Liver enzyme levels in adolescents with obesity and insulin resistance: a propensity score matching analysis.

BACKGROUND: Elevated liver enzyme levels have been associated with metabolic syndrome in both obese and non-obese pediatric populations. This study aims to compare the serum liver enzyme levels in obese adolescents with and without insulin resistance (IR). METHODS: A cross-sectional analysis was conducted involving obese adolescents aged 10-18. We assessed somatometry, serum insulin levels, lipid profiles, and liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and gamma-glutamyl transferase [GGT]). Statistical differences between groups were evaluated using Student's t-test or the Chi-squared test, with IR (wIR) status matched by propensity scores based on body mass index (BMI) z-scores. RESULTS: The study included 365 adolescents with obesity, 229 wIR, and 136 without (woIR). Before matching, the wIR group had a significantly higher BMI z-score (2.21 vs. 2.14, p = 0.032). After matching for BMI z-scores (n = 122 each group), the wIR group displayed significantly higher levels of AST (32.3 vs. 24.7, p < 0.001) and ALT (42.4 vs. 30.9, p < 0.001), but no significant differences were observed in GGT levels (37.4 vs. 32.5, p = 0.855). CONCLUSION: Obese adolescent's wIR exhibit higher serum ALT and AST levels, suggesting that altered AST is a potential risk factor for IR.

INTRODUCCIÓN: Se ha observado asociación entre niveles elevados de enzimas hepáticas y síndrome metabólico en población pediátrica con y sin obesidad. El objetivo del estudio fue comparar los niveles séricos de enzimas hepáticas entre adolescentes con obesidad con y sin resistencia a la insulina (RI). MÉTODOS: Se realizó un estudio transversal en adolescentes con obesidad entre 10 y 18 años. Se analizaron los datos somatometricos, insulina sérica, perfil lipídico y niveles de enzimas hepáticas (aspartato aminotransferasa [AST], alanina aminotransferasa [ALT] y gamma-glutamil transferasa [GGT]). Análisis estadístico: se utilizó t de Student o la prueba de Chi-cuadrado para evaluar diferencias entre grupos. Los pacientes con RI se emparejaron con pacientes sin RI utilizando puntuaciones de propensión basadas en la puntuación z del IMC. RESULTADOS: Se incluyeron un total de 365 adolescentes con obesidad (229 con RI y 136 sin RI). El grupo con RI tuvo un IMC mayor (con RI 2.21 vs sin RI 2.14 p = 0.032). Después de emparejar los grupos según el IMCz (n = 122 por grupo), el grupo con RI tuvo niveles de AST (24.7 vs., 32.3, p < 0.001) y ALT (30.9 vs., 42.4, p < 0.001) significativamente más altos en comparación al grupo sin RI. Sin embargo, no hubo diferencia en los niveles de GTT (37.4 vs 32.5, p = 0.855). CONCLUSIONES: Los niveles séricos de ALT y AST en adolescents con obesidad y RI fueron mayores. La AST alterada fue un factor de riesgo para presentar RI.

Direct-Acting Antiviral Therapy in Patients with Chronic Hepatitis C Shows Liver Fibrosis Regression on Three Noninvasive Tests: A Puerto Rican Cohort.

OBJECTIVE: Direct-acting antiviral (DAA) drugs have resulted in high rates of virological cure in chronic hepatitis C (CHC)-infected patients. We used noninvasive tests to assess fibrosis in subjects who had been cured with DAA. METHODS: Retrospective data collection (2014-2019) from the medical record of CHC patients at the hepatology clinic was performed. Subjects co-infected with HIV and hepatitis B, post-liver transplant, and lost to follow-up were excluded. We evaluated fibrosis at baseline and 1 year after completing therapy using vibration-controlled transient elastography (VCTE), fibrosis-4 (FIB-4), and aspartate aminotransferase-toplatelet ratio index (APRI) scores. RESULTS: With 210 medical records reviewed, 41 were included. The mean age was 62.8 years; 61% were men. Significant fibrosis regression was observed 1-year post-treatment using 3 noninvasive methods: VCTE, APRI, and FIB-4 score. Prior to treatment, 46% of the patients had advanced fibrosis compared to 25% 1 year after treatment. The VCTE scores of 4 subjects (with body mass indices [BMIs] > 30) indicated a worsening of fibrosis. We did not find a statistically significant association between BMI and VCTE, FIB-4, or APRI score. CONCLUSION: In most CHC patients, DAA therapy leads to liver fibrosis regression. Obesity may play an important role in the worsening of hepatic fibrosis or the absence of fibrosis regression.

