ALCOHOLIC LIVER DISEASE

1. ALCOHOLIC
LIVER
DISEASE

2. INTRoDUCT
→ Alcohol liver disease
→ 501. of mortality from all CIRRHOSIS
-
-
→
pathology
consists of ③ major lesions :
① Fatty Liver
@ Alcoholic Hepatitis
③ CIRRHOSIS -
→ FATTY
LIVER
-
:
present in > got .
of Bialy as well as
Binge
drinkers .
→ A smaller percentage of Heavy
drinkers progress
to
Alcoholic hepatitis
@o-2o
If
The Explanation for this apparent paradox
is
unclear but involves
factors such as drinking patter , D .
ob-ity-Ggendee.es
The mortality of patients with Alcoholic hepatitis concurrent with
CIRRHOSIS
is Goy.
at 4 Years .
→ There is no diagnostic test that can predict individual suggestibility to
- Alcoholic
disease .

3. ETI0L0aYEPATH0GEN
→
Qua E diva of alcohol intake are the
most important risk factors in development of disease
→
the ERK of Bozos type (
t
) 5
Peaty of drinking (Bialy vusus Binge
] are
less dear
→
Women are MOIL sucephble
to Alcoholicity
when compared to meng
t
They develop
advanced liver disease with substantially
less alcoholic .
→
Time taken to develop liver d At otoanksohmdd.
=
disease
→
one BEER
④ ounces of wine
① ounce of soy
.
spirit }contain ~
129M of alcohol

4. →
The threshold for developing Alcoholic liver disease
is higher in men
(> 14 drinks (week (2. drinks(day)
for WOMEN (37 drinks (week
(7-drink (das
))
→ 6¥ dependant dif¥s result from
a) poorly understood efkhi of estrogen
b) proportion of Dodiyfat
c) Gashicmtabolism
of Alcohol .
→
OBESTY
High fat did-
(Napa
) } are Risk factors
→ COFFEE → Protective effect .
→ MALNUTRITION →
Does not have a major
Role .

5. tCVEALCOhoLkUVERDlsEh
→
chronic
Hovind
play role in
progression
of Alcoholics
to cirrhosis
alcott
→
Even Light to moderate intake of 1523*1day
+
in Hou patients
Increase risk of CRR/ =
→
patient with both [Alcohol:c
liver
injury
t
infection
)
I
Develop decompensation
at
Foye
E have pi
overall survival
→ Increased Liver stores
PORPHYRIA
cutaneapa A }
cm as a consequence
of
ovalappinginju.io#pocss
Secondary to A
V
-
infection .

6. Pathom
→ The
pathogenesis is unclear
→
Alcohol acts as a direct
hepatoto-x.gl
Initials an
inflammatory
cascade by its metabolism
1
Resulting in Variety of Metabolic Responses .
-
-
STEATOSLS
' '
' acid
;÷÷÷÷÷! II.
'
i'
'
II:c..no .
F- ACTOR
Depression G
PPAR -
d peroxisome proliferator
[Activated Receptor - d )
→
Intestinal duivcd Endotoxin
d
initials pathogenic process through Toll ace Receptor 4 ,
G TNF -
N
I
facilitate Hepatocyte Apoptosis 9 Necrosis .

7. Cell Injury) Endotoxin
Release (alcohol Metabolites
÷
Acte
Innate Adaptive
Immunity pathways
to
Release proinflammatory cytokines (g : TNF -
d)
{ Cp!: II.on offers cells .
→ Ethanol ingestion
effcyh
on INTESTINAL
PERMEABILITY
V
influence hiposachav.de Hepatic influ#ICROBIOME
DYSBIOSIS
lipids
PROTEIN -
ALDEHYDE
Adducts
→
production of toxic
qq.gg?;;gfsRg.gggcirgeoivaknb/P?Ea
→
Hepatocyte injury G Impaired Regeneration
from chronic Alcohol ingestion
I
STELLATE CELL ACTIVATION G COLLAGEN PRODUCTION
H
FIBRO GENESIS

8. -
-
-
-8
-
E
-
a -

9. Pattu
→ FATTY LIVER (STENOSIS
) : is the initial f most common
-
histologic response
to HEPATOT
oxic
stimuli
(Not only Alcohol
)
→
Accumulation of FAT within the PERNENULAR
HEPATOCYTES
I
coincide with location of ALCOHOL
DEHYDROGENASE
(major enzyme
for Alcohol metabolism)
→
CONTINUING Alcohol ingestion
- -
-
d
Results in FAT accumulation throughout entities
- LOBULE
-
→ DESPITE ,
Extensive fatty change E distortion of hepatocytes with
-
-
-
Macrovcsiadaefaty ( MACRI
)
t
cessation of drinking results in Normalization of Hepatic
Architecture
{ FAT CONTENT .

