NON ALCOHOLIC

STEATOHEPATITIS
(NASH )
 NON ALCOHOLIC STEATOHEPATITIS
(NASH )
Non Alcoholic Fatty Liver Disease (NAFLD) is a clinicopathological syndrome encompasses
several clinical entities ranging from simple steatosis to steatohepatitis, fibrosis and ESLD in the
absence of significant alcohol intake
NASH is a part of spectrum of NAFLD and defined as steatosis with hepatocellular ballooning
plus lobular inflammation
NAFLD
FATTY LIVER IN A NON ALCOHOLIC PT IR A PT WITHOUT SIGNIFICANT ALCOHOL USE
FAT DEPOSITION IN >5% HEPATOCYTE IS CALLED AS FATTY LIVER
NAFLD has wide histopathological spectrum
hepatic steatosis- simple accumulation of triglycerides in hepatocytes
NASH- complicated by hepatocyte death and inflammation
cirrhosis, primary liver cancer – 3 %
 CAUSES OF FATTY LIVER
ACQUIRED OTHER DRUGS
CYTOTOXIC DRUGS • AMIODARONE
• T2DM • L-ASPARGINASE
• DLP • CAMPHOR
• AZCITIDINE • CHLOROFORM
• KWASHIORKER • BLEOMYCIN
• OBESITY • COCAINE
• CISPLATIN • ESROGENS
• RAPID WT LOSS • 5-FLUOROURACIL
• STARVATION • GLUCORTICOIDS
• METHOTREXATE • NSAIDS
• TETRACYCLINES • VALPROIC ACID
• HAART
METALS • NIFEDIPINE
• ANTIMONY • NFT
• Ba SALTS
• Hg
• P
• THALLIUM
COMPOUNDS
 NATURAL COURSE
NAFLD

80% 20%
ISOLATED NASH
FATTY LIVER

11% OVER
15YEARS CIRRHOSIS

7%
3% OVER 8 DECOMPENSATION OVER HCC
YEARS 6.5
YEARS
MACRO VASCULAR FATTY LIVER
◦ FAT DEPOSITION IN LIVER DISPLACES HEPATOCYTE NUCLEUS TO PERIPHERY SO THE NUCLEUS IS NOT
VISIBLE.

MICROVASCULAR FATTY LIVER

◦ FAT DEPOSITION IN LIVER DISPLACES HEPATOCYTE NUCLEUS TO PERIPHERY SO THE NUCLEUS IS VISIBLE.
DIFFERENTIATE NASH AND FATTY
LIVER
LIVER BIOPSY

DETERMINING DEGREE OF
◦ STEATOSIS
◦ BALLOONING
◦ LOBULAR INFLAMMATION
0-2 LIKELY NOT NASH
3-4 INTERMEDIATE LIKELY NASH
5-8 LIKELY NASH
Chicken wire pattern fibrosis in zone 3 in nash
Normal liver histology
CLINICAL FEATURES IN PTS WITH
NASH
SYMPTOMS-
COMMON-NONE
UNCOMMON-VAGUE RUQ PAIN,MALAISE ,FATIGUE
SIGNS
COMMON-HEPATOMEGALY
UNCOMMON-SPLENOMEGALY,SPIDERANGIOMATA,PALMAR ERETHEMA,ASCITES
NASH WHEN
ALT OR AST-30-150U/L
ALT>AST LEVELS
Ferritin levels are elevated in nash
FIBROSCAN
Principle-vibration controlled transient elastography (vcte) and controlled attenuation
parameter(CAP).
FibroScan is a non invasive device that assesses the stiffness of liver via technique of transient
elastography.
Liver hardness is evaluated by measuring the velocity of a vibration wave(shear wave) generated
by the skin.
FIBROSCAN SHOULD DONE IN NASH PTS TO CHECK ON CIRRHOSIS OF LIVER
A minimum of 10 valid readings with 60% success rate and interquartile range of <30% median
value are taken and expressed in kPa(kilopascals).
PROCEDURE
PREPARATION-NPO FOR 3HOURS PRIOR TO PROCEDURE
PT. POSITION-SUPINE
AN USG LIKE PROBE IS PLACED ON THE SKIN OVER LIVER AREA IN THE MAL. PT FEELS A GENTLY
FLICK EACH TIME A VIBRATION IS GENERATED .
DURATION-10MIN
 FIBROSCAN
INTERPRETATION
A fibrosis score of F0 to F1 ( 2 to 7 kPa) means there is little or no scarring on the liver.
A fibrosis score of F2 (7.5 to 10 kPa) indicates moderate scarring that has spread outside the
liver.
A fibrosis score of F3 (10 to 14 kPa) indicates severe scarring which has spread and disrupts
normal blood flow.
A fibrosis score of F4 ( 14 kPa or higher) means late-stage scarring or cirrhosis, where the
scarring is permanent and the damage is irreversible.
USES OF FIBROSCAN
TO ESTIMATE DEGREE OF LIVER DAMAGE
MONITOR DISEASE PROGRESSION OR REGRESSION VIA SERIAL MEASUREMENTS
TO GUIDE PROGNOSIS AND FURTHER MANAGEMENT.
CONS OF FIBROSCAN
Over estimation of fibrosis which may be due to
Liver inflammation
Cholestasis
Mass in liver (e.g.tumour)
Liver congestion(e.g. heart failure)
 CAUSES FOR MICRO VS MACRO
VASCULAR STEATOSIS
MICRO VASCULAR STEATOSIS:- MACRO VASCULAR STEATOSIS:-

