The Pattern of Dyslipidemia in Chronic Liver Disease Patients

Introduction Patients with chronic liver disease are expected to report derangements in serum lipid profiles. Lipid profile monitoring is not a part of the routine management of these patients in our hospital. Few recent studies show how lipid profile varies with the severity of disease and should be considered in the management planning of such patients. The objective of this study was to determine the pattern of dyslipidemia in chronic liver disease patients. Materials and methods A cross-sectional study was conducted involving 171 patients of all genders aged between 18 years and 60 years presenting with chronic liver disease with disease severity graded on Child-Pugh class as A, B, and C. Lipid profile was acquired in all these patients and was compared across various subgroups. Individual serum lipid parameters were graded as normal, high, or very high. Each patient was required to provide written informed consent. Statistical Package for Social Sciences (SPSS) version 21.0 (IBM Corp. Armonk, NY) was used to analyze data statistically, taking a p-value of ≤0.05 as significant. Results The mean age of patients was 51.2±7.3 years. The male to female ratio came out to be 1.5:1, with 103 (60.2%) male and 68 (39.8%) female patients included in the study. The disease was classified as Child-Pugh A in 20 (11.7%) patients, Child-Pugh B in 67 (39.2%) patients, and Child-Pugh C in 84 (49.1%) patients. Forty-four (25.7%) patients were hypertensive while 62 (36.3%) were diabetic. The mean body mass index (BMI) of these patients was 25.9±2.4 kg/m2. Mean serum values among Child-Pugh A, Child-Pugh B, and Child-Pugh C of low-density lipoproteins (LDL) (113.15±14.08 vs. 95.58±14.25 vs. 53.46±5.90 mg/dl; p-value 0.001), high-density lipoproteins (HDL) (50.60±3.19 vs. 40.70±2.95 vs. 35.40±3.88 mg/dl; p-value 0.001), total cholesterol (174.20±17.33 vs. 164.00±17.82 vs. 128.64±24.73 mg/dl; p-value 0.001), and triglycerides (127.15±8.98 vs. 100.84±27.12 vs. 93.36±25.56 mg/dl; p-value 0.001) decreased significantly with increasing severity of disease. Nineteen (11.1%) patients had hyperlipidemia (serum values of two or more parameters above normal) while 152 (88.9%) patients had normal lipid profile. When stratified, no statistically significant difference was found in the frequency of hyperlipidemia across various subgroups based on the patient's gender, age, duration, and severity of the disease, BMI, or diabetic and hypertensive status. Conclusions A substantial proportion of patients with chronic liver disease had hyperlipidemia which varied with the severity of disease on Child-Pugh classification. Routine monitoring of the lipid profile of such patients is necessary for timely identification and management of dyslipidemia to improve the outcome of such patients. It also suggests an important role of lipid profile in the risk stratification and treatment of chronic liver disease patients and warrants further studies in this regard.


Introduction
Several hepatic disorders in which normal liver tissue is replaced by fibrotic tissue are collectively termed chronic liver disease (CLD) [1]. Several metabolic abnormalities are common in CLD like dyslipidemias, clotting factor deficiencies, and in some cases venous thromboembolism due to deficiency of anticoagulation factors [2]. Dyslipidemia is a metabolic anomaly that causes an imbalance in lipids or lipoproteins [3]. Fat-soluble vitamins, dietary cholesterol, and long-chain fatty acids are absorbed and transported by lipoproteins. Lipids are present in the cell membrane and are important regulators of cellular function and the internal body environment. Exogenous and endogenous lipid metabolism cycles are controlled by the liver. The liver is also responsible for the formation of apolipoproteins, which activate enzymes responsible for lipoprotein metabolism and attachment to their specific receptors [4].
Imbalance in serum lipoprotein can be due to cirrhosis of the liver, where cholesterol of low-density lipoprotein (LDL) variant and high-density lipoprotein (HDL) variant are reduced [5]. Dyslipidemia reported in patients of CLD is remarkable in contrast with other causes of secondary dyslipidemia as the composition, appearance, serum levels, and mobility of lipoproteins is disturbed [3,6]. Ress and Kaser have reported that CLD interferes with the metabolism of lipid by disrupting the functionality of the liver, resulting in the accumulation of lipid drops in hepatocytes. Abnormal secretion of very-low-density lipoprotein (VLDL) leads to hepatic steatosis [7].
A previous study reported that the total cholesterol was markedly decreased in 15% of patients. Overall, 82.5% of patients presented with hypocholesterolemia, and 2.5% of patients presented with hypercholesterolemia. Whereas, 63.13% of patients reported low triglyceride levels, 88.13% of patients reported decreased LDL, and increased levels were reported in 4.38% of patients [4]. In another study, 69.09% of patients had decreased total cholesterol, hypercholesterolemia was not reported, and 12.72% of patients had low serum triglyceride [8].
As variation in results is mentioned in the studies above, the present study is conducted to see the pattern of dyslipidemia and lipid metabolism derangement in CLD patients and to have an idea of local prevalence. This study will help the patients and healthcare providers by early identification of the pattern of dyslipidemia and taking steps to improve the survival and outcomes of the patients.

