Higher Alanine Aminotransferase Levels Research Articles

Irisin as a marker of hepatic steatosis in children with metabolic dysfunction-associated steatotic liver disease.

The purpose of this study was to evaluate irisin, myonectin and high-sensitivity interleukin-6 (hs IL-6) levels in obese children and adolescents and to determine the association of these parameters with metabolic dysfunction-associated steatotic liver disease (MASLD) in children. Sixty-one overweight/obese children with suspected liver disease and seventeen healthy controls were included in the study. MASLD was diagnosed according to the latest consensus. Circulating irisin, myonectin and hs IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). The study group included 38 children meeting MASLD criteria and 23 children without diagnosed hepatic steatosis. The concentrations of the analysed myokines were comparable in the MASLD and non-MASLD groups. Patients with MASLD were further divided according to the severity of hepatic steatosis. Significantly higher levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase, uric acid and irisin were observed in patients with severe hepatic steatosis compared to mild hepatic steatosis. There were borderline statistically significant positive correlations of irisin with ALT and AST. We revealed that elevated irisin levels were associated with the degree of hepatic steatosis in MASLD. We also found a borderline significant positive association of irisin with liver enzymes.

7055 Metabolic Disorders In Thalidomide Embryopathy

Abstract Disclosure: A. Tanabe: None. Thalidomide embryopathy (TE) is a congenital limb defect that occurs in neonates born to pregnant women who have taken thalidomide. Typical abnormalities of the TE are upper limb hypoplasia and and/or auditory dysfunction. In Japan, thalidomide was marketed as an agent for sleep-induce and digestive ulcers from 1958 to 1962. Up to now, approximately 290 cases have been certified and are supported by the government as drug-induced disease. Currently, many of the victims are in their late 50s, and in addition to congenital disabilities, various health issues such as lifestyle-related diseases can be developed. We investigated their metabolic condition using data of medical health checkup between 2017 and 2018. Fifty-one Japanese cases of TE (28 men and 23 women) were included in this study. The mean age was 56.4±1.6 years in men and 55.9±1.2 years in women. The prevalence of upper limb deformities was 64% in men and 74% in women; the remaining patients had only hearing impairment. The mean body mass index (BMI) was 22.7±2.1 in men and 22.5±4.0 in women. Eleven percent of men and 17% of women had a BMI between 25-30, while 9% of women and no men had a BMI of 30 or greater. Liver dysfunction was seen in 32% of men and 9% of women. The mean high-density lipoprotein cholesterol level was 60±17 mg/dL in men and 68±18 mg/dL in women. The mean low-density lipoprotein (LDL) cholesterol level was 120±28 mg/dL in men and 136±35 mg/dL in women, with 25% of men and 48% of women had LDL level of 140 mg/dL or greater. The mean triglyceride (TG) level was 144±85 mg/dL in men and 116±61 mg/dL in women, with 43% of men and 17% of women had a level of 150 mg/dL or greater. The mean HbA1c level was 6.0±1.0% in men and 5.9±0.4% in women. The prevalence of impaired glucose tolerance was 25% in men and 13% in women. Fatty liver (FL) evaluated by ultrasonography or CT scan was 61% in men and 39% in women. The patients with FL showed significantly high body fat percentage and TG level in men, high alanine aminotransferase, γ-glutamyl transpeptidase and TG levels in women, respectively, compared to the patients without FL. The prevalence of hypertriglyceridemia was significantly higher in men with FL compared with men without FL. There was no significant difference in with or without the upper limb abnormalities in both groups. Although without obvious overweight, more than 40 % of the patients had dyslipidemia and 50% of the patients had FL. The limb abnormalities can result in movement limitations however other factors may be involved in the development of metabolic disorders in TE. The results of this study provide valuable information for future health management in thalidomide embryopathy. (This study was conducted by a research grant from the National Center for Global Health and Medicine, Japan: 21A1015 and a Grant-in-Aid from the Ministry of Health, Labour, and Welfare, Japan: 20KC2005, 23KC2017). Presentation: 6/2/2024

E3 Ubiquitin Ligase Smurf1 Regulates the Inflammatory Response in Macrophages and Attenuates Hepatic Damage during Betacoronavirus Infection.

