Alcoholic liver disease is a result of over-consuming alcohol that damages the liver, leading to a buildup of fats, inflammation, and scarring. It can be fatal.

1. Alcoholic liver diseases
Dr. ZEEL NAIK

2. Introduction
• Chronic and excessive alcohol ingestion is one of
the major causes of liver disease
• The pathology of alcoholic liver disease
comprises three major lesions:
(1) fatty liver
(2) alcoholic hepatitis
(3) cirrhosis

4. RISK FACTORS FOR ALCOHOLIC LIVER
DISEASE
• Drinking patterns
• Gender
• Malnutrition
• Infections
• Genetic factors
• Hepatitis C infection

5. PATHOGENESIS
1. Direct hepatotoxicity by ethanol
2. Hepatotoxicity by ethanol metabolites
i) Production of protein-aldehyde adducts
ii) Formation of malon-di-aldehyde-
acetaldehyde (MAA) adduct

6. PATHOGENESIS
3. Oxidative stress
4. Immunological mechanism
5. Inflammation
6. Fibrogenesis

7. PATHOGENESIS
7. Increased redox ratio
8. Retention of liver cell water and proteins
9. Hypoxia
10. Increased liver fat

10. Fatty Liver

13. Cirrhosis

18. Alcohol Withdrawal
• Many pharmacological agents have been used for
treatment of AUD including disulfiram,
acamprosate, gabapentin, naltrexone,
topiramate, sertraline, and baclofen
• Of these, only baclofen, a γ -amino butyric acid-B
receptor agonist has been found to be safe in
patients with ALD and cirrhosis
• Its efficacy is shown with increase in abstinence
rates

19. Alcohol Withdrawal
• Baclofen can be started in a dose of 5 mg three
times a day and the dose can be increased at a 3–
5 days interval based on patient tolerance to a
maximum dose of 15 mg three times a day
• Considering its excellent safety profile, even
among patients with advanced liver disease and
AH, patients on baclofen therapy can be
monitored by hepatologists or addiction
specialists

20. Management of alcohol withdrawal
• AWS is a common condition affecting alcohol-
dependent patients who abruptly discontinue or
markedly decrease alcohol consumption
• Light or moderate AWS usually develops within
6–24 h after the last drink and symptoms may
include nausea/vomiting, hypertension,
tachycardia, tremors, hyperreflexia, irritability,
anxiety, and headache.

21. Management of alcohol withdrawal
• These symptoms may progress to more severe
forms of AWS, characterized by delirium
tremens, generalized seizures, coma, and even
cardiac arrest and death
• Older patients are at greater risk for delirium
tremens

22. Management of alcohol withdrawal
• Patients with moderate or severe alcohol withdrawal
should be closely monitored in an intensive care unit
(ICU), where vital signs, volume status, and
neurological function are monitored on a regular basis
• Severity scores for AWS such as the Clinical Institute
Withdrawal Assessment for Alcohol score are useful in
the management of patients, although they have not
been validated in patients with severe ALD and a
symptom-triggered approach is preferred

23. Management of alcohol withdrawal
• Benzodiazepines are the most commonly used
drugs to treat AWS
• Long-acting benzodiazepines (e.g., diazepam
and chlordiazepoxide) predominantly protect
against seizures and delirium; short and
intermediate-acting benzodiazepines (e.g.,
lorazepam and oxazepam) are safer for
patients with poor liver function.

24. Management of alcohol withdrawal
• Patients with AWS and concomitant hepatic
encephalopathy should be treated for both
the conditions
• Of note, high-dose benzodiazepines may
precipitate and worsen hepatic
encephalopathy; thus, careful monitoring and
titration is critical for optimal outcomes

25. Management of alcohol withdrawal
• Given the side effects of benzodiazepines in
patients with advanced liver disease and the
potential for abuse in an addictive population,
other drugs such as baclofen, clonidine,
gabapentin, and topiramate have been
proposed to treat AWS in patients with ALD
including alcoholic cirrhosis

26. Nutshell
• A promising approach is to use baclofen to
prevent and treat moderate AWS first, and
continue the medication to prevent alcohol
relapse

