Epidemiological Study On Prevelance of Liver Cancer in District Gujranwala

EPIDEMIOLOGICAL STUDY ON PREVELANCE OF
LIVER CANCER IN DISTRICT GUJRANWALA
Ammara Rafiq
USKT/20104024-082
MS- ZOOLOGY
DEPARTMENT OF ZOOLOGY
FACULTY OF SCIENCES
UNIVERSITY OF SIALKOT
August, 2022
Epidemiological study on prevalence of liver cancer in
district Gujranwala
By
Ammara Rafiq
USKT/20104024-082
MS- ZOOLOGY
Department of Zoology
Faculty of sciences
UNIVERSITY OF
SIALKOT
August, 2022
A thesis submitted in conformity with the requirements for the Degree of MS zoology,
Department of Zoology, Faculty of Sciences, University of Sialkot, Punjab, Pakistan.
Research Scholar
Miss. Ammara Rafiq

USKT/20104024-082
MS Zoology
University of Sialkot
Supervisor
Dr. Aqeela Zahra

Assistant Professor
Department of zoology
Co-Supervisor
Dr. Adeel Khalid

Assistant Professor
Department of zoology
II
Certificate
It is certified that Ammara Rafiq, Registration No. 20105017, has carried out all the work
related to this proposal under my supervision at the Department of Zoology, University of
Sialkot and the topic/area is satisfactory in terms of its originality and contribution.
Date: Supervisor:
Dr. Aqeela Zahra
Assistant Professor
III
Plagiarism Undertaking
I solemnly declare that research work presented in the thesis titled “Epidemiological
study on prevalence of liver cancer in district Gujranwala” is solely my own research
work.
I understand the zero-tolerance policy of HEC and University of Sialkot towards

plagiarism. Therefore, I as an author of the above titled thesis declare that no portion of
my thesis has been plagiarized and any material used as reference is properly referred /
cited/acknowledged.
I undertake if I am found guilty of any formal plagiarism in the above titled thesis even
after award of MS Degree, the University reserves the right to withdraw/revoke my MS
degree and that HEC and the university has the right to publish my name on the
HEC/University website on which names of students are placed who submitted
plagiarized thesis.
Ammara Rafiq
USKT/20104024-082
Date:
IV
Final Approval
Epidemiological Study on prevalence of liver cancer in district Gujranwala
By
Ammara Rafiq
USKT/201040-082
Has been approved
For the University of Sialkot
External Examiner:
Dr.
Assistant Professor
Department of
Supervisor:
Dr Aqeela Zahra
Assistant Professor
Department of zoology University of Sialkot
HOD:
Dr Rooma Adalat
Department of zoology University of Sialkot
V
To
My Beloved Parents
Specially My Father
For his endless
Support
VI
Acknowledgment
All praise for Allah Almighty, our creator. I express my utmost thanks to Almighty Allah
who has endowed my brain to utilize my proficiencies along with self-conscience for the
technology and scientific ingenuity to man questionnaire base study and remarkable
deduction to ponder over the forces of nature.
I offer my gratitude to prophet Muhammad (SAW) who is the light of guidance and
knowledge for humanity. He taught us “If any one travels on a road in search of
knowledge, God will cause him to travel to one of the roads of paradise”
I feel great pleasure in expressing my heartiest obligation to my respected and eruditely
supervisor, Dr. Aqeela Zahra admiringly pleased manners to listen my problems during
my research.
I say special thanks to my parents and my friends for their encouragement and sport
during the preparation of my thesis.
Ammara Rafiq
VII
TABLE OF CONTENTS
Certificate…………………………………………………………………………………….. ⅲ
Plagiarism Undertaking…………………………………………………………………... …. ⅳ
Final Approval……………………………………………………………………………….. ⅴ
Dedications…………………………………………………………………………………... ⅵ
Acknowledgement………………………………………………………………………... … ⅶ
Table of Content……………………………………………………………………………... ⅷ
List of Figures………………………………………………………………………………... ⅸ
List of Tables…………………………………………………………………………….. …. ⅹ
List of Abbreviations………………………………………………………………………… ⅻ
Abstract…………………………………………………………………………………….. ⅹiv
Chapter 1 Introduction…………………………………………………………………….. 1
1.1 Introduction of the Study………………………………………………………………… 1
1.2 Purpose of Study……………………………………………………………………......... 5
1.2.1 Research Objective……………………………………………………………….. 5
1.2.3 Problem Statement ………………………………………………………………. 5
1.3 Hypothesis of Study……………………………………………………………………… 5
1.4 Significance of Study…………………………………………………………………….. 5
VII
I
Chapter 2 Review of Literature……………………………………………………………. 6
Chapter 3 Research Methodology…………………………………………………………. 19
4.1 Study Design and Population……………………………………………………………… 19
4.2 Exposure Assessment……………………………………………………………………… 19
4.3 Outcome Assessment………………………………………………………………………. 20
4.4 Statistical analysis………………………………………………………………………….. 20
Chapter 4 Results and Data Analysis……………………………………………………….. 21
Chapter 5 discussion and Conclusion……………………………………………………….. 32
References …………………………………………………………………………………...... 37
IX
LIST OF FIGURES
Figure 1.1 Primary HCC tumor metastasizes to the lung via bloodstream………. ……. 2
Figure 1.2 The Ras/Raf/MAPK Pathway………………………………………………. 4
X
LIST OF TABLES
Table 4.1 Percentage distribution of different age groups of liver Cancer
patients……………………………………………………………………..... 21
Table 4.2 Percentage distribution of different age groups according to
Alcohol consumption………………………………………………………… 22
Bloating ……………………………………………………………………... 22
Jaundice ……………………………………………………………………… 23
Obesity ………………………………………………………………………. 23
Urine color…………………………………………………………………… 24
Anxiety ……………………………………………………………………… 24
Fever ………………………………………………………………………… 25
Skin color …………………………………………………………………… 25
Hepatitis C …………………………………………………………………… 26
XI
Blood pressure ………………………………………………………… 26
Chemotherapy ……………………………………………………………… 27
Diabetes …………………………………………………………………… 27
Exposure to Aflatoxins ……………………………………………………. 28
Lifestyle.…………………………………………………………………… 28
Hepatitis C ……………………………………………………………… 29
Abdominal mass ………………………………………………………… 29
Reduce weight …………………………………………………………. 30
Heart problem……………………………………………………………. 30
Loss of appetite …………………………………………………………. 31
XII
LIST OF ABBREVIATIONS
HCC Hepatocellular carcinoma
HBV Hepatitis C virus
HBV Hepatitis B virus
pRB retinoblastoma protein
CDK2 Cyclin dependent kinase 2
MAPK Mitogen-activated protein kinase
EGFR Epidermal growth factor receptor
TGF-@ Transforming growth factor alpha
PBC primary biliary cholangitis
IARC International Agency for Cancer Research
XII
I
ABSTRACT
One of the primary causes of mortality in Asia is due to liver cancer. Chronic hepatitis C
virus (HCV) infection has a greater impact on the epidemiology of liver cancer in Asia
than hepatitis B virus (HBV). The second greatest cause of cancer-related fatalities
worldwide is liver cancer. It is becoming more prevalent in Pakistan and may be the most
frequent cancer among adults and older guys. Global contribution for hepatitis C of
Pakistan significantly increased and has males. Global contribution for hepatitis C of
Pakistan significantly increased and has high rates of prevalence (>3%) in the world. In
order to find out how common liver cancer is in the Gujranwala district; this study was
carried out. For these study 100 infected patients (68% males and 32% females) was
visited in local hospital of district Gujranwala. The study was conducted with the help of
questionnaire.
Which include sex, areas, job, age etc. results revealed that male population were more
effected with liver cancer than females (68% male and 32% females), it was also
observed that these patients were also infected with different diseases diabetes, hepatitis
C, hepatitis B, obesity jaundice (52%, 71%, 67%, 41% and 69%) respectively. Moreover,
it was observed people live in industrial areas were more infected by liver cancer and
liver disease than other areas. Results revealed that population of elder age were more
suffer from this disease. Hepatitis B and C were also prevailing and continue infection of
these were resulted in liver cancer. Results revealed that population of elder age were
more suffers. People living in industrial areas suffer more than people living in non-
industrial areas. The study was significantly helpful to find the most effective sites of
liver cancer. Moreover, to identify the expected sign and symptoms which was
commonly observed in patients? Such documented data was being helpful for different
institutions to pinpoint that site and overcome by taking helpful measures.
It is predicted that hepatitis B-related HCC will decrease with vaccination, while
hepatitis C-related HCC will become an increasing problem. Antiviral treatment and
chemopreventive agents will prevent HCC development.
XI
V
CHAPTER 1
INTRODUCTION
One of the primary causes of mortality in Asia is due to liver cancer. Chronic hepatitis C
virus (HCV) infection has a greater impact on the epidemiology of liver cancer in Asia
than hepatitis B virus (HBV). Hepatocarcinogenesis is mostly caused by HBV. In south-
east Asia, there is an unusually high frequency of HCV (Tsukuma et al. 2005) Pakistan is
at a juncture in its socioeconomic development insecurity and a sharp preference for
change. With an estimated population of 142,182,594, it is the sixth most populated
country in the world. Due to our low income, we fall behind peer countries in a number of
important healthcare indicators (Nishtar et al., 2013).
Cancer occurrence and mortality are growing inside the underdeveloped countries.
Threatening barriers to cancer care exist in Pakistan, negatively affecting patient
outcomes. Hepatobiliary cancer prevalence has been found to be steadily rising.
According to data from a credible hospital-based registry in Pakistan, hepatobiliary
malignancies account for 10.7% of all cancers in adult men and are the most common type
of cancer (Hafeez Bhatti et al., 2016). The incidence of cirrhosis is expected to be
excessive in Pakistan. Hepatocellular carcinoma (HCC), is the primary kind of liver
malignancies, is a recognized complication of cirrhosis. All cirrhosis sufferers may be
complicated by means of HCC, but the cancer risk is suggested to be maximum in
instances of HBV /HCV infection (Farooqi et al., 2000).
The other type of primary liver cancer is intrahepatic cholangiocarcinoma, which is a

