Non alcoholic fatty liver disease

Gastroenterology

Clinicals - History

Fact Explanation
Diagnosed incidentally in asymptomatic patients Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disease including hepatic steatosis, non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is the commonest cause of abnormal liver functions detected among adults of the United States. Majority of patients are asymptomatic and are identified during routine liver function assessment. Diagnosed incidentally in asymptomatic patients
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disease including hepatic steatosis, non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is the commonest cause of abnormal liver functions detected among adults of the United States. Majority of patients are asymptomatic and are identified during routine liver function assessment.
Fatigue, malaise, mild right upper quadrant pain The patient may present with non-specific symptoms Fatigue, malaise, mild right upper quadrant pain
The patient may present with non-specific symptoms
Presentation with cirrhosis Most patients are diagnosed in advance disease. Majority of patients previously diagnosed as cryptogentic cirrhosis are now thought to be due to NAFLD. Presentation may be with minimum non-specific symptoms. The patient may develop right hypochondrial pain, jaundice, bleeding manifestations and abdominal swelling due to ascites. Presentation with cirrhosis
Most patients are diagnosed in advance disease. Majority of patients previously diagnosed as cryptogentic cirrhosis are now thought to be due to NAFLD. Presentation may be with minimum non-specific symptoms. The patient may develop right hypochondrial pain, jaundice, bleeding manifestations and abdominal swelling due to ascites.
Presentation with complications of cirrhosis and portal hypertension Patients with esophageal and gastric varices may present acutely with severe haematamesis. Acute abdominal pain in the presence of ascites may indicate spontaneous bacterial peritonitis. Acute confusion with other features of liver failure may be due to hepatic encephalopathy. There is high risk of developing hepatocellular carcinoma among patients with cirrhosis due to NAFLD. Presentation with complications of cirrhosis and portal hypertension
Patients with esophageal and gastric varices may present acutely with severe haematamesis. Acute abdominal pain in the presence of ascites may indicate spontaneous bacterial peritonitis. Acute confusion with other features of liver failure may be due to hepatic encephalopathy. There is high risk of developing hepatocellular carcinoma among patients with cirrhosis due to NAFLD.
Risk factors for disease NAFLD is strongly linked with metabolic syndrome. Risk factors linked with NAFLD include diabetes mellitus, insulin resistance, dyslipidaemia and hypertension. The pathogenesis of NAFLD is described as a ‘two-hit hypothesis’. In the first hit excess fatty acids accumulate within the hepatocytes as a result of deranged fatty acid flux. This results in Hepatic steatosis. Further inflammation and fibrosis within the fat laden liver results in conversion to NASH. The second hit describes the hepatocellular injury resulting from free radicals generated from fatty acids, effect of cytokines and direct lipotoxicity. Risk factors for disease
NAFLD is strongly linked with metabolic syndrome. Risk factors linked with NAFLD include diabetes mellitus, insulin resistance, dyslipidaemia and hypertension. The pathogenesis of NAFLD is described as a ‘two-hit hypothesis’. In the first hit excess fatty acids accumulate within the hepatocytes as a result of deranged fatty acid flux. This results in Hepatic steatosis. Further inflammation and fibrosis within the fat laden liver results in conversion to NASH. The second hit describes the hepatocellular injury resulting from free radicals generated from fatty acids, effect of cytokines and direct lipotoxicity.

Clinicals - Examination

Fact Explanation
General examination : Peripheral stigmata of chronic liver disease Spider telangiectasia, palmer erythema represent circulatory changes. Hemorrhagic tendency may lead to development of bruises and purpura. Features of endocrine changes : gynaecomastia, testicular atrophy in males and breast atrophy in females General examination : Peripheral stigmata of chronic liver disease
Spider telangiectasia, palmer erythema represent circulatory changes. Hemorrhagic tendency may lead to development of bruises and purpura. Features of endocrine changes : gynaecomastia, testicular atrophy in males and breast atrophy in females
General examination : Acanthosis nigricans This is a dark colored thickening noted around the flexures of the body - axillae, neck. This is associated with diabetes mellitus. General examination : Acanthosis nigricans
This is a dark colored thickening noted around the flexures of the body - axillae, neck. This is associated with diabetes mellitus.
General examination : Jaundice Excess bilirubin will be accumulating in the body due to impaired conjugation and biliary stasis. General examination : Jaundice
Excess bilirubin will be accumulating in the body due to impaired conjugation and biliary stasis.
Abdominal examination : Hepatomegaly Isolated hepatomegaly is usually the only sign found on physical examination. Abdominal examination : Hepatomegaly
Isolated hepatomegaly is usually the only sign found on physical examination.
Abdominal examination : Splenomegaly Due to portal hypertension. Abdominal examination : Splenomegaly
Due to portal hypertension.
Abdominal examination : Ascites Due to portal hypertension. Abdominal examination : Ascites
Due to portal hypertension.
Reduced conscious level Due to hepatic encephalopathy Reduced conscious level
Due to hepatic encephalopathy

