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ULTRASOUND GRADING OF NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) AND ITS RELATION TO LIVER TRANSAMINASES

ULTRASOUND GRADING OF NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) AND ITS RELATION TO LIVER TRANSAMINASES

Ultrasound= US Non-Alcoholic Fatty Liver Disease= NAFLD

General Information
NMRR ID
NMRR-21-988-58239
Date of NMRR Registration
26/01/2021 16:22:09
Type of Submission
Investigator Initiated Research (IIR)
Protocol ID
Research Scope
Clinical
Research Type
Registry / Biobanking / Clinical Database
Study Information
RMK Priority Area
Research Area

Disease Area


Investigational Product/ Process /Intervention
Research Level
Research Description/ Research Lay Summary
Non-alcoholic fatty liver disease (NAFLD) is described as the fatty infiltration of the hepatocytes more than 5% of the liver weight with the nonexistence of other condition such as excessive alcohol intake or hepatitis C. It comprises a spectrum of diseases from simple hepatic steatosis (non-alcoholic fatty liver, NAFL) to steatosis with necroinflammation and progressive fibrosis (non-alcoholic steatohepatitis, NASH).
NAFLD is a common condition associated with metabolic syndrome. From this study, we want to identify the correlation of ultrasound grading of fatty liver with liver transaminase value mainly aspartate aminotransferase (AST) and alanine aminotransferase (ALT).

NFLD appears to be common in some ethnic groups like Philipinos, Indians and aboriginals of Australia/Malaysia. Abdul Sattar et al reported 37.4% of the overall prevalence of NAFLD involved urban area. This was much higher than the prevalence rates reported in suburban area in Malaysia, and other Asia Pacific countries, which have ranged from 12-24% . Their figure is consistent with another study carried out among urban subjects in Malaysia as the prevalence has been reported 49.6%. This indicates that prevalence of NAFLD is alarmingly high among urban population in Malaysia (Khammas et al., 2018)

Biomarkers offer a potential prognostic or diagnostic indicator for disease manifestation, progression or both. Serum biomarkers, including total cholesterol, liver enzymes, triglycerides, insulin resistance and C-peptide, have been used for many years. However there is no single biochemical marker that can confirm a diagnosis of NAFLD or distinguish between steatosis, NASH, and cirrhosis. Increased levels of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are commonly used as non-invasive methods to predict the presence of NAFLD or NASH.

Although mildly elevated serum aminotransferase levels are the primary abnormality seen in patients with NAFLD, liver enzymes may be normal in up to 78% of patients with NAFLD. The elevations in ALT and aspartate aminotransferase (AST) are typically mild when present and are usually not greater than four times the upper limit of normal. The ratio of AST/ALT is usually less than 1 in patients who have either no or minimal fibrosis, although this ratio may be greater than 1 with the development of cirrhosis. Gamma-glutamyltransferase (GGT) in the serum is frequently elevated in patients with NAFLD, and it has been reported to be associated with increased mortality. However, the diagnosis of NAFLD cannot be made using only GGT. Increased serum GGT levels have also been shown to be associated with advanced fibrosis in NAFLD patients, with a study of 50 NAFLD patients demonstrating an area under the receiver operating characteristic curve (AUROC) of 0.74 for the prediction of advanced fibrosis. Using a cutoff serum GGT value of 96.5 U/L, GGT predicted advanced fibrosis with 83% sensitivity and 69% specificity. Alkaline phosphatase is sometimes slightly elevated, but it is rarely the only liver function test abnormality (Obika & Noguchi, 2012).

Elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels reflect nonspecific hepatocellular damage. In NAFLD/NASH, aminotransferase levels may be elevated two to four times over the upper limit of normal, with ALT being higher than AST, in contrast to alcoholic steatohepatitis. However, in the absence of advanced disease, routine liver function tests are either normal or typically show only mild elevations in aminotransferase levels, with alkaline phosphatase and gamma-glutamyl transferase (GGT) 1.5 to three times the upper limit of normal (Neuman, Cohen, & Nanau, 2014).
Several studies involving hepatology clinic patients undergoing liver biopsy and morbidly obese individuals undergoing bariatric surgery have found ALT levels to be higher in the presence of NASH than in those with simple steatosis, although this has not been universally observed. However, close to 80% of patients with fatty liver in cohort studies have shown ALT levels within normal limits. Adams et al. reported that aminotransferase levels fall over time as hepatic steatosis and inflammation improve. Aminotransferase levels do not correlate with the degree of fibrosis (Mofrad et al., 2003).

