Frequency of gallstones and mean BMI in decompensated cirrhosis

Introduction The aim of the study was to determine the frequency of gallstones in patients with decompensated cirrhosis and to know about mean Body mass index (BMI) in patients of decompensated cirrhosis i.e End stage liver disease (ESLD) with and without gallstones. Methods it is a cross sectional descriptive study, conducted at the department of Hepato-gastroenterology, Sindh Institute of Urology and Transplantation (SIUT), Karachi from 1st August 2014 to 28 February 2015. Two hundred patients were enrolled from outpatient clinics of Hepato-gastroenterology that fulfilled the defined selection criteria. Questionnaire was filled for data collection. SPSS version 20.0 was used to analyze data. Mean value of age and BMI was calculated by mean ± S.D. values. Mean ± SD was also calculated for BMI in patients with and without gallstones. Stratification of the age, gender, and liver disease severity were done and chi-Square test was applied. p-values less than 0.05 considered statistically significant. Results Two hundred consecutive patients were enrolled among them 112(56%) were male. Mean age was 46.89 ± 11.9, BMI 23.59 ± 4.7 and CTP score was 9.7 ± 1.9. Most of the patient had Child class 'B' cirrhosis 102(51%), most common etiology was found to be Hepatitis C 133 (66.5%), cholelithiasis was found in 59(29.5%), sludge in 36 (18%) and both stone and sludge in 24(12%) of the cases. Advanced liver disease that is, more CTP score and child class 'C' was associated with increased frequency of gall stone formation (p-value = 0.012), and advancing age on age stratification (p-value = 0.024) however no relation was observed with increase BMI, gender, ethnicity, cause or duration of disease in this population. Conclusion Gallstone formation is associated with advanced stage of cirrhosis and hepatitis C Virus related CLD, contrary to the established risk factors, no relation of gender or BMI was found in decompensated liver disease.


Introduction
Cirrhosis is considered a major health problem causing significant morbidity and mortality worldwide [1][2][3]. In Pakistan cirrhosis is mostly caused by chronic Hepatitis C (28%) and Hepatitis B (22%) infections but alcoholic liver disease is common globally [4]. Gall stones are among the most common cause of gall bladder pathology. It could be cholesterol or pigment stones or mixed.
Cholesterol stones occur mostly solitary and are more common in western countries, whereas pigment stones are commonly found in Asian people and are usually, multiple in number [5]. About one third of cirrhotic patients have gallstones, and most of them have pigmented stones [6]. The prevalence of gall stones in cirrhosis is reported to be around 23% with annual incidence of 3.4% [7], whereas in general population it was found to be 10-30% [8][9][10].
Gall stone formation is associated with many risk factors. Its prevalence increases linearly with advancing age, female gender, pregnancy, multiparity, undiagnosed diabetes, glucose intolerance, viral etiology and prolonged duration of cirrhosis, H. pylori infection, heavy ethanol intake, carbohydrate rich diet, gall bladder wall thickness (>4mm) and portal hypertension [8][9][10][11][12][13][14][15]. Higher Body Mass Index (BMI) is also an independent risk factor for gall stone formation [16]. The increased frequency of gall stones in fertile women is primarily attributed to estrogens that cause excessive secretion of cholesterol into bile, whereas gall bladder stasis and autonomic neuropathy are mainly implicated in advanced cirrhosis.
A study done at Taiwan by Li et al concluded that there's no difference in the mean BMI of patients with gallstones (22.2±0. 6) and without gallstones (23.7 ± 0.5) [17] in liver cirrhosis and it included patients of both compensated and decompensated cirrhosis, he also concluded that risk of gallstone formation increases with severity of cirrhosis, that is most of the patient having gallstones belongs to child class 'C', in this study sample size was also not calculated, so the results cannot be generalized to patients with decompensated cirrhosis. No local study have been done so there is a need of further study in this respect. The rationale of this study is to assess the frequency of gallstones and Mean BMI specifically in patients with or without gallstones decompensated cirrhosis, in order to ascertain the magnitude of disease, possible relation to BMI.