27. Alcoholic cirrhosis
• Patients with alcoholic cirrhosis should be
screened for varices with upper
gastrointestinal endoscopy
• These patients are also at an increased risk of
developing HCC, with a life-time risk of about
3–10% and an annual risk of about 1%

28. Alcoholic cirrhosis
• Obesity and cigarette smoking are risk factors for
HCC in patients with alcoholic cirrhosis
• Patients with alcoholic cirrhosis should undergo
screening with ultrasound examination with or
without α –fetoprotein testing every 6 months for
HCC
• Immunization against hepatitis A and B,
pneumococcal pneumonia and influenza is also
recommended

29. Ascites

30. Ascites

31. Water restriction
• Most experts agree that there is no role for
water restriction in patients with
uncomplicated ascites
• However, water restriction for patients with
ascites and hyponatraemia has become
standard clinical practice in many centres

32. Water restriction
• Most hepatologists treat these patients with
severe water restriction
• However, based on pathogenesis of
hyponatraemia, this treatment is probably
illogical and may exacerbate the severity of
effective central hypovolaemia that drives the
non-osmotic secretion of antidiuretic
hormone (ADH).

33. Water restriction
• This may result in further increases i
circulating ADH, and a further decline of renal
function
• Impaired free water clearance is observed in
25–60% of patients with ascites due to
cirrhosis, and many develop spontaneous
hyponatraemia

34. Serum sodium >126 mmol/l
• For patients with ascites who have a serum
sodium >126 mmol/l, there should be no
water restriction, and diuretics can be safely
continued, providing that renal function is not
deteriorating or has not significantly
deteriorated during diuretic therapy

35. Serum sodium less than 25 mmol/l
• All experts in the field recommend stopping
diuretics if serum sodium is (120 mmol/l. If
there is a significant increase in serum
creatinine or serum creatinine is 150 mmol/l,
• Use volume expansion. Gelofusine,
haemaccel, and 4.5% albumin solutions
contain sodium concentrations equivalent to
normal saline (154 mmol/l).

36. Serum sodium less than 25 mmol/l
• This will worsen their salt retention but we
take the view that it is better to have ascites
with normal renal function than to develop
potentially irreversible renal failure.

37. Diuretics - Spironolactone
• Spironolactone is the drug of choice in th
initial treatment of ascites due to cirrhosis
• The initial daily dose of 100 mg may have to
be progressively increased up to 400 mg to
achieve adequate natriuresis. There is a lag of
3–5 days between the beginning of
spironolactone treatment and the onset of the
natriuretic effect

38. Diuretics - Spironolactone
• Controlled studies have found that
spironolactone achieves a better natriuresis and
diuresis than a ‘‘loop diuretic’’ such as frusemide
• Most frequent side effects of spironolactone in
cirrhotics are those related to its antiandrogenic
activity, such as decreased libido, impotence, and
gynaecomastia in men and menstrual irregularity
in women (although most women with ascites do
not menstruate anyway).

39. Diuretics - Spironolactone
• Gynaecomastia can be significantly reduced when
the hydrophilic derivative potassium canrenoate
is used
• Tamoxifen at a dose 20 mg twice a day has been
shown to be useful in the management of
gynaecomastia
• Hyperkalaemia is a significant complication that
frequently limits the use of spironolactone in the
treatment of ascites.

40. Diuretics - Frusemide
• Frusemide is a loop diuretic which causes
marked natriuresis and diuresis in normal
subjects. It is generally used as an adjunct to
spironolactone treatment because of its low
efficacy when used alone in cirrhosis
• The initial dose of frusemide is 40 mg/day and
it is generally increased every 2– 3 days up to
a dose not exceeding 160 mg/day.

41. Diuretics - Frusemide
• High doses of frusemide are associated with
severe electrolyte disturbance and metabolic
alkalosis, and should be used cautiously.
• Simultaneous administration of frusemide and
spironolactone increases the natriuretic effect

42. Practice Points
• Generally, a ‘‘stepped care’’ approach is used
in the management of ascites starting with
modest dietary salt restriction, together with
an increasing dose of spironolactone.
• Frusemide is only added when 400 mg of
spironolactone alone has proved ineffective.

