THE ROLE OF CHOLELITHIASIS RISK FACTORS IN STONE TYPES

IN CHOLELITHIASIS PATIENTS AT USU HOSPITAL

Denny Rifsal Siregar,* Adi Muradi Muhar**, Doddy Prabisma Pohan*

* Staff Department of Surgery, Medical Faculty, University of Sumatera Utara,
** Digestive Surgery Consultant Department of Surgery, Medical Faculty,
University of Sumatera Utara.

Abstract
Introduction
Cholelithiasis is the common disease in population. The prevalence of
cholelithiasis occurs in 17% of the ASIA population, 10% of the population in
Western countries and 11-36% of all countries in the world. The occurrence of
stone formation is influenced by several risk factors namely obesity, sedentary
lifestyle, geriatric age group and female gender. Types of gall bladder stones can
be classified into cholesterol stones (containing cholesterol> 50%), mixed stones
(containing 20-50% cholesterol), and pigment stones (containing cholesterol
<20%). The general objective of this study was to determine the role of risk
factors for cholelithiasis in stone types in cholelithiasis patients at USU Hospital.

Method
Study design was cross sectional. The sample of this study was 35 samples of
cholelithiasis patients who underwent cholecystectomy either by open or
laparoscopic cholecystectomy at USU Hospital. Gallstones will be examined by a
laboratory. Risk factors assessed were age, gender, body mass index, hemoglobin
bilirubin, cholesterol levels. Data analysis will use the Kruskal Wallis test.

Result
From 35 study samples was found the most types of stones were mixed stones
with 17 (48.6%). Based on the Kruskal Wallis test found a significant relationship
between the type of stone with gender, body mass index, total bilirubin, total
cholesterol, HDL, and LDL.

Conclusion
Factors related to the type of cholelithiasis stone are gender, body mass index,
bilirubin levels, total cholesterol levels, HDL and LDL

Keyword
Cholelithiasis, risk factors, gallbladder

1
INTRODUCTION
Cholelithiasis is the common disease in population. The prevalence of
cholelithiasis occurs in 17% of the Asian population, 10% of the population in
Western countries and 11-36% of all world countries. 1 The occurrence of stone
formation is influenced by several risk factors, namely obesity, sedentary lifestyle,
geriatric age group and female gender.2,3 Some behavioral factors such as physical
activity, tobacco, and alcohol consumption and some personal factors (weight,
height, waist circumference, hip circumference, and parity) also determine the
prevalence of cholelithiasis.2,4
Types of gall bladder stones can be classified into cholesterol stones
(containing cholesterol> 50%), mixed stones (containing 20-50% cholesterol), and
pigment stones (containing cholesterol <20%).5 To distinguish the type of stone
can also be seen from colors such as cholesterol stones will be brownish yellow,
amorphous pigmented stones, brittle, calcium carbonate stones shaped like black
granules, green granules such as mud or black, and others.6
Age, obesity, weight loss, multiparity, hyperlipidemia, diabetes mellitus,
high-calorie diets, and the drugs used will reduce normal storage and motility
functions and cause the formation of cholesterol stones. While cirrhosis, ileal
disease, hemolytic anemia, truncal vagotomy, hyperparathyroidism, and bile duct
infections are risk factors for pigment stone formation. 7 The purpose of this study
was to determine the role of cholelithiasis risk factors for stone types in patients at
USU Hospital.

METHOD
This research is an analytical study using cross sectional method. The study was
conducted at the USU Hospital in the period March-October 2019. The number of
samples in this study was 35 samples. The inclusion criteria in this study were
people with cholelithiasis who performed either cholecystectomy by open or
laparoscopic cholecystectomy. The exclusion criteria were people with
cholelithiasis accompanied by cholecystitis, cholangitis, and no stones were found
in the gallbladder after surgery. The type of gall bladder was examined at the
USU Laboratory. The risk factors assessed in this study were age, gender, body

2
mass index, hemoglobin, cholesterol levels, bilirubin levels. Data is processed
using the SPSS program. The role of cholelithiasis risk factors in stone types was
analyzed by Kruskall Wallis.

