Liver Function Indices Research Articles

Establishment and validation of a population pharmacokinetic model for apatinib in patients with tumors

ObjectiveThis study aimed to develop a population pharmacokinetic (PPK) model for oral apatinib in Chinese oncology patients and investigate the factors influencing the pharmacokinetics of apatinib.MethodsWe gathered 199 blood concentration monitoring data points from 91 inpatient oncology participants receiving oral apatinib at the Third Affiliated Hospital of Soochow University. Covariates, such as age, gender, body weight, and indices of liver and renal function, were examined to assess their influence on the pharmacokinetic parameters of apatinib. The PPK model was developed using the nonlinear mixed-effects modeling procedure (NONMEM), and model validation was conducted using the bootstrap method and normalized prediction distribution error (NPDE) method.ResultsThe structural model adopted a one-compartment structure with first-order elimination. Notably, aspartate aminotransferase (AST) and the co-administered drug type emerged as primary covariates affecting apatinib clearance (CL/F). The finalized model was expressed as CL/F (L/h) = 56.7 × (AST/26.6)−0.298 × θ, when apatinib was combined with monoclonal antibodies, θ was 1; when combined with paclitaxel, θ was 0.58; when combined with other drugs (e.g., platinum, capecitabine, or the combination of tegafur, gimeracil, and oteracil potassium), θ was 1.60; When used as monotherapy, θ was 1.38. V/F = 674 L, and the absorption rate constant (Ka) was fixed at 0.08 h−1. Bootstrap results affirmed the model’s reliability and stability, while NPDE outcomes attested to the model’s fit.ConclusionOur study successfully established a PPK model for apatinib in oncology patients, revealing that liver function status and co-administered drug types significantly impacted apatinib CL/F. This finding underscored the potential necessity for dose adjustments to optimize efficacy, particularly in patients undergoing different chemotherapy regimens involving apatinib.

Effectiveness of Internet + E-Coach chronic disease management on blood glucose, lipid levels, liver function, and quality of life in patients with chronic diabetic retinopathy: a comparative study

ObjectiveThis study aims to explore the effect of Internet + E-Coach chronic disease system intervention on fasting blood glucose (FPG), 2-hour postprandial blood glucose(2hPG), fasting serum insulin (FINS), triglyceride (TG), alanine transaminase (ALT) and quality of life in patients with chronic diabetic retinopathy.Methods208 patients with chronic diabetic retinopathy who were treated in the hospital from March 2021 to March 2023 are chosen and separated into two groups by random number Table 104 patients in the control group received routine continuous intervention, and the research group received Internet + E-Coach chronic disease system intervention. The cognition of disease related knowledge, blood related indicators inflammatory factor levels and improvement of life quality between the two groups before intervention, 6 and 12 months after intervention were compared.ResultsBefore the intervention, the comparison between the two groups in disease related knowledge scores, blood glucose, blood lipid, liver function indicators, inflammatory factor, and low vision quality of life scale (CLVQOL) scores was with P > 0.05. After 6 and 12 months of intervention, the research group had significantly higher scores for basic blood glucose intervention, healthy diet, reasonable exercise, and correct medication use compared to the control group (P < 0.05). FPG, 2hPG, TG and ALT in the research group were lower than those in the control group. FINS were higher in the control group, with P < 0.05. Interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and hypersensitive C-reactive protein (Hs-CRP) in the research group were obviously lower than those in the control group (P < 0.05). The scores of far vision, movement and light perception, adjustment ability, reading and fine work, and daily living ability in the research group were higher than those in the control group, with P < 0.05.ConclusionThe intervention of Internet + E-Coach chronic disease system can improve the knowledge of chronic diabetic retinopathy patients about their own condition, stabilize the levels of blood sugar, blood lipid and liver function indicators, reduce the inflammatory reaction of the body, and improve the quality of life.

Ultrasound-guided percutaneous microwave ablation for metabolic-associated fatty liver disease-related hepatocellular carcinoma (HCC) versus hepatitis virus B-related HCC: a propensity score matching study

Objectives To compare the long-term outcomes of microwave ablation (MWA) for primary hepatocellular carcinoma (HCC) in patients with metabolic-associated fatty liver disease (MAFLD) with those infected by hepatitis virus B (HBV). Methods The clinical data of HCC patients under the treatment of MWA were analyzed retrospectively between 2010 and 2021 at Chinese PLA General Hospital. Patients were divided into MAFLD-HCC and HBV-HCC group according to the chronic liver disease etiology. The propensity score matching (PSM) was performed to reduce the interference of confounders. The primary outcomes were overall survival (OS), recurrence-free survival (RFS), cancer-specific survival (CSS) and intrahepatic distant recurrence (IDR). Results A total of 648 patients (age range, 18–91 years) with 1019 lesions were enrolled including 601 with HBV-HCC and 47 with MAFLD-HCC. After a variable ratio of 1:n ≤ 4 PSM, 100 patients were included in the HBV-HCC and 41 in the MAFLD-HCC group. No statistical differences in OS and CSS (p = 0.880 and p = 0.980, respectively) were observed between the two groups in the matched cohort, while MAFLD-HCC exhibited better RFS and lower IDR rates compared to HBV-HCC (p = 0.043 and p = 0.041, respectively). Additionally, MAFLD-HCC generated lower ascending range in the liver function indexes like ΔALT (46.7 vs. 98.5, p < 0.001), ΔTBIL (1.9 vs. 7.5, p = 0.001) and ΔAST (38.1 vs. 148.6, p < 0.001) than HBV-HCC after MWA. Conclusions MWA is an effective treatment for HCC patients with MAFLD. The recurrence prognosis of MAFLD-HCC was better than HBV-HCC and the degree of liver injury after MWA was lower.