43. Therapeutic paracentesis
• Patients with large or refractory ascites are
usually initially managed by repeated large
volume paracentesis
• Several controlled clinical studies have
demonstrated that large volume paracentesis
with colloid replacement is rapid, safe, and
effective

44. Therapeutic paracentesis
• The first study demonstrated that serial large
volume paracentesis (4–6 l/day) with albumin
infusion (8 g/litre of ascites removed) was
more effective and was associated with fewer
complications and shorter duration of
hospitalisation compared with diuretic
therapy

45. Therapeutic paracentesis
• Following paracentesis, ascites recurs in the
majority (93%) if diuretic therapy is not
reinstituted, but recurs in only 18% of patients
treated with spironolactone
• Reintroduction of diuretics after paracentesis
(usually within 1–2 days) does not appear to
increase the risk of postparacentesis
circulatory dysfunction

46. SPONTANEOUS BACTERIAL
PERITONITIS
• Spontaneous bacterial peritonitis (SBP) is th
development of a monomicrobial infection of
ascites in the absence of a contiguous source
of infection
• SBP is a frequent and serious complication of
cirrhotic patients with ascites. The prevalence
of SBP in cirrhotic hospitalised patients with
ascites ranges between 10% and 30%.

47. Diagnosis
• Patients with SBP are frequently asymptomatic
• However, a significant proportion have some
symptoms such as fever, mild abdominal pain,
vomiting, or confusion.
• Diagnosis should also be suspected in those who
present with hepatic encephalopathy,
impairment of renal function, or peripheral
leucocytosis without any obvious precipitating
factors

48. Ascitic fluid analysis
• The diagnosis of SBP is confirmed when ascitic
neutrophil count is 250 cells/mm3
(0.256109/l) in the absence of an intra-
abdominal and surgically treatable source of
sepsis

49. Antibiotics
• The commonest organisms isolated in patients
with SBP include Escherichia coli, gram
positive cocci (mainly streptococcus species)
and enterococci.
• These organisms account for approximately
70% of all cases of SBP

50. Antibiotics
• Cefotaxime has been the most extensively
investigated in patients with SBP because it
covers 95% of the flora isolated from ascitic
fluid and achieves high ascitic fluid
concentrations during therapy

51. Antibiotics
• Five days of treatment with cefotaxime is as
effective as 10 day therapy,143 and low dose (2 g
twice daily) is similar in efficacy to the higher
doses (2 g four times daily)
• Other cephalosporins, such as ceftriaxone and
ceftazidime as well as co-amoxiclav (amoxicillin
plus clavulanic acid), have been shown to be as
effective as cefotaxime in resolving SBP

52. Antibiotics
• In patients who are ‘‘well’’ (asymptomatic),
with bowel sounds, SBP can be treated with
oral antibiotics
• Under these circumstances either oral
ciprofloxacin (750 mg twice daily) or oral co-
amoxiclav (1000/200 mg amoxicillin/clavulanic
acid three times daily), subject to renal
function, is logical

53. Antibiotics Treatment Failure
• A reduction in ascitic fluid neutrophil count of
less than 25% of the pretreatment value after
two days of antibiotic treatment suggests failure
to respond to therapy
• This should raise the suspicion of ‘‘secondary
peritonitis’’ (secondary to perforation or
inflammation of intra-abdominal organs) and
indicate further evaluation or modification of
antibiotic treatment according to in vitro
sensitivity or on an empiric basis

54. Antibiotics Treatment Failure
• Mutiple Microbial Organism involvment
• Although algorithms, including estimation of
ascetic fluid protein, glucose, lactate
dehydrogenase, carcinoembryonic antigen,
and alkaline phosphatase levels have been
proposed to distinguish ‘‘secondary
peritonitis’’ from SBP

55. Hepatic encephalopathy
• Precipittaing Factors:
• The leading causes are gastrointestinal bleeding,
sepsis and dehydration resulting from diuretics,
diarrhoea or vomiting
• Also important are hyponatraemia, surgical
intervention, constipation and the use of sedative
and narcotic drugs.
• Another important cause in patients with prior
OHE is non-adherence to medications

56. Hepatic encephalopathy
• Cerebral damage, malnutrition, and infections
among patients with alcohol-related cirrhosis and
continued alcohol use may lower the threshold in
development of hepatic encephalopathy
• However, other causes of altered mental status
should be screened for, especially among patients
who present with atypical neuro-psychiatric
features that warrant questioning the diagnosis
of hepatic encephalopathy or AWS.

