Development of a biodegradable prosthesis through tissue engineering, for the organ-replacement or substitution of the extrahepatic bile duct.

INTRODUCTION AND OBJECTIVES: There are different situations in which an extrahepatic bile duct replacement or substitute is needed, such as initial and localized stages of bile duct cancer, agenesis, stenosis, or bile duct disruption. MATERIALS AND METHODS: A prosthesis obtained by electrospinning composed of Poly (D,L-lactide-co-glycolide) (PGLA) - Polycaprolactone (PCL) - Gelatin (Gel) was developed, mechanical and biological tests were carried out to evaluate resistance to tension, biocompatibility, biodegradability, cytotoxicity, morphological analysis and cell culture. The obtained prosthesis was placed in the extrahepatic bile duct of 15 pigs with a 2-year follow-up. Liver function tests and cholangioscopy were evaluated during follow-up. RESULTS: Mechanical and biological evaluations indicate that this scaffold is biocompatible and biodegradable. The prosthesis implanted in the experimental model allowed cell adhesion, migration, and proliferation, maintaining bile duct permeability without altering liver function tests. Immunohistochemical analysis indicates the presence of biliary epithelium. CONCLUSIONS: A tubular scaffold composed of electrospun PGLA-PCL-Gel nanofibers was used for the first time to replace the extrahepatic bile duct in pigs. Mechanical and biological evaluations indicate that this scaffold is biocompatible and biodegradable, making it an excellent candidate for use in bile ducts and potentially in other tissue engineering applications.

Administration of silymarin in NAFLD/NASH: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with a high prevalence worldwide and poses serious harm to human health. There is growing evidence suggesting that the administration of specific supplements or nutrients may slow NAFLD progression. Silymarin is a hepatoprotective extract of milk thistle, but its efficacy in NAFLD remains unclear. MATERIALS AND METHODS: Relevant studies were searched in PubMed, Embase, the Cochrane Library, Web of Science, clinicaltrails.gov, and China National Knowledge Infrastructure and were screened according to the eligibility criteria. Data were analyzed using Revman 5.3. Continuous values and dichotomous values were pooled using the standard mean difference (SMD) and odds ratio (OR). Heterogeneity was evaluated using the Cochran's Q test (I2 statistic). A P<0.05 was considered statistically significant. RESULTS: A total of 26 randomized controlled trials involving 2,375 patients were included in this study. Administration of silymarin significantly reduced the levels of TC (SMD[95%CI]=-0.85[-1.23, -0.47]), TG (SMD[95%CI]=-0.62[-1.14, -0.10]), LDL-C (SMD[95%CI]=-0.81[-1.31, -0.31]), FI (SMD[95%CI]=-0.59[-0.91, -0.28]) and HOMA-IR (SMD[95%CI]=-0.37[-0.77, 0.04]), and increased the level of HDL-C (SMD[95%CI]=0.46[0.03, 0.89]). In addition, silymarin attenuated liver injury as indicated by the decreased levels of ALT (SMD[95%CI]=-12.39[-19.69, -5.08]) and AST (SMD[95% CI]=-10.97[-15.51, -6.43]). The levels of fatty liver index (SMD[95%CI]=-6.64[-10.59, -2.69]) and fatty liver score (SMD[95%CI]=-0.51[-0.69, -0.33]) were also decreased. Liver histology of the intervention group revealed significantly improved hepatic steatosis (OR[95%CI]=3.25[1.80, 5.87]). CONCLUSIONS: Silymarin can regulate energy metabolism, attenuate liver damage, and improve liver histology in NAFLD patients. However, the effects of silymarin will need to be confirmed by further research.

Non-linear associations of circulating total bilirubin concentration with the risk of nonalcoholic fatty liver disease and all-cause mortality.