Effect of clustered nursing on liver function indexes, nutrition, and emotional status of patients with severe liver failure.

Liver failure is a metabolic disorder caused by a variety of mixed factors. For such diseases, adopting cluster care can effectively improve the relevant symptoms of patients. To explore the nursing effect of nutritional nursing combined with clustered nursing for patients with severe liver failure. A total of 129 patients with severe liver failure were selected as retrospective study subjects. Nine cases were due to an end event, such as death. The other patients were divided into control group and observation group according to different nursing methods. Among them, the control group adopted nutrition nursing, and the observation group implemented cluster nursing on this basis. The differences of liver function, anxiety and depression score, gastrointestinal recovery, nutritional status, and sleep quality were compared between the 2 groups before and after nursing. After nursing, the total bilirubin, albumin, and aspartate aminotransferase of the observation group were significantly higher than those of the control group (P < .05). The nursing staff used Self-Rating Anxiety Scale and Self-Rating Depression Scale of the observation group, which were slightly lower than those of the control group. The difference was statistically significant after testing (P < .05). After nursing, the observation group's upper arm circumference, brachial tri-scalp fold thickness, and hemoglobin were better than those of the control group. Statistics showed that the difference was statistically significant (P < .05). The depth of sleep, time to fall asleep, number of awakenings, time to fall asleep after awakening, overall sleep quality, and intensive care unit environmental noise intensity in the Richards-Campbell Sleep Questionnaire sleep scale after nursing in the 2 groups were significantly higher than those before nursing, and the scores of the observation group were significantly lower than those in the observation group. In the control group, this difference was statistically significant (P < .05). Nutritional nursing combined with clustered nursing can effectively promote the recovery of gastrointestinal function in patients with severe liver failure.

Impact of CFTR modulatory therapies on liver function and fibrosis indices in cystic fibrosis patients: a retrospective analysis from two Romanian medical centers

Background. Patients with cystic fibrosis (CF) frequently require modulatory therapies such as Lumacaftor/Ivacaftor (LI) and Elexacaftor/Tezacaftor/Ivacaftor (ETI) to manage their condition. Given the potential hepatic complications associated with CF, it is critical to understand the impact of these therapies on liver function and fibrosis indices. This study aimed to evaluate the changes in liver function markers and fibrosis indices in CF patients undergoing LI and ETI therapies, with a specific focus on the influence of underlying hepatic disease. Methods. In this retrospective analysis, liver function markers and fibrosis indices were assessed in CF patients receiving ETI (n=24), LI (n=4), or a combination of both (LI/ETI, n=8). Key liver function markers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, platelet count, and fibrosis indices (APRI and FIB-4), were measured at baseline and at various time points up to 12 months. Results. In patients receiving LI therapy, ALT and AST levels demonstrated a slight but non-significant decrease over six months, accompanied by significant fluctuations in total bilirubin levels. Among those receiving ETI therapy, ALT and AST levels initially increased but stabilized over time, while total bilirubin levels significantly increased from baseline to 12 months. No significant differences were observed in liver function markers between patients with and without hepatic disease under ETI therapy. Trends in fibrosis indices (APRI and FIB-4) were modest and largely non-significant across both therapies. Conclusions. ETI therapy appears to be safe for CF patients, including those with pre-existing hepatic disease, with no significant deterioration in liver function over a 12-month period. However, the observed fluctuations in bilirubin levels underscore the necessity for ongoing monitoring. Further research is warranted to investigate the long-term hepatic effects of LI and ETI therapies.

Efficacy of Laparoscopic Left Hemihepatectomy Combined With Choledochoscopic Lithotomy for Complex Intrahepatic Bile Duct Stones and Its Impact on Postoperative Liver Function.