Investigation of the effect of Myricetin on Cisplatin-induced liver hepatotoxicity.

OBJECTIVE: Cisplatin, a widely used anticancer agent, induces hepatotoxicity alongside organ damage. Understanding Cisplatin's toxicity mechanism and developing preventive measures are crucial. Our study explores Myricetin, a flavonoid, for its protective effects against Cisplatin-induced hepatotoxicity. METHODS: In our study, a total of 32 Wistar albino male rats were utilized, which were categorized into four distinct groups: Control, Myricetin, Cisplatin, and Myricetin+Cisplatin. For the histological assessment of hepatic tissues, hematoxylin-eosin and periodic acid Schiff staining were employed, alongside immunohistochemical measurements of TNF-α, interleukin-17, and interleukin-6 immunoreactivity. Additionally, aspartate transaminase and alanine transaminase values were examined by biochemical analysis. RESULTS: In the histological evaluation of the tissues, a normal healthy cell structure and a strong periodic acid Schiff (+) reaction were observed in the hepatocyte cells in the tissues of the Control and Myricetin groups, while intense eosinophilia, minimal vacuolization, congestion, and sinusoidal expansions were observed in the hematoxylin-eosin stainings, and a decrease in the positive reaction in the periodic acid Schiff staining was observed in the Cisplatin group. Consistent with these histological findings, an increase in TNF-α, interleukin-17, and interleukin-6 expressions (p<0.0001) and a concomitant increase in aspartate transaminase and alanine transaminase values were observed in the Cisplatin group. In the group protected by Myricetin, a significant improvement was observed in all these histological and biochemical values. CONCLUSION: Cisplatin induces notable histopathological alterations in the liver. In this context, Myricetin exhibits the potential to alleviate Cisplatin-induced damage by modulating histological parameters and biochemical processes.

Clinical, biochemical and histological features related to treatment response and prognosis in autoimmune hepatitis.

INTRODUCTION AND OBJECTIVES: Autoimmune hepatitis (AIH) is a rare disease with a complex and not fully understood pathogenesis. Prognostic factors that might influence treatment response, relapse rates, and transplant-free survival are not well established. This study investigates clinical and biochemical markers associated with response to immunosuppression in patients with AIH. MATERIALS AND METHODS: This retrospective cohort study included 102 patients with AIH treated with immunosuppressants and followed at the Federal University of Minas Gerais, Brazil, from 1990 to 2018. Pretreatment data such as clinical profiles, laboratory, and histological exams were analyzed regarding biochemical response at one year, histological remission, relapse, and death/transplantation rates. RESULTS: Cirrhosis was present in 59 % of cases at diagnosis. One-year biochemical remission was observed in 55.7 % of the patients and was found to be a protective factor for liver transplant. Overall survival was 89 %. Patients with ascites at disease onset showed a higher aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ratio and elevated Model of end-stage liver disease (MELD) score. The presence of ascites was significantly associated with a 20-fold increase in mortality rate. CONCLUSIONS: AIH has a severe clinical phenotype in Brazilians, with high rates of cirrhosis and low remission rates. Early diagnosis and treatment are essential for achieving remission and reducing complications. The presence of ascites is significantly associated with mortality, emphasizing the importance of monitoring and prompt intervention. This study also stresses the need for further research on AIH in Latin America.

Hepatic enzymes and immunoinflammatory response to Bio-C Temp bioceramic intracanal medication implanted into the subcutaneous tissue of rats.