tumor of the cells that line the bile ducts. Chronic hepatitis C virus (HCV) and hepatitis
B virus (HBV) infections are associated with HCC as well as additional threating factors
include alcohol consumption, caffeine cirrhosis, hyperlipidemia, obesity, diabetes,
dietary aflatoxicosis and oxidative stress. Despite accounting for just 10% to 25% of
primary hepatic malignancies in most parts of the world, ICC is the most frequent subtype
of liver cancer (Center et al., 2011).
The World Health Organization (WHO) reports that there is an increase in obesity
worldwide, particularly among youngsters. Obesity has also been linked to type 2
1
diabetes, non-alcoholic steatohepatitis, metabolic syndrome, and non-alcoholic fatty liver
disease. Obesity and various types of hepatitis have lately been discovered to be
significant risk factors for a number of common malignancies, with pancreatic and liver
cancer exhibiting the highest increase in risk (Sun et al., 2012). In Pakistan liver cancer is
prevailing due to many reasons. The world sixth most severe type of cancer is liver cancer
that causes death. Incidence rates of liver cancer are highest in South Asia, accounting for
about half of all occurrences. All 80% primary liver cancers are caused by HCC (Kim et
al., 2018).
Figure 1.1: Primary HCC tumor metastasizes to the lung via bloodstream (Li, 2020)
The most fundamental organic characteristic of cancer and the main factor in treating
failure and death from cancer is metastasis. The metastasis and recurrence rate might reach
up to 50%, even in tiny HCC. Most HCC metastasizes through blood vessels, with
lymphatic metastasis being the second most common route to other organs. In HCC
metastasis, direct dissemination, invasion, or implantation has also been found (Lin et al.,
2020).
The cell cycle contains five main phases, which are as follows: Cell cycle stages include
G0 (quiescent state), G1, S, and G2 phases, as well as M phase (cell division stage). Cyclin
D/E interacts to and activates CDK2/four/6 during the transition from the G1 to the S
phase; at the conclusion, CDK2/4/6 phosphorylates the retinoblastoma protein (pRB). In
2
order for the cell to enter the S phase, complexes of E2Fs must be dissociated by
hyperphosphorylated pRB. The cyclin B-CDK1 complex controls the change from the G2
to the M section. With the help of Wee1 and Myt1, CDK1 is phosphorylated, becoming
inactive. Entry into mitosis is made possible by the phosphatase CDC25C's removal of the
CDK1's inhibitory phosphate. As a result, several herbal drugs prevent the growth of
tumours by focusing on either the activity of CDKs or the production of cyclins. In
eukaryotic cells, cell cycle checkpoints are monitoring mechanisms that allow the repair of
cell damage in response to demand (Sheen et al., 2018). The usual MAPK pathway is the
Raf/MEK/Erk pathway, which is also known as epidermal growth factor, luteinizing
hormone releasing hormone, and mitogen-activated protein kinase (Siegfried et al., 2013).
Malignancies are a broad category of diseases characterised by abnormal cell formation

and the ability to infiltrate or disseminate to different areas of the body. The distinctions
between benign and malignant tumours are not blurred. They are responsible for the
structure of a subset of neoplasms. A neoplasm, often known as a tumour, is a collection
of cells that have gone through uncontrolled growth and often form a lump or bump, but
can also spread widely (Abbas et al., 2018). Potential signs and manifestations
incorporate weight misfortune, cough, palpation of breast irregularity, rectal draining,
skin variation from the norm change in a spot or mole, coughing up blood/chest torment,
red territories, change in bowl habits, and blood in pee, abdominal torment and difficulty
swallowing (Koo et al., 2020). Most of malignancies, some 90–95% of cases, are because
of hereditary changes from ecological and way of life factors. The staying 5–10% is
because of acquired genetics. Common factors that incorporate to cancer death are diet,
tobacco (25–30%), pharmaceutical, sunlight, radiations and absence of physical action,
salted fish, and pollution. There are additional causes of cancer which comprise red meat,
low fibre diets, beta carotene, obesity, not breast feeding, and sedentary lifestyles. The
International Agency for Cancer Research (IARC) claims that there is now adequate
proof of mutagenicity in humans for human papillomavirus, human immunodeficiency
virus, T-cell lymph trophic virus, hepatitis C virus and hepatitis B virus (Blackadar,
2016).
3
Different types of gene loci discovered that regulate the growth and multiplicity of
neoplastic lesions and pre neoplastic in liver that perform the action of multiple genes and
epistasis relations. The research of genetic processes of inherited HCC has resulted from
the regulation of HCC exposure susceptibility to HCC, affecting gene–gene and gene–
environment interaction (Pascale et al., 2019).
Extracellular receptor kinase (ERK) is a protein that binds to extracellular receptors. This
is a type of crucial protein that regulates a wide range of cytosolic and nuclear proteins
(about 160 in total), many of which are involved in cell survival, proliferation, and
metastasis (Zhang et al., 2002).
Figure1.2:The Ras/Raf/MAPK Pathway (Marampon et al.,2019)
MAPKs are evolutionary preserved catalysts associating cell-surface receptors to basic

administrative targets inside cells. The mitogen activated protein kinase (MAPK) cascade
is responsible for this route. In humans, there are four MAPK cascades (Chang et al.,
2001).
4
The MAPK pathways, which include a progression of protein kinase falls, play a critical
role in cell multiplication regulation. At the start of the route, EGFR is one of the most
essential regulators of RAS. EGFER activated by TGF-α. Surprisingly this pathway is
actually leaded to the transcription production of more TGF-α which can keep activating
the pathway. Other regulator of EGFR includes EGF and epiregulin. Then EGFR activate
RAS by going through SOS and Grb2 proteins, which then activate RAS. RAS activate B-
RAF which activates MEK1/2. ERK1/2 is then activated as a result of this. When ERK is
active, it is translated in the nucleus, causing a number of genes and transcription factors
to become active (Zhang et al., 2002).
1.2 Purpose of Study

The study was helpful to identify the patients who are suffering from liver cancer. The
study identify different factors that cause liver cancer. This study was also help to find
the most effected area and number of patients in district Gujranwala.
1.2.1 Research objectives:

1. To find out the number of patients and most effective sites of district Gujranwala.
2. Convert the results in documented form.
1.2.2 Problem statement:

 Prevalence of hepatitis B and C cause major problems among people of district Gujranwala.
 The impact of long-term exposure on the incidence of liver disorders, chronic
Hepatitis B and C in urban people.
1.3 Hypothesis:
Liver cancer may prevail in district Gujranwala.
1.4 Significance of study:

The study was significantly helpful to find the most effective sites of liver cancer.
Moreover, to identify the expected sign and symptoms which was commonly observed in
patients? Such documented data was being helpful for different institutions to pinpoint
that site and overcome by taking helpful measures.
5
CHAPTER 2
REVIEW OF LITERATURE
Hepatitis B was the most common cause of hepatocellular carcinoma (HCC) in Pakistan
from the 1970s through the 1990s. Following that, a shift in the etiology of HCC was
discovered along with a steady rise in the number of cases of HCC caused by the hepatitis
C virus (HCV). HCV-3a, the most prevalent HCV genotype, is also the genotype that
predominates in HCC linked to HCV. Hepatitis C-related chronic liver disease is the
main factor contributing to the rise in the prevalence of HCC in Pakistan. By taking
precautions, the pandemic increase in hepatitis C and B incidence can be slowed down in
the ensuing decades (Butt et al., 2012).
Hepatocellular carcinoma is the third most common cancer-related cause of death

worldwide with an average survival rate of 3-5%. Up to 82% of HCC cases are recorded
from developing nations, with China accounting for 55% of those cases. The majority of
HCC burden is borne by developing countries (Raza et al., 2007).
There were between 60 and 70% of HCC cases that also had HCV. Only 20% of cases
had HBV testing results that were positive, and 10% to 15% of those cases were non-B
non-C. Liver cancer development in Pakistan is also influenced by levels of Aflatoxins
pollution. In Pakistan, the age-specific rates of HCC were approximately 7.6 per 100,000
men and 2.8 per 100,000 women per year. Hepatitis viruses with genotypes 3a and D,
which were most prevalent in Pakistan, are also present in the majority of HCC cases.
However, it appears that the genotypes are less important than the time period of
contamination for the development of HCC. It's also crucial to note that the inferred HCV
RNA levels in our HCC patients were found to be much greater than those in those with
liver cirrhosis who did not have HCC. Having a male gender, being older, and having
higher alkaline phosphatase levels were all significant risk factors for HCC (Butt et al.,
2012).
In Pakistan, HCV-3a epidemic expanded earlier than in other nations where this genotype
has been identified, and this may be related to an increase in HCC incidence (Khan et al.,
2009)
6
In contrast to infection with other HCV genotypes, studies carried out in specific
populations around the world discovered a link between HCV genotype 1 infection and
the development of hepatocellular carcinoma (HCC). HCV genotype 3a (HCV-3a) has
been associated with hepatic statuses and fibrosis in several studies, while its connection
to the development of HCC has not yet been investigated. In Pakistan, where the
incidence of HCC is increasing, 189 patients with chronic liver disease were enrolled, of
whom 82 had HCC. HCV genotypes have been identified using the NS5B site, and the
history of the HCV-3a epidemic has been evaluated using coalescent idea-based
approaches (Khan et al., 2009)
The hepatitis C virus (HCV) is classified into 7 genotypes and several subtypes due to its
considerable genetic variability. It was unequally dispersed across different risk groups
and geographical areas. A well connected evolutionary relationship can make it easier to
trace HCV hierarchical levels into specific geographic regions. The goal of the current
study was to map the genetic phylogeny of HCV isolates of subtypes 1a and 1b in Iran
and other Eastern European countries. Through the phylogenetic analysis of all
sequences, specific groups within the phylogenetic trees were discovered. The results
showed that some HCV-1a and -1b isolates from Iranian patients might have come from
regional sources. It's possible that the HCV-1b isolates from Iranian patients will also
resemble those from individuals in Europe. Phylogenetic reconstruction of HCV-1
sequences revealed straightforward molecular tracing and ancestral links of the HCV
genotypes in Iran and also showed the likelihood of a domestic origin for HCV-1a and
multiple origins for HCV-1b (Hesamizadeh et al., 2016).
The second greatest cause of cancer-related death worldwide is hepatocellular carcinoma

(HCC). It might be the most common type of cancer in adult males, and it's becoming
worse in Pakistan. Pakistan contributes significantly to the global burden of hepatitis C,
which is recognised as a risk factor for HCC, and has one of the highest prevalence rates
(>3%) in the world. Lack of awareness of the risk factors for the disease among the
populace has led to an increase in the incidence of hepatitis C in Pakistan. Additionally,
there is an increase in risk factors that are far less common. When HCC first manifests,
7
the majority of patients are ineligible for long-term treatment because it is advanced
(Hafeez Bhatti et al., 2016).
There are several known risk factors for HCC, including chronic hepatitis C and B
infection, alcohol use, alpha1 antitrypsin deficiency, autoimmune hepatitis, congenital
hemochromatosis, Wilson disease, and porphyrias. There is growing evidence showing a
connection between HCC, diabetes, and obesity (Hafeez Bhatti et al., 2016). In 2018,
there were 841,080 new cases of liver cancer, making it the sixth most common cancer
globally and the fourth leading cause of cancer-related mortality. East Asia and Africa
continue to have the greatest rates of HCC, despite the fact that incidence and death are
rising in a number of regions of Europe and the USA. Indeed, HCC has been the fastest-
rising cause of cancer-related death in the USA since the early 2000s, and if current
trends continue, HCC will rank third among all causes of cancer-related death by 2030.
This information comes from Screening Epidemiology End Results (SEER) (Ferenci et
al., 2010).
Epidemiological studies have amply demonstrated the strong link between HBV infection
and liver cancer. It is widely accepted that the virus is to blame because cirrhosis is
frequently connected to long-term chronic infection. This shows that an ad hoc
mechanism is activated by the immunological response. The persistence of liver
inflammation, continuous cell death, and aberrant cell creation would result in an increase
in the frequency of genetic defects and disease risk. However, statistics show that only
roughly one-fifth of HBV carriers will go on to develop HCC over the course of their
lifetime, indicating that a person's unique genetic variation may ultimately affect HCC
risk (Su et al., 2013). The present increase in hepatocellular carcinoma among
hospitalised veterans was mostly caused by HCV infection, which accounted for more
than half of the increase, according to past studies. However, no statistically significant
links between HBV, alcohol, or idiopathic cirrhosis and a rise in the incidence of
hepatocellular carcinoma have been discovered. According to a study conducted by the
MD Anderson Cancer Centre at one institution, the percentage of hepatocellular
carcinomas linked to HCV rose from 18% from 1993 to 1995 to 31% from 1996 to 1998.
Despite the lack of thorough research on hepatocellular carcinoma temporal patterns,
8
rising evidence points to a link between non-alcoholic steatohepatitis and diabetes and an
elevated risk of the illness (El-Serag et al., 2003).
Startling age-specific trends were discovered when state-specific liver cancer fatality
rates were split down by age group between 2000 and 2010. Liver cancer fatality rates
nationally and two risk variables Cirrhosis and chronic liver disease come first, followed
by diabetes mellitus. The trend in liver cancer mortality was comparable to the trends in
cirrhosis and chronic liver disease. Ages 35 to 49 saw a considerable drop in both causes
of mortality, whereas 50 to 64 saw a significant increase. Furthermore, among individuals
aged 50 to 64, there was a statistically significant connection between cirrhosis and
chronic liver diseases including liver cancer (Altekruse et al., 2014).
Malignancies, a broad category of diseases, are characterised by aberrant cell

development and the ability to invade or spread to numerous bodily regions. There is no
blending of the lines separating benign from malignant tumours. They are in charge of
how some types of neoplasms are structured. A neoplastic, commonly referred to as a
tumour, is a group of cells that have experienced uncontrolled growth. Neoplasms
frequently take the form of lumps or bumps but can also spread far (Abbas and Rehman
2018). Weight loss, coughing up blood or feeling chest pain, rectal draining, skin
variations from the norm change in a spot or mole, red areas on the body, altered bowel
habits, blood in the urine, abdominal pain, and difficulty swallowing are all potential
symptoms and indicators (Ko Swann et al.,2020).
About 90–95% of cases of malignancies are caused by genetic alterations brought on by