The E3 ubiquitin ligase Smurf1 catalyzes the ubiquitination and proteasomal degradation of several protein substrates related to inflammatory responses and antiviral signaling. This study investigated the role of Smurf1 in modulating inflammation induced by Betacoronavirus infection. Bone marrow-derived macrophages (BMDMs) from C57BL/6 (wild-type) or Smurf1-deficient (Smurf1-/-) mice were infected with MHV-A59 to evaluate the inflammatory response in vitro. Smurf1 was found to be required to downregulate the macrophage production of pro-inflammatory mediators, including TNF, and CXCL1; to control viral release from infected cells; and to increase cell viability. To assess the impact of Smurf 1 in vivo, we evaluated the infection of mice with MHV-A59 through the intranasal route. Smurf1-/- mice infected with a lethal inoculum of MHV-A59 succumbed earlier to infection. Intranasal inoculation with a 10-fold lower dose of MHV-A59 resulted in hematological parameter alterations in Smurf1-/- mice suggestive of exacerbated systemic inflammation. In the lung parenchyma, Smurf1 expression was essential to promote viral clearance, downregulating IFN-β mRNA and controlling the inflammatory profile of macrophages and neutrophils. Conversely, Smurf1 did not affect IFN-β mRNA regulation in the liver, but it was required to increase TNF and iNOS expression in neutrophils and decrease TNF expression in macrophages. In addition, Smurf1-/- mice exhibited augmented liver injuries, accompanied by high serum levels of alanine aminotransferase (ALT). These findings suggest that Smurf1 plays a critical role in regulating the inflammatory response in macrophages and attenuating systemic inflammation during Betacoronavirus infection.

Clinical characteristics and outcomes of neonatal SARS-CoV-2 infection after the release of the epidemic situation of COVID-19

BackgroundWith the release of the coronavirus disease 2019 (COVID-19) pandemic in late 2022 in China, the number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) roared, including neonatal cases. However, there were few studies on neonatal COVID-19, especially multi-center case reports. This study aimed to explore clinical characteristics and short-term outcomes of neonatal COVID-19 in China.MethodsWe reviewed 187 cases of neonatal COVID-19 between December 11, 2022, and January 12, 2023. The diagnosis was assessed by symptoms, laboratory tests, X-ray manifestations, and diagnosis code. Clinical characteristics and outcomes were evaluated.ResultsIn 187 neonatal cases with COVID-19, 84 (44.9%) had severe SARS-CoV-2 infection. Most patients had confirmed exposure to SARS-CoV-2. Fever and respiratory symptoms were common (75.4% and 71.7%, respectively). Severe patients were more likely to have high alanine transaminase (ALT) (> 40U/L) (11.9% vs. 3.9%) and high N-terminal pro-brain natriuretic peptide (NT-proBNP) (> 2000pg/mL) (38.0% vs. 19.6%), compared with nonsevere ones (P < 0.05). None of the patients received COVID-19-specific medical interventions. A few severe patients received corticosteroids (1.1%), and immunoglobulin (0.5%), respectively. All patients were discharged home after the medical care with a median length of stay (LOS) of four days and none of them met the criteria of multisystem inflammatory syndrome in neonates (MIS-N).ConclusionsAfter the release of the epidemic situation of COVID-19 in late 2022 in China, more neonatal cases with severe COVID-19 had high ALT and NT-proBNP level. Few specific medical interventions were given, and the outcome was satisfying.

Bovine lactoferrin alleviates aflatoxin B1 induced hepatic and renal injury in broilers by mediating Nrf2 signaling pathway

Aflatoxin B1 (AFB1) a mycotoxin found in chicken feed that possess a global hazard to poultry health. However different potent compounds like bovine lactoferrin (bLF) may prove to be protective effects against AFB1. This study aims to explore the protective effect of bLF against AFB1-induced injury in the liver and kidney in broiler. For this purpose, 600 broilers chicks were randomly alienated into five groups (n=120 each): negative control; positive control (3mg/kg AFB1), and bLF high, medium, and low dosage groups (600 mg/kg, 300 mg/kg, and 150 mg/kg, respectively). The results highlight that AFB1 toxicity in birds exhibited low feed intake, reduction in weight gain, and a decrease in FCR while, bLF regulated these adverse effects. Meanwhile, AFB1 group showed higher levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) and lower levels of superoxide dismutase (SOD) and glutathione (GSHpx) in liver, while urea and creatinine were decline in kidney. Supplementation with bLF effectively controlled these biomarkers and control the negative effects of toxicity. Furthermore, hematoxylin and eosin (H&E) staining exhibited normal morphological structures within liver and kidney in the bLF treated groups, while degenerative changes were observed in AFB1 group. Similarly, bLF, decreased oxidative stress and thus prevented apoptosis in the liver and kidney cells of the birds. Whereas, mRNA level of mitochondrial apoptosis related gene including Bcl-2 (Bak and Bax), caspase-3 and caspase-9 was upregulated, while bcl2 gene were downregulated in AFB1 group. Dietary supplementation of bLF effectively normalizes the expression of these genes. AFB1 exposed birds shown to decrease gene expression level of the crucial component of Nrf2 pathway, responsible to regulate antioxidant defense. Interestingly, bLF reverse these detrimental effects of and restore the normal expression levels of Nrf2 pathway. Conclusively, our findings demonstrate that bLF mitigates the detrimental effects of AFB1, besides regulation of the apoptosis-related genes via mitochondrial pathways. These findings validate that the bLF (600 mg/kg) could be used as protective agent against AFB1-induced liver and kidney damage.

