Brief overview of cirrhosis and its complications, management overview, General Medicine

2. Defined as diffuse process characterized by fibrosis and conversion
of normal liver architecture into structurally abnormal nodules which lack
normal lobular architecture.
• Morphology may be classified as micronodular, macronodular, or mixed.
• Histology may be classified as portal, postnecrotic, posthepatitic, biliary,or
congestive.
• Etiology corresponds to specific morphologic and histologic findings.
• Clinical classification using Child-Turcotte-Pugh score

3. VIRAL
• HBV
• HCV
• HDV
AUTOIMMUNE
• AUTOIMMUNE HEPATITIS
• PRIMARY BILIARY CIRRHOSIS
• PRIMARY SCLEROSING CHOLANGITIS
TOXIC
• ALCOHOL
• ARSENIC
METABOLIC
• α1-Antitrypsin deficiency
• Galactosemia
• Glycogen storage disease
• Hemochromatosis
• Nonalcoholic fatty liver disease and
steatohepatitis
• Wilson disease
BILIARY- ATRESIA, STONE,TUMOUR VASCULAR
• BUDD CHIARI SYNDROME
• CARDIAC FIBROSIS
GENETIC
• CYSTIC FIBROSIS
• LYSOSOMAL ACID LIPASE
DEFICIENCY
IATROGENIC
• BILIARY INJURY
• HIGH DOSE VITAMIN A,
METHOTREXATE

5. • In men, 40–80 g/d of ethanol produces fatty liver;
160 g/d for 10–20 years causes hepatitis or cirrhosis.
Only 15% of alcoholics develop alcoholic liver disease.
Women exhibit increased susceptibility to alcoholic Liver disease at
amounts >20 g/d;
two drinks per day is probably safe
• Of patients exposed to the hepatitis C virus (HCV), ~80% develop chronic
hepatitis C, and of those, about 20–30% will develop cirrhosis over 20–30
years
• Of adult patients exposed to hepatitis B, about 5% develop chronic
hepatitis B, and about 20% of those patients will go on to develop cirrhosis

7. SPIDER NAEVI
LEUKONYCHIA

8. SCORES
• AST/platelet ratio index (APRI) greater than 2 suggest cirrhosis
• Bonacini cirrhosis discriminant score (CDS)
Platelet score + ALT/AST ratio score + INR score
Score of 7 or more suggests cirrhosis
• Lok Index ( 0 to 1) - more than 0.2

10. COMPLICATIONS

11. PORTAL HYPERTENSION
GASTRO-ESOPHAGEAL VARICES
PORTAL HYPERTENSIVE
GASTROPATHY
SPLENOMEGALY
HYPERSPLENISM
ASCITES
SPONTANEOUS BACTERIAL
PERITONITIS
HEPATORENAL SYNDROME
TYPE 1 AND 2
HEPATIC ENCEPHALOPATHY
HEPATOPULMONARY SYNDROME
PORTOPULMONARY HYPERTENSION
MALNUTRITION

12. COAGULOPATHY
FACTOR DEFICIENCY
FIBRINOLYSIS
THROMBOCYTOPENIA
BONE DISEASE
OSTEOPOROSIS
OSTEOMALACIA
OSTEOPENIA
HAEMATOLOGIC ABNORMALITIES
ANEMIA
HEMOLYSIS
THROMBOCYTOPENIA
NEUTROPENIA

13. PORTAL HYPERTENSION

14. • PH is defined as a portal pressure gradient (the difference in
pressure between the portal vein and the hepatic veins) greater
than 5mm Hg.
• The best method to assess PP is through the catheterization of the hepatic
vein with determination, through a balloon catheter, of the HVPG, which is
the difference between the wedged (or occluded) Hepatic venous pressure
and the free hepatic venous pressure
Normal HVPG is 3-5mm Hg.

15. • Portal Hypertension(PH) is the initial and main consequence of cirrhosis
and is responsible for the majority of its complications.
• In fact, it has been shown that portal pressure (PP), determined by
the hepatic venous pressure gradient (HVPG), is better than liver
biopsy in predicting development of complications of cirrhosis in
patients with chronic liver disease (CLD) without cirrhosis on liver
biopsy.
• Therefore, a new entity denominated compensated advanced chronic
liver disease (cACLD) has been proposed, emphasizing that PH may
occur before a formal anatomical diagnosis of cirrhosis is established.