environmental and lifestyle factors. Acquired genetics is the cause of the remaining 5–
10%. Diet, cigarette use (25–30%), medication, sunshine, radiation exposure, lack of
physical activity, salted fish, and pollution are all common causes of cancer death. Red
meat, low-fiber diets, beta-carotene, obesity, and sedentary lifestyles are additional
cancer-causing factors. According to the International Agency for Cancer Research
(IARC), sufficient evidence exists to demonstrate that the human papillomavirus, human
immunodeficiency virus, T-cell lymphotrophic virus, hepatitis C virus, and hepatitis B
virus are mutagenic in humans (Blackadar, 2016).
9
Hepatitis is an inflammatory illness of the liver that can be self-limiting or, in certain
cases, lead to liver cancer, cirrhosis, or fibrosis. Globally, hepatitis is primarily caused by
hepatitis viruses. Hepatitis C patients are most likely to develop type II diabetes because
the HCV virus contributes to its development. The HCV virus causes pathogenesis in two
different ways: either it directly kills pancreatic beta cells or helps these cells develop a
specific autoimmune (Sadia et al., 2013).
Sadly, there was no population-based complete study available from which a real
prevalence and prevalence rate of HCC could be determined. The majority of the research
was exclusively hospital-based. However, several most cancers registries have been set
up in Pakistan. The Karachi Cancer Registry (KCR), established in 1995 by the Sindh
Government in technical cooperation with the Unit of Descriptive Epidemiology of the
International Agency for Research on Cancer (IARC) of the World Health Organization,
became the first population-based cancer registry (Bhurgri et al., 2000).
HCC patients had considerably higher prevalence of hepatitis B surface antigen (HBsAg)
and antibody to HCV (anti-HCV) than did control patients (5.2% and 3.5%, respectively),
according to a case study done in China. There was a considerable difference between the
two companies. HBV and HCV infections have been major risk factors for HCC in
Henan, China, per a risk aspect study. This study also shows a strong correlation between
persistent HBV infection and the development of HCC in this population. According to
findings, HCV and HBV infections are distinct but maybe complementary risk factors for
developing HCC. However, the connection between primary biliary cholangitis (PBC)
and HCC is still unclear because of a lack of epidemiological studies and occasionally
conflicting findings. Some have argued that PBC does not increase the chance of
developing HCC, despite other research showing that PBC patients have a high incidence
of the disease. The second study revealed that the development of HCC was associated
with a history of blood transfusion, advanced-stage PBC, super infection with the
hepatitis C virus, and male gender. In actuality, the majority of HCC cases were found in
patients with histological level IV PBC. As a result, the majority of HCC cases are
reported to occur in the advanced cirrhotic stages of PBC, while only a few cases of HCC
have been found to emerge in the non-cirrhotic phases of PBC. However, it's crucial to
10
remember that our patient had a liver biopsy five years before being diagnosed with HCC
(Meza-Junco et al., 2007).
Several theories have been proposed to explain the existence of HCC in PBC patients,
including the relationship between ductal proliferation and oval cells, which are assumed
to develop from stem cells. Numerous pieces of data also lend credence to the theory that
oval cells are the cause of HCC. Oval cells can be transfected with an active oncogene or
a tiny amount of a tumour suppressor gene, which can lead to the formation of HCC and
the overexpression of c-Myc during hepatocarcinogenesis. HCC cells differentiated into
hepatocytes and biliary cells as a result of C-Myc inactivation, resulting in the formation
of bile duct architecture. 23 Additionally, proapoptotic bile acid retention in cholestasis
results in apoptotic stress and promotes the expression of cellular genes alterations that
are more likely to result in most malignancies (Wu et al., 2006).
With the help of the RNA virus known as the hepatitis C virus (HCV), 180 million
people worldwide suffer from chronic inflammation. A deeper understanding of HCV
and its interactions with cell components is required to develop new antiviral medicines
because each of these connections has a functional purpose. Additionally, there is a
continuing need for fresh structural information that will aid in understanding the
underlying molecular processes behind significant HCV lifecycle phases. Understanding
the structural and/or functional links between the human Cyclophiline A and the two
HCV proteins, NS5A and NS5B, is the main goal of this assignment. For viral RNA
replication and the creation of infectious particles, NS5A and NS5B are essential. While
the structure and functionality of NS5B, the viral RNA polymerase, are known,
information on NS5A is less clear. Three domains make up the protein NS5A. The X-ray
structure has been determined for the zinc-binding region known as domain 1 (NS5A-
D1). Inherently disordered and lacking a strong three-D structure are domains 2 and 3
(NS5A-D2,-D3). Cyclosporine A (CsA), a well-known inhibitor of human cyclophilines,
has been shown to have anti-HCV activity, and changes in the virus's NS5A and NS5B
that confer resistance to CsA have been found. This demonstrates that these viral proteins
can interact with host Cyclophilines as well. But more has to be understood about the
underlying molecular pathways. To achieve this, it calls for to get an in depth molecular
11
characterization of every of these proteins and then to recognize the relationships which
can exist among them (Ago et al., 1999).
The E motif, which joins the thumb and palm domains, is a flap that covers the active
site. The one finger loop, which stretches across to closely interact with the thumb, is
particularly active at Leu 30. These motifs are either directly contacted by the residues
constituting the thumb's inhibitor-binding cleft or are connected to them via secondary
structural components. Additionally, the location of inhibitor 1 is close to His 502, which
is thought to be important for the functional dimerization of NS5B (along with Glu 18).
On the electrostatic potential surface for NS5B, a significant area of conserved positive
charge can be seen adjacent to the thumb's inhibitor binding site (blue, positive; red,
negative). When oligonucleotides and/or nucleotides are bound to this region during
RNA elongation, if an inhibitor is bound to this region, this could interfere satirically or
electrostatically (Rosnoblet et al., 2012).
This research was done to look at how the aetiology and demography of hepatocellular
carcinoma interact. The tumour characteristics in connection to anti-viral therapy, the
treatment modalities provided, the existence of acid/ribonucleic acid, viral-
deoxyribonucleic acid, and other factors were then examined. The patients in the cross-
sectional study ranged in age from 18 to 70 and had been diagnosed with hepatocellular
carcinoma. The study took place at the Pak Emirates Military Hospital's Department of
Gastroenterology in Rawalpindi, Pakistan, and it ran from January 1 to December 31,
2019. Biochemical analysis, viral status, demographic factors, tumour staging, and the
therapeutic methods available, such as the liver profile and stage of cirrhosis, were noted
parameters. An estimated 76% (148) of the 195 patients were men, and 24% (47) were
women. Their average age was between 59 and 60 years. 96% (186 patients) had
cirrhosis, ninety-four per cent (183) had viral hepatocellular carcinoma, 82 (160) had
hepatitis C, nine per cent (18) had hepatitis B, and 3% had co-infection. Platelets and
alanine transaminase revealed a significant relationship along aetiological groups (p
0.05). The influence of viral polymerase chain reaction on tumour aggressiveness was
significant (p 0.05), and 32% (62) of patients were willing to receive curative treatment.
Finally, it was determined that lack of competence and expensive treatment options along
12
with viral infection was the primary factor contributing to the increased prevalence of
hepatocellular carcinoma (Alam.,2021).
According to this study, the chronic hepatitis B virus infection is one of the most serious
illnesses and a major risk factor for liver cancer and cirrhosis-related fatalities. The
prevalence of chronic HBV infection was assessed for each sex, age group, and
geographic location. The absolute number of people with chronic HBV infection was also
calculated. The methodology involves a thorough examination of the published papers on
HBV infection, and data on HBsAg seroprevalence around the world were gathered
during a 27-year period (1980–2007). On a worldwide scale and for all globe areas
between 1990 and 2005, it was noted that endemicity and age-specific prevalence were
estimated using an empirical Bayesian hierarchical model. It was discovered that between
1990 to 2005, the prevalence of chronic HBV infection reduced in the majority of
locations. Tropical and Central Latin America, South East Asia, Central Europe, and
Central sub-Saharan Africa were the regions where this was most noticeable. Despite the
decline in prevalence, there were 240 million HBsAg-positive patients worldwide in
1990–2005, up from 223 million. Regional differences in age-specific prevalence might
be seen. The regions of North America and Western Europe, Tropical and Central Latin
America, and Sub-Saharan Africa had the greatest endemicity levels and the lowest (2%)
levels, respectively. While the prevalence of HBsAg varied throughout Asian areas, with
a lower intermediate frequency in South Asia and 8.6% prevalence in East Asia. Children
from South East Asia showed a significant drop. Finally, it was observed that the
increased immunisation was linked to decreases in the prevalence of HBV infection.
Targeted strategies are required to combat HBV-related death and disease because of the
global variations in HBV prevalence and the overall rising number of people with chronic
HBV infection. Data on HBV infection prevalence are required at the national and sub-
national levels in order to quantify the disease burden, inform vaccine policy, and
promote health (Ott et al., 2012).
Hepatocellular carcinoma (HCC) and alcohol use were separately examined for their
dose-effect relationship in men and women. Hepatitis B and C viruses are also regarded
as infections. They enlisted 824 people (686 men) as controls who had not been afflicted
13
by hepatic disorders and 464 subjects (380 men) as cases who had received an initial
diagnosis of HCC. Between 1995 and 2000, they were treated in hospitals in Brescia and
northern Italy. With no statistically significant differences between men and women,
Spline regression models showed a constant linear increase in the odds ratio of HCC for
increasing alcohol intake for values of more than 60 g of ethanol per day. Age at first
drinking did not affect the odds ratio when alcohol intake was taken into account. HCC
was more common among former drinkers than among current drinkers who had quit one
to ten years prior. Alcohol consumption had a noticeable impact even in the absence of
hepatitis B or C virus infection. Additionally, a synergistic relationship between alcohol
consumption and infection was discovered, with drinkers who consume more than 60 g of
alcohol per day having odds ratios for hepatitis virus infections that are approximately
two times higher (Donato et al., 2002).
The study on Familial Clustering of Hepatocellular Carcinoma (HCC) has been widely
reported in eastern Asian nations where hepatitis B infection is widespread. It has to do
with the connection between HCC and a family history of liver cancer in western
populations. In an Italian case-control research, 431 hospital controls and 229 HCC
patients were compared to each other. To report information on family history that was
condensed through chosen family features, a binary indicator (yes/no) and a family
history score (FHscore) were utilised. The relevant 95% confidence intervals (CIs) and
odds ratios were computed using the unconditional multiple logistic regression models
(ORs). Age, study location, education, sex, alcohol consumption, tobacco use, hepatitis B
surface antigen positivity, and/or anti-hepatitis C virus positive are all terms that are
included. Random-effects models were used to conduct a meta-analysis on a family
history of liver cancer that was updated to April 2011. When utilising both the FHscore
and the binary indicator, there was an association between a family history of liver cancer
and an increased risk of developing HCC with higher ORs for higher score categories.
The chronic infection was adjusted using hepatitis B/C viruses. The OR for people
exposed to both risk factors was 72.48 (95% CI, 21.92-239.73) compared to subjects
without family history and those with no history of chronic hepatitis B/C infection. For a
total of about 3,600 liver cancer cases, the meta-pooled analysis's relative risk for family
history of liver cancer was 2.50 (95% CI, 2.06-3.03), based on nine case-control and four
cohort studies. Independent of hepatitis, HCC risk rises in families with a history of liver
14
cancer. Hepatitis B/C blood indicators and a family history of liver cancer increase the
risk of HCC by more than 70 times (Turati et al., 2012).
cohort studies. Independent of hepatitis, HCC risk rises in families with a history of liver
cancer. Hepatitis B/C blood indicators and a family history of liver cancer increase the
risk of HCC by more than 70 times (Turati et al., 2012).
The hepatitis B virus (HBV) is a dangerous illness that has caused a significant global
health issue with a focus on southern Europe, southern Asia, and Latin America. Around
400 million of the two billion HBV infections in the world's population are chronic,
affecting at least two billion people. There are already nine million HBV-positive
individuals in Pakistan, and the infection incidence is steadily rising. Lack of appropriate
guidelines, appropriate medical facilities, a precarious economic situation, and a lack of
public knowledge of the development of major contagious illnesses like HCV, HBV, and
HIV may all contribute to this (Ali et al., 2011).
This study analyzed the prevalence, awareness state, risk factors, and genotypes of HBV
in Pakistan using the search terms HBV prevalence, awareness status, risk factors, and
genotypes in the population of Pakistan in PakMediNet, PubMed, Google Scholar, and
Directory of Open Access Journals (DOAJ). Pakistan has 7-9 million people who are
hepatitis B virus (HBV) carriers at a carrier rate of 3-5%. Approximately 106 articles
between 1998 and 2010 are covered by this inquiry. For each demographic group, the
standard deviation and weighted mean were calculated individually. Hepatitis B virus
infection rates in the general population ranged from 4.3318% to 1.644%, while they
were higher in military recruits (4.276% to 1.646%), pregnant women (5.872% to 4.984),
healthy blood donors (3.93% to 1.58%), healthcare workers (3.25% to 1.202%), surgical
patients (7.397% to 2.012%), prisoners (5.75% to 0.212%), patients with HCC (22% to
2.645%), patients with cirrhosis (28.8 The most common genotype in the population of
Pakistan is genotype D (63.71%). In populations where HBV infection rates are greater
than 5%, it is essential to start immediate awareness campaigns and mass vaccination
campaigns (Ali et al., 2011).
The ASIR for HCC in Pakistan is 2.8 for girls and 7.6 for males per 100,000 people
annually. According to estimates, persistent HCV infection can be the cause of 60–70%
15
of all HCC cases. As opposed to many other Asian neighbours where chronic HBV is the
primary problem. Because there is no national cancer registry there, much
epidemiological research based on single-centre approaches and comparative studies
based on application of worldwide criteria remain suspect for the local residents.
Eliminating racial/ethnic health inequalities is a primary goal because of the
disproportionately high incidence rate of liver cancer among Asian Americans, one of the
greatest health disparities in the U.S. (Surveillance, Epidemiology and End Results
(SEER) Program, 2006). The high prevalence of chronic hepatitis B virus (HBV)
infection among Asians and Asian immigrants where it can range from 10–25%
compared to a prevalence of less than 0.5% among the whole U.S. population might be
partially attributed to this disparity. Jenkins et al. (2001) and Beasley et al. (1981) both
found that a persistent HBV infection doubles the risk of liver cancer and quadruples the
risk of dying from HBV-related liver cancer or cirrhosis (World Health Organization,
2000). Liver cancer is the second leading cause of cancer death in API men and the
seventh leading cause in API women, despite being relatively uncommon in the wider
American population (United States Cancer Statistics Working Group, 2005) (Charlotte
et al., 2007).
The incidence of liver cancer is where there is the highest health difference between
Asian Americans and Pacific Islanders (AAPIs) and Caucasian Americans. Compared to
Caucasian Americans, male liver cancer rates are 13 times higher among Vietnamese
Americans, 8 times higher among Korean Americans (KA), and 6 times higher among
Chinese Americans. Hepatitis B virus (HBV) infection is the etiological cause of about
80% of cases of liver cancer, and HBV is 100 times more contagious than the human
immunodeficiency virus. HBV infection is prevalent in the AAPI community at 12% in
children and 3-19% in adults, compared to 0.1-0.2% in the general U.S. population.
According to multiple surveys, hepatitis B infection among close AAPI relatives has been
found to cluster; as a result, if one family member develops the disease, the rest of the
family, including children, are at a high risk of catching it as well (Lee et al., 2007)
Chronic liver disease (CLD), one of the leading causes of morbidity and mortality
worldwide, can be brought on by a wide variety of illnesses. The tenth most common
cause of death in the US is liver disease or one of its complications. Infection with the
16
chronic hepatitis B or C virus (HCV or HBV) affects about 5 million Americans, and
17
millions more have various chronic hepatocellular or cholestasis liver diseases. 4
Numerous symptoms that are frequently experienced by patients with chronic liver
disease have a negative impact on their health and quality of life (HRQL). The causes of
this disability have not yet undergone a thorough analysis. A recent research of HCV-
infected individuals without cirrhosis found no differences in HRQL according to the
severity of liver inflammation or the method of acquisition. 5 We would anticipate that as
the severity of the liver disease develops, patients will suffer a progression of symptoms
and functional limits because of the biology of chronic liver disease and our clinical
experience with these patients. Cirrhosis consequences could further affect patients'
health. On the other hand, it is unlikely that there will be a strong association between the
severity of the disease and HRQL impairment (Younossi et al., 1999).
Finding the individuals within populations who are most at risk of acquiring cancer as a
result of exposure to recognized etiological agents is one of the objectives of molecular
epidemiology. Aflatoxins-contaminated food consumption and ongoing HBV4 infection
are two of the main risk factors for HCC, which is anticipated to kill at least 250,000
people annually worldwide. There is a little likelihood that a given person will get HCC,
despite the fact that both exposures are frequent in regions with a high frequency of the
illness. HBV-positive persons can be identified by the immunological detection of
antibodies against viral gene products in blood, and prospective studies using this
biomarker have shown the significance of HBV as a risk factor for HCC. Population-
based estimates of food intake along with food sampling and analysis were used to derive
estimates of Aflatoxins ingestion in various populations; however, up until recently, the
evidence that Aflatoxins consumption contributes to the development of HCC has been
largely reliant on these estimates. Analytical detection of DNA, protein adducts, and
antitoxin metabolites in urine and blood are now possible. The validity of these indicators
as biomarkers of Aflatoxins consumption by people within exposed groups is currently
being studied. With more than 100,000 fatalities each year, HCC ranks third among the
causes of cancer mortality in the PRC and accounts for more than 5% of all cancer-
related deaths. Significant geographic disparities in liver cancer mortality surveys are
revealed by the PRC's national cancer mortality data In the PRC, there are large
geographical differences in liver cancer mortality. High incidence areas frequently have
particular climatic traits. Liver cancer chances were higher in coastal regions (Qian et al.,
18
1994).
19
When we analyzed mortality rates for primary liver tumors in England and Wales over
the period 1968–1998 from the Office of National Statistics, we discovered that deaths
from all causes of malignant liver tumors had nearly doubled, but deaths from
hepatocellular carcinoma had remained largely stable. Because the prognosis for liver and
pancreatic tumors is generally fairly poor, mortality numbers may be utilized as a useful
proxy for incidence. The rise in deaths from primary liver tumors in England and Wales
was due to surprisingly high age-standardized mortality rates (ASMR) for intrahepatic
cholangiocarcinoma. Since the mid-1990s, this has become the most commonly reported
reason for a malignant liver tumor mortality in England and Wales has become the most
often reported cause of death from a malignant liver tumor in England and Wales. We
looked to check if a similar pattern was seen in other industrialized countries using the
official World Health Organization (WHO) death statistics.
Data from earlier research indicate increased mortality rates for pancreatic tumours in
Japan and across many European nations, as well as for liver tumours in the United
States, France, Italy, and Japan. Recently, there have also been reports of a rise in biliary
tumours in the US. However, the majority of epidemiological studies concentrate on a
single tumour type, or a group of tumours as a whole, and frequently solely on a specific
cohort within a nation. McGlynn and colleagues examined incidence rates for all primary
liver malignancies as a group from 21 carefully chosen cancer registries in carefully
chosen cohorts worldwide. Data from the United Kingdom, for instance, were only
available for the South Thames region, whereas data from Spain were provided from
Navarra. It was determined that there had been a significant shift in worldwide time
trends, with primary liver cancer incidence rates rising mainly in wealthy countries and
falling in some developing countries (Khan et al., 2002).
A significant risk factor for hepatocellular carcinoma and a primary cause of chronic
hepatitis globally is the hepatitis C virus (HCV) (HCC). In Asia, particularly in Japan,
HCV-1b is the most common genotype and is more likely to develop into HCC than other
genotypes. Although there are many published data about the correlation between HCV
20
infection and HCC development, details of hepatocarcinogenesis by HCV are still
lacking. The ability of the HCV core protein to regulate cellular gene transcription and
protein expression, intracellular signal transduction, cell proliferation, and apoptosis is a
key factor in the development of hepatocarcinogenesis. (6–9) Considering that HCV is an
RNA virus, there is a substantial amount of sequence variation in its genome. Studies
have shown that specific types of mutations can cause functional changes in the virus,
such as resistance to antiviral drugs and associations with HCC. In addition, patients
with HCC have a higher rate of mutations in the core region than do patients without
HCC. Additionally, isolates from HCC patients have a considerably higher prevalence of
nucleotide changes in the core gene than isolates from those with chronic hepatitis. It
was also discovered that tumour tissue isolates had much higher core region variability
than isolates from non-tumor tissue (Hu et al., 2009).
The affiliation among hemochromatosis and HCC is widely recognized. Some of the
early cohort research files a 200-fold increase within the threat of HCC in patients with
genetic hemochromatosis. A population-based study take a look at from Denmark located
a standardized occurrence ratio of 92.5% in a cohort of patients with hemochromatosis as
compared with the anticipated rate in the population. Although later studies have
confirmed this association among hemochromatosis and HCC, they have got arrived at
lower ORs for development of HCC. Whether this reflects earlier identity and treatment
of sufferers remains to be seen. In a big population have a look at from Sweden; Elmberg
et al followed 1847 sufferers with hemochromatosis for a total of 12,398 person-years. A
overall of 62 instances of liver most cancers had been identified in this population,
corresponding to a 20-fold multiplied risk. A majority (79%) of those cancers were HCC.
There turned into a difference in the threat of liver cancer between genders. Men with
hemochromatosis had a 30-fold expanded chance of improvement of liver cancer, and
girls had simplest a sevenfold accelerated risk (Anantha krishnan et al., 2006).
21
CHAPTER 3
MATERIALS AND METHODS
3.1 Study design and population
This is a large and dynamic prospective cohort study, was initiated in 2022 and based on
a group of liver cancer patients in Gujranwala city. Participants were enrolled in the
present study if they met the following criteria: (1) males with age >13, (2) providing
informed consent, (3) completing the questionnaire interview. Ultimately, a total of 100
male and female subjects were enrolled in the present study. This study is carried out in
the accordance with recommendations of ethical review committee of the DHQ hospital.
3.2 Primary data:

Different surveys were collected for data collection through self-administrated questionnaires.
Surveys were conducted related to liver cancer from civil hospital, Gujranwala. The research was
conducted from January 2021 to June 2022.
3.3 Sample Size and selection criteria
This research was conducted among the population of district Gujranwala. A convenience selection
methodology was used to choose 200 research participants aged 18 and above. For each group, such
as sedentary, stone query employees, farmers, and field laborers’, the ratio was maintained at 1:1:1.
Patients with liver diseases were included in this research. Their information was gathered from
DHQ hospital Gujranwala.
3.4 Study Tool
Gujranwala is a flat region which is characterized by populated areas and urban and inter-urban
roads. The mintab17 and the survey form were used with the support of two assistant professors
from different universities, the questionnaire was evaluated. Age group, height, weight, hepatitis B
and C, smoking history, alcohol consumption, heart diseases, blood pressure, education, and illness
status were among the personal and job variables obtained.
22
Minitab17 software enables the computation of expected mean values for age, weight, and height, as well
as the recording of all parameters adjusted for the research population (Richeldi et al., 2017).
 Professional
 Intermediates
 Manual skilled
 Partially skilled
 Retired and jobless
3.5 Study Method
The research was done by a competent Chemist from 10 AM to 03 PM every Sunday to Friday at a
desk location for all the survey participants on farmers, stone query workers, field workers and
sedentary from urban areas of district Gujranwala, Pakistan, and the data was entered in the survey
and minitab17 was done connectedly. After a brief explanation of the procedure, the individuals
were given three exercises to complete after sufficient rest.
3.6 Statistical Investigation
We determined the frequency, percent, mean value, and variance. The data was precisely examined
using Excel Software 2019, minitab17, and relevant sample analysis for the statistical significance
level (P0.05) was done (Croft et al., 2020).
3.7 Inclusion criteria
All patients whose age is above 15 years were included in the study.
3.8 Exclusion criteria
All patients whose age < 15 and > 86 was excluded from the study.
23
CHAPTER 4
RESULT AND DISCUSSION
Table: 4.1 Percentage distributions of different age groups of reproductive aging in hospital
population.
Combined
Age Groups Male % Female
Sex %
13-22 11 16.17 04 12.5 15 15
23-32 02 2.94 01 3.12 3 3
33-42 08 11.76 05 15.62 13 13
43-52 13 19.11 07 21.87 19 19
53-62 11 16.17 08 25 19 19
63-72 09 13.23 05 15.62 14 14
73-82 10 14.7 02 6.25 12 12
83-86 03 4.41 00 00 3 3
Table 4.1 shows different numbers and percentage of different age groups patient. G4
show highest percentage (19.11) in male. G1 and G5 show second highest percentage
(16.17) in male. G4 and G5 show highest percentage (21.87, 25) respectively in female.
Other groups show least percentage in both female and male.
24
Table: 4.2 Alcohol Consumptions and Risk of Cancer
Alcohol Femal Combine

