Table 2.

Diagnostic and Screening Criteria of Different Phenotypes of CLD

DILI	The CIOMS has laid down the guidelines for the evaluation of the (1) hepatocellular injury, ALT ≥3 ULN and R ≥ 5; (2) cholestatic injury, alkaline phosphatase (ALP) ≥2 ULN and R ≤2; (3) and hepatocellular-cholestatic mixed injury, ALT ≥3 ULN, ALP ≥2 ULN and 2 < R < 5.24,51 The general diagnosis of DILI is primarily based on the elevation in serum ALT, ALP, GGT, and total bilirubin.26 Drug-induced autoimmune hepatitis diagnosis is based on serology, genetic test, and liver biopsy whenever possible whereas drug-induced secondary sclerosing cholangitis on MRCP or ERCP.23
NAFLD/MAFLD	Liver biopsy is considered the gold standard for differentiating the phenotypes of NAFLD/MAFLD (NAFL and NASH) and their progression (fibrosis and cirrhosis),32,34 nonetheless, noninvasive preliminary diagnostic evaluation includes imaging to determine steatosis and evaluation of conventional liver biochemistry, in addition to fasting blood glucose, total blood count, hemoglobin A1c, and OGTT.10,21 To assess the presence of steatosis, FLI, SteatoTest, and NAFLD liver fat score are determined.32,52 Cytokeratin-18 fragment biomarker is currently being used to assess the extent of inflammation.32,53 In case NAFLD and NASH progress to fibrosis, NAFLD fibrosis score, fibrosis 4 calculator, AST/ALT ratio index, ELF panel, Fibrometer, Fibrotest, Hepascore, NAFLD activity score, in conjunction with imaging techniques such as TE, MRE, and shear wave elastography are used.10,54
	In the case of normal-weight individuals with hepatic steatosis and not having type II diabetes, the diagnostic criteria include the presence of at least 2 of the following metabolic conditions:
	(1) risk factors identifying the metabolic syndromes (example specific cut-off points for the waist circumference, blood pressure ≥130/85 mm Hg, plasma triglycerides ≥150 mg/dL, plasma HDL-cholesterol <40 mg/dL for men and <50 mg/dL for women, prediabetes, that is, fasting glucose levels 100–125 mg/dL, or 2-h postload glucose levels 140–199 mg/dL, hemoglobin A1c 5.7%–6.4%).
	(2) homeostatic assessment, that is, determine the HOMA-IR score ≥2.5;
	(3) high plasma high sensitivity-C-reactive protein level >2 mg/L.
	Abdominal ultrasonography is usually performed in clinical practice; however, CAP determination using VCTE and MRS, or MRI-PDFF, are also used to quantify liver fat.44,55 The FLI ultrasonographic fatty liver indicator and APRI are scoring systems to determine steatohepatitis and fibrosis.44,42 LSM by VCTE is widely preferred over biopsy in the Asia–Pacific region.42
	Furthermore, physicians also prefer to wait for at least 5 y to perform a liver biopsy postdiagnosis of elevated liver function tests; additionally, if the body mass index of the patient is ≥25 kg/m2, there is an increased risk of progression to NASH.10,21,56
ALD	The general diagnosis of ALD involves the use of a series of questionnaire.19,46 The screening procedure is either invasive, such as liver biopsy for evaluating the degree of steatosis and fibrosis; or noninvasive, such as TE or quantification of biological markers encompassing GGT, serum ALT, serum AST, MCV, and %CDT.19,48 In case of advanced fibrosis or cirrhosis, serum albumin, prothrombin time, INR, serum bilirubin levels, platelets, or white blood cell counts should be analyzed followed by endoscopy.48
Liver fibrosis	The LSM and TE are noninvasive diagnostic tools for determining fibrosis.57 Other tests such as Fibrotest, Fibrometer, FIB-4, NFS, and ELF are also performed.48

ALD, alcoholic liver disease; ALP, alkaline phosphatase; ALT, alanine aminotransferase; APRI, AST-to-platelet ratio index; AST, aspartate aminotransferase; CAP, controlled attenuation parameter; CDT, carbohydrate-deficient transferrin; CIOMS, Council for International Organizations of Medical Sciences; CLD, chronic liver diseases; DILI, drug-induced liver injury; ELF, enhanced liver fibrosis; ERCP, endoscopic retrograde cholangiopancreatography; FIB-4, fibrosis-4, index; FLI, fatty liver index; GGT, gamma-glutamyl transpeptidase; HDL, high-density lipoprotein; HOMA-IR, homeostasis model assessment-estimated insulin resistance; INR, international normalized ratio; LSM, liver stiffness measurement; MAFLD, metabolic associated fatty liver disease; MCV, mean corpuscular volume; MRCP, magnetic resonance cholangiopancreatography; MRE, magnetic resonance elastography; MRI, magnetic resonance imaging; MRI-PDFF, magnetic resonance imaging proton density fat fraction; MRS, magnetic resonance spectroscopy; NAFL, nonalcoholic fatty liver; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; NFS, NAFLD, fibrosis score; OGTT, oral glucose tolerance test; TE, transient elastography; ULN, upper limit of normal; VCTE, vibration-controlled transient elastography.