Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
FATTY LIVER
Dr. Suhaemi, SpPD,finasim
Fatty liver
Normal liver
Fatty Infiltration
increased sound attenuation =poor definition of posterior aspect of liver ( bright liver)
A. Demonstrates a heterogeneous-appearing echotexture bright liver B. Relatively hypodense liver compared to the spleen (liver-to-spleen ratio <1)
Areas of lower attenuation than normal portal vein/IVC density Hyperdense intrahepatic vessels
Lipid Accumulation
Oxidative Stress
1st HIT
2nd HIT
Cytokine Activation
10
1st Hit
2nd Hit
Apoptosis
Damaged Liver
11
Donnelly et al. J. Clin. Invest. 113: 1343, 2005; Day and James. Gastroenterol. 114: 842, 1998
Normal
FAT >5%
1st HIT
NASH
Inflammatio n
2nd HIT
Scarring
DCLD
NAFLD
IR and MS
Cirrhosis
IR and MS
CV Risk
12
NAFLDHistological Spectrum
Cirrhosis Time Progression
Fibrosis
Lobular Inflammation
Macrovesicular Steatosis
Benign course
3% develop cirrhosis
Worse prognosis
5 yr survival 67%
10 yr survival 45%
14
NAFLDPathogenesis
TRIGLYCERIDE ACCUMULATION INSULIN RESISTANCE Lipid Peroxidation and Hepatic Lipotoxicity Cytokine Activation and Fibrosis
90 (M), 80 (F)
Triglycerides >150 mg
HDL
2 of 5
Dysglycemia
FPG >100 or DM
Hypertension
>130 or 85
16
16
NAFLD
IR
DM
MS
17
NAFLD NASH
18
IR
Leptin, IL-6 FFA, PC1 Rad, TNF-
Adiponectin
NEFAs
Obesity, PPAR-
NO
TNF-
ATP
CC P450 A,E1
Glutathione PPAR- ,
Kuffer Cells
NF-B
in oxidative stress
SREBP1a,1c,2
NASH, CV Risk
O2 stress, Inflmma.
19
20
Wilsonss Disease
-1 Anti-trypsin AI Hepatitis
Triglycerides
Medicines*, TPN
Hepatitis C
Inherited syndromes
NAFLDRisk Factors
Acquired Metabolic Disorders *Obesity* Obesity Diabetes *Diabetes Mellitus* Mellitus *Hypertriglyceridemia* Hypertriglyceridemi a Parenteral Nutrition ,Rapid Total weight loss, Acute starvation Jejunoileal Bypass
Extensive Small Bowel Loss
in 38%
Surgery
Diltiazem; Nifedipine
Occupational Exposures Others Organic Solvents Wilson's dis,Abetalipoproteinemia Jejunal diverticulosis
Clinical Presentation
Asymptomatic Routine blood tests Liver enzymes Enlarged Liver (1/3) RUQ periumb. Pain Fatigue. Malaise
Anorexia, Nausea > 90% are obese USG e/o fatty liver Acanthosis Nigricans DM, HTN, Lipid abn. OSAS, Snoring
23
Laboratory Abnormalities
2 - 4 fold GPT & GOT SGOT: SGPT Ratio <1 AKP slight in 1/3 Dyslipidemia - TG FBG and PPBG BUN & Creatinine N
Normal Albumin. PT Low ANA + < 1 in 320 Serum Ferritin Iron saturation SGOT: SGPT Ratio >1 if Cirrhosis sets in
24
How to Treat?
Insulin Sensitizers Antihyperlipidemics Antioxidants Cytoprotectants
First Hit
Insulin resistance Fatty acids
Steatosis
Second Hit
Lipid peroxidation
NASH
Membrane-Stabilizing
Lipid-Lowering Agents
Anti-Oxidants
Anti-fibrotics;
Vitamin B Complex
Evidence of efficacy in NASH/NAFLD is equivocal 300 mg bid or 10 mg/kg in two divided doses PO Given up to 12 to 24 months - depends on response Cholestasis, PBC, PSC, Acute viral hepatitis, HBV, HCV Chronic hepatitis, Alcoholic liver disease Dissolution of cholesterol microliths / gallstones
27
NAFLD and NASH may resolve with weight loss Liver fat content ; No effect on fibrosis & Inflam. Diet and exercise improve insulin sensitivity, increase oxidative capacity and utilization of FFAs
It is the main cause of liver enzymes; Isnt that benign Spectrum of disease NAFLD NASH Cirrhosis HCC Insulin resistance, MS are the key pathogenic features DM, TG, Non fatty abdominal obesity, increasing age Always look for DM, TG, CVD if you see fatty liver Presently, the management is to improve IR, TG, DM
29