A pilot study for the prediction of liver function related scores using breath biomarkers and machine learning.

Volatile organic compounds (VOCs) present in exhaled breath can help in analysing biochemical processes in the human body. Liver diseases can be traced using VOCs as biomarkers for physiological and pathophysiological conditions. In this work, we propose non-invasive and quick breath monitoring approach for early detection and progress monitoring of liver diseases using Isoprene, Limonene, and Dimethyl sulphide (DMS) as potential biomarkers. A pilot study is performed to design a dataset that includes the biomarkers concentration analysed from the breath sample before and after study subjects performed an exercise. A machine learning approach is applied for the prediction of scores for liver function diagnosis. Four regression methods are performed to predict the clinical scores using breath biomarkers data as features set by the machine learning techniques. A significant difference was observed for isoprene concentration (p < 0.01) and for DMS concentration (p < 0.0001) between liver patients and healthy subject's breath sample. The R-square value between actual clinical score and predicted clinical score is found to be 0.78, 0.82, and 0.85 for CTP score, APRI score, and MELD score, respectively. Our results have shown a promising result with significant different breath profiles between liver patients and healthy volunteers. The use of machine learning for the prediction of scores is found very promising for use of breath biomarkers for liver function diagnosis.

Association between liver stiffness measurement by transient elastography and chronic kidney disease.

ABSTRACT: Transient elastography or elastometry (TE) is widely used for clinically cirrhosis and liver steatosis examination. Liver fibrosis and fatty liver had been known to share some co-morbidities that may result in chronic impairment in renal function. We conducted a study to analyze the association between scores of 2 TE parameters, liver stiffness measurement (LSM) and controlled attenuation parameter (CAP), with chronic kidney disease among health checkup population.This was a retrospective, cross-sectional study. Our study explored the data of the health checkup population between January 2009 and the end of June 2018 in a regional hospital. All patients were aged more than 18 year-old. Data from a total of 1940 persons were examined in the present study. The estimated glomerular filtration rate (eGFR) was calculated by the modification of diet in renal disease (MDRD-simplify-GFR) equation. Chronic kidney disease (CKD) was defined as eGFR < 60 mL/min/1.73 m2.The median of CAP and LSM score was 242, 265.5, and 4.3, 4.95 in non-CKD (eGFR > 60) and CKD (eGFR < 60) group, respectively. In stepwise regression model, we adjust for LSM, CAP, inflammatory markers, serum biochemistry markers of liver function, and metabolic risks factors. The P value of LSM score, ALT, AST, respectively is .005, <.001, and <.001 in this model.The LSM score is an independent factor that could be used to predict renal function impairment according to its correlation with eGFR. This result can further infer that hepatic fibrosis may be a risk factor for CKD.

Responsiveness on metabolic syndrome criteria and hepatic parameters after 12 weeks and 24 weeks of multidisciplinary intervention in overweight adolescents.

PURPOSE: This study aimed to evaluate the effect and individual responsiveness after 12 (12wk) and 24 weeks (24wk) of physical exercise (PE) and nutritional guidance (NG) on metabolic syndrome (MetS) criteria and hepatic parameters in overweight adolescents. METHODS: The study comprised 94 overweight adolescents, aged between 10 and 16 years old, from both sexes, allocated into groups: PE and NG (PENGG, n = 64) and control with NG (NGCG, n = 30). Variables were collected at baseline, 12wk, and 24wk. Weight, height, abdominal circumference (AC), blood pressure, and peak oxygen consumption (VO2peak), as well as insulin, triglycerides (TAG), high-density lipoprotein (HDL-c), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were evaluated. HOMA-IR and QUICKI were calculated. PE session consisted of 45 min of indoor cycling, 45 min of walking, and 20 min of stretching, three times a week. The NG consisted of three collective sessions in the first 12wk. Anova, effect size, and prevalence of responders were used for statistical analysis. RESULTS: The PENGG12wk reduced anthropometric and metabolic measurements, while increased VO2peak and HDL-c. The PEG24wk promoted anthropometric, blood pressure, metabolic, and VO2peak improvements, but participants without PE returned to pre-exercise status and presented worsening AST and ALT concentrations. Frequencies of respondents in PENGG12wk versus (vs) NGCG12wk were, respectively, AC (69.1% vs 17.6%, p < 0.01), HDL-c (87.2% vs 23.5%, p < 0.01), TAG (67.3% vs 41.7%, p = 0.05) and ALT (45.5% vs 5,9%; p = 0.003). CONCLUSION: Interventions with PE were effective to reduce MetS components in 12wk and maintenance in 24wk, showing anthropometric, metabolic, and VO2peak improvements. Higher individual responses were observed in 12wk and in 24wk, important changes in overweight adolescent's therapy. LEVEL OF EVIDENCE: Level I, evidence obtained from well-designed controlled trials randomization. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: Brazilian Registry of Clinical Trials (RBR-4v6h7b) and date of registration April 4th, 2020.