This is a retrospective cohort study. Data will be collected respectively from patientÂ’s clinical histories, blood investigation and ultrasound of the liver from January 2020 till December 2020.Ultrasound images will be collected retrospectively from GEPACS. Correlation will be made with the liver transaminases mainly (AST and ALT) of the patients.


Our hypothesis will be:
1. The AST will be the most transaminases that correlate most with ultrasound grading.
2. The higher AST/ALT ration, the higher grading of fatty liver in ultrasound

At the end of the study we would like to highlight that early diagnosis and risk stratification are essential for effective management. An effective risk stratification and management of NAFLD requires evaluation of hepatic parenchymal fat, fibrosis, and inflammation.
As we know current imaging methods such as ultrasound, computed tomography, and magnetic resonance elastography have demonstrated their values to serve as non-invasive imaging biomarkers to evaluate NAFLD progression. However, ultrasound is more widely available, less expensive and maybe potential for monitoring of parenchymal fat content and evaluation of NAFLD progression.
It current setting, when patient is first diagnosed with NAFLD on ultrasound, AST/ALT follow up is done but ultrasound monitoring is not routinely done to see progression of NAFLD. However, AST/ALT ratio is not specific for patient. So it is important to routinely monitor patient with fatty liver disease for early detection of liver fibrosis.
Research Keyword
Ultrasound= US
Non-alcoholic fatty liver disease =NAFLD
Liver function test= LFT
Aspartate aminotransferase = AST
Alanine aminotransferase = ALT
Research Objective
General Objective:
Relationship of ultrasound grading NAFLD with liver transaminase among patient who attend radiology department in Serdang Hospital.

Specific Objectives:
1. To determine which liver transaminases profile correlate most with ultrasound grading.
2. To determine is AST/ALT ratio correlate with ultrasound grading.
Inclusion & Exclusion Criteria
Inclusion Criteria
Inclusion criteria:
1. All patient done ultrasound hepatobiliary system from Jan 2020 to December 2020 which shows fatty liver changes.
2. Outpatient and inpatient patient including patient with diabetes and obese patient.
3. Liver transaminases (AST and ALT) of these patients during same year as ultrasound.

Exclusion criteria:
1. Patient with known hepatic pathology i.e: hepatitis, liver chirrosis or hepatic malignancy.
2. Patient who is on drug (eg: statins) which may alter lipid profile and liver enzymes.
3. Alcoholic patient.
Exclusion Criteria
Inclusion criteria:
1. All patient done ultrasound hepatobiliary system from Jan 2020 to December 2020 which shows fatty liver changes.
2. Outpatient and inpatient patient including patient with diabetes and obese patient.
3. Liver transaminases (AST and ALT) of these patients during same year as ultrasound.

Exclusion criteria:
1. Patient with known hepatic pathology i.e: hepatitis, liver chirrosis or hepatic malignancy.
2. Patient who is on drug (eg: statins) which may alter lipid profile and liver enzymes.
3. Alcoholic patient.
Study Timeline
Expected / Actual Date Study Starts - First Enrolment of subject / Collecting data
Jun, 02 2021
Expected / Actual Date Study Completed
Oct, 30 2021
Expected / Actual Duration of Study Enrollment / Data Collection
21 weeks
Subject (Sample Size) Description
Age Range :
Gender :
Outcome Measure
The AST will be the most transaminases that correlate most with ultrasound grading.


The higher AST/ALT ration, the higher grading of fatty liver in ultrasound
Biospecimen Collection & Archiving
-


Current Study Status
Not Yet Recruiting
Sites
Sites Description
No. of site :
Sites List
HOSPITAL SERDANG
Team Members
Principal Investigator Information
DR Laila Mastura Binti Ahmad Apandi
UNIVERSITY PUTRA MALAYSIA (UPM)
Sponsor
HOSPITAL SERDANG
Ethical Application Status
Study URL
-
-
Individual Clinical Trial Participant–level Data of Individual Participant Data (IPD) Sharing
Result Summary