scholarly journals Physiologically based modeling of the effect of physiological and anthropometric variability on indocyanine green based liver function tests

2021 ◽  
Author(s):  
Adrian Köller ◽  
Jan Grzegorzewski ◽  
Matthias König

Accurate evaluation of liver function is a central task in hepatology. Dynamic liver function tests (DLFT) based on the time-dependent elimination of a test substance provide an important tool for such a functional assessment. These tests are used in the diagnosis and monitoring of liver disease as well as in the planning of hepatobiliary surgery. A key challenge in the evaluation of liver function with DLFTs is the large inter-individual variability. Indocyanine green (ICG) is a widely applied test compound used for the evaluation of liver function. After an intravenous administration, pharmacokinetic (PK) parameters are calculated from the plasma disappearance curve of ICG which provide an estimate of liver function. The hepatic elimination of ICG is affected by physiological factors such as hepatic blood flow or binding of ICG to plasma proteins, anthropometric factors such as body weight, age, and sex, or the protein amount of the organic anion-transporting polypeptide 1B3 (OATP1B3) mediating the hepatic uptake of ICG. Being able to account for and better understand these various sources of inter-individual variability would allow to improve the power of ICG based DLFTs and move towards an individualized evaluation of liver function. Within this work we systematically analyzed the effect of various factors on ICG elimination by the means of computational modeling. For the analysis, a recently developed and validated physiologically based pharmacokinetics (PBPK) model of ICG distribution and hepatic elimination was utilized. Key results are (i) a systematic analysis of the variability in ICG elimination due to hepatic blood flow, cardiac output, OATP1B3 abundance, liver volume, body weight and plasma bilirubin level; (ii) the evaluation of the inter-individual variability in ICG elimination via a large in silico cohort of n=100000 subjects based on the NHANES cohort with special focus on stratification by age, sex, and body weight; (iii) the evaluation of the effect of various degrees of cirrhosis on variability in ICG elimination. The presented results are an important step towards individualizing liver function tests by elucidating the effects of confounding physiological and anthropometric parameters in the evaluation of liver function via ICG.

2021 ◽  
Vol 12 ◽  
Author(s):  
Adrian Köller ◽  
Jan Grzegorzewski ◽  
Matthias König

Accurate evaluation of liver function is a central task in hepatology. Dynamic liver function tests (DLFT) based on the time-dependent elimination of a test substance provide an important tool for such a functional assessment. These tests are used in the diagnosis and monitoring of liver disease as well as in the planning of hepatobiliary surgery. A key challenge in the evaluation of liver function with DLFTs is the large inter-individual variability. Indocyanine green (ICG) is a widely applied test compound used for the evaluation of liver function. After an intravenous administration, pharmacokinetic (PK) parameters are calculated from the plasma disappearance curve of ICG which provide an estimate of liver function. The hepatic elimination of ICG is affected by physiological factors such as hepatic blood flow or binding of ICG to plasma proteins, anthropometric factors such as body weight, age, and sex, or the protein amount of the organic anion-transporting polypeptide 1B3 (OATP1B3) mediating the hepatic uptake of ICG. Being able to account for and better understand these various sources of inter-individual variability would allow to improve the power of ICG based DLFTs and move toward an individualized evaluation of liver function. Within this work we systematically analyzed the effect of various factors on ICG elimination by the means of computational modeling. For the analysis, a recently developed and validated physiologically based pharmacokinetics (PBPK) model of ICG distribution and hepatic elimination was utilized. Key results are (i) a systematic analysis of the variability in ICG elimination due to hepatic blood flow, cardiac output, OATP1B3 abundance, liver volume, body weight and plasma bilirubin level; (ii) the evaluation of the inter-individual variability in ICG elimination via a large in silico cohort of n = 100,000 subjects based on the NHANES cohort with special focus on stratification by age, sex, and body weight; (iii) the evaluation of the effect of various degrees of cirrhosis on variability in ICG elimination. The presented results are an important step toward individualizing liver function tests by elucidating the effects of confounding physiological and anthropometric parameters in the evaluation of liver function via ICG.