Investigations - Diagnosis

Fact Explanation
Diagnosis depends on both clinical information and investigations There is no single diagnostic test for NAFLD. Diagnosis of NAFLD requires exclusion of other causes of liver dysfunction such as heavy alcoholism and previous hepatitis infection from the clinical history. Laboratory findings and imaging studies are used to confirm the diagnosis. Diagnosis depends on both clinical information and investigations
There is no single diagnostic test for NAFLD. Diagnosis of NAFLD requires exclusion of other causes of liver dysfunction such as heavy alcoholism and previous hepatitis infection from the clinical history. Laboratory findings and imaging studies are used to confirm the diagnosis.
Liver function tests The serum aspartate aminotransferase, alanine aminotransferase or both show mild elevation. The level is usually less than twice the upper limit of normal. The ratio of AST : ALT is usually less than 1 in early disease. This ratio gradually increases with progressive hepatic fibrosis. Serum alkaline phosphatase and γ-glutamyltransferase levels may be normal or slightly elevated. In advanced disease the serum bilirubin level will be increased and albumin level will be reduced. Liver function tests
The serum aspartate aminotransferase, alanine aminotransferase or both show mild elevation. The level is usually less than twice the upper limit of normal. The ratio of AST : ALT is usually less than 1 in early disease. This ratio gradually increases with progressive hepatic fibrosis. Serum alkaline phosphatase and γ-glutamyltransferase levels may be normal or slightly elevated. In advanced disease the serum bilirubin level will be increased and albumin level will be reduced.
Ultrasound scan-abdomen Ultrasound scan is commonly used for diagnosis and has a high sensitivity and specificity for diagnosis of NAFLD. The echogenicity of the liver is diffusely increased in hepatic steatosis. Local fatty infiltration and focal fatty sparing may be difficult to diagnose by USS where MRI or CT scanning may be required. Magnetic resonance spectroscopy is an imaging modality which can quantitatively assess fatty infiltration. In advance disease the cirrhotic liver may appear as shrunken and fibrosed. Ascites may be detected. Ultrasound scan-abdomen
Ultrasound scan is commonly used for diagnosis and has a high sensitivity and specificity for diagnosis of NAFLD. The echogenicity of the liver is diffusely increased in hepatic steatosis. Local fatty infiltration and focal fatty sparing may be difficult to diagnose by USS where MRI or CT scanning may be required. Magnetic resonance spectroscopy is an imaging modality which can quantitatively assess fatty infiltration. In advance disease the cirrhotic liver may appear as shrunken and fibrosed. Ascites may be detected.
Liver biopsy Liver biopsy is considered the gold standard in diagnosis of NAFLD. The characteristic features of NAFLD include fatty infiltration, inflammation and hepatocellular injury which is seen predominantly in the centrilobular zone and acinar zone. Specific features identified include inflammatory cell infiltrate, hepatocyte ballooning, hepatocyte necrosis, glycogen nuclei, Mallory–Denk bodies and perisinusoidal fibrosis. Histological scoring systems have being developed to grade and stage the histological findings. Liver biopsy
Liver biopsy is considered the gold standard in diagnosis of NAFLD. The characteristic features of NAFLD include fatty infiltration, inflammation and hepatocellular injury which is seen predominantly in the centrilobular zone and acinar zone. Specific features identified include inflammatory cell infiltrate, hepatocyte ballooning, hepatocyte necrosis, glycogen nuclei, Mallory–Denk bodies and perisinusoidal fibrosis. Histological scoring systems have being developed to grade and stage the histological findings.