Sr. Male % %
Consumption e d Sex %
1 No 24 35.29 31 96.87 55 55
2 Yes 44 64.7 1 3.12 45 45
3 Total 68 99.99 32 99.99 100 100
Table 4.2 Show the association of alcohol consumption with liver cancer. According to
these male patients who are addicted to alcohol are more prior to liver cancer with 64.7
percentages as compared to female.
Table: 4.3 Association of Bloating With Cancer
Combined
Sr. Bloating Male % Female %
Sex %
1 No 18 26.87 21 65.63 39 39.39
2 Yes 49 73.13 11 34.38 60 60.61
3 Total 67 100 32 100 99 100
Table 4.3 showed that bloating has a strong association with liver cancer. Patients who
bloated were more affected with liver cancer. Patients who bloated showed (73.13)
percentage in male (34.38) in female were more prior to liver cancer.
25
Table: 4.4 Association of Jaundice with Cancer
Combined
Sex %
1 Normal 15 22.06 15 48.39 30 30
2 High bilirubin 53 77.94 16 51.61 69 69
3 Total 68 100 31 100 99 99
Table 4.4 shows bilirubin percentage in jaundice patients which are strongly associated
with liver cancer. It showed high (77.94) percentage in male and (51.61) percentage in
female who are with high bilirubin and are more affected with live cancer as compared to
non-jaundiced patients.
Table: 4.5 Obesity and liver Cancer
Combined
Sr. Obesity Male % Female %
Sex %
1 Normal 37 55.22 21 65.63 58 58
2 Obese 30 44.78 11 34.38 41 41
3 Total 67 100 32 100 99 99
Table 4.5 shows the relation of obesity with liver cancer. Being obese was associated
with a 44.78 % in male and 34.38 % in female increased risk of liver cancer and the more
obese, higher the risk. There was a 38 and 25% increase in the risk for liver cancer in
men and women, respectively.
26
Table: 4.6 Association of urine colour with liver cancer
Urine Combined
Sr. Male % Female %
Colour Sex %
1 Normal 32 47.76 28 87.5 60 60
2 Dark urine 35 52.24 4 12.5 39 39
3 Total 67 100 32 100 99 99
Table 4.6 shows that liver cancer patient’s urine turned yellow with 52.24% in male and
12.5% in female. Urine is usually dark because of the bilirubin excreted through the
kidneys. High levels of bilirubin may be attributed to turn the urine colour into darker
which lead to abnormalities of liver cells.
Table: 4.7 Anxiety and liver cancer
Combined
Sr. Anxiety Male % Female %
Sex %
1 No 20 29.85 23 71.87 43 43
2 Yes 47 70.15 9 28.13 56 56
3 Total 67 100 32 100 99 99
Table 4.7 indicates that most of the patients with liver diseases experience anxiety and
depression symptoms. Male patients with 70.15% experienced more anxiety and were
more affected with liver cancer as compared to female with 28.13%.
27
Table 4.8 Low grade but persistent fever a symptom of liver cancer
Combined
Sex %
1 Low grade 35 52.24 8 25 43 43
2 High grade 32 47.76 24 75 56 56
3 Total 67 100 32 100 99 99
Table 4.8 indicates that low-grade, but persistent fever, sometime leads to severe health
issues. Patients with low grade fever but persistently were more prior to liver cancer with
52.24% in male.
Table: 4.9 Skin colour and liver cancer
Combined
Sr. Skin Colour Male % Female %
Sex %
1 White 44 53.66 16 94.12 60 60
2 Yellow 38 46.34 1 5.88 39 39
3 Total 82 100 17 100 99 99
Table 4.9 indicates that liver cancer patient skin or the white of eyes turned yellow in
male with 46.34%
28
Table: 4.10 Hepatitis C and Liver Cancer
Hepatitis Combined
Sr. Male % Female %
C Sex %
1 No 22 31.88 6 20 28 28
2 Yes 47 68.12 24 80 71 71
3 Total 69 100 30 100 99 99
Table 4.10 indicates that about 71 per cent of people who get exposed to the hepatitis C
virus had chronic hepatitis C. This on-going infection caused inflammation in the liver.
This extended inflammation caused scarring, called cirrhosis, and ultimately lead to liver
cancer.
Table: 4.11 Blood Pressure and risk of Liver Cancer
Blood Combined
Sr. Male % Female %
pressure Sex %
1 Hypotension 25 37.31 11 34.38 36 36
2 Hypertension 42 62.69 21 65.63 63 63
3 Total 67 100 32 100 99 99
Table 4.11 shows linear associations in fluctuations of blood pressure with cancer
incidence and mortality in men and women. This study showed that elevated BP was
statistically significantly associated with incident cancer in men with 62.69% and in
women with 65.63%, which lead to several specific cancers. Cancer risk increased
linearly with increasing BP levels, and for both cancer incidence and mortality the
association was stronger for men than for women. Among men, the absolute 20-year risk
of cancer incidence or mortality at age 50 years was 1% to 2% points higher with
hypertensive systolic or diastolic BPs compared with men with normal BP.
29
Table: 4.12 Chemotherapy and liver cancer
Chemotherap Combined
Sr. Male % Female %
y Sex %
1 No 38 56.72 29 90.63 67 67
2 Yes 29 43.28 3 9.38 32 32
3 Total 67 100 32 100 99 99
Table 4.12 shows that 32% people with Late-stage liver cancers have done chemotherapy
in male and female.
Table: 4.13 Diabetes and risk of liver cancer
Combined
Sr. Diabetes Male % Female %
Sex %
1 Normal 35 52.24 12 37.5 47 47
2 Diabetic 32 47.76 20 62.5 52 52
3 Total 67 100 32 100 99 99
Table 4.13 indicates that diabetes increase the risk of liver cancer from 20 to 50% in both
male and female. Female with diabetes are more prior to get liver cancer with 62.5%.
30
Table: 4.14 Aflatoxins and developing cancer
Sr Exposure Combined
Male % Female %
. Aflatoxins Sex %
1 No 29 43.29 15 46.88 44 44
2 Yes 38 56.72 17 53.13 55 55
3 Total 67 100 32 100 99 99
Table 4.14 shows that exposure to Aflatoxins is associated with an increased risk of liver
cancer. According to this study 55% patients had Chronic low-level exposure to
Aflatoxins, particularly Aflatoxins B1, is associated with increased risk of developing
liver cancer, impaired immune function, and malnutrition.
Table: 4.15 Life style association with liver cancer
Sr Combined
Life style Male % Female %
. Sex %
1 Normal 17 25.37 21 65.63 38 38
2 Sedentary 50 74.63 11 34.38 61 61
3 Total 67 100 32 100 99
Table 4.15 show that Sedentary lifestyles increases 61% all causes of mortality and
double the risk of diabetes, cardiovascular diseases and obesity, and increase the risks of
liver cancer, high blood pressure, depression and anxiety.
31
Table: 4.16 Hepatitis B and risk of liver cancer
Sr Combined
Hepatitis B Male % Female %
. Sex %
1 No 23 34.33 8 25 32 32
2 Yes 44 65.67 24 75 67 67
3 Total 67 100 32 100 99 99
Table 4.16 Indicated that the most common risk factor of liver cancer in male and female
is chronic infection with the hepatitis B virus. Patient affected with hepatitis C showed
67% in both male and female are at higher risk level.
Table: 4.17 abdominal mass and risk of liver cancer
Sr Abdominal Combined
Male % Female %
. Mass Sex %
1 No 12 17.91 15 46.88 27 27
2 Yes 55 82.81 17 53.13 72 72
3 Total 32 100 32 100 99 99
Table 4.17 when cells begin to reproduce at an increased rate tumors is formed that are
abnormal masses of tissue. Both noncancerous (benign) and cancerous (malignant)
tumors developed in the liver cancer patients with 82.81% in male and 53.13% in
women.
32
Table: 4.18 Reduce weight associations with liver cancer
Reduce Combined
Sr. Male % Female %
Weight Sex %
1 No 41 61.19 18 56.25 59 59
2 Yes 26 38.81 14 43.75 40 40
3 Total 67 100 32 100 99 99
Table: 4.19 Heart Problem and risk of liver cancer
Sr Heart Combined
Male % Female %
. Problem Sex %
1 No 28 41.79 15 47.87 43 43
2 Yes 39 58.21 17 53.13 56 56
3 Total 67 100 32 100 99 99
Table 4.19 show that clinical practice, combined heart and liver dysfunction coexist in
the setting of the main heart and liver diseases because of complex cardio hepatic
interactions. According to this patients with heart problems were more prior to liver
cancer with 56%.
Table: 20 Loss of appetite and risk of liver cancer
Sr Loss of Combined
Male % Female %
. Appetite Sex %
1 No 26 38.81 10 31.25 36 36
2 Yes 41 61.19 22 68.75 63 63
3 Total 67 100 32 100 99 99
33
Table: 20 show that in cancer patients as time goes by and more healthy tissue is
replaced with scar tissue, the liver begins to fail and a patient experienced: Weakness and
exhaustion, Nausea and vomiting, Loss of appetite and weight loss with 63%.
DISSCUSION
Hepatocellular carcinoma is one of the most common malignancies worldwide. We

