiology
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NAFLD affects about 30% of people in Western countries and 10% of people in Asia.
In the United States rates are around 35% with about 7% having the severe form NASH. NAFLD affects about 10% of children in the United States. Recently the term Metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed to replace NAFLD. MAFLD is a more inclusionary diagnostic name as it is based on the detection of fatty liver by histology (biopsy),medical imaging or blood biomarkers but should be accompanied by either overweight/obesity, type 2 diabetes mellitus, or metabolic dysregulation. The new definition no longer excludes alcohol consumption or coexistence of other liver diseases such as viral hepatitis. Using this more inclusive definition, the global prevalence of MAFLD is an astonishingly high 50.7%. Indeed, also using the old NAFLD definition, the disease is observed in up to 80% of obese people, 35% of whom progress to NASH, and in up to 20% of normal weight people, despite no evidence of excessive alcohol consumption. FLD is the most common cause of abnormal liver function tests in the United States. Fatty liver is more prevalent in Hispanic people than white, with black people having the lowest prevalence.In the study Children of the 90s, 2.5% born in 1991 and 1992 were found by ultrasound at the age of 18 to have non-alcoholic fatty liver disease; five years later transient elastography found over 20% to have the fatty deposits on the liver, indicating non-alcoholic fatty liver disease; half of those were classified as severe. The scans also found that 2.4% had a degree of liver fibrosis, which can lead to cirrhosis.After the lockdown of the COVID-19 pandemic, a study demonstrated that 48% of patients with liver steatosis gained weight, while 16% had a worsened steatosis grade. Weight gain was associated with poor adherence to the suggested diet, reduced levels of physical activity, and increased prevalence of homozygosity for the PNPLA3 rs738409 single nucleotide polymorphism. PNPLA3 rs738409 is already a known risk factor for NAFLD. - Intractability
- Fatty liver disease, also known as hepatic steatosis, is not inherently intractable. Depending on the type (non-alcoholic fatty liver disease or alcoholic fatty liver disease) and stage, it can often be managed or even reversed with lifestyle changes such as diet, exercise, and avoiding alcohol. Advanced stages, like cirrhosis, may be more challenging to treat but early intervention can significantly improve outcomes.
- Disease Severity
-
Fatty liver disease, also known as hepatic steatosis, can range in severity:
1. **Simple Steatosis (Nonalcoholic Fatty Liver)**: Fat accumulates in the liver without significant inflammation or damage. It is generally benign but can progress if left unmanaged.
2. **Nonalcoholic Steatohepatitis (NASH)**: More severe form characterized by liver inflammation and damage. NASH can lead to fibrosis, cirrhosis, or liver cancer.
3. **Fibrosis**: Occurs when chronic inflammation leads to scar tissue formation in the liver, impairing its function.
4. **Cirrhosis**: Advanced scarring that severely impacts liver function and can lead to liver failure and other complications.
5. **Hepatocellular Carcinoma**: A possible outcome in severe cases, particularly from long-term cirrhosis.
Early detection and lifestyle changes, such as diet and exercise, can help manage and potentially reverse fatty liver disease. - Healthcare Professionals
- Disease Ontology ID - DOID:9452
- Pathophysiology
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Pathophysiology of fatty liver disease involves the accumulation of excess fat in liver cells. This accumulation can be due to increased fat delivery to the liver from dietary intake and fat stores, decreased fatty acid oxidation, or impaired export of fats from the liver. The condition can progress from simple steatosis (fat accumulation) to non-alcoholic steatohepatitis (NASH), which includes inflammation and liver cell damage. This can eventually lead to fibrosis, cirrhosis, and liver failure if left untreated.
nan is not applicable in the context of fatty liver disease. If you meant to ask for something specific associated with fatty liver disease, please clarify. - Carrier Status
- Fatty liver disease does not have a "carrier status" as it is not an infectious disease. It is a condition characterized by an accumulation of fat in the liver, often associated with factors such as obesity, diabetes, and excessive alcohol intake.