Effect of corticosteroid dosing on outcomes in high-grade immune checkpoint inhibitor hepatitis.

BACKGROUND AND AIMS: Consensus guidelines recommend high-dose corticosteroids (1-2 mg/kg/day methylprednisolone equivalents) for treating grade ≥3 immune checkpoint inhibitor (ICI) hepatitis. We examined the effect of corticosteroid dosing on time to alanine aminotransferase (ALT) normalization, need for additional immunosuppression, and steroid-related complications. APPROACH AND RESULTS: We conducted a retrospective cohort study of 215 ICI-treated patients from 2010 to 2020 who developed grade ≥3 (ALT > 200 U/L) ICI hepatitis. Patients were grouped by initial corticosteroid dose (≥1.5 mg/kg or <1.5 mg/kg methylprednisolone equivalents). Propensity scores were calculated predicting the risk of receiving the higher steroid dose and used in inverse probability of treatment weighted (IPTW) logistic or Cox regression. The 87 patients in the ≥1.5 mg/kg group received higher initial (2.0 vs. 0.8 mg/kg/day, p < 0.001) and maximum (2.0 vs. 1.0 mg/kg/day, p < 0.001) steroid doses than the 128 patients in the <1.5 mg/kg group. There was no difference between the higher versus lower-dose groups in development of steroid-refractory hepatitis (OR 1.22, 95% CI 0.79-1.89, p = 0.365) on IPTW-logistic regression. In patients with steroid-responsive disease, there was no difference between the two groups in time to ALT normalization using either standard Cox regression (HR 1.02, 95% CI 0.72-1.45, p = 0.903) or IPTW-Cox regression (HR 1.09, 95% CI 0.78-1.51, p = 0.610). The ≥1.5 mg/kg group had longer exposure to corticosteroids (median 60 vs. 44 days, p = 0.005) and higher incidences of infection (18.4% vs. 7.0%, relative risk [RR] 2.6, 95% CI 1.2-5.6, p = 0.011) and hyperglycemia requiring treatment (23.3% vs. 7.8%, RR 3.0, 95% CI 1.5-6.0, p = 0.001). CONCLUSIONS: In patients with high-grade ICI hepatitis, initial treatment with 1 mg/kg/day methylprednisolone equivalents provides similar hepatitis outcomes with reduced risk of steroid-related complications when compared with higher-dose regimens.

Long-term sequelae of drug-induced liver injury.

Drug-induced liver injury (DILI) has a very variable clinical and biochemical phenotype and differs widely in severity, from mild injury to life-threatening liver failure. Chronic injury has also been reported to occur at a variable frequency, ranging from 3.4% to 39%, 6-12 months after discontinuing the implicated agent. This wide range is probably related to various definitions of chronic liver injury and variable selection of patients. The long-term sequalae of this chronic injury in terms of morbidity and mortality are unclear, although rare vanishing bile duct syndrome is associated with an unfavourable prognosis, with increased risk of chronic liver failure and need for liver transplantation. Other forms of long-term sequalae associated with DILI are progressive fibrosis, autoimmune-like hepatitis, secondary sclerosing cholangitis, sinusoidal obstruction syndrome and, as a common final stage, the development of cirrhosis, portal hypertension and its complications. Immune checkpoint inhibitors, which can cause an autoimmune-like phenotype have also recently been shown to cause sclerosing cholangitis with cytotoxic T CD8+ cell infiltration in biliary tracts. DILI has been shown to have a significant impact on health-related quality of life but very little is known about its psychological consequences in the long-term. Further investigations with structured long-term follow-up and periodic quality of life surveys are needed to assess the impact of DILI on psychological outcomes, particularly in those with chronic sequelae.

Hallmarks of the human intestinal microbiome on liver maturation and function.