Demographic Factors, Biochemical Markers, and Obstetric History Associated with the Risk of Preeclampsia in a Sudanese Population Sample

Background: Preeclampsia significantly contributes to maternal and perinatal illness and death, particularly in low and middle-income countries like Sudan. It is classified by onset timing (early vs. late) and severity (mild vs. severe) and is one of the four hypertensive disorders in pregnancy, including chronic hypertension, gestational hypertension, and chronic hypertension with superimposed preeclampsia. This study aimed to evaluate the demographic, clinical, and biochemical predictors of preeclampsia among Sudanese women. Methods: This case-control study involved 100 women diagnosed with preeclampsia and 100 healthy pregnant women who acted as the control group at Omdurman Maternity Hospital in Khartoum State, Sudan, from 2019 to 2021. Data on sociodemographic characteristics, obstetric history, and biochemical markers, including platelet counts, were collected using a comprehensive questionnaire and blood sample analysis. Results: Women with preeclampsia were more frequently over the age of 40 (OR=9.33, 95% CI: 4.54-19.19, p &lt; 0.001) and had a longer median duration of marriage (OR=2.9, 95% CI: 1.51-5.58, p=0.001). Lower educational levels (p=0.008) and being housewives (p=0.024) were also more prevalent in the preeclampsia group. Clinically, headache (OR=18.98, 95% CI: 2.44-147.5, p=0.005) and blurring of vision (OR=25.83, 95% CI: 1.17-572.6, p=0.04) were more prevalent in women with preeclampsia. Biochemical markers showed lower platelet counts (p=0.002), higher levels of alanine aminotransferase (ALT) (OR=2.23, 95% CI: 1.51-3.28, p &lt; 0.001) and creatinine (OR=16.76, 95% CI: 2.31-121.5, p=0.005), while aspartate aminotransferase (AST) was not significantly associated with preeclampsia. Conclusion: Family history of preeclampsia was the most significant predictor. Other important risk factors included older age, longer duration of marriage, lower education levels, headache, blurring of vision, and higher levels of alanine aminotransferase (ALT) and creatinine.

Establishment of Reference Intervals for Common Renal and Liver Function Parameters in Healthy Adults in Mogadishu, Somalia: A Cross-Sectional Study.

Reference intervals (RIs) are crucial for the accurate interpretating of laboratory test results in clinical settings, serving as benchmarks for evaluating individual health status. This study investigates the influence of sex and age on common liver function tests (LFTs) and renal function tests (RFTs) in healthy adults in Mogadishu, Somalia. A community-based cross-sectional study was carried out from October 2022 to January 2023 on a randomly selected sample of 255 healthy participants from Mogadishu, Somalia. Approximately 5 mL of whole blood was collected from each participant and processed screening of hepatitis B and C, and human immunodeficiency virus, and then biochemical analyses were conducted for common liver and kidney parameters. The study found significant sex and age-related differences in the measured LFTs and RFTs parameters. For LFTs, males had higher levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared to females (ALT: 11.5 vs 7.5 U/L; AST: 25.5 vs 19.1 U/L; both p < 0.001). Age-related differences were also observed, with individuals aged 30 and above had higher levels of ALT and AST compared to those aged 18-29 (ALT: 10.9 vs 8.5 U/L; AST: 24.3 U/L vs 21.0 U/L, both p < 0.001). For RFTs, males had higher levels of creatinine (0.9 vs 0.7 mg/dL), urea (23.1 vs 16.1 mg/dL), and uric acid (5.2 vs 4.2 mg/dL) than females, all with p < 0.001. The study established population specific RIs for common liver and renal function parameters and revealed significant variations across sex and age groups. These findings underscore the importance of developing and using local RIs to ensure accurate clinical interpretation and effective patient management. Further research with larger sample sizes and in diverse regions of Somalia is highly recommended.

Efficacy of steroid therapy for improving native liver survival after pediatric acute liver failure with immune activation.

Recent evidence suggests that acute liver failure (ALF) in some patients may reflect a dysregulated immune response, and that corticosteroids improve survival of the native liver in ALF patients with high serum alanine aminotransferase levels, which are an indication of liver inflammation. However, it is unclear whether steroids are effective for pediatric acute liver failure (PALF). The aim of this retrospective case-control study is to examine whether steroid therapy for PALF accompanied by immune activation improves the survival of native liver and to identify factors that predict responses to steroid treatment. Of 38 patients with PALF treated at Kyoto University Hospital from February 2006 to August 2022, 19 receiving steroids who met the specific criteria for identifying the pathophysiology of immune activity in the liver (the "Steroid group"), and seven steroid-free patients who also met the criteria ("Nonsteroid group") were enrolled. Patients in the "Steroid group" were categorized as "responders" or "nonresponders" according to treatment outcome. Clinical and histological data were analyzed. Survival of the native liver in the Steroid group was significantly higher than that in the Nonsteroid group (68% vs. 0%, respectively; p=0.0052). Nonresponders were significantly younger, with higher Model for End-stage Liver Disease and pediatric end-stage liver disease scores, higher prothrombin time - international normalized ratio, and higher serum ferritin levels than responders. Massive hepatic necrosis was more common in nonresponders. Steroid therapy is effective for PALF patients with liver inflammation; however, liver transplantation should be prioritized for young children with ALF accompanied by severe coagulopathy or massive hepatic necrosis.

