Association of Serum Lipids, Oxidized LDL Antibody and High-Sensitivity C-Reactive Protein with Elevated Liver Enzymes in Subjects with Metabolic Syndrome

( Rojeet Shrestha ),( Suraj Parajuli ),( Puja Neopane ),( Madhav Khanal ),( Sunil C Jha ),( Bharat Jha ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: The presence of multiple metabolic disorders such as diabetes mellitus, obesity, dyslipidemia, and hypertension is associated with non-alcoholic liver disease (NAFLD) that can potentially progress to severe liver disease. Although the pathogenesis of NAFLD is poorly understood, there is a considerable amount of evidence that it is associated with abnormal lipid metabolism and dyslipidemia. Therefore, NAFLD not only increases the risk of advanced liver diseases but also associated with future coronary events. Hence, we aimed to examine the association Serum lipids, anti-oxidized-LDL Antibody (Anti-oxLDL Ab), and high-sensitivity C-reactive protein (hsCRP) in the metabolic syndrome (MetS) patients with and without elevated liver enzymes. Methods: A total of 82 individuals (male/female:35/47) with MetS as defined by NCEP ATP III, and 68 healthy control (male/ female:36/32), were recruited for this study. Fasting blood samples were analyzed for blood glucose, eGFR, lipid profile, liver function test (bilirubin, ALT, AST, ALP, γ-GT, LDH, albumin, globulin), anti-oxLDL Ab, and hsCRP. Urine samples were analyzed for albumin-creatinine ratio (UACR). Results: MetS is significantly associated with elevated serum ALT compared to control. 22.0%, 17.8% and 10.3% of individuals with MetS have elevated ALT, AST, and γ-GT, respectively. In contrast, only 6.0%, 4.7%, and 2.6% of healthy control have elevated ALT, AST, and γ-GT, respectively. Interestingly, we found significant elevation of anti-oxLDL Ab and hsCRP in MetS with elevated ALT compared to normal ALT level (38.7±24.7 vs 20.35±10.6 U/L, P<0.001 for anti-oxLDL Ab and 5.55±7.6 vs 2.15±1.2 mg/L, P<0.001 for hsCRP). No such association was observed with serum AST and γ-GT. In addition, the level of ALT is significantly correlated with anti-oxLDL Ab and hsCRP in the MetS with elevated ALT (P=0.021). Although the mean of serum triglyceride, total and LDL-cholesterol, UACR, and eGFR is significantly increased in MetS compared to controls, no such difference was observed between MetS with normal and elevated liver enzymes. Conclusions: MetS is associated with elevated liver enzymes. The individuals with MetS with elevated liver enzymes are associated with increase in hsCRP and anti-oxLDL Ab. The oxidative and inflammatory process might involved in progressive deterioration of liver functions in the MetS.

PE-163: Association Liver Enzymes with Blood Pressure in Diabetic Patients

( Shrestha Rojeet ),( Shrestha Nirajan ),( Bhatt Nirmal Prasad ),( Dahal Sudimna ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Gamma-glutamytransferase (GGT) is routinely used laboratory investigation for liver damage and alcohol consumption. Serum GGT concentration is determined by body fat content, lipid and glucose levels, alcohol consumption and various medications. Several lines of evidence show that serum GGT is associated with cardiovascular and all-case mortality. It is also a marker of oxidative stress. Although serum GGT is associated with hypertension, the correlation between GGT and blood pressure has not been well established. The aim of the present study was to investigate the association between serum GGT and blood pressure in type 2 diabetic patients (T2DM). Methods: A total number of 105 patients with T2DM, who attended Nepal Medical College Teaching Hospital, Kathmandu, Nepal, were recruited for the study. There were 39 males (mean age: 56.6±5.2 years) and 66 females (mean age: 49.6±6.3). The patients with history of liver disease and alcohol intake were excluded from the study. After basic anthropometric measurement, fasting venous blood was collected and subjected for the estimation of liver enzymes. All data were expressed as mean± SD. p-values less than 0.05 were considered as statistically significant. Results: Although serum ALT and AST levels were significantly elevated within the normal range in T2DM compared to control, they are not correlated with systolic blood pressure (SBP) (r= 0.07 and 0.128, respectively) and diastolic blood pressure (DBP) (r= 0.08 and 0.02, respectively) in both men and women. However, serum GGT levels within their normal range were positively correlated with SBP (r=0.4, p<0.01) and DBP (r=0.275, p<0.05) in women. Interestingly, neither of these liver enzymes was correlated with blood pressure among men diabetic patients. Conclusions: These findings suggest that GGT may be linked with blood pressure balance in women and evaluating the levels of GGT could help in the monitoring of hypertension in diabetic individuals.