INTRODUCTION AND OBJECTIVES: Accumulating evidence has supported that mild elevated total bilirubin exerts antioxidant and anti-inflammatory properties in multiple metabolic diseases. We aimed to explore the association of circulating total bilirubin concentration with non-alcoholic fatty liver disease (NAFLD) risk and all-cause mortality and examine the potential nonlinear relationships between them. MATERIAL AND METHODS: We used nationally representative data from the National Health and Nutrition Examination Survey (NHANES). NAFLD was assessed using the fatty liver index (FLI) and United States fatty liver index (USFLI), respectively. RESULTS: A total of 35 912 and 17 329 participants were included in FLI-NAFLD (case with NAFLD was diagnosed by FLI) and USFLI-NAFLD (case with NAFLD was diagnosed by USFLI) groups, respectively. The mean age of total population was 46.25 years, and 48.51% were male. Compared to participants with lowest quintile of total bilirubin concentration, those with highest quintile had lower risk of NAFLD in both FLI-NAFLD (OR: 0.48, 95% CI: 0.40, 0.59) and USFLI-NAFLD (OR: 0.55, 95% CI: 0.43, 0.70) groups. Compared to participants with lowest quintile of total bilirubin concentration, the association between total bilirubin concentration and all-cause mortality was not significant among those with highest quintile of total bilirubin concentration (HR: 0.89, 95% CI: 0.66, 1.20). The restricted spline curves showed the nonlinear U-shaped association of total bilirubin concentration with NAFLD risk and all-cause mortality. The segmented linear regression analysis showed negative associations between total bilirubin concentration and risk of NAFLD in both FLI-NAFLD (OR: 0.94, 95% CI: 0.93, 0.95) and USFLI-NAFLD (OR: 0.95, 95% CI: 0.93, 0.96) groups when total bilirubin concentration was below the turning point (FLI-NAFLD: 18.81 µmol/L; USFLI-NAFLD: 15.39 µmol/L) and these associations were not significant when total bilirubin concentration was higher than the turning point. Furthermore, all-cause mortality decreased (OR: 0.97, 95%CI: 0.95, 1.00) with increased total bilirubin concentration up to the turning point (11.97 µmol/L), and then all-cause mortality increased with increasing total bilirubin concentration (OR: 1.03, 95%CI: 1.02, 1.04). CONCLUSIONS: We found that higher circulating total bilirubin concentration within the physiological range was associated with decreased risk of NAFLD and all-cause mortality among NAFLD patients.

Altered liver function test after Covid-19 vaccines: A retrospective control group study.

BACKGROUND AND PURPOSE: Liver injury after Covid-19 vaccine has been described, although the incidence was not well established. We aimed to compare cumulative incidence of new onset liver test alteration after Covid-19 vaccination, and to compare with an historical control of influenza vaccination. METHODS: We conducted a retrospective cohort study which included adults who received at least one dose of Covid-19 vaccine from January 1 to May 30, 2021 and a control group who received a single dose of influenza vaccine during 2019, in a tertiary medical center from Argentina. RESULTS: We included 29 798 patients in Covid-19 vaccine group and 24 605 in influenza vaccine group. Liver function tests were performed in 7833 (26.9%) in Covid-19 vaccine group and 8459 (34.37%) in influenza vaccine group. Cumulative incidence at 90 days of new onset liver enzyme test alteration was 4.7 per 1000 (95% 4.0-5.5) for Covid-19 group, and 5.1 per 1000 (95% 4.3-6.1) for the influenza vaccine group (p value = 0.489). Two patients in the Covid-19 vaccine group developed immune mediated liver injury. CONCLUSIONS: We found no difference in liver test alteration between groups. These findings support the safety of Covid-19 vaccines. While we have identified two cases that are consistent with immune mediated liver injury following COVID-19 vaccination, we believe that the available data is insufficient to attribute them solely to the vaccination.

Liver Function in Patients with Long-Term Coronavirus Disease 2019 of up to 20 Months: A Cross-Sectional Study.

The long-term laboratory aspects of the effects of coronavirus disease 2019 (COVID-19) on liver function are still not well understood. Therefore, this study aimed to evaluate the hepatic clinical laboratory profile of patients with up to 20 months of long-term COVID-19. A total of 243 patients of both sexes aged 18 years or older admitted during the acute phase of COVID-19 were included in this study. Liver function analysis was performed. Changes were identified in the mean levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), and ferritin. A ferritin level of >300 U/L was observed in the group that presented more changes in liver function markers (ALT, AST, and GGT). Age ≥ 60 years, male sex, AST level > 25 U/L, and GGT level ≥ 50 or 32 U/L were associated with an ALT level > 29 U/L. A correlation was found between ALT and AST, LDH, GGT, and ferritin. Our findings suggest that ALT and AST levels may be elevated in patients with long-term COVID-19, especially in those hospitalised during the acute phase. In addition, an ALT level > 29 U/L was associated with changes in the levels of other markers of liver injury, such as LDH, GGT, and ferritin.

