Non-alcoholic Fatty Liver Disease

AUGUST 29, 2021


Fat accumulation in the liver is a common finding during abdominal imaging studies and on liver biopsies. Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of progressive liver diseases ranging from fatty infiltration alone (steatosis) to infiltration with inflammation (Non-alcoholic steatohepatitis-NASH) that may progress to cirrhosis (scarring of liver tissue) and primary liver carcinoma.

NAFLD is considered by many a hepatic manifestation of metabolic syndrome as it is strongly associated with obesity, dyslipidemia, type-2 diabetes, and hypertension. NAFLD is diagnosed if there is evidence of hepatic steatosis by imaging or biopsy after ruling out other causes of fat accumulation (Such as alcohol consumption or medications that cause fat accumulation). NAFLD is very common worldwide. The frequency of steatosis varies with different populations. As with many other liver diseases subtle inter-patient genetic variations and environmental factors play a role so only small percentage progress to cirrhosis or end-stage liver disease.

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It represents an important comorbidity of type 2-diabetes. Some studies show that over half of the type 2-diabetes population has NAFLD.

NAFLD includes simple fatty infiltration (a benign condition called fatty liver) and non-alcoholic steatohepatitis (NASH), a less common but more important variant.

Non-alcoholic fatty liver (NAFL)

NAFL is a common and potentially reversible condition that occurs when there is greater than 5% fat accumulation in the liver but without evidence of liver cell injury. It has been estimated that 10% of patients with NAFLD progress to cirrhosis over a period of 20 years.

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Non-alcoholic Steatohepatitis (NASH)

NASH is diagnosed most often in patients between 40-60 years but can occur in all ages. In NASH there are both a fatty liver and inflammation with liver cell injury and fibrosis that can lead to cirrhosis. The development of NAFLD is not well understood but is clearly related to insulin resistance leading to the accumulation of triglycerides. Fatty acids and other metabolites cause liver cell injury. Cellular damage triggers cell death and inflammation leading to gradual fibrosis of liver tissue.

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Symptoms

NAFLD frequently causes no symptoms. There may be fatigue and mild upper right abdominal discomfort. It is commonly found during routine blood tests or during an ultrasound or CT scan of the abdomen. Patients with progressive NASH may present late with complications of liver cirrhosis and portal hypertension such as variceal hemorrhages or with hepatocellular carcinoma.

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Risk factors

NAFLD is strongly associated with obesity, Dyslipidemia, type-2 diabetes, and hypertension. Risk factors are:

  • Age greater than 45 years.
  • Diabetes mellitus or prediabetes.
  • BMI greater than 30 kg/m2.
  • Hypertension.
  • Polycystic ovarian syndrome.
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Diagnosis

The investigation is done to rule out other causes of liver disease such as excess alcohol consumption, viral, autoimmune, and other metabolic causes. The diagnosis of NASH should be suspected in patients with metabolic syndrome (obesity, type-2 diabetes, hypertension, or dyslipidemia) and unexplained laboratory abnormalities suggesting liver disease.

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Differentiating simple steatosis from NASH can be difficult by laboratory findings alone. A liver biopsy can be performed to diagnose the extent of fat infiltration and fibrosis. As it is invasive and unsuitable for widespread use so a fibroscan or a clinical scoring system such as a FIB 4 score, NAFLD fibrosis score (NFS score), and APRI Score are used to calculate the risk of NASH and advanced disease. Scores are based on the results of routine blood tests and anthropometrics. This allows care to focus on those who are having advanced diseases. The investigations performed are of the following:

  • Blood count.
  • Liver function test.
  • Fasting blood glucose and HbA1c.
  • Lipid profile.
  • Viral markers for hepatitis A, B, or C.
  • Ultrasound, ultrasound elastography, or fibroscan.
  • CT scan, MRI, or MR spectrometry.
  • Liver biopsy.
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Treatment

The mainstay of treatment is weight loss through a combination of a healthy diet and exercise. Ideally, a loss of 7-10% of body weight is desirable, but improvement in risk factors can become apparent if you lose even 3% to 5% of your starting weight.

Simple steatosis or fatty liver is a potentially reversible condition. Treatment comprises lifestyle Intervention to promote weight loss and improve insulin sensitivity through dietary changes and physical exercises. Weight-loss surgery is also an option for those who need to lose a great deal of weight. Screening and treatment of cardiovascular risk factors should be done in all patients.

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For those who have already developed cirrhosis (Severe liver fibrosis) due to NASH, liver transplantation may be an option. Currently, there is no medicine for NASH therapy. Treatment is directed towards coexisting metabolic disorders like Dyslipidemia and hyperglycemia. Statins are used for Dyslipidemia. Insulin sensitizing agents are helpful. Several new liver-targeted medicines are under trial, and will hopefully be available in the coming years.

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