Our purpose was to evaluate the biocompatibility and hepatotoxicity of a new bioceramic intracanal medicament, Bio-C Temp (BIO). The biological properties of BIO were compared with calcium hydroxide-based intracanal medicament (Calen; CAL), used as gold pattern. Polyethylene tubes filled with BIO or CAL, and empty tubes (control group, CG) were implanted into subcutaneous tissue of rats. After 7, 15, 30 and 60 days, the samples were embedded in paraffin for morphological, quantitative and immunohistochemistry analyses. At 7 and 60 days, blood samples were collected for analysis of serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels. The data were submitted to two-way ANOVA and Tukey's test (p ≤ 0.05). No significant difference was detected in serum GOT and GPT levels among BIO, CAL and CG specimens. In all periods, BIO specimens exhibited lower number of inflammatory cells and immunoexpression of IL-6, a pro-inflammatory cytokine, than CAL specimens. The reduction of these parameters was accompanied by significant increase in the collagen content and in the immunoexpression of IL-10, a cytokine involved in the tissue repair, over time. Our findings indicate that Bio-C Temp is biocompatible and had no hepatotoxicity effect.

A novel non-invasive score for the prediction of advanced fibrosis in patients with chronic hepatitis B.

INTRODUCTION AND OBJECTIVES: Evaluation of liver fibrosis is important for treatment decisions, complications and to predict prognosis in patients with chronic hepatitis B (CHB). Our aim was to develop a new non-invasive fibrosis scoring method and prove its accuracy in the differentiation of no/low grade and advanced fibrosis in patients with CHB. PATIENTS AND METHODS: Our study included 273 chronic hepatitis B patients who underwent liver biopsy from February, 2007 to February, 2019 with medical records retrospectively reviewed. Preparations of these patients were divided into two groups as ≤ 3 no-low grade fibrosis (n=236) and ≥ 4 advanced fibrosis (n=37) according to histological ISHAK fibrosis scoring system. RESULTS: The newly developed AGAP score and other non-invasive fibrosis scores; Fibrosis-4 index, Aspartate aminotransferase to platelets ratio, Gamma glutamyl transpeptidase to platelet ratio, Goteborg University Cirrhosis Index, King's score, Albumin-bilirubin index, Fibrosis cirrhosis index, Fibrosis index, Fibrosis quotient, Lok score and mean and/or median values of Fibroindex were significantly higher in the advanced fibrosis group compared to the no/low grade fibrosis group (p<0.001). However, there was no significant difference in AAR score among the groups (p=0.265). With cut-off value of 4.038, AUROC value of 0.803, sensitivity of 75.7%, specificity of 73.7% and accuracy of 0.740, AGAP score showed the best performance in advanced fibrosis differentiation compared to 12 other non-invasive fibrosis scoring methods. CONCLUSIONS: The newly developed AGAP score showed better performance in patients with CHB compared to 12 other non-invasive fibrosis scores in differentiation of no/low grade fibrosis and advanced fibrosis.

Evidence-based protocol for diagnosis and treatment of hepatorenal syndrome is independently associated with lower mortality.

BACKGROUND: Hepatorenal syndrome (HRS) is the deadliest complication of cirrhosis. The purpose of this study is to analyze if the use of a protocol for HRS is associated with higher survival in these patients. METHODS: An evidence-based protocol for the diagnosis and treatment of HRS was instituted in 2013. Data from medical records from 2010 to 2016 were obtained by searching the hospital database for patients who received terlipressin, in the three years before and after the institution of the protocol. Data were reviewed to confirm the diagnosis of HRS and multiple variables were collected. Liver-specific scores were calculated and a stepwise Cox regression approach was used for univariate and multivariate analysis. RESULTS: The study included 46 patients, 20 from the pre-protocol period and 26 from the post-protocol period. Respectively, mortality at 30 days, 90 days and 365 days was 75%, 75% and 90% for the pre-protocol period, and 61%, 69% and 80% for the post-protocol period. In the multivariate analysis, an aspartate aminotransferase (AST) of <40U/L, the pre-protocol period and higher Child-Turcotte-Pugh scores were associated with higher 30-day and 90-day mortality. The total mean dose of terlipressin and human albumin used per patient was reduced from 27mg to 22mg and from 236g to 144g, respectively, after the institution of the protocol. This was not associated with higher mortality. CONCLUSION: The use of an evidence-based protocol for the treatment of HRS translated into a higher survival. The authors suggest that the use of evidence-based protocols for the diagnosis and treatment of HRS could reduce cost and mortality in tertiary hospitals.