Investigations - Management

Fact Explanation
Liver function tests The disease progression should be monitored with regular liver function tests ( 6 monthly). Patients with NASH require more intense follow-up than paitents with hepatic steatosis. Liver function tests
The disease progression should be monitored with regular liver function tests ( 6 monthly). Patients with NASH require more intense follow-up than paitents with hepatic steatosis.
Ultrasound scan of the abdomen An annual ultrasonic assessment of the abdomen should be carried out to assess the liver, gall-bladder and spleen. Ultrasound scan of the abdomen
An annual ultrasonic assessment of the abdomen should be carried out to assess the liver, gall-bladder and spleen.
Blood glucose testing For monitoring of glycaemic control. Adjust therapy accordingly. Blood glucose testing
For monitoring of glycaemic control. Adjust therapy accordingly.
Serum lipid profile Dyslipidaemia should be monitored frequently. Serum lipid profile
Dyslipidaemia should be monitored frequently.
BMI, waist circumference and blood pressure These parameters can be used to monitor control of metabolic syndrome. BMI, waist circumference and blood pressure
These parameters can be used to monitor control of metabolic syndrome.
Disease severity and prognosis can be assessed using scoring systems Commonly used is the NAFLD
fibrosis score (NFS). The parameters considered includes age, hyperglycemia, body mass index, platelet count, albumin level and ratio of aspartate aminotransferase to alanine aminotransferase. This scoring system is considered to be sensitive and specific at determining the disease severity and future outcome. The BARD score composed of body mass index, AST:ALT ratio and diabetes mellitus is also used for staging the disease.
Disease severity and prognosis can be assessed using scoring systems
Commonly used is the NAFLD
fibrosis score (NFS). The parameters considered includes age, hyperglycemia, body mass index, platelet count, albumin level and ratio of aspartate aminotransferase to alanine aminotransferase. This scoring system is considered to be sensitive and specific at determining the disease severity and future outcome. The BARD score composed of body mass index, AST:ALT ratio and diabetes mellitus is also used for staging the disease.

Management - Supportive

Fact Explanation
Patient education The patient should be provided information regarding the natural course, aetiology, complications and investigations of the disease. Provide information about the treatment options available. It is important to motivate the patient on life style modifications and treatment compliance. Patient education
The patient should be provided information regarding the natural course, aetiology, complications and investigations of the disease. Provide information about the treatment options available. It is important to motivate the patient on life style modifications and treatment compliance.
Weight loss Weight reduction achieved by dietary changes and regular exercise may contribute to improvement in liver function test values. Rapid weight loss has being linked with worsening of hepatic inflammation, fibrosis and necrosis. A weight loss of 1600 g per week in adults is advocated. There is limited evidence to suggest the possibility of reversing of fatty infiltration and fibrosis of the liver with weight reduction alone. Weight loss
Weight reduction achieved by dietary changes and regular exercise may contribute to improvement in liver function test values. Rapid weight loss has being linked with worsening of hepatic inflammation, fibrosis and necrosis. A weight loss of 1600 g per week in adults is advocated. There is limited evidence to suggest the possibility of reversing of fatty infiltration and fibrosis of the liver with weight reduction alone.
Management of diabetes, hyperlipidaemia and hypertension Pre-existing conditions such as diabetes mellitus, hyperlipidaemia and hypertension should be managed appropriately with pharmacological and non-pharmacological measures. The patient should be motivated to maintain good glycaemic and blood pressure control over longer periods of time. Management of diabetes, hyperlipidaemia and hypertension
Pre-existing conditions such as diabetes mellitus, hyperlipidaemia and hypertension should be managed appropriately with pharmacological and non-pharmacological measures. The patient should be motivated to maintain good glycaemic and blood pressure control over longer periods of time.

Management - Specific

Fact Explanation
Patients with steatohepatitis require more intensive therapy than patients with simple steatosis The risk of progression to cirrhosis and its associated complications are higher among patients with NASH. These patients require frequent monitoring of disease progression. Patients with steatohepatitis require more intensive therapy than patients with simple steatosis
The risk of progression to cirrhosis and its associated complications are higher among patients with NASH. These patients require frequent monitoring of disease progression.
Drug therapy Studies evaluating drug therapy for NAFLD are limited and no specific therapy is recommended so far. Anti-hypertensives, hypoglycaemic agents and statin therapy should be continued for treatment of hypertension, diabetes and dyslipidaemia respectively. Studies have shown improvement in liver function test results when treated with Gemfibrozil, vitamin E (α-tocopherol) and metformin. Other agents which have shown potential benefits are thiazolidinedione, Ursodiol and betaine. Drug therapy
Studies evaluating drug therapy for NAFLD are limited and no specific therapy is recommended so far. Anti-hypertensives, hypoglycaemic agents and statin therapy should be continued for treatment of hypertension, diabetes and dyslipidaemia respectively. Studies have shown improvement in liver function test results when treated with Gemfibrozil, vitamin E (α-tocopherol) and metformin. Other agents which have shown potential benefits are thiazolidinedione, Ursodiol and betaine.
Liver transplantation Liver transplantation may be indicated in severe decompensated liver disease. The chances of recurrence of disease in the transplanted liver is high due to the persistence of risk factors. Liver transplantation
Liver transplantation may be indicated in severe decompensated liver disease. The chances of recurrence of disease in the transplanted liver is high due to the persistence of risk factors.

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