Cirrhosis of the liver

Maia Zhamutashvili
MD PhD
 Liver Functions
• Manufacturing blood proteins that aid in clotting,
oxygen transport and immune system function.
• Storing excess nutrients and returning some of the
nutrients to the bloodstream.
• Manufacturing bile, a substance needed to digest food.
• Helping the body store sugar (glucose) in the form of
glycogen.
• Ridding the body of harmful substances in the
bloodstream, including drugs and alcohol.
• Breaking down saturated fat and producing cholesterol.
 Laboratory Investigations
• Alkaline phosphatase: shows bile duct obstructive process
• Bilirubin – for assessing the severity of jaundice (Direct,
Indirect
• Aspartate transaminase (AST): shows hepatocellular injury
• Alanine transaminase (ALT): hepatocellular injury
• Gamma -glutamyl transpeptidase (GGT): obstructive, alkohol
• Albumin
• Prothrombin time
• Thrombocytopenia: a relatively common feature in chronic
liver disease found in 30% to 64% of cirrhotic patients.
 Description
•The first known description of the condition is by Hippocrates in
the 5th century BCE. The word cirrhosis is from Greek :
κίρρωσις; kirrhos κιρρός "yellowish" and -osis (-ωσις) meaning
"condition“(describing the appearance of a cirrhotic liver).
•A chronic, progressive disease of the liver.
•With the prolonged course.
•With liver cell degeneration and destruction, when normal
lobular structure distorted by fibrotic connective tissue.
•Lobules are irregular in size and shape with impaired vascular
flow.
 Definition
Cirrhosis is defined histologically as a diffuse hepatic process
characterized by fibrosis and conversion of the normal liver
architecture into structurally abnormal nodules.
Cirrhosis is an end result of parenchymal degeneration,
regeneration, and scarring. Liver is firm and appears either micro-
or macronodular as a result of formation of regenerative nodules
with surrounding fibrosis in the parenchyma of the liver.
Portal hypertension develops because of liver stiffness and
increased resistance to flow. As a result, the blood is shunted
away from the liver, and new thin dilated vessels form, shunting
the blood away from the portal to the systemic circulation.
Examples include esophageal, gastric, and rectal varices.
Babylonian clay model of a sheep's liver, 1900–1600 BC.
Reproduced with permission from the British Museum
Structural Organisation of the Liver
 Etiology. Causes of liver cirrhosis

Several types of cirrhosis:

• Alcoholic (outdate ,,Laennec’s) cirrhosis
• Postnecrotic cirrhosis (hepatitis viruses: B, D, C;
Toxic or Autoimmune hepatitis)
• Nonalcoholic fatty liver disease
• Biliary cirrhosis (Associated with chronic biliary
obstruction and infection.)
• Cardiac cirrhosis (Results from longstanding
severe right-sided heart failure)
 epidemoology

• Cirrhosis affected about 2.8 million people and

resulted in 1.3 million deaths in 2015.
• Of these deaths, alcohol caused 348,000,
hepatitis C caused 326,000, and hepatitis B
caused 371,000.
• In the Global, more men die of cirrhosis than
women.
 Pathophysiology
• liver cell damage result in inflammation, necrosis.
• Destroyed liver cells are replaced by scar tissue.
• Normal liver architecture becomes nodular.
• attempts at regeneration eventually result to fibrosis
and a decrease in liver size (a small nodular liver).
• hepatic function is slowly impaired
• obstruction of venous channels
• blocks hepatic blood flow and cause portal
hypertension.
 Normal histological picture

CV

PT

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 histological picture in Liver Cirrhosis

Fibrosis

Regenerating Nodule

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 Depend of nodules size, cirrhosis are:

• Micronodular cirrhosis (nodules less than 3 mm in

diameter): Cirrhosis due to alcohol, hemochromatosis,
hepatic venous outflow obstruction, and Indian
childhood cirrhosis.
• Macronodular cirrhosis (irregular nodules with a
variation greater than 3 mm in diameter): Cirrhosis due
to hepatitis B and C, and primary biliary cholangitis.

