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FATTY LIVER
Medicine, Seattle
Definition
Term NASH was coined by Ludwig et all in 1980
It is steatohepatitis in absence of significant
Prevalence
NAFLD is most common liver disease High incidence in cases of obesity DM
Pathogenesis
Metabolic syndrome
Central obesity Hyperglycemia(type II DM)
Low HDL
Hypertriglyceridemia HT
( 3 out of 5)
Insulin resistance
TNF activates inhibitor Kinase Kappa-
NAFLD classification
Class 1: simple steatosis Class2 :steatosis with lobular inflammation Class3 : 2+ ballooned hepatocytes Class 4: 3+ mallory hyaline or fibrosis
NASH: class3 or 4
-Fatigue (correlates poorly with histologic stage) -Right upper quadrant pain (usually mild but may be mistaken for gallstone disease) -Hepatomegaly -Bowel dysmotility and small bowel bacterial overgrowth
Laboratory findings
Mild elevation of aspartate AST and ALT levels; levels seldom
exceed 10X the upper level of normal and more typically are <1.5 X the upper normal level (altered with antidiabetic therapy) elevation
ALT > AST; AST > ALT suggests significant fibrosis or cirrhosis Glutamyltransferase and alkaline phosphatase level
to 25%
patients
Abnormal iron indices (common but generally do not indicate genetic hemochromatosis
- hepatocellular ballooning; most apparent near steatotic liver cells, typically in zone 3
- zone 3 perisinusoidal fibrosis - zone 1 hepatocellular glycogenated nuclei - lipogranulomas in the lobules; of varying size, but usually small - occasional acidophil bodies or PAS stained Kupffer cells - fat cysts
- Mallorys hyaline in ballooned hepatocytes *usually zone 3 in NASH, may be in zone 1 in diabetes, amiodarone
- Mild (1+) granular periportal (zone 1) hepatocellular iron or scattered iron granules in
Unusual for NASH, consider other causes of liver test abnormalities - macrovesicular steatosis:<30% of parenchyma involved/ nonzonal distribution
Grading of NASH
Grade 1 (mild)
Grade 2 (moderate)
- steatosis: any degree, usually mixed macrovesicular & microvesicular - ballooning: present in zone 3 - lobular inflammation: polymorphs associated with ballooned hepatocytes and/or pericellular fibrosis; mild chronic inflammation - portal inflammation :none, mild to moderate
- ballooning: predominantly zone 3; marked lobular inflammation :scattered acute & chronic inflammation; polymorphs concentrated in zone 3 areas of ballooning and perisinusoidal fibrosis
- portal inflammation: mild or moderate; not predominant or marked
Staging
Stage 1: zone 3 perivenular, perisinusoidal, or
fibrosis
Stage 3: bridging fibrosis, focal or extensive Stage 4: cirrhosis with or without residual
perisinusoidal fibrosis
Ballooning
0 none 1 few 2 many/prominent
Lobular inflammation
Fibrosis
Stage 0 none Stage 1a - zone 3 perisinusoidal fibrosis ,MT Stage 1b - zone 3 perisinusoidal fibrosis Stage 1c - fibrosis limited to portal tracts Stage 2 Stage 3 Stage 4
NAS 5
NAS > 2 to < 5 NAS 2
Diagnostic of NASH
Indeterminate Simple Steatosis
NASH Vs ASH
More common in ASH
Sclerosing hyaline necrosis (bridging necrosis) Veno-occlusive lesions
Ductular reaction
Cholangiolitis Bilirubinostasis
Mallory hyaline
Pediatric NASH
Clinically
Obesity Hepatomegaly
Acanthosis nigricans
Histologically
More sever steatosis
insulin resistance? role of FFA in cellular injury in NAFLD ? Insulin signaling pathways affected? Best pharmacological approach?
share many features & it is often not possible to distinguish them on histological grounds alone A HPE diagnosis of steatosis , steatohepatitis should be made & subsequently correlated clinically. Pediatric NASH more often shows portal based fibrosis & inflammation together with severe steatosis & less ballooning , inflammation & pericellular fibrosis.
Grading & staging of NAFLD is mainly performed in the context of epidemiological studies & clinical trials. NAS is a potentially valuable tool in the systematic assessment of NAFLD in liver Bx & its components could be scored & described
in the report/
Thank you