Assessing the efficacy of tocotrienol-rich fraction vitamin E in obese children with non-alcoholic fatty liver disease: a single-blind, randomized clinical trial

BackgroundChildhood obesity is a growing concern, and non-alcoholic fatty liver disease (NAFLD) is a significant consequence. Currently, there are no approved drugs to treat NAFLD in children. However, a recent study explored the potential of vitamin E enriched with tocotrienol (TRF) as a powerful antioxidant for NAFLD. The aims of the present study were to investigate the effectiveness and safety of TRF in managing children with obesity and NAFLD.MethodsA total of 29 patients aged 10 to 18 received a daily oral dose of 50 mg TRF for six months (January 2020 to February 2022), and all had fatty liver disease were detected by ultrasonography and abnormally high alanine transaminase levels (at least two-fold higher than the upper limits for their respective genders). Various parameters, including biochemical markers, FibroScan, LiverFASt, DNA damage, and cytokine expression, were monitored.ResultsAPO-A1 and AST levels decreased significantly from 1.39 ± 0.3 to 1.22 ± 0.2 g/L (P = 0.002) and from 30 ± 12 to 22 ± 10 g/L (P = 0.038), respectively, in the TRF group post-intervention. Hepatic steatosis was significantly reduced in the placebo group from 309.38 ± 53.60 db/m to 277.62 ± 39.55 db/m (p = 0.048), but not in the TRF group. Comet assay analysis showed a significant reduction in the DNA damage parameters in the TRF group in the post-intervention period compared to the baseline, with tail length decreasing from 28.34 ± 10.9 to 21.69 ± 9.84; (p = 0.049) and with tail DNA (%) decreasing from 54.13 ± 22.1to 46.23 ± 17.9; (p = 0.043). Pro-inflammatory cytokine expression levels were significantly lower in the TRF group compared to baseline levels for IL-6 (2.10 6.3 to 0.7 1.0 pg/mL; p = 0.047 pg/mL) and TNF-1 (1.73 5.5 pg/mL to 0.7 0.5 pg/mL; p = 0.045).ConclusionThe study provides evidence that TRF supplementation may offer a risk-free treatment option for children with obesity and NAFLD. The antioxidant and anti-inflammatory properties of TRF offer a promising adjuvant therapy for NAFLD treatment. In combination with lifestyle modifications such as exercise and calorie restriction, TRF could play an essential role in the prevention of NAFLD in the future. However, further studies are needed to explore the long-term effects of TRF supplementation on NAFLD in children.Trial registrationThe study has been registered with the International Clinical Trial Registry under reference number (NCT05905185) retrospective registration on (15/06/2023).

MicroRNA levels in patients with chronic hepatitis B virus and HIV coinfection in a high-prevalence setting; KwaZulu-Natal, South Africa

BackgroundHepatitis B virus (HBV) and human immunodeficiency virus (HIV) co-infection are significant public health issues, despite the availability of an effective HBV vaccine for nearly three decades and the great progress that has been made in preventing and treating HIV. HBV and HIV both modulate micro-ribonucleic acids (microRNA) expression to support viral replication. The aim of this study was to describe the pattern of microRNA expression in patients coinfected with chronic HBV and HIV with varying disease severity, as indicated by Hepatitis B e antigen (HBeAg) status, HBV viral load, alanine transaminase (ALT) levels, and HIV viral load.MethodsPlasma microRNAs, specific to HBV, were measured by quantitative real-time polymerase chain reaction (qRT-PCR) in HBV and HIV-negative healthy controls (n = 23) and patients coinfected with chronic HBV-HIV (n = 50). MicroRNA expression levels were compared between patients with high vs low HBV viral load, HBeAg positive vs HBeAg negative, high vs low ALT levels, and high vs low HIV viral load. Additionally, HBV viral load, ALT levels, and HIV viral load were correlated with microRNA expression levels.ResultsSignificantly higher expression levels of selected microRNAs were observed in chronic HBV-HIV coinfected patients compared to healthy controls. Significantly higher expression levels of hsa-miR-122-5p, hsa-miR-192-5p, and hsa-miR-193b-3p were observed in patients with high HBV viral load compared with low HBV viral load patients, and the levels of these microRNAs were correlated with HBV viral load levels. Significantly higher levels of hsa-miR-15b-5p and hsa-miR-181b-5p were observed in HBeAg-negative patients.ConclusionThis study demonstrates the potential use of hsa-miR-15b-5p, hsa-miR-122-5p, hsa-miR-181b-5p, hsa-miR-192-5p and hsa-miR-193b-3p as additional diagnostic biomarkers in chronic HBV disease progression.

Prevalence of Non-Alcoholic Fatty Liver Disease and Its Impact on Fibrosis Risk in Inactive Chronic Hepatitis B Patients: Insights from a Cross-Sectional Study.

Background: Chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD) are significant causes of chronic liver disease, potentially leading to liver cirrhosis and hepatocellular carcinoma. Moreover, the coexistence of CHB and NAFLD is increasingly common, although the relationship between NAFLD and inactive CHB infection remains poorly understood. Objectives: This study aimed to investigate the prevalence of NAFLD among patients with inactive CHB, identify risk factors for NAFLD, and determine predictors of significant fibrosis in these patients. Methods: This single-center cross-sectional study targeted patients with inactive CHB at Sultan Qaboos University Hospital from January 2010 to November 2021. Results: A total of 425 patients with inactive CHB were identified, of which 53.1% were male and 62.6% were aged 40-60 years. The prevalence of NAFLD was 47.8%. Various independent factors were associated with NAFLD, including type 2 diabetes mellitus, elevated low-density lipoprotein levels, high hemoglobin levels, low platelet counts, and normal alpha-fetoprotein levels. Significant associations were noted between NAFLD and significant fibrosis, with 10.5% of CHB patients with NAFLD exhibiting significant fibrosis compared to 1.4% of those without NAFLD. Other significant parameters included male gender, increased age, high alanine transaminase levels, elevated hemoglobin, and decreased platelet levels. Conclusions: The high prevalence of NAFLD in patients with inactive CHB and its associations with increased fibrosis and cirrhosis risk underscore the need for comprehensive management strategies for these patients.

Cognitive impairment in patients awaiting kidney and liver transplantation-A clinically relevant problem?

Cognitive impairment (CI) is common in both end-stage kidney disease (ESKD) and alcohol-related liver cirrhosis. The aim of this study was to assess the prevalence and patterns of CI in patients awaiting kidney and liver transplantation, and to identify its determinants. In this cross-sectional, prospective study, 31 consecutive patients with ESKD and 31 consecutive patients with alcohol-related liver cirrhosis, all currently on transplant waiting lists, were screened for cognitive decline using the Addenbrooke's Cognitive Examination. Medical history, demographics, and laboratory test results were also collected. The prevalence of CI among patients with ESKD and alcohol-related liver cirrhosis was 26% and 90%, respectively. In both groups, memory was the most affected cognitive domain, along with verbal fluency in patients with ESKD, and visuospatial abilities in patients with alcoholic cirrhosis. The most statistically significant increase in the prevalence of CI was found in patients with lower educational attainment, in both alcohol-related liver cirrhosis and ESKD populations as well as in older patients with alcoholic cirrhosis. Furthermore, better cognitive functioning in ESKD patients was associated with higher levels of total lymphocyte count and alanine transaminase (ALT), and in alcohol-related liver cirrhosis patients with higher levels of ALT and aspartate transaminase. A nonsignificant trend toward lower memory domain scores was also observed with increasing ammonia levels and increasing severity of liver disease (higher Child-Pugh scores). Finally, suboptimal performance on the screening test was correlated with the severity of liver disease as assessed by the Model for End-Stage Liver Disease Sodium (MELD-Na), but not at the statistically significant level. The prevalence of CI, especially in patients with alcohol-related liver cirrhosis, is high and can be a significant clinical problem, negatively affecting the transplantation process. Routine screening tests in this group would contribute to the implementation of appropriate management, such as rehabilitation program or psychosocial treatments and facilitate the provision of specialized health care.

Association of Beverage Consumption with Cardio-metabolic Risk Factors and Alanine Transaminase Levels in Children and Adolescents: The CASPIAN-V Study.

This study aims to evaluate the association of beverage consumption with cardiometabolic risk factors and alanine transaminase (ALT) levels in children and adolescents. This nationwide study is a part of the fifth survey of a national surveillance program in Iran. Overall, 4200 students, aged 7-18 years, were selected from 30 provinces by multi-stage cluster sampling. In addition to filling in questionnaires, blood sampling and biochemical tests were done. The weekly use of six different beverage types including milk, juice, tea, coffee, soda, and non-alcoholic beer, was documented by interview. The participation rate was 91.5% (n = 3843), and data of 3733 students were complete for the current study. Beverages containing high levels of sugar such as soda and non-alcoholic beer were significantly associated with higher levels of ALT. Model coefficient of regression (SD) was 0.66 (0.31) (P value: 0.034). Healthy beverages such as milk and fresh juice and also beverages containing high levels of caffeine did not have significant association with ALT levels (P value = 0.32, P value = 0.60). Healthy beverages had a significant and inverse relationship with triglycerides (TG) (P value = 0.029), total cholesterol (TC) (P value = 0.008) and low-density lipoprotein (LDL) (P value = 0.008) levels. This study showed that consuming sugar-sweetened beverages is significantly associated with higher levels of ALT, whereas healthy beverages are associated with a better cardiometabolic profile meaning that consuming healthy beverages leads to lower TG, TC, and LDL levels. The effects of beverages on children's health should be emphasized in health recommendations.

Clinical characteristics of pediatric patients hospitalized with community-acquired pneumonia and cytomegalovirus DNA detected in bronchoalveolar lavage fluid.

This study aimed to investigate the clinical characteristics of pediatric patients hospitalized with community-acquired pneumonia (CAP) and concomitant cytomegalovirus (CMV) infection. This cross-sectional study enrolled consecutive pediatric patients admitted with CAP who tested positive for CMV DNA in bronchoalveolar lavage fluid (BALF). Flexible fiberoptic bronchoscopy was performed when routine treatment for CAP proved ineffective. The study participants were further stratified into two groups based on CMV serological test results: recent CMV infection group and CMV replication group. Clinical characteristics were compared between these two groups. Among 124 patients aged 1-11 months included in this study, 80 (64.5%) patients were categorized as having recent CMV infection, and 44 (35.5%) tested positive for CMV replication. Co-infection with other pathogens was detected more frequently in the CMV replication group (n = 29, 65.9%) than in the recent CMV infection group (n = 35, 43.7%; P = 0.018). Patients with recent CMV infection were younger and exhibited higher levels of alanine transaminase (ALT) and aspartate aminotransferase compared to those with CMV replication (all P < 0.05). Multivariable regression analysis showed age was independently associated with recent CMV infection (odds ratio [OR], 0.707; 95% confidence interval [CI], 0.586-0.853; P < 0.001). Notably, receiver operating characteristic curve analysis showed that a CMV PCR level of 3,840 copies/ml in blood samples had a sensitivity of 34.7% and specificity of 90.0% for diagnosis of recent CMV infection with an area under the curve (AUC) of 0.625 (95% CI: 0.513-0.736, P = 0.048). A CMV PCR level of 6,375 copies/ml in urine samples had a sensitivity of 77.1% and specificity of 61.5% for diagnosis of recent CMV infection with an AUC of 0.695 (95% CI: 0.531-0.858, P = 0.04). Furthermore, multivariate linear regression analysis revealed that the blood CMV DNA copy number was associated with ALT (B = 0.001; P < 0.001). The CMV DNA copy numbers in blood and urine could serve as discriminatory markers between recent CMV infection and CMV replication. Measuring CMV DNA levels in blood may be an effective method for monitoring liver function impairment in pediatric patients presenting with CAP and concurrent CMV infection.

Importance of gamma-glutamyl transferase elevation in patients with Fontan-associated liver disease.

In patients with Fontan-associated liver disease (FALD), gamma-glutamyl transferase (GGT) levels are often elevated, however, its clinical importance is unclear. We investigated the relationship between the clinical course of FALD and GGT levels. We enrolled 145 patients with FALD who underwent right-heart catheterization (RHC) and visited our department. Ursodeoxycholic acid (UDCA) was administered to 62 of the patients. Patients with GGT levels <50 and ≥50U/L were compared. Follow-up RHC was undertaken in 76 patients. Cases in which GGT levels decreased by ≥10% or <50U/L were defined as improved (n=33). Patients with GGT levels ≥50U/L had significantly lower levels of albumin and higher levels of alanine transaminase (ALT) but no significant differences in RHC factors. Over a 4.6-year period, 43.4% showed improvement in GGT levels. Improved cases had significantly lower total bilirubin (1.1 vs. 1.6mg/dL), AST (22 vs. 28U/L), and ALT (18 vs. 27U/L) levels than nonimproved cases (n=29, p<0.05), and the change in platelet count (-0.5 vs. -3.0×10-4/μL) was significantly lower in the latter (p=0.03). The improvement rate was significantly higher in UDCA-treated cases (55.2%) with GGT levels ≥50U/L compared to cases not treated with UDCA (18.2%, p=0.04). In cases of FALD with no improvement in GGT level, the platelet count decreased over time, suggesting progression of fibrosis. Physicians should be aware of the importance of a high GGT level in patients with FALD.

PET/CT-Based Absorbed Dose Maps in 90Y Selective Internal Radiation Therapy Correlate with Spatial Changes in Liver Function Derived from Dynamic MRI.