This study was designed to investigate the clinical efficacy of laparoscopic left hemihepatectomy combined with choledochoscopic lithotomy for patients with complex intrahepatic bile duct stones. The clinical data of 97 patients with complex intrahepatic bile duct stones treated in our hospital between February 2019 and April 2022 were retrospectively collected. Patients were allocated into 2 groups based on their surgical approaches. In the control group, 46 patients underwent laparoscopic left hemihepatectomy, while in the combined group, 51 patients underwent laparoscopic left hemihepatectomy combined with choledochoscopic lithotomy. Parameters such as clinical efficacy, surgical indices, stress response markers (CRP, EP, COR), coagulation metrics (FIB, APTT, PT), liver function indicators (GGT, TBIL, ALT), complications, and quality of life were compared between the 2 groups. The combined group exhibited a significantly higher total effective rate compared with the control group (98.04% vs. 82.61%) (P<0.05). The operation duration of the combined group was longer than that of the control group. However, the duration for postoperative anal exhaustion, postoperative bed mobility, postoperative drainage, and hospital stay was shorter in the combined group than in the control group (P<0.05). CRP, EP, and COR concentrations were substantially elevated in both groups on the third postoperative day (P<0.05), but were lower in the combined group. Similarly, levels of FIB, APTT, and PT were markedly increased in both groups on the third postoperative day (P<0.05), but were lower in the combined group. On the seventh postoperative day, GGT, TBIL, and ALT were notably decreased in both groups, with the combined group exhibiting lower levels (P<0.05). The incidence of complications in the combined group was lower than that of the control group (5.88% vs. 19.57%) (P<0.05). At 3 months postoperatively, all GIQLI scores were markedly elevated in both groups, with superior scores observed in the combined group (P<0.05). The combined laparoscopy and choledochoscopy demonstrate a remarkable efficacy for complex intrahepatic bile duct stones, which significantly facilitate liver function recuperation, reduce stress reactions, reduce complications, enhance the quality of life, and exert a minimal impact on coagulation functions.

Palmitoleic Acid Inhibits Hepatotoxic Effects by Reducing Trimethylamine-N-Oxide (TMAO) Formation in High L-Carnitine-Treated Mice

Background/Objectives: This study investigated the effects of palmitoleic acid (POA) consumption on liver function, intestinal microbiota, and trimethylamine-N-oxide (TMAO) levels in the serum of mice treated with 3% L-carnitine drinking water. The purpose was to highlight the impact of POA on liver injury associated with high L-carnitine intake. Methods: A correlation analysis was carried out. The physiological and biochemical results showed that the administration of POA could alleviate liver injury induced by high L-carnitine ingestion, as reflected by a reduction in liver function indices (ALT, AST, AKP, and TBA activities) and modulation of antioxidant enzyme activities (SOD, GSH-Px, MDA, and RAHFR). The study also monitored the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Additionally, to assess the impact of POA on intestinal microbiota, we conducted a 16S rRNA high-throughput sequencing analysis. Results: The findings indicated that POA administration resulted in lower levels of TMAO in treated mice. Furthermore, POA could regulate the composition of intestinal microbiota in L-carnitine mice, particularly affecting Bacteroides vulgatus, Parabacteroides distasonis, Alistipes shahii, Lachnospiraceae NK4A136 group, and Parasutterella secunda, which were closely related to liver injury. Conclusions: In summary, POA could repair liver damage caused by high intake of L-carnitine by regulating the distribution of intestinal flora and subsequently decreasing serum TMAO levels.

Changes in interoception before and after treatment in patients with alcohol use disorder.

To investigate the factors associated with interoception in patients with alcohol use disorder and determine whether treatment causes changes in their interoception. The Body Perception Questionnaire-Body Awareness ultra-short version Japanese version (BPQ-BAVSF-J) was used to measure interoception in 50 alcohol-dependent participants (27 in the inpatient group and 23 in the outpatient group). The BPQ-BAVSF-J was administered and data on aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), mean corpuscular volume, platelet count, and Fib-4 index were extracted at admission and immediately before discharge for the inpatient group and at the first outpatient visit and approximately 3 months after the visit for the outpatient group. The mean age of the 50 participants was 51.0 ± 12.3 years. Significant associations were found between the BPQ-BAVSF-J and Fib-4 index and AST. The BPQ-BAVSF-J score significantly decreased at discharge in the inpatient group. AST, ALT, γ-GTP, and Fib-4 index of liver function were also significantly lower at discharge. In contrast, in the outpatient group, there were no significant changes in the BPQ-BAVSF-J score, AST level, ALT level, γ-GTP level, and Fib-4 index between at the first outpatient visit and approximately 3 months after the visit. Interoception in patients with alcohol use disorder increased with worsening liver function and decreased with improvement in liver function owing to treatment. This suggests that the BPQ-BAVSF-J score, an easily accessible scale, may be used to detect early deterioration of liver function through regular administration.

Diagnostic value of CT liver-to-spleen attenuation ratio in patients with non-alcoholic fatty liver disease and atherosclerotic plaque