57. Hepatic encephalopathy
• For example, seizures, focal neurological
deficits, severe headache, and
encephalopathy refractory to all measures
should point towards an alternate cause for
altered consciousness such as stroke, subdural
hematoma, drug overdose, meningitis, and
fungal infections of the central nervous system

58. Hepatic encephalopathy
• Lactulose is a non-absorbable disaccharide
that is fermented in the colon
• The exact mechanism of action remains
unclear; however, acidification of colonic
contents and mass evacuation of bacteria
have been proposed

59. Hepatic encephalopathy
• Lactulose should be given in enema form in
patients with stage 3 or higher OHE, and orally if
the patient is able to tolerate it through that
route
• Lactulose enemas are mixed with water and
specifically aid in patients with poor stool output
• Adverse effects of lactulose range from minor
gastroenterological issues with nausea, vomiting
and diarrhoea to severe dehydration,
hypernatraemia and ileus

60. Hepatic encephalopathy
• Initial lactulose dosing is 30 mL orally, daily or
twice daily
• The dose may be increased as tolerated. Patients
should be instructed to reduc lactulose dosing in
the event of diarrhea, abdominal cramping, or
bloating
• Patients should take sufficient lactulose as to
have 2-4 loose stools per day

61. Hepatic encephalopathy
• Rifaximin is a non-absorbable antibiotic that
has been used to treat HE in several European
countries.
• It has a favourable impact and the Cochrane
review recommends the use of non-
absorbable antibiotics.

62. Hepatic encephalopathy
• It is currently available in 200 mg form, which
is given up to 1200 mg⁄ day
• Use of rifaximin is slowly becoming
mainstream and is well tolerated. The drug
expense remains a concern, although a recent
study noted the reduced hospitalization rates
after rifaximin therapy compared with that of
lactulose

64. Hepatic encephalopathy
• A recent trial showed that rifaximin 550 mg
BID along with lactulose was significantly
more effective than lactulose alone in the
prevention of HE episodes in patients who had
had two or more HE episodes in the past 6
months
• The safety profile was good in this large trial

65. Hepatic encephalopathy
• There is no significant role of neomycin,
flumazenil, metronidazole and zinc as stand-alone
therapies for HE.
• There are several other drugs in the pipeline for
HE that are undergoing trials in the US
• Other drugs that have been used outside the US
are L-ornithine-L-aspartate infusion and oral
forms, acetylcarnitine and acarbose.

66. Corticosteroids
• A meta-analysis of randomized studies
(including the STOPAH study) showed that
corticosteroids were effective in reducing
short-term mortality by 46%.

67. Corticosteroids
• Prednisolone is preferred over prednisone, as
the latter requires conversion to prednisolone,
which may be impaired in patients with
impaired liver synthetic function
• Moreover, prednisone did not improve patient
survival in a randomized clinical trial

68. Corticosteroids
• Prednisolone is used in a dose of 40 mg per
day for a total duration of 4 weeks
• Methylprednisolone 32 mg per day by
intravenous route is used for patient unable to
take oral medications.
• There are no studies examining different
doses and durations of corticosteroid therapy

69. Corticosteroids
• Active hepatitis B virus infection and active
tuberculosis are contraindications for use of
corticosteroids ( 99 ).
• Although HCV infection may potentially
worsen the outcome of AH patients ( 30,100–
102 ), there are no data on whether 4 weeks
of corticosteroid therapy will increase HCV
replication or that HCV infection worsens the
response to corticosteroids.

70. Corticosteroids
• Active infection or sepsis, uncontrolled
diabetes mellitus, and gastrointestinal
bleeding remain relative contraindications to
the use of corticosteroids.
• In these situations, corticosteroids can be
used once the contraindication has been
reversed with appropriate therapy.