Functional liver parenchyma can be damaged from treatment of liver malignancies with 90Y selective internal radiation therapy (SIRT). Evaluating functional parenchymal changes and developing an absorbed dose (AD)-toxicity model can assist the clinical management of patients receiving SIRT. We aimed to determine whether there is a correlation between 90Y PET AD voxel maps and spatial changes in the nontumoral liver (NTL) function derived from dynamic gadoxetic acid-enhanced MRI before and after SIRT. Methods: Dynamic gadoxetic acid-enhanced MRI scans were acquired before and after treatment for 11 patients undergoing 90Y SIRT. Gadoxetic acid uptake rate (k1) maps that directly quantify spatial liver parenchymal function were generated from MRI data. Voxel-based AD maps, derived from the 90Y PET/CT scans, were binned according to AD. Pre- and post-SIRT k1 maps were coregistered to the AD map. Absolute and percentage k1 loss in each bin was calculated as a measure of loss of liver function, and Spearman correlation coefficients between k1 loss and AD were evaluated for each patient. Average k1 loss over the patients was fit to a 3-parameter logistic function based on AD. Patients were further stratified into subgroups based on lesion type, baseline albumin-bilirubin scores and alanine transaminase levels, dose-volume effect, and number of SIRT treatments. Results: Significant positive correlations (ρ = 0.53-0.99, P < 0.001) between both absolute and percentage k1 loss and AD were observed in most patients (8/11). The average k1 loss over 9 patients also exhibited a significant strong correlation with AD (ρ ≥ 0.92, P < 0.001). The average percentage k1 loss of patients across AD bins was 28%, with a logistic function model demonstrating about a 25% k1 loss at about 100 Gy. Analysis between patient subgroups demonstrated that k1 loss was greater among patients with hepatocellular carcinoma, higher alanine transaminase levels, larger fractional volumes of NTL receiving an AD of 70 Gy or more, and sequential SIRT treatments. Conclusion: Novel application of multimodality imaging demonstrated a correlation between 90Y SIRT AD and spatial functional liver parenchymal degradation, indicating that a higher AD is associated with a larger loss of local hepatocyte function. With the developed response models, PET-derived AD maps can potentially be used prospectively to identify localized damage in liver and to enhance treatment strategies.

Sleep and liver function biomarkers in relation to risk of incident liver cancer: a nationwide prospective cohort study

BackgroundTo assess the largely undetermined separate and joint effects of sleep and liver function biomarkers on liver cancer.MethodsData of 356,894 participants without cancer at baseline in the UK Biobank were analyzed. Sleep score was evaluated using five sleep traits (sleep duration, chronotype, insomnia, snoring, and excessive daytime sleepiness) and dichotomized into healthy or unhealthy sleep. Circulating liver function biomarkers were measured. Cox proportional hazard model was performed to investigate the independent and joint associations of sleep and liver function biomarkers with liver cancer incidence.ResultsAfter a median follow-up time of 13.1 years, 394 cases of incident liver cancer were documented. The multivariable-adjusted hazard ratio (HR) for liver cancer was 1.46 (95% confidence interval: 1.15–1.85) associated with unhealthy sleep (vs. healthy sleep), and was 1.17 (1.15–1.20), 1.20 (1.18–1.22), 1.69 (1.47–1.93), 1.06 (1.06–1.07), 1.08 (1.07–1.09), 1.81 (1.37–2.39), or 0.29 (0.18–0.46) associated with each 10-unit increase in alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total protein (TP), or albumin (ALB), respectively. Individuals with unhealthy sleep and high (≥ median) ALT, AST, TBIL, GGT, ALP, or TP or low (< median) ALB level had the highest HR of 3.65 (2.43–5.48), 4.03 (2.69–6.03), 1.97 (1.40–2.77), 4.69 (2.98–7.37), 2.51 (1.75–3.59), 2.09 (1.51–2.89), or 2.22 (1.55–3.17) for liver cancer, respectively. Significant additive interaction of unhealthy sleep with high TP level on liver cancer was observed with relative excess risk due to an interaction of 0.80 (0.19–1.41).ConclusionsUnhealthy sleep was associated with an increased risk of liver cancer, especially in participants with lower ALB levels or higher levels of ALT, AST, TBIL, GGT, ALP, or particularly TP.

Genotype-phenotype relationship and genetics study of 115 cases with Wilson's disease

Objective: To explore the genotype-phenotype relationship of Wilson's disease (WD) and further study the mutation spectrum in the ATP7B gene. Methods: The clinical data and genetic test results of 115 cases with WD diagnosed in the First Affiliated Hospital of Zhengzhou University from 2015 to 2022 were retrospectively analyzed. The rank sum test was used for quantitative data comparison, and χ(2) test was used for count data comparison. Multivariate logistic regression was used to analyze the relationship between patients' genotype and phenotype. Results: The onset of liver manifestations (hepatic type) accounted for 60.9%, neurological symptoms (cerebral type) for 13.0%, and mixed hepato-cerebral symptoms for 26.1%. Presymptomatic individuals (hepatic types) accounted for 62.9%. Next-generation sequencing- diagnosed WD cases accounted for 87.8%. Combined multiplex ligation-dependent probe amplification assay-diagnosed WD cases accounted for 89.6%. A single case with a detected pathogenic locus accounted for 10.4%. The diagnostic rate of WD by genetic testing combined with clinical data was 100%. A total of 76 ATP7B mutations were detected, and the top three mutation frequencies were c.2333G>T (p.Arg778Leu) (30.7%), c.2975C>T (p.Pro992Leu) (7.3%), and c.2621C>T (p.Ala874Val) (6.4%). The mutations were mainly distributed in exons 8, 11-13, and 15-18, accounting for more than 90% of the total mutations. Eight new mutations were found, including c.3724G>A (p.Glu1242Lys), c.3703G>C (p.Gly1235Arg), c.3593T>C (p.Val1198Ala), c.2494A>C (p.Lys832Gln), c.1517T>A (p.Ile506Lys), c.484G>T (p.Glu162Ter), c.1870-49A>G, and the missing of exons 10-21. Liver histopathology showed cellular edema, degeneration, inflammation, and necrosis, as well as a 42.8% copper staining positive rate. Genotype-phenotype analysis showed that the p.Arg778Leu mutation had higher alanine aminotransferase (ALT) levels than those carrying other mutations (P=0.024), while the homozygous mutation of p.Arg778Leu was associated with cerebral-type patients (P=0.027). Conclusion: Genetic testing plays an important role in the diagnosis of WD. p.Arg778Leu is the first high-frequency mutation in the Chinese population, and patients carrying it have higher ALT levels. The p.Arg778Leu homozygous mutation is prone to causing cerebral-type WD. This study expands the ATP7B gene mutation spectrum.

