II.Bibliographic review and analysis [601597]

1
II.Bibliographic review and analysis

2.1 Cirrhosis
Definition:
Cirrhosis is defined histologically as a diffuse hepatic process characterized
by fibrosis and the conversion of normal liver architecture into structurally
abnormal nodules resulting in h epatic insufficiency. [1]
 This results in decrease in hepatocellular mass, thus function .[1]
 Pathologic features: development of fibrosis to the point that there is
architectural distortion with formation of regenerative nodules
(micronodular / macronodular .)[2][3]

Fig.2. 1 Liver macronodular and micronodular cirrhosis
(www.pathguy.com/lectures/liver.htm )

2
2.1.2 Epidemiology

 Cirrhosis and chronic liver disease were the tenth leading cause of death
for men and the twelfth for women in the United S tates in 2001, killing
about 27 .000 peo ple each year. Also, the cost of cirrhosis in terms of
human suffering, hospital costs, and lost productivity is high. [4][5]
 Established cirrhosis has a 10 -year mortality of 34 –66%, largely
dependent on the cause of the cirrhosis; alcoholic cirrhosis h as a worse
prognosis than primary biliary cirrhosis and cirrhosis due to hepatitis. The
risk of death due to all causes is increased twelvefold; if one excludes the
direct consequences of the liver disease, there is still a fivefold increased
risk of death in all disease categories .[6]
 Little is known on modulators of cirrhosis risk, apart from other diseases
that cause liver injury (such as the combination of alcoholic liver disease
and chronic viral hepatitis, which may act synergistically in leading t o
cirrhosis). Studies have recently suggested that coffee consumption may
protect against cirrhosis, especially alcoholic cirrhosis. [7]
 Cirrhosis is the ninth leading cause of death worldwide and is responsible
for 1.2% of all deaths .

Fig. 2.2 Epidemiology of liver cirrhosis

3
2.1.3 Etiolog y of liver cirrhosis

Cirrhosis is caused by scar tissue that forms in the liver in response to
damage occurring over many years. Each time the liver is injured, it tries to
repair itself. In the process, scar tissue forms. As the scar tissue builds up, liver
function worsens. In advanced cirrhosis, the liver no longer works very well. [8]
It's important to determine the cause of cirrhosis because treating that
underlying cause can help prevent further liver damage. A wide range of
diseases and conditions can damage the liver and lead to cirrhosis.

 I. The c ommon causes of cirrhosis include:
 Chronic alcohol abuse – it is considered to be the predominant cause of
cirrhosis in the US (21%) .
 Chronic viral infections of the liver ( Hepatitis B- infection (15%);
Hepatitis C has emerged as the natio n's leading cause of both chronic
hepatitis and cirrhosis (u p to 26% can develop cirrhosis); Hepatitis D is
extremely rare) .
 Fat accumulating in the liver – it’s a very importa nt and increasing cause
of cirrhosis is NASH (nonalcoholic fatty liver disease) , which develops
from nonalcoholic fatty liver disease (NAFLD). In this condition excess
fat is deposited in the liver leading to inflammation which may progress
to cirrhosis. N ASH is due to insulin resistance and is particularly seen in
diabetics, those who are over -weight and patients with high blood fat
levels (particularly triglycerides). In th e USA, NASH now accounts for
50% of new cases of cirrhosis.
 Destruction of the bile ducts – which carries bile formed in the liver to
the intestines , where it h elps in the digestion of fats. In adults, bile ducts
may become inflamed, blocked, or scarred, du e to another liver disease
called primary biliary cirrhosis .
 Hardening and scarring of the bile ducts – primary sclerosing
cholangitis) .
 Infection by a parasite common in developing countries
(schistosomiasis) .

4
 II. Less common causes (5%) include:
A. Genetic conditions :
 Wilson disease ( copper accumulates in the liver and other parts of the
body) .
 Hemochromatosis ( iron accumulates in the liver and other parts of the
body ).
 alfa1-antitrypsin deficienc y.
 Cystic fibrosis .
 Porfiria .
B. Metabolic conditions:
 Violation of carbohydrate metabolism : glycogenosys l, lll, lV, such as
galactosemia, fructose -1-phosphate aldolase deficiency .
 Violation of lipid metabolism : Gaucher disease, Hand -Schyuller –
Christian, Niemann P ick, family hyperlipidemia (Burger -Grutz) .
 Genera lised xanthomatosis (Wolmand disease) .
 Violation of amino acid metaboIism : Hereditary tyrosinemia, cyst inosis.
 Violation of bile acids metaboIism: Progressive intrahepatic cholestasis
(Beihler disease), hereditary lymphedema (lymphatic vessels defe ct) with
recurrent coilestasis.
C. Others conditions:
 Cholestatic liver diseases – the violation of bile outflow – chronic
cholangitis, Caroli's syndrome, biliary duct stenosis, gall bladder at resia,
congenital biliary cysts.
 Zellweger syndrome – (cerebro -hepato -renal syndrom)
 Drugs including – methotrexate, amiodarone , isoniazid, alpha –
methyldopa.
 Chemical and other toxins – copper, arsenicus, phosphorus, myco – and
phytotoxins .
 Other diseases – Congestive heart failure or tricuspid regurgitation
(although this is rarely seen now due to improved management).

5
2.1.4 Pathophysiology
A. Hepatocytes injury and necrosis
B. Fibrosis
C. Cell regeneration
A. Hepatocytes injury and necrosis:
The cardinal feature of cirrhosis is an increase in fibrous tissue, progressive
and widespread death of liver cells, and inflammation leading to loss of the
normal liver architecture.
Following liver injury, stellate cells in the space of Disse are activated by
cytokines produced by Kupffer cells and hepatocytes. This transforms the
stellate cell into a myofibroblast -like cell, capable of producing collagen, pro-
inflammatory cytokines and other mediators which promote hepatocyte damage
and cause tissue fibrosis.
Destruction of the liver architecture causes distortion and loss of the normal
hepatic vasculature with the development of portosystemic vascular shunts and
the formation of nodules.
Cirrhosis evolves slowly over years to decades, and normally continues to
progress even after removal of the aetiological agent (e.g. a bstinence from
alcohol, venesection in haemochromatosis).
Cirrhosis is a histological diagnosis characterised by diffuse hepatic fibrosis
and nodule formatio.

Fig.2.3 Hepatocytes injury and necrosis (www.nature.com)

6
B. Fibrosis:
– reflects an alteration in the normall y balanced processes of extracellular
matrix production and degradation. The extracellular matrix, the normal
scaffolding for hepatocytes, is composed of collagens (especially types l, lll,
and V), glycoproteins and proteoglycans. [9]

Fibrosis progresse s in stages: [9]
I stage – activation of Kupffer's cells and other cells that participate in necro –
inflammatory process.
ll stage – activation of hepatic stellate cells (HSC).
lll stage – activation of overproduction of myofibroblasts, with the subsequen t
secretion of components of fibrosis in the absence of cytokine.

Fig.2.4 Staging according to Metavir Score (PathologyOullines.com)

7
 Fibrogenesis commences with the activation of Ito cells (Hepatic stellate
cells) by cytokines such as TGF β1(transfo rming growth factor), PDGF
(platelet -derived growth factor), TNF α, EGF1 (epidermal growth factor).