Results
The total number of patients enrolled were 200, out of which 112 (56%) were male. Table 1 showed basic demographic data of patients, mean age of patients with end stage liver disease (ESLD) was found to be 46.8 ± 11.9 years, most of these were in CTP class B 102 (56%) and mean CTP score was found to be 9.7 ± 1.9 while median CTP score was found to be 9. Overall calculated mean BMI was 23.59 ± 4.7. Most of the patients included in analysis belonged to ethnic group who spoke Urdu language 75(37.5%), followed by Sindhi 55(27.5%) and Punjabi speaking 31(15.5%). Majority of the patients with BMI > 23.59 belonged to Pathan ethnicity, 11 out of 19(57.9%), followed by Balochi 5 out of 9 (55.6%). However, gall stones were more frequently found among Urdu speaking, 25 out of 75(33.3%), followed by Sindhi speaking 16 out of 55(29%). Overall viral etiology was found to be commonest cause of CLD out of which Hepatitis C was found to be the commonest causative agent in study population that is 133(66.5%), followed by cryptogenic CLD and autoimmune related CLD in 21(10.5%) and 9(4.5%) respectively as shown in Table 1. Out of total observed patients 141(70.5%) had no stones while multiple stones were seen in 40(20%) and single in 19(9.5%). Sludge was present in 36(18%) patients, both sludge and stones were observed in 24(12%) patients. Table 2demonstrated stratification of data with respect to gallstones and 46 (34.5%) patients with anti HCV positive were found to have gallstones as compared to only 13(19.5%) of anti HCV negative had gall stones with significant p-value of 0.032.
Significant association was also found for CTP score and CTP class, i.e. 0.013 and 0.013 respectively while no association of gallstones could be elicited for age, gender, BMI, duration of disease and ethnicity. Statistically significant association was found for CTP score and CTP class with respect to number of gallstones also, that is pvalue of 0.022 and 0.022 respectively, as demonstrated in Table 3.
Data was also stratified with respect to mean BMI along with all effect modifiers and it was found to be significant only with Anti HCV (p-value = 0.03), while no association could be elicited for other parameters age, gender, number of gallstones, duration of disease, CTP score, CTP class and ethnicity (Table 4).

Discussion
Chronic liver disease is one of the major health problems globally, causing increased morbidity and mortality. In our country the most common cause of chronic liver disease is hepatitis C 28% followed by hepatitis B 22%, whereas alcoholic liver disease is more common etiologic agent worldwide [4]. This is also maintained in present study, viral etiology was found to be most common of decompensated liver disease, of which hepatitis C virus related was found to be predominant (66%). This disease results in various complications and is also considered an important risk factor for gall stone formation. Based on the findings of our study the frequency of gallstone formation in decompensated CLD was found to be 29.5% which is almost similar to the study based in Lahore by Naheed et al, who reported gall stones in 31% of patients [2]. This Advanced age was found to be significantly associated with increased GSD by Zhang et al [20] and this was also maintained by our study which revealed highest gallstones incidence in patients above 50 years of age, 33 out of 121 (27.2%) had gallstones but that was not found to be statistically significant. Furthermore, advanced cirrhosis was significantly associated with gall stone formation in our study. We reported gallstones in 62.7% of child class C patients as in conformity with other studies, including  Obesity is a risk factor for gall stone formation in general population.

What this study adds
 Gall stone formation is more common in HCV related ESLD;  Increased BMI has no role in gall stone formation in ESLD;  There is no statistical significance in gall stone formation in female in patient with ESLD.

Competing interests
The authors declare no competing interests.

Authors' contributions
Ayesha Aslam Rai: had collected data, analyzed it and wrote manuscript; Aisha Nazeer: had participated in data analysis and wrote manuscript; Nasir Hassan Luck: had written manuscript and critically analyzed study. All the authors have read and agreed to the final manuscript. Table 1: Basic demographic data of study population