Objective: To explore the clinical value of computed tomography (CT) liver-to-spleen (L/S) attenuation ratio in patients with non-alcoholic fatty liver disease (NAFLD) accompanied by atherosclerotic plaque (AP). Methods: This was a single-center, retrospective, observational study of patients who were diagnosed with NAFLD undergoing CT scans at Beijing Changping Hospital of Chinese Medicine from April 2020 to April 2022. Patients were grouped according to whether they had a diagnosis of AP or not. Healthy individuals without NAFLD undergoing CT scans during the same period were also included as a control group. The patients were matched for gender, age, and BMI in a 1:1:1 ratio. Correlations between the CT L/S attenuation ratio, liver function indicators, and blood lipid levels were assessed in the three groups. The predictive value of the CT L/S attenuation ratio was evaluated using the receiver operating characteristic (ROC) curve and the area under the curve (AUC) analyses. Results: Eighty-nine cases in each group. The three groups had significant differences in liver function and blood lipid levels (P&lt;0.05). The CT L/S attenuation ratio in the NAFLD+AP and NAFLD groups was lower than that in the control group and was the lowest in the NAFLD+AP group (P&lt;0.05). There was no significant correlation between the CT L/S attenuation ratio and liver function indicators (P&gt;0.05), but it positively correlated with high-density lipoprotein (HDL) and negatively correlated with low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC) (P&lt;0.05). The CT L/S attenuation ratio had a high predictive value for NAFLD patients with AP (AUC=0.859). Conclusions: The CT L/S attenuation ratio in NAFLD patients with AP is significantly reduced and is closely related to the levels of blood lipid indicators. The CT L/S attenuation ratio has a high predictive value for NAFLD patients with AP. doi: https://doi.org/10.12669/pjms.40.10.10578 How to cite this: Han D, He C, Gu S, Zhang D, Xu L. Diagnostic value of CT liver-to-spleen attenuation ratio in patients with non-alcoholic fatty liver disease and atherosclerotic plaque. Pak J Med Sci. 2024;40(10):2416-2421. doi: https://doi.org/10.12669/pjms.40.10.10578 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

A comparison of the therapeutic efficacy of Tenofovir Disoproxil Fumarate and Entecavir in patients with chronic Hepatitis-B

Objective: To compare the therapeutic efficacy of tenofovir disoproxil fumarate (TDF) and entecavir (ETV) in patients with chronic Hepatitis-B (CHB). Methods: This retrospective study included 110 patients with CHB who received treatment at The First People’s Hospital of Linping District, Hangzhou from January 2021 to January 2023. Clinical data of the patients were reviewed and the patients were classified according to the treatment received: TDF group (n=53, patients received TDF treatment) and ETV group (n=57, patients received ETV treatment). Hepatitis-B virus deoxyribonucleic acid (HBV DNA) levels, liver function indicators, hepatitis-B e antigen (HBeAg) seroconversion rate, alanine transaminase (ALT) normalization rate, HBV DNA negative conversion rate, overall efficacy, and incidence of adverse reactions were compared. Results: The total efficacy of the treatment in the TDF group was 94.33%, significantly higher than that in the ETV group (78.95%; P&lt;0.05). After the treatment, the HBV DNA levels in both groups decreased compared to pretreatment levels, and were significantly lower in the TDF group compared to the ETV group (P&lt;0.05). Both groups showed significant post-treatment improvement in liver function that was markedly better in the TDF group compared to the ETV group (P&lt;0.05). The HBeAg seroconversion rate, ALT normalization rate, and HBV DNA conversion rate in the TDF group were significantly higher compared to the ETV group (P&lt;0.05). There was no difference in the incidence of adverse reactions between the two groups. Conclusions: Compared with ETV, TDF has comparable adverse reaction profile but has more significant clinical effects in patients with CHB, improving HBeAg seroconversion rate, ALT normalization rate, and HBV DNA negative conversion rate. TDF is associated with lower HBV DNA levels after treatment and better improvements in liver function of patients. doi: https://doi.org/10.12669/pjms.40.10.10307 How to cite this: Wang H, Wu L. A comparison of the therapeutic efficacy of Tenofovir Disoproxil Fumarate and Entecavir in patients with chronic Hepatitis-B. Pak J Med Sci. 2024;40(10):2390-2394. doi: https://doi.org/10.12669/pjms.40.10.10307 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Chidan Tuihuang granule modulates gut microbiota to influence NOD1/RIPK2 pathway in cholestatic liver injury recovery

BackgroundCholestatic liver injury (CLI), which occurs if bile acids are imbalanced and the liver becomes inflamed, is difficult to treat effectively ObjectiveWe investigated how the Chinese patent medicine Chidan Tuihuang granule (CDTH) ameliorates cholestatic liver injury with a focus on its effects on the NOD1/RIPK2 pathway and intestinal flora MethodsWe used an ANIT-induced SD rat model of CLI to evaluate the therapeutic effects of CDTH. The experimental design included control, model, UDCA (ursodeoxycholic acid) and CDTH treatment groups. UHPLC-Q-Orbitrap-HRMS was used to analyse the blood components of CDTH. The efficacy of CDTH was assessed by liver function tests, histopathological examination (HE and TUNEL staining), transmission electron microscopy, and ELISA to measure apoptosis and inflammatory markers. Mechanistic insights were obtained using transcriptomics and RT-qPCR, while alterations in the expression of key proteins were studied using western blotting, immunohistochemistry, and immunofluorescence. Furthermore, the impact of CDTH on the gut microbiota and its associated metabolite, meso-2,6-diaminopimelic acid (DAP), which is linked to NOD1 activation, was examined and confirmed through in vitro ResultsThe experimental results demonstrated a notable elevation in serum levels of AST, ALT, ALP, TBA, TBIL, and DBIL in the rats belonging to the model group, accompanied by the infiltration of inflammatory cells, hepatocyte degeneration, and necrosis in the liver tissue. CDTH administration significantly improved liver function and cholestasis indicators. Transmission electron microscopy and TUNEL staining revealed a marked reduction in liver cell apoptosis with CDTH treatment. ELISA results showed that CDTH effectively reduced inflammatory markers. Transcriptomic analysis showed that CDTH inhibited the NOD1/RIPK2 pathway, resulting in a significant decrease in the expression of NOD1, RIPK2 and associated genes in liver tissue. Gut microbiota analysis demonstrated that CDTH regulated intestinal flora structure, reducing the abundance of DAP-producing Gram-negative bacteria such as lactobacilli. In vitro experiments confirmed that CDTH enhanced cell viability by downregulating the DAP-mediated NOD1/RIPK2 signaling pathway secreted by intestinal bacteria ConclusionCDTH ameliorated liver damage in cholestatic rats by inhibiting the NOD1/RIPK2 signaling pathway through regulation of gut flora and downregulation of DAP metabolites.