71. Pentoxifylline
• A phosphodiesterase inhibitor, pentoxifylline
inhibits tumor necrosis factor-α activity, one
of the major cytokines speculated in the
pathogenesis of AH ( 107,108 )
• As the first seminal study on the benefit of
pentoxifylline used as 400 mg 3 times a day

72. Pentoxifylline
• Pentoxifylline has consistently shown benefit
in reducing the risk of renal injury and deaths
from hepatorenal syndrome ( 109,114 ).
• Although pentoxifylline is known to inhibit
tumor necrosis factor, levels of tumor necrosis
factor did not change with pentoxifylline (PTX)
in the reported seminal study

73. Pentoxifylline
• Pentoxifylline compared with corticosteroids
showed benefit in one study ( 115 ) and no
difference in another study

74. Pentoxifylline
• Contraindications Hypersensitivity to
pentoxifylline or xanthine derivatives
• Recent retinal or cerebral hemorrhage

75. Other Researches
• Tumor necrosis factor-α inhibitors .
• Based on pre-clinical efficacy and beneficial effects in
open label pilot studies ( 122–125 ), trials examining
infliximab and etanercept in the management of
severe AH had to be terminated prematurely due to
higher number of deaths in the treatment arm, with
most deaths due to infections ( 126,127).
• Th e mechanisms of these findings are speculated to be
due to blocking the beneficial effects of tumor necrosis
factor on hepatic regeneration

76. Antioxidants
• Oxidative stress is a major player in the
pathogenesis of ALD and AH ( 129
• Antioxidant cocktails and vitamin E examined
earlier have not shown beneficial effects in
the management of severe AH

77. Antioxidants
• A network meta-analysis comparing various
pharmacological agents showed moderate quality
evidence that combination of prednisolone and N
-acetylcysteine provides best survival benefi t at
28 days with 85% risk reduction of death from AH
( 121 )
• However, more data on the effi cacy of N
acetylcysteine in severe AH patients are needed
before recommending its routine use in practice

78. Miscellaneous drugs
• Recently, the use of growth factors with
granulocyte colony stimulating factor and
erythropoietin have shown encouraging data
in improving liver disease, reducing infectious
complications, and patient survival

79. Portal HTN
• Portal hypertension is a frequent clinical
syndrome that is defined by an increase in
portosystemic pressure gradient in any
portion of the portal venous system.

81. Portal HTN
• Although portal hypertension can result from pre-
hepatic abnormalities (e.g. portal or splenic vein
thrombosis), post-hepatic abnormalities (e.g.
Budd-Chiari syndrome) or intrahepatic non-
cirrhotic causes (e.g. schistosomiasis, sinusoidal
obstruction syndrome)
• Cirrhosis is by far the most common cause of
portal hypertension and, as such, has been the
most widely investigated

82. Portal HTN
• A normal HVPG is 3-5 mmHg
• An HVPG above 5 mmHg defines portal
hypertension

83. Portal HTN
• When HVPG reaches 10 mmHg or above the
patient with cirrhosis is at a higher risk of
developing varices , clinical decompensation (i.e.
development of ascites, variceal hemorrhage and
hepatic encephalopathy and hepatocellular
carcinoma
• Therefore, a HVPG equal or above 10 mmHg has
been designated “clinically significant portal
hypertension” (CSPH).

84. Portal HTN
• The complications that directly result from
portal hypertension are the development of
varices and variceal hemorrhage.

86. Compensated patients without clinically-
significant portal hypertension (CSPH)
• Patients with an HVPG >5 but lower than 10
mmHg have cirrhosis but do not have CSPH.
• The goal of therapy in these patients is to
prevent the development of CSPH.

87. Compensated patients without clinically-
significant portal hypertension (CSPH)
• Since these patients have not yet reached the
threshold portal pressure that predicts
development of complications (varices,
decompensation), therapy has to be directed
towards the etiology of cirrhosis and/or to
antifibrogenic therapies

88. Compensated patients without clinically-
significant portal hypertension (CSPH)
• Life-style modification (diet and exercise that
has been shown to decrease HVPG in
overweight or obese cirrhotics) and alcohol
abstinence, as obesity and superimposed
alcohol-induced liver damage can facilitate
progression of disease.

89. Compensated patients without clinically-
significant portal hypertension (CSPH)
• Statins may have a benefit in cirrhosis of
any etiology as they may decrease
fibrogenesis, improve liver
microcirculation and decrease portal
pressure in cirrhosis and may also
facilitate hepatitis C viral suppression

90. Statins and liver disease: from
concern to 'wonder' drugs?
• The benefits of statins go beyond decreasing
cholesterol levels; in liver disease, statins reduce
the risk of progressive liver fibrosis and provide
protection during infections and ischaemia–
reperfusion injury
• New evidence shows that statins improve
response to interferon-based anti-HCV therapy,
decrease progression to cirrhosis and likelihood
of developing hepatocellular carcinoma.