RESULT
In this study 35 samples were collected with the mean age of the samples in this
study was 47.74 (± 7.63) years, consisting of 12 men (34.3%) and 23 women
(65.7%). Judging from the most body mass index with overweight category of 19
samples (54.3%) and the lowest category of underweight was 1 sample (2.9%).
The mean hemoglobin level in this study was 12.45 (± 1.19), with an average total
bilirubin level of 0.95 (± 0.36). In terms of total cholesterol levels, the average
total cholesterol level in this study was 189, 91 (± 24.52), the mean HDL level
was 73.3 (± 14.62) and the mean LDL was 95.8 (± 8.93). As for the type of stone,
mixed stone is the most stone type with 17 samples (48.6%), and the type of
cholesterol stone is found in 6 samples (17.1%).
Based on the analysis of the Kruskal Wallis Test found a significant
relationship between the type of stone with gender, body mass index, total
bilirubin levels, total cholesterol levels, HDL, and LDL with p-values <0.05 while
age and hemoglobin levels do not contribute to the formation of stone types. This
can be seen in Table 1.

Table 1. Characteristics of Research Samples

Characteristics Mean (±SD) n (%) p-value
Age 47,74 (±7,63) 0,766
Gender 0,023*
Male 12 (34,3)
Female 23 (65,7)
Body Mass Index 0.089*
Underweight 1 (2,9)
Normowieght 7 (20,0)
Overweight 19 (54,3)
Obese 8 (22,9)
Hemoglobin 12,45 (±1,19) 0.110
Total Bilirubin 0,95 (±0,36) 0.022*
Total cholesterol 189, 91 (± 24,52) 0.025*
HDL 73,3(± 14,62) 0.048*
LDL 95,8 (± 8,93) 0.087*

3
 Stone type
cholesterol 6 (17,1)
Pigment 12 (34,3)
Mix 17 (48,6)

DISCUSSION
Cholelithiasis is the common disease in population. According to Abbas, 1 the
prevalence of cholelithiasis occurs in 17% of the Asia population, 10% of the
population in Western countries and 11-36% of all world countries. In Indonesia
the incidence of cholelithiasis per year has not been officially published.
The occurrence of stone formation is influenced by several risk factors,
namely obesity, sedentary lifestyle, geriatric age group and female gender. 2,3 In
this study, found 35 patients who had cholelithiasis, with the average age of the
sample in this study was 47.74 ± 7.63 years. The frequency of cholelithiasis
increases with age, increasing sharply to 4 to 10 times more often found in
patients aged over 40 years.8 This is similar to the study of Dhamnetiya (2018) 2
the mean age of patients with cholelithiasis was 45.74 ± 11.6 years.
In this study, mixed stones were the most types of stones, found in 17
people (48.6%), followed by pigment stones (12 people (34.3%)), and cholesterol
with 6 people (17.1%). This is comparable to research conducted by Chandran et
al (2017), which states that of the 200 gallstones studied in the population of
Haryana, India, 76 of them were mixed stones (38%).9
 In this study it was found that the number of female patients was higher
than the number of male patients (12 men (34.3%) and 23 women (65.7%)).
Female gender is twice as likely to develop cholelithiasis during the fertile period
(before 40 years) when compared to men, related to female gender hormones
(estrogen); parity, use of oral contraceptives and estrogen replacement therapy. 10,11
The hormone estrogen plays a role in the formation of cholesterol in the
gallbladder by increasing cholesterol saturation.12,13
In this study, body mass index affects the type of gall bladder with p-value
0,089. This is similar to the study of Dhamnetiya et al. 3 which states that with a
BMI >23 kg/m2 is strongly associated with gallstones, because fat accumulation in
adipose tissue increases cholesterol synthesis, biliary cholesterol secretion,
cholesterol supersaturation, and sloping stone formation. Increased BMI has been

4
associated with an increase in residual volume after gallbladder contraction,
impaired contractility, and reduced sensitivity to cholecystokinin, which usually
stimulates gallbladder contraction, all of which supports gall stasis and gallstone
formation.14 This is supported also by the study of Moghaddam et al which states
that obese sufferers will be at twice the risk of suffering from cholelithiasis
compared to a normal body mass index.15
In terms of hemoglobin levels in this study, the mean hemoglobin level
was found in patients with cholelithiasis 12.45 (± 1.19) with a p-value> 0.05. In
contrast to the research of Kim et al. Stated that hemoglobin levels were
associated with the incidence of cholelithiasis with a p-value <0.05. In this study
total bilirubin levels affect the type of gall bladder stone with a p-value of 0.022.
This is consistent with the research of Kim et al (2019) states that bilirubin levels
are associated with the incidence of cholelithiasis with a p-value <0.05.10 The
presence of a gene variant encoding UGT1A1 (uridine5-diphosphate (UDP)-
glucuronosyl transferase 1A1) which plays a role for conjugation of bilirubin
correlates with the risk of gallstones.16
In the study found a total cholesterol level of 189, 91 (± 24.52) and with a
p-value of 0.025. This is similar to the research of Narayanasamy et al (2017) and
Moghaddam et al (2016) which states that cholesterol is a risk factor for the
formation of gallstones. The emergence of gallstones is caused by increased bile
cholesterol secretion. This increase is caused by increased HMG CoA reductase
activity.15,17

CONCLUSION
Factors related to the type of cholelithiasis stone are gender, body mass index,
bilirubin levels, total cholesterol levels, HDL and LDL.