Author(s):  
Giuseppe Chiarioni ◽  
Stefan Lucian Popa ◽  
Andrea Dalbeni ◽  
Carlo Senore ◽  
Daniel Corneliu Leucuta ◽  
...  

Background and Aims: The Western diet is rich in saturated fats, refined sugars and meat consistent with a high-energy load and secondary risk of increased metabolic diseases including nonalcoholic fatty liver disease (NAFLD). However, no data are available on potential benefit of vegan diets in NAFLD and/or nonalcoholic steatohepatitis (NASH). We aimed to study prospectively the effect of a vegan diet, excluding all animal products on liver chemistry in a group of consecutive NAFLD patients. Methods: This was a prospective, pilot study run on 40 consecutive patients affected by NAFLD. Eight subjects refused to join the study for poor diet palatability, leaving 32 patients (19 males, mean age 50 years), with abnormal measures of liver function who agreed to adhere to a vegan diet for six months. The caloric intake was tailored by the dietitian to obtain a weight loss ≥5% of body weight in overweight patients [body-mass index (BMI) ≥25] and ranged from 1500 Kcal to 1800 Kcal. Patients were contacted monthly by phone to reinforce diet and lifestyle advice and were seen at the gastrointestinal clinic when doubtful about diet advice. Results: At six-month follow-up, 6 subjects did not attend the clinic leaving only 26 patients for data analysis. Initial anthropometric values were mean weight 78 kg (range 52-95), mean body mass index (BMI) 26.8 Kg/m2 (range 20.3-31.2). Liver function tests showed mean ALT value 99 U/L (SD±45), mean AST value 54 U/L (SD±44), mean GGT value 160 U/L (SD±122), pre-treatment. After six months mean body weight was 73 Kg (range 52-87), mean BMI was 25.2 Kg/m2 (range 20.3-29.7) (p<0.001 compared to baseline for both parameters). Liver enzymes improved to a mean of ALT value 36 U/L (SD±21), AST value 27 U/L (SD±10) and GGT value 55 U/L (SD±57), respectively (p<0.001 compared to baseline for all enzymes). Normalization of liver function tests as a whole was observed in 20/26 patients (76.9%). A loss of ≥ 5% of body weight was observed in 12 patients (46.1%), but it did not correlate with the normalization of liver function tests (p=0.5). Conclusions: Our data provide preliminary evidence of improved liver enzymes in NAFLD patients with a strict vegan diet and although our study sample is limited, decreased body weight did not seem critical to the outcome.


Author(s):  
Asna Urooj ◽  
Namratha Pai Kotebagilu ◽  
Lohith Mysuru Shivanna ◽  
Satish Anandan ◽  
Akshatha Nagaraja Thantry ◽  
...  

Background: Muslims fast during the month of Ramadan by abstinence from food and drink every day from dawn to sunset. Studies have reported contradictory results with respect to the changes in body weight and biochemical parameters. No study has been conducted on the association between fasting and body weight and biochemical parameters in the Indian setting on healthy Muslim subjects. Objectives: To assess the effect of fasting during Ramadan on biochemical parameters such as lipid profile, liver function test, renal function test, antioxidant status, random blood sugar, hemoglobin, body composition, and blood pressure in a sample of healthy individuals. Methods: In this study, 52 healthy free-living participants (25 males, 27 females, 21-64 years) who met the inclusion and exclusion criteria and completed both follow-ups (before and after Ramadan) were studied. Participants were fasting 12 hours a day for at least 21 days, including menstruating women. It was a free-living study with no dietary restrictions. Anthropometry, lipid profile, liver and renal function tests were measured by standard methods. Body composition was analyzed by bioelectrical impedance. Results: Significant beneficial changes in albumin, alanine aminotransferase, creatinine, and high-density lipoprotein (HDL) were observed, while total cholesterol, random blood sugar, aspartate aminotransferase, and alkaline phosphatase enzymes remained unchanged after Ramadan. Fasting did bring in some changes in body composition; among both men and women, mean weight loss ranged from 0.81 - 1.4 kg in majority of the subjects, which was due to loss in muscle mass. Moderate changes in intra- and extracellular water content was observed after fasting. Conclusions: Significant improvements were observed in HDL levels and liver function tests, which can be attributed to the loss of body weight. Improvement in liver function tests may be related to the changes in cytokines and alteration in sleep patterns. Ramadan-like fasting, along with the nutritional education prior to fasting, may be beneficial and effective in the spiritual and overall well-being.