10. →
presence of GIANT MITOCHONDRIA
PERNENULAR
FIBROSIS
MACROvesicular ra
, }
associated with
Progressive
liver
-
-
.
→
Fatty liver -
Alcohol Hepatitis
(transition
is
)
HALLMARK OF ALCOHOLIC
HEPATITIS !
-
BALLOONING
DEGENERATION
{ ::÷:::c::# in .am
.ie
FIBROSIS in Paivcnulae
Pa: sinusoidal space
of Disse
MALLORY DENK BODIES !
Nfo!fmµ%aey to establish the
→ # .
=
diagnosis
→ Like Fatty liver →
Alcoholic Hepatitis is
potentially
reversible
with czssaylionofsmokng
.
→ ALCOHOL HEPATITIS - precursor for CIRRHOSIS .
→ CIRRHOSIS is present in
,
set of patients with Biopsyprovcnfegkohaf.li
and its is UNCERTAIN ,
even with Alcohol ABSTINENCE .

11. CLINICAL FEATURES
-
FATTER
→ SUBTLE as detected
incidentally
→
HEPATOMEGALY -
only clinical finding
→
occasionally patients with fatty liver present
with
RUQ discomfort
Nausea, vomiting
Rarely jaundice .
→ Differentiation of Alcoholic fatty live from Non-alcoholic
fatty liver is diff.cat/-s PROPER Drinking History
will
help .
ALCOh02lGHEPATIt
→ Asymptomatic to wide gamut of clinical features
→ Fever
spider Nevi
Abdominal pain
.
}
-
Jaundice

12. LABORATORYFEATUREQFATTYL.tv
→ Non specific Abnormalities
→
Moderate elevation is AST .
ALT
,
f - GAT
→ T Triglycerides
T Sr - Bilirubin .
ALcoHOLHEPAT€T
① ASJIALT
→ Two -
SEVENFOLD
elevated
Rarely > 40010
• >
Ifta:&,
@ → sis
)
③ T
sr-
Bilirubin (standard - > Fylde)
① Moderato f of s.
-
ALP
→ Hypoalbuminuria
and coagulopathyf.sn/helicfunchonD-sfI7amncnedi7.iuu
injury
-
USG helpful in
- detecting fatty infiltration of LIVER g
determining LIVER SIZE -

14. Prognosis
→ Critically ill patients with Alcoholic Hepatitis have
short turn ( so day) mortality
rates 3504
→ SEVERE
ALCOHOLIC
HEPATITIS
'
.
-
Coagulopalh ( WR - > I - 5)
y
-
Anemia
Sr .
Albumin (s 2- 5gm/de)
-
Sr . Bilirubin (28mg/dl
)
Renal failure
ASCITES .
MADDres Disarm want
Fun If I ¥3, }I÷÷f÷j!n
Alcoholic
| Hepatitis
✓
§.
G X
(PT of control - PT of teh
) t Sr - Bilirubin .
]
presence
of
A
,
}
ES
}
predicts Bad prognosis
.
Varied Hemorrhage
Deep Encephalopathy

15. TREATMENT
-
-
ABSTINENCE
from Alcohol → Improves
survival
→ COMPLETE ↳ perusal of Histologic
←
injury
-
→ Alcohol deaddiction
→ NUTRITION
corticosteroid
→ pathogenic
mechanisms
involve cytokine
Release
✓ q perpetuation of injury by immuno
!°§%sscs.
DF → 232
me. .→
. }
- si"
÷:c:÷::÷7ggxqw.
Hb
Tapering
-
CONTRAINDICATION
for sheoids -
-
→
Active g.
i
bleeding
→ Renal failure }
→
Pancreatitis .
patients c- infection concurrently treated with ANTIBIOTCSS STEROIDS
→ patients with Encephalopathy from severe Alcoholic Hepatitis are good
candidates for glucocorticoids.

16. LIVE.SC/0R# →
20.452
for STEROID RESPONSE
USES pretreatment vairabhs pI change in
Total Bilirubin of Day 7
I
of glucocorticoids
No change in
Bilirubin →
patient is uc#u
to
=
therapy E Stop STEROIDS
=
continuing
STEROIDS after ①days
→
poor PROGNOSIS
in unresponsive patients
PENTONFYVINQ.in pathogenesis
has made
→ Role of TNR -
a expression
PENTON FYLLINE (NON SPECIFIC
TNF INHIBITOR
]
either by itself Ca) with glucocorticoids for seven AH .
Improved
survival mainly due to decrease
In one
study ,
it demonstrated in HRs
1
Subsequent trails failed to find increased benefit from PENTOXIFIELUNE .

17. LIVE.RTRANSPLANTATIOX-SI.in
Selected patrons,
as RECNIDBM nato is high
→
Following transplantation ,
outcome is very good -