 This induction of Ito cells leads to quantitatively increased (up to ten times
the norm) and qualitatively altered synthesis of the extracellular matrix,
which consists of collagens, glycoproteins, proteoglycans and
glucosaminoglycans.
 Degeneration of the matrix is reduced by a decrease in matrix
metalloproteinases (MMP) with a simultaneous increase in the tissue
inhibitors of metalloproteinases (TIMP).
 Both factors reduce further degradation of connective tissue. [9]
 The hepatocytes are now multilayered instead of normal single -layered
cell plates and lose their microvilli.
 Fenestration of the sinusoids disappears, whereas the sinusoidal
extracellular matri x increases, leading to capillarization of the sinusoids.
 In this way, the distance between the hepatocytes and the blood becomes
greater, and the clearance of macromolecular substances is reduced.
 Stronger flow resistance in the liver leads to portal hyp ertension.
 Portoportal and portocentral bands of connective tissue form, in which
portosystemic intrahepatic shunts develop.

C. Cell regeneration:

Liver cell mass can be restored via an average of less than two cell division
cycles, albeit indivi dual hepatocytes seem to have an intrinsic capacity for up to
70 doublings.
Regeneration is rebundant, appear units and nodules of regeneration that
compress the parenchymal and fibrotic tissue around these 2 processes –
fibrosis and regeneration in th e form of nodules required for the diagnosis of
the liver cirrhosis. [10]

8
2.1.5 Signs and symptoms

Symptoms depend on the etiology of liver cirrhosis, activity of the liver
process and evolutionary stage of actual cirrhosis. [1][2]

 The most common symp toms of cirrhosis are as follows:
 Tiredness (fatigue) or even exhaustion
 Weakness
 Nausea
 Loss of appetite leading to weight loss
 Loss of sex drive
Clinical classification :
A. Latent cirrhosis :
There are no subjective c omplaints or clinical symptoms. This stage is
identified by laboratory parameters, imaging procedures or histological
examination of the liver. Frequency is between 10 and 20%.
B. Manifest cirrhosis:
Manifest cirrhosis is characterized by subjective com plaints and clinical
findings.
Manifest cirrhosis can present in two forms:
Two causative mechanisms:
 Portal hypertension
 Hepatocellular failure
1. liver cirrhosis with portal hypertension , is characterized by:
 ascites
 “medusa head” on the anterior abdominal wall
 hydrothorax
 cardiovascular syndrome
 portal gastropathy
 splenomegaly

9
 hypersplenis m
2. liver ci rrhosis with hepatocellular failure , is characterized by:
 astheno -neurotic syndrome
 encephalopathy
 endocrine/articulare symptoms
 hepatic failure

10
2.1.6 Child -Pugh cl assification of liver cirrhosis
The Child -Pugh classification is a means of assessing the severity of liver
cirrhosis.
The score employs five clin ical measures of liver disease. Each measure is
scored 1 -3, with 3 indicating most severe derangem ent. Modified Child -Pugh
classification of severity of liver disease according to the degree of ascites, the
plasma concentrations of bilirrubin and albumin, the prothrombin time, and the
degree of encephalopathy.
A total score of 5 -6 is considered grad e A (well -compensated disease); 7 -9 is
grade B (significant functional compromise – subcompensated ); and 10 -15 is
grade C ( descompensated disease). These grades correlate with one – and two –
year patient survival.
Measure Compensate d
(class A) Subcompensate d
(class B) Decompensate d
(class C)
Total
bilirubin ,
μmol/l
(mg/dl) <34 (<2) 34-50 (2 -3) >50 (>3)
Serum
albumin , g/dl >3.5 2.8-3.5 <2.8
PT INR <1.7 1.71-2.30 > 2.30
Ascites None Mild Moderate to Severe
Hepatic
encephalopat
hy None Grade I -II (or suppressed
with medication) Grade III -IV (or
refractory)
Total Points 5-6 7-9 10-15
1-Year
Survival 100% 85% 45%
Tab.2.1 Child-Pugh c lassification class A to C

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2.1.7 Diagnosis

A physical examination m ay reveal the following in a patient with cirrhosis:
 The cirrhotic liver is firm and often enlarged in early stages of the disease. The
liver may feel rock -hard. (In advanced stages of cirrhosis, the liver may
become small and shriveled).
 If the abdomen is swollen, we will check for ascites by tapping the flanks and
listening for a dull thud and feeling the abdomen for a shifting wave of fluid.
 Also we will check for signs of jaundice, muscle wasting, and (in male
patients) breast enlargement. [12]
 Patient s with a history of alcoholism, hepatitis B or C, or certain other medical
conditions are at high risk.
 Other tests (blood tests, imaging tests, liver biopsy) may also be performed.
The results of these tests along with the presence of specific compli cations (ascites
and encephalopathy) are used for calculating the Child -Pugh Classification. This is a
staging system (A to C) that helps doctors determine the severity of cirrhosis and
predict the development of future complications. [12][13]

Blood tests
A patient’s medical history can reveal risk factors(such as alcoholism) that warrant
screening for conditions such as hepatitis. Blood tests are also performed to measure
liver enzymes associated with liver function. Enzymes known as aminotransferases ,
including aspartate (AST) and alanine (ALT), are released when the liver is
damaged. [14]

Blood tests may also measure:
 Serum albumin concentration. Serum albumin measures protein in the blood
(low levels indicate poor liver function). [15][16][17]
 Prothro mbin time (PT) . The PT test measures in seconds the time it takes for
blood clots to form (the longer it takes the greater the risk for bleeding). [18][19]
 Alkaline phosphatase(ALP). High ALP levels can indicate bile duct blockage.
[17][20]
 Bilirubin. One o f the most important factors indicative of liver damage is
bilirubin, a red -yellow pigment that is normally metabolized in the liver and
then excreted in the bile. In patients with hepatitis, the liver cannot process
bilirubin, and blood levels of this sub stance rise, sometimes causing
jaundice. [16][19]

12
Imaging tests
Magnetic resonance imaging (MRI), computed tomography (CT), and
ultrasound are all imaging techniques that are useful in detecting and defining
the complications of cirrhosis, such as asci tes and hepatocellular carcinoma.
(However, screening patients with cirrhosis or hepatitis for hepatocellular
carcinoma has not yet been proven to be beneficial. The National Cancer
Institute recommends against it). These imaging tests can also provide
information on the extent of liver damage. [21][22]

Liver biopsy
A liver biopsy is the only definite method for confirming a diagnosis of
cirrhosis. It also helps determine its cause, treatment possibilities, the extent of
damage, and the long -term outloo k.
For example, hepatitis C patients who show no significant liver scarring when
biopsied may have a low risk for cirrhosis. [23]
A biopsy involves a doctor inserting a biopsy fine needle, guided by
ultrasound, to remove a small sample of liver tissue . Local anesthetic is used to
numb the area. Patients may feel pressure and some dull pain. The procedure
takes about 20 minutes to perform. [23]