present data on 100 patients admitted to the DHQ Civil Hospital Gujranwala. Mean age
was 52.2 +/- 11.3 years. 68% were males and 14% females. 68% patients had underlying
cirrhosis documented on ultrasound examination. Main clinical features were abdominal
pain, fever, diabetes, jaundice, hepatitis C and B. Bilirubin percentages in jaundice
patients were strongly associated with liver cancer. It showed high (77.94) percentage in
male and (51.61) percentage in female who are with high bilirubin and are more affected
with live cancer as compared to non-jaundiced patients.
Being obese was associated with liver cancer with a 44.78 % in male and 34.38 % in
female there was a 38 and 25% increase in the risk for liver cancer in men and women,
respectively. This study indicates that about 71 per cent of people who get exposed to the
hepatitis C virus had chronic hepatitis C. This on-going infection caused inflammation in
the liver. This extended inflammation caused scarring, called cirrhosis, and ultimately
lead to liver cancer. This study showed that elevated BP was statistically significantly
associated with incident cancer in men with 62.69% and in women with 65.63%. In
diabetic patient’s risk of liver cancer increases from 20 to 50% in both male and female.
Female with diabetes are more prior to get liver cancer with 62.5%. Patients with low
grade fever but persistently were more prior to liver cancer with 52.24% in male.
In this epidemiological investigation, it was shown that a number of factors are