1977 ◽  
Vol 5 (1) ◽  
pp. 53-60
Author(s):  
F Franchi ◽  
M Luisi

Six women with normal menstrual cycles were treated over six cycles with Fysioquens, a normophasic contraceptive consisting of 7 tablets of ethinyloestradiol (EE) 0·050 mg and 15 tablets containing 1·0 mg lynestrenol +0·050 mg EE. In the 1st, 3rd and 6th treatment cycles and in the cycles before and after treatment, hormonal assays and other tests were carried out to determine whether ovulation had occurred. No treatment cycles showed any signs of ovulation, but it did occur in the pre- and post-treatment cycles. Blood pressures and liver function tests remained normal, but two of the six volunteers showed a slight increase in body-weight.


Author(s):  
Andreas Kortgen ◽  
Michael Bauer

The liver with its parenchymal and non-parenchymal cells plays a key role in the organism with manifold functions of metabolism, synthesis, detoxification, excretion, and host response. This requires a portfolio of different tests to obtain an overview of hepatic function. In the critically ill hepatic dysfunction is common and potentially leading to extrahepatic organ dysfunctions culminating in multi-organ failure. Conventional laboratory measures are used to evaluate hepatocellular damage, cholestasis, or synthesis. They provide valuable (differential) diagnostic data and can yield prognostic information in chronic liver diseases, especially when used in scoring systems such as the ‘model for end-stage liver disease’. However, they have short-comings in the critically ill in assessing rapid changes in hepatic function and liver blood flow. In contrast, dynamic quantitative liver function tests measure current liver function with respect to the ability to eliminate and/or metabolize a specific substance. In addition, they are dependent on sinusoidal blood flow. Liver function tests have prognostic significance in the critically ill and may be used to guide therapy.


2019 ◽  
Vol 6 (4) ◽  
pp. 1194
Author(s):  
Fazle Rab Malik ◽  
Ankur Dutt Tripathi ◽  
Santosh Kumar Singh ◽  
Anish Kola ◽  
Devendra Kumar Shukla

Background: It has been shown that there is a transient elevation of serum liver enzymes after laparoscopic surgeries and major causative factor seemed to be the CO2 pneumoperitoneum. In most of the cases, it does not have any clinical significance in the patient with normal preoperative liver function. However, in patients with deranged liver function, these changes can have great significance.Methods: The present study was designed to determine and compare changes in liver function tests and renal function test following laparoscopic cholecystectomy and open cholecystectomy. This study was conducted on 100 patients admitted to Swaroop Rani Nehru Hospital, Allahabad, India from August 2017 to January 2019 who were having symptomatic cholelithiasis with a history of either acute cholecystitis, biliary colic or chronic cholecystitis. All patients were investigated for complete liver function tests and renal function test including serum bilirubin, SGOT, SGPT, alkaline phosphatase, LDH, S. urea, S. creatinine, S. Na+, S. K+, S. Ca+ and urinary sodium (UNa+). The laboratory tests were carried out in the same laboratory using one type of instrument.Results: In open cholecystectomy, bilirubin decreased by 11% (p value equals 0.191) and remained decreased to the preoperative value on day 1 and day 7. While, laparoscopic cholecystectomy at 14 mmHg pressure, mean bilirubin decreases by 14% immediately postoperatively (p value equals 0.1733) and returns to normal level in 7 days. These changes are clinically insignificant and statistically insignificant.Conclusions: Enzyme elevations could mostly be attributed to the adverse effects of the pneumoperitoneum on the hepatic blood flow and renal blood flow and CO2 absorption in the blood. Though, these changes do not seem to be clinically significant, care should be taken before deciding to perform laparoscopic cholecystectomy. This study suggested that laparoscopic cholecystectomy is a safe operative procedure and have added advantages. The disturbances in the function of the kidney after laparoscopic cholecystectomy are self-limited and not associated with any morbidity in patients with a healthy kidney function.


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