Fig.2.5 Liver biopsy procedure

13
The biopsy may be performed using various approaches, including:
 Percutaneou s Liver Biopsy. This approach uses a needle inserted
through the skin over the liver area to obtain a tissue sample from the
liver. Various forms of needles are used, including those that use suction
or those that cut out the tissue. This approach should n ot be used in
patients with bleeding problems, and it must be used with caution in
patients with ascites or severe obesity.
 Transjugular Liver Biopsy. This approach uses a catheter (a thin tube)
that is inserted in the jugular vein in the neck and threaded through the
hepatic vein (which leads to the liver). A needle is passed through the
tube, and a suction device collects liver samples. This procedure is risky
but may be used for patients with severe ascites.
 Laparoscopy. This procedure requires a small a bdominal incision
through which the doctor inserts a thin tube that contains small surgical
instruments and a tiny camera to view the surface of the liver. This is
generally reserved for staging cancer or for ascites of unknown cause .[32]

Other tests use d to detect complications of cirrhosis
 Endoscopy. Some doctors recommend endoscopy for patients newly
diagnosed with mild -to-moderate cirrhosis in order to screen for
esophageal varices. (These are enlarged veins in the esophagus that
increase the risk for bleeding). In this test, a fiber optic tube is inserted
down the throat. The tube contains tiny cameras to view the inside of the
esophagus, where varices are most likely to develop .[24][25]
 Paracentesis . If ascites is present, paracentesis is performed t o determine
its cause. This procedure involves using a thin needle to withdraw fluid
from the abdomen. The fluid is tested for different factors to determine
the cause of ascites:
 Tests for Liver Cancer . Patients diagnosed with cirrhosis should be
screened every 6 months to check for the development of liver cancer.
Your doctor will use both a blood test to check for levels of alpha –
fetoprotein and an imaging test (ultrasound, MRI, or CT scan). [22]

14
Complications associated with cirrhosis of the liver in clude :
 Ascites (fluid buildup in the abdomen).
 Variceal hemorrhage (bleeding in the upper stomach and esophagus
from ruptured blood vessels).
Variceal bleeding is caused by portal hypertens ion, which is an increase
in the pressure within the portal vein (the large vessel that carries blood
from the digestive organs to the liver). This increase in pressure is caused
by a blockage of blood flow through the liver as a result of cirrhosis.
Increased pressure in the portal vein causes other veins in the body to
enlarge (varices), such as those in the esophagus and stomach , to bypass
the blockage. These varices become fragile and can bleed easily, causing
severe hemorrhaging and fluid in the abdomen.
 Spontaneous bacterial peritonitis is a form of peritonitis (inflammation
of the membrane t hat lines the abdomen), which is associated with
ascites. Other bacterial infections are also a common complication of
cirrhosis.
 Hepatic encephalopathy (damage to the brain).
Hepatic encephalopathy most often occurs when cirrhosis has been
present for a long time. Toxins produced in our intestines are normally
detoxified by the liver, but once cirrhosis occurs, the liver cannot detoxify
as well.
 Infections. If the patient have cirrhosis, his body may have difficulty fighting
infections. Ascites can lead to bacterial peritonitis, a serious infection.
 Malnutrition. Cirrhosis may make it more difficult for the body to process
nutrients, leading to weakness and weight loss.
 Buildup of toxins in the brain (hepatic encephalopathy). A liver damaged by
cirrhosis isn't able to clear toxins from the blood as well as a healthy liver can.
These toxins can then build up in the brain and cause mental confusion and
difficulty concentrating. With time, hepatic encephalopathy can progress to
unresponsiveness or coma.
 Bone disease. Some people with cirrhosis lose bone strength and are at greater
risk of fractures.
 Gallstones and bile duct stones. Blocked flow of bile can lead to irritation,
infection and the creation of stones.
 Increased risk of liver cancer .
 Acute -on-chroni c cirrhosis. Some people end up experiencing multiorgan
failure.

15
2.2 Viral Hepatitis B

Chronic hepatitis, both hepatitis B and hepatitis C, is another primary cause
of cirrhosis .[26][27]
Chronic hepatitis C is a more common cause of cirrhosis in developed
countries, while hepatitis B is a more common cause of cirrhosis worldwide,
especially in sub -Saharan Africa and parts of Asia. People with chronic
hepatitis B who are co -infected with hepatitis D are especially at risk for
cirrhosis. The long er a patient has had chronic hepatitis, the greater the risk for
eventually developing cirrhosis. [28][29]
The hepatitis virus can produce inflammation in liver cells, causing injury or
destruction. If the condition is severe enough, the cell damage bec omes
progressive, building a layer of scar tissue over the liver. In advanced cases, as
with alcoholic cirrhosis, the liver shrivels in size, a condition called
postnecrotic or posthepatic cirrhosis. [29][30 ]

Hepatitis B
 Hepatitis B virus (HBV) is a member of the hepadnavirus family. [31]
 The virus particle (virion) consists of an outer lipid envelope and an
icosahedral nucleocapsid core composed of protein. The nucleocapsid
encloses the viral DNA and a DNA polymerase that has reverse
transcriptase activity. [32]
 The virus is divided into eight genotypes (A -H) according to overall
nucleotide sequence variation of the genome .[32][33 ][34]

2.2.1 Transmission
Hepatitis B is transmitted through blood and infected bodily fluids .
This can occur through:
 direct blood -to-blood contact
 unprotected sex
 unsterile needles
 from an infected woman to her newborn during the delivery process.

16
Other possible routes of infection include sharing sharp instruments such as
razors, toothbrushes or earrings. Body piercing, ta ttooing and acupuncture are
also possible routes of infection unless sterile needles are used .[35][36]
Hepatitis B is NOT transmitted casually . It cannot be spread through
sneezing, coughing, hugging or eating food prepared by someone who is
infected wi th hepatitis B. Everyone is at some risk for a hepatitis B infection,
but some groups are at higher risk because of their occupation or life choices.

High Risk Groups :
 Health care workers and emergency personnel
 Infants born to mothers who are infected at the time of delivery
 Partners or individuals living in close household contact with an infected
person
 Individuals with multiple sex partners, past or present
 Individuals who have been diagnosed with a sexually transmitted disease
 Illicit drug users (inje cting, inhaling, snorting, popping pills)
 Men who have sex with men
 Individuals who received a blood transfusion prior to 1992
 Individuals who get tattoos or body piercing
 Individuals who travel to countries where hepatitis B is common (Asia, Africa,
South America, the Pacific Islands, Eastern Europe, and the Middle East)
 Individuals emigrating from countries where hepatitis B is common, or born to
parents who emigrated from these countries (see above)
 Families adopting children from countries where hepatit is B is common (see
above)
 Individuals with early kidney disease or undergoing kidney dialysis
 Individuals who use blood products for medical conditions (i.e.hemophilia)
 Residents and staff of correctional facilities and group homes .[36][37 ]

17
2.2.2 Epid emiology of HBV
 patients exposed to HBV, about 5 % develop chronic hepatitis & about
20% of those patients go on to develop cirrhosis.
 Liver is small & shrunken and has mixed micro & macronodular cirrhotic
pattern .
 Invg : Routine investigations + HCV RNA, HBsAg, anti – HBs, HBeAg,
anti – HBe, HEV DNA.
 Of patients exposed to HBV, about 5 % develop chronic hepatitis & about
20% of those patients go on to develop cirrhosis.
 Invg : Routine investigations + HCV RNA, HBsAg, anti – HBs, HBeAg,
anti – HBe, HEV DNA .

