Liver involvement in dengue: A systematic review.

Liver involvement is an unusual yet frequently overlooked dengue complication. Pivotal for an efficient clinical management, the early diagnosis of dengue-associated liver involvement relies on an accurate description of its clinical and biological characteristics, its prognosis factors, its association with severe dengue and its clinical management. We conducted a systematic review by searching PubMed and Web of Science databases for original case reports, cohort and cross-sectional studies reporting the clinical and/or biological features of dengue-associated liver involvement. The study was registered in PROSPERO (CRD42021262657). Of the 2552 articles identified, 167 were included. Dengue-associated liver involvement was characterised by clinical features including abdominal pain, hepatomegaly, jaundice, nausea/vomiting, and an echogenic liver exhibiting hepatocellular necrosis and minimal inflammation. Elevated Aspartate Aminotransferase and Alanine Aminotransferase but also elevated bilirubin, Alkaline Phosphatase, gamma-glutamyl transferase, increased International Normalised Ratio, creatinine and creatine kinase, lower albumin and prolonged prothrombin and activated partial thromboplastin time were prevalent in dengue-associated liver involvement. Cardiovascular and haematological systems were frequently affected, translating in a strong association with severe dengue. Liver involvement was more common in males and older adults. It was associated with dengue virus serotype-2 and secondary infections. Early paracetamol intake increased the risk of liver involvement, which clinical management was mostly conservative. In conclusion, this systematic review demonstrates that early monitoring of transaminases, clinical assessment, and ultrasound examination allow an efficient diagnosis of dengue-associated liver involvement, enabling the early identification and management of severe dengue.

Disruption of hepatic mitochondrial pyruvate and amino acid metabolism impairs gluconeogenesis and endurance exercise capacity in mice.

Exercise robustly increases the glucose demands of skeletal muscle. This demand is met by not only muscle glycogenolysis but also accelerated liver glucose production from hepatic glycogenolysis and gluconeogenesis to fuel mechanical work and prevent hypoglycemia during exercise. Hepatic gluconeogenesis during exercise is dependent on highly coordinated responses within and between muscle and liver. Specifically, exercise increases the rate at which gluconeogenic precursors such as pyruvate/lactate or amino acids are delivered from muscle to the liver, extracted by the liver, and channeled into glucose. Herein, we examined the effects of interrupting hepatic gluconeogenic efficiency and capacity on exercise performance by deleting mitochondrial pyruvate carrier 2 (MPC2) and/or alanine transaminase 2 (ALT2) in the liver of mice. We found that deletion of MPC2 or ALT2 alone did not significantly affect time to exhaustion or postexercise glucose concentrations in treadmill exercise tests, but mice lacking both MPC2 and ALT2 in hepatocytes (double knockout, DKO) reached exhaustion faster and exhibited lower circulating glucose during and after exercise. Use of 2H/1³C metabolic flux analyses demonstrated that DKO mice exhibited lower endogenous glucose production owing to decreased glycogenolysis and gluconeogenesis at rest and during exercise. Decreased gluconeogenesis was accompanied by lower anaplerotic, cataplerotic, and TCA cycle fluxes. Collectively, these findings demonstrate that the transition of the liver to the gluconeogenic mode is critical for preventing hypoglycemia and sustaining performance during exercise. The results also illustrate the need for interorgan cross talk during exercise as described by the Cahill and Cori cycles.NEW & NOTEWORTHY Martino and colleagues examined the effects of inhibiting hepatic gluconeogenesis on exercise performance and systemic metabolism during treadmill exercise in mice. Combined inhibition of gluconeogenesis from lactate/pyruvate and alanine impaired exercise endurance and led to hypoglycemia during and after exercise. In contrast, suppressing either pyruvate-mediated or alanine-mediated gluconeogenesis alone had no effect on these parameters. These findings provide new insight into the molecular nodes that coordinate the metabolic responses of muscle and liver during exercise.

Patients with chronic hepatitis B who have persistently normal alanine aminotransferase or aged < 30 years may exhibit significant histologic damage.