Small particle drug-eluting beads-transarterial chemoembolization combined with targeted therapy in the clinical treatment of unresectable liver cancer.

Liver cancer is a highly malignant tumor with significant clinical impact. Chemotherapy alone often yields suboptimal outcomes in both the short and long term, characterized by high rates of local recurrence and distant metastasis, leading to a poor long-term prognosis. To evaluate the clinical efficacy of small particle drug-eluting beads-transarterial chemoembolization (DEB-TACE) combined with targeted therapy for the treatment of unresectable liver cancer. We analyzed clinical data from 74 patients with unresectable liver cancer admitted between January 2019 and December 2020. Based on the different treatment regimens administered, patients were divided into the control (36 patients receiving sorafenib alone) and joint (38 patients receiving small particle DEB-TACE combined with sorafenib) groups. We compared liver function indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB)] and serum tumor markers [alpha fetoprotein (AFP)] before and after treatment in both groups. Short-term efficacy measures [complete response (CR), partial response, progression disease, stable disease, objective response rate (ORR), and disease control rate (DCR)] were assessed post-treatment. Long-term follow-up evaluated median overall survival (OS), progression-free survival (PFS), and adverse reaction rates between the two groups. One month post-treatment, the joint group demonstrated significantly higher rates of CR, ORR, and DCR compared to the control group (P < 0.05). Three days after treatment, the joint group showed elevated levels of ALT, AST, and TBIL but reduced levels of ALB and AFP compared to the control group (P < 0.05). The median OS was 18 months for the control group and 25 months for the joint group, while the median PFS was 15 months for the control group and 22 months for the joint group, with significant differences observed (log-rank: χ 2 = 7.824, 6.861, respectively; P = 0.005, 0.009, respectively). The incidence of adverse reactions was not significantly different between the groups (P > 0.05). The combination of small particle DEB-TACE and sorafenib significantly improves both short- and long-term outcomes in the treatment of unresectable liver cancer while preserving liver function.

Utility of Quantitative Assessment of Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl Human Serum Albumin SPECT/CT in the Identification of Severe Liver Fibrosis: Its Complementary Diagnostic Value with Other Liver Function Indices.

To evaluate the value of Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl human serum albumin (99mTc-GSA) single photon emission computed tomography (SPECT) for assessing liver fibrosis, and to assess its complementary value to other liver function indices such as fibrosis-4 (FIB-4) index and indocyanine green (ICG) clearance test parameters (ICG-R15 and ICG-K). Seventy-eight patients with chronic liver disease and hepatocellular carcinoma who underwent 99mTc-GSA scintigraphy and other liver function tests including ICG test and FIB-4 index prior to hepatectomy were studied. 99mTc-GSA imaging was performed with SPECT/CT scanner (Discovery NM/CT 670). Immediately after injection of 99mTc-GSA, dynamic imaging was performed for 20min, followed by SPECT data acquisition for 6min. LHL15 which is a conventional index by 99mTc-GSA planar images, and liver uptake ration (LUR) was measured from 99mTc-GSA SPECT images. From the liver resection specimens, the degree of liver fibrosis was graded according to the Ludwig scale (F0-4). Significant differences in LUR, LHL15, ICG-R15, ICG-K, platelet count and FIB-4 index were found between the F0-3 and F4 liver fibrosis patient groups (P < 0.05). Multivariate logistic regression analysis revealed that LUR and ICG-K were independent factors for identifying severe liver fibrosis (F4). Area under the curve of receiver operating curve analysis for the logistic regression model using LUR and ICG-K was 0.83. In the patient group with higher FIB-4 (≥ 3.16), the diagnostic performance of LUR for detecting severe liver fibrosis was significantly better than LHL15 (AUC: 0.83 vs. 0.75, P = 0.048). In the high FIB-4 index group, the sensitivity and specificity for identifying F4 was 88% and 85%, respectively, with LUR cutoff value of 41.2%. LUR, measured by 99mTc-GSA SPECT, is a useful indicator for identifying sever liver fibrosis. Particularly in patients with high FIB-4 index (≥ 3.16), LUR can be a valuable indicator to identify severe liver fibrosis with high diagnostic accuracy.