Fig.2.6 Epide miology of HBV

 25% of those with chronic hepatitis B end up with liver cirrhosis and/or
cancer without proper management .[38][39]
 60-80% of primary liver cancer worldwide is caused by chronic hepatitis
B1
– Hepatitis B is Serious – Global
– It’s a common disease
– Over 350 million people in the world have chronic hepatitis B1
– Chronic hepatitis B is one of the top 10 causes of death worldwide1
– The hepatitis B virus is 100 times more infectious than HIV2 .[40][41 ]

18
2.2.3 Natural History of HBV I nfection

 Special stains for hepatitis B core (HBc) and hepatitis B surface (HBs)
antigen will be positive and ground -glass hepatocytes signifying hepatitis
B surface antigen (HBsAg) may be present. [42]
 Over 300 -400 million individuals are thought to have hepatitis B
worldwide ,approximately 25% of these individuals may ultimately
develop cirrhosis . [42][43][44]

Fig.2.7 Infection of HBV

2.2.4 Pathophysiology
The virus does not directly kill hepatocytes. The host's immune response to viral
antigens is thought to be the cause of the liver injury in HBV infection. The cellular
immune response, rather than the humo ral immune response, seems to be primarily
involved in disease pathogenesis. Induction of antigen -specific T -lymphocyte
response is thought to occur when host T lymphocytes are presented with viral
epitopes by antigen -presenting cells in lymphoid organs. T hese antigen -specific T
cells mature and expand and then migrate to the liver.
In acute HBV infection, most HBV DNA is cleared from hepatocytes through non –
cytocidal effects of inflammatory byproducts of CD8+ T lymphocytes, stimulated by
CD4+ T lymphoc ytes, notably interferon -gamma and tumour necrosis factor –
alfa.[38][45][46]

19
These cause down -regulation of viral replication, and trigger direct lysis of infected
hepatocytes by HBV -specific CD8+ cytotoxic T cells. In contrast, people with
chronic HBV infection display weak, infrequent, and narrowly focused HBV -specific
T-cell responses, and the majority of mononuclear cells in livers of chronic HBV –
infected people are non -antigen -specific. Due to the presence of HBV in extrahepatic
sites, as well as the presence of covalently closed circular DNA (cccDNA) within
hepatocytes, eradication of the virus is an unrealistic goal based on the currently
available drugs. Covalently closed circular DNA serves as a template for
transcription of pregenomic messenger RNA, a vital initial step in HBV replication.
The continued presence of cccDNA within hepatocytes is considered as a marker of
viral persistence. Unfortunately, current therapies have not been effective in
eradicating cccDNA and are only able to decrease levels. Persistence of even low
levels of cccDNA in the hepatocyte nucleus has been shown to correlate with viral
rebound after discontinuation of therapy. In addition, the integration of HBV DNA to
the hepatocyte nucleus during replication process could explain increased risk for
hepatocellular carcinoma. [33][34][47 ][48]
Furthermore, co -infection with hepatitis C virus (HCV) can synergistically
increase the rate of fibrosis, cirrhosis, and hepatocellular cancer, since both HBV and
HCV occupy the same hepatocyte independently .[49][50]

2.2.5 Signs and symptoms
Signs and symptoms of hepatitis B , ranging from mild to severe, usually
appear abo ut one to four months after you've been infected.
Not everyone who is infected with HBV will experience symptoms of acute
hepatitis —between 30% – 40% of people infected with the virus do not
experience any noticeable symptoms. If symptoms do occur, th ey usually do so
within 4 to 6 weeks after being infected and can last anywhere from one or two
weeks to several months.
Signs and symptoms of hepatitis B may include:
 Abdominal pain / diarrhea
 Dark urine and/or pale stool
 Fever
 Joint pain
 Loss of appetite
 Nausea and vomiting
 Weakness and fatigue

20
 Yellowing of the skin, whites of the eyes, and under the fingernails (jaundice)
[30][37]
Symptoms of chronic hepatitis B can include those typically seen in acute
hepatitis B. They tend to be mild to moderate i n intensity and typically come
and go. Other symptoms can occur, particularly in people who have been
dealing with chronic hepatitis B for many years. Additional symptoms include
rash, hives (urticaria), arthritis and burning/tingling in the arms and legs
(polyneuropathy).

2.2.6 Diagnosis
Separate laboratory tests can diagnose HBV infection and monitor p eople
with chronic hepatitis B. [51]
Blood tests can determine if somebody have the virus in the system and
whether it's acute or chronic. The diagnos is of HBV infection requires the
evaluation of the patient's blood for HBsAg, hepatitis B surface antibody
(HBsAb), and hepatitis B core antibody (HBcAb). Although the presence of
HBsAg indicates that the person is infectious, the presence of HBsAb indicat es
recovery and immunity from HBV infection or successful immunization against
HBV. HBcAb appears at the onset of acute HBV infection, but may also
indicate chronic HBV infection. Interpretation of HBV immunol ogic markers is
shown in Table 5.[52]
Here’s a look at the most important test results to know:
Hepatitis B status HBsAg Anti -HBc
(total) Anti -HBc
(IgM) Anti –
HBs
Never infected with the virus (consider getting the vaccine). Negative Negative Negative Negative
Infection likely took place over the last six months and is still
active. Positive Positive Positive Negative
Infection likely took place over the past six months and is in the
process of clearing. A false -positive is another possibly (HIV –
positive people with this particular test result should have their
HBV viral load checked). Negative Negative Positive Negative
Infection likely took place more than six months ago and has
been successfully controlled by the immune system. Negative Positive Negative Positive
The vaccine was successfully given to prevent HBV infection. Negative Negative Negative Positive
Chronic HBV infection. Positive Negative Positive Negative
Tab.2.2 Interpretation of HBV immunol ogic markers

21
III. Materials and methods of research

The clinical material was selected by the section of hepatology of The
Republican Clinical Hospital, Chisinau, Moldova.
The study was done by working on 30 patients (10 patients with compensated
cirrhosis, 10 patients with subcompensated,10 patients with decompensated)
from different locat ions in the republic of Moldo va.

According to Child -Pugh score

Fig.3.1 – patients according to Child –Pugh score – 34% with compensated, 33%
with subcompensated and 33% with decompensated.

34%
33% 33% According to Child -Pugh score

Class A
Class B
Class C

22

According to sex

Fig.3.2 – patients according to sex, 57 % Male (17 patients), 43% Female (13 patients).

Conclusion: according to the sex, the males have more risk to be affected with
hepatic cirr hosis than females.

According to age

Fig.3.3 – patients according to age , wer e 73% ( 22 patients) > 55 y.o. and 27% (8 patients)
were < 55 y.o.

43%
57% According to sex
female
male
27%
73% According to age
<55
>55

23
Conclusion: according to age, patients with age > 55 y.o. are more affected
with hepatic cirrhosis.

According to origin

Fig.3.4 according to origin, 33% (10pacients) were from urban regions and 67%
(20 pacients) were from rural regions.

Conclusion: according to the origin, pacients living in rural regions are more
affected than these wich are living in urban regions.