BACKGROUND: The timing of antiviral therapy for chronic hepatitis B (CHB) patients with normal alanine transaminase (ALT) or aged < 30 years is still undetermined. We aimed to elucidate the correlation between liver histology, age, and ALT level in CHB patients and analyze the histological characteristics of the liver among patients with persistently normal ALT or aged < 30 years. METHODS: A retrospective analysis was conducted on 697 treatment-naive CHB patients. Liver biopsies were performed, and significant histological damage was defined as the grade of liver inflammation ≥ G2 and/or fibrosis ≥ S2 based on the Scheuer scoring system. RESULTS: The liver inflammation grades and fibrosis stages correlated positively with age, ALT, AST, GGT levels and negatively with the counts of PLT (all p < 0.050) in HBeAg-positive patients. Higher ALT levels and lower PLT counts were independently associated with significant liver inflammation and fibrosis in both HBeAg-positive and HBeAg-negative patients. Furthermore, among those with persistently normal ALT levels, the incidence of significant liver inflammation and fibrosis were 66.1% and 53.7% in HBeAg-positive groups, and 63.0% and 55.5% in HBeAg-negative groups. Moreover, there was no significant difference in the prevalence of significant liver damage between patients aged < 30 years and those aged ≥ 30 years, in both HBeAg-positive (≥ G2 or ≥ S2: 63.8% vs. 75.8%, p = 0.276) and HBeAg-negative (≥ G2 or ≥ S2: 65.9% vs. 72.5%, p = 0.504) groups, among patients with persistently normal ALT levels. CONCLUSIONS: A considerable proportion of CHB patients with persistently normal ALT, including those below the age of 30 years, exhibited significant histological damage. This highlights the importance of initiating early antiviral therapy for HBV-infected individuals, even in the absence of elevated ALT levels.

Evaluation of clinically relevant serum proteins as biomarkers for monitoring COVID-19 severity, and end-organ damage among hospitalized unvaccinated patients.

BACKGROUND: The extensive variability and conflicting information in Coronavirus Disease 2019 (COVID-19) patient data have made it difficult for the medical community to gain a comprehensive understanding and develop clear, reliable guidelines for managing COVID-19 cases. As the world uncovers the diverse side effects of the pandemic, the pursuit of knowledge about COVID-19 has become crucial. The present study aimed to evaluate some clinically relevant serum proteins, providing analysis of the obtained results to employ them in the diagnosis, prognosis, and disease monitoring among COVID-19 patients. METHODS: Samples were collected from 262 COVID-19 unvaccinated hospitalized patients. Measurement of certain serum proteins, namely C-reactive protein (CRP), ferritin, D-dimer, procalcitonin, interleukin-6 (IL-6), serum creatinine (SCr), alanine transaminase (ALT), aspartate transaminase (AST) was done using standard methods. Statistical analysis was performed on the obtained data and the results were correlated to the severity and prognosis. RESULTS: The calculated Mortality rate was found to be 30% with a higher percentage observed among females. The results showed elevation in serum CRP, ferritin, D-dimer, and procalcitonin in most of the patients, also some patients had elevated SCr, ALT, and AST levels indicating end-organ damage. The statistical analysis displayed a strong correlation between serum levels of CRP and ferritin, between D-dimer and ferritin, and between ferritin and procalcitonin. No significant difference was observed between male and female patients' serum levels of the tested serum proteins. A significant correlation between increased serum procalcitonin and mortality was observed. CONCLUSION: The levels of measured serum proteins were impacted by SARS-CoV-2 infection. Serum ferritin, CRP, D-dimer, and procalcitonin are good predicting tools for end-organ damage and acute kidney impairment in COVID-19. Procalcitonin is a strong indicator of severity and mortality in hospitalized COVID-19 patients.

Elevated serum hepatic transaminases in apical periodontitis individuals.

AIM: Apical periodontitis (AP) is the chronic inflammation of the periradicular tissues in response to root canal infection. Whilst AP has been linked with systemic inflammation and noncommunicable diseases, its potential association with nonalcoholic fatty liver disease (NAFLD) is unknown. We aimed to evaluate the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels as surrogate markers of hepatic injury, and the systemic inflammatory burden in otherwise healthy individuals with and without AP diagnosis. METHODOLOGY: Cross-sectional study. Individuals with AP (n = 30) and healthy controls (n = 29) were recruited. The number, mean diameter (mm) and periapical index of the apical lesions of endodontic origin (ALEO) were assessed. ALT and AST levels (pg/mL) were measured through enzyme-linked immunosorbent assays. The serum levels of TNF-α, IL-4, IL-9, IL-10, IL-17A and IL-22 were evaluated by Multiplex assay. Inferential analysis was performed using t-test or Mann-Whitney tests according to data distribution and linear regression models. Data were analysed with StataV16 (p < .05). RESULTS: ALT and AST levels were significantly higher in individuals with AP compared to controls (p < .05). Serum inflammatory biomarkers showed no significant differences between the study groups. Bivariate and multivariate analyses confirmed that AP diagnosis was independently associated with ALT and AST elevations (p < .05). Additionally, the number of ALEO positively influenced AST levels (p = .002). IL-22 on the other hand, was associated with reduced ALT levels (p = .043). CONCLUSION: AP is associated with higher serum hepatic transaminases ALT and AST, potentially contributing to NAFLD physiopathology in young adults.