- Mechanism
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Fatty liver disease, also known as hepatic steatosis, is characterized by the accumulation of excess fat in liver cells.
**Mechanism:**
1. **Imbalance of Lipid Metabolism**: There is an imbalance between the uptake, synthesis, and oxidation of fatty acids and triglycerides in the liver.
2. **Insulin Resistance**: Often linked with conditions like metabolic syndrome and type 2 diabetes, insulin resistance promotes the uptake of free fatty acids by the liver and fosters lipid synthesis.
3. **Inflammation and Oxidative Stress**: Chronic inflammation and oxidative stress contribute to liver damage and fibrosis.
**Molecular Mechanisms:**
1. **De Novo Lipogenesis (DNL)**: This pathway involves the liver synthesizing fatty acids from carbohydrates. Key enzymes in DNL, such as ACC (acetyl-CoA carboxylase) and FAS (fatty acid synthase), are upregulated.
2. **SREBP-1c Activation**: Sterol Regulatory Element-Binding Protein 1c (SREBP-1c) is a transcription factor that regulates genes involved in fatty acid synthesis and is activated by insulin.
3. **PPARs (Peroxisome Proliferator-Activated Receptors)**: PPAR-α and PPAR-γ are nuclear receptors that regulate lipid metabolism. PPAR-α is involved in fatty acid oxidation, whereas PPAR-γ promotes lipid storage.
4. **Lipid Droplet Formation**: Proteins like perilipins and adipose differentiation-related protein (ADRP) coat lipid droplets and regulate lipid storage and release.
5. **Endoplasmic Reticulum (ER) Stress**: Accumulation of misfolded proteins in the ER can trigger a stress response, contributing to liver cell injury and inflammation.
6. **Mitochondrial Dysfunction**: Impaired mitochondrial function hampers fatty acid oxidation, leading to lipid accumulation and increased production of reactive oxygen species (ROS).
Understanding these mechanisms provides insight into potential targets for therapeutic interventions for fatty liver disease. - Treatment
- Decreasing caloric intake by at least 30% or by approximately 750–1,000 kcal/day results in improvement in hepatic steatosis. For people with NAFLD or NASH, weight loss via a combination of diet and exercise was shown to improve or resolve the disease. In more serious cases, medications that decrease insulin resistance, hyperlipidemia, and those that induce weight loss such as bariatric surgery as well as vitamin E have been shown to improve or resolve liver function.Bariatric surgery, while not recommended in 2017 as a treatment for FLD alone, has been shown to revert FLD, NAFLD, NASH and advanced steatohepatitis in over 90% of people who have undergone this surgery for the treatment of obesity.In the case of long-term total-parenteral-nutrition-induced fatty liver disease, choline has been shown to alleviate symptoms. This may be due to a deficiency in the methionine cycle.
- Compassionate Use Treatment
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Compassionate use treatments, off-label, or experimental treatments for fatty liver disease, particularly nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), include:
1. **Obeticholic Acid (OCA):** Used off-label for NASH. It is originally intended for primary biliary cholangitis.
2. **Elafibranor:** An experimental drug that activates peroxisome proliferator-activated receptors (PPARs), aiming to reduce liver inflammation and fat accumulation.
3. **Semaglutide:** Typically used for type 2 diabetes but under investigation for its potential benefits in liver disease due to its impact on weight loss and metabolic health.
4. **Resmetirom (MGL-3196):** An experimental thyroid hormone receptor-β agonist aimed at reducing liver fat content and improving liver histology.
5. **Lanifibranor:** Another experimental drug targeting multiple nuclear receptors to address the fibrotic aspects of NASH.
These treatments are still under various stages of clinical research and are not universally approved for standard care in fatty liver disease. - Lifestyle Recommendations
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For fatty liver disease, the following lifestyle recommendations can help manage and improve the condition:
1. **Weight Loss**: Gradual weight loss through a combination of diet and exercise can significantly reduce liver fat.