33%
67% According to origin
Urban
Rural

24
IV.Results

A. The clinical parameters that were studied and checked are:
I. Right upper quadrant pain
II. Left upper quadrant pain
III. Fatigue and weakness
IV. Abdominal Distention (Bloating)
V. Liver palpation
VI. Liver Percussion

B. The biochemical parameters that were studied and checked are:
I. Alanine T ransaminase (ALT)
II. Aspartate Transaminase (AST)
III. Total B ilirubin
IV. Alkaline Phosphatase
V. Gamma -Glutamyl T ranspeptidase (GGT)
VI. Prothro mbin T ime
VII. Albumin

C. The clinical complications that were studied an d checked are:
I. Ascites
II.Thrombocytopenia
III. Hepatomegaly
IV. Spleenomegaly

D. The extrahepatic manifestations that were studied and checked are:
I. Pancreatitis
II. Cholecystitis
III. Anemia

25
Results

A. I. Right upper quadrant pain

Fig.4.1 – checking the percentage of patients that have moderate /slight right upper quadrant pain.

In the figure Fig.4 .1, in the compensated category we can see that 70% of the
patients have moderate pain in the right upper quadrant and 30% of them have a
slight pain.
In subcompensated – 80% of patients have moderate pain and 20% with slight
pain.
In decompensated – 40% of patients have moderate pain and 60% with slight
upper quadrant pain.

Conclusion: During physical examination, patients wi th compensated and
subcompensated have Moderate Right upper quadrant pain.

70% 80%
40%
30%
20% 60%
0%10%20%30%40%50%60%70%80%90%
Class A Class B Class C
Moderate Right upper quadrant pain
Slight right upper quadrant pain

26
II. Left upper quadrant pain

Fig.4.2 – checking the percentage of patients that have slight / moderate left upper quadrant pain.

In the figure Fig.4.2 , we can see that in c ompensated and decompensated
category – 80% patients have slight left upper quadrant pain and just 20% – have
moderate left upper pain.
In subcompensated -70% of patients have slight pain in the left upper quadrant
and 30% – have moderate left upper qua drant pain.

Conclusion: During physical examination, the patients with hepatic cirrhosis
have s light left upper quadrant pain.

20% 30%
20% 80%
70% 80%
0%10%20%30%40%50%60%70%80%90%
Class A Class B Class C
Moderate Left upper quadrant pain
Slight Left upper quadrant pain

27
III. Fatigue and weakness

Fig. 4.3 – checking the percentage of patients that have slight or moderate fatigue and weakne ss.

We can see in the figure Fig.4.3 that in compensated category 30% of patients
have a slight fatigue and weakness and 70% have a moderate fatigue/weakness.
In subco mpensated, 40% of patients have slight fatigue/weakness and 60%
with moderate fatig ue/weakness.
In decompensated, 10% of patients have slight fatigue and weakness and 90%
with moderate.

Conclusion: During physical examination, the patients with hepatic cirrhosis
decompensated have moderate fatigue and weakness.

70%
60% 90%
30% 40%
10%
0%10%20%30%40%50%60%70%80%90%100%
Class A Class B Class C
Moderate fatigue and weakness
Slight fatigue and weakness

28
IV. Abdominal Di stention (Bloating)

Fig.4.4 – checking the percentage of patients that have/doesn’t have abdominal distention (bloating).

In the figure Fig.4.4 , we can see that in compensated 60% of patients have
abdominal distention and 40% doesn’t have.
In subco mpesated, 80% of patients have abdominal distention, while 20%
doesn’t have.
In decompensated, 70% of them have abdomina l distention and 30% of them
doesn ’t have.

Conclusion: During physical examination, in hepatic cirrhosis all the patients
complaint a bdominal distention.

60% 80%
70%
40%
20% 30%
0%10%20%30%40%50%60%70%80%90%
Class A Class B Class C
have Abdominal Distention(bloating)
doesn't have Abdominal Distention(bloating)

29
V. Liver palpation

Fig.4.5 – checking the percentage of patients that have slightly rough surface and regular edges /
rough surface and round edges of liver during palpation.

In the figure Fig.4.5 , we can see that in compens ated and decompensated
30% of patients have a slightly rough surface and regular edges of liver while
70% have a rough surface and round edges during palpation.
In subcompensated, 40% of patients have a slightly rough surface and regular
edges of live r and 60% have a rough surface with round edges during palpation.

Conclusion: According to physical examination, more r ough surface and
regular edges of liver (during palpation) almost all patients.

70%
60% 70%
30% 40%
30%
0%10%20%30%40%50%60%70%80%
Class A Class B Class C
Rough surface and regular edges of liver (during palpation)
Slightly rough surface and regular edges of liver (during palpation)

30
VI. Liver Percussion

Fig.4.6 – checking the perce ntage of patients that have normal liver span at midsternal and
midclavicular line/ abnormal liver span at midsternal and midclavicular line during percussion.

In the figure Fig.4.6 , we can see that in compensated and decompensated
30% of patients hav e a normal liver span in the mi dsternal and midclavicular
line, while 70% have abnormal liver span at the midsternal and midclavicular
line during percussion.
In subcompe nsated, 40% of patients have a normal liver span at midsternal
and midclavicular l ine and 60% have abnormal liver span at the midsternal and
midclavicular line during percussion.

Conclusion: According to physical examination , almost all patients have more
abnormal liver span at midsternal and midclavisular(during percussion) .

70%
60% 70%
30% 40%
30%
0%10%20%30%40%50%60%70%80%
Class A Class B Class C
Abnormal liver span at midsternal and midclavicular line (during percussion)
Normal liver span at midsternal and midclavicular line (during percussion)

31
B. I. Alanine T ransaminase (ALT)
Control group ρ<0.05 between class B and class C
Tab.4 .1 – ALT amounts in the patients according to thei r categories.
In general, normal ALT amoun t ranges between 0 U/L – 41 U/L, so according
to this, we will see the percentage of the patients that have elevated ALT in the
following figure Fig.4.7:

Fig.4.7 – checking the percentage of patien ts that have normal/elevated ALT according to their
category.
30% 40% 40% 70%
60% 60%
0%10%20%30%40%50%60%70%80%
Class A Class B Class C
Normal ALT
Elevated ALTClass A
patient Nr. ALT (U/L) Class B
Patient Nr. ALT (U/L) Class C
Patient Nr. ALT (U/L)
1. 24 1. 32.4 1. 23
2. 20.7 2. 20.9 2. 33.4
3. 41.2 3. 70 3. 49
4. 50.7 4. 19.1 4. 118
5. 70.2 5. 67.2 5. 64.2
6. 10.6 6. 37 6. 78.5
7. 50.2 7. 64.2 7. 151.3
8. 153 8. 93.5 8. 34
9. 67.1 9. 47 9. 33.7
10. 69.8 10. 70.1 10. 52.4
MEAN
55.75± 1.17 52.14±1.27 63.75±0.93

32
We can observe in the figure Fig.4.7 that in compensated there were 30% of
patients that have normal ALT and 70% that have elevated ALT in their
biochemical analysis.
In subcompensated and decompensated, 40% of patients have normal ALT
while 60% have elevated ALT in their biochemical analysis.