As one of the most metabolically complex systems in the body, the liver ensures multi-organ homeostasis and ultimately sustains life. Nevertheless, during early postnatal development, the liver is highly immature and takes about 2 years to acquire and develop almost all of its functions. Different events occurring at the environmental and cellular levels are thought to mediate hepatic maturation and function postnatally. The crosstalk between the liver, the gut and its microbiome has been well appreciated in the context of liver disease, but recent evidence suggests that the latter could also be critical for hepatic function under physiological conditions. The gut-liver crosstalk is thought to be mediated by a rich repertoire of microbial metabolites that can participate in a myriad of biological processes in hepatic sinusoids, from energy metabolism to tissue regeneration. Studies on germ-free animals have revealed the gut microbiome as a critical contributor in early hepatic programming, and this influence extends throughout life, mediating liver function and body homeostasis. In this seminar, we describe the microbial molecules that have a known effect on the liver and discuss how the gut microbiome and the liver evolve throughout life. We also provide insights on current and future strategies to target the gut microbiome in the context of hepatology research.

Non-invasive evaluation of response to obeticholic acid in patients with NASH: Results from the REGENERATE study.

BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is a chronic, progressive fibrotic liver disease that can lead to cirrhosis. While liver biopsy is considered the reference standard for the histologic diagnosis of NASH and staging of fibrosis, its use in clinical practice is limited. Non-invasive tests (NITs) are increasingly being used to identify and stage liver fibrosis in patients with NASH, and several can assess liver-related outcomes. We report changes in various NITs in patients treated with obeticholic acid (OCA) or placebo in the phase III REGENERATE study. METHODS: Patients with NASH and fibrosis stage F2 or F3 (n = 931) were randomized (1:1:1) to receive placebo, OCA 10 mg, or OCA 25 mg once daily. Various NITs based on clinical chemistry and/or imaging were evaluated at baseline and throughout the study. RESULTS: Rapid, sustained reductions from baseline in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase levels, as well as in Fibrosis-4 (FIB-4), FibroTest, FibroMeter, and FibroScan-AST scores were observed in OCA-treated vs. placebo-treated patients. Reduction in liver stiffness by vibration-controlled transient elastography was observed in the OCA 25 mg group vs. the placebo group at Month 18. NIT changes were associated with shifts in histologic fibrosis stage. The greatest improvements were observed in patients with ≥1-stage fibrosis improvement; however, improvements in ALT, AST, FIB-4, and FibroTest were also observed in OCA-treated patients whose histologic fibrosis remained stable. CONCLUSIONS: Based on the REGENERATE Month 18 interim analysis, rapid and sustained improvements in various NITs were observed with OCA treatment. Dynamic changes in selected NITs separated histologic responders from non-responders. These results suggest that NITs may be useful in assessing histologic response to OCA therapy. CLINICALTRIALS. GOV NUMBER: NCT02548351 LAY SUMMARY: Non-alcoholic steatohepatitis (NASH) is a chronic, progressive liver disease that can lead to cirrhosis. To diagnose and assess liver fibrosis (scarring) in patients with NASH, non-invasive tests (NITs) are increasingly being used rather than liver biopsy, which is invasive, expensive, and can be risky. In the REGENERATE study, which is evaluating the effects of obeticholic acid vs. placebo in patients with NASH, various NITs were also evaluated. This analysis shows that improvements in levels of certain blood components, as well as favorable results of ultrasound imaging and proprietary tests of liver function, were associated with improvements in liver fibrosis after treatment with obeticholic acid, suggesting that NITs may be useful alternatives to liver biopsy in assessing NASH patients' response to therapy.

AL Lambda Amyloidosis Activates Acute Liver Failure in the Absence of Plasma Cell Dyscrasia.

A patient with systemic amyloidosis developed portal hypertension, acute liver failure and multiorgan dysfunction. Extensive testing was unrevealing for paraproteinemia, plasma cell dyscrasia, infectious, or inflammatory conditions. He was transferred to our institution for orthotopic liver transplant evaluation but was ultimately declined given clinical instability and dysautonomia. Post-mortem evaluation revealed extensive amyloid deposition in multiple organs determined to be AL-lambda amyloidosis.

Safety and effectiveness of up to 3 years' bulevirtide monotherapy in patients with HDV-related cirrhosis.

