4. Introduction
What Is Chronic Liver Disease?
Chronic liver disease is marked by the gradual
destruction of liver tissue overtime Liver diseases
in this category include: Cirrhosis and Fibrosis of
the liver.
Chronic liver disease" refers to disease of the
liver which lasts over a period of six months. It
consists of a wide range of liver pathologies
which include inflammation (chronic hepatitis),
liver cirrhosis, and hepatocellul carcinoma. The
entire spectrum need not be experienced.
4
5. What causes different types of liver
disease ?
Different types of liver disease result from different
causes.
Viral infections: Hepatitis A, hepatitis B and hepatitis
C are diseases caused by a viral infection.
Problems with your immune system: , cause
autoimmune liver diseases. include primary biliary
cholangitis and autoimmune hepatitis
Inherited diseases: a genetic condition (one you inherit
from your parents). include Wilson
disease and hemochromatosis
Cancer: abnormal cells multiply in your liver, you may
develop tumors. (noncancerous) or malignant (liver
cancer).
Consuming too many toxins: Alcohol-related fatty liver
disease . Non-alcohol related fatty liver disease
5
6. Epidemiology
Estimate is that 1% of populations have
histologically
diagnosable cirrhosis
• Acute variceal bleeding and spontaneous
bacterial
peritonitis (SBP) …
– life-threatening complications of cirrhosis.
• Approximately 50% of patients with cirrhosis
develop
ascites during 10 years and, within 2 years,
nearly
half of patients who develop ascites will die
6
7. Etiology
Result of chronic, long-term insult to liver
• Most common causes
– Chronic alcohol abuse
• Ethanol and metabolites are direct hepato toxins
– Hepatitis
• Hep C and Hep B
• Other causes
– Immunological disease[autoimmune hepatitis]
– Drugs: isoniazid, methotrexate, methyldopa,
Tamoxifen, propylthiouracil
7
8. Pathophysiology
The pathological hallmark of cirrhosis is the
development of scar tissue that replaces normal
parenchyma(hepatocytes), blocking the portal
flow
of blood through the organ and disturbing
normal
function.
• Fatty liver or steatosis from chronic ethanol
abuse…followed by liver inflammation
(steatohepatitis), hepatocyte death, and collagen
deposition leads to fibrosis resulting increased
intrahepatic resistance.
8
9. contt…..
portal hypertension and cirrhosis
The portal vein comes from the splenic, superior
mesenteric, inferior mesenteric, and gastric veins,
and
ends in the sinusoids of the liver.
• Blood in the portal vein contains substances
absorbed
from the intestine, and delivers these substances to
the
liver to be metabolized before entering the systemic
circulation.
• Once the portal blood reaches the liver, it crosses
through a high-resistance capillary system
within the
hepatic sinusoids
9
10. Contt…
The increased intra-hepatic resistance is an
initial
process leading to portal hypertension.
• Intra-hepatic resistance is not only structural but
also
functional …increase in blood flow to the
splanchnic
vasculature.irrhosis results in changes in
• Both the rise in resistance and the enhanced
portal
inflow play an important role in the development
of
10
11. Contt……..
Portal pressure is a function of flow and
resistance
to that flow across the hepatic vasculature
• Resistance to blood flow secondary to hepatic
fibrosis. Increasing portal vein pressure.
• Nitric oxide released to counter elevated
pressure -
systemic vasodilation and decreasing blood
pressure ..Increasing renin, aldosterone,
antidiuretic hormone to maintain renal perfusion,
leads to sodium and water
retention
11
12. Contt….
Normal portal pressure is generally below 6 mm
Hg,
and in cirrhotic patients may increase to 7 to 9
mmHg.
• Clinically significant…10 to 12 mm Hg, the
threshold
for complications of portal hypertension, such as
esophageal varices and ascites
• Persistent portal hypertension---
– lead to ascites formation
– Lead to the formation of esophageal varices
12
14. Risk factors
Excessive alcohol use
Obesity
Metabolic syndrome including raised blood lipids
Health care professionals who are exposed
to body fluids and infected blood
Sharing infected needle and syringes
Having unprotected sex and multiple sex partners
Working with toxic chemicals without wearing
safety clothes
Certain prescription medications
14
17. sign and Symptoms
Fluid buildup in the belly (ascites)
Vomiting blood,
Itching, Spider-like veins in the skin
Yellowing of the skin and eyes (jaundice)
Kidney failure, Gallstones
Muscle loss, Low energy and weakness (fatigue)
Loss of appetite, Weight loss
Easy bruising
Confusion as toxins build up in the blood
17
19. Investigations –lab and
imaging
Liver function tests ( AST, ALT, PT, Alb, Bili)
– Elevated aspartate transaminase (AST),
alanine transaminase (ALT)
• Hypoalbuminemia
• Elevated prothrombin time (PT)
• Thrombocytopenia
Cholangiography: A specialized X-ray of your
bile ducts
ENDOSCOPY AND COLONSCOPY
19
20. Contt..
• Ultrasound
CT scan (computed tomography)
MRI (magnetic resonance imaging)
Liver biopsy
– Ascetic fluid analysis: total protein, bacterial
culture, albumin (SA-AG(serum-ascites albumin
gradient) differentiates cause of ascites with 97%
accuracy)
– SAAG >1.1 g/dL… Presence of low albumin in
ascites fluid ….is indicative of ascites secondary to
portal hypertension
20
21. Scoring systems for chronic liver disease (CLD)
MELD (model of end-stage liver disease)
Bilirubin
Creatinine
INR
UKELD (UK model of end-stage liver disease)
Bilirubin
Creatinine
INR
Sodium
Childs-Pugh
Ascites
Bilirubin
Albumin
PT
Encephalopathy
21
22. MANAGEMENT AND TREATMENT
How is liver disease managed or treated?
depends on the type of liver disease :
Medications: take medicine for viral infections
like hepatitis or inherited conditions like Wilson
disease.
Lifestyle changes: If you have fatty liver
disease, avoiding alcohol, limiting fat and calories
and increasing fiber intake can help.
Liver transplant: .
22
23. Treatments
General approaches;
• Identify and eliminate, where possible, the
causes of cirrhosis (e.g., alcohol abuse).
• Assess the risk for variceal bleeding and begin
pharmacologic prophylaxis when indicated.
• Evaluate the patient for clinical signs of ascites
and
manage with pharmacologic therapy and
paracentesis.
• Careful monitoring for SBP in patients with
ascites.
• HE dietary restriction, elimination of CNS
depressants,
and therapy to lower ammonia levels
23
24. I. Varices and management
• Veins in the esophagus, stomach, and rectum
enlarge
to accommodate blocked blood flow through the
liver.
• The presence of enlarged veins (varices) usually
causes no symptoms…. But as the disease
progress…
there will be further enlargement and bleeding
24
25. Contt…
It is one of most severe complications of cirrhosis
• Approximately one-third of all cirrhotic
patients….
– with varices will develop a variceal bleed
• Incidence of bleeding…25-35%
• Mortality rate…30-50% per bleeding
• Recurrence rates…70% within the first 6
months after initial bleed
25
26. Contt…
Treatment goals:
– volume resuscitation,
– acute treatment of bleeding,
– prevention of recurrence of variceal bleeding.
• Treatment for variceal bleeding is challenging
and
include medicines as well as endoscopic therapy
(endoscopic banding or sclerotherapy).
• Treatment includes; primary tx, acute bleeding
management and secondary tx.
26
27. ACUTE VARICEAL BLEEDING TREATMENT
Goal of medical therapy is to
– Decrease portal HTN by decreasing spanchnic blood
flow
• Steps in Treatment
– Fluid resuscitation
– Medical management, endoscopic
• Hypovolemia should be immediately managed to
maintain mean arterial pressure at 80 mm Hg and the
hemoglobin at approximately 8 g/dL.
• Fresh frozen plasma or platelets for ... patients with
Prolongation of the PT
27
28. Vasopressin…0.2-0.4 U/min plus Nitroglycerine
40-400 mcg/min for 3-5 days
• Octreotide is a …………
– parenteral synthetic analog of the naturally
occurring hormone somatostatin
– Preferred agent in combination with
…endoscopy
– 50 mcg IV bolus, then 50 mcg/hr IV x 3-5 days
• ADR..Hyperglycemia and abdominal cramping
28
29. Contt…
Endoscopy
– Sclerotherapy (80%-90%) …effective …..Sclerosing
agents includes ethanolamine or sodium tetradecyl
sulfate
• Non-drug therapy
– Balloon compression directly to bleeding varices to stop
the bleeding
– Tran jugular intrahepatic port systemic
shunt….Shunting away blood from portal circulation
• Antibiotics…….decrease mortality(prevent rebreeding
and SBP)
– Fluoroquinolone (cipro 500MGor norfloxacin 400MG)
BID for 7 days
29
30. II, VARICES BLEEDING PRIMARY TREATMENT
• Prophlaxis….is not needed for cirrhosis unless
varices identified.
• Use non-selective beta blockers(propranolol and
nadolol)…. Life long
– Decrease cardiac output and spanchnic blood
flow
– Usual starting dosages of propranolol are 10 mg
three times a day, or nadolol 20 mg daily.
• Goal of HR………> 55 beats/min or 25%
reduction in
blood flow to splanchnic area
30
31. ASCITES AND MANAGEMENTS
• Excess free fluid in the abdomen…. more than 3 L
of fluid…occur over a few weeks.
• Hypoalbuminemia from decrease protein synthesis,
and increase capillary permeability and volume
overload allow
fluid to escape the vascular space & accumulate in
peritoneal space …leading to ascites
• Clinical features
– protuberant abdomen
– shifting dullness
– fluid wave, abdominal pain
31
33. Contt…
Goal is ……..
– weight loss of no more than 1.0 kg/day for
patients with both ascites and peripheral edema
and ……no more than 0.5 kg/day for patients with
ascites alone
• In those with severe ascites causing a tense
abdomen……. hospitalization is generally
necessary
for paracentesis
33
34. Contt….
Salt restriction…….
– is the initial treatment, which allows diuresis since
the patient has more fluid than salt concentration.
– Salt restriction is effective in about 15% of
patients
• Diuretics……
– Since salt restriction is the basic concept in
treatment, and aldosterone is one of the
hormones that acts to increase salt retention, a
medication that counteracts aldosterone should
be sought.
34
35. Contt….
Spironolactone is the drug of choice since -they
block the aldosterone receptor in the collecting
tubule.
• Generally, the starting dose is …
– oral spironolactone 100 mg/day (max 400
mg/day).
– 40% of patients will respond to spironolactone
• For non-responders…
– a loop diuretic may also be added and
generally….furosemide is added at a dose of
40 mg/day (max 160 mg/day)
35
36. Contt…
Diuretic resistance can be predicted when……..
– 80 mg IV furosemide after 3 days without
diuresis.
• Paracentesis……..is for those severe (tense)
ascites,
– therapeutic paracentesis may be needed in
addition to medical treatments.
36
37. III, SPONTANEOUS BACTERIAL PERITONITIS (SBP)
• SBP is an acute bacterial infection of ascitic fluid.
– Incidence--10-30% of hospitalized patients with
cirrhosis
and ascites
• Mortality…………20-40% of in-hospital
• Pathophysiology
– Increased gut permeability secondary to portal
hypertension or translocation of the gut wall
• Enteric gram-negative most common and
usually
only a single organism is involved. e.g
E.coli,Klebsiella
37
38. Contt…
Clinical and Laboratory Features
• Common symptoms….
– Fever, abdominal pain, nausea, vomiting,
diarrhea,
– Peritoneal signs (eg, abdominal tenderness and
rebound)
• Laboratory
– Blood culture positive in 50-70% of cases
– Ascetics cultures positive in 67% of cases
38
39. (SBP) Treatments
• Antibiotic therapy
– Empiric therapy for gram-negative organisms
– Third generation cephalosporin's…..studied the
most
• Cefotaxime 2 gm q8-12 hrs or Ceftriaxone 2
g/day, fluoroquinolones for 5 days
39
40. (SBP) PROPHYLAXIS
All patients who have survived an episode of SBP
should receive long-term antibiotic prophylaxis.
• Oral antibiotics can be used as prophylaxis to
reduce
bacterial translocation
– Norfloxacin 400 mg/day or ciprofloxacin 750 mg
• The prophylaxis might be indicated to those with
a
history of SBP, those presenting with an upper GI
hemorrhage.
40
41. IV, HEPATIC ENCEPHALOPATHY (HE)
Hepatic coma or encephalopathy is a metabolic
disorder of the central nervous system (CNS),
which
occurs in patients with advanced cirrhosis.
• Ammonia(NH3) ..neurotoxic metabolic
manufactured by gut bacteria and by product of
protein catabolism.
– Decreased conversion of NH3 to urea
accumulates
encephalopathy
• Also aggravated by other substances that are
formed
or accumulate because of decreasing hepatic
metabolism.
41
42. (HE) TREATMENT
Therapeutic management is aimed primarily at
reducing the amount of ammonia or nitrogenous
products in the circulatory system
Lactulose: non-absorbable disaccharide; decrease
colonic
pH allows conversion of NH3 (ammonia) to
ammonium (NH4+), trapping it in GI lumen &
leading
to excretion.
42
43. Contt…
Acute HE treatment: 45 mL PO Q1-2h until
loose bowel
Moment(2-3 times /day) …….if unable to take
PO, retention enema 300 mL in 700 mL water
retained for 1 hr, repeated Q2h until mental
function improves
• Maintenance: 15-30 mL PO BID-TID….
Adverse Effect : flatulence, diarrhea, abdominal
cramping
43
44. Contt…
Antibiotics – 2nd line
– decreasing number of intestinal urease-producing bacteria
associated with excess NH3 production
• Rifaximin 400 mg TID
– Very expensive; better tolerated than lactulose
• Metronidazole 250 BID
– Not FDA approved for use
• Neomycin 3-6 g/d divided Q6-8H x 1-2 weeks, then 1-2
g/d maintenance
– Last line therapy, poorly tolerated and many
AEs
(renal toxicity, ototoxicity)
44
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