Efficacy of combined use of octreotide and sodium tanshinone IIA sulfonate in patients with cirrhosis complicated with severe acute pancreatitis

Purpose: To assess the prognosis of liver cirrhosis complicated with severe acute pancreatitis (SAP) after treatment with octreotide in combination with sodium tanshinone IIA sulfonate. Methods: A total of 164 patients with cirrhosis complicated with SAP were randomly assigned to two groups, each with 82 patients. Serum levels of inflammatory factors, as well as vascular endothelial function and liver function indices were determined. Treatment outcomes in the patients were recorded in terms of abdominal pain relief time, gastrointestinal function recovery time, hospital stay duration, and incidence of complications. Results: Relative to the control group, there were decreases in concentrations of inflammatory indices in the study cohort. Endothelial function index levels increased in the two groups, but the levels of endothelin (ET) and von Willebrand Factor (vWF) decreased more in the study group of patients, when compared to the control group, while nitric oxide (NO) level was raised (p &lt; 0.05). Liver function improved in both groups. There were marked reductions in serum ALT, AST and total bilirubin (TBIL) in study cohort, relative to the control cohort (p &lt; 0.05). However, albumin (ALB) levels were comparable in the two groups. Abdominal pain relief time, duration of hospitalization and time taken for normal digestive system function were shorter in the study cohort (p &lt; 005). Receiver operating characteristic (ROC) curve analysis revealed that after treatment with octreotide and sodium tanshinone IIA sulfonate, values of area under the curve (AUC) for abdominal pain relief time, gastrointestinal function recovery time and hospital stay were 0.886, 0.918 and 0.794, respectively. Conclusion: The combined use of octreotide and sodium tanshinone IIA sulfonate inhibits the release of inflammatory factors in cirrhotic patients with SAP, and improves vascular endothelial and liver functions, thereby improving disease prognosis. These data constitute a good scientific basis for the use of octreotide and sodium tanshinone IIA sulfonate in the treatment of liver cirrhosis complicated with SAP.

Comparative effectiveness of five Chinese patent medicines for non-alcoholic fatty liver disease: A systematic review and Bayesian network meta-analysis

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a metabolically stressed liver injury closely related to insulin resistance and genetic susceptibility and has become the leading chronic liver disease in China. PurposeTo analyze the effectiveness of five Chinese patent medicines used alone or in combination with western medications (WM) for NAFLD using Bayesian network meta-analysis. MethodsSearches were conducted in Embase, Cochrane Library, PubMed, CNKI, Wanfang Database, VIP, and SinoMed for randomized controlled trials (RCTs) on Danning tablets, Huazhi Rougan granules, Dangfei Liganning capsules, Kezhi capsules, and Qianggan capsules, either alone or in combination with WM for NAFLD, up to January 10, 2024. This study was screened based on pre-designed inclusion and exclusion criteria, and the risk of bias was evaluated using the Cochrane ROB2 tool. The primary outcome was clinical efficacy rate, while secondary outcomes included levels of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Triglycerides (TG), and Low-density lipoprotein cholesterol (LDL-C). These data will be analyzed using WinBUGS 1.4.3 and then visualized using Stata 14.0 software. ResultsA total of 77 RCTs involving 7770 patients were included. The results indicated that Huazhi Rougan granules combined with WM (OR = 0.13, 95 % CI 0.05 ∼ 0.26) had a SUCRA probability value of 81.7 %, ranked first in clinical efficacy and significantly improved blood lipids levels including TG, High-density Lipoprotein Cholesterol (HDL-C), and LDL-C, Total cholesterol (TC). For the Chinese patent medicines alone, Danning tablets led with a 75.3 % clinical efficacy rate. Huazhi Rougan granules significantly increased levels of ALT (96.2 %) and AST (MD = -14.48, 95 % CI -23.38 ∼ -5.32). Dangfei Liganning capsules demonstrated significant efficacy in improving TG (73.1 %) and TC (83 %) levels. ConclusionIn the treatment of NAFLD, the combination of Huazhi Rougan granules and WM demonstrated significant clinical effectiveness and improvement in blood lipid profiles. For different outcome indicators, Danning tablets used alone showed the highest clinical efficacy, while significant improvement in liver function indicators was best achieved with Huazhi Rugan granules used alone.

Clinical Efficacy of Autologous Bone Marrow Mesenchymal Stem Cell Transplantation for the Treatment of Patients with Refractory Cirrhotic Ascites

Objective: To analyze the efficacy of autologous bone marrow mesenchymal stem cell (BMSC) transplantation for the treatment of cirrhotic ascites (refractory). Methods: 64 patients with cirrhosis ascites (refractory) who were admitted to the hospital between May 2022 and April 2024 were selected and divided equally by random number table, the observation group was treated with BMSC autologous transplantation, and the reference group was treated with conventional medication, and the total effective rate, therapeutic indexes, liver and renal function indexes, and the change of urine volume were compared. Results: The total effective rate of the observation group was higher than that of the reference group (P &lt; 0.05). Before treatment, there was no difference between the two groups in terms of therapeutic indexes such as depth of ascites, liver and kidney function indexes and 24-hour urine volume (P &gt; 0.05). After treatment, the observation group’s ascites depth and other indicators were better than that of the reference group, liver and kidney function indicators were better than that of the reference group, and 24h urine volume was more than that of the reference group (P &lt; 0.05). Conclusion: BMSC autotransplantation can improve the clinical efficacy of patients with cirrhosis ascites (refractory), accelerate the absorption of ascites, reduce the values of body mass and abdominal circumference, and protect the liver and kidney functions and increase the amount of urination.