The hepatoprotective potentials of Olea europaea L. leaves against carbon tetrachloride-induced hepatic injury in rats.

OBJECTIVE: To examine the therapeutic effects of Olea europaea L. leaves extract on carbon tetrachloride-induced liver injury in rats. Methods: The experimental study was conducted at the Department of Physiology, University of Karachi, Karachi, in July 2021, and comprised Albino Wistar male rats weighing 180-220gm. The animals were divided into control group I, carbon tetrachloride group II, Olea europaea L. + carbon tetrachloride group III and Olea europaea L. group IV. In Vitro model of hepatic toxicity was developed by carbon tetrachloride. A daily dose of 50mg/kg of aqueous extract of olive leaves was administered orally and 0.8ml/kg of carbon tetrachloride was administered twice a week subcutaneously for 28 days. On the 29th day, the animals were sacrificed, and tested for hepatic enzymes, lipid peroxidation markers and histopathology. Data was analysed using SPSS 20. RESULTS: Of the 24 rats, 6(25%) were in each of the 4 groups. Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin levels were significantly reduced (p<0.05) in group II whereas, 4- hydroxynonenal, isoprostane and malondialdehyde levels were significantly increased (p<0.05). However, total antioxidant level increased significantly (p<0.05) in group III compared to group II. Histopathology showed severe liver damage in group II and mild damage in group III. Conclusion: Olea europaea L. leaves extract was found to have profound hepatoprotective effects.

[HBeAg-positive patients hepatic tissue inflammatory activity and influencing factors during normal ALT and indeterminate phases].

Objective: To analyze the hepatic tissue inflammatory activity and influencing factors in HBeAg-positive patients during normal alanine aminotransferase (ALT) and indeterminate phases so as to provide a basis for evaluating the disease condition. Methods: Patients with HBeAg-positive with normal ALT and HBV DNA levels below 2 × 10(7) IU/ml from January 2017 to December 2021 were selected as the study subjects. A histopathologic liver test was performed on these patients. Age, gender, time of HBV infection, liver function, HBsAg level, HBV DNA load, genotype, portal vein inner diameter, splenic vein inner diameter, splenic thickness, and others of the patients were collected. Significant influencing factors of inflammation were analyzed in patients using logistic regression analysis, and its effectiveness was evaluated using receiver operating characteristic (ROC) curves. Results: Of the 178 cases, there were 0 cases of inflammation in G0, 52 cases in G1, 101 cases in G2, 24 cases in G3, and one case in G4. 126 cases (70.8%) had inflammatory activity ≥ G2. Infection time (Z=-7.138, P<0.001), γ-glutamyltransferase (t =-2.940, P=0.004), aspartate aminotransferase (t =-2.749, P=0.007), ALT (t =-2.153, P=0.033), HBV DNA level (t =-4.771, P=0.010) and portal vein inner diameter (t =-4.771, P<0.001) between the ≥G2 group and < G2 group were statistically significantly different. A logistic regression analysis showed that significant inflammation in liver tissue was independently correlated with infection time [odds ratio (OR)=1.437, 95% confidence interval (CI): 1.267-1.630; P<0.001)] and portal vein inner diameter (OR=2.738, 95% CI: 1.641, 4.570; P<0.001). The area under the curve (AUROC), specificity, and sensitivity for infection time and portal vein inner diameter were 0.84, 0.71, 0.87, 0.72, 0.40, and 0.95, respectively. Conclusion: A considerable proportion of HBeAg-positive patients have inflammation grade ≥G2 during normal ALT and indeterminate phases, pointing to the need for antiviral therapy. Additionally, inflammatory activity has a close association with the time of infection and portal vein inner diameter.

[Strategic considerations in health economics for the complete treatment of patients with chronic HBV infection].