Association of Oxidized LDL and High-Sensitivity C-Reactive Protein with Elevated Liver Enzymes in Hypertensive Subjects

( Rojeet Shrestha ),( Madhav Khanal ),( Sunil C Jha ),( Bharat Jha ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Hypertension is frequently associated with the development of non-alcoholic liver disease (NAFLD). Although the pathogenesis of NAFLD is poorly understood, there is a considerable amount of evidence that it is associated with abnormal lipid metabolism and dyslipidemia. Therefore, NAFLD not only increases the risk of advanced liver diseases but also associated with future coronary events. Hence, we aimed to examine the association of oxidize-LDL (oxLDL), and high-sensitivity C-reactive protein (hsCRP) in the hypertensive individuals with elevated liver enzymes. Methods: 150 newly diagnosed hypertensive subjects, aged between 30-74 years (male/female:71/79), were recruited. As a control, 150 age- and sex-matched healthy volunteers were also included. Fasting blood samples were analyzed for blood glucose, eGFR, lipid profile, liver function test (bilirubin, ALT, AST, ALP, γ-GT, LDH, albumin, globulin), oxLDL, and hsCRP. Urine samples were analyzed for albumin- creatinine ratio (UACR). Results: Hypertension is significantly associated with elevated serum ALT compared to control. 32.0%, 27.3% and 12.6% of hypertensive individuals have elevated ALT, AST, and γ-GT, respectively. In contrast, only 6.0%, 8.7%, and 2.6% of healthy control have elevated ALT, AST, and γ-GT, respectively. Interestingly, we found significant elevation of oxLDL and hsCRP among the hypertensive individuals with elevated ALT compared to normal ALT level (44.8±24.7 vs 30.65±12.6 U/L, p<0.001 for oxLDL and 4.85±6.6 vs 2.65±3.2 mg/L, p=0.023 for hsCRP). No such association was observed with serum γ-GT. In addition, the level of ALT is significantly correlated with oxLDL in the subjects with elevated ALT (p=0.031). Although the mean of serum triglyceride, total and LDL-cholesterol, UACR, and eGFR is significantly increased in hypertensive subjects compared to controls, no such difference was observed between hypertensive subjects with normal and elevated liver enzymes. Conclusions: Hypertensive subjects with elevated liver enzymes are associated with increase in oxidative and inflammatory markers but not with other traditional cardiac risk factors.

Waist Circumference, Not Body Mass Index, Is Associated with Increased Gamma-glutamyltranspeptidase in Type Diabetes Mellitus

( Nirajan Shrestha ),( Nirmal Prasad Bhatt ),( Sudimna Dahal ),( Rojeet Shrestha ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Serum gamma-glutamyltranspeptidase ( GGT), a marker of liver injury, alcohol consumption, and oxidative stress, has been shown to be associated with obesity and diabetes mellitus. Obese individuals with higher GGT are associated with complications in type 2 diabetic patients. There is evidence that waist circumference (WC) measured obesity more accurately than body mass index (BMI). In the present study, we aimed to evaluate association of GGT with WC and BMI in diabetic subjects. Methods: The study subjects were 105 type 2 diabetic patients (39 men and 66 women), who attended outpatient department of Nepal Medical College Teaching Hospital, Kathmandu, Nepal. The patients with the history of alcohol intake and liver disease were excluded from the study. Anthropometric measurement was taken and venous blood was collected for biochemical analysis. Statistical analysis was done using SPSS 16.0. The p-values less than 0.05 were considered as significant. Results: The serum GGT levels were positively correlated with blood sugar levels in diabetic subjects. Similarly, GGT levels were positively associated with WC (r=0.269, p<0.05) in women diabetic patients. However, no such correlation was observed in men diabetic subjects (r=0.14). Also, there was no correlation between serum GGT levels and BMI (r=0.03), suggesting that regional fat distribution in type 2 diabetes is associated with the increased levels of serum GGT. Conclusions: In conclusion, WC, not the BMI, is correlated with serum GGT levels in women with type 2 diabetics. Hence, it is important to evaluate central obesity and GGT in patients with diabetes mellitus.