A retrospective study to determine the correlation among HBV PreS1 antigen, HBV e antigen, alanine aminotransferase, and HBV DNA

Background and aimHepatitis B virus (HBV) infection presents with indicators of varying clinical significance. We aimed to evaluate the correlation among HBV Pre-S1 antigen (HBV PreS1-Ag), HBV e antigen (HBeAg), HBV DNA, and alanine aminotransferase (ALT) levels. MethodsWe retrospectively analyzed 6180 serum samples collected between 2020 and 2022 at the Shanghai General Hospital, China. Data regarding PreS1-Ag, HBeAg, ALT, and HBV DNA were compiled. Correlation analyses and cross-tabulations were employed to explore the diagnostic indicators. ResultsThe detection rates of both antigen indicators showed a proportional increase with HBV DNA loads. The correlation between PreS1-Ag and HBV DNA (r = 0.616) was stronger than that between HBeAg and HBV DNA (r = 0.391). The specificity of PreS1-Ag (84.30 %) was lower than that of HBeAg (97.44 %), whereas the sensitivity of HBeAg (91.13 %) significantly surpassed that of PreS1-Ag (29.56 %). Among the HBV DNA positive patients, 92.04 % tested positive for at least one indicator, which exceeded the rate of PreS1+HBeAg- and PreS1-HBeAg+ (52. 28 % and 68. 56 %, respectively). Only 1.75 % of the patients exhibited double negativity, which was lower than the percentage of patients with single negativity (1.95 % and 12.00 % for PreS1-Ag and HBeAg, respectively). The PreS1 levels correlated with ALT levels (r = 0.317); patients with PreS1-positive status had higher ALT levels than patients with PreS1-negative status. ConclusionPreS1-Ag is a more robust HBV replication indicator than HBeAg. PreS1-Ag displayed high sensitivity, whereas HBeAg demonstrated high specificity. Moreover, PreS1-Ag levels correlated with ALT levels. A combination of these indicators demonstrated dependable clinical value for detecting HBV infection and evaluating liver function.

Genetic and Lifestyle Risk Factors of Metabolic Dysfunction-Associated Fatty Liver Disease and Its Relationship with Premature Coronary Artery Disease: A Study on the Pars Cohort.

The main objective of this study is to identify the risk factors of metabolic dysfunction-associated fatty liver disease (MAFLD) in coronary artery disease (CAD) patients. The present retrospective cohort study is part of the Pars Cohort Study (PCS). The participants were categorized as having MAFLD or not. The pattern of independent variables in patients was compared with those who did not have MAFLD. All variables were retained in the multivariable logistic regression model. Totally, 1862 participants with CAD were enrolled in this study. MAFLD was diagnosed in 647 (40.1%) participants. Gender, diabetes, hypertension, tobacco, opium, alcohol, age, weight, waist circumference, cholesterol, HDL, triglyceride, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were significantly different in MAFLD and non-MAFLD patients. Also, the results of multivariable logistic regression show male gender (OR=0.651, 95% CI: 0.470‒0.902, P value=0.01) and opium consumption (OR=0.563, 95% CI: 0.328‒0.968, P value<0.001) to be negative risk factors of MAFLD occurrence in CAD patients. Having diabetes (OR=2.414, 95% CI: 1.740-3.349, P value<0.001), high waist circumference (OR=1.078, 95% CI: 1.055‒1.102, P value<0.01), high triglyceride (OR=1.005, 95% CI: 1.001‒1.008, P value=0.006), and high ALT (OR=1.039, 95% CI: 1.026‒1.051, P value<0.01) were positive risk factors of MAFLD in CAD patients. Our study found that consuming opium decreases the likelihood of MAFLD in CAD patients, since these patients have decreased appetite and lower body mass index (BMI). On the other hand, female gender, having diabetes, high waist circumference, high triglyceride levels, and high ALT levels increase the probability of MAFLD in CAD patients.