Fig.4.7.1 – checking the differences of the ALT average in the patients according to their categories

According to this figure Fig.4.7 .1 we ca n see that in subcompensated the
patients have the lower ALT average of 52.14 U/L.
In compensated the patien ts have an ALT average of 55.75 U/L.
In decompensated the patients have the highest ALT average of 63.75 U/L.

Conclusion: According to bioche mical tests , in patients with decompensated
the average of ALT is more elevated, ρ<0.05 between class B and class C .

Class A Class B Class C55.75± 1.17 52.14±1.27 63.75±0.93 ALT average
Class A
Class B
Class C

33
II. Aspartate T ransaminase (AST)
Control group ρ<0.05 between class A and class B / ρ<0.05 between class B and class C
Tab.4 .2- AST amounts in the patients according to their categories.
In general, normal AST amoun t ranges between 0 U/L – 31 U/L, so according
to this, we will see the percentage of the patients that have elevated AST in the
following figure Fig.4.8:

Fig.4 .8- checking the percentage of patients that have normal/elevated AST according to their
category.
20%
10% 10% 80% 90% 90%
0%10%20%30%40%50%60%70%80%90%100%
Class A Class B Class C
Normal ALT
Elevated ALTClass A
Patient Nr. AST(U/L) Class B
Patient Nr. AST(U/L) Class C
Patient Nr. AST(U/L)
1. 67 1. 73.2 1. 29.6
2. 12.2 2. 112.7 2. 51.2
3. 44.2 3. 97 3. 83
4. 52.8 4. 29.0 4. 124
5. 99.5 5. 80.6 5. 113.1
6. 19.0 6. 60 6. 60.2
7. 92.3 7. 56.5 7. 88.6
8. 193.6 8. 111.3 8. 66
9. 74.1 9. 52.7 9. 48.5
10. 66.3 10. 95.1 10. 60.2
MEAN
72.1±1.46 76.81±1.12 73.97 ±1.39

34
We can observe that in compensated there were 20% of pat ients that have
normal AST and 80% that have elevated AST in their biochemical analysis.
In subcompensated and decompensated , 10% of patients have normal AST
and 90% have elevated AST in their biochemical analysis.

Fig.4.8 .1- checking the difference s of the AST average in the patients according to their categories.

According to this figure Fig.4.8.1, we can see that in the compensated the
patients have lowest AST average of 72.1 U/L.
In decompensated, the patients have an AST average of 73.97 U/L.
In subcompensated, the patients have the highest AST average of 76.81 U/L .

Conclusion: According to biochemical tests, in patients with hepatic cirrhosis
subcompena ted the AST average it’s highe r, ρ<0.05 between class A and class
B / ρ<0.05 between class B and class C.

Class A Class B Class C72.1±1.46 76.81±1.12
73.97±1.39 AST average
Class A
Class B
Class C

35
III. Total B ilirub in
Control group ρ<0.05 between class C and class A / ρ<0.05 between class C and class B
Tab.4.3 – Total B ilirubin amounts in the patients according to their categories .
In general, normal T otal Bilirubin amount ranges between 5.1 UMOL/L –
22 UMOL/L. So according to this, we will see the percentage of t he patients that have
elevated T otal Bilirubin in the following figure Fig.4.9:
Fig.4 .9 – checking the percentage of pati ents that have normal/elevated Total B ilirubin according to
their category.
80%
30%
10% 10% 70% 90%
10%
0%10%20%30%40%50%60%70%80%90%100%
Class A Class B Class C
Normal Total Bilirubin
Elevated Total Bilirubin Decreased Total bilirubinClass A P atient
Nr. Total B ilirubin
(UMOL/L) Class B
Patient Nr. Total B ilirubin
(UMOL/L) Class C
Patient Nr. Total B ilirubin
(UMOL/L)
1. 24 1. 91 1. 81
2. 6.2 2. 33.3 2. 64.5
3. 10.0 3. 40.6 3. 121
4. 9.5 4. 43.3 4. 122
5. 15.8 5. 25.2 5. 51
6. 4.8 6. 33 6. 10.1
7. 17.2 7. 15.8 7. 239
8. 18 8. 13.9 8. 117
9. 13 9. 24.6 9. 124.4
10. 18.5 10. 15.8 10. 42.8
MEAN
13.7±0.43 33.65 ±026 97.28 ±0.21

36
In the figure Fig.4.9, we can see that in compensated 80% of patients have
normal Total Bilirubin, 10% of pacients have elevated Total B ilirubin and 10%
of pacients have decreased total bilirubin .
In subcompensated, just 30% of pacients have normal Total B ilirubin and
70% of patients have elevated.
In decompensated, 90% have elevated Total B ilirubin and on ly 10% of
pacients have normal Total B ilirubin.

Fig.4.9 .1- checking the differences of the Total Bilir ubin average in the patients according to their
categories.

According to this figure Fig.4.9.1, we can see that in compensat ed the
patients have the lower Total B ilirubin average of 13.70 UMOL/L.
In subco mpensated, the patients have a Total B ilirubin average of 33.65
UMOL/L.
In decompensated, the patien ts have the hi gher Total B ilirubin average of
97.28 UMOL/L.

Conclusion: According to biochemical analysis, in patients with hepat ic
cirrhosis decompensated the Total B ilirubin average is more elevated, ρ<0.05
between class C and class A / ρ<0.05 between c lass C and class B .
Class A Class B Class A13.7±0.43 33.65±026 97.28±0.21 Total Bilirubin average
Class A Class B Class A

37
IV. Alkaline Phosphatase
Control group ρ<0.05 between class C and class A / ρ<0.05 between class C and class B
Tab.4.4 – Alkaline Phosphatase amounts in the patients according to their categories.
In general, normal Alkaline P hosphatase amount ranges between 30 U/L – 115 U/L,
so according to thi s, we will see the percentage of t he patients that have elevated
Alkaline P hosphatase in the following figure Fig.4.10:
Fig 4.10 – checking the percentage of pati ents that have normal/elevated Alkaline P hosphatase
according to their category.
80%
60%
20% 20% 40% 80%
0%10%20%30%40%50%60%70%80%90%
Class A Class B Class C
Normal alkaline phosphatase
Elevated alkaline phosphataseClass A
Patient Nr. Alkaline
Phosphatase
(U/L) Class B
Patient Nr. Alkaline
Phosphatase
(U/L) Class C
Patient Nr. Alkaline
Phosphatase
(U/L)
1. 78.9 1. 190.4 1. 211.5
2. 66.7 2. 149.8 2. 140.9
3. 127.4 3. 129.1 3. 365.9
4. 125.3 4. 61.2 4. 160.1
5. 84.4 5. 49.1 5. 129
6. 112 6. 75.8 6. 98
7. 98.7 7. 79.9 7. 134.1
8. 100.8 8. 112 8. 139.8
9. 99.4 9. 240.9 9. 185.9
10. 62.6 10. 81.8 10. 108
MEAN
95.65 ±0.56 117±0.44 167.32 ±0.28

38
In the fig ure Fig.4.10, we can observ e that in compensated 80% of patients
have normal Alkaline P hosphatase in their bi ochemical analysis and only 20%
have elevated Alkaline P hosphatase.
In subcompensated, 60% of patients have normal Alkaline P hosphatase in
their biochemical analysis and 40% have elevated Alkaline Phosphatase .
In decompensated, just 20% of patients have normal and 70% have elevated
Alkaline P hosphatase amounts in their biochemical analysis.