Fractionated Bilirubin Among 252 892 Utah Newborns with and Without Biliary Atresia: A 15-year Historical Birth Cohort Study.

OBJECTIVES: To determine whether neonatal conjugated or direct bilirubin levels were elevated in infants with biliary atresia (BA) and to estimate the number of newborns who would have positive screens in the nursery necessitating repeat testing after discharge. STUDY DESIGN: We used administrative data from a large integrated healthcare network in Utah to identify newborns who had a fractionated bilirubin recorded during birth admission from 2005 through 2019. Elevated conjugated bilirubin was defined as greater than 0.2 mg/dL and direct bilirubin was defined as greater than 0.5 mg/dL (>97.5th percentile for the assays). We performed simulations to estimate the anticipated number of false-positive screens. RESULTS: There were 32 cases of BA and 468 161 live births during the study period (1/14 700). There were 252 892 newborns with fractionated bilirubin assessed, including 26 of those subsequently confirmed to have BA. Conjugated or direct bilirubin was elevated in all 26 infants with BA and an additional 3246 newborns (1.3%) without BA. Simulated data suggest 9-21 per 1000 screened newborns will have an elevated conjugated or direct bilirubin using laboratory-based thresholds for a positive screen. Screening characteristics improved with higher thresholds without increasing false-negative tests. CONCLUSIONS: This study validates the previous findings that conjugated or direct bilirubin are elevated in the newborn period in patients with BA. A higher threshold for conjugated bilirubin improved screening performance. Future studies are warranted to determine the optimal screening test for BA and to assess the effectiveness and cost-effectiveness of implementing such a program.

Diagnostic accuracy of blood biomarkers and non-invasive scores for the diagnosis of NAFLD and NASH: Systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Fatty liver disease is an important public health problem. Early diagnosis is critical to lower its rate of progression to irreversible/terminal stages. This study aimed to evaluate the accuracy of non-invasive prediction scores for fatty liver disease (NAFLD and NASH) diagnosis in adults. MATERIALS AND METHODS: A search was conducted in 10 databases, a qualitative synthesis of 45 studies, and quantitative analysis of the six most common scores. There were 23 risk scores found for NAFLD diagnosis and 32 for NASH diagnosis. The most used were Fatty Liver Index (FLI), aspartate aminotransferase (AST) to Platelet Ratio Index, Fibrosis-4 Index (FIB-4), AST/alanine aminotransferase (ALT) ratio, BARD score, and NAFLD fibrosis score (NFS). RESULTS: The results from the meta-analysis for FLI: Area under the curve (AUC) of 0.76 (95% Confidence Interval [CI] 0.73, 0.80), sensitivity 0.67 (CI 95% 0.62, 0.72) and specificity 0.78 (CI 95% 0.74, 0.83). The AST to Platelet Ratio Index: AUC 0.83 (CI 95% 0.80, 0.86), sensitivity 0.45 (95% CI 0.29, 0.62), and specificity of 0.89 (95% CI 0.83, 0.92). The NFS: AUC of 0.82 (CI 95% 0.78, 0.85), sensitivity 0.30 (CI 95% 0.27, 0.33) and specificity 0.96 (CI 95% 0.95,0.96). CONCLUSIONS: The FLI for NAFLD and AST to Platelet Ratio Index for NASH were the risk scores with the highest prognostic value in the included studies. Further research is needed for the application of new diagnostic risk scores for NAFLD and NASH.

Níveis séricos de vitamina D e alterações hepáticas em pacientes com malária na região Amazônica / Serum levels of vitamin d and hepatic changes in patients with malaria in the Amazon region / Niveles séricos de vitamina d y alteraciones hepáticas en pacientes con malaria en la Amazonia