91. Compensated patients with CSPH but
without varices
• CSPH is defined as HVPG≥10 mmHg
• An increase in portal pressure to this level is a
hallmark of advanced compensated chronic
liver disease, as it heralds the development of
varices , decompensation (variceal
haemorrhage, ascites and encephalopathy) ,
as well as hepatocellular carcinoma and
predicts poor outcomes with liver resection

92. Compensated patients with CSPH but
without varices - Management
• mainstay of treatment is to correct the etiologic
factor (whenever possible) and associated
aggravating conditions (obesity, alcohol intake),
and the use of statins and/or drugs that will have
an effect on intrahepatic resistance
• A large multicenter placebocontrolled study is
being conducted in Spain to examine if
decreasing HVPG by means of
propranolol/carvedilol can prevent
decompensation in these patients

93. Compensated patients with
gastroesophageal varices
• Size of varices, red wale signs on varices and severity of
liver disease (Child class C) identify patients at the
highest risk of variceal hemorrhage
• Therefore, within this stage, patients need to be
stratified by the risk of hemorrhage into a) high-risk
patients, i.e. those with medium/large varices or those
with small varices that have red signs or occur in a
Child C patient, and b) low risk patients, i.e. those with
small varices without red signs or occurring in a Child A
or B patient.

94. Patients with medium/large varices
• in the prevention of first variceal hemorrhage
in these patients either NSBB (propranolol,
nadolol) or EVL can be used and the choice of
treatment should be based on local resources
and expertise, patient preference and
characteristics, contra-indications and adverse
events

95. Patients with medium/large varices
• Based on two trials that compare EVL to
carvedilol (a NSBB with vasodilatory effect due
to intrinsic anti-a1 adrenergic activity) and
that show either a greater efficacy of
carvedilol or comparable efficacy , carvedilol
was added to the list of NSBB that can be used
in this setting

96. Patients with medium/large varices
• Advantages of NSBB include low cost, ease of
administration and not requiring specific
expertise
• As they act by decreasing portal pressure,
NSBB may also reduce the development of
ascites and decompensation

97. Patients with medium/large varices
• Disadvantages are that approximately 15% of
patients may have absolute or relative
contraindications to therapy and another 15%
require dose-reduction or discontinuation due
to its common side-effects (e.g. fatigue,
weakness, shortness of breath) that resolve
upon discontinuation but may discourage
patients from using these drugs

98. Patients with medium/large varices
• Patients who are intolerant to propranolol or
nadolol could be switched to carvedilol (not
recommended in those with refractory
ascites) or to EVL

99. Patients with medium/large varices
• Advantages of EVL are that it can be done at the
same time as screening endoscopy and has few
contraindications. The risks are those of conscious
sedation plus the risk of causing esophageal
ulcerations and bleeding.
• Although the quantity of side-effects is greater with
NSBB than with EVL, the severity of side-effects is
greater with EVL with several reports of deaths
resulting from EVL-induced bleeding ulcers.
Importantly, as this is a local therapy it is unlikely to
have a role in preventing other decompensating
events.

100. Patients with high-risk small varices
(red wale marks and/or occurring in a
Child C Patients)
• Treatment is NSBBs because technically
performing EVL in these varices may be
challenging (although there is no clear
evidence for this).

101. Patients with small varices without
signs of increased risk
• There is limited evidence showing that their
growth may be slowed by the use of NSBB to
prevent bleeding but further studies are
required to confirm their benefit. Therefore,
the use of NSBB in this setting is considered
optional and should be discussed with the
patient.

102. Patients presenting with acute
variceal haemorrhage
• In these patients the goal of therapy is to control
acute hemorrhage and to prevent its early
recurrence (within 5 days) and death.
• Per the recent Baveno conference, the main
treatment outcome in acute variceal hemorrhage
should be six-week mortality. Child-Pugh class C,
the recalibrated MELD score, and failure to
achieve primary hemostasis are the variables
most consistently found to predict 6-week
mortality

103. Patients presenting with acute
variceal haemorrhage
• Acute variceal hemorrhage is a medical
emergency requiring intensive care
• The basic medical principles of airway, breathing
and circulation are followed to achieve
hemodynamic stability.
• The goal of this resuscitation is to preserve tissue
perfusion. Volume restitution should be initiated
to restore and maintain hemodynami stability.