PRETTY VISITS JAMAICA WITH ALCOHOL AND

ACID

• PREGENANCY • CHRONIC VIRAL HEPATITIS(HCV)

• REYES SYNDROME • WILSONS DISEASE
• ECLAMPSIA • NASH
• TETRACYCLINE
• VALPROATE
• JAMAICAN SLEEPING SICKNESS
• ALC.
• ACID LIPASE DEF.
Not heavy drinker – who drink < 20gm/day for men – 2 drink
< 10gm/day for women – 1 drink
1 drink means 10 gm of ethanol, 1 can of beer, 4 ounce of wine , 1.5 ounce of distilled spirit
EPIDIMIOLOGY
Incidence 10-24% in general population
Mostly in 4th- 6th decade of life
More common in females
Very common in type 2 DM and metabolic syndrome
75% of type 2 DM have some form of NAFLD
2-3% of NASH present with cirrhosis
Risk factors
Obesity
Type 2 DM
dyslipidemia
Metabolic syndrome
Polycystic ovarian syndrome
Hypothyroidism
Hypopituitarism
Hypogonadism
OSA
PATHOGENESIS
Described by 2 hit hypothesis
First hit- dysregulation of fatty acid metabolism leads to steatosis
Second hit- oxidative stress
may be environmental / genetic factors
Hepatic steatosis
triglyceride synthesis > triglyceride disposal
 obesity
Obese adipose depots- release adipokines- inhibit insulin sensitivity
 reduced intestinal barrier function- release inflammatory mediators- inhibit insulin action
 hyperglycemia- hyperinsulinemia- lipid uptake, synthesis and storage
Oxidative stress
Precursors- fatty acids, diacylglycerols
Metabolic by products – ROS
Lipotoxicity
Inflammatory cytokines
Hepatocyte death
DIAGNOSIS
Incidental diagnosis- most asymptomatic
Hepatic steatosis by imaging or histology
No significant alcohol consumption
No coexisting causes for CLD
Biochemical test- LFT, FBS,FLP
CBC
Markers of fibrosis- high sensitivity CRP, plasma pentraxin 3, IL 6, cytokeratin 8,18
Liver biopsy
Imaging- USG, NCCT,MRI
Elastography- to assess liver fibrosis
MANAGEMENT
-THROUGH NON PHARM.

DIET
Targetted Wt Loss-7-10% Over 6mnth
Increased Pufa,omega 3 Fa Consumption(eg. Walnut,sunflower Seeds,fish,soybean Oil, Safflower
Oil,corn Oil.)
Caffeine Intake-2-3 Cups/Day-decerases Risk Of Fibrosis
Moderate Calorie Restriction By 500-700kcal And Reduce Wt Loss Of 7-10%. Improves
Histopatholgical Features Of Nash
Eliminate Or Reduce Sfa And High Fructose Corn Syrup Form Diet.Fructose Inceases Lipogenesis
Via Pyruvate Dehydrogenase And Transcriptional Activation Of Sterol Regulatory Elementbinding
Protein.
EXERCISE
REGULAR EXERCISE-150 HOURS MODERATE ACIVITY/WEEK OR 75HRS HIGH
INTENSITY/WEEK.IDEALLY 5 DAYS WORKOUT F/B 2 DAYS REST.
RESISTANCE TRAINING 3 TIMES /WEEK-IMPROVES INSULIN RESISTANCE,STEATOSIS
MANAGEMENT
-THROUGH PHARM.
VITAMIN-E -800-1000IU/DAY-IMPROVES NASH WHEN USED FOR 2YRS,NO IMROVEMENT IN
FIBROSIS
PIOGLITAZONE-30-45mg/DAY(PPAR GAMMA AGONIST)
◦ ADV.EFFECTS
◦ ARE BAD EFFECTS IN BONE
◦ INCREASED SALT AND H2O RETENTION
◦ BLADDER MALIGNANCY

PENTOXIPHYLLINE-NEEDS FURTHER STUDY

METFORMIN-NOT RECOMMENDED
REFERENCES
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229519/#!po=27.7778
https://www.racgp.org.au/afp/2013/july/fibroscan
Marrow
THANK YOU!