• Usually micronodular cirrhosis progresses into

macronodular cirrhosis over time.
Micronodular cirrhosis

17
 Macronodular cirrhosis
Macronodular cirrhosis

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Manifestations of Liver Cirrhosis
 Clinical Manifestations

• Early Manifestations • Late Manifestations

– Anorexia – Jaundice (High Bilirubin)
– Dyspepsia – Skin (cutaneous
– Flatulence manifestation)
– Abdominal pain – Endocrine Disturbances
– Fever – Hematologic Disorders
– Weight loss – Peripheral Neuropathy
– Enlarged liver or spleen
 Clinical Manifestations:
Hematologic Disorders
• Bleeding tendencies as a result of decreased
production of clotting factors in liver (II, VII, IX,
and X)
• Anemia, leukopenia, and thrombocytopenia
are believed to be result of hypersplenism
(enlarged spleen)
CLINICAL MANIFESTATIONS OF LIVER CIRRHOSIS
 CHILD-PUGH CLASSIFICATION OF THE
SEVERITY OF LIVER DISEASE

Parameter Points assigned

1 2 3
Ascites Absent Slight Moderate
Bilirubin, mg/dl ≤2 2-3 >3
Albumin, g/dl >3.5 2.8-3.5 <2.8
INR <1.8 1.8-2.3 >2.3
Encephalopathy None Grade 1-2 Grade 3-4

Interpretation:
Chronic liver disease is classified into Child–
Pugh
Points classClass
A to C.
5-6 A (compensated)
7-9 B (decompensated)
10 - 15 C (decompensated)
LIVER CIRRHOSIS

A spider angiomata is a type of

telangiectasis (swollen blood
vessels) found slightly beneath
the skin surface, often containing
a central red spot and reddish
extensions which radiate hepa
 ASSESSMENT OF DISEASE
SEVERITY
LIVER FUNCTION
PANEL
Alanine transaminase (ALT)
Aspartate aminotransferase
(AST)
MARKERS REFLECTING Gamma glutamyl transferase
LIVER FUNCTION (GGT)
Alkaline phosphatase (ALP)
Prothrombin Bilirubin
Factor V
Albumin
Bilirubin
Ammonia

hepa
 ASSESSMENT OF LIVER
FIBROSIS/CIRRHOSIS USING METAVIR
CLASSIFICATION

Liver fibrosis
• No fibrosis F0
• Portal fibrosis (fibrous portal
expansion) F1

F2 • Periportal fibrosis (Periportal or

rare portal-portal septa)

F3 • Septal fibrosis without cirrhosis

• Cirrhosis F4

Bl Liv L
ee
d
er
fa ca iver
g in ilu nc
er
re

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ASSESSMENT OF HEPATIC
FIBROSIS/CIRRHOSIS

Liver Non-invasive
biopsy Methods
“biological” “physical” approach
approach based on the
based on the measurement of liver
quantification of stiffness
biomarkers in serum Ultraso
Direct serum samplesIndirect serum und
biomarkers biomarkers CT
laminin,
type IV collagen, platelet count (PLT), MRI
collagenases, prothrombin index,
ratio of AST to ALT LIVER
metalloproteases etc.
ELASTOGRAPHY
 PREVALENCE OF LIVER
FIBROSIS/CIRRHOSIS AMONG HIGH
RISK GROUPS
HBV/HCV 50 %

ALCOHOL 10 %

DIABETES
MELLITUS 8%

INSULIN
RESISTANCE 5%

Liver fibrosis/cirrhosis prevalence

among general population - 3%
hepa
CHRONIC HCV COMPLICATIONS

Healthy liver
Liver fibrosis

Liver cirrhosis
Hepatocellular carcinoma

hepa
 LIVER FIBROSIS/CIRRHOSIS
ASSESSMENT

INVASIVE METHOD NON-INVASIVE

METHODS
Serum markers, ultrasound, liver elastography,
Liver biopsy and it's limitations CT, MRI etc.
 The sample obtained during the procedure represents small part of
the liver (1/50000)
 Therefore, sampling error can occur (15-30%)
 Pain – 20%
 Bleeding – 0.5%
 Risk of death– 0.01-0.1%
 Difficultly in performing repeated measures
 Limitations of this procedure have led to the
development of non-invasive methods for assessment of liver fibrosis
hepa
 WHY DO WE PREFER NON-INVASIVE METHODS