The World Health Organization (WHO) released the Global Health Sector Strategy 2016, which explicitly proposes a 90% reduction in the new hepatitis B virus (HBV) infection rate and a 65% reduction in HBV-related mortality by 2030. However, at present, there are still 296 million chronic hepatitis B virus-infected patients worldwide, and nearly 900,000 patients die every year from cirrhosis and liver cancer caused by HBV infection. Antiviral treatment for chronic hepatitis B virus infection can effectively inhibit HBV replication, reduce liver inflammation and necrosis, effectively block and reverse liver fibrosis, and even early cirrhosis, thereby lowering cirrhosis-related complications, liver cancer, and liver disease-related mortality. Although the domestic and foreign guidelines have gradually eased antiviral treatment indications for chronic hepatitis B, there are still a considerable number of chronic hepatitis B patients with nonconformity who cannot receive antiviral treatment because they do not meet the existing standards, resulting in the progression of more severe diseases. This study analyzed the prevalence of hepatitis B, the therapeutic effect of antiviral drugs, domestic and international guideline treatment standards, the assessment of key indicators changes in the guidelines, comprehensively considered the coverage rate and treatment standards for antiviral treatment, and explored the changes in disease burden and cost-effectiveness following increasing the coverage rate and reducing treatment thresholds in order to achieve the global strategic goal of eliminating hepatitis B as soon as possible as a public health threat.

Low ALT Is Associated with IBD and Disease Activity: Results from a Nationwide Study.

Background: Sarcopenia is underdiagnosed in patients with inflammatory bowel disease (IBD). Low alanine transaminase (ALT) is associated with sarcopenia. We evaluated the association between low ALT and the presence of IBD and disease activity. Methods: Data were collected from a national Israeli health insurer cohort comprising 976,615 patients. Patients with a diagnosis of IBD were compared to healthy controls. After exclusion of patients with liver disease, ALT > 40 IU/L and age < 18, a total of 233,451 patients were included in the analysis. Low ALT was defined as <10 IU/L. Results: Low ALT was more common amongst patients with IBD than in healthy controls (7.76% vs. 5.7% p < 0.001). Low ALT was found in 148 (7.9%) of the patients with CD and 69 (6.9%) of the patients with UC. For CD, low ALT was associated with increased fecal calprotectin (FC) and CRP (223.00 µg/mg [63.45-631.50] vs. 98.50 [31.98-324.00], p < 0.001, 9.10 mg/L [3.22-19.32] vs. 3.20 [1.30-8.30], p < 0.001) and decreased albumin and hemoglobin (3.90 g/dL [3.60-4.20] vs. 4.30 [4.00-4.50], p < 0.001,12.20 g/dL [11.47-13.00] vs. 13.60 [12.60-14.70], p < 0.001). For UC, low ALT was associated with higher FC and CRP (226.50 µg/mg [143.00-537.00] vs. 107.00 [40.85-499.50], p = 0.057, 4.50 mg/L [1.90-11.62] vs. 2.30 [1.00-6.20], p < 0.001) and with lower albumin and hemoglobin (4.00 g/dL [3.62-4.18] vs. 4.30 [4.10-4.40], p < 0.001, 12.40 g/dL [11.60-13.20] vs. 13.60 [12.60-14.60], p < 0.001). These findings remained consistent following multivariate regression and in a propensity score-matched cohort. Conclusions: Low ALT is more common in patients with IBD and is associated with biochemical disease activity indices.

Glucose and lipid-related indicators in relation to elevated alanine aminotransferase in a pediatric population.

OBJECTIVES: To determine the associations between various glucose and lipid-related indicators with elevated alanine aminotransferase (ALT) in pediatric population. METHODS: We analyzed the cross-sectional data of 3,771 Iranian children and adolescents aged 7-18 years using the fifth survey of a national school-based surveillance program. The predictive power of 11 different glucose and lipid-related indicators for predicting elevated ALT was examined using receiver operating characteristic (ROC) curve. RESULTS: In the total sample non-HDL-C, non-HDL-C/HDL-C, and TC/HDL-C showed the largest area under the curve (AUC) for elevated ALT detection, with 0.731 (cut-off, 129.5 mg/dL), 0.706, and 0.706, respectively. In girls, non-HDL-C had the highest predictive value (AUC, 0.741, cut-off, 129.5 mg/dL). Among boys, non-HDL-C/HDL-C and TC/HDL-C showed the largest AUC of 0.753 with optimum cut-off values of 2.63 and 3.63, respectively. CONCLUSIONS: The findings of this study suggest that non-HDL-C, non-HDL-C/HDL-C, and TC/HDL-C can be predictors of elevated ALT in the pediatric population. These indices can be useful in large population-based studies for predicting children and adolescents at risk of fatty liver.