16. Based on PP, patients with CC can be divided into those with
• Mild PH (HVPG > 5 but< 10 mm Hg)
• Clinically significant portal hypertension (CSPH), defined by an HVPG 10
mm Hg.
• CSPH is associated with an increased risk of developing
 Varices,
 Overt clinical decompensation (ascites, VH, and HE)
 Postsurgical decompensation
 Hepatocellular carcinoma

17. • There is clear evidence that shows that reducing the HVPG to levels of
12mm Hg or below is associated with protection from variceal
haemorrhage
• An HVPG>16mm Hg indicates a higher risk of death.
• HVPG 20mm Hg predicts failure to control bleeding, early rebleeding
, and death during acute VH,
• And in patients with cirrhosis awaiting liver transplantation, each 1-mm-
Hg increase in HVPG predicts a 3% increase in the risk of death in a
median follow-up of 19 months.

18. • CSPH is present in approximately 50%-60% of patients with CC
without gastroesophageal varices
• Among patients with CSPH, two substages are recognized based on
the absence or presence of Gastro oesophageal Varices

20. Prehepatic
• Portal vein thrombosis
• Splenic vein thrombosis
• Massive splenomegaly (Banti’ s syndrome)
Hepatic
 Presinusoidal
- Schistosomiasis
- Congenital hepatic fibrosis
- Sarcoidosis and Idiopathic
 Sinusoidal
- Cirrhosis—Alcoholic, Cryptogenic, PostNecrotic
- Alcoholic hepatitis
 Post sinusoidal
- Hepatic sinusoidal obstruction (veno occlusive syndrome)
Post hepatic
• Budd-Chiari syndrome
• Inferior vena caval obstruction
• Right sided heart failure
• Restrictive cardiomyopathy
• Constrictive pericarditis
• Severe tricuspid regurgitation

21. Coagulation disorders that can lead to the development of portal
vein thrombosis include
• Polycythemia vera
• Essential thrombocytosis
• Deficiencies in protein C, protein S, antithrombin 3, and
• Factor V Leiden
• Abnormalities in the gene-regulating prothrombin production.

22. DIAGNOSIS
 In a step-wise diagnostic approach, specific signs of PH should be first
looked for on physical examination.
Portal hypertension should be suspected in all patients with GI bleeding
and peripheral stigmata of liver disease namely-
Jaundice, spider telangiectasias, palmar erythema, Dupuytren’s
contractures, parotid enlargement, testicular atrophy, loss of secondary sexual
characteristics, ascites, and encephalopathy
 The absence of physical signs cannot be used to rule out CSPH.
Laboratory studies frequently reveal evidence of hepatic synthetic dysfunction,
including prolongation of the prothrombin time, hypoalbuminemia, and
hyperbilirubinemia, as well as anemia, Thrombocytopenia and leukopenia,
reflecting hypersplenism and, in alcoholics, bone marrow suppression,

23. Usg-
Portal vein diameter greater than 13 mm and the absence of
respiratory variations in the splenic and mesenteric veins are sensitive
but nonspecific markers of portal hypertension
Liver Stiffness
LS by transient elastography (TE; Fibro-Scan) has proved very
accurate for discriminating patients with and without CSPH
LSPS
Liver stiffness [in kPa] * spleen size [in cm]/platelet count [in number/
mm3]
score>2.06 was 90% specific in ruling in CSPH with a positive
predictive value of >90%.
Recent advance- magnetic resonance elastography- needs further studies
Screening Endoscopy for varices

24. • Cruveilhier-Baumgarten syndrome refers to recanalisation of the
paraumbilical vein with prominent periumbilical (portosystemic) collaterals
manifesting as abdominal wall bruit (the Cruveilhier-Baumgarten bruit)
and a palpable thrill in patients with cirrhosis or portal hypertension

25. TREATMENT OF VARICEAL HAEMORRHAGE
1. PRIMARY PROPHYLAXIS – through screening endoscopy of all pts with
cirrhosis
* Non Selective Beta Blockers
* Variceal Band Ligation
2. PREVENTION OF RE-BLEEDING

27. PATHOPHYSIOLOGICAL BASIS OF THERAPY
It has been recently shown that patients with mild PH (HVPG>5
but<10mm Hg) have a normal cardiac index (i.e., they have not yet
developed the hyperdynamic circulatory state), whereas those with
CSPH, especially if varices are present, have already developed
a hyperdynamic state.
Accordingly, response to Non Selective Beta Blockers (NSBB) in
patients with mild PH is suboptimal compared to that of those with
CSPH, indicating that there is no role for NSBB in the setting of mild
PH.