Fig 4.10 .1- checking t he differences of the Alkaline Phosphatase average in the patients according
to their categories.

According to this figure Fig.4.10.1, we can see that in compen sated the
patients have lowest Alkaline P hosphatase average of 95.65U/L.
In subcom pensated, the patients have an Alkaline Phosphatase average of 117
U/L.
In decompensated, the patients have the highest Alkaline P hosphatase average
of 167.32 U/L.

Conclusion: According to biochemical analysis tests, in patients with hepat ic
cirrhosis decompensated the Alkaline P hosp hatase a verage is more elevated,
ρ<0.05 between class C and class A / ρ<0.05 between class C and class B .
Class A Class B Class C95.65±0.56 117±0.44 167.32±0.28 Alkaline Phosphatase average
Class A
Class B Class C

39
V. Gamma -glutamyl transpeptidase (GGT)
Contr ol group ρ<0.05 between class C and class A
Tab.4.5 – Gamma -Glutamyl T ransferase (GGT) amounts in the patients according to their categories.
In general, normal GGT amoun t ranges between 0 U/L – 50 U/L, so according to
this, we will see the percentage of the p atients that have elevated GGT in the
following figure Fig.4.11:
Fig.4.11 – checking the percentage of patients that have normal/elevated GGT according to their
categories.
30% 30%
20% 70% 70% 80%
0%10%20%30%40%50%60%70%80%90%
Class A Class B Class C
Normal GGT
Elevated GGTClass A
Patient Nr. GGT(U/L) Class B
Patient Nr. GGT(U/L) Class C
Patient Nr. GGT(U/L)
1. 39.5 1. 161 1. 151.6
2. 23.9 2. 50.4 2. 32.9
3. 294.8 3. 28.2 3. 1543.01
4. 195.9 4. 18.9 4. 82.7
5. 279.9 5. 141.6 5. 56
6. 29.8 6. 28.2 6. 46.1
7. 87.64 7. 90.1 7. 85.6
8. 70.6 8. 242.2 8. 150.2
9. 59.7 9. 145.8 9. 142.7
10. 59 10. 246.6 10. 112
MEAN
114.07 ±0.40 115.3 ±0.41 248.55 ±0.12

40
In the figure Fig.4.11, we can see than in compensated and subcompensated,
just 30% of patients have normal GGT amounts and 70% have elevated GGT.
In decompensated, 20% of patients have normal GGT amounts and 80% of
them have elevated GGT amounts in their biochemical analysis.

Fig.4.11 .1 – checking the differences of t he Gamma -Glutamyl T ransferase (GGT) average in the
patients according to their categories.

According to this figure Fig.4.11 .1, we can see that the patients have in
compensated the GGT average of 114.07U/L and in subcompensated an
average of 115.3 U/L.
In dec ompensated category, the patients have a highest GGT average of
248.55U/L.

Conclusion: According to biochemical analysis tests, in patients with hepatic
cirrhosis decompensated, the GGT average is more elevated , ρ<0.05 between
class C and class A .

Class A Class B Class C114.07±0.40 115.3±0.41 248.55±0.12 GGT average
Class A
Class B
Class C

41
VI. Prothrombin T ime
Control group ρ<0.05 between class A and class C
Tab.4 .6- Prothrombin T ime in the patients according to their categories.
In general, normal Prothromb in Time ranges between 80% -100%, so according to
this, we will see the percentage of the patients that have decreased Prothromb in Time
in the following figure Fig.4.12:
Fig.4.12 – checking the percentage of patients that hav e normal/decreased Prothrombin T ime
according to their categories.
20%
10% 10% 80% 90% 90%
0%10%20%30%40%50%60%70%80%90%100%
Class A Class B Class C
Normal Prothrombin Time
Decreased Prothrombin TimeClass A
Patient Nr. Prothrombin
Time % Class B
Patient Nr. Prothrombin
Time % Class C
Patient Nr. Prothrombin
Time %
1. 62% 1. 61% 1. 42%
2. 86% 2. 74% 2. 70%
3. 64% 3. 65% 3. 11%
4. 60% 4. 55% 4. 25.8%
5. 53% 5. 64% 5. 60.6%
6. 72% 6. 55% 6. 77%
7. 55.7% 7. 58% 7. 70%
8. 73% 8. 80% 8. 48%
9. 73% 9. 61% 9. 81%
10. 85% 10. 70% 10. 66%
MEAN
68.37 ±1.32 64.30 ±1.44 55.14 ±1.67

42
In the figure Fig.4.12 , we can see that in compensated just 20% of pa tients
have normal Prothrombin T ime and 80% have a decreased Prothrombin T ime.
In subcompensated and decompensated, just 10% of pa tients have normal
Prothrombin T ime and 90% have decreased Prothrombin T ime.

Fig.4.12 .1- checking the differences of the Prothrombin T ime average in the patients according to
their categories.

According to this figure Fig.4.12 .1, we can see that in c ompensated the
patients have a Prothrombin T ime average of 68.37%.
In subco mpensated, the patients have a Prothrombin T ime average of 64.3%.
In decompensated, the pac ients have the lowest Prothrombin T ime average of
55.14%.

Conclusion: According to biochemical analysis tests, in patients hepatic
cirrhosis with decompensated Prothrom bin Time average it’s decreased, ρ<0.05
between class A and class C .

Class A Class B Class C68.37±1.32 64.30±1.44
55.14±1.67 Prothrombin Time average
Class A Class B Class C

43
VII. Albumin
Control group ρ<0.05 between class A and class C
Tab.4.7 – Albumin amounts in the patients according to their categories.
In general, normal Albumin ranges between 35 – 55 g/l, so according to this, we will
see the percentage of the patients that have decreased Albu min amount according to
their categories Fig.4.13:
Fig.4.13 – checking the percentage of patients that have normal/elevated Albumin according to their
categories.
100%
90%
20%
0% 10% 80%
0%20%40%60%80%100%120%
Class A Class B Class C
Normal Albumin
Decreased AlbuminClass A
Patien t Nr. Albumin (g/l) Class B
Patient Nr. Albumin (g/l) Class C
Patient Nr. Albumin (g/l)
1. 38.7 1. 41.4 1. 28.8
2. 44.5 2. 40.3 2. 35.5
3. 40.5 3. 36.7 3. 41.7
4. 42 4. 41.7 4. 22.2
5. 40.2 5. 39 5. 24.5
6. 37.7 6. 37.9 6. 32.7
7. 46 7. 44.4 7. 13.4
8. 44.5 8. 29.6 8. 17.9
9. 43 9. 38.4 9. 22
10. 45.4 10. 42.7 10. 30
MEAN
42.25 ±1.15 39.21 ±1.09 26.87 ±0.82

44
We can observe in the figure Fig.4.13, that in compensated all 100% of
patients have norma l Albumin in their biochemical analysis.
In subcompensated, there were 90% of patients that have normal Albumin
and just 10% that have elevated A lbumin.
In decompensated, just 20 % of patients have a normal amount of Albumin
and 80% that have elevat ed Albumin.

