Sandbox:Gunnam

Nonalcoholic fatty liver disease

• 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 is more than 5 -10 percent of the liver’s weight is fat, then it is called a fatty liver (steatosis).NAFLD is marked by inflammation that can progress to irreversible damage.NAFLD 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 NAFLD. NAFLD 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 is relatively new concept first introduced in 1980.
• Based on histology it is classified into the non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH).NAFL mostly considered as a benign condition but recent studies show it can progress to NASH up to 44%. The more severe form of NAFLD is called non-alcoholic steatohepatitis (NASH).
• One of the leading cause for cirrhosis in adults in united states is NASH. Almost 25 percent of adults with NASH may lead to cirrhosis.
• On the other hand, NASH progress to fibrosis that can lead to cirrhosis and hepatocellular cancer (HCC).
• Rate of progression does not correlate with body mass index (BMI) or hyperlipidemia

Pathophysiology

• It is thought that pathophysiology of NAFLD is multifactorial that includes numerous genetic, dietary, metabolic and hormonal factors.
• Most experts believe that NAFLD is a 2 hit hypothesis.
  • The first hit resulting in increased fat accumulation especially triglycerides within the hepatocyte and increases the risk of liver injury.
  • On the second hit inflammatory cytokines causes mitochondrial dysfunction and oxidative stress which in turn lead to steatohepatitis and/or fibrosis..
• Free fatty acids (FFA) play very crucial role in damaging the liver indirectly by either undergoing β-oxidation or are esterified with glycerol to form triglycerides, leading to hepatic fat accumulation.
• Now there is new evidence that FFA is directly causing the liver damage by increasing the oxidative stress by upregulation of TNF-alpha expression via a lysosomal pathway.

• Oxidative stress inhibits the replication process in the mature hepatocytes, Results in the proliferation of progenitor (oval ) cell population and later they differentiate into hepatocyte-like cells. Now both the oval and hepatocyte-like cells play a very important role in the process of fibrosis and hepatocellular carcinogenesis.
• Alterations in MTP/apoB synthesis and secretion have been implicated as one of the potential mechanisms in the pathogenesis of NAFLD which in turn leads to a decreased capacity for lipid export
• Normally triglycerides are transported from the liver in the form of VLDL particles which are then formed by the incorporation of triglyceride into apolipoprotein B (apoB) by microsomal transfer protein (MTP).

Risk Factors

• Common risk factors in the development of NAFLD is related to obesity which will result in insulin resistance and metabolic syndrome.It is estimated that approximately 80% of the obese people suffer from NAFLD.
• Patients who are having type 2 diabetes mellitus are more prone to develop Nafld

• Less commonly Patients with hypertension and dyslipidemia are also associated with developing NAFLD

Other Common Causes are :

• Medications like Tamoxifen ,corticosteriods , methotrxate
• Viral Hepatitis.
• Rapid weight loss.
• Malnutrition.

Signs and Symptoms

Usually, NAFLD [Nonalcoholic fatty liver disease] presents with no or few symptoms and sighs but when it does it shows the following

• Hepatomegaly
• Patient presents with fatigue
• Abdominal swelling (ascites)
• Enlarged breasts in men ( due to decreased estrogen clearance by liver damage )
• Pain in the upper right abdomen
• Yellowing of the skin and eyes (jaundice)
• Enlarged spleen (usually observed by a physician during physical exam)

PREVENTION

There are some ways to prevent NAFLD,

• Eating a healthy diet is the first and very important step.
• Exercise on regular basis.
• Maintain a healthy weight.
• Alcohol cessation, If Patient drinks.
• Take medications under the guidance of physician when needed,don't take unnecessary medications .

Diagnosis

Incidental finding of Fatty liver on ultrasound

Check for persistently raised LFTs

Ask the patient for significant alcohol intake

NO

YES

Diagnose NAFLD

Consider other alcoholic related diseases

Monitor severity of the disease

Offer Enhanced Liver Fibrosis Test (ELF)

(>10.51) ELF Positive

(<10.51) ELF Negative

Indicating advanced fibrosis and risk of progression to cirrhosis

Typically Benign -- Advanced fibrosis unlikely

Refer the patient to Heptologist

• On negative ELF test offer retest for every 3 years for adults and 2 years for children.