29. NSBB- non selective beta blockers
BRTO- Balloon occluded retrograde transvenous obliteration
ACUTE VARICEAL HAEMORRHAGE
 Somatostatin or octreotide ( 50-100mcg/hr infusion)
 Vasopressin – earlier, no longer used now
 Endoscopic therapy- 1st line
 Balloon tamponade by Sengstaken Blakemore tube or Minnesota tube
 Sclerotherapy
 TIPS – reserved for recurrent variceal bleed

30. RECURRENT VARICEAL HEMORRHAGE
|
ENDOSCOPIC THERAPY
+/-
PHARMACOLOGICAL THERAPY
|
CONTROL OF BLEEDING
Compensated cirrhosis Decompensated Cirrhosis
Child’s class A Child's class B and C
| |
Surgical shunt Transplant Evaluation
vs TIPS Endoscopic Therapy or BB
| |
Liver transplantation Consider TIPS
|

31. ASCITES

32. MECHANISM :
1. The development of hepatic fibrosis, which defines cirrhosis, disrupts
the normal architecture of the hepatic sinusoids and impedes
normal blood flow through the liver.
2. Activation of hepatic stellate cells, which mediate fibrogenesis,
leads to smooth-muscle contraction and fibrosis.
3. Cirrhosis is associated with a decrease in endothelial
nitric oxide synthetase (eNOS) production, which results in decreased
nitric oxide production and increased intrahepatic vasoconstriction.

33. CAUSES OF ASCITES APART FROM CIRRHOSIS-
Cirrhosis accounts for 84% of cases of ascites.
• Cardiac ascites
• Peritoneal carcinomatosis
• “Mixed” ascites resulting from cirrhosis and a second disease account for
10–15% of cases
• Perforation
• Massive hepatic metastasis
• Infection – T.B, Chlamydia
• Pancreatitis ( Ascitic amylase >1000 mg/dL)
• Nephrotic syndrome
• Hypothyroidism
• Familial Mediterranean fever

34.  Peritoneal coccidioidomycosis can mimic tuberculous peritonitis,
including its appearance at laparoscopy, and can occur in patients
without AIDS
 Chlamydial (or rarely gonococcal) peritonitis should be suspected
in sexually active young women with fever and neutrocytic, high-
protein, low-gradient ascites and no evidence of liver disease.
 Aggressive hormone administration to induce ovulation can lead to
ascites from ovarian hyperstimulation syndrome
 Other rare causes of ascites include the POEMS syndrome
(polyneuropathy, organomegaly, endocrinopathy, M component,
and skin changes) and hemophagocytic syndrome

36. Ascitic protein > 2.5 indicates that hepatic sinusoids are normal and
are allowing passage of protein into the ascites
TREATMENT OF ASCITES :
 Restriction of dietary sodium intake to 2g per day
 Diuretic therapy
-Furosemide is a loop diuretic that is generally combined with
spironolactone in a ratio of 40:100;
-Maximal daily doses of spironolactone and furosemide are
400 mg and 160 mg, respectively
 Paracentesis

37. Definition and diagnostic criteria for refractory ascites in cirrhosis.
• Diuretic-resistant ascites:
Ascites that cannot be mobilized or the early recurrence of which
cannot be prevented because of a lack of response to sodium
restriction and diuretic treatment
• Diuretic-intractable ascites
Ascites that cannot be mobilized or the early recurrence of which
cannot be prevented because of the development of Diuretic
Induced complications that preclude the use of an effective diuretic
dosage

