High Liver Enzymes Research Articles

The Prognostic Values of Serum Liver Enzymes in Intrahepatic Cholangiocarcinoma Patients After Liver Resection: A Multi-Institutional Analysis of 605 Patients.

The value of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT), in predicting the prognosis of intrahepatic cholangiocarcinoma (ICC) patients who underwent curative resection has not been elucidated. Therefore, we aimed to construct prognostic nomograms for surgically treated ICC patients. The impact of liver enzymes on overall survival (OS) and recurrence-free survival (RFS) was analysed using Kaplan-Meier analysis and evaluated by univariate and multivariate analyses. Nomograms were constructed for predicting the probability of 1-, 3-, and 5-year OS and RFS and evaluated by receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA). High ALT, AST, ALP and GGT levels were associated with worse prognoses in surgically treated ICC patients. Nomograms for OS and RFS were constructed based on five prognostic factors: number of high liver enzyme (No. HLE), CA19-9 ≥ 37 U/mL, multiple tumours, lymph node invasion and microvascular invasion (MVI). Compared with 8th edition TNM stage, these nomograms showed better predictive value. The C-index and 1-, 3- and 5-year areas under the curve (AUCs) of the nomograms for OS and RFS in the discovery and validation cohorts were higher than those of the 8th TNM stage. The calibration plots indicated that there was good agreement between the actual observations and predictions. Preoperative ALT, AST, ALP and GGT levels could predict prognosis in surgically treated ICC patients. The nomograms showed good predictive ability for predicting the survival of ICC patients.

Disparities in the Cardiometabolic Impact of Adiposity among African American and Hispanic Adolescents.

As adiposity increases in youth, so does the prevalence of cardiometabolic risk factors (CMRFs). The etiology of adiposity-based chronic disease and CMRFs includes ethnoracial disparities that are rarely considered in current treatment approaches. Precision interventions require further characterization of these disparities among high-risk youth. The objective of this study was to characterize differences in CMRF among African American (AA) and Hispanic (H) adolescents with varying levels of adiposity. A cross-sectional analysis of 2284 adolescents aged 12-17 was conducted using 3-year clinical data from Lifedoc Health. CMRF prevalence were compared using χ2, with logistic regression models (LRM) applied to explore the relationships between exposures (age, sex, ethnoracial group, adiposity) and CMRF outcomes. Prevalence of CMRF rose with increasing adiposity, which was the strongest determinant of risk overall. However, individual risk profiles differed between the two groups, with H having higher prevalence of metabolic syndrome (MetS), higher triglycerides and liver enzymes, and low high-density lipoprotein cholesterol (HDL-c). Meanwhile, AA had higher prevalence of elevated blood pressure (BP) in the overweight category, prediabetes in overweight to severe obesity, and type 2 diabetes in obesity. LRM showed 3.0-fold greater chance of impaired glucose metabolism in AA than H, who were 1.7, 5.9, and 8.3 times more likely to have low HDL-c, high liver enzymes, and high triglycerides, respectively. Overweight/obesity prevalence was very high among AA and H adolescents. Excess adiposity was associated with an increased prevalence of CMRF, with individual risk factors differing between groups as adiposity increased. Research within routine clinical settings is required to better characterize these discrepancies and ameliorate their adverse impact on health in the transition to adulthood.

Risk Factors for Progressive Fibrosis and Cirrhosis in Patients With Chronic Hepatitis C in India.

Background Liver cirrhosis (LC) caused by chronic hepatitis C (CHC) infection is a major global public health concern. This study will look at the risk factors for progressive fibrosis and cirrhosis in patients with persistent hepatitis C virus (HCV) infection. Methods In this cohort study, a total of 300 patients were included. We collected comprehensive diagnostic records for the entire study group of 200 people with chronic hepatitis C infection. For the comparison, 100 healthy people were recruited and assessed. FibroScan (Echosens, Paris, France) scores were used to categorize liver fibrosis stages: F0-F1 (no or mild fibrosis, <7 kPa), F2 (moderate fibrosis, 7-8.99 kPa), F3 (significant fibrosis, 9-12.49 kPa), and F4 (cirrhosis, ≥12.5 kPa). Their demographic, biochemical, and serological data were evaluated and compared. Results Most patients were males (47% femalesand 53% males). In the CHC group, the mean age of diagnosis was 37.68±11.57 years, whereasin the chronic hepatitis C-related liver cirrhosis (CHC-LC) group, the mean age was 48.89±12.30 years (p=0.01).Compared to normal individuals, CHC patients had higher body mass index (BMI) (22.37±1.89 versus 21.72±1.95, p=0.01), alanine aminotransferase (ALT) (36.70±7.13 versus 82.78±82.53, p=0.01), and aspartate aminotransferase (AST) (34.96±6.04 versus 80.82±91.77, p=0.01). However,compared to the patients with CHC, the patients with LC have lower platelet (PLT) count (1.51±0.78 versus 1.7±0.41, p=0.01) and higher liver enzymes (AST: 117.7±186.9 versus 80.8±91.7, p=0.01; ALT: 86.71±80.24 versus 82.78±82.53, p=0.01). On regression analysis, higher BMI, older age, low hemoglobin (Hb), and higherbilirubin, ALT, AST, and prothrombin time (PT) were associated with LC. Conclusion It is imperative to shift towardprevention and early intervention as the new approach to managing patients with HCV-related cirrhosis. Cirrhosis should be suspected in older patients with CHCwho are obese and have low platelet counts with higher liver enzymes.