BIBLIOGRAPHY
1. Abbass S,Ahmad I dkk Gyedu, A., Adae-Aboagye, K., Badu-Peprah, A.
2015. Prevalence of Cholelithiasis among persons undergoing abdominal

5
 ultrasound at the Komfo Anokye Teaching Hospital, Kumasi, Ghana. Africa
Health Science. 15: 246-252.
2. Bhatti AY, Waqar AB, Zia SA, Hussain N, Zulfiqar T. 2016. A Cross
Sectional Study on The Risk Of Gallbladdder Stone. International Journal of
Reasearch in Medical Science. 4(11): 5041-5046. DOI:
http://dx.doi.org/10.18203/2320-6012.ijrms20163814.
3. Dhamnetiya D, Goel MK, Dhiman BR, Pathania OP. 2018. Risk Factor
Asscotiated with Gallstone Disease. Indian Journal of Community Health.
Vol 30.
4. Park Y, Kim D, Lee JS, Jeong YK, Lee KG, Cjoi D. 2017. Association
Between Diet and Gallstone of Cholesterol and Pigmen Among Patients ith
Cholecystectomy: A Case –Control Study in Korea. J Health Popul Nutr;
36;39.
5. Kereh DS., Lampus H., Sapan H., Loho, LL. 2015. Hubungan antara Jenis
Batu dan Perubahan Mukosa Kandung Empedu pada Pasien Batu Kandung
Empedu. Jurnal Biomedik. Vol 7: 41-47.
6. Qiaou T, Ma , Luo X, Yang L, Luo Z, Zheng P. 2013. The Systematic
Classification of Gallbladder Stone. Plos One.
https://doi.org/10.1371/journal.pone.0074887.
7. Goktas SB, Manukyan M, Sellmen M. 2015. Evaluation of Factor Affecting
The Type of Gallstone. Indian Journal Surgery. 78(1): 20-26.
8. Völzke H, Baumeister SE, Alte D, et al. 2005. Independent risk factors for
gallstone formation in a region with high cholelithiasis prevalence. Digestion;
71:97–105.
9. Chandran,P, N.K. Kuchhal, et al. An Extended Chemical Analysis Of
Gallstone. Indian Journal of Clinical Biochemistry, 2007 / 22 (2) 145-150.
10. Cirillo DJ, Wallace RB, Rodabough RJ, et al. 2005. Effect of estrogen
therapy on gallbladder disease. JAMA;293:330–339.
11. Kim HS, Cheo SK, Kim CS, Park JS. 2019. Big Data and Analysis of Risk
Factors for Gallbladder Disease in the Young Generation of Korea. Plos One.
https://doi.org/10.1371/journal.pone.0211480.
12. Sharma R, Sachan1 SG, dan Sharma SR. 2013. Preponderance of Gallstone in
Female. World Journal of Pharmacy and Pharmaceutical Sciences, 2(6),
5871-5877. http://www.wjpps.com/wjpps_controller/abstract_id/615.
13. Febyan, Dhilion HRS, Ndraha S, Tendean M. 2017. Karakteristik Penderita
Kolelotiasis Berdsarkan Faktor Risiko di Rumah Sakit Umum Daerah Koja.
Jurnal Kedokteran Mediek Vol 23: 50-56.
14. Shabanzadeh DM, Sørensen LT, Jørgensen T. 2016. Determinants For
Gallstone Formation – A New Data Cohort Study and A Systematic
Review With Meta- Analysis; 5521(November).
15. Moghaddam AA, Khorram A, Bonjar MM, Mohammadi M, Ansari H. 2016.
The Prevalence and Risk Factors of Gallstone Among Adults in South-East of
Iran: A Population-Based Study. Global Journal of health Science vol 8 (4):
60-67.
16. Van Erpecum KJ. 2011. Pathogenesis of cholesterol and pigment gallstones:
An update. Clin Res Hepatol Gas.35(4):281–7.

6
17. Narayanasamy K, Kirankumar B, Karthick R. 2017. A Cross Sectional Study
on Gallstone Disease and Its Risk Factors in A Tertiary Care Hospital of
South India. JSM Gastroenterol Hepatol 5(3): 1090.