Clinical indicators for progression of nonalcoholic steatohepatitis to cirrhosis

Table 1 Role of noninvasive liver function testing in clinical progression of nonalcoholic steatohepatitis

Sr. No.	Indicator	Ref.	Journal	Year	Results
1	Bilirubin	Demir et al[24]	PLoS One	2013	Total bilirubin was identified as a significant predictor of advanced fibrosis and used to construct the NIKEI score which can reliably exclude advanced fibrosis in subjects with NAFLD
		Ratziu et al[25]	BMC Gastroenterol	2006	FibroTest which includes total bilirubin in its panel is a simple and noninvasive quantitative estimate of liver fibrosis which reliably predicts advanced fibrosis
		Adams et al[11]	J Hepatol	2005	Hepascore, a model of 4 serum markers plus age and sex provides clinically useful information regarding different fibrosis stages among hepatitis C patients
2	Serum AST/ALT	Martin-Rodriguez et al[20]	Medicine (Baltimore)	2017	Serum ALT level is the most predictive laboratory investigation for the NAFLD. The AST-ALT Ratio (AAR) is higher in increasing liver fat content, fibrosis and other metabolic derangements like diabetes and dyslipidemia
		Enomoto et al[21]	World J Gastroenterol	2015	AAR > 1 is consistent with NASH
		Arora et al[22]	J Clin Exp Hepatol	2012	AAR > 1 may indicate the progression of NAFLD and aid in diagnosing liver fibrosis
		Shah et al[17]	Clin Gastroenterol Hepatol	2009	The FIB-4 score composed of age, AST and ALT and platelet counts is an invasive and inexpensive method which has shown superiority to BAAT (BMI, Age, ALT, Triglycerides) and BARD (BMI, AST: ALT, Diabetes) scores in monitoring the progress of NASH
		McPherson et al[18]	Eur J Gastroenterol Hepatol	2013	The FIB-4 score was reliable in ruling out advanced fibrosis in patients with histological evidence of NAFLD who had normal or increased levels of ALT, thus decreasing the need for invasive liver biopsy
3	Platelet Count	Enomoto et al[21]	World J Gastroenterol	2015	A reducing level of platelet count has been well documented in advancing liver diseases
		Kawamura et al[26]	Hepatol Int	2015	FSN score of 17 variables including platelet count could accurately predict fibrotic stage and discriminates patients with advanced fibrosis of NASH
		Kessoku et al[27]	World J Gastroenterol	2014	PLALA Score is a very unique scoring system as it has shown usefulness in distinguishing cirrhosis in NAFLD when compared with most fibrosis scoring systems
		Abdel-Razik A et al[47]	Eur J Gastroenterol	2016	MPV is a noninvasive novel marker to predict advanced disease as it was increased in NASH patients and advance liver fibrosis
		Cengiz et al[48]	Eur J Gastroenterol	2015	Red cell volume distribution width-to-platelet ratio was both correlated and able to predict liver fibrosis. It may reduce liver biopsy in NAFLD
4	Fasting blood glucose and glycosylated protein	Pelusi et al[49]	PLoS One	2016	Nonalcoholic steatohepatitis with greater degree of fibrosis was discovered in patients with insulin resistance. Type 2 diabetes in patients with NAFLD tends to drive the rate of fibrosis
5	Hyaluronic acid (hyluroante) tissue metaloproteinase	Arora et al[22]	J Clin Exp Hepatol	2012	European Liver Fibrosis score ELF scoring system has indicators for cellular matrix activities including Hyaluronic acid (hyluroante) tissue metalloproteinase which has been indicative of fibrosis
6	Type IV collagen	Nakamura et al[30]	J Diabetes Investig	2013	NAFIC Score including type IV collagen 7S and Modified NAFIC score were proven to be clinically useful in screening for NASH in NAFLD patients
7	Glycosylated Albumin to Glycosylated Hemoglobin Ratio	Hu et al[28]	World J Gastroenterol	2014	HOMA-IR score indicates NAFLD progression using a formula that involves insulin levels and fasting glucose to calculate insulin resistance. The score has a high sensitivity for NASH
		Stål[29]	World J Gastroenterol	2015	NAFLD fibrosis score, a non- invasive score which includes the presence of diabetes or impaired fasting glucose is the most predictive of mortality in NASH as compared to NAFL patients
8	Prothrombin time	Assy et al[31]	World J Gastroenterol	2005	Increase prothrombin time is usually associated with cirrhotic changes
9	Albumin	Bazick et al[5]	Diabetes Care	2015	Serum albumin gets reduced in patients progressing to NASH and fibrosis from NAFLD

ALT: Alanine aminotransferases; BMI: Body mass index; NAFIC: Nonalcoholic steatohepatitis, ferritin, insulin, and type IV collagen 7S; NASH: Nonalcoholic steatohepatitis; AAR: Aspartate aminotransferases-alanine aminotransferases ratio; RPR: Red cell volume distribution width-to-platelet ratio; NFS: Non-alcoholic fatty liver disease fibrosis score; NIKEI: Non-invasive koeln-essen-index; NAFLD: Non-alcoholic fatty liver disease.

Table 2 Role of imaging techniques in clinical progression of nonalcoholic steatohepatitis

Sr. No.	Imaging modality	Ref.	Journal	Year	Results
1	Ultrasound	Sanyal[32]	Gastroenterology	2002	US is currently the preferred method in United States for screening asymptomatic patients with elevated liver enzymes and suspected NAFLD with sensitivity in detecting steatosis varying between 60%–94%
2	Magnetic Resonance Elastography	Iijima et al[35]	Hepatol Res	2007	Magnetic resonance elastography has excellent diagnostic accuracy with sensitivity and specificity of 98% and 99%, respectively, for detecting all grades of fibrosis
		Huwart et al[36]	Gastroenterology	2008	Magnetic resonance elastography was associated with a higher technical success rate than US elastography
3	Fibroscan	Wong et al[39]	Gut	2012	Transient elastography had shown good results in patients with NAFLD. It is a non-invasive method of assessing liver fibrosis which can be performed at the bedside or in the outpatient clinic
		Wong et al[40]	Hepatology	2010	Transient elastography had shown good results in patients with NAFLD. It is a non-invasive method of assessing liver fibrosis which can be performed at the bedside or in the outpatient clinic
		Ratziu et al[43]	Gastroenterology	2005	Fibroscan has now been validated in NAFLD, and represents a useful tool for rapid, non-invasive assessment of liver fibrosis and determining the need for biopsy. Nonetheless, fibroscan values should be interpreted in consonance with clinical, biological, and morphological data

US: Ultrasonography; NAFLD: Non-alcoholic fatty liver disease.

Table 3 Nonalcoholic steatohepatitis activity score; steatosis, activity, and fibrosis score; and brunt grading and staging systems

NASH activity score	Steatosis, activity and fibrosis score	Brunt grading and staging
Steatosis grade 0-3	Steatosis S0-S3	Grade 1 (Mild)
Lobular inflammation 0-3	Activity A1-A3	Grade 2 (Moderate)
Ballooning 0-2	Lobular inflammation 0-2	Grade 3 (Severe)
Fibrosis 0-4 (grade 1 has subgrade A, B, C)	Ballooning 0-2	Stages fibrosis
	Fibrosis F0-F4	Stage 1-4

NASH: Nonalcoholic steatohepatitis.