• Non-invasive
• Simple
• Rapid
• Highly reproducible
• Without complications

hepa
Transient Elastography: FibroScan®
TE measures the velocity of a low frequency (50Hz) elastic shear wave
propagating through the liver. The velocity is directly related to tissue
stiffness. The results are expressed in kilopascals (kPa) and range from 1.5
•to 75 kpa withnon-invasive;
Validated, normal values around 5 kpa.

• rapid and highly reproducible; appears advantageous over liver biopsy

for follow-up determinations;

• has been shown to identify fibrosis stage accurately;

• Performs well in detection of cirrhosis

fibroskaniT miRebuli Sedegebi
91% specificity
kpa-Si and an 87% sensitivity compared to liver biopsy
Metavir
• Most widely qulebTan Semdegnairad
used and validated technique; can be considered the non-
korelirebs.
invasive standard for the measurement of LS

Elasticity 8.6- 9.6- 12.6-

<7.0 7.1-8.5 >14.5
(kPa) 9.5 12.5 14.5
F4
Metavir F0-F1 F1-F2 F2 F3 F3-F4 (cirrhosi
s) hepa
 Diagnosis

• Clinical pictures
• Visualization (ultrasound liver imaging, CT, MRI)
• Liver biopsy
• Laboratory analyses:
–Liver function tests (LFTs). Standard liver panel -
Total bilirubin, Alanine transaminase (ALT), Aspartate
transaminase (AST), AST/ALT ratio, Alkaline
phosphatase (ALP), Gamma glutamyl transpeptidase
(GGT), Albumin.
–Coagulation test
Liver Biopsy
 Complications

• Ascites and peripheral edema

• Portal hypertension
• Esophageal varices and bleeding
• Hepatic encephalopathy
 Liver cirrhosis complications.
Hepatic Encephalopathy
Syn. Hepatoencephalopathy, or Portosystemic
Encephalopathy (PSE)
• Frequently a terminal complication
 Complications: Hepatic Encephalopathy
Definition/Background Information
• It is defined as a spectrum of neuropsychiatric
abnormalities in patients with liver dysfunction, when
other known brain disease has been excluded.
• Signs and symptoms can begin mildly and gradually, or
occur suddenly and severely.
• They may include personality or mood changes,
intellectual impairment, abnormal movements, a
depressed level of consciousness, and other symptoms.
• Fetor Hepaticus: musty, sweetish odor detected on the
patient’s breath, from accumulation of digested by-
products
 Etiology

• Hepatic Encephalopathy is caused a damaged

liver that is incapable of efficiently removing
toxins from blood
• The toxins build up in blood, travel to the
brain, and lead to temporary alteration in
brain function(s)
• It has been suggested that one of the toxins
that is main pathogenic is NH3 (ammonia),
which accumulates in brain cells.
 Risk Factors for Hepatic Encephalopathy
• Binge alcohol drinking
• Constipation
• Dehydration
• Gastro-intestinal bleeding
• Medications such as sleeping pills, or anti-
depressants
• Infection
• Kidney malfunction
• A surgery
Signs and Symptoms of Hepatic Encephalopathy

The signs and symptoms of Hepatic

Encephalopathy may develop gradually over
days, or can occur suddenly.
• Mood and Personality changes
• Forgetfulness
• Inappropriate behavior
• Altered sleep pattern
• Problems with writing, doing simple math
Hepatic Encephalopathy
is a sign of
 Treatment
• Goal: reduce NH3 formation
– Protein restriction (< 40 g/day)
– Sterilization of GI tract with antibiotics and
lactulose
• Antibiotics (such as rifamixin), which can
treat infections as well as help reduce the
amount of toxin-producing bacteria.
• Lactulose, which helps the body flush out
toxins by drawing water from the rest of the
body to the colon
• Liver transplantation, if liver failure
progresses.