The entry inhibitor bulevirtide (BLV) received conditional approval from the EMA in July 2020 for the treatment of adult patients with compensated chronic hepatitis delta. However, the effectiveness and safety of BLV administered as monotherapy beyond 48 weeks in difficult-to-treat patients with HDV-related cirrhosis is presently unknown. Herein, we describe the first patients with HDV-related compensated cirrhosis who were treated with BLV (10 mg/day as a starting dose) for up to 3 years on a compassionate use program. Patients were also monitored for HBcrAg and HBV RNA levels, and HDV- and HBV-specific T-cell markers. In the patient who stopped BLV at week 48, after achieving a virological and biochemical response, the initial virological and biochemical rebound was followed by alanine aminotransferase normalization coupled with low HDV RNA and HBsAg levels. In the 2 patients treated continuously for 3 years, virological and biochemical responses were maintained throughout the treatment period even after dose reduction. In a patient with advanced compensated cirrhosis, liver function tests significantly improved, esophageal varices disappeared, and histological/laboratory features of autoimmune hepatitis resolved. Overall, no safety issues were recorded, as bile salt increase was asymptomatic. While serum HBV RNA levels remained undetectable in all patients, HBV core-related antigen levels showed a progressive, yet modest decline during long-term BLV treatment. No HDV-specific interferon-γ-producing T cells were detected, neither after HDV reactivation (after BLV withdrawn in Patient 1) nor during 3 years of BLV treatment. In conclusion, this report shows that continuous administration of BLV monotherapy for 3 years leads to excellent virological and clinical responses in patients with HDV-related cirrhosis who had contraindications to interferon-based therapies.

A Prognostic Prediction Model of Transarterial Radioembolization in Hepatocellular Carcinoma: SNAP-HCC.

BACKGROUND: Prognosis prediction in patient with hepatocellular carcinoma (HCC) after transarterial radioembolization (TARE) remains difficult. The aim of this study was to develop a prognostic model to aid in the decision to use TARE. METHODS: A total of 174 patients in Korea who underwent TARE for HCC as the initial treatment were included. We developed a prediction model for overall survival (OS) based on independent risk factors for OS and validated the model by bootstrap method. RESULTS: The median maximal size of the tumors was 8.2 cm, the median number of tumors was 2, and the median albumin level was 4.0 g/dL. Portal vein tumor thrombosis was found in 46.0% (Vp1-3 [39.7%] and Vp4 [6.3%]). Four independent risk factors associated with OS (maximal tumor size, tumor number, albumin, and portal vein tumor thrombosis) were used to develop the SNAP-HCC score. Bootstrap validation of the scoring index determined that the Harrell's c-index for OS was 0.756 (95% confidence interval: 0.729-0.783). Patients grouped based on their SNAP-HCC (scores 0-5) were well discriminated, with significant differences between the groups (all P < 0.05). Patients with SNAP-HCC < 3 showed significantly longer OS than patients with SNAP-HCC ≥ 3 (P < 0.001). The respective survival probabilities at years 1 and 3 were 0.81 and 0.73 in the low-risk (SNAP-HCC < 3) and 0.32 and 0.14 in the high-risk (SNAP-HCC ≥ 3) patients. CONCLUSIONS: The SNAP-HCC scoring system predicted the outcome of HCC patients undergoing TARE as an initial treatment. This model could be helpful for initial planning the treatment of HCC patients.

Disease-Based Risk Stratification of Postendoscopic Retrograde Cholangiopancreatography Pancreatitis for Common Bile Duct Stones.

BACKGROUND: Risk stratification of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) for common bile duct (CBD) stones is needed for clinicians to adequately explain to patients regarding the risk of PEP in advance of ERCP and to proactively take preventive measures in high-risk patients. AIMS: To stratify the risk of PEP for CBD stones based on CBD-related diseases. METHODS: A total of 1551 patients with naïve papilla who underwent ERCP for CBD stones were divided into three groups: Group A: asymptomatic CBD stones, Group B: obstructive jaundice and elevated liver test values without cholangitis, and Group C: mild, moderate, and severe cholangitis. We stratified the risk of PEP by comparing its incidence among the three groups using the Holm's method. Furthermore, we performed one-to-one propensity score matching between Group A and the other groups to examine the risk of PEP in Group A. RESULTS: The incidence rates in Groups A, B, and C were 13.7%, 7.3%, and 1.8%, respectively. The Holm-adjusted p values between Groups A and B, Groups A and C, and Groups B and C were 0.023, < 0.001, and < 0.001, respectively. Propensity score matching revealed that the incidence of PEP was significantly more in Group A than in the other groups (13.3% vs. 1.5%; p < 0.001). CONCLUSIONS: The risk of PEP for CBD stones was stratified into low risk (Group C), intermediate risk (Group B), and high risk (Group A). This simple disease-based risk stratification may be useful to predict the risk of PEP in advance of ERCP.