38. Requisites
• Treatment duration-
Patients must be on intensive diuretic therapy (spironolactone 400
mg/day and furosemide 160 mg/day) for at least 1 week and on
a salt-restricted diet of less than 90 mmol/day
• Lack of response-
Mean weight loss of <0.8 kg over 4 days and urinary sodium output less
than the sodium intake
• Early ascites recurrence-
Reappearance of grade 2 or 3 ascites within 4 weeks of initial mobilization

39. • Diuretic-induced complications
 Diuretic-induced hepatic encephalopathy is the development
of encephalopathy in the absence of any other precipitating factor
 Diuretic-induced renal impairment is an increase of serum creatinine by
>100% to a value >2 mg/dl (177 lmol/L) in patients with ascites
responding to treatment
 Diuretic-induced hyponatremia is defined as a decrease of serum sodium
by >10 mmol/L to a serum sodium of <125 mmol/L
 Diuretic-induced hypo- or hyperkalemia is defined as a change in serum
potassium to <3 mmol/L or >6 mmol/L despite appropriate measures

40. REFRACTORY ASCITES
- Persistence of ascites despite maximal or maximally tolerated
diuretic use and sodium restricted diet
- Pharmacotherapy : addition of these to diuretics
• Midodrine, alpha 1 agonist
• Clonidine, alpha 2 agonist
- Large volume Paracentesis (LVP)
- TIPS
- Liver transplantation
* addition of albumin infusion (6-8g/L ascitic fluid)to LVP
decreases post paracentesis circulatory dysfunction and death-
not routinely recommended

41. • Hepatic hydrothorax occurs when ascites, right sided migrates via
fenestrae in the diaphragm into the pleural space. This condition can
result in SOB , hypoxia, and infection.
• Treatment is similar to that for cirrhotic ascites and includes sodium
restriction, diuretics, and, if needed, thoracentesis or TIPS placement.
Chest tube placement should be avoided
* The prognosis for patients with cirrhosis with ascites is poor, and
some studies have shown that <50% of patients survive 2 years after
the onset of ascites. Thus, there should beconsideration for
liver transplantation in patients with the onset of ascites.

42. SPONTANEOUS BACTERIAL
PERITONITIS

43. SBP is the infection of the ascitic fluid that occurs in the absence of a
visceral perforation and in the absence of an intra-abdominal
Inflammatory focus such as abscess, acute pancreatitis
or Cholecystitis.
CRITERIA
• Ascitic fluid PMNL > 250 cells/mm3
• Monomicrobial culture positive
ETIOLOGY-
The most common organisms are Escherichia coli and Klebsiella ..,
however, gram-positive bacteria, including Streptococcus viridans,
Staphylococcus aureus, and Enterococcus sp., can also be
found.

44. VARIANTS PMNL CULTURE
Spontaneous Bacterial
Peritonitis ≥250 Single Bacteria
Culture Negative
Neutrocytic Ascites
(CNNA)
≥250 Negative
Monomicrobial Non-
neutrocytic
Bacterascites (MNB)
<250 Single Bacteria
Secondary Bacterial
Peritonitis
≥250 Polymicrobial
Polymicrobial
Bacterascite
<250 Polymicrobial

45. Recommendations on treatment of SBP
1. Antibiotic therapy must be empirically initiated in patients with ascitic
fluid PMN count >250/mm3
2. Recommended antibiotics for initial empirical therapy: 3rd gen
cephalosporins
Cefotaxime- minimum dose 2 g/12 h, minimum duration 5 days
In patients with uncomplicated SBP and not under quinolone prophylaxis:
oral ofloxacin is another option
In patients under quinolone prophylaxis: cefotaxime
In patients with beta-lactam hypersensitivity: quinolones
Aminoglycosides should be avoided
3. Assessment of response to antibiotic therapy:
Periodical clinical evaluation and, at least, one follow-up paracentesis (i.e.
after 2 days of antibiotic therapy) to determine ascitic fluid PMN count

46.  INTRAVENOUS ALBUMIN-
1.5g/kg on day 1 and 1g/kg on day 3 in pts hospitalised for SBP, have
reduced short and intermediate term mortality
 PROKINETICS
Reduce intestinal transit time thereby reducing bacterial overgrowth and
bacterial translocation
 PROBIOTICS
Intestinal flora re-equilibration