Vários estudos sugerem a importância da vitamina D ­ 25(OH)D ­ na evolução clínica dos pacientes com malária. Entretanto, a prevalência de deficiência de 25(OH)D na população amazônica é pouco conhecida, havendo também poucos estudos com pacientes diagnosticados com malária. Assim, o objetivo deste estudo foi avaliar os níveis séricos de 25(OH)D em pacientes com malária e sua relação com dados epidemiológicos, parasitológico e provas de função hepática. Para tanto, foi realizado um estudo transversal analítico com um grupo de pacientes com malária e um grupo controle no município de Itaituba (PA), Brasil, no período de janeiro de 2018 a outubro de 2019. Elaborou-se um protocolo para avaliação dos dados sociodemográficos, parasitológicos e laboratoriais, adotando-se o nível de significância de 5%. A prevalência de deficiência de 25(OH)D foi observada nos pacientes com malária (28,5%) e no grupo controle (24,6%), sem diferença estatística; porém, entre os residentes no garimpo, os níveis séricos foram estatisticamente menores nos pacientes com malária. Os níveis séricos de transaminase glutâmico-pirúvica (TGP) apresentaram correlação inversa com os de 25(OH)D. As provas de função hepática foram significativamente maiores no grupo com malária. Dessa forma, este estudo evidenciou a deficiência de 25(OH)D em Itaituba. Alterações hepáticas pela infecção plasmodial podem ter contribuído para a correlação inversa observada entre os níveis de TGP e 25(OH)D.

Several studies suggest the importance of vitamin D ­ 25(OH)D ­ in the clinical evolution of patients with malaria. However, the prevalence of 25(OH)D deficiency in the Amazonian population is little known, and studies with patients diagnosed with malaria are scarce. Thus the objective of this study is to evaluate the serum levels of 25(OH)D in patients with malaria and its relationship with epidemiological and parasitological data and liver function tests. To that end, an analytical cross-sectional study was carried out with a group of patients with malaria and a control group in the municipality of Itaituba (PA), Brazil, from January 2018 to October 2019. A protocol was elaborated for the evaluation of sociodemographic, parasitological, and laboratory data, adopting a significance level of 5%. Results: The prevalence of 25(OH)D deficiency was observed in patients with malaria (28.5%) and in the control group (24.6%), with no statistical difference; however, among residents in the mining, serum levels were statistically lower in patients with malaria. The glutamic-pyruvic transaminase (GPT) serum levels showed an inverse correlation with 25(OH)D levels. Liver function tests were significantly higher in the malaria group. Thus, this study evidenced 25(OH)D deficiency in Itaituba. Hepatic changes due to plasmodial infection may have contributed to the inverse correlation observed between GPT and 25(OH)D levels.

Diversos estudios sugieren la importancia de la vitamina D ­[25(OH)D]­ en la evolución clínica de pacientes con malaria. Sin embargo, la prevalencia de la deficiencia de 25(OH)D en la población amazónica es poco conocida y existen pocos estudios en pacientes con malaria. Ante esto, el objetivo de este estudio fue evaluar los niveles séricos de 25(OH)D en pacientes con malaria y su relación con datos epidemiológicos, parasitológicos y pruebas de función hepática. Para ello, se realizó un estudio transversal analítico en el grupo de pacientes con malaria y en un grupo control en el municipio de Itaituba (PA), Brasil, de enero de 2018 a octubre de 2019. Se elaboró un protocolo para la evaluación de datos sociodemográficos, parasitológicos y de laboratorio, adoptando un nivel de significancia del 5%. La prevalencia de deficiencia de 25(OH)D se observó en pacientes con malaria (28,5%) y en el grupo control (24,6%), sin diferencia estadística; sin embargo, entre los residentes en la minería, los niveles séricos fueron estadísticamente inferiores en pacientes con malaria. Los niveles séricos de transaminasa glutámico pirúvica (TGP) mostraron una correlación inversa con los niveles de 25(OH)D. Las pruebas de función hepática fueron significativamente más altas en el grupo de malaria. De esta manera, se evidenció deficiencia de 25(OH)D en la población de Itaituba. Los cambios hepáticos debido a la infección plasmodial pueden haber contribuido a la correlación inversa observada entre los niveles de TGP y 25(OH)D.

Liver disease accompanied by enteropathy in common variable immunodeficiency: Common pathophysiological mechanisms.

Common variable immunodeficiency (CVID) is one of the inborn errors of immunity that have the greatest clinical impact. Rates of morbidity and mortality are higher in patients with CVID who develop liver disease than in those who do not. The main liver disorder in CVID is nodular regenerative hyperplasia (NRH), the cause of which remains unclear and for which there is as yet no treatment. The etiology of liver disease in CVID is determined by analyzing the liver injury and the associated conditions. The objective of this study was to compare CVID patients with and without liver-spleen axis abnormalities in terms of clinical characteristics, as well as to analyze liver and duodenal biopsies from those with portal hypertension (PH), to elucidate the pathophysiology of liver injury. Patients were divided into three groups: Those with liver disease/PH, those with isolated splenomegaly, and those without liver-spleen axis abnormalities. Clinical and biochemical data were collected. Among 141 CVID patients, 46 (32.6%) had liver disease/PH; 27 (19.1%) had isolated splenomegaly; and 68 (48.2%) had no liver-spleen axis abnormalities. Among the liver disease/PH group, patients, even those with mild or no biochemical changes, had clinical manifestations of PH, mainly splenomegaly, thrombocytopenia, and esophageal varices. Duodenal celiac pattern was found to correlate with PH (p < 0.001). We identified NRH in the livers of all patients with PH (n = 11). Lymphocytic infiltration into the duodenal mucosa also correlated with PH. Electron microscopy of liver biopsy specimens showed varying degrees of lymphocytic infiltration and hepatocyte degeneration, which is a probable mechanism of lymphocyte-mediated cytotoxicity against hepatocytes and enterocytes. In comparison with the CVID patients without PH, those with PH were more likely to have lymphadenopathy (p < 0.001), elevated ß2-microglobulin (p < 0.001), low B-lymphocyte counts (p < 0.05), and low natural killer-lymphocyte counts (p < 0.05). In CVID patients, liver disease/PH is common and regular imaging follow-up is necessary. These patients have a distinct immunological phenotype that may predispose to liver and duodenal injury from lymphocyte-mediated cytotoxicity. Further studies could elucidate the cause of this immune-mediated mechanism and its treatment options.

Postoperative liver function tests can predict anastomotic dysfunction after bile duct injury repair.

Liver function tests help in the follow-up of postoperative patients with iatrogenic bile duct injury. There is not clear evidence regarding their predictive role on anastomosis dysfunction. We describe our experience with postoperative liver function tests and a predictive model of long-term patency after repair. This is retrospective cohort study of patients with bilioenteric anastomosis for bile duct injury and their long-term follow-up. A binomial logistic regression model was performed to ascertain the effects of the grade of bile duct injury and liver function test in the postoperative period. A total of 329 patients were considered for the analysis. In the logistic regression model two predictor variables were statistically significant for anastomosis stenosis: type of bilioenteric anastomosis and alkaline phosphatase levels. A ROC curve analysis was made for alkaline phosphatase with an area under the curve of 0.758 (95% CI 0.67-0.84). A threshold of 323 mg/dL was established (OR 6.0, 95% CI 2.60-13.83) with a sensitivity of 75%, specificity of 67%, PPV of 20%, NPV of 96%, PLR of 2.27 and NLR of 0.37. Increased alkaline phosphatase (above 323 mg/dL) after the fourth operative week was found to be a predictor of long-term dysfunction.

Responsiveness on metabolic syndrome criteria and hepatic parameters after 12 weeks and 24 weeks of multidisciplinary intervention in overweight adolescents.

PURPOSE: This study aimed to evaluate the effect and individual responsiveness after 12 (12wk) and 24 weeks (24wk) of physical exercise (PE) and nutritional guidance (NG) on metabolic syndrome (MetS) criteria and hepatic parameters in overweight adolescents. METHODS: The study comprised 94 overweight adolescents, aged between 10 and 16 years old, from both sexes, allocated into groups: PE and NG (PENGG, n = 64) and control with NG (NGCG, n = 30). Variables were collected at baseline, 12wk, and 24wk. Weight, height, abdominal circumference (AC), blood pressure, and peak oxygen consumption (VO2peak), as well as insulin, triglycerides (TAG), high-density lipoprotein (HDL-c), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were evaluated. HOMA-IR and QUICKI were calculated. PE session consisted of 45 min of indoor cycling, 45 min of walking, and 20 min of stretching, three times a week. The NG consisted of three collective sessions in the first 12wk. Anova, effect size, and prevalence of responders were used for statistical analysis. RESULTS: The PENGG12wk reduced anthropometric and metabolic measurements, while increased VO2peak and HDL-c. The PEG24wk promoted anthropometric, blood pressure, metabolic, and VO2peak improvements, but participants without PE returned to pre-exercise status and presented worsening AST and ALT concentrations. Frequencies of respondents in PENGG12wk versus (vs) NGCG12wk were, respectively, AC (69.1% vs 17.6%, p < 0.01), HDL-c (87.2% vs 23.5%, p < 0.01), TAG (67.3% vs 41.7%, p = 0.05) and ALT (45.5% vs 5,9%; p = 0.003). CONCLUSION: Interventions with PE were effective to reduce MetS components in 12wk and maintenance in 24wk, showing anthropometric, metabolic, and VO2peak improvements. Higher individual responses were observed in 12wk and in 24wk, important changes in overweight adolescent's therapy. LEVEL OF EVIDENCE: Level I, evidence obtained from well-designed controlled trials randomization. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: Brazilian Registry of Clinical Trials (RBR-4v6h7b) and date of registration April 4th, 2020.

Approach to the patient with cholestasis and jaundice syndrome. Joint AMH, AMG, and AMEG scientific position statement.

The term cholestasis refers to bile acid retention, whether within the hepatocyte or in the bile ducts of any caliber. Biochemically, it is defined by a level of alkaline phosphatase that is 1.67-times higher than the upper limit of normal. Cholestatic diseases can be associated with an inflammatory process of the liver that destroys hepatocytes (hepatitis), withjaundice (yellowing of the skin and mucus membranes, associated with elevated serum bilirubin levels), or with both, albeit the three concepts should not be considered synonymous. Cholestatic diseases can be classified as intrahepatic or extrahepatic, depending on their etiology. Knowing the cause of the condition is important for choosing the adequate diagnostic studies and appropriate treatment in each case. A complete medical history, together with a thorough physical examination and basic initial studies, such as liver ultrasound and liver function tests, aid the clinician in deciding which path to follow, when managing the patient with cholestasis. In a joint effort, the Asociación Mexicana de Hepatología (AMH), the Asociación Mexicana de Gastroenterología (AMG) and the Asociación Mexicana de Endoscopia Gastrointestinal (AMEG) developed the first Mexican scientific position statement on said theme.

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.

Correlation Between Clinical and Pathological Findings of Liver Injury in 27 Patients With Lethal COVID-19 Infections in Brazil.

Liver test abnormalities are frequently observed in patients with coronavirus disease 2019 (COVID-19) and are associated with worse prognosis. However, information is limited about pathological changes in the liver in this infection, so the mechanism of liver injury is unclear. Here we describe liver histopathology and clinical correlates of 27 patients who died of COVID-19 in Manaus, Brazil. There was a high prevalence of liver injury (elevated alanine aminotransferase and aspartate aminotransferase in 44% and 48% of patients, respectively) in these patients. Histological analysis showed sinusoidal congestion and ischemic necrosis in more than 85% of the cases, but these appeared to be secondary to systemic rather than intrahepatic thrombotic events, as only 14% and 22% of samples were positive for CD61 (marker of platelet activation) and C4d (activated complement factor), respectively. Furthermore, the extent of these vascular findings did not correlate with the extent of transaminase elevations. Steatosis was present in 63% of patients, and portal inflammation was present in 52%. In most cases, hepatocytes expressed angiotensin-converting enzyme 2 (ACE2), which is responsible for binding and entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), even though this ectoenzyme was minimally expressed on hepatocytes in normal controls. However, SARS-CoV-2 staining was not observed. Most hepatocytes also expressed inositol 1,4,5-triphosphate receptor 3 (ITPR3), a calcium channel that becomes expressed in acute liver injury. Conclusion: The hepatocellular injury that commonly occurs in patients with severe COVID-19 is not due to the vascular events that contribute to pulmonary or cardiac damage. However, new expression of ACE2 and ITPR3 with concomitant inflammation and steatosis suggests that liver injury may result from inflammation, metabolic abnormalities, and perhaps direct viral injury.

Alteration in liver function tests among patients hospitalized for COVID-19: a multicentric study in Peru.

INTRODUCTION: COVID-19 affects the liver, causing alteration in liver biochemistry tests such as aspartate transferase (AST), alanine transferase (ALT), alkaline phosphatase (ALP), total bilirubin and albumin. OBJECTIVE: To determine the prevalence of alteration in liver functions tests and associated factors for severity among Peruvian COVID-19 patients. MATERIALS AND METHODS: A descriptive, retrospective and cross-sectional study was performed in 4 public hospitals in Peru. Patients admitