non aLCOHOLIC STEATO HEPATITIS

1. DR. Padma Lochan Prusty

2.  Fatty liver disease is the most common liver
disease in the world.
 About 25% of adults in the United States have
fatty livers in the absence of excessive alcohol
consumption, a condition termed nonalcoholic
fatty liver disease.
 More than a quarter of adults with non-
alcoholic fatty liver disease are presumed to
have nonalcoholic steatohepatitis on the basis
of elevated serum aminotransferase levels and
an absence of other identifiable causes of liver
injury.

3.  Macrovesicular fat accumulation in more than 5%
of hepatocytesis the defining feature of NAFLD.
The majority of patients with NAFLD have IFL,
which is defined as hepatic steatosis in the absence
of significant necroinflammation or fibrosis.
 Hepatocyte ballooning degeneration , lobular
inflammation of a mixed inflammatory cell
infiltrate and fibrosis predominantly perisinusoidal
and pericellular in acinar zone 3, although it may
extend to portal and periportal regions with disease
progression, are required to meet criteria for
NASH.

4. FATTY LIVER(STEATOSIS) NASH

6. NAFLD ACTIVITY SCORE
FIBROSIS
 no fibrosis [F0]
 portal fibrosis without
septa [F1],
 portal fibrosis with
few septa[F2]
 bridging septa
between central and
portal veins [F3]
 cirrhosis [F4]

7.  Nonalcoholic steatohepatitis is strongly associated
with overweight or obesity and the metabolic
syndrome.
 A recent analysis of studies involving more than 8.5
million persons from 22 countries showed that
more than 80% of patients with nonalcoholic
steatohepatitis are overweight or obese, 72% have
dyslipidemia, and 44% have received a diagnosis of
type 2 diabetes mellitus.
 Nonalcoholic steatohepatitis will most likely be the
top reason for liver transplantation in the United
States by 2020.

8.  Prevalence-(9-32%) varying from 44.1% in
western India to 72.4% in northern states.
 female (60%)> male(54.8%)
 It is mostly associated with obesity, T2DM.
 Prevalence increases with age i.e. aged 25-50
years (45.8%) , aged 51-60 years(54.2%) ; with
highest prevalence recorded in 61-70 year age
group, at 61.8%.
J Assoc Physicians India. 2013 Jul;61(7):448-53.

9.  Hepatic steatosis is the hallmark histologic feature of
NAFLD and is the net result of excessive accumulation of
free fatty acid (FFA).
 Fatty acid metabolism is under tight regulatory control by
catecholamines, glucagon, growth hormone, and insulin.
 Insulin resistance from excessive accumulation of FFA is
thought to be a primary factor in the development of
steatosis in most patients with NAFLD.

10.  Polymerphism in
petatin-like
phospholipase domain
containing 3(PNPLA3)
 PNPLA3 encodes
adiponeutrin
 Regulates triglyceride
and retinoid
metabolism
 polymorphisms in trans
membrane 6 superfamily,
member 2 (TM6SF2)
 TM6SF2 regulates
hepatocyte lipid
content.
 Increase in VLDL
secretion & risk of
cardiovascular disease

11. TM6SF2
11.2.
3.
4.
5.
6.

13.  Mostly asymptomatic (48%-100%)
 Sometimes associated with vague right upper
quadrant pain, fatigue,malaise.
 On examination most of the time there is only
hepatomegaly but some time associated with
 1) splenomegaly,
 2) ascites,
 3) features of hepato cellular failure.

14.  CBC
 LFT
 FBS, 2HR PPBS,HbA1C
 LIPID PROFILE
 USG OF ABDOMEN
 CT SCAN OF ABDOMEN
 FIBROSCAN
 MR ELASTOGRAPHY
 LIVER BIOPSY
 BIOMARKER-CYTOKERATIN-18,
PROCOLLAGEN3

15.  Age
 BMI
 IMPAIRED FASTING GLUCOSE(YES/NO)
 AST/ALT RATIO
 PLATELET COUNT
 ALBUMIN
 <-1.455-Advanced liver firosis
 -1.455 to 0.676 - intermediate

16.  Unidimensional vibration
controlled transient
elastography (VCTE) is a 10
minute, non-invasive,
painless procedure
experienced much like a
liver ultrasound.
 The technique measures
the stiffness in a cylindrical
volume 1 cm in diameter
and 4 cm in length,
amounting to about 1/500
of the entire liver volume –
100 times larger than the
volume of the liver biopsy
specimen.

20.  NON INVASIVE
 PAIN LESS
 TIME REQUIRED
10MIN.
 MORE VOL. OF
LIVER BEING
EXAMINED
 LESS INTER-
OBSERVER
VARIATION
 COST EFFECTIVE
 INVASIVE
 PAINFUL
 TIME REQUIRED
24HR
 VEEY LESS VOL. OF
LIVER BEING
EXAMINED
 MORE INTER-
OBSERVER
VARIATION
 COSTLY

21.  LIFE STYLE MODIFICATION
 TREATMENT OF COMORBID CONDITIONS
 MEDICAL TREATMENT
 BARIATRIC SURGERY
 LIVER TRANSPLANTATION

22.  Lose 7% of body weight if overweight or obese
 Limit consumption of fructose enriched
beverages.
 Limit consumption of alcohol(<1 drink/day for
women and <2 drink/day for men).
 Drink two or more cups of caffeinated coffee
daily.

23.  Dyslipidemia- statins are helpful
 Diabetes mellitus – strict glycemic control.
1) Metformin(first-line therapy)
2) consider early use of pioglitazone
3)consider GLP-1 analouge & SGLT-2 for wt loss
4)bariatric surgery on limited cases

24. Pharamacological
agents
Metabolic
stress
Inflammation Fibrosis
Vitamin E YES YES NO
PIOGLITAZONE YES YES YES
OBETICHOLIC ACID YES YES YES

25.  PPAR-ALPHA AND PPAR-GAMMA AGONIST
 GALECTIN 3
 BOVINE MILK COLOSTRUM
 FGF- 21

26.  Nonalcoholic steatohepatitis is a dynamic condition that can
regress to isolated steatosis, smolder at a relatively constant
level of activity, or cause progressive fibrosis that leads to
cirrhosis.
 NASH is strongly associated with visceral adiposity and the
metabolic syndrome.
 NAFLD is central to development of diabetes.
 Lifestyle management including diet and exercise should be
more aggressive, would help in prevention of diabetes.
 There is increasing medical therapy options (pioglitazone
,vitamin E) more drugs will come in practice soon.
 Bariatrics surgery needs to be judiciously applied.

27.  Deihl, Anna M., Christopher Day.,”Cause,
Pathogenesis And Treatment of nonalcoholic
steatohepatitis.”The New England Journal Of
Medicine 2017;377:2063-72