Liver Involvement in Multiple Myeloma: A Hospital Based Retrospective Study

Poudel, Bibek,Mittal, Ankush,Shrestha, Rojeet,Farooqui, Mohammad Shamim,Yadav, Naval Kishor,Shukla, Pramod Shanker Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Objective: This study was to assess liver involvement in multiple myeloma with the aid of liver function tests. Materials and Methods: A hospital based retrospective study was undertaken using data retrieved of multiple myeloma from the register maintained in the Department of Biochemistry of the Manipal Teaching Hospital, Pokhara, Nepal between $1^{st}$ January, 2007 and $28^{th}$ February, 2012. We collected biomarkers of liver profiles including bilirubin (Total, Direct and Indirect), total protein, albumin, AG ratio, SGOT, SGPT, ALP, ${\gamma}GT$, LDH, ferritin, renal profile and hematological profile. Descriptive statistics and testing of hypothesis were used for the analysis using EPI INFO and SPSS 16 software. Results: Out of 37 cases of multiple myeloma, serum level of AST, ALT, ALP, ${\gamma}GT$ and LDH were increased above the cut-off point in 22 (59.5%), 24 (64.86%), 13 (35.13%), 9 (24.3%) and 11 (29.7%) respectively. The mean values of AST ($65.5{\pm}28.18$ U/L), ALT ($68.37{\pm}29.74$ U/L), ALP ($328.0{\pm}148.4$ U/L), ${\gamma}GT$ ($44.5{\pm}29.6$ U/L) and LDH ($361.7{\pm}116.5$ U/L), total protein ($9.79{\pm}1.03$ gm/dl) were significantly increased when compared with controls. In contrast, albumin ($3.68{\pm}0.43$ gm/dl) and the AG ratio ($0.62{\pm}0.15$) were significantly decreased. Similarly, anemia, hyperuricemia, azotemia, hypercalcaemia and Bence Jones proteinuria were found in 30 (78.9%), 27 (71.1%), 19 (51.5%), 15 (39.5%) and 16 (42.1%) respectively, in cases of multiple myeloma. Conclusions: While clinical manifestation of liver disease among the multiple myeloma was not common, abnormalities in liver function were characteristic.

Prostate Biomarkers with Reference to Body Mass Index and Duration of Prostate Cancer

Poudel, Bibek,Mittal, Ankush,Shrestha, Rojeet,Nepal, Ashwini Kumar,Shukla, Pramod Shanker Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Objective: This study was performed to assess prostate biomarkers with reference to body mass index and duration of prostate cancer. Materials and Methods: A hospital based retrospective study was undertaken using data retrieved from the register maintained in the Department of Biochemistry of Manipal Teaching Hospital, Pokhara, Nepal between $1^{st}$ January, 2009 and $28^{th}$ February, 2012. Biomarkers studied were prostate specific antigen (PSA), acid phosphatase (ACP) and prostatic acid phosphatase (PAP), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (${\gamma}GT$). Demographic data including age, duration of disease, body weight, height and body mass index (BMI) were also collected. Duration of disease was categorized into three groups: <1 year, 1-2years and >2 years. Similarly, BMI ($kg/m^2$) was categorized into three groups: <23 $kg/m^2$, 23-25 $kg/m^2$ and >25 $kg/m^2$. Descriptive statistics and testing of hypothesis were used for the analysis using EPI INFO and SPSS 16 software. Results: Out of 57 prostate cancers, serum level of PSA, ACP and PAP were increased above the cut-off point in 50 (87.5%), 30 (52.63%) and 40 (70.18%) respectively. Serum levels of PSA, ACP and PAP significantly declined with the duration of disease after diagnosis. We observed significant and inverse relation between PSA and BMI. Similar non-signficiant tendencies were apparent for ACP and PAP. Conclusions: Decreasing levels of prostate biomarkers were found with the duration of prostate cancer and with increased BMI. Out of prostate biomarkers, PSA was found to be significantly decreased with the duration of disease and BMI.

Association of Serum Aminotransferases with High Density Lipoprotein Cholesterol (HDL-C) in Diabetic Patients

( Nirmal Prasad Bhatt ),( Nirajan Shrestha ),( Sudimna Daha ),( Rojeet Shrestha ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Alanine aminotransferase ( ALT) and aspartate aminotransferase AST) are commonly used markers of liver-disorders. Non-alcoholic fatty liver disease (NAFLD) is associated with lipid abnormalities and type 2 Diabetes. Previous studies have suggested elevation in levels of ALT and AST which may serve as markers for NAFLD. However, correlation of liver enzymes and lipid profile has not been well established. Hence, current study was performed to observe the association between aminotransferases and HDL-C in type-2 diabetic patients. Methods: The study was carried out in Department of Pathology, Nepal Medical College and Teaching Hospital, Kathmandu, Nepal. A total of 103 type 2 diabetic patients, 41 males (mean age: 55.9±13.4) and 62 females (mean age: 49.9±10.6) were included in this study. Patient’s anthropometric measurements were performed before collecting the fasting blood for aminotransferases and lipid profile analysis. The results were shown as mean ± SD. P-values less than 0.05 were considered as statistically significant. Results: In the present study, serum ALT and AST levels were correlated with fasting HDL (r= -0.419, P < 0.05 and r= -0.354, P < 0.05 respectively) in women with type 2 diabetes. However, there was no such correlation among these parameters in men diabetic patients. Furthermore, there was no correlation between aminotransferase and fasting TC, TG and LDL levels. Conclusions: This finding suggests the correlation between aminotransferase and FHDL in diabetic patients. Hence, measurement of aminotransferase and lipid profile has clinical significance in diabetic patients.

Hepatic Association with Increased ALT and GGT in Type 2 Diabetic Patients

( Nirmal Prasad Bhatt ),( Nirajan Shrestha ),( Sudimna Dahal ),( Rojeet Shrestha ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Diabetes mellitus (DM) has been associated with liver dysfunction and dyslipidemia, is a leading cause of global mortality, inducing various secondary complications, such as coronary heart disease, neuropathy and chronic kidney disease. DM is associated with non-alcoholic fatty liver disease (NAFLD), including its severe form, non-alcoholic steatohepatitis. NAFLD among diabetic patients in western countries is highly prevalent. However, there is a paucity of data showing such an association in Nepalese patients with DM. Thus, the current study was conducted for a better understanding of liver dysfunction in Nepalese patients with type 2 diabetes mellitus (T2DM). Methods: We conducted a prospective study to determine if any correlation exists between serum liver enzymes in T2DM and different confounding factors. One hundred and five patients (male:female= 0.6) with a median age of 52±1.09 years, newly diagnosed as having T2DM, were recruited from the outpatient department of tertiary hospital during one year. Results: We observed a marginal, yet statistically significant, increase of serum alanine transaminase and γ-glutamyl in the diabetic patients compared to healthy controls. However, elevation of serum AST was statistically insignificant. Conclusions: Elevation of the liver enzymes, ALT and GGT, within the normal range in T2DM may indicate initiation of pathological processes in the liver. Hence, regular monitoring of liver function is advantageous to prevent advanced liver injury in T2DM.

Effects of Long-term Use of Depo-medroxyprogesterone Acetate on Lipid Metabolism in Nepalese Women

Binod Kumar Yadav,Rajesh Kumar Gupta,Prajwal Gyawali,Rojeet Shrestha,Bibek Poudel,Manoj Sigdel,Bharat Jha 대한진단검사의학회 2011 Annals of Laboratory Medicine Vol.31 No.2

Various synthetic progestogens that are used as contraceptives have been reported to influence lipid and lipoprotein fractions differently. Depo-medroxyprogesterone acetate (DMPA), a synthetic progestogen, is used by Nepalese women as a contraceptive agent. Our study aims to determine the effects of long-term use of DMPA on lipid metabolism. We performed this study on 60 healthy Nepalese women who had been using DMPA for more than 2 yr and age- and weight-matched control subjects who were not using hormonal contraceptives. Fasting blood samples were collected from the subjects for the estimation of total cholesterol (TC) and triglyceride (TG) levels, and the levels of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were estimated using the Friedewald’s equation. TC and LDL-C levels in DMPA users were significantly higher than those in non-users. Our study concluded that DMPA use induces lipid metabolism changes that can increase the risk of cardiovascular diseases.