Single-center experience of intraoperative ligation of the splenic artery for prevention of splenic artery steal syndrome in patients after living donor liver transplant

Background. Living donor liver transplant is an effective method of treatment in patients with different types of endstage liver diseases. Unfortunately, patients undergoing such a complex treatment sometimes develop various vascular complications. Splenic artery steal syndrome has emerged as a cause of graft ischemia in living donor liver transplant recipients and may lead to high liver enzyme levels, cholestasis, hepatic artery thrombosis, and even a graft loss in some severe cases.Objective. Evaluation of the first results in the experience of our center with a routine intraoperative ligation of the splenic artery during the procedure of right lobe living donor liver transplantation in adult recipients for the prevention of the steal syndrome development in the postoperative period.Material and methods. Living donor liver transplant recipients with known hepatic arterial flow impairment were retrospectively studied. Patients were allocated into groups with regard whether the splenic artery had been ligated or not during the transplant procedure. Arterial complications were reviewed in both groups.Results. None of 30 patients with ligated splenic artery developed splenic artery steal syndrome after living donor liver transplant. splenic artery steal syndrome occurred in 60% patients with non-ligated splenic artery. Surgical technique of performing arterial anastomosis was not related to the splenic artery steal syndrome development (p&lt;0.01 There was no local ischemic necrosis noted in the spleen in patients with the ligated splenic artery.Conclusion. Based on the analysis of our own experience and literature data, the splenic artery ligation appears to be an effective and safe method for preventing a splenic artery steal syndrome in patients following right lobe liver transplantation, with a minimal risk of ischemic complications for the spleen. However, further studies with larger sample sizes are needed to obtain more reliable results. Ultrasound examination and endovascular intervention are the primary tools for an early detection of abnormalities and rapid restoration of arterial blood flow in the hepatic artery of the graft.

Hepatozoon Canis in Labrador Dog with Azotaemia and its Therapeutic Management

A 10-year-old female Labrador dog weighing around 30 kg was presented at Department of Teaching Veterinary Clinical Complex, Mumbai Veterinary College, Parel, Mumbai (Maharashtra). Previous history of oral medications of doxycycline that leads to vomition, recent tooth eruption which leads to anorexia, dull in appearance, lethargic. Clinical examination revealed pyrexia (103°F), pale mucous membrane, dehydration (+), azotemic. Upon blood reports revels low haemoglobin and platelet count and high kidney and liver enzyme values. The dogs were treated with inj. Imidocarb dipropionate @5 mg/ kg B.W. twice in month and inj. Metronidazole @ 20mg/kg B.W. for 10 days along with haematinics, liver tonics and antacids. Dogs showed complete recovery after 8 days of therapy.

An Observational Study to Find the Association of Viral Load, NS1 Antigen, IgG Antibody, and Other Laboratory Parameters With the Outcome of Dengue Patients in Eastern India.