Materials And Methods
This cross-sectional study was done for six months from August 2019 to January 2020 at the Department of General Medicine, Peoples Medical College, and Hospital, Nawabshah, Pakistan.

Sample size, inclusion, and exclusion criteria
A sample size of 171 was calculated using the World Health Organization (WHO) software, taking the prevalence of low serum triglyceride levels in patients 12.72%, the margin of error 5%, and confidence level 95%. Patients suffering from the CLD aged between 18 years and 60 years, confirmed by history and medical record of either gender were enrolled in the study. Whereas, the patients undergoing concomitant illnesses like heart failure, renal failure, or a thyroid problem, patients taking lipid-lowering drugs, patients consuming alcohol, or patients with a body mass index (BMI) of >30 kg/m 2 were excluded from the study sample.

Sampling technique and data collection
Non-probability consecutive sampling technique was employed to sample patients. The study was conducted after approval from the ethical committee of the institute. Informed consent was also taken from all the patients enrolled before including them in the study. After taking a complete history and physical examination, a lipid profile was done to investigate the pattern of dyslipidemia. The data was entered in a predesigned proforma. Confounding variables and bias were controlled by strictly following inclusion criteria.

Statistical analysis
Statistical Package for Social Sciences (SPSS) version 21.0 (IBM, Armonk, NY) was used to analyze the collected data. Continuous variables, such as age, BMI, duration of liver disease, LDL, total cholesterol, HDL, and triglycerides, were presented as mean±SD. Serum levels of triglycerides, LDL, total cholesterol, and HDL have been compared across various subgroups using independent sample t-test/ANOVA. A p-value of ≤0.05 was considered significant. Categorical variables like gender, the severity of liver disease (Child-Pugh class), diabetes mellitus, hypertension, and pattern of dyslipidemia were presented using percentages and frequencies. Age, gender, BMI, duration, the severity of the disease, diabetes mellitus, and hypertension were stratified to address the effect of modifiers. Chi-square test was applied to assess categorical variables, taking a p-value of ≤0.05 as significant.

Results
The mean age of the patients enrolled was 51.2±7.3 years. There were 103 (60.2%) male and 68 (39.8%) female patients who comprised the study population; male to female ratio was reported to be 1.5:1. The duration of disease ranged from six to 18 months with a mean of 12.1±3.7 months. The disease was classified as Child-Pugh A in 20 (11.7%) patients, Child-Pugh B in 67 (39.2%) patients, and Child-Pugh C in 84 (49.1%) patients. Forty-four (25.7%) patients were hypertensive while 62 (36.3%) were diabetic. BMI of these patients ranged from 21.3 kg/m 2 to 29.9 kg/m 2 with a mean of 25.9±2.4 kg/m 2 as shown in Table 1.

Characteristics Participants n=171
Age ( Table 7. Very high or low levels were not observed in any patient.

Discussion
Liver injury persisting six months or more is a manifestation of CLD, which can be caused by infection, inflammation, toxic, or congenital predisposition. Dyslipidemia is one of the systemic effects produced by CLD. Healing response due to liver injury causes hepatic fibrosis [9,10]. Liver impairment causes disturbed protein anabolism, excretion of bilirubin, and lipid metabolism. Such patients should be managed to improve liver metabolism [9]. Lipid profile monitoring is not a part of the routine management of such patients in our hospital; however, recent studies showed that lipid profile varies with the severity of disease and should be considered in the management of such patients [4,7].
Patients with CLD in our study had a mean age of 51. We observed a male to female ratio of 1.5:1 in our study. A similar male predominance among such patients has been reported previously by Ali et al. who observed it to be 1.5:1 in the local population [11].  [4,30].
A large sample size of 171 cases, strict exclusion criteria, and stratification of the results to minimize bias were the strengths of our study. However, a possible limitation could be our inability to account for serum lipid profile's role in terms of response to treatment and mortality which could have highlighted its role in CLD patients and could have helped in the risk stratification and management of these patients.
this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.