Fig.4.13.1 – checking the differences of the Albumin average in the patients according to their
categories.

According to this figure Fig.4 .13.1, we can see that in decompensated the
patients have the lower Albumin average of 26.87 g/l.
In subcompensated, the patients have a n Albumin average of 39.21 g/l.
In compensated, the patients have the highest Albumin average of 42.25 g/l.

Conclusion: According to biochemical analysis tests, in patients with hepatic
cirrhosis decompens ated the Albumin it’s decreased , ρ<0.05 between class A
and class C .

Class A Class B Class C42.25±1.15 39.21±1.09
26.87±0.82 Albumin average
Class A Class B Class C

45
C. I. Ascites

Fig.4 .14- checking the percentage of patients with or without ascites according to their categories.

In the figure Fig.4 .14, we can see that in compensated 30% of patient s have
ascites and 70% doesn’t have.
In subcompensated, 6 0% of patients have ascites and 40% of them doesn’t
have.
In decompensated, 8 0% of patients have ascites and 20% of patients doesn’t
have.

Conclusion: During the physical examination we found that 1/3 of the patients
complaint ascites.

30% 60% 80%
70%
40%
20%
0%10%20%30%40%50%60%70%80%90%
Class A Class B Class C
With ascites
Without ascites

46
II. Thrombocytopenia

Fig.4 .15- checking the percentage of patients with normal average of thrombocytes and wich have
thrombocytopenia or thrombocytosis according to their categories.

In the figure Fig.4 .15, we can see that in compensated 6 0% of p atients have
thrombocytopenia, 3 0% of pacients h ave a normal amount of thrombocy tes and
just 10% of them have thrombocytosis.
In decompensated, 70% of pat ients have thrombocytopenia, 20% have a
normal am ount of thrombocy tes and just 10% of them have thrombocytosis.
In subcompensated, just 10% of patient s have normal amount of trombocy tes
and 90% have thrombocytopenia.

Conclusion: Patients with hepatic cirrhosis subcompensated have
thrombocytopenia mo re common than compensated and decompensated
patients.

60% 70% 90%
30%
20%
0% 10% 10% 10%
0%10%20%30%40%50%60%70%80%90%100%
Class A Class B Class C
Thrombocytopenia Normal Thrombocytosis

47
III. Hepatomegaly

Fig.4 .16- checking the percentage of patients with/without hepatomegaly according to their
categories

In the figure Fig.4 .16, we can see that in compensated 60% of pat ients have
hepatomegaly, and 40% of them doesn’t have.
In subcompensated, 70% of pat ients have hepatomegaly and 3 0% from them
doesn’t have.
In decompensated, 80% of pat ients have hep atomegaly and just 20% of
patients doesn’t have.

Conclusion: During p hysical examination to patients with decompensated it’s
more common hepatomegaly and compensated and subcompensated patients
are equals.

60% 70% 80%
40%
30%
20%
0%10%20%30%40%50%60%70%80%90%
Class A Class B Class C
With hepatomegaly without hepatomegaly

48
IV. Spleenomegaly

Fig.4 .17- checking the percentage of patients with/without spleenomegaly according to their
categories

In the figure Fig.4.17 , we can see that in compensat ed and subcompensated
70% of pat ients have spleenomegaly, and 30% of them doesn’t have.
In decompensated, 9 0% of p atients have spleenomegaly and 1 0% from them
doesn’t have.

Conclusion: During physical examination, patients with compensated and
decompensated complaint spl eenomegaly.

70% 70% 90%
30% 30%
10%
0%10%20%30%40%50%60%70%80%90%100%
Class A Class B Class C
With spleenomegaly
without spleenomegaly

49
D. I. Pancreatitis

Fig.4.18 – checking the percentage of patients with/without pancreatitis according to their categories

In the figure Fig.4.18 , we can se e that in compensated 50% of pat ients have
pancreatitis and 50% doesn’t have.
In subcompensated, 60% of pat ients have pancreatits and 40% – doesn’t have.
In decompensated, 90% of pat ients have pancreatitis and just 10% of the
patients doesn ’t have.

Conclusion: During physical examination and bioch emical test, are found
changes in pancreas in 1/2 of patients and more common in decompensated
patients.

50% 60% 90%
50%
40%
10%
0%10%20%30%40%50%60%70%80%90%100%
Class A Class B Class C
With pancreatitis
Without pancreatitis

50
II. Cholecy stitis

Fig.4 .19- checking the percentage of patients with/without cholec ystitis according to their
categories

In the figure Fig.4 .19, we can see that in compensated just 30% of pat ients
have cholecystitis and 7 0% of them doesn’t have.
In su bcompensated, 6 0% of p atients have cholecystitis and 40% of pat ients
doesn’t ha ve.
In decompensated, 8 0% of p atients have cholecystitis and just 20% of them
doesn’t have.

Conclusion: During ultrasound investigation methods, the patients with hepatic
cirrhosis compensated are with complications of cholecystitis.

30% 60% 80%
70%
40%
20%
0%10%20%30%40%50%60%70%80%90%
Class A Class B Class C
With cholecystitis
Without cholecystitis

51
III. Anemia

Fig.4 .20- checking the percentage of patients with or without anemia according to their categories .

In the figure Fig.4.20, we can see that in compensated just 30% of patients
have anemia and 70% – doesn’t have.
In su bcompensated, 4 0% of p atients have anemia and 60% of pat ients doesn’t
have.
In decompensated, 8 0% of p atients have anemia and just 20% of pat ients
doesn’t have.

Conclusion: During CBC test the hemoglobulin level it’s slightly decreased in
patients with hepatic cirrhosis.

30% 40% 80%
70%
60%
20%
0%10%20%30%40%50%60%70%80%90%
Class A Class B Class C
Anemia
Normal

52
V. Conclusion

1. After all investigations, we concluded that the males have more
risks to be affected than females with hepatic ci rrhosis, with age
> 50 y.o. and people living in rural regions are more affected.

2. During physical examination, in patients with liver cirrhosis (child
class B and C) we determin ed a more serious abdominal distention,
fatigue and weakness.

3. According to biochemical analysis tests, in patients with hepatic
cirrhosis we determined a more common hepatic syndrome:
cytolitic syndrome( high ALT,AST ) and cholestatic syndrome (high
Bilirubin Level, Phosphate Alkaline ) . The h epato – depres sion
syndrome (low A lbumin level , decrease of the Prothrombin Time )
in patients with liver cirrhosis child class C .

4. According hematological abnormalities , we determined
thrombocytopenia , the leukocytes are decreased in patients with
hepatic cirr hosis child class C more severe .

53
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58
VII. Statement

I hereby decla re that the license thesis titled – Evaluation of clinico –
biochemical syndroms and instrumental data in patients with Cirrhosis by
Hepatitis B viral etiology is written by me and has never been submitted to
another university or institution of higher edu cation in the country or abroad.
Also, that all sources used, including those on the Internet, are given in the
paper with the rules for avoiding plagiarism:
– all the fragments of text reproduced exactly, even in his own translation from
another language are written between quotation marks and have a detailed
reference source;
– reformulation of the texts in own words written by other authors have detailed
reference;
– summarizing the ideas of other authors have detailed reference to the original
text.

Date Nashat Abu Amer