responsible for helping the bacteria that cause liver problems or cancer. It has been found
that HBV infection is linked to liver cirrhosis's earlier onset (10–365 days), higher
concentrations of its harmful bacteria, elevated levels of direct bilirubin, and unusual
illnesses that already affect those who have the condition. HBV, particularly its advanced
forms produced at specific points in continuous contamination and its embedded
documentation, directly encourages the growth of HCC (Chang et al., 2016). Compared
34
to current-day medical staging arrangements, the prediction strength is stronger. The
evidence suggests that HBV infection encourages HCC to spread aggressively, at least
within HBV endemic regions.
Numerous challenges face our observation. First, it is impossible to prevent selection bias
in a single middle. Aflatoxins exposure, metabolic syndrome, dietary modifications,
alcohol consumption, and cigarette smoking statistics were no longer present in the
relatives' medical records, making it impossible to determine the severity of their
cirrhosis. Patients who were correctly followed-up had high ALT, AST, or ALP levels, or
one of them was determined to be already unwell, in compared to patients who failed to
follow-up. Additionally, unusual eating habits, the effects of postoperative radiotherapy,
chemotherapy, stereotactic radiation, percutaneous ethanol injection, antiviral treatment,
and targeted therapy because particular illness also promotes this liver infection.
Throughout this examination, it has been established that the district of Gujranwala has a
high incidence of liver cancer. Similar situations are found in notable cities and nations
around the world. This disease is prevalent on a daily basis; in 2014, it was discovered
that 68% of men and 38% of women had liver infections and were in the early stages of
liver cancer (Eom et al., 2018). Age 59 (19%) was when the majority of liver cancers
were first discovered, followed by ages 60–69 and 70–79. Number one liver cancers are
most frequently detected in girls between the ages of 63 and 72 (15.62%), followed by
those between the ages of 73 and 86 (6.25%), and between the ages of 43 and 53
(21.87%). While cases in men (13%) were discovered between the age of 43 and 52
(19.11%). The industrial sector was found to have the highest number of liver cancer
cases. Another global investigation found that long-term hepatitis B or C carriers
eventually develop liver cancer (Kim et al., 2013).
The incidence of liver cancer varies by region. City inhabitants typically experience
kidney stones because of particular activities including eating, exercising, and walking. A
national assessment revealed that Jeju, Jeollanam-do, Guwanju, Busan, and
Gyeongsangnam-do had higher HbsAg-positivity quotations (Barton et al., 2013). Some
different national surveys noted better expenses of anti-hepatitis C virus (HCV) checks in
Jeollanam-do, Busan, Geyongsangbuk-do, and Gyeon-do (Kim et al., 2012).
After thyroid and stomach cancers, colon and rectal cancers, breast cancer, colon and
35
rectal cancers, colon and rectal cancers, and prostate cancers, liver cancer is now the
seventh most common cancer in terms of incidence (Lee et al., 2016).
The number of common cases increased from 351 in 2010 to 57,691 in 2014 among
Koreans. Extended infected persistence may be used to characterise the improved
occurrence in spite of the decreased incidence of primary liver maximal cancers because
this occurrence is influenced by both the superiority rate and the average duration of the
aspect. In 2014, primary liver tumours surpassed thyroid, breast, belly, prostate, and
lungs malignancies to rank seventh among the most serious cancers. Primary liver cancer
has a higher incidence while having a lower incidence, and this is defined by patients
living longer since the prevalence of the disease is influenced by both the disease's
superiority rate and its prevalence through time.
According to (Ladner et al., 2015) hepatitis Bvirus (HBV) is prevalent in korea, china,
and taiwan for a variety of industrial reasons and because there is no legislation
governing the effluents these industries discharge into the environment. According to
reports, roughly 95,000 people in China suffered from liver cancer (Kim et al., 2012;
Barton et al., 2013). The Hepatitis B virus is prevalent through sex and other close
contact (Cho et al., 2017). People in Asian countries frequently contract live infectious
diseases like hepatitis A, hepatitis B, hepatitis C, and HIV, making the likelihood of their
prevelance in future generations higher (Cho et al., 2020). It was found that those over
the age of 55 tended to have weak immune systems, which explains why they were more
likely to contract hepatitis.A,B and ,C virus (Anand et al., 2008). From all liver cases, it
was found that the Hepatitis C virus was present in 10% of cases in North America,
Japan, and Europe (Han et al., 2013). The prevalence of HCV infection based only on
anti-HCV positive decreased to zero in 2014 (Kim et al., 2017). For the HB virus
transmitted by antiviral treatment, there is no available prophylactic vaccination (Zhang
and Shu 2010). Antiviral vaccine was authorized and would be 95% effective in
preventing the virological responses (kuwamori et al., 2008; Winte et al., 2012).
According to research, drinking excessive amounts of alcohol increases the risk of

developing HCC in patients who have been exposed to HBV or HCV (Lu et al., 2015).
According to a prospective observational study, 67% of newly diagnosed HCC patients in
Korea had past or present alcohol consumption histories (Organization 2014). These viral
36
infections were very common in developing nations. It does not imply that industrialized
37
countries are immune because thousands of cases are reported every day and are steadily
rising (Organization 2014). This typical practice persisted at the same rate Asian
comparison a number of the year 2008-2010 and the year 2003-2005.
Diabetes and weight issues are a growing hazard since they may encourage HCV, HBV,
or other liver infections because of non-alcoholic fatty liver. Diabetes and obesity are
becoming more common (Barton et al., 2013). According to recent investigations,
diabetes developed in 21.8-37.1% of Korean patients with cryptogenic HCC (Barton and
Lee 2013). The fact that HCC can develop in a non-cirrhotic liver and be caused by non-
alcoholic fatty liver disease is not a serious concern. Here are some things that we know
increase your risk of developing liver cancer. If you have chronic infection of hepatitis B
or C cirrhosis, certain inherited liver diseases such as Jaundice, diabetes, non-alcoholic
fatty liver diseases or an exposure to Aflatoxins, your area more prior to liver cancer.
There is an extensive variety of symptom presentation in advanced HCC; compensated

patients can be asymptomatic for months or decades. In patients who're symptomatic
from HCC, the most not unusual providing medical capabilities are weight loss, HBV,
HCV. These are regularly superimposed on signs and symptoms of cirrhosis (jaundice,
diabetes, fatigue) and portal high blood pressure, and may additionally be related to boom
in liver transaminases (2). It has a widespread effect on the affected person’s functioning
and well-being. Emotional issues associated with the sickness and remedy give upward
push to anxiety in patients. The quality of life, which includes physical, emotional, and
practical well-being are notably affected because of the headaches and additional-hepatic
manifestations of advanced disease.
38
CONCLUSION
Hepatitis C is widely prevalent in district Gujranwala Pakistan. Such high proportion of

hepatitis C prevalence will result in the high rate of mortality and morbidity in the area;
therefore, possible steps are required for the prevention and cure of such viral infections.
It is concluded that for the development of appropriate vaccines, research at the
molecular level is required to understand the predominant genotypes circulating in
district Gujranwala Pakistan. Typically, viral hepatitis and underlying liver disorders lead
to liver cancer as complications (continuation of hepatitis A, B can also result in liver
cancers). As a result, the epidemiology of the underlying illness drives that of liver
cancer. It is projected that significant advancements in the prevention and treatment of
viral hepatitis will have an immediate or long-term impact on the epidemiology of liver
cancer. Tempura betterment in general survival from liver cancer has been confirmed but
liver most cancers is still in sixth maximum common place most cancers and the second
biggest reason of all most cancers Gujranwala. Currently, age-adjusted occurrence
expenses are falling while crude occurrence fees are steady and prevalence charges are
rising. The most prevalence sort in in the study was male population. Thinking that the
disorder burden correlates with crude charges of the sickness for a given populace a
cautious technique has to be taken. Results revealed that population of elder age were
more suffers. People living in industrial areas suffer more than people living in non-
industrial areas.
39
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Epidemiological Study On Prevelance of Liver Cancer in District Gujranwala

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EPIDEMIOLOGICAL STUDY ON PREVELANCE OF

LIVER CANCER IN DISTRICT GUJRANWALA

Miss. Ammara Rafiq

Dr. Aqeela Zahra

Dr. Adeel Khalid

Dr. Aqeela Zahra

I understand the zero-tolerance policy of HEC and University of Sialkot towards

Has been approved

For the University of Sialkot

deduction to ponder over the forces of nature.

I feel great pleasure in expressing my heartiest obligation to my respected and eruditely

during the preparation of my thesis.

1.1 Introduction of the Study………………………………………………………………… 1

1.2 Purpose of Study……………………………………………………………………......... 5

1.2.1 Research Objective……………………………………………………………….. 5

1.2.3 Problem Statement ………………………………………………………………. 5

1.3 Hypothesis of Study……………………………………………………………………… 5

1.4 Significance of Study…………………………………………………………………….. 5

Chapter 3 Research Methodology…………………………………………………………. 19

4.1 Study Design and Population……………………………………………………………… 19

4.2 Exposure Assessment……………………………………………………………………… 19

4.3 Outcome Assessment………………………………………………………………………. 20

4.4 Statistical analysis………………………………………………………………………….. 20

Chapter 4 Results and Data Analysis……………………………………………………….. 21

Chapter 5 discussion and Conclusion……………………………………………………….. 32

Figure 1.2 The Ras/Raf/MAPK Pathway………………………………………………. 4

Table 4.2 Percentage distribution of different age groups according to

Table 4.3 Percentage distribution of different age groups according to

Table 4.4 Percentage distribution of different age groups according to

Table 4.5 Percentage distribution of different age groups according to

Table 4.6 Percentage distribution of different age groups according to

Table 4.7 Percentage distribution of different age groups according to

Table 4.8 Percentage distribution of different age groups according to

Table 4.9 Percentage distribution of different age groups according to

Skin color …………………………………………………………………… 25

Table 4.10 Percentage distribution of different age groups according to

Table 4.12 Percentage distribution of different age groups according to

Table 4.13 Percentage distribution of different age groups according to

Table 4.14 Percentage distribution of different age groups according to

Exposure to Aflatoxins ……………………………………………………. 28

Table 4.15 Percentage distribution of different age groups according to

Table 4.16 Percentage distribution of different age groups according to

Abdominal mass ………………………………………………………… 29

Table 4.18 Percentage distribution of different age groups according to

Reduce weight …………………………………………………………. 30

Table 4.19 Percentage distribution of different age groups according to

Table 4.20 Percentage distribution of different age groups according to

Loss of appetite …………………………………………………………. 31

HCC Hepatocellular carcinoma

HBV Hepatitis C virus

HBV Hepatitis B virus

pRB retinoblastoma protein

CDK2 Cyclin dependent kinase 2

MAPK Mitogen-activated protein kinase

EGFR Epidermal growth factor receptor

TGF-@ Transforming growth factor alpha

PBC primary biliary cholangitis

IARC International Agency for Cancer Research

The other type of primary liver cancer is intrahepatic cholangiocarcinoma, which is a

Malignancies are a broad category of diseases characterised by abnormal cell formation

Figure1.2:The Ras/Raf/MAPK Pathway (Marampon et al.,2019)

MAPKs are evolutionary preserved catalysts associating cell-surface receptors to basic

1.2 Purpose of Study