Assessing Non-Invasive Liver Function in Patients With Intestinal Failure Receiving Total Parenteral Nutrition-Results From the Prospective PNLiver Trial

Liver abnormalities in intestinal failure (IF) patients receiving parenteral nutrition (PN) can progress undetected by standard laboratory tests to intestinal failure associated liver disease (IFALD). The aim of this longitudinal study is to evaluate the ability of non-invasive liver function tests to assess liver function following the initiation of PN. Twenty adult patients with IF were prospectively included at PN initiation and received scheduled follow-up assessments after 6, 12, and 24 months between 2014 and 2019. Each visit included liver assessment (LiMAx [Liver Maximum Capacity] test, ICG [indocyanine green] test, FibroScan), laboratory tests (standard laboratory test, NAFLD [non-alcoholic fatty liver disease] score, FIB-4 [fibrosis-4] score), nutritional status (bioelectrical impedance analysis, indirect calorimetry), and quality of life assessment. The patients were categorized post-hoc based on their continuous need for PN into a reduced parenteral nutrition (RPN) group and a stable parenteral nutrition (SPN) group. While the SPN group (n = 9) had significantly shorter small bowel length and poorer nutritional status at baseline compared to the RPN group (n = 11), no difference in liver function was observed between the distinct groups. Over time, liver function determined by LiMAx did continuously decrease from baseline to 24 months in the SPN group but remained stable in the RPN group. This decrease in liver function assessed with LiMAx in the SPN group preceded deterioration of all other investigated liver function tests during the study period. Our results suggest that the liver function over time is primarily determined by the degree of intestinal failure. Furthermore, the LiMAx test appeared more sensitive in detecting early changes in liver function in comparison to other liver function tests

Renal and Hepatic Dysfunction in Malaria Patients in Minna, North Central Nigeria

Information on kidney and liver involvement in malaria in Africa is still very scanty. Kidney and liver functions were assessed in 70 malaria patients using serum levels of creatinine and urea and urinary protein levels as test indicators of kidney function and serum levels of bilirubin, aspartate aminotranferase (AST or SGOT), alanine aminotransferase (ALT or SGPT), and alkaline phosphatase (ALP) as indicators of liver function. Descriptive analysis of results obtained showed that 67.14% of patients had creatinine level above the 126µmole/L which is considered the upper limit of the normal range. Three cases (4.29%) had creatinine levels well above 265µmoles/L. The serum concentrations of creatinine, urea, protein, conjugated and total bilirubin, AST, ALT, and ALP in malaria patients were significantly higher (p<0.05) than those of malaria free individuals. We conclude that renal dysfunction, acute renal failure and liver dysfunction are clinical features of malaria in Minna, North Central Nigeri

Are liver function tests required for patients taking isoniazid for latent TB?

Routine liver function test monitoring is not required for all patients on isoniazid therapy for latent tuberculosis (TB) infection (strength of recommendation: B, based on case series). No clinical trials have studied the potential risks and benefits of routinely monitoring liver function tests for all patients taking isoniazid for latent TB infection. Data from 2 case series suggest that routine liver function test monitoring leads to withdrawal of isoniazid prophylaxis from about 6% of patients because of abnormal lab results. This is 10 to 60 times the hepatitis rate found in case series using a symptom-based monitoring strategy. Data are insufficient, however, to conclude that routine liver function test monitoring leads to a lower rate of fatal isoniazid hepatitis compared with a strategy of symptom-based screening. Given that complete recovery from nonfatal hepatitis is the rule, and that patients withdrawn from isoniazid prophylaxis remain at risk for developing active tuberculosis, current evidence does not support routine liver function test monitoring for all patients

Development of a decision support tool to facilitate primary care management of patients with abnormal liver function tests without clinically apparent liver disease [HTA03/38/02]. Abnormal Liver Function Investigations Evaluation (ALFIE)

Liver function tests (LFTs) are routinely performed in primary care, and are often the gateway to further invasive and/or expensive investigations. Little is known of the consequences in people with an initial abnormal liver function (ALF) test in primary care and with no obvious liver disease. Further investigations may be dangerous for the patient and expensive for Health Services. The aims of this study are to determine the natural history of abnormalities in LFTs before overt liver disease presents in the population and identify those who require minimal further investigations with the potential for reduction in NHS costs

The effect of low volume sprint interval training in patients with non-alcoholic fatty liver disease

Objectives: Exercise is an important part of disease management in patients with non-alcoholic fatty liver disease (NAFLD), but adherence to current exercise recommendations is poor. Novel low-volume sprint interval training (SIT) protocols with total training time commitments of ≤30 min per week have been shown to improve cardiometabolic risk and functional capacity in healthy sedentary participants, but the efficacy of such protocols in the management of NAFLD remains unknown. The aim of the present study was to examine whether a low-volume SIT protocol can be used to improve liver function, insulin resistance, body composition, physical fitness, cognitive function and general well-being in patients with NAFLD.Methods: In the present study, 7 men and 2 women with NAFLD (age: 45±8 y, BMI: 28.7±4.1 kg·m−2) completed a 6-week control period followed by 6 weeks of twice-weekly SIT sessions (5-10×6-s ‘all-out’ cycle sprints). Body composition, blood pressure, liver function, metabolic function, functional capacity, cognitive function and quality of life were assessed at baseline, following the control period, and following the SIT intervention.Results: Walking speed during the walk test (+12%), estimated V̇O2max (+8%), verbal fluency (+44%), and blood platelet count (+12%; all p&lt;0.05) significantly increased during the control period. These measures remained significantly raised compared to baseline following the SIT intervention, but did not significantly change any further compared to the post-control time-point. Diastolic blood pressure decreased from 87±10 to 77±8 mm Hg from the end of the control period to the end of the SIT intervention (p&lt;0.05).Conclusion: This study does not support the use of 6 weeks of a low volume SIT protocol involving twice-weekly sessions with 5-10×6-s ‘all-out’ cycle sprints as an intervention for NAFLD disease management

The Role of Insulin Resistance in Diabetic Patients with Chronic Liver Disease

Background: The association between diabetes and chronic liver disease has been well documented. However, the mechanism remains unknown. The aim of this study was to investigate the insulin resistance in chronic liver disease and normal liver in diabetic patient. Method: A total of 31 diabetic, non-alcoholic patients with multiple oral hypoglycemic drugs, either with or without lipid abnormalities were enrolled in this study. Subjects were recruited from outpatient clinic of Department of Endocrine at Dr. Sardjito Hospital, Jogjakarta, Indonesia from May-June 2004. This was a cross sectional study. Fasting insulin and glucose level, liver function test, body mass index, and the presence of fatty liver by ultrasound were examined. Insulin resistance was estimated by calculating fasting insulin and glucose plasma level as the homeostasis model assessment (HOMA) index ratio. Data was described with mean ± SD and analyzed by independent sample t-test. Results: Thirty one patients were enrolled to the study, i.e. 8 patients with normal liver and 23 patients with fatty liver. Only 14 patients agreed to continue the study including 10 patients with fatty liver and 4 patients with normal liver. Mean of age was 59.1 ± 8.7 and mean value of BMI was 24.62 ± 3.05. The liver function test revealed normal Results. Triglyceride, cholesterol, fasting glucose level, and HOMA index (2.77 ± 1.95 vs. 1.66 ± 1.02) in patients with fatty liver were higher than patients with normal liver. No correlation was found between fasting insulin level as well as HOMA index and mean value of BMI (obese and non-obese) as well as hypertension. There was significant correlation between triglyceride level and fasting insulin among fatty liver patients (p = 0.048; CI 95% -7.404; -0.032). Conclusion: The non-alcoholic fatty liver disease in diabetic patients with normal liver enzymes and multiple oral hypoglycemic drugs appear to be related with insulin resistance and hypertriglyceridemia

Abnormal liver function tests as predictors of adverse maternal outcomes in women with preeclampsia.

OBJECTIVES: To evaluate whether (1) the absolute magnitude of liver function test values, (2) the percentage change in liver function test values over time, or (3) the rate of change in liver function test values over time predicts adverse maternal outcomes in women with preeclampsia. METHODS: We used data from the PIERS (Pre-eclampsia Integrated Estimate of RiSk) study, a prospective multicentre cohort study assessing predictors of adverse maternal outcomes in women with preeclampsia. Women with at least one liver function test performed at the time of hospital admission were included. Liver functions were tested by serum concentrations of aspartate amino transferase (AST), alanine amino transferase (ALT), lactate dehydrogenase (LDH), albumin, total bilirubin, and the international normalized prothrombin time ratio. Parameters investigated were absolute levels, change within 48 hours of hospital admission, change from admission to delivery or outcome, and rate of change from admission to delivery or outcome of each liver function test. The ability of these parameters to predict adverse outcomes was assessed using logistic regression analyses and by calculating the receiver operating characteristic (ROC) area under the curve (AUC). RESULTS: Of the 2008 women, 1056 (53%) had at least one abnormal liver function test result. The odds of having an adverse maternal outcome were higher in women with any abnormal liver function test than in women with normal results. When test results were stratified into quartiles, women with results in the highest quartile (lowest quartile for albumin) were at higher risk of adverse outcomes than women in the lowest quartile for all parameters (highest for albumin). The absolute magnitude of AST, ALT, and LDH predicted adverse maternal outcomes (AST: ROC AUC 0.73 [95% CI 0.67 to 0.97]; ALT: ROC AUC 0.73 [95% CI 0.67 to 0.79]; LDH: ROC AUC 0.74 [95% CI 0.68 to 0.81]). Neither change of liver function test results, within 48 hours of admission or from admission to delivery or outcome, nor rate of change were predictive. CONCLUSION: We found abnormal liver function test results to be associated with an increased risk for adverse maternal outcomes. Levels of AST, ALT, and LDH were found to be modestly predictive of these outcomes

Indocyanine green elimination test in orthotopic liver recipients.

OBJECTIVE: To determine its predictive capability on graft quality and resultant clinical outcome, the indocyanine green (ICG) elimination test was performed by a spectrophotometric method and a noninvasive finger-piece method with 50 orthotopic liver transplantations. BACKGROUND: Early detection of poor-functioning hepatic grafts is one of the most important issues in liver transplantation, but no reliable methods exist. METHODS: The ICG test was performed after 50 orthotopic liver transplantations on postoperative days 1, 3, and 7. Indocyanine green elimination constants (K(ICG)) were measured by both a standard spectrophotometric analysis (K(ICG)-B) and by a finger-piece method (K(ICG)-F). The patients were followed for a minimum of 3 months after transplantation. Results of ICG tests were correlated with various clinical determinations. RESULTS: Twelve of the 50 grafts were lost within three months, of which 7 were related to graft failure. Multivariate analysis using the Cox proportional hazard model revealed that K(ICG) on postoperative day 1 was a better predictor of liver-related graft outcome than any of the conventional liver function tests. Furthermore, K(ICG) values showed significant correlation with the severity of preservation injury, longer intensive care unit (ICU) and hospital stay, prolonged liver dysfunction, and septic complications. Correlation of K(ICG) values by the spectrophotometric method with those by the finger-piece method was highly satisfactory in the grafts that had K(ICG)-B <0.15 min-1 (y = 0.868x -0.011, r = .955). CONCLUSION: The ICG elimination test, conducted spectrophotometrically or optically on the day after liver transplantation, is a reliable indicator of graft quality and subsequent graft outcome early after liver transplantation

Relationship Between Serum Zinc Concentration and Neutrophil Phagocytic Function in Liver Cirrhosis Patients

Background: Liver cirrhosis patients are susceptible to infection. The incidence of infections depends on several factors. One of the factors is decreasing immune system i.e. the deterioration of neutrophil phagocytic function. The deterioration of neutrophil phagocytic function is caused by complement deficiency, bowel endotoxemia, decreasing tuftsin activity, and zinc deficiency. Zinc deficiency is caused by impairment of bowel absorption and increasing zinc excretion by urine. Zinc influences the specific and non specific immune system. Aim: To determine whether there is relationship between serum zinc concentration with neutrophil phagocytic function in liver cirrhosis patients. Subject &amp; Method: This was a cross-sectional study from August 2004 until September 2005. Study population are ambulatory liver cirrhosis patients and in patient liver cirrhosis. Correlation analysis was done to asses relationship between zinc concentration and neutrophil phagocytic function, which used Nitro Blue Tetrazolium (NBT) dye reduction test. Result: There were 58 subjects fulfilled the criteria. The mean of serum zinc concentration was 114 mmol/L. The mean of NBT was 3.4 ± 3.1%. The coefficient correlation between zinc serum concentration and neutrophil phagocytic function was 0.13, p= 0.58. Conclusion: There was a weak and non significant positive correlation between serum zinc concentration with neutrophil phagocytic function in liver cirrhosis patients

Flexible combination of multiple diagnostic biomarkers to improve diagnostic accuracy

In medical research, it is common to collect information of multiple continuous biomarkers to improve the accuracy of diagnostic tests. Combining the measurements of these biomarkers into one single score is a popular practice to integrate the collected information, where the accuracy of the resultant diagnostic test is usually improved. To measure the accuracy of a diagnostic test, the Youden index has been widely used in literature. Various parametric and nonparametric methods have been proposed to linearly combine biomarkers so that the corresponding Youden index can be optimized. Yet there seems to be little justification of enforcing such a linear combination. This paper proposes a flexible approach that allows both linear and nonlinear combinations of biomarkers. The proposed approach formulates the problem in a large margin classification framework, where the combination function is embedded in a flexible reproducing kernel Hilbert space. Advantages of the proposed approach are demonstrated in a variety of simulated experiments as well as a real application to a liver disorder study