Alterations in Alanine Transaminase, Aspartate Transaminase, Gamma-Glutamyl Transpeptidase, and Creatine Kinase in Acne Patients Undergoing Isotretinoin Treatment: A Retrospective Evaluation of Laboratory Tests.

Background Isotretinoin therapy is a commonly prescribed medication by dermatologists for the treatment of acne. Regular laboratory assessments are recommended throughout the treatment period to detect any potential complications. Objectives This study aims to present the alterations in laboratory parameters throughout the course of isotretinoin therapy and identify required diagnostic testing. Methods This study involved 136 patients undergoing isotretinoin treatment at doses of 0.3-0.5 mg/kg/day, with ages ranging from 18 to 41 years. A retrospective evaluation was conducted on biomarkers including aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), creatine kinase (CK), triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hemoglobin, white blood cells, and thrombocytes. Levels of these parameters were analyzed prior to treatment and at the third month of treatment from the records of patients and the data were compared statistically. Moreover, the parameters of ALT, AST, CK, and GGT were graded objectively, and any alterations were noted in the patients. Results The levels of ALT, AST and GGT, along with triglycerides, total cholesterol, LDL-C, and thrombocyte levels showed significant elevation (p=0.001, p<0.001, p<0.001, p=0.001, p<0.001, p<0.001, and p=0.003, respectively). A significant decrease in HDL-C with hemoglobin was also noted (p=0.022, p=0.006, respectively). One patient (0.73%) exhibited grade 1 elevations in ALT, AST, and CK. One patient (0.73%) displayed grade 1 elevations in ALT and AST. One patient (0.73%) exhibited grade 1 elevations in AST and CK, while another patient (0.73%) had grade 1 elevation in AST and grade 3 elevation in CK. Furthermore, one patient (0.73%) had a grade 1 elevation exclusively in ALT, two patients (1.47%) had a grade 1 elevation exclusively in AST, and six patients (4.41%) exhibited a grade 1 elevation in CK only. No grade changes were observed in the GGT levels in the patients. Conclusion During isotretinoin treatment, changes in ALT and AST levels were more frequently associated with the muscle enzyme CK, while GGT levels remained unaffected. Therefore, GGT can be considered a reliable parameter for evaluating liver function in patients undergoing isotretinoin treatment.

Evaluation of elevated serum liver enzymes and metabolic syndrome in the PERSIAN Guilan cohort study population.

Objective: The purpose of this study is to evaluate the association between elevated serum liver enzymes and Metabolic Syndrome (MetS) in Prospective Epidemiological Research Studies of the Iranian Adults (PERSIAN) Guilan Cohort Study (PGCS) population. Methods: This cross-sectional study involved 10,519 individuals between the ages of 35 and 70 enrolled in the PGCS. The gathered data encompassed demographic information, anthropometric measurements, blood pressure, and biochemical indicators. MetS was defined by the National Cholesterol Education Program-Adult Treatment Panel III criteria (NCEP-ATP III). The associations between elevated liver enzymes and MetS were examined using logistic regression analysis. Odds ratio (OR) and 95 % confidence interval (CI) were calculated. Results: The prevalence of MetS was 41.8 %, and the prevalence of elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) were 19.4, 4.6, 11.6, and 5.1 %, respectively. In the unadjusted model, elevated ALT, AST, and GGT were associated with increased odds of MetS (OR = 1.55, 95 % CI: 1.41-1.71; OR = 1.29, 95 % CI: 1.07-1.55, and OR = 1.90, 95 % CI: 1.69-2.14, respectively). These associations remained significant for ALT and GGT after adjustment for some demographic and clinical characteristics (aOR = 1.31, 95 % CI: 1.17-1.46 and aOR = 1.30, 95 % CI: 1.14-1.49, respectively). In addition, the odds of MetS increased with the number of elevated liver enzymes, up to almost 1.32-fold among subjects with three/four elevated liver enzymes. Conclusion: The higher incidence of elevated liver enzymes was associated with an increased likelihood of MetS. Including liver markers in diagnosing and predicting MetS holds promise and is considered a possible approach.

Association between AST/ALT ratio and diabetic retinopathy risk in type 2 diabetes: a cross-sectional investigation.