Background Dengue, the mosquito-borne febrile disease caused by the dengue virus, has become one of the major concerns of public health. It may present with only fever, or there may be a hemorrhagic manifestation or septic shock. As there is no specific treatment for dengue, early detection of the disease, assessment of progression, and prediction of outcome by studying the laboratory markers will help guide the management of cases and lower morbidity and mortality. Methodology This clinico-observational study was conducted at the Department of Microbiology in a tertiary care hospital in Kolkata, India, from February 2020 to August 2022 to determine the outcome of dengue patients in correlation with viral load, NS1 antigen, IgM and IgG antibodies, ferritin level, platelet count, and other laboratory parameters. Results Out of 316 samples from fever patients, 103 (32.5%) were NS1 antigen reactive. We followed up the dengue patients (n = 103) for 15 days and divided them into three groups according to their duration of symptoms (group A suffered for ≤5 days, group B for 5 to 10 days, and group C for >10 days) and per the WHO classification of disease severity, namely dengue without warning signs (DOS), dengue with warning signs (DWS), and severe dengue (SD). Based on severity, 65 (63.1%) patients had DOS, whereas 31 (30.09%) patients had DWS, and seven (6.79%) patients had SD. Secondary infection was present in 83.33% of patients in group C, 71% of DWS cases, and 57% of SD cases, which positively correlates with liver enzymes, viral load (mean value 102195 in secondary infection vs. 1195 copies/10 µl in primary infection), and negatively correlates with platelet counts (mean value 60,213 in secondary infection vs. 1,25,516 in primary infection). Patients in group C had higher liver enzymes, a lower platelet count, and a higher initial viral load than groups A and B. Similarly, SD cases had a higher ferritin level (9215 ug/l), a lower platelet count (mean value 23,250), and a higher initial viral load (mean value 2,74,257 copies/10 µl). An increase in hematocrit value considering the peak value and its baseline value is an important marker for disease severity rather than its absolute value. Conclusion Poor outcome of dengue infection, i.e., an increase in the duration of symptoms and disease severity depends on concurrent associations between high serum ferritin, increased hematocrit level, thrombocytopenia, secondary infection, increasing liver enzymes, and increased initial viral load.

Incidence of Elevated Liver Enzyme Levels in Patients Receiving Remdesivir and Its Effective Factors.

Emergency use of remdesivir was approved for COVID-19 in some countries. Based on the promising results of remdesivir, the most common side effects were nausea, worsening respiratory failure, increased alanine aminotransferase levels, and constipation. The aim of this study was to determine the incidence of elevated liver enzymes in patients with COVID-19 receiving remdesivir. In this retrospective study, information was collected from patients' files. The study population included patients with moderate to severe COVID-19 who were admitted to Rouhani Babol Hospital. For daily patient selection, the list of patients was extracted from the system, and based on the census, the patient file was selected. Data were analyzed using Stata 16. 620 patients suffering from moderate to severe COVID-19 were included in this study, 43% of whom were men. Of these patients, 120 were selected as the control group who did not receive remdesivir. The increase in liver enzymes in patients receiving remdesivir compared with the control, for alanine transaminase (ALT) and aspartate transaminase (AST), respectively, was 6.20 and 3.64 times, but it was not statistically significant for alkaline phosphatase (ALP). Also, the increase in bilirubin levels in patients receiving remdesivir was not statistically significant. The recipients of remdesivir had high liver enzymes, which is one of the possible side effects of this drug. The intensity of the enzymes was mild and moderate, and they were not dangerous to the health of any of the consumers. Deaths in patients with COVID-19 were not due to drug-induced liver complications but to other factors such as disease-related complications.

Comparison between Highly Sensitive C - Reactive Protein in Subjects with Preeclampsia with Severe Features and Preeclampsia without Severe Features

Background: Preeclampsia (PE) develops in 4-5% of pregnancies in humans. It appears after 20 weeks of gestation and is defined by increased blood pressure and proteinuria. When convulsions occur or the hemolysis, high liver enzymes, and low platelet count (HELLP) condition materializes, PE can lead to eclampsia. It is well recognized that eclampsia and HELLP syndrome are linked to serious side effects include liver hemorrhage, lung edema, brain hemorrhage, and renal failure. Objective: The aim of this study is to compare between highly sensitive c- reactive protein in subjects with preeclampsia with severe features and preeclampsia without severe features. Methods: This case-control study was carried out in the Department of Obstetrics &amp; Gynecology of Dhaka Medical College Hospital, Dhaka, from January 2023 to December 2023. A total of 68 patients were enrolled and analyzed in this study. The questionnaire was pretested, corrected and finalized. Data were collected by face-to-face interview and analyzed by appropriate computer based programmed software Statistical Package for the Social Sciences (SPSS), version 24. Results: In this study, maximum study subjects were in 21 – 30 years age group. Mean age of the study subjects was 26.12 ± 4.02 and 24.04 ± 4.32 years in PE with severe features and PE without severe features respectively. Majority of the patients 27(79.4%) and 25 (73.5%) were housewife in both cases. Illiterate 2 (5.9%), higher secondary 9(26.5%) and graduate 10(29.4%) were higher in PE with severe features than PE without severe features. Most of the patients 25 (73.5%) and 21 (61.8%) came from rural area. Nullipara was higher in PE with severe feature and multigravida was higher in PE without severe features. Antenatal care was found more irregular in PE patients with severe features subjects than PE without severe features. Preterm pregnancy was higher in PE with severe feature than PE without severe features. Systolic and diastolic blood pressure were found significantly higher in PE patients with severe features than without severe features. hsCRP was found significantly higher in PE with severe features than PE without severe features. APGAR score of the neonate was significantly better of PE patients without severe features than with severe features patients both at birth and at 5 minutes. Average birth weight of the neonate was found higher of the PE patients without severe features than with severe features patients. There was 6(17.6%) very LBW of neonates of PE with severe features patients but none in PE without severe features patients. Intrauterine growth retardation, and prematurity were found higher in PE with severe features patients comparing PE without severe features. Conclusion: Women with PE have higher serum hsCRP levels. Clinical and biochemical markers of PE are linked with elevated serum levels of hsCRP in preeclamptic women. Serum hsCRP levels can be measured to determine the severity of PE.

Association between the ZJU index and risk of new-onset non-alcoholic fatty liver disease in non-obese participants: a Chinese longitudinal prospective cohort study.

Non-alcoholic fatty liver disease (NAFLD) is increasingly observed in non-obese individuals. The ZJU (Zhejiang University) index has been established as a new and efficient tool for detecting NAFLD, but the relationship between the ZJU index and NAFLD within non-obese individuals still remains unclear. A post-hoc evaluation was undertaken using data from a health assessment database by the Wenzhou Medical Center. The participants were divided into four groups based on the quartile of the ZJU Index. Cox proportional hazards regression, Kaplan-Meier analysis and tests for linear trends were used to evaluate the relationship between the ZJU index and NAFLD incidence. Subgroup analysis was conducted to test the consistency of the correlation between ZJU and NAFLD in subsgroups. Receiver operative characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the ZJU index, compared with the Atherogenic index of plasma (AIP) and Remnant lipoprotein cholesterol (RLP-C) index. A total of 12,127 were included in this study, and 2,147 participants (17.7%) developed NAFLD in 5 years follow-up. Participants in higher ZJU quartiles tended to be female and have higher liver enzymes (including ALP, GGT, ALT, AST), GLU, TC, TG, LDL and higher NAFLD risk. Hazard Ratios (HR) and 95% confidence intervals (CI) for new-onset NAFLD in Q2, Q3, and Q4 were 3.67(2.43 to 5.55), 9.82(6.67 to 14.45), and 21.67(14.82 to 31.69) respectively in the fully adjusted model 3. With increased ZJU index, the cumulative new-onset NAFLD gradually increased. Significant linear associations were observed between the ZJU index and new-onset NAFLD (p for trend all<0.001). In the subgroup analysis, we noted a significant interaction in sex, with HRs of 3.27 (2.81, 3.80) in female and 2.41 (2.21, 2.63) in male (P for interaction<0.01). The ZJU index outperformed other indices with an area under the curve (AUC) of 0.823, followed by AIP (AUC=0.747) and RLP-C (AUC=0.668). The ZJU index emerges as a promising tool for predicting NAFLD risk in non-obese individuals, outperforming other existing parameters including AIP and RLP-C. This could potentially aid in early detection and intervention in this specific demographic.

Padrão de resistência a antibióticos e características patológicas de Escherichia coli patogênica aviária O78:K80 em galinhas

Avian pathogenic Escherichia coli (APEC) induces colibacillosis, an acute and systemic disease, resulting in substantial economic losses in the poultry sector. This study aimed to investigate the antibiotic resistance pattern associated with frequent virulence gene distribution in APEC O78:K80 that may cause pathological alterations in chickens. The antibiogram profile showed high resistance to erythromycin, chloramphenicol, tetracycline, ampicillin, and co-trimoxazole, followed by intermediate resistance to ciprofloxacin, levofloxacin, enrofloxacin, norfloxacin, nitrofurantoin, and doxycycline hydrochloride, and sensitive to amikacin, streptomycin, gentamicin, and colistin. Virulence gene distribution identifies eight (irp-2, iutA, ompT, iss, iucD, astA, hlyF, iroN) genes through a conventional polymerase chain reaction. APEC O78:K80 caused significantly high liver enzyme concentrations, serum interleukin-6 and tumor necrosis factor-alpha levels in experimental birds. Also, infected birds have hypoproteinemia, hypoalbuminemia, and hyperglobulinemia. Necropsy examination revealed fibrinous perihepatitis and pericarditis, congested lungs, intestinal ecchymotic hemorrhages and necrotizing granulomatosis of the spleen. Histopathological examination depicted hepatocellular degeneration, myocardial necrosis, interstitial nephritis, intestinal hemorrhages and lymphopenia in the spleen. This study is the first evidence to assess the antibiotic resistance profile linked with virulence genes and clinicopathological potential of APEC O78:K80 in chickens in Pakistan, which could be a useful and rapid approach to prevent and control the disease by developing the control strategies.

Clinical and radiological characteristics of Covid-19 patients with acute cerebrovascular vents: A meta-analysis

The Information on the 2019 coronavirus illness (COVID-19) in Egypt's severe cerebrovascular consequences is scant. In cases of acute cerebrovascular disease (CVD), this study aimed to examine the radiological and clinical characteristics of patients with and without COVID-19. Prospective research evaluated CVD patients with and without COVID-19 who were hospitalized at Qena University Hospital (QUH) before the global epidemic. Patients diagnosed with COVID-19 and able to be treated at either assist or Aswan University Hospitals (AAUH) for cardiovascular disease were compared. The data included patient demographics, medical history, risk factors, clinical presentation, comorbidities, and imaging results from CT and MRI scans of the chest and brain. In overall 439 individuals with COVID-19, 55 (12.5%) experienced acute CVD. Of these, 13 patients (2.9%) experienced hemorrhagic CVD, whereas 42 (9.6%) suffered an ischemic stroke. 180 of the 250 non-COVID-19 individuals suffered from ischemic stroke, and 70 from hemorrhagic stroke. Many COVID-19 patients had large vascular occlusions (LVO), which is a significant portion of individuals who had ischemic stroke symptoms (40 vs. 7.2%, P &lt;0.001) and was considerably more reciprocal than in CVD patients who were not COVID-19. Comorbidities were noted in 44 instances (80% of the total). Sufferers of ischemic stroke who had COVID-19 were much more likely to have dangerous elements such as hypertension and Ischemic Heart Disease (IHD) as well as concomitant conditions like hepatitis and kidney disease. Additionally, 6.5% of individuals with LVO had a hemorrhagic transition, and 23.5% had hemorrhagic CVD. In our research, individuals with COVID-19 often had severe CVD. The most typical LVO was. The most frequent risk factors, such as hypertension, IHD, and anemia, may make the clinical presentation worse. Patients with CVD often had comorbid conditions, but many also had high liver enzymes and creatinine levels that were partly brought on by the COVID-19 disease itself. The new findings start to describe the range of CVD linked to COVID-19 in patients from Upper Egypt.&#x0D;

Hepatic steatosis in women with polycystic ovary syndrome

BackgroundThis multi-center, cross-sectional study intended to explore the prevalence and risk factors of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with polycystic ovary syndrome (PCOS).MethodsPatients who met the PCOS Rotterdam diagnostic criteria were enrolled in 6 centers in China, and age-matched healthy volunteers were also recruited. Data were collected including medical history, physical characteristics, and blood tests (liver function, blood lipids, blood glucose and insulin, sex hormones, etc.). Transvaginal or transrectal ultrasound was employed to identify polycystic ovarian morphology (PCOM). The serological score Liver Fat Score (LFS) >-0.640 was used for the diagnosis of NAFLD, and the diagnosis of MAFLD was made according to the 2020 new definition.ResultsA total of 217 PCOS patients and 72 healthy controls were included. PCOS patients had impaired glucose and lipid metabolism, higher liver enzymes and LFS. Both NAFLD (33.6%) and MAFLD (42.8%) was more prevalent in PCOS patients than in controls (4.2%, P < 0.001). Logistic regression results showed that HOMA-IR ≥ 3.54 and ALT ≥ 18.2 were independently associated with NAFLD (P < 0.001) and MAFLD (P ≤ 0.001). The prevalence of NAFLD was significantly higher in PCOS patients with free androgen index (FAI) > 8 (53.8% versus 17.4%, P < 0.001) and BMI ≥ 24 kg/m2 (57.3%, 11.3%, P < 0.001).ConclusionThe prevalence of NAFLD/MAFLD in PCOS patients was significantly higher than that in healthy controls and was independently associated with HOMA-IR and ALT. PCOS patients with overweight and elevated FAI have a higher prevalence of fatty liver.

A follow up on the feasibility after national implementation of magnesium sulfate for neuroprotection prior to preterm birth.

The risk for brain injury manifested as cerebral palsy is higher in very preterm born children than in term. Prenatal administration of magnesium sulfate (MgSO4 ) has been shown to be neuroprotective and reduces the proportion of very preterm born children later diagnosed with cerebral palsy. A Swedish national clinical practice guideline was implemented in March 2020, stipulating the administration of a single intravenous dose of 6 g MgSO4 1-24 h prior to delivery before gestational age 32+0, aiming for 90% treatment coverage. The aim of this study was to evaluate the feasibility of this new clinical practice guideline in the first year of its implementation. Data on MgSO4 treatment were collected by reviewing the medical charts of women who gave birth to live born children in gestational age 22+0-31+6 during the period of March 1, 2020 to February 28, 2021, at five Swedish university hospitals. Women with pre-eclampsia, eclampsia, or high elevated liver enzymes low platelets (HELLP) were excluded. A total of 388 women were eligible and 79% received treatment with MgSO4 . Of the 21% not receiving treatment, 9% did not receive treatment due to lack of knowledge about the clinical practice guideline, 9% were not possible to treat and 3% had missing data. The proportion treated increased from 72% to 87% from the first to the last 3 months. Of those treated, 81% received the drug within the stipulated timeframe (mean 8.7 h, median 3.4 h). There was a positive trend over time in the proportion of women receiving MgSO4 treatment, but the a priori target of 90% was not reached during the first year of implementation. Our findings indicate that this target could be reached with additional information to clinicians.

Impact of PNPLA3 I148M on alpha-1 antitrypsin deficiency-dependent liver disease progression.

Genetic risk factors are major determinants of chronic liver disease (CLD) progression. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M polymorphism and alpha-1 antitrypsin (AAT) E342K variant, termed PiZ, are major modifiers of metabolic CLD. Both variants are known to affect metabolic CLD through increased endoplasmic reticulum stress, but their combined effect on CLD progression remains largely unknown. Here, we aimed to test our working hypothesis that their combined incidence triggers CLD disease progression. We showed that patients with PiZZ/PNPLA3 I148M from the European alpha-1-antitrypsin deficiency (AATD) liver consortium and the UK Biobank had a trend towards higher liver enzymes, but no increased liver fat accumulation was evident between subgroups. After generating transgenic mice that overexpress the PiZ variant and simultaneously harbor the PNPLA3 I148M knockin (designated as PiZ/PNPLA3 I148M ), we observed that animals with PiZ and PiZ/PNPLA3 I148M showed increased liver enzymes compared to controls during aging. However, no significant difference between PiZ and PiZ/PNPLA3 I148M groups was observed, with no increased liver fat accumulation over time. To further study the impact on CLD progression, a Western-styled diet was administered, which resulted in increased fat accumulation and fibrosis in PiZ and PiZ/PNPLA3 I148M livers compared to controls, but the additional presence of PNPLA3 I148M had no impact on liver phenotype. Notably, the PiZ variant protected PNPLA3 I148M mice from liver damage and obesity after Western-styled diet feeding. Our results demonstrate that the PNPLA3 polymorphism in the absence of additional metabolic risk factors is insufficient to drive the development of advanced liver disease in severe AATD.

Sustained weight loss with semaglutide once weekly in patients without type 2 diabetes and post-bariatric treatment failure.

About 20%-25% of patients experience weight regain (WR) or insufficient weight loss (IWL) following bariatric surgery (BS). Therefore, we aimed to retrospectively assess the effectiveness of adjunct treatment with semaglutide in patients without type 2 diabetes (T2D) with post-bariatric treatment failure over a 12 months period. Post-bariatric patients without T2D with WR or IWL (n = 29) were included in the analysis. The primary endpoint was weight loss 12 months after initiation of adjunct treatment. Secondary endpoints included change in body mass index, HbA1c, lipid profile, high sensitive C-reactive protein and liver enzymes. Total weight loss during semaglutide treatment added up to 14.7% ± 8.9% (mean ± SD, p < .001) after 12 months. Categorical weight loss was >5% in 89.7% of patients, >10% in 62.1% of patients, >15% in 34.5% of patients, >20% in 24.1% of patients and > 25% in 17.2% of patients. Adjunct treatment with semaglutide resulted in sustained weight loss regardless of sex, WR or IWL and type of surgery. Among patients with prediabetes (n = 6), 12 months treatment led to normoglycemia in all patients (p < .05). Treatment options to manage post-bariatric treatment failure are scarce. Our results imply a clear benefit of adjunct treatment with semaglutide in post-bariatric patients over a 12 months follow-up period.

Thermoneutral housing does not accelerate metabolic dysfunction-associated fatty liver disease in male or female C57Bl/6J mice fed a Western diet.

Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a growing cause of mortality and morbidity and encompasses a spectrum of liver pathologies. Although dozens of preclinical models have been developed to recapitulate stages of MAFLD, few achieve fibrosis using an experimental design that mimics human pathogenesis. We sought to clarify whether the combination of thermoneutral (TN) housing and consumption of a classical Western diet (WD) would accelerate the onset and progression of MAFLD. Male and female C57Bl/6J mice were fed a nutrient-matched low-fat control or Western diet (WD) for 16 wk. Mice were housed with littermates at either standard temperature (TS; 22°C) or thermoneutral-like conditions (TN; ∼29°C). Male, but not female, mice housed at TN and fed a WD were significantly heavier than TS-housed control animals. WD-fed mice housed under TN conditions had lower levels of circulating glucose compared with TS mice; however, there were select but minimal differences in other circulating markers. Although WD-fed TN males had higher liver enzyme and higher liver triglyceride levels, no differences in markers of liver injury or hepatic lipid accumulation were observed in females. Housing temperature had little effect on histopathological scoring of MAFLD progression in males; however, although female mice retained a level of protection, WD-TN conditions trended toward a worsened hepatic phenotype, which was associated with higher macrophage transcript expression and content. Our results indicate that interventions coupling TN housing and WD-induced MAFLD should be longer than 16 wk to accelerate hepatic steatosis and increase inflammation in both sexes of mice.NEW & NOTEWORTHY Mouse models leading to accelerated fatty liver onset are a useful translational tool. Here we show that coupling thermoneutral-like housing and Western diet feeding in mice for 16 wk does not lead to significant disease progression in either sex, though the molecular phenotype indicates priming of immune-related and fibrotic pathways.

Thoracic lymphatic anomalies in patients with univentricular hearts: correlation of morphologic findings in isotropic T2-weighted MRI with the outcome after fontan palliation.

In this study we examined the correlation between the extent of thoracic lymphatic anomalies in patients after surgical palliation by total cavopulmonary connection (TCPC) and their outcome in terms of clinical and laboratory parameters. We prospectively examined 33 patients after TCPC with an isotropic heavily T2-weighted MRI sequence on a 3.0 T scanner. Examinations were performed after a solid meal, slice thickness of 0.6 mm, TR of 2400 ms, TE of 692 ms, FoV of 460 mm, covering thoracic and abdominal regions. Findings of the lymphatic system were correlated with clinical and laboratory parameters obtained at the annual routine check-up. Eight patients (group 1) showed type 4 lymphatic abnormalities. Twentyfive patients (group 2) presented less severe anomalies (type 1-3). In the treadmill CPET, group 2 reached step 7.0;6.0/8.0 vs. 6.0;3.5/6.8 in group 1 (p = 0.006*) and a distance of 775;638/854 m vs. 513;315/661 m (p = 0.006*). In the laboratory examinations, group 2 showed significantly lower levels of AST, ALT and stool calprotectin as compared to group 1. There were no significant differences in NT-pro-BNP, total protein, IgG, lymphocytes or platelets, but trends. A history of ascites showed 5/8 patients in group 1 vs. 4/25 patients in group 2 (p = 0.02*), PLE occurred in 4/8 patient in group 1 vs. 1/25 patients in group 2 (p = 0.008*). In the long-term follow-up after TCPC, patients with severe thoracic and cervical lymphatic abnormalities showed restrictions in exercise capacity, higher liver enzymes and an increased rate of symptoms of imminent Fontan-failure such as ascites and PLE.

Genetic variation and elevated liver enzymes during childhood, adolescence and early adulthood.

Genetic factors influence the risk of fatty liver disease (FLD) in adults. The aim of this study was to test if, and when, genetic risk factors known to affect FLD in adults begin to exert their deleterious effects during childhood, adolescence and early adulthood. We included up to 4018 British children and adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Three genetic variants known to associate robustly with FLD in adults (PNPLA3 rs738409, TM6SF2 rs58542926 and HSD17B13 rs72613567) were tested for association with plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST) during childhood (mean age: 9.9 years), early adolescence (15.5 years), late adolescence (17.8 years), and early adulthood (24.5 years). We also tested the associations of a 17-variant score and whole-genome polygenic risk scores (PRS) derived from associations in adults with plasma ALT and AST at the same four time points. Associations with elastography-derived liver steatosis and fibrosis were tested in early adulthood. Genetic risk factors for FLD (individually, combined into a 3-variant score, a 17-variant score and as a genome-wide PRS), were associated with higher liver enzymes, beginning in childhood and throughout adolescence and early adulthood. The ALT-increasing effects of the genetic risk variants became larger with increasing age. The ALT-PRS was associated with liver steatosis in early adulthood. No genetic associations with fibrosis were observed. Genetic factors that promote FLD in adults associate with elevated liver enzymes already during childhood, and their effects get amplified with increasing age.

Analysis of Biochemical and Inflammatory Markers for Predicting COVID-19 Severity: Insights From a Tertiary Healthcare Institution of Eastern India.

Background Coronavirus disease-19 (COVID-19) patients often deteriorate rapidly based on viral infection-related inflammation and the subsequent cytokine storm. The clinical symptoms were found to be inconsistent with laboratory findings. There is a need to develop biochemical severity score to closely monitor COVID-19 patients. Methods This study was conducted in the department of biochemistry at All India Institute of Medical Sciences (AIIMS) Bhubaneswar in collaboration with the intensive care unit. Laboratory data of 7,395 patients diagnosed with COVID-19 during the first three waves of the pandemic were analyzed. The serum high sensitivity high-sensitivity C-reactive protein (hs-CRP, immuno-turbidity method), lactate dehydrogenase (LDH, modified Wacker et al. method), and liver enzymes (kinetic-UV method) were estimated by fully automated chemistry analyzer. Serum ferritin and interleukin-6 (IL-6) were measured by one-step immunoassay using chemiluminescence technology. Three models were used in logistic regression to check for the predictive potential of biochemical parameters, and a COVID-19 biochemical severity score was calculated using a non-linear regression algorithm. Results The receiver operating characteristic curve found age, urea, uric acid, CRP, ferritin, IL6, and LDH with the highest odds of predicting ICU admission for COVID-19 patients. COVID-19 biochemical severity scores higher than 0.775were highly predictive (odds ratio of 5.925) of ICU admission (AUC=0.740, p<0.001) as compared to any other individual parameter. For the validation, 30% of the total dataset was used as testing data (n=2095) with a sensitivity of 68.3%, specificity of 74.5%, and odds ratio of 6.304. Conclusion Age, urea, uric acid, ferritin, IL6, LDH, and CRP-based predictive probability algorithm calculating COVID-19 severity was found to be highly predictive of ICU admission for COVID-19 patients.

The Frequency of Abnormally High Liver Enzymes and their Connection to Type 2 Diabetes Mellitus

Objective: The purpose of this research is to measure liver enzyme activity in Pakistani people with type 2 diabetes. Study Design: Cross sectional Place and Duration: The study was conducted in department of Pathology Women Medical&amp; Dental College Abbottabad from January 2022 to June 2022. Methods: 400 people were enlisted for the study (200 in the healthy control group I, and another 200 with type 2 diabetes). Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were assessed, as was body mass index (BMI). We also checked total protein (TP), albumin, and fasting blood glucose (FBG), and we tested glycosylated haemoglobin (HbA1c). Averages and standard deviations were used to describe quantitative data, whereas frequencies were used to characterize qualitative information. Tests for associations, significance, and correlations between groups were conducted using the Pearson/Spearman correlation test, the unpaired t-test, and the Chi-squared test. Statistical significance was defined as a P-value less than.05. Each piece of information was put via SPSS 24.0 for statistical analysis. Results: Among 200 patients of Type 2 DM females were higher in numbers than males. Type 2 DM patients had a mean age of 48.8 years (SD 11.12), whereas the healthy population had a mean age of 40.6 years (SD 11.3) (P .0001). AST activity in Type 2 DM was found to be similar to that of healthy individuals (P =.060). Type 2 DM is associated with elevated levels of ALT, total bilirubin, and alkaline phosphatase when compared to healthy controls (P .0001). Hepatic enzyme levels were abnormal in 60% of those with type 2 diabetes compared to 30% of those without the disease. Conclusion: Liver function tests (LFTs) were shown to be significantly abnormal in the diabetic community as a whole, demonstrating widespread co-existing derangements. It is possible that early diagnosis and therapy might benefit from a thorough workup in such patients. Furthermore, reducing liver-related morbidity and mortality in Type 2 DM would benefit from early diagnosis and therapy of aberrant liver parameters. Keywords: Liver Hepatic pathology, Diabetes mellitus type 2, Liver function tests