B-034 Performance Evaluation of the Total Bile Acids (TBA) Assay on Mindray BS-2800M Analyzer

Abstract Background Bile acids (BA) are synthesized in the liver and secreted into bile. The function of BA is to promote absorption of lipids including fat-soluble vitamins. During liver diseases such as viral hepatitis and liver injury by hepatotoxic drugs, and cholestasis condition, BA secretion to bile is impaired, causing serum BA level to rise. Therefore, the determination of serum BA can be used as a sensitive indicator of liver function. TBA reagent contains NADH that requires pH ≥ 9 to be stable that is usually difficult to be maintained during reagent opened and stored on the analyzer. Meanwhile, 3α-Hydroxysteroid Dehydrogenase (3α-HSD) is required for the reaction. 3α-HSD is sensitive to pH condition. Minor changes in pH results in significant changes of enzyme activity. We formulated our TBA reagent with prolonged stability when reagent is onboard on the analyzer. This study evaluated the performance of the new Mindray TBA assay on Mindray BS-2800M. Methods TBA assay was based on the method with coupled Thio-NAD and NADH reaction for BA. The R1 contains Thio-NAD. The R2 contains NADH and 3α-HSD. R1 is incubated with serum sample containing BA for 5 min at 37°C and R2 is then added. During further incubation in the presence of Thio-NAD, 3α-HSD converts BA to 3-ketosteroids and Thio-NADH. The reaction is reversible, and 3α-HSD can convert 3-keto steroids and Thio-NADH to BA and Thio-NAD. In the presence of excess NADH, enzyme cycling occurs efficiently and the rate of formation of Thio-NADH is determined by measuring specific change of absorbance at 412 nm. Two-point-line calibration is used by this assay. The TBA concentrations for the test samples are obtained by the absorbances of test samples from the calibration line. The performances of precision, linearity, onboard stability, interference (hemolysis, lipid and bilirubin), correlation are evaluated following CLSI protocols. Results The precision study was run according to EP05A3 with two commercial controls (about 21 and 36μmol/L) and two serum sample pools(about 9.9 and 24.2 μmol/L)on the Mindray BS-2800M system. The repeatability and within-lab CVs ranged from 0.74% to 1.97%, respectively. The linearity of the assay was determined as from 2.0 μmol/L to 180 μmol/L. The reagent onboard stability is for 28 days without recalibration that is superior to TBA reagents from other manufacturers. The interference of hemolysis, lipid and bilirubin are with less than ±10% impact with hemolysate Hemoglobin up to 500 mg/dL, Intralipids up to 500 mg/dL, and Conjugated bilirubin up to 30 mg/dL, Unconjugated bilirubin up to 30mg/dL. This assay (Y) also correlated well with SEKISUI TBA assay (x), (Y = 0.9965X + 0.2694, r= 0.9993). Conclusions From this evaluation, we concluded that Mindray TBA assay can measure serum TBA precisely and accurately with good performances, especially for onboard stability. It is suitable for use in routine clinical laboratories.

Aquamimicry feeding system improved growth, physiological status, muscle and intestine histomorphology, and flesh quality of keeled mullet, Liza carinata

The aquamimicry feeding system (AMFS) is one of the modern aquaculture systems that aim to reduce feed costs and water exchange rates to improve the sustainability of aquaculture projects. In AMFS, the aquatic environment is simulated to produce natural food by adding probiotics to carbon sources. Therefore, a 108-day field study was conducted to evaluate the efficiency of AMFS as a solo feed or in combination with a commercial diet for the rearing of keeled mullet, Liza carinata. The L. carinata fingerlings with an initial body weight of 30.0 ± 3.25 g were randomly distributed into three experimental treatments in triplicate rectangular polyethylene ponds (measured 7 × 3 × 1 m) at an initial stocking density of 105 fish per pond. The fish were fed one of the following regimes: the 1st is a commercial floating diet (CFD, 30 % crude protein; T1), the 2nd is a combination of 50 % CFD: 50 % AMFS (T2), the 3rd is a solo of AMFS (T3). Water quality parameters did not differ significantly among different treatments except for a significant reduction in total ammonia nitrogen and a higher zooplankton count in the water of the AMFS group. The fish reared with AMFS as a solo feed (T3) experienced a significant growth performance, somatic indexes, and digestive enzyme activities compared to the fish reared in other treatments. Fish fed AMFS alone (T3) or in combination with CFD (T2) had an improved hematological profile, liver and kidney function indicators, serum lipid, and protein profiles than those fed CFD (T1). Histological and histometric analysis of the intestine showed an improved architecture with AMFS feeding. Furthermore, AMFS feeding increased the diameter of muscle bundles and the protein content of the dorsal muscles. The flesh quality parameters, including water holding capacity, stored loss, drip loss, and frozen leakage rate were improved in fish fed on AMFS alone or in combination with CFD. Therefore, from the above-mentioned beneficial effects of AMFS, it could be used as a promising, economical, and sustainable technology for rearing L. carinata.