2. **Healthy Diet**: Adopt a balanced diet rich in fruits, vegetables, whole grains, and lean proteins. Reduce intake of saturated fats, trans fats, and refined carbohydrates.
3. **Exercise Regularly**: Aim for at least 150 minutes of moderate-intensity aerobic activity or 75 minutes of vigorous-intensity activity per week, along with strength training exercises.
4. **Limit Alcohol Consumption**: Reduce or eliminate alcohol intake, as alcohol can worsen liver damage.
5. **Manage Diabetes**: Keep blood sugar levels under control if you have diabetes.
6. **Lower Cholesterol**: Maintain healthy levels of cholesterol and triglycerides through diet, lifestyle changes, and medications if necessary.
7. **Avoid Unnecessary Medications**: Be cautious with medications and supplements that can affect the liver, and consult a healthcare provider before taking them.
8. **Regular Monitoring**: Follow up regularly with your healthcare provider to monitor liver health and make necessary adjustments to your management plan. - Medication
- There is no specific medication approved to treat fatty liver disease (non-alcoholic fatty liver disease, NAFLD) directly. Management typically involves lifestyle changes such as weight loss, diet improvement, and increased physical activity. Controlling related conditions like diabetes, high cholesterol, and hypertension is also crucial. In some cases, doctors may prescribe medications like vitamin E or pioglitazone, though these are not universally recommended. For alcoholic fatty liver disease, abstaining from alcohol is essential.
- Repurposable Drugs
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As of the latest research, several existing drugs show potential for repurposing in the treatment of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH):
1. **Metformin**: Commonly used for type 2 diabetes, it may help improve liver enzymes and reduce liver fat.
2. **Pioglitazone**: Another diabetes drug that has shown promise in reducing liver fibrosis and inflammation.
3. **Vitamin E**: Antioxidant properties might be beneficial, especially in non-diabetic patients with NASH.
4. **Statins**: While primarily used to lower cholesterol, they might also help reduce liver inflammation and fibrosis.
5. **GLP-1 agonists**: Drugs like liraglutide, used for diabetes, are being studied for their potential benefits in NAFLD.
These drugs are not yet universally approved specifically for NAFLD/NASH but have been highlighted in clinical trials and ongoing research as promising candidates. Always consult with a healthcare provider for treatment options. - Metabolites
- Fatty liver disease is associated with several altered metabolites. Key metabolites include elevated levels of triglycerides, free fatty acids, and various lipid intermediates like diacylglycerol and ceramides. Additionally, abnormalities in glucose metabolism and amino acid levels can be observed. An important marked metabolite is alanine aminotransferase (ALT), often elevated in liver diseases.
- Nutraceuticals
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Nutraceuticals, which are products derived from food sources with extra health benefits, are being researched for their potential in managing fatty liver disease. Some commonly studied nutraceuticals include:
1. **Omega-3 Fatty Acids**: Found in fish oil, they may help reduce liver fat and inflammation.
2. **Vitamin E**: An antioxidant that may help reduce liver inflammation.
3. **Silymarin (Milk Thistle)**: Known for its liver-protective effects.
4. **Probiotics**: May improve gut health and reduce liver fat.
5. **Curcumin**: Found in turmeric, has potential anti-inflammatory and antioxidant properties.
While promising, the efficacy and safety of these nutraceuticals require further large-scale, controlled studies to establish clear benefits for fatty liver disease treatment. Always consult healthcare providers before starting any supplement regimen. - Peptides
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Fatty liver disease involves the accumulation of fat in liver cells. Peptides are short chains of amino acids that can have various biological activities. Researchers are investigating certain peptides for their potential therapeutic effects in fatty liver disease, such as improving lipid metabolism and reducing inflammation.
Nanotechnology (nan) is also being explored in the context of fatty liver disease. Nanocarriers can enhance the delivery of drugs or therapeutic agents directly to the liver with increased precision, potentially improving treatment outcomes and reducing side effects. These innovative approaches aim to address the complex mechanisms underlying fatty liver disease more effectively.