Prevalence and predictors of elevated liver enzyme levels in Mexico: The Mexican National Health and Nutrition Survey, 2016.

INTRODUCTION AND OBJECTIVE: To determine the prevalence of elevated liver enzyme levels and the fatty liver index according to specific sociodemographic, clinical, anthropometric, and metabolic risk factors in Mexican adult population. MATERIAL AND METHODS: The present analysis was conducted using data from the Mexican National Health and Nutrition Survey 2016. For the present study, 3,490 adults with complete information on liver enzymes, sociodemographic, lifestyle, and metabolic factors were analyzed. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) levels were determined from blood samples. We computed the fatty liver Index (FLI), as a surrogate marker of non-alcoholic fatty liver disease. The associations are reported as adjusted odds ratios (OR) and 95% confidence intervals (95%CI). RESULTS: At the national level, the prevalence of high serum levels of ALT, AST, and GGT were 7.9%, 13.5, and 12.9 respectively. We observed that men had higher prevalences of altered ALT, GGT and FLI compared to women. Additionally, we observe that individuals with obesity, metabolic syndrome and insulin resistance are significantly more likely to present elevated concentrations of AST, ALT, GGT and FLI. Finally, we found that the subjects of the lowest socioeconomic level and indigenous population were more likely to present elevated levels of AST, ALT, GGT, and FLI. CONCLUSION: In Mexico, non-alcoholic fatty liver disease affect people with obesity, diabetes, and metabolic syndrome as well as men, subjects of low socioeconomic status, subjects who live in rural areas and indigenous population. Interventions to reduce this condition should be a public health priority.

Rotundic acid ameliorates non-alcoholic steatohepatitis via SREBP-1c/ SCD1 signaling pathway and modulating gut microbiota.

Non-alcoholic steatohepatitis (NASH) is a devastating form of non-alcoholic fatty liver disease (NAFLD) with distinguished hallmarks of steatosis and inflammation. Rotundic acid (RA) is a natural pentacyclic triterpene compound extracted from the bank of Ilex rotunda Thunb with a wide range of biological activities. The aim of the study is to evaluate the pharmacological effect and action mechanism of RA on NASH in vitro and in vivo. RA has weak lipid lowering ability in rat primary hepatocytes, significantly decreases serum LDL level, hepatic TG and TC levels and lipid droplets, reduces NAS compared with the NASH group, and alleviates hepatic inflammation. RA also enhances the recovery of intestinal bacterial community and intestinal-derived short-chain fatty acid caused by high food diet (HFD). Further investigation shows that RA protects against HFD-induced NASH via downregulating the expression of SREBP-1c/SCD1 signaling pathway and improving gut microbiota. These findings imply that RA might be helpful for the alleviation of NASH.

Protective effect of genistein pre-treatment on paraquat hepatotoxicity in rats.

Paraquat (PQ), an herbicide widely used in agriculture, is considered a highly toxic compound. In hepatocytes, P-glycoprotein (P-gp/Abcb1) is a canalicular transporter involved in PQ extrusion from the cell. Previously, we demonstrated that genistein (GNT) induces P-gp in rat liver. In this study, the protective role of GNT pretreatment towards hepatic damage in a model of acute intoxication with PQ in rats, was investigated. Wistar rats were randomized in 4 groups: Control, GNT (5 mg/kg/day sc, 4 days), PQ (50 mg/kg/day ip, last day) and GNT+ PQ. Hepatic lipoperoxidation (LPO) was evaluated by the thiobarbituric acid reactive substances method. Hepatic levels of 4-hydroxynonenal protein adducts (4-HNEp-add) and glutathione-S-transferase alpha (GSTα) protein expression were evaluated by Western blotting. Hepatic glutathione levels and plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST) were also measured. Biliary excretion of PQ was studied in vivo and in isolated perfused liver. PQ was quantified by HPLC. PQ significantly increased AST and ALT activities, malondialdehyde and 4-HNEp-add levels, whereby pretreatment with GNT ameliorated this effect. PQ biliary excretion remained unchanged after treatments in both experimental models. Hepatic GSTα expression was augmented in GNT group. GNT pretreatment increased hepatic glutathione levels in PQ + GNT group. These results agree with the lower content of 4-HNEp-adds in GNT + PQ group respect to PQ group. Unexpectedly, increased activity of P-gp did not enhance PQ biliary excretion. Thus, GNT protective mechanism is likely through the induction of GSTα which results in increased 4-HNE metabolism before formation of protein adducts.