Modulation of SIRT6 Related Signaling Pathways of p-AKT/mTOR and NRF2/HO-1 by Memantine Contributes to Curbing the Progression of Tamoxifen/HFD-Induced MASH in Rats

Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic liver disorder marked by hepatic fat accumulation and inflammatory infiltrates which may evolve to cirrhosis. Clinical studies have demonstrated the higher risk of MASH development after tamoxifen (TAM) therapy, especially in obese patients. Therefore, we aimed to evaluate MASH induction by TAM combined with high fat diet (HFD) and the potential interference of memantine (MEMA) with MASH progression via modulation of SIRT6 and its related signaling pathways. MASH was induced in female Wistar rats by co-administration of TAM (25 mg/kg/day, p.o.) and HFD for 5 weeks. Liver function biomarkers, tissue triglyceride and cholesterol, MASH scoring, SIRT6 and its related signals, and lipid synthesis/oxidation markers were estimated. By comparison to MASH group, MEMA improved liver function indices (ALT, AST, ALP, albumin) and reduced the progression of MASH, evidenced by decreased accumulation of lipids in hepatic tissue, improved histological features, and reduced MASH scoring. MEMA enhanced hepatic SIRT6 and downregulated p-AKT/mTOR signaling, that subsequently reduced expressions of the lipid synthesis biomarkers (SREBP1c, CPT1), while elevating the lipid oxidation markers (PPAR-α, SCD). Moreover, MEMA enhanced NRF2/HO-1 signaling, with subsequently improved antioxidant defense and pro-inflammatory/anti-inflammatory cytokines balance. Analysis of SIRT6 correlations with p-AKT/mTOR, NRF2/HO-1, SREBP1c, and PPAR-α further confirmed our results. Consequently, we conclude that MEMA could interfere with MASH progression, at least in part, via enhanced SIRT6 expression and modulation of its related p-AKT/mTOR and NRF2/HO-1 signaling pathways, eventually reducing liver steatosis and inflammation. That could be a promising therapeutic modality for curbing MASH progression.

Caffeoylquinic acids from Silphium perfoliatum L. show hepatoprotective effects on cholestatic mice by regulating enterohepatic circulation of bile acids

Ethnopharmacological relevanceThe incidence of cholestatic liver disease (CLD), which is primarily marked by abnormal bile acids (BAs) metabolism and can result in significant hepatic injury, is rising. Nevertheless, there remains a lack of effective treatments and drugs in clinical practice. Silphium perfoliatum L. (SP) is rich in various structural types of caffeoylquinic acid (CQA) compounds, and it is a traditional herb of North American Indians with hepatobiliary therapy effects. However, its therapeutic effect and mechanism of action on CLD have never been studied. Aim of the studyTo determine if SP-8, an extract rich in CQAs from SP, protects against cholestatic liver injury induced by alpha-naphthylisothiocyanate (ANIT) and to clarify its mechanism based on the farnesoid x receptor (FXR) signaling pathway and enterohepatic circulation of BAs. Materials and methodsThe therapeutic efficacy of SP-8 was evaluated by assessing the serum biochemical indices, inflammatory factors, and liver histopathology. Targeted metabolomics of the BAs was studied in the feces, liver, serum, and bile using UPLC-MS/MS. Additionally, a Western blot analysis was used to examine the expression levels of the peroxisome proliferator-activated receptor γ (PPARγ), the FXR, and proteins related to the synthesis and transport of BAs. 16S rRNA gene sequencing was performed to evaluate the gut microbiota (GM). Finally, molecular docking simulations were conducted to assess the interaction between seven types of CQAs from SP-8 with FXR and PPARγ. ResultsSP-8 significantly enhanced the health status of cholestatic mice induced by ANIT as evidenced by a notable reduction in the liver function indices and pro-inflammatory factors, restoration of liver pathological damage, and acceleration of BAs excretion through the feces. In addition, the levels of harmful secondary BAs in the liver and blood were significantly reduced by SP-8. Furthermore, the results of the study on the mechanism of action confirmed that SP-8 not only regulated FXR and PPARγ but also significantly ameliorated the GM structure, thereby promoting the enterohepatic circulation of BAs and achieving the homeostasis of the BAs in the blood and liver. In addition, SP-8 successfully reduced the inflammatory response by strongly suppressing the nuclear translocation of NF-κBp65. According to the molecular docking results, the extract's primary active ingredients could be the seven CQAs in SP-8, as they exhibited a strong affinity for both FXR and PPARγ. Finally, the Mantel test analysis revealed a significant correlation among cholestatic-associated parameters, the GM, and BAs. ConclusionIt was confirmed for the first time that the SP-8 extract of Silphium perfoliatum L. that is rich in seven CQAs had a strong therapeutic effect on ANIT-induced CLD. Its mechanism may involve the regulation of the FXR signaling pathway and the amelioration of the GM structure to promote the homeostasis of BAs enterohepatic circulation. This study provides a potential candidate medicinal herb and its components for the development of CLD therapeutic drugs.