Objective: This study aimed to explore the association between the aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio) and diabetic retinopathy (DR) in patients with type 2 diabetes. Methods: In this cross-sectional study, clinical data from 3002 patients with type 2 diabetes admitted to the Department of Endocrinology of our hospital between January 1, 2021, and December 1, 2022, were retrospectively collected. Measurements of AST and ALT were conducted and diabetes-related complications were screened. The association between AST/ALT ratio and diabetic retinopathy was assessed using multivariate logistic regression, and a generalized additive model (GAM) was used to investigate nonlinear relationships. Subgroup analyses and interaction tests were also conducted. Results: Among the 3002 patients, 1590 (52.96%) were male and 1412 (47.04%) were female. The mean AST/ALT ratio was 0.98 ± 0.32, ranging from 0.37 (Min) to 2.17 (Max). Diabetic retinopathy was present in 40.47% of the patients. After multivariate adjustments, for each 0.1 unit increase in AST/ALT ratio, the risk of DR increased by 4% (OR = 1.04, 95% CI: 1.01-1.07, p=0.0053). Higher AST/ALT ratio quartiles were associated with Higher prevalence of DR (OR vs. Q1: Q4 = 1.34 (CI: 1.03-1.75, p=0.0303).The GAM and smoothed curve fit indicated a linear relationship between AST/ALT ratio and DR risk, with no significant interaction effects across different subgroups. Conclusion: Our study demonstrates a positive correlation between the AST/ALT ratio and diabetic retinopathy risk in type 2 diabetes, suggesting its potential role in assessing DR risk.

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

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Clinical Characteristics of Genuine Acute Autoimmune Hepatitis.

Introduction: Autoimmune hepatitis (AIH) has a spectrum of symptoms ranging from asymptomatic disease to acute severe hepatitis, chronic hepatitis, and decompensated cirrhosis. The acute presentation is not rare and could represent genuine acute AIH (GAAIH) or acute exacerbation of chronic autoimmune hepatitis. We aimed to identify the prevalence, clinical features, and prognostic factors associated with GAAIH and compare these cases with acute exacerbation of chronic AIH. Methods: This cross-sectional observational study evaluated patients with acute AIH presentation, defined as total bilirubin >5 times the upper limit of normality (xULN) and/or alanine aminotransferase >10 xULN, and no prior history of liver disease. Histology findings of acute disease defined GAAIH. Bivariate analyses were performed to identify factors associated with the GAAIH, when compared with acute exacerbation of chronic AIH. Results: Seventy-two patients with acute presentation of AIH were included and six (8.3%) of them presented GAAIH. Comparative analysis between patients with GAAIH and patients with acute exacerbation of chronic AIH revealed that prothrombin activity (96% [74-100] vs. 61% [10-100]; p = 0.003) and albumin levels (3.9 ± 0.2 g/dL vs. 3.4 ± 0.5 g/dL; p < 0.001) were higher in patients with GAAIH. The International Autoimmune Hepatitis Group score was higher in patients with acute exacerbation of chronic AIH (18.5 [8-23] vs. 16.5 [15-17]; p = 0.010). Compared to 15.2% of acute exacerbation of chronic AIH, complete therapeutic response to treatment was achieved in 67.7% of cases with GAAIH (p = 0.018). Conclusions: GAAIH was rare (8.3%), and patients with this presentation exhibited more preserved liver function tests, suggesting that most cases presenting with loss of function are acute exacerbation of chronic AIH. Additionally, patients with GAAIH had a better complete therapeutic response, suggesting a more preserved liver function at presentation, and early diagnosis has a positive therapeutic implication.

