Non-alcoholic fatty liver disease overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2]
Overview
Nonalcoholic fatty liver disease [NAFLD] is due to the deposition of extra fat in liver cells that is not caused by alcohol. It is normal for the liver to contain some fat. However, when there fat amount exceeds more than 5 -10 percent of the liver’s weight then it is called a fatty liver (steatosis). Nonalcoholic fatty liver disease is marked by inflammation that can progress to irreversible damage. Nonalcoholic fatty liver disease is similar to the damage caused by alcohol consumption in most of the cases. It is estimated that in united states approximately 80 to 100 million people are affected with Nonalcoholic fatty liver disease. Reflecting the obesity worldwide now Nonalcoholic fatty liver disease has become one of the leading cause of chronic liver disease. Nonalcoholic fatty liver disease most commonly affects people in the age group 2-19 and 40-50 years.It is most commonly seen in Hispanic population when compared to Caucasian and African American populations.
Historical Perspective
NAFLD/NASH was first described as a medical entity in a 1980. Though its histological capabilities had lengthy been recognized , the time period non-alcoholic steatohepatitis (NASH) became first used by Ludwig et al. as recently as 1980 .Ludwig et al. described ‘‘the pathological and medical features of non-alcoholic disease of the liver related with the pathological features maximum generally seen inside the alcoholic liver disorder itself.
Classification
Non-alcoholic fatty liver disease may be classified into non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) based on histopathology.
Pathophysiology
The exact pathogenesis of NAFLD is not fully understood.It is thought that NAFLD is the caused by either obesity, Insulin resistance, and metabolic syndrome. The exact reasons and mechanisms by which this disease progresses from steatosis to steatohepatitis and fibrosis is a subject of much research and debate. The prevailing wisdom comes from the so-called ‘two-hit hypothesis.’ The first hit is steatosis. The second hit is controversial and is likely numerous; likely any injury which causes a change that leads from hepatic steatosis to hepatic inflammation and fibrosis by way of lipid peroxidation.
Causes
Common causes in the development of Nonalcoholic fatty liver disease is related to obesity which will result in insulin resistance and metabolic syndrome. Less commonly Patients with hypertension and dyslipidemia are also associated with developing Nonalcoholic fatty liver disease
Differentiating Non-alcoholic fatty liver disease from Other Diseas
Nonalcoholic fatty liver disease must be differentiated from Auto Immune Hepatitis,α1-antitrypsin deficiency,Wilson disease and Hereditary hemochromatosis.
Epidemiology and Demographics
In the third National Health and Nutrition Examination Survey (NHANES III), the peak prevalence of NAFLD in men occurred in the fourth decade and in the sixth decade for women.NAFLD is associated with visceral obesity and diabetes. It has mirrored the epidemiologic course of obesity in the US and is detected in 73–90% of obese individuals on biopsy. Approximately 1/3 of the usa population are estimated to have NAFL. Through most estimates, NASH accommodates approximately 15% of all NAFLD and 3–5% of the american populace.
Risk Factors
The most potent risk factor in the development of NAFLD is obesity. Other risk factors include insulin resistance and metabolic syndrome.
Screening
There is insufficient evidence to recommend routine screening for Nonalcoholic fatty liver disease.
Natural History, Complications and Prognosis
NASH may progress to fibrosis and, later, cirrhosis. Studies of serial liver biopsies estimate a 26-37% rate of hepatic fibrosis and 2-15% rate of cirrhosis in less than 6 years.The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies.The natural history of nonalcoholic fatty liver disease:a clinical histopathological study.Long-term follow-up of patients with NAFLD and elevated liver enzymes. In 2001, NASH represented 2.9% of the indications of liver transplantation.The frequency of Nonalcoholic Steatohepatitis as a Cause of Advanced Liver Disease. The impact of NAFLD is manifest at each step along the spectrum of the disease. Studies in the United States and Sweden have revealed that both simple steatosis as well as steatohepatitis significantly reduce life expectancy, even when the diagnosis is made in children.The natural history of the non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years.
Diagnosis
History and Symptoms
Most patients with NAFLD have no or few symptoms. Infrequently patients may complain of fatigue, malaise and dull right upper quadrant abdominal discomfort. Mild jaundice can rarely be noticed. More commonly it is diagnosed as a result of abnormal liver function tests during routine blood tests. Often following an asymptomatic course, the disease may present first with cirrhosis and/or the complication of portal hypertension.
Physical Examination
Patients with NAFLD usually appear asymptomatic. Physical examination of patients with NAFLD is usually unremarkable.
Laboratory Findings
Elevated liver function tests are common. Typically, one finds a 2-4 fold elevation of the ALT above the normal limit and an ALT/AST ratio of greater than 1.This ratio is imperfect, as AST tends to rise with the degree of fibrosis. The Ratio of Aspartate Aminotransferase to Alanine Aminotransferase: Potential Value in Differentiating Nonalcoholic Steatohepatitis From Alcoholic Liver disease.Furthermore, high ALT values within the reference range (less than 40 IU) are still predictive of NAFLD/NASH. Higher Concentrations of Alanine Aminotransferase within the Reference Interval Predict Nonalcoholic Fatty Liver Disease.Another blood test that can be elevated is the ferritin. Typically, and except in very advanced disease, the liver's synthetic function is intact with normal albumin and INR.
Electrocardiogram
There are no ECG findings associated with NAFLD.
X-ray
There are no x-ray findings associated with NAFLD.
Ultrasound
Ultrasound may be helpful in the diagnosis of complications of NAFLD, which include detection of fat percentage in the liver. Ultrasound is a qualitative test and should be considered as the reliable imaging test to diagnose NAFLD. Ultrasound is non- invasive, Inexpensive and no threat of radiation exposure to the patient. However, the accuracy of ultrasound is limited if the patient has hepatic fibrosis which Ultrasound cannot differentiate between hepatic fibrosis and steatosis.
CT scan
CT scan may be helpful in the diagnosis of complications of NAFLD, which include the structure of the liver. But using CT is limited because of the exposure to ionizing radiation. Contrast-enhanced CT has a sensitivity up to 84-87% and specificity of 75-86%.
MRI
An MRI is one of the best tools in imaging modalities available to diagnose NAFLD. An MRI is simple to test which allows quantification of the hepatic steatosis. MRI has a sensitivity of 96% and specificity of 93% in diagnosing NAFLD. However, it uses is limited because of the cost.
Other Imaging Findings
There are no other imaging findings associated with non-alcoholic fatty liver disease.
Other Diagnostic Studies
Liver biopsy may be helpful in the diagnosis of non-alcoholic fatty liver disease. Findings on biopsy include macrovesicular steatosis, inflammation, ballooning degeneration, zone 3 perivenular/periportal/perisinusoidal fibrosis and, finally, mallory bodies.
Medical Therapy
There is no standard treatment for the non-alcoholic fatty liver disease; the mainstay of therapy is dietary and life style modifications which include improving metabolic risk factors -weight loss, treating diabetes, managing lipids and reducing alcohol intake.
Surgery
Surgery is not the first-line treatment option for patients with NAFLD.The mainstay of treatment for NAFLD is medical therapy and weight loss.
Primary Prevention
Effective measures for the primary prevention of non-alcoholic fatty liver disease include eating a healthy diet and regular exercise.