104. Patients presenting with acute
variceal haemorrhage
• Packed red blood cell transfusion should be
done conservatively for a target hemoglobin
level between 7-8 g/dL because a more liberal
transfusion strategy (i.e transfusing for a
target hemoglobin of 9-11 g/dL) has been
shown in a RCT to be associated with
increased mortality and a significant increase
in HVPG

105. Patients presenting with acute
variceal haemorrhage
• Patients with gastrointestinal hemorrhage are
at a high risk of developing bacterial infections
and it has been shown that antibiotic
prophylaxis in this setting leads to a decrease,
not only in the development of infections, but
also of early recurrence of hemorrhage and
death

106. Patients presenting with acute
variceal haemorrhage
• The specific antibiotic recommended should
be based on individual patient risk
characteristics and local antimicrobial
susceptibility patterns, with ceftriaxone
(1g/24 h) being the first choice in patients
with advanced cirrhosis, in those on quinolone
prophylaxis and in hospital settings with high
prevalence of quinolone-resistant bacterial
infections

107. Patients presenting with acute
variceal haemorrhage
• Safe vasoactive drugs should be started as soon
as possible, together with antibiotics, and
• prior to diagnostic endoscopy. All vasoactive
drugs used in the control of acute hemorrhage
are
• used in intravenous infusion (Table 3) and overall,
their use is associated to a significant effect
• on control of hemorrhage but also a significant
reduction in mortality

108. Patients presenting with acute
variceal haemorrhage
• A recent study comparing the three most
utilized worldwide (somatostatin, octreotide,
terlipressin) found no significant differences
among them
• Octreotide is the only vasoactive drug
available in the U.S. and in a meta-analysis of
11 trials was shown to significantly improve
control of acute hemorrhage

109. Patients presenting with acute
variceal haemorrhage
• Endoscopy is done as soon as possible and not
more than 12 hours after presentation
• If a variceal source is confirmed, EVL should be
performed

110. Patients presenting with acute
variceal haemorrhage
• others should continue standard therapy with vasoactive drugs
continued for up to 5 days depending on control of bleeding and
severity of liver disease.
• Vasoactive drugs can be discontinued once the patient has been
free of bleeding for at least 24 hours at which timethe patient
should be started on secondary prophylaxis.
• Persistent bleeding or severe rebleeding despite combined
pharmacological and endoscopic therapy is best managed by PTFE-
covered TIPS.
• If rebleeding is modest, a second session of endoscopy therapy can
be attempted.

117. Thiamine Deficiency
• Alcohol consumption can damage the brain
through numerous mechanisms
• One of these mechanisms involves the
reduced availability of an essential nutrient,
thiamine, to the brain as a consequence of
chronic alcohol consumption

118. Thiamine Deficiency
• A daily intake of 1.1 mg thiamine is currently
recommended for adult women and 1.2 mg
for adult men.
• Lower levels are recommended for children,
and slightly higher levels [1.4 mg thiamine per
day] are recommended for pregnant and
breast–feeding women.

119. Thiamine Deficiency
• In the body, particularly high concentrations of
thiamine are found in skeletal muscles and in the
heart, liver, kidney, and brain (Singleton and
Martin 2001)
• In the tissues, thiamine is required for the
assembly and proper functioning of several
enzymes that are important for the breakdown,
or metabolism, of sugar molecules into other
types of molecules (i.e., in carbohydrate
catabolism).

120. Thiamine Deficiency
• Proper functioning of these thiamine–using
enzymes is required for numerous critical
biochemical reactions in the body, including
the synthesis of certain brain chemicals (i.e.,
neurotransmitters); production of the
molecules making up the cells’ genetic
material (i.e., nucleic acids); and production of
fatty acids, steroids, and certain complex
sugar molecules.

121. Thiamine Deficiency
• The cells of the nervous system and heart
seem particularly sensitive to the effects of
thiamine deficiency.
• Therefore, the resulting impairment in the
functioning of the thiamine–using enzymes
primarily affects the cardiovascular and
nervous systems.

122. Thiamine Deficiency
• In the brain, thiamine is required both by the
nerve cells (i.e., neurons) and by other supporting
cells in the nervous system (i.e., glia cells)
• Thiamine deficiency is the established cause of an
alcohol–linked neurological disorder known as
Wernicke–Korsakoff syndrome (WKS), but it also
contributes significantly to other forms of
alcohol–induced brain injury, such as various
degrees of cognitive impairment

123. Wernicke’s Encephalopathy and
Korsakoff’s Psychosis
• WKS typically consists of two components, a
short–lived and severe condition called
Wernicke’s encephalopathy (WE) and a long–
lasting and debilitating condition known as
Korsakoff’s psychosis
• WE is an acute life–threatening neurologic
disorder caused by thiamine deficiency. In
affluent countries, where people normally receive
adequate thiamine from their diets, thiamine
deficiency is most commonly caused by
alcoholism

124. Wernicke’s Encephalopathy and
Korsakoff’s Psychosis
• The symptoms of WE include mental
confusion, paralysis of the nerves that move
the eyes (i.e., oculomotor disturbances), and
an impaired ability to coordinate movements,
particularly of the lower extremities (i.e.,
ataxia)

125. Wernicke’s Encephalopathy and
Korsakoff’s Psychosis
• Approximately 80 to 90 percent of alcoholics with
WE develop Korsakoff’s psychosis, a chronic
neuropsychiatric syndrome characterized by
behavioral abnormalities and memory
impairments (Victor et al. 1989).
• Although these patients have problems
remembering old information (i.e., retrograde
amnesia), it is the disturbance in acquisition of
new information (i.e., anterograde amnesia) that
is most striking.

126. Wernicke’s Encephalopathy and
Korsakoff’s Psychosis
• For example, these patients can engage in a
detailed discussion of events in their lives but
cannot remember ever having had that
conversation an hour later. Because of these
characteristic memory deficits, Korsakoff’s
psychosis also is called alcohol amnestic
disorder

127. Dosing of Thiamine
• Little evidence is available regarding the
optimal dose, frequency, duration, and route
in patients with Wernicke-Korsakoff syndrome
due to alcohol abuse
• 100 mg IV followed by 50 to 100 mg IM daily
until consuming a regular, balanced diet (FDA
dosage)

128. Dosing of Thiamine
• Definitive diagnosis of Wernicke
encephalopathy/Wernicke-Korsakoff syndrome
associated with alcohol use disorder, depending
on state of malnutrition: Initiate as soon as
possible, preferably within the first 48 to 72 hours
of symptom onset, at a dose of 200 to 500 mg IV
by slow IV infusion in 100 mL NS over 15 to 30
minutes 3 times daily for 5 to 7 days, followed by
thiamine 100 mg orally 3 times daily for 1 to 2
weeks, then 100 mg orally once daily (off-label
dosage)

129. Dosing of Thiamine
• Suspected or at risk of Wernicke
encephalopathy/Wernicke-Korsakoff syndrome
associated with alcohol use disorder: Initiate as
soon as possible, preferably within the first 48 to
72 hours of symptom onset, at a dose of at least
100 to 200 mg IV by slow IV infusion in 100 mL NS
over 15 to 30 minutes 3 times daily for 3 to 5
days; may give IM if IV is not possible; followed
by thiamine 100 mg orally 3 times daily for 1 to 2
weeks, then 100 mg orally once daily (off-label
dosage

130. ADRs
• CommonImmunologic: Injection site reaction
• SeriousImmunologic: Hypersensitivity
reaction, Parenteral administration (rare)

131. Silymarin
• Antioxidative and antifibrotic properties
• Believed to enhance liver regeneration and
protect hapetocytes from toxicity
• Recommended dose is 140 mg 2-3 times /day

132. Assignment
• Is Vitamin K therapy essential in patient with ALD ??
• What is the role of Metadoxine in ALD?
• Management of Ascites, HE, Portal HTN, EV
• Note on corticosteroids, anti-oxidants and
Pentoxyphyline use in ALD
• Role of antibiotics in ALD patients