Effects of Vanadium Inhalation and Sweetened Beverage Ingestion in Mice: Morphological and Biochemical Changes in the Liver.

The aim of this report was to evaluate the morphological and biochemical changes in the liver by the inhalation of vanadium and consumption of sweetened beverages in a subchronic murine model. Forty CD-1 male mice were randomly divided into four groups: control, vanadium (V), sucrose 30% (S), and vanadium-sucrose (V + S). V was inhaled (1.4 mg/m3) for 1h, twice/week; 30% sucrose solution was given orally ad libitum. Blood samples were obtained for AST, ALT, and LDH determination. Liver samples were processed for histological and oxidative stress immunohistochemical evaluation with 4-hydroxynonenal at weeks 4 and 8 of exposure. Regarding liver function tests, a statistically significant increase (P < 0.05) was observed in groups V, S, and V + S at weeks 4 and 8 compared to the control group. A greater number of hepatocytes with meganuclei and binuclei were observed in V and V + S at week 8 compared to the other groups. Steatosis and regenerative changes were more extensive in the eighth week V + S group. 4-Hydroxynonenal immunoreactivity increased in the V + S group at both exposure times compared to the other groups; however, the increment was more evident in the V + S group at week 4 compared to the V + S group at week 8. An increase in De Ritis ratio (>1) was noticed in experimental groups at weeks 4 and 8. Findings demonstrate that in the liver, V, S, and V + S induced oxidative stress and regenerative changes that increased with the length of exposure. Results support possible potentiation of liver damage in areas with high air pollution and high-sweetened beverage consumption.

Saccharomyces boulardii modulates oxidative stress and renin angiotensin system attenuating diabetes-induced liver injury in mice.

Type 1 diabetes (T1DM) is a chronic disease characterized by hyperglycemia due to a deficiency in endogenous insulin production, resulting from pancreatic beta cell death. Persistent hyperglycemia leads to enhanced oxidative stress and liver injury. Several studies have evaluated the anti-diabetic and protective effects of probiotic strains in animal models. In the present study, we investigated, through histopathological and biochemical analyses, the effects of eight weeks of administration of Saccharomyces boulardii (S. boulardii) yeast on the liver of streptozotocin (STZ) induced diabetic C57BL/6 mice. Our results demonstrated that S. boulardii attenuates hepatocytes hydropic degeneration and hepatic vessels congestion in STZ-induced diabetic mice. The treatment attenuated the oxidative stress in diabetic mice leading to a reduction of carbonylated protein concentration and increased activity of antioxidant enzymes superoxide dismutase and glutathione peroxidase, compared to untreated diabetic animals. The results also show the beneficial influence of S. boulardii in regulating the hepatic concentration of renin angiotensin system (RAS) peptides. Therefore, our results demonstrated that S. boulardii administration to STZ-induced diabetic mice reduces oxidative stress and normalizes the concentration of RAS peptides, supporting the hypothesis that this yeast may have a role as a potential adjunctive therapy to attenuate diabetes-induced liver injury.

Hypertonic saline solution decreases oxidative stress in liver hypothermic ischemia.

BACKGROUND: Liver ischemia reperfusion injury is still an unsolved problem in liver surgery and transplantation. In this setting, hypothermia is the gold standard method for liver preservation for transplantation. Hypertonic saline solution reduces inflammatory response with better hemodynamic recovery in several situations involving ischemia reperfusion injury. Here, we investigated the effect of hypertonic saline solution in hypothermic liver submitted to ischemia reperfusion injury. METHODS: Fifty male rats were divided into 5 groups: SHAM, WI (animals submitted to 40 minutes of partial warm liver ischemia and reperfusion), HI (animals submitted to 40 minutes hypothermic ischemia), HSPI (animals submitted to hypothermic ischemia and treated with 7.5% hypertonic saline solution preischemia), and HSPR (animals submitted to hypothermic ischemia and treated with hypertonic saline solution previously to liver reperfusion). Four hours after reperfusion, the animals were euthanized to collect liver and blood samples. RESULTS: Aspartate aminotransferase and alanine aminotransferase, histologic score, and hepatocellular necrosis were significantly decreased in animals submitted to hypothermia compared with the warm ischemia group. Malondialdehyde was significantly decreased in hypothermic groups with a further decrease when hypertonic saline solution was administrated preischemia. Hypothermic groups also showed decreased interleukin-6, interleukin-10, and tumor necrosis factor-α concentrations and better recovery of bicarbonate, base excess, lactate, and glucose blood concentrations. Moreover, hypertonic saline solution preischemia was more effective at controlling serum potassium concentrations. CONCLUSION: Hypertonic saline solution before hypothermic hepatic ischemia decreases hepatocellular oxidative stress, cytokine concentrations, and promotes better recovery of acid-base disorders secondary to liver ischemia reperfusion.

Ultrasound Findings and Laboratory Predictors of Early Mortality in Patients With Severe Yellow Fever.

OBJECTIVE. Yellow fever is a hemorrhagic disease caused by an arbovirus endemic in South America; outbreaks have occurred in recent years. The purpose of this study was to describe abdominal ultrasound findings in patients with severe yellow fever and correlate them with clinical and laboratory data. MATERIALS AND METHODS. A retrospective cohort study was performed between January and April 2018. The subjects were patients admitted to an ICU with polymerase chain reaction-confirmed yellow fever. Bedside sonography was performed within 48 hours of admission. Images were independently analyzed by two board-certified radiologists. Laboratory test samples were collected within 12 hours of image acquisition. Multivariable logistic regression analysis was performed to identify 30-day mortality predictors; p < .05 was considered statistically significant. RESULTS. Forty-six patients (40 [87%] men, six [13%] women; mean age, 47.5 ± 15.2 years) were evaluated with bedside sonography. Laboratory tests showed high serum levels of aspartate aminotransferase (5319 U/L), total bilirubin (6.2 mg/dL), and creati-nine (4.3 mg/dL). Twenty-six (56.5%) patients died within 30 days of admission (median time to death, 5 days [interquartile range, 2-9 days]). The most frequent ultrasound findings were gallbladder wall thickening (80.4%), increased renal cortex echogenicity (71.7%), increased liver parenchyma echogenicity (65.2%), perirenal fluid (52.2%), and ascites (30.4%). Increased renal echogenicity was associated with 30-day mortality (84.6% versus 55.0%; p = .046) and was an independent predictor of this outcome after multivariate analysis (odds ratio, 10.89; p = .048). CONCLUSION. Reproducible abdominal ultrasound findings in patients with severe yellow fever may be associated with severity of disease and prognosis among patients treated in the ICU.

Acute oral treatment with resveratrol and Lactococcus Lactis Subsp. Lactis decrease body weight and improve liver proinflammatory markers in C57BL/6 mice.

The present study aimed to evaluate the effects of resveratrol, a nutraceutical polyphenol, and Lactococcus lactis (bacteria probiotic), on metabolic parameters and hepatic proinflammatory markers expression. C57BL/6 mice were divided into 4 groups: Standard (ST), Lactococcus lactis (LL), Resveratrol (RSV), and Lactococcus lactis plus resveratrol (LL + RSV). Lactococcus lactis and resveratrol were administered by orogastric gavage. Blood parameters were assessed (total cholesterol, triglycerides, ALT and AST). IL-6 mRNA expression was evaluated by Real-time PCR and TNF-α protein expression was assessed by immunohistochemistry. The main findings showed that resveratrol and Lactococcus lactis association decreased body weight, aspartate aminotransferase and total cholesterol levels. LL and LL + RSV decreased triglycerides levels and IL-6 and TNF-α expression. These results open a perspective of using resveratrol and Lactococcus lactis to improve metabolic parameters and Lactococcus lactis in preventing inflammation and the hepatic diseases development.

Liver fibrosis in patients with metabolic associated fatty liver disease is a risk factor for adverse outcomes in COVID-19.

BACKGROUND: Metabolic diseases are risk factors for severe Coronavirus disease (COVID-19), which have a close relationship with metabolic dysfunction-associated fatty liver disease (MAFLD). AIMS: To evaluate the presence of MAFLD and fibrosis in patients with COVID-19 and its association with prognosis. METHODS: Retrospective cohort study. In hospitalized patients with COVID-19, the presence of liver steatosis was determined by computed tomography scan (CT). Liver fibrosis was assessed using the NAFLD fibrosis score (NFS score), and when altered, the AST to platelet ratio index (APRI) score. Mann-Whitney U, Student´s t-test, logistic regression analysis, Kaplan-Meier curves and Cox regression analysis were used. RESULTS: 432 patients were analyzed, finding steatosis in 40.6%. No differences in pulmonary involvement on CT scan, treatment, or number of days between the onset of symptoms and hospital admission were found between patients with and without MAFLD. The presence of liver fibrosis was associated with higher severity scores, higher levels of inflammatory markers, requirement of mechanical ventilation, incidence of acute kidney injury (AKI), and higher mortality than patients without fibrosis. CONCLUSION: The presence of fibrosis rather than the presence of MAFLD is associated with increased risk for mechanical ventilation, development of AKI, and higher mortality in COVID-19 patients.

Improvement in Liver Stiffness in Pediatric Patients with Hepatitis C Virus after Treatment with Direct Acting Antivirals.

OBJECTIVES: To assess the degree of liver stiffness using transient elastography in Egyptian children infected with hepatitis C virus (HCV) at baseline and 1 year after achievement of sustained virologic response (SVR) with direct acting antivirals. STUDY DESIGN: This prospective study included children infected with HCV who received treatment with sofosbuvir/ledipasvir and achieved SVR. At baseline and 1 year after achievement of SVR, the extent of hepatic fibrosis was assessed by transient elastography using FibroScan to measure liver stiffness, in addition to noninvasive markers including aspartate aminotransferase/platelet ratio index (APRI) and fibrosis-4 (FIB-4) index. RESULTS: The study included 23 cases that had variable degrees of fibrosis at baseline; their ages ranged between 10 and 18 years. At baseline, 13 patients had F1; 3 patients had F1-F2; 1 patient had F2; 3 patients had F3; 2 had F3-F4; and 2 patients with F4. One year after achievement of SVR, there was a statistically significant improvement in liver stiffness, APRI, and FIB-4 index (P = .03, <.001, .02, respectively). In 13 patients (56.5%), the liver stiffness improved; in 7 patients, it was stationary; and the remaining 3 patients showed mild increase in liver stiffness that was, however, associated with improvement in APRI and FIB-4 index. Comorbid conditions and previous treatment with interferon were not associated with increased liver stiffness 1 year after SVR. CONCLUSIONS: Egyptian children infected with HCV genotype 4 achieved significant regression in liver stiffness after treatment with direct acting antivirals.

Concordance between hepatic biopsy and the APRI index (Ast to Platelet Ratio Index) for the diagnosis of cirrhosis in patients with autoimmune liver disease. / Concordancia entre el resultado de la biopsia hepática y el índice APRI (Ast to Platelet Ratio Index) en el diagnóstico de cirrosis en pacientes con enfermedad hepática autoinmune.

INTRODUCTION AND OBJECTIVES: It has been proposed that non-invasive methods may replace liver biopsy for the diagnosis of tissue damage in patients with autoimmune liver disease (ALD). The aim of this study was to determine diagnostic performance and degree of concordance between the APRI index and liver biopsy for diagnosing cirrhosis in these patients. MATERIAL AND METHODS: In a cohort of patients with ALD, the value of the APRI index and liver biopsy results were determined according to the METAVIR score. The AUC and the degree of concordance between an APRI value >2 and a METAVIR score of F4 were evaluated as markers of liver cirrhosis, through a kappa statistic. RESULTS: In total, 70 patients (age 51 ± 13 years) were included. The most common autoimmune liver diseases were primary biliary cirrhosis (PBC) (40%), autoimmune hepatitis (AIH) (24.3%) and AIH-PBC overlap syndrome (32.9%). Cirrhosis was confirmed by biopsy in 16 patients (22.9%). 15 patients (21.4%) had an APRI index >2 (Cirrhosis) and only six met both criteria. The AUC of the APRI was 0.77 (95% CI 0.65-0.88). The degree of concordance between the tests was low for an APRI cut-off point >2 (kappa 0.213; 95% CI 0.094-0.332), as well as for cut-off points >1.5, >1 and >0.5 (kappa 0.213, 0.255, 0.257, respectively) CONCLUSION: Our results suggest that there is little concordance between APRI and liver biopsy for the diagnosis of cirrhosis in patients with ALD. It should therefore not be used as a single diagnostic method to determine cirrhosis.

Liver injury predicts overall mortality in severe COVID-19: a prospective multicenter study in Brazil.

BACKGROUND/PURPOSE: The relationship between liver injury and mortality remains unclear in patients with COVID-19. We aimed to evaluate the prognostic value of aminotransferases levels at hospital admission to predict mortality in patients with COVID-19. METHODS AND RESULTS: This prospective study included 406 patients [57% male, aged 56 years] with COVID-19 hospitalized in 26 centers in Brazil. Overall, 36.7% (95% CI 32.1-41.5) presented at admission with severe disease requiring respiratory support. The prevalence of elevated ALT and AST levels at admission [> 2 × ULN] was 14.0% (95% CI 11.0-17.8) and 12.9% (95% CI 10.0-16.6), respectively. Sixty-two patients [15.3% (95% CI 12.1-19.1)] died during hospitalization and the overall mortality rate was 13.4 (10.5-17.2) deaths per 1000 persons-years. The 15-day-overall survival (95% CI) was significantly lower in patients with ALT levels ≥ 2 × ULN compared to those with ALT < 2 × ULN [67.1% (48.4-80.2) vs 83.4% (76.1-88.6), p = 0.001] and in those with AST levels ≥ 2 × ULN compared to those with AST < 2 × ULN [61.5% (44.7-74.6) vs 84.2% (76.5-89.5), p < 0.001]. The presence of elevated aminotransferases levels at hospital admission significantly increased the risk of in-hospital all-cause mortality adjusted for age-and-sex. Those findings were present in the subgroup of critically ill patients already admitted in need of respiratory support (n = 149), but not in patients without that requirement at admission (n = 257). CONCLUSIONS: Elevated aminotransferases at hospital admission predicted in-hospital all-cause mortality in patients with COVID-19, especially in those with severe disease. Measurement of transaminases levels at hospital admission should be integrated to the care of patients with COVID-19 as an auxiliary strategy to identify patients at higher death risk.

HEMATOLOGY, PLASMA BIOCHEMISTRY, AND PLASMA PROTEIN ELECTROPHORESIS REFERENCE INTERVALS FOR BLUE IGUANAS (CYCLURA LEWISI) FROM GRAND CAYMAN ISLAND.

The blue iguana (Cyclura lewisi) is an endangered rock iguana species native to Grand Cayman, in the Cayman Islands. Health assessments were conducted on captive and free-roaming iguanas in 2001 and 2003-2014 and were performed in the summer wet season (June-July) of 2003-2004 and 2010-2014 and in the winter dry season (November-December) of 2001 and 2005-2009. Morphometric data were recorded from iguanas when blood samples were collected: 903 samples were collected and data from 890 samples from 775 iguanas were included. Samples were analyzed for hematology, plasma biochemistry, protein electrophoresis, mineral panels, 25-hydroxyvitamin D, and testosterone. Reference intervals were created for captive subadults, captive adults, and free-roaming adults when data were sufficient. Significant differences among these groups were described, as were differences on the basis of sex, season, and origin (captive vs free-roaming). In captive iguanas, most analytes were significantly different between subadults and adults, mature heterophils and copper were significantly higher in the dry season, zinc levels were significantly higher in the wet season, and cholesterol and triglycerides were significantly higher in adult females than adult males. Testosterone in adult males was significantly higher in the dry season. These results will aid in future health assessments and disease investigations in wild and captive populations of blue iguanas and are of comparative value for other Cyclura species that are free-roaming, captive, and, especially, in similar conservation release programs.