Introdução: A hepatite autoimune (HAI) apresenta um espectro de sintomas que varia de doença assintomática a hepatite aguda grave, hepatite crónica e cirrose descompensada. A apresentação aguda não é rara e pode representar hepatite autoimune aguda genuína (HAIAG) ou exacerbação aguda de hepatite autoimune crónica (EAHAIC). O nosso objetivo foi identificar a prevalência, caraterísticas clínicas e fatores prognósticos associados à HAIAG, e comparar esses casos com EAHAIC. Métodos: Estudo observacional, transversal, incluindo doentes com apresentação aguda de HAI, definida como bilirrubina total > 5 vezes o limite superior da normalidade (xLSN) e/ou ALT > 10 xLSN, e sem história prévia de doença hepática. HAIAG foi definida pela presença de achados histológicos de doença aguda. Análises bivariadas foram realizadas para identificar fatores associados à HAIAG, quando comparado com o EAHAIC. Resultados: Foram incluídos setenta e dois doentes com apresentação aguda de HAI, dos quais seis (8.3%) com HAIAG. A análise comparativa entre doentes com HAIAG e doentes com EAHAIC mostrou que a atividade de protrombina (96% (74-100) versus 61% (10-100; p=0.003) e os níveis de albumina (3,9 ± 0,2 g/dL vs. 3,4 ± 0,5 g/dL; p < 0,001) foram significativamente mais elevados em pacientes com HAIAG. O score do Grupo Internacional de Hepatite Autoimune foi mais elevado em doentes com EAHAIC (18.5 (8-23) versus 16.5 (15-17); p=0.010). A resposta terapêutica completa ao tratamento foi alcançada em 66.7% dos casos de HAIAG (vs. 15,2% na EAHAIC, p=0,018). Conclusões: A HAIAG é rara (8.3%), e os doentes com esta apresentação mostraram testes de função hepática mais preservados, sugerindo que a maioria dos casos com perda de função são EAHAIC. Além disso, os doentes com HAIAG tiveram maior taxa de resposta terapêutica completa, sugerindo que uma função hepática mais preservada na apresentação e o diagnóstico precoce tem uma implicação terapêutica positiva.

Anthocyanins as Adjuvant Treatment for Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Recent studies suggest a role for anthocyanins in the treatment of non-alcoholic fatty liver disease (NAFLD). The purpose of the present review was to assess the effect of anthocyanins as an adjuvant treatment in patients with NAFLD. The literature search was conducted on MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), the Web of Science, and Scopus without language or time limits up to March 27, 2024. The primary outcomes included the severity of liver fibrosis and the level of liver transaminases. Secondary outcomes included obesity and lipid profile assessments. Standardized mean differences (SMDs) with 95% CIs were calculated for numerical outcomes. Five studies were included. The pooled effect sizes showed lower levels of liver fibrosis and liver transaminases in the anthocyanin group, but the difference was nonsignificant and small in size. The same result was obtained with anthropometric measurements of total cholesterol, low-density lipoprotein, and serum triglycerides, where effect sizes ranged from negligible to medium in magnitude but were all nonsignificant. The anthocyanin group showed a significantly lower body fat percentage (SMD = -0.41 (95%CI: -0.76; -0.06), P = 0.021). Currently, no evidence is available on the efficacy of anthocyanins in improving liver fibrosis or dyslipidemia in patients with NAFLD. There is limited evidence that anthocyanins can lower body fat percentages, but the effect was not reflected in the pooled results of other obesity indices. The few available clinical trials showed several limitations and variations regarding the doses of anthocyanins. Future clinical trials should avoid the limitations of the current studies and provide evidence supporting or refuting the use of anthocyanins in NAFLD patients.

Effectiveness and safety of tenofovir amibufenamide in chronic hepatitis B patients.

This letter to the editor relates to the study entitled "Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B: A real-world study", which was recently published by Peng et al. Hepatitis B virus infection represents a significant health burden worldwide and can lead to cirrhosis and even liver cancer. The antiviral drugs currently used to treat patients with chronic hepatitis B infection still have many side effects, so it is crucial to identify safe and effective drugs to inhibit viral replication.

Nutritional management of a dog with hepatic enzymopathy suspected to be secondary to copper-associated hepatitis: a case report.

A 4-year-old, female-spayed American Bulldog presented to the Ontario Veterinary College's Health Sciences Center's Clinical Nutrition Service for nutritional management of hepatic enzymopathy and suspected copper-associated hepatitis. Medical history revealed a 3-month history of gradually increasing serum ALT. Additional diagnostics included negative Leptospira titters, normal bile acids, and laparoscopic liver biopsy. Histopathology findings were consistent with diffuse moderate vacuole hepatocellular degeneration, mild positive copper staining, mild chronic lymphoplasmacytic hepatitis both portal and central, and mild biliary hyperplasia. Hepatic copper quantification results were above normal ranges (630 µg/g dry tissue), but below those seen in familial copper-associated hepatitis (>800-1,000 µg/g dry tissue). The patient was prescribed ursodeoxycholic acid, recommended to be fed a homemade diet (HMD), and referred for a nutrition consult. Two days before the nutrition consult, serum ALT fell within the normal range. The body condition score was 5/9, with a good muscle condition score and the dog's appetite and body weight remained stable. Energy intake was appropriate for maintenance. Key nutrient levels of all diets reported were compared to industry standards (AAFCO, NRC, and FEDIAF). Diet history included a commercially available raw meat-based diet (RMBD), of unknown copper content; a high energy commercial dry food (HEC), with copper content higher than the maximum recommended by FEDIAF and immediately prior to nutrition consult the patient had been eating an unbalanced homemade diet (HMD1) for 4 weeks. HMD1 was low in copper and deficient in the hepatoprotectant nutrients vitamin E and zinc. As per the owner's preference and to accommodate the patient's unique nutritional needs, a homemade diet addressing key nutrients for liver disease was formulated (HMD2), with copper content just above the recommended minimum. The new diet was found palatable and the patient's body weight, body, and muscle condition scores remained unchanged. Two months after starting HMD2, all bloodwork values remained within the normal range, including ALT. The reduction of dietary copper content likely reduced serum ALT. However, unbalanced diets cause a risk of nutrient deficiencies and excess. This dog was maintained with no known adverse effects on a complete and balanced HMD diet with a moderately low copper content, moderate protein, and inclusion of hepatoprotective nutrients.

Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B: A real-world study.

BACKGROUND: The efficacy and safety profile of tenofovir amibufenamide (TMF) in chronic hepatitis B (CHB) patients is not well-established. AIM: To compare the efficacy and safety of TMF and tenofovir alafenamide (TAF) over a 48-wk period in patients with CHB. METHODS: A total of 215 subjects meeting the inclusion criteria were enrolled and divided into two groups: TMF group (n = 106) and the TAF group (n = 109). The study included a comparison of virological response (VR): Undetectable hepatitis B virus DNA levels, alanine transaminase (ALT) normalization rates, renal function parameters, and blood lipid profiles. RESULTS: At 24 and 48 wk, VR rates for the TMF group were 53.57% and 78.57%, respectively, compared with 48.31% and 78.65% for the TAF group (P > 0.05). The VR rates were also similar in both groups among patients with low-level viremia, both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative subgroups. The TMF cohort showed ALT normalization and renal safety profiles similar to the TAF group. There was a notable increase in total cholesterol levels in the TAF group (P = 0.045), which was not observed in the TMF group (P > 0.05). In patients with liver cirrhosis, both groups exhibited comparable VR and ALT normalization rates and renal safety profiles. However, the fibrosis 4 score at 48 wk showed a significant reduction in the TAF group as compared to the TMF group within the liver cirrhosis subgroup. CONCLUSION: Our study found TMF is as effective as TAF in treating CHB and has a comparable safety profile. However, TAF may be associated with worsening lipid profiles.

Serum uric acid level in chronic liver disease and its correlation with Child-Pugh score in a tertiary care hospital from South India.

Background: Chronic liver disease (CLD) is one of the important causes of morbidity and mortality in our country, and since the damage to the liver is irreversible, we have to look for many severity markers or predictors for the prognosis of the patient. In this study, we have tried to correlate the level of serum uric acid (UA) with the severity of CLD presented as a Child-Pugh score. Methods: A cross-sectional observational study was conducted at Vijayanagar Institute of Medical Science (VIMS), Ballari, Karnataka, from October 2015 to June 2017 in the Department of General Medicine. Fifty patients diagnosed with CLD, aged between 18 and 65 years, of either gender, were enrolled in the study. Serum UA levels were measured, and liver function and coagulation parameters were assessed. A statistical analysis was performed to evaluate the association between serum UA levels, liver function test, and coagulation parameters. Results: In our study, the mean serum UA level was 6.52 mg/dl and was raised in patients with CLD in correlation to its severity. Alcoholic liver disease (ALD) was the most common etiology for CLD (80%) followed by hepatitis B (Hep B) virus infection (12%) and hepatitis C (Hep C) virus infection (6%). Serum UA levels increased as the Child-Turcotte-Pugh (CTP) score increased. The mean UA level in CTP class C was 8.29 mg/dl. Various parameters such as serum aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase, total bilirubin, international normalized ratio (INR), calcium, and albumin were significantly associated with serum UA levels in CLD patients. Conclusion: The correlation between rising blood UA levels and the Child-Pugh score shows that UA estimate may be a valid and affordable indicator for assessing the extent of liver cirrhosis in CLD.