47. Treatment failure when one of the following
• Deterioration of clinical condition within the first hours of
antibiotic therapy
• Less than 25% decrease in ascitic fluid PMN in follow-up
paracentesis as compared to pre-treatment value
If treatment failure
• Modify antibiotic therapy according to in vitro susceptibility
of isolated organisms or empirically
• Consider the possibility of secondary peritonitis

48. PROPHYLAXIS
Given to pts with-
• UGI bleed
Norfloxacin 400mg PO 12th hrly for 7 days
• Prior SBP
Norfloxacin 400mg PO OD or
Ciprofloxacin 750mg PO weekly or
TMP-SMX 160/800mg daily for 5 days/week
To be given indefinitely until transplantation or resolution of Ascites
• Low Ascitic Protein <1g/dL
Norfloxacin 400mg PO OD or
Ciprofloxacin 750mg PO weekly or
TMP-SMX 160/800mg daily for 5 days/week
To be given only during hospitalisation

49. HEPATOPULMONARY SYNDROME

50. Pulmonary changes complicating chronic hepatocellular disease
• Hypoxia
• Intra-pulmonary shunting
• Ventilation–perfusion mismatch
• Reduced transfer factor
• Pleural effusion
• Raised diaphragms
• Basal atelectasis
• Primary pulmonary hypertension
• Porto-pulmonary shunting, Chest X-ray mottling
Hepato-pulmonary syndrome is chh by-
• Advanced chronic liver disease
• Arterial hypoxaemia
• Intra-pulmonary vascular dilatation
• No primary cardiopulmonary disease

51. • Platypnea-
Worsening of dyspnea moving from supine to upright posture
• Orthodeoxia-
Decrease of PaO2 of more than 5% or more than 4 mmHg moving
from supine to upright position
• Clubbing and cyanosis in pts with liver disease in the absence of intrinsic
cardiac disease
• Diffuse telangiectasia
• 70%- marked hypoxia during sleep
• An established screening tool is pulse oximetry as it can identify all
patients with PaO2 <70 mmHg using an oxygen saturation cut-off <96%

52. Criteria 1: Chronic liver disease
Criteria 2: Abnormal oxygenation is defined by elevated alveolar-arterial oxygen
gradient (>15 mmHg or >20 mmHg in patients >64 years, respectively) while
breathing room air in the sitting position at rest
Criteria 3: intrapulmonary vascular dilatation at CE-TTE or 99mTcMAA
The hepatopulmonary syndrome (HPS) is defined by the combination of
intrapulmonary vascular dilatation (IPVD) and hypoxemia in patients with
chronic liver disease or portal hypertension
IPVD can cause a right to left shunt resulting in an elevated alveolar-arterial
oxygen pressure gradient (A-a O2) and hypoxemia.
CE-TTE: Contrast-enhanced transthoracic echocardiography;
99mTcMAA: Technetium macroaggregated albumin lung perfusion scan.

53. Stages PaO2, mmHg
Mild ≥ 80
Moderate ≥ 60 and < 80
Severe ≥ 50 and < 60
Very severe < 50
Severity score of hepatopulmonary syndrome

54. PATHOPHYSIOLOGY
1. Right to left shunt
2. Diffusion limitation
3. Ventilation-perfusion mismatch

57. The primary tool for detection of IPVD is transthoracic contrast-enhanced
echocardiography.
Agitated saline is commonly used as a contrast agent as it creates
microbubbles of >10 µm diameter that are usually not able to pass the
normal pulmonary vascular bed.
However, in case of IPVD and HPS, microbubbles appear in the left
chambers of the heart three or more cardiac cycles following visualization in
the right heart

58. Click to add text

59. There are 2 patterns seen with pulmonary angiography:
• Type 1 HPS as characterized by pre-capillary pulmonary artery dilatation
without arteriovenous fistulas – RESPONDS TO 100% O2
• Type 2 HPS where localized pulmonary arteriovenous fistulous
communications are seen – DOES NOT RESPOND TO 100% O2

60. DIFFERENTIAL DIAGNOSIS:
 Diseases of pul parenchyma : COPD, pneumonitis, pneumonia
 Diseases of pleura and Diaphragm
 Hepatic hydrothorax
 Portopulmonary hypertension
 Pulmonary function effect due to Ascites

61. TREATMENT
- Long term O2 therapy – transtracheal catheter is an option
- Orthotopic liver transplantation- treatment of choice, reverses HPS
- Cavoplasty has been shown to be an effective treatment for the
hepatopulmonary syndrome when it is associated with the Budd–
Chiari syndrome
- Methylene Blue : It might be used in the post-operative period of liver
transplantation in cases with transient hypoxemia, however its routine and
long term use is not recommended yet.
-Embolotherapy
- TIPS : palliative

62. PORTOPULMONAR
Y HYPERTENSION

63. Criteria 1
Portal hypertension (15 mmHg, or portocaval gradient > 5 mmHg) and
Criteria 2
mPAP > 25 mmHg and mPAOP < 15 mmHg
mPAP - mPAOP (transpulmonary gradient) > 10 mmHg
PVR > 240 dyn.s.cm-5 = 3 UI WOOD

65. • It is a life-threatening disease characterized by a marked and
sustained elevation of pulmonary vascular resistance, leading to
increased pulmonary artery pressure, right ventricular failure, and
Ultimately death.
• Dyspnea on exertion is the most common symptom, accounting for
about 80% of the presenting complaint
• However, this symptom is non-specific and frequently related to
other conditions such as refractory ascites, hepatic hydrothorax,
heart disease, or maybe even underlying lung.
• On physical examination, an accentuated pulmonary component
of the second heart sound and a systolic murmur indicating
pulmonary artery hypertension are the most common findings

66. MALNUTRITION IN CIRRHOSIS
Because the liver is principally involved in the regulation of protein and
energy metabolism in the body,patients with advanced liver disease
are commonly malnourished.
-Poor dietary intake, alterations in gut nutrient absorption, and
alterations in protein metabolism
BONE DISEASE IN CIRRHOSIS
Osteoporosis is common in patients with chronic cholestatic liver
disease because of malabsorption of vitamin D and decreased calcium
ingestion.

67. ABNORMALITIES IN COAGULATION
Coagulopathy is almost universal in patients with cirrhosis.
• Decreased synthesis of clotting factors
• Impaired clearance of anticoagulants.
Vitamin K absorption is frequently diminished.
Intravenous or intramuscular vitamin K can quickly correct this
abnormality.
The synthesis of vitamin K–dependent clotting factors is
diminished because of a decrease in hepatic mass, and, under
these circumstances, administration of parenteral vitamin K
does not improve the clotting factors or the prothrombin time

68. HEPATO-RENAL
SYNDROME

69. Hepato-renal syndrome is the development of renal failure in patients
with severe liver disease in the absence of any identifiable renal
pathology
Hepato-renal syndrome may be classified into two types:
TYPE 1 TYPE 2
Patients have a rapidly progressive
(less than 2 weeks) reduction of renal
function with doubling of the initial
serum creatinine to greater than
2.5mg/dl (220mmol/l) or a 50%
reduction in the initial 24H
creatinine clearance to less than 20
ml/min.
• 80% mortality
Patients satisfy the criteria for the
diagnosis but the renal failure does
not progress rapidly.
These patients usually have relatively
preserved hepatic
function with refractory ascites

70. Criteria for diagnosis of hepato-renal syndome
Major criteria
 Cirrhosis with ascites
 Serum creatinine >1.5 mg/dl (133 lmol/L)
 Absence of shock
 Absence of hypovolemia as defined by no sustained improvement of renal function (creatinine
decreasing to <133 lmol/L) following at least 2 days of diuretic withdrawal (if on diuretics), and
volume expansion with albumin at 1 g/kg/day up to a maximum of 100 g/day
 No current or recent treatment with nephrotoxic drugs
 Absence of parenchymal renal disease as defined by proteinuria <0.5 g/day,
no microhaematuria (<50 red cells/high powered field), and normal renal ultrasonography
Additional criteria (not necessary for diagnosis)
1 Urine volume <500ml/day
2 Urine sodium <10mmol/day
3 Urine osmolarity > plasma osmolarity
4 Urine red cells <50/high-power field
5 Serum sodium <130mmol/l

72. SBP is precipitating factor for HRS. 30% of pts with SBP develop HRS
eventually.
Urinary Biomarkers- Current data shows that NGAL (neutrophil
gelatinase associated Lipocalin) is most useful marker.
NGAL detects pts with ATN.
In contrary, it can't differentiate between Pre renal Azotemia and HRS.

73. TREATMENT
• Once the patients have received volume expansion with albumin (1 g
per kilogram) with no response achieved in the following 48 h, and criteria
of HRS are fulfilled
Then treatment with terlipressin 2mg/day is recommended.
Expansion with albumin should be continued at the dose of 20-40 g
daily.
Response to treatment should be assessed regularly and terlipressin
should be titrated gradually up to a maximum dose of 12 mg/Day
• Terlipressin should be used for a maximum of 14 d and stopped in case of
lack of response
• Response is defined as a reduction of at least 25% from baseline sCr level,
that is from sCr level before treatment with terlipressin was started

74. Other options-
- Midodrine And Octreotide
- Renal Replacement therapy
- Liver transplantation
- Noradrenaline- similar efficacy as terlipressin when used with albumin
- Dopamine- no proven efficacy
- Serelaxin – Recombinant form of Relaxin-2
PREVENTION
• Albumin with LVP
• Antibiotic prophylaxis in SBP

75. HEPATIC ENCEPHALOPATHY

76. Cirrhosis and Portal HTN
Increased Blood NH3 level
And increased permeability of BBB
Brain edema
Astrocyte swelling ( increased Glu and Gln)
Neurotransmitter and receptor alterations ( increased GABA)
Altered brain glucose metabolism
Hepatic Encephalopathy

77.  HE may present as a spectrum of reversible neurocognitive symptoms
and signs that range from mild changes in cognition to profound coma in
patients with acute or chronic liver disease.
 Subtle findings in overt HE may include forgetfulness, alterations in
handwriting, difficulty with driving, and reversal of the sleep-wake
cycle.
 As HE worsens, findings may include asterixis, agitation, disinhibited
behavior, seizures, and coma.
 Other causes of altered mental status—particularly
hypoglycemia, hyponatremia, medication ingestion, and
structural intracranial abnormalities resulting from coagulopathy
or trauma—should be considered and rapidly excluded inpatients
suspected of having HE.

78. There are 3 major types of HE:
• Type A, associated with acute liver
failure;
• Type B, associated with
portosystemic shunts in the absence
of liver disease;
• Type C, associated with chronic and
end-stage liver disease and portal
hypertension.
• Type C HE is the most common type
and has historically been graded
from 0 to 4 based on the West Haven
criteria

79. Based on the SONIC classification, cirrhotic patients are divided into 3
categories:
• Unimpaired patients- have no clinical, neurophysiologic, or
neuropsychometric abnormalities.
• Covert HE -have minimal HE (clinically normal patients with
Abnormal cognition or neurophysiologic test results) or grade 1 HE by
the West Haven criteria.
• Overt HE- have grade 2 HE or higher by the West Haven criteria

81. Precipitants of acute hepatic encephalopathy in the cirrhotic patient
Electrolyte imbalance
• Diuretics
• Vomiting
• Diarrhoea
Bleeding
• Oesophageal and gastric varices
• Gastro-duodenal erosions
• Mallory–Weiss tear
Drugs
• Alcohol withdrawal
Infection
Spontaneous bacterial peritonitis
Urinary
Chest
Constipation

82. DIFFERENTIAL DIAGNOSIS
• Hyponatremia
• Acute Alcoholism
• Wilsons
• Wernickes
• Functional psychosis

83. Nonabsorbable disaccharides have been the cornerstone
of the treatment of HE.
• Oral lactulose or lactitol are metabolized by colonic bacteria to by-
products that appear to have beneficial effects by causing catharsis and
reducing intestinal pH, thereby inhibiting ammonia absorption.
• Rifaximin given orally in a dose of 550 mg twice daily for the treatment of
chronic HE and reduction in the risk of recurrence of overt HE in patients
with advanced liver Disease.
• Other antibiotics, including neomycin, metronidazole, and vancomycin,
have been studied in small trials and case series, but their effectiveness
in patients with chronic HE is not established.
• A randomized controlled double-blind crossover trial has demonstrated
that acarbose improves mild HE in patients with cirrhosis and adult-onset
diabetes mellitus
• L-ornithine –L-Aspartate and Zinc

84. THANK YOU