Anti-HBc IgG Levels: A Predictor of HBsAg Seroclearance in Chronic Hepatitis B Patients with Nucleos(t)ide Analogue-Induced HBeAg Seroclearance.

BACKGROUND/AIMS: We investigated the efficiency of the indirect ratio of anti-HBc IgG at predicting HBsAg seroclearance in patients with nucleos(t)ide analogue (NA)-induced HBeAg seroclearance. METHODS: We performed a retrospective study that included 366 chronic hepatitis B patients (March 2007 to December 2016) at a single tertiary hospital. These patients were HBsAg seropositive, and experienced NA-induced HBeAg seroclearance. The indirect ratio of light absorbance of anti-HBc IgG levels were measured with chemiluminescent microparticle immunoassay using the Architect Anti-HBc assay (Abbott Laboratories, IL, USA) as a qualitative method prior to antiviral therapy. We calculated the cumulative incidences of HBsAg seroclearance based on the anti-HBc IgG levels. RESULTS: After a 10-year follow-up, 48 patients experienced HBsAg seroclearance (13.1%). Thirty-three of 179 patients who had an indirect ratio of light absorbance of anti-HBc IgG < 11 RLU (relative light unit) showed HBsAg seroclearance (18.4%); 15 of 187 patients who had an indirect ratio of light absorbance of anti-HBc IgG ≥ 11 RLU showed HBsAg seroclerance (8.0%) (p = 0.003). In multivariate analysis, age, and ALT at the time of HBeAg seroclearance were predictors of HBsAg seroclearance. Especially, the relative risk of HBsAg seroclearance in patients with baseline anti-HBc IgG levels < 11 RLU was 2.213 (95% CI, 1.220-4.014), compared to that in patients with higher levels of anti-HBc IgG at baseline (p = 0.009). CONCLUSION: Using an indirect method for anti-HBc IgG levels, baseline anti-HBc IgG levels (< 11RLU), age (≥ 50 years), and ALT (≥ 40 IU/L) might be associated with HBsAg seroclearance in patients with NA-induced HBeAg seroclearance.

The protective effects and mechanisms of modified Lvdou Gancao decoction on acute alcohol intoxication in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute alcohol intoxication (AAI) is a ubiquitous emergency worldwide, whereas the searching for both effective and safe drugs is still a task to be completed. Modified Lvdou Gancao decoction (MLG), a traditional Chinese medicine decoction, has been confirmed to be valid to alcohol-induced symptoms and hepatotoxicity clinically, whereas its protective mechanisms have not been determined. MATERIALS AND METHODS: AAI mice model was established by alcohol gavage (13.25 mL/kg) and MLG (5, 10, 20 g/kg BW) was administered to mice 2 h before and 30 min after the alcohol exposure. Assay kits for alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamine transferase (GGT), total superoxide dismutase (T-SOD), malondialdehyde (MDA), nitric oxide (NO), and glutathione peroxidase (GSH-Px), as well as histopathology were used to explore the effects of MLG on acute alcohol-induced intoxication and hepatotoxicity. Mechanisms of MLG on oxidative stress and inflammatory were evaluated with RT-qPCR and Western Blot. RESULTS: MLG remarkably decreased the drunkenness rate, prolonged the tolerance time and shortened the sober-up time of AAI mice. After acute alcohol exposure, MLG treatment induced significant increment of ADH, ALDH, T-SOD and GSH-Px activities in liver, while serum ALT, AST, GGT and NO levels as well as hepatic MDA activity were reduced, in a dose-dependent manner. In contrast to the model group, the mRNA expression of TNFα, IL-1ß and NF-κB in the MLG treated groups had a downward trend while the Nrf-2 showed an upward trend simultaneously. Furthermore, the protein levels of p65, p-p65, p-IκBα in the MLG treated groups were considerably diminished, with HO-1 and Nrf2 elevated. To sum up, our results suggested that MLG could efficaciously ameliorate AAI via accelerating the metabolism of alcohol, alleviating acute hepatotoxicity, and weakening the oxidative stress coupled with inflammation response, which might be attributed to the inhibition of the NF-κB signaling pathway and the activation of the Nrf2/HO-1 signaling pathway. CONCLUSIONS: Taken together, our present study verified the protective effect and mechanisms of MLG to AAI mice, and we further conclude that MLG may be a potent and reliable candidate for the prevention and treatment of AAI.

Abiraterone acetate versus nonsteroidal antiandrogen with androgen deprivation therapy for high-risk metastatic hormone-sensitive prostate cancer.

BACKGROUND: Although prostate cancer is a very common form of malignancy in men, the clinical significance of androgen deprivation therapy (ADT) with abiraterone acetate versus the nonsteroidal antiandrogen bicalutamide has not yet been verified in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). The present study was designed to initiate this verification in real-world Japanese clinical practice. METHODS: We retrospectively analyzed the records of 312 patients with high-risk mHSPC based on LATITUDE criteria and had received ADT with bicalutamide (n = 212) or abiraterone acetate (n = 100) between September 2015 and December 2020. Bicalutamide was given at 80 mg daily and abiraterone was given at 1000 mg daily as four 250-mg tablets plus prednisolone (5-10 mg daily). Overall survival (OS), cancer-specific survival (CSS), and time to castration-resistant prostate cancer (CRPC) were compared. The prognostic factor for time to CRPC was analyzed by Cox proportional hazard model. RESULTS: Patients in the bicalutamide group were older, and more of them had poor performance status (≧2), than in the abiraterone group. Impaired liver function was noted in 2% of the bicalutamide group and 16% of the abiraterone group (p < 0.001). Median follow-up was 22.5 months for bicalutamide and 17 months for abiraterone (p < 0.001). Two-year OS and CSS for bicalutamide versus abiraterone was 77.8% versus 79.5% (p = 0.793) and 81.1% versus 82.5% (p = 0.698), respectively. Median time to CRPC was significantly longer in the abiraterone group than in the bicalutamide group (NA vs. 13 months, p < 0.001). In multivariate analysis, Gleason score ≧9, high alkaline phosphatase, high lactate dehydrogenase, liver metastasis, and bicalutamide were independent prognostic risk factors for time to CRPC. Abiraterone prolonged the time to CRPC in patients with each of these prognostic factors. CONCLUSIONS: Despite limitations regarding the time-dependent bias, ADT with abiraterone acetate significantly prolonged the time to CRPC compared to bicalutamide in patients with high-risk mHSPC. However, further study with longer follow-up is needed.

Assessment of hepatic function, perfusion and parenchyma attenuation with indocyanine green, ultrasound and computed tomography in a healthy rat model: Preliminary determination of baseline parameters in a healthy liver.

BACKGROUND: Defining reference intervals in experimental animal models plays a crucial role in pre-clinical studies. The hepatic parameters in healthy animals provide useful information about type and extension of hepatic damage. However, in the majority of the cases, to obtain them require an invasive techniques. Our study combines these determinations with dynamic functional test and imaging techniques to implement a non-invasive protocol for liver evaluation. The aim of the study was to determine reference intervals for hepatic function, perfusion and parenchyma attenuation with analytical and biochemical blood parameters, indocyanine green, ultrasound and computed tomography in six healthy SD rats. METHODS: Six males healthy SD rats were followed for 4 weeks. To determine hepatic function, perfusion and parenchyma attenuation analytical and biochemical blood parameters, indocyanine green, ultrasound and computed tomography were studied. Results were expressed as Means ± standard error of mean (SEM). The significance of differences was calculated by using student t-test, p < 0.05 was considered statistically significant. RESULTS: Indocyanine green clearance 5 and 10 minutes after its injection was 80.12% and 96.59%, respectively. Approximate rate of decay during the first 5 minutes after injection was 38% per minute. Hepatic perfusion evaluation with the high-frequency ultrasound was related to cardiovascular hemodynamic and renal perfusion. Portal area, hepatic artery resistance index, hepatic artery and portal peak systolic velocity and average between hepatic artery and porta was 3.41 ± 0.62 mm2, 0.57 ± 0.04 mm2/s, 693.24±102.53 mm2/s, 150.72 ± 17.80 mm2/s and 4.82 ± 0.96 mm2/s, respectively. Heart rate, cardiac output, left renal artery diammetre and renal blood flow were 331.01 ± 22.22 bpm, 75.58 ± 8.72 mL/min, 0.88 ± 0.04 mm2 and 13.65 ± 1.95 mm2/s. CT-scan hepatic average volume for each rat were 21.08±3.32, 17.57±2.76, 14.87±2.83 and 13.67±2.45 cm3 with an average attenuation coefficient of 113.51±18.08, 129,19±7.18, 141,47±1.95 y 151,67±1.2 HU. CONCLUSION: Indocyanine green and high-frequency ultrasound could be used in rats as a suitable marker of liver function. Computed tomography, through the study of raw data, help to characterize liver parenchyma, and could be a potential tool for early detection of liver parenchymal alterations and linear follow-up of patients. Further studies in rats with liver disease are necessary to verify the usefulness of these parameters.

Use of bile acids as potential markers of liver dysfunction in humans: A systematic review.

OBJECTIVE: This study aimed to determine the effectiveness of using total, individual serum, or urinary bile acids (BA) as potential markers of liver dysfunction. METHODS: We searched the PubMed and Web of Science databases using the following keywords- "serum bile acids," "liver dysfunction," "liver injury," "liver disease," "traditional liver function tests," "Chronic liver disease," "acute liver injury". The search was complemented by manual screening of the list of references for relevant articles. We selected only English-language manuscripts for adult patients based on predetermined inclusion and exclusion criteria. Animal studies and studies on neonates and children were not included. OUTCOME MEASURES: Changes in BA concentrations or ratios at or prior to changes in liver function tests. RESULTS: A total of 547 studies were identified, of which 28 were included after reading the entire manuscript. These studies included 1630 patients and 836 controls published between 1990 and 2017. The methods used in BA assays varied significantly, and the studies did not agree. on specific individual BA or BA ratios as biomarkers of specific liver injury or dysfunction. Except for the prognostic value of BA in intrahepatic cholestasis of pregnancy (ICP), studies have failed to provide evidence for BA as a liver biomarker. CONCLUSIONS: Despite the research conducted on BA for over 27 years, there are inconsistencies in the reported results and a lack of solid evidence to support the use of individual BA or BA ratios as biomarkers of liver injury. Adequately conducted studies needed to resolve this limitation in the literature.

Assessment of liver function test and associated factors among visceral leishmaniasis patients attending university of gondar leishmaniasis research and treatment center, Northwest Ethiopia.

BACKGROUND: Visceral leishmaniasis (VL) is one of the major public health burden, mainly distributed throughout tropical and subtropical regions of the world. Among the Sub-Saharan African countries, Ethiopia is the second most affected country with VL. An Alteration of liver function is a typical manifestation of the disease. OBJECTIVE: The purpose of conducting this study was to assess liver function tests and associated risk factors among VL patients at Leishmaniasis Research and Treatment Center of University of Gondar Comprehensive Specialized Hospital, North West Ethiopia. METHOD: Hospital based comparative cross-sectional study design was conducted. A total of 102 study participants were involved in this study. Newly diagnosed VL patients who were attended at Leishmaniasis Research and Treatment Center of University of Gondar Comprehensive Specialized Hospital from 21st February 2020 to 30th September 2020 were included under case group category. On the other hand, age-sex matched apparently healthy study subjects were categorized as control group. Written consent was obtained willingness of patients to participate after ethical clearance was obtained from the Institutional Review Board of School of Medicine, University of Gondar. After overnight fasting, 5ml venous blood was drawn from both VL patients and controls to evaluate liver function tests, including AST, ALT, total bilirubin, albumin, and total protein. Thus, senior health professionals (laboratory technologist) investigate the results using Cobas Integra 400 Plus clinical chemistry analyzer. Data was entered into Epi-data version 4.6 and exported to STATA 14 for analysis of liver function tests and associated risk factors. RESULT: The result of this study showed that significant mean difference was exhibited in aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, serum albumin, and total protein level among VL patients and controls. It showed that there was a statistically significant elevation in the level of AST, ALT, and total bilirubin among cases as compared to control. The serum AST level was significantly (p<0.001) elevated among cases as compared to controls. Serum ALT was significantly (p<0.001) elevated among cases compared to controls. Additionally, the total serum bilirubin level was significantly increased (P<0.001) among cases as compared to controls. There was a statistically significant (P<0.001) reduction of serum albumin level among VL patients as compared to controls. Similarly, serum total protein was significantly (P<0.001) reduced in VL patients than control groups. CONCLUSION: There were significantly higher mean levels of serum AST, ALT, and total bilirubin among VL patients as compared to controls. On the other hand, VL patients showed significantly lowered level of albumin and total protein as compared to controls.