الفهرس 
AcknowledgementOnly 14 pages are availabe for public view
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Abstract
Non alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with a global prevalence estimated at 25% of the world‘s population. Its estimated prevalence in Egypt about 31.6% among young adults.
Liver biopsy is the gold standard for diagnosis of NASH. However, liver biopsy is an invasive procedure, costly and is associated with rare but potential complications and sampling errors. New methods are being developed to assess NAFLD, particularly the presence or absence of NASH and the severity of any complicating fibrosis or cirrhosis. To achieve this aim, the tests should be non-invasive, accurate, reproducible and affordable. These non invasive tests are either radiological or serum biomarkers.
Our study aimed to assess the ability of serum steatosis markers: Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI), visceral adiposity index (VAI) and triglyceride x glucose index (TyG) to differentiate between early and advanced steatosis measured by CAP score, To study serum level of Pentraxin 3 as a marker of inflammation and Cytokeratin 18 as a marker of apoptosis in patients with different grades and stages of NAFLD, To study the ability of serum fibrosis markers: NAFLD fibrosis score, Fibrosis-4 (FIB-4), APRI and BARD score in differentiation between mild/ moderate and advanced stages of fibrosis assessed by transient elastography (Fibroscan).
Before starting, the study protocol was approved by Sohag Faculty
of Medicine Ethical Committee and all participants signed a written
consent. This case-control study was conducted on 180 subjects screened by abdominal ultrasound, of whom 87 patients (48.3%) were found to have NAFLD (32 males and 55 females, their ages ranged from 23-65 years). And 93 subjects of those without NAFLD served as controls (32 males and 61 females, their ages ranged from 19-70 years).
All subjects underwent complete history taking, thorough clinical examination, arterial blood pressure measurements and anthropometric measurements were calculated: BMI and WC. Then patients with bright liver in ultrasound were subjected to Fibroscan for assessment of steatosis and fibrosis. Fasting blood samples were collected from all participants for complete blood count, liver function tests, serum creatinine, fasting blood sugar, lipid profile and serum Cytokeratin 18 & serum Pentraxin 3. The following indices and scores were calculated: FLI, HSI, VAI, TyG, NAFLD fibrosis score, FIB-4, APRI and BARD score.
Fibroscan showed 19 (21.84%) patients with mild steatosis (S1) and 68 (78.167%) patients had moderate/advanced steatosis (S2, S3). Sixty-two (71.264%) patients had no or mild fibrosis (F0-F1), while 25 (28.735%) patients had moderat/advanced fibrosis (F2,3,4).
Univariate analysis of the predictors of moderate/advanced hepatic steatosis in our study revealed that active smoking, body weight, BMI, higher obesity classes, larger right lobe diameter, higher fatty degrees with ultrasound predicted advanced steatosis. However, multivariate analysis revealed that active smoking, high VAI, higher degrees of fatty liver by ultrasound and larger liver size were significant predictors of hepatic steatosis. While the final logistic regression model showed that VAI, moderate and severe degrees of fatty liver with ultrasound and larger liver size were the only significant predictors of hepatic steatosis.
We found that FLI, HSI and VAI scores had moderate diagnostic performance for predicting advanced steatosis in patients with NAFLD with FLI having the largest AUC (0.681).
Univariate analysis of the predictors of moderate/advanced hepatic fibrosis in our study revealed that DM, HTN, higher weight, waist circumference, higher fatty degree by ultrasound, high FBS, AST, GGT, FIB 4, APRI, BARD and lower platelets count were significant predictors of moderate/advanced hepatic fibrosis. However, multivariate analysis revealed that DM, HTN and high FIB 4 score were significant predictors of advanced hepatic fibrosis. While the final logistic regression model showed that FIB 4 were the only significant predictors of hepatic fibrosis. We found that FIB-4 and APRI had good diagnostic performance for predicting advanced fibrosis in patients with NAFLD with FIB 4 having the largest AUC (0.949) and the best diagnostic accuracy (90%).
Pentraxin-3 (marker of inflammation) and Ck-18 (marker of apoptosis) didn’t show any significant association with the degree of steatosis or stage of fibrosis and hence they couldn’t predict advanced steatosis or fibrosis.
In NAFLD patients, VAI independently predicts advanced steatosis. FLI and HSI and VAI have moderate diagnostic performance for advanced steatosis. FIB-4 is a significant predictor of advanced fibrosis and has a very good diagnostic accuracy. These tests may be used in clinical practice together with ultrasound when Fibroscan is not available. Pentraxin 3 and Cytokeratin 18 are not helpful in predicting advanced steatosis or fibrosis.
Recommendations
- FLI, HSI and VAI (steatosis indices) could be considered suitable tests for non invasive diagnosis of advanced hepatic steatosis.
- FIB 4 could be valuable non invasive diagnostic tools for non invasive evaluation of advanced liver fibrosis in NAFLD patients.
- Serum Pentraxin 3 and Cytokeratin 18 can be used as screening tests for NAFLD.
- Future studies are needed in biopsy-proven NAFLD for evaluation of Pentraxin 3 and Cytokeratin in differentiating NASH from simple steatosis.
- Further studies are recommended for non invasive evaluation of NAFLD using other non invasive serum biomarkers and also for evaluation of NAFLD in special populations as pediatrics, diabetics, and lean individuals.
- Use of these non invasive serum markers could help guide clinicians in assessment of patients response to treatment.