Clinical Dilemmas in Non-Alcoholic Fatty Liver Disease

acoustic radiation force imaging (ARFI)
adenosine monophosphatase-activated protein kinase (AMPK)
adiponectin
- agonist therapy
adiponutrin
- see also PNPLA3 gene polymorphism
adipose tissue
- inflammation
adipose triglyceride lipase (ATGL)
Africa, prevalence studies
alanine aminotransferase (ALT)
- AST/ALT ratio
- screening application
alcoholic foamy degeneration
alcoholic liver disease (ALD)
- grading and staging
- NAFLD comparison
  - differentiation
  - fibrosis
  - hepatocellular injury
  - inflammation
  - steatosis
alcoholic steatohepatitis (ASH)
American Association for the Study of Liver Diseases (AASLD) guidelines
- NAFLD definition
- NAFLD/NASH distinction
- paediatric patients
- screening
- therapy
American Board of Obesity Medicine (ABOM)
anti-LOXL2 monoclonal antibody
anti-LPS hyperimmune bovine colostrum (Imm124-E)
antifibrotic therapies
- clinical trial design challenges
  - knowledge of disease natural history
  - non-invasive monitoring
  - patient selection
  - trial end points
- emerging therapies
- targets
- trial results to date
- see also fibrosis
antilipolytic insulin sensitivity measurement
antioxidant therapy
- see also oxidative stress
apoptosis
APRI score
aramchol
Asia, prevalence studies
aspartate aminotransferase (AST)
- AST/ALT ratio
- screening application
atorvastatin
Australasia, prevalence studies
autoimmune liver disease
- cryptogenic cirrhosis relationship

BARD score
bariatric surgery
- benefits of
- development of
- diabetes incidence reduction
- duodenal switch
- gastric bypass
- guidelines
- jejunoileal bypass
- laparoscopic AGB
- laparoscopic sleeve gastrectomy
- mini-gastric bypass
- patient management
- risks of
  - acute complications
  - long-term complications
  - mortality
- vertical banded gastroplasty
Barker’s hypothesis
Belfiore insulin sensitivity index
bile acids
biliary atresia
bilirubinostasis
Blx-1002
bone mineral density (BMD), bariatric surgery patients
both alcoholic and metabolic steatohepatitis (BASH)
British Society of Gastroenterology (BSG) guidelines
- paediatric patients
- therapy
burned-out NASH

caffeine
candidate gene studies
cannabinoid receptor blockade
carbohydrate response element-binding protein (ChREBP)
cardiovascular disease (CVD)
- mechanistic link between NAFLD and CVD
  - ER stress
  - inflammation
  - insulin resistance role
  - lipid metabolism disturbance
  - oxidative stress
- NAFLD association
  - genetic association
- post-liver transplant cardiovascular events
CC chemokine receptor antagonists
cell death
- fibrogenic liver repair relationship
chemical-associated steatohepatitis (CASH)
childhood NAFLD see paediatric NAFLD
choledocholithiasis
cholestasis
choline deficiency
chromosome 19 locus
chromosome 22 locus
chronic kidney injury (CKI)
cirrhosis
- causes
- cryptogenic
  - definition
  - future directions
  - NAFLD/NASH as cause
  - other possible causes
- hepatocellular cancer association
- paediatric population
- risk factors for progression
clinical trials
- antifibrotic therapies
  - trial design challenges
- shortage of
coffee consumption benefits
Colesevelam
computed tomography (CT)
- fatty liver appearance
- screening
  - advantages and limitations
controlled attenuation parameter (CAP)
cryptogenic cirrhosis see cirrhosis
Cushing’s syndrome
cyclosporine
cysteamine
cytokeratin-18 (CK-18) fragments
cytokines
- fibrogenesis regulation

damage-associated molecular patterns (DAMPs)
developmental programming
- animal models
- human studies
- mechanisms
  - epigenetic mechanism
  - gut microbiota
  - immune mechanism
  - nervous system
diabetes
- bariatric surgery benefits
- hepatocellular carcinoma association
- liver transplantation outcome studies
- pharmacotherapies
- screening implications
diacylglycerol acyltransferase (DGAT)
dietary management of obesity
- weight loss effects on metabolic syndrome
dipeptidyl peptidase-4 (DPP-4) inhibition
docosahexaenoic acid (DHA)
drug-associated steatohepatitis (DASH)
ductular reaction (DR)
- paediatric population
duodenal switch
dysbiosis
- see also intestinal microbiome

familial aggregation
- see also genetic factors
familial combined hyperlipidaemia
farnesoid X receptor (FXR)
- agonists
farnesyl-diphosphate farnesyltransferase 1 (FDFT1) genotype
fasting-induced adipose factor (Fiaf)
fat mass and obesity-related protein (FTO) gene polymorphism
fatty acid mobilisation
- free fatty acids (FFAs)
- hepatic fatty acid uptake
fatty acid transport proteins (FATPs)
fatty liver index (FLI)
fenofibrate
ferritin
FIB-4 score
fibrates
fibroblast-specific protein (FSP)
FibroMeter™
FibroScan™
fibrosis
- alcoholic versus nonalcoholic liver disease
- diagnosis
  - serum markers
- fibrogenesis mechanisms
  - link between hepatocyte injury/death and repair
  - local regulation
  - non-liver factors
- following liver transplantation
- lobular
- molecular pathways
  - hedgehog signalling
  - osteopontin
  - TGF-β
- paediatric population
- perisinusoidal
- progression
  - monitoring
  - risk factors for
- staging
  - liver biopsy
- see also antifibrotic therapies
FibroTest™
FLIP algorithm
FoxO1 phosphorylation
free fatty acids (FFAs)

galectin inhibitors
gamma-glutamyltranspeptidase (GGT)
gastric bypass
- laparoscopic
- mini-gastric bypass
genetic factors
- candidate gene studies
- cardiovascular disease link with NAFLD
- heritability evidence
  - familial aggregation
  - interethnic differences in susceptibility
- metabolically normal NAFLD
- obesity
- see also PNPLA3 gene polymorphism; TM6SF2 gene polymorphism
genome-wide association studies (GWAS)
- rapid fibrosis progression
GFT-505
ghrelin
glitazones
glucagon-like peptide 1 (GLP-1)
- agonists
glucokinase regulator (GCKR)
gluconeogenesis regulation
glycaemic control, bariatric surgery patients
glycogen synthase kinase-3β (GSK3β)
glycogenated nuclei
growth hormone (GH)
guidelines
- NAFLD definition
- NAFLD/NASH distinction
- paediatric NAFLD
- screening
- therapy
gut flora see intestinal microbiome

hedgehog (Hh) signalling
- clinical relevance
- modulation of
- pathway components
- summary of actions
hemoglobin (Hb) concentrations
Hepascore
hepatic fatty acid uptake
hepatic insulin resistance
hepatic insulin resistance index
hepatic progenitor cells (HPCs)
hepatic steatosis index (HSI)
hepatitis B virus (HBV)
- comorbidity with NAFLD
- cryptogenic cirrhosis relationship
- prevalence
hepatitis C virus (HCV)
- comorbidity with NAFLD
- cryptogenic cirrhosis relationship
- paediatric population
- prevalence
hepatocellular carcinoma (HCC)
- causes
- cirrhosis association
- diabetes association
- genetic factor
- metabolic syndrome association
- noncirrhotic HCC
- obesity association
- pathogenesis
- prevalence
  - NASH association
- screening
- treatment
hepatocyte ballooning
- alcoholic versus nonalcoholic liver disease
- diagnostic significance
herniation following gastric bypass surgery
high-risk population
high-sensitivity C-reactive protein (CRP)
histological findings
homeostasis model assessment (HOMA) index
hypercortisolaemia
hyperinsulinaemia
hypoxia

idiopathic thrombocytopenia purpura (ITP)
inflammation
- adipose tissue
- alcoholic versus nonalcoholic liver disease
- cardiovascular disease association
- hepatocarcinogenesis promotion
- intestinal microbiome relationship
- obesity-related
- portal
- proinflammatory state
insulin actions
insulin receptor substrate 1 (IRS1)
insulin resistance (IR)
- cardiovascular disease association
- hepatic insulin resistance
- intestinal microbiome relationship
- measurement
  - antilipolytic insulin sensitivity
  - euglycaemic hyperinsulinaemic clamp
  - intravenous glucose tolerance test (IVGTT)
  - surrogate measures
- NAFLD relationships
- NAFLD treatment effects on
- prevalence
- screening implications
- steatohepatitis and
- see also metabolic syndrome
insulin sensitivity
- antilipolytic insulin sensitivity measurement
- surrogate measures
- see also insulin resistance (IR)
insulin sensitizers
insulin therapy
insulin tolerance test
insulinoma
INT-747 see obeticholic acid (INT-747)
interleukin-6 (IL-6)
intestinal microbiome
- choline deficiency promotion
- developmental programming mechanism
- endogenous ethanol production
- inflammation relationship
- insulin resistance relationship
- liver disease relationship
- NAFLD relationship
- obesity relationship
- therapeutic approaches
intravenous glucose tolerance test (IVGTT)
- portal venous insulin levels
iron overload
- iron depletion therapy
Italian Association for the Study of the Liver (IASL) guidelines
- NAFLD definition
- NAFLD/NASH distinction
- therapy

laparoscopic AGB
laparoscopic gastric bypass
laparoscopic sleeve gastrectomy
leptin
- resistance
lifestyle interventions
- guidelines
lipid-lowering therapies
lipodystrophy
lipogenesis
lipopolysaccharide (LPS)
lipotoxicity
liraglutide
liver biopsy
- contraindications
- cost considerations
- fibrosis staging
- guidelines
- hepatic comorbidity diagnosis
- indications
- management implications
- NAFLD diagnosis
- paediatric patients
- patient safety
- sample size and quality
- steatohepatitis diagnosis
- steatosis quantification
- techniques
- timing
liver enzyme analysis
liver priming
liver repair
- deregulated repair
  - see also fibrosis
- hormonal regulation
- restorative repair
liver transplantation
- chronic kidney injury relationship
- NAFLD recurrence
- obesity impact
- post-transplant cardiovascular events
- results
LPS binding protein (LBP)
lysyl oxidase (LOX) L2
- anti-LOXL2 monoclonal antibody

magnetic resonance elastography (MRE)
magnetic resonance imaging (MRI)
- qualitative fat estimation
  - frequency-selected (FS) technique
  - OIP technique
- quantitative fat estimation
- screening
magnetic resonance spectroscopy (MRS)
malabsorption, bariatric surgery patients
Mallory–Denk bodies
matrix metalloproteinases (MMPs)
megamitochondria
melanocortin receptor 4 gene mutation
metabolic physician
- bariatric surgery patient management
- definition
- medical management of obesity
- obese patient diagnosis and assessment
- see also metabolic syndrome; obesity
metabolic risk factors
metabolic syndrome
- as NAFLD risk factor
- hepatocellular carcinoma association
- liver transplantation outcome relationships
- NAFLD treatment effects on
  - bariatric surgery
  - dietary weight loss
  - pharmacotherapies
- prevalence
- screening implications
- see also insulin resistance (IR); metabolic physician
metabolically normal NAFLD
- genetic factors
- prognostic implications
- treatment approach
metadoxine
metformin
microbiota see intestinal microbiome
microRNAs (miRNAs)
mini-gastric bypass
mitochondriopathies

NAFLD see nonalcoholic fatty liver disease (NAFLD)
NAFLD activity score (NAS)
NAFLD fibrosis score (NFS)
NAFLD index
NAFLD liver fat score
NashTest™
necrosis
needle biopsy
- see also liver biopsy
nesidioblastosis
neurocan (NCAN)
nicotinic acid
non-esterified fatty acid (NEFA)
- antilipolytic insulin sensitivity evaluation
nonalcoholic fatty liver disease (NAFLD)
- alcoholic liver disease comparison
  - differentiation
  - see also alcoholic liver disease (ALD)
- cardiovascular disease association
  - genetic association
  - mechanistic link
- comorbidity
- definition
- diagnosis
  - hepatic comorbidity
  - histological
  - scoring systems
  - see also screening
- disease severity
- grading and staging
- heritable component
  - see also genetic factors
- high-risk population
- insulin resistance relationships
- intestinal microbiome relationship
- liver transplantation relationship
  - disease recurrence following transplantation
- loss of steatosis in late disease
  - possible causes
- metabolic syndrome relationships
- pathogenesis related to hepatocellular carcinoma
- prevalence
  - worldwide studies
- primary
- risk factors
  - identification of
- scoring systems
- secondary
  - causes
- see also metabolically normal NAFLD; paediatric NAFLD
nonalcoholic steatohepatitis (NASH)
- burned-out NASH
- cryptogenic cirrhosis relationship
- diagnosis
  - diagnostic criteria
  - histological
  - liver biopsy
  - noninvasive diagnostic procedures
  - recommendations
- hepatocellular carcinoma association
- high-risk population
- histological features
- insulin resistance relationship
- loss of steatosis in late disease
- oxidative stress role
- screening
- simple steatosis distinction
noninvasive fibrosis tests (NILTs)
norepinephrine
nuclear erythroid 2-related factor (Nrf2)
nuclear factor-κβ (NF-κβ)

obesity
- diagnosis and assessment
- dietary management
  - weight loss effects on metabolic syndrome
- genetic factors
  - syndromes
- hepatocellular carcinoma association
- heritability
- intestinal microbiome relationship
- liver transplantation outcome relationship
- medical management
- NAFLD relationship
- prevalence
- related disease spectrum
- screening implications
- see also bariatric surgery
obeticholic acid (INT-747)
obstructive sleep apnea (OSA)
omega-3 polyunsaturated fatty acids
oral glucose insulin sensitivity (OGIS) index
oral glucose tolerance test (OGTT)
orlistat
osteopontin (OPN)
- clinical relevance
- summary of actions
oxidative stress

paediatric NAFLD
- developmental origins
- distinct pattern of disease
- guidelines
- histological evidence of early progression
- long-term outcome
- maternal BMI as predictor
pancreatitis
pentoxifylline
peptide YY
peroxisome proliferator-activated receptors (PPARs)
- agonists
phlebotomy
phosphatase and tensin homolog (PTEN)
phosphatidylethanolamine N-methyltransferase (PEMT)
Pima Indian studies
pioglitazone
pirfenidone
PNPLA3 gene polymorphism
- fibrosis association
  - severity relationship
- hepatocellular carcinoma association
- metabolically normal NAFLD
- NASH relationships
- product biological functions
polycystic ovary syndrome
polyphenols
portal hypertension
portal venous insulin levels
post-prandial hypoglycaemia (PPH)
prevalence
- disease severity
- hepatitis B
- hepatitis C
- hepatocellular carcinoma
- metabolic syndrome
- obesity
- worldwide studies
priming of the liver
probiotic benefits
procollagen III terminal peptide (PIIINP)
prolonged QTc interval

SAF score
scar tissue deposition
- see also fibrosis
sclerosing hyaline necrosis
screening
- guidelines
- hepatocellular carcinoma (HCC)
- high-risk population
- methods
  - computed tomography (CT)
  - liver enzyme analysis
  - magnetic resonance imaging (MRI)
  - magnetic resonance spectroscopy (MRS)
  - ultrasonography
- NASH
- practical approach
- risk factor identification
- scoring systems
selective PPAR modulators (SPPARM)
serum markers
- direct
- indirect
short-chain fatty acids (SCFAs)
silymarin
sirolimus
sleeve gastrectomy
small intestinal bacterial overgrowth (SIBO)
SREBP-1c pathway
statins
steatohepatitis see alcoholic steatohepatitis (ASH); nonalcoholic steatohepatitis (NASH)
steatosis
- alcoholic versus nonalcoholic liver disease
  - macrovesicular steatosis
  - microvesicular steatosis
- choline deficiency and
- diagnosis
- distinction from NASH
- quantification
- see also alcoholic steatohepatitis (ASH); nonalcoholic steatohepatitis (NASH)
SteatoTest
superoxide dismutase 2 (SOD2)
supersonic shear imaging (SSI)

tacrolimus
TGR5 receptor
thiamine deficiency
thiazolidinediones (TZDs)
- side effects
thyroid disease
tissue inhibitors of metalloproteinases (TIMPs)
tissue repair
- deregulated repair
  - see also fibrosis
- restorative repair
TM6SF2 gene polymorphism
- product biological function
Toll-like receptors (TLRs)
- activation
transforming growth factor-beta (TGF-β)
- clinical relevance
- overexpression
transient elastography
triglyceride (TG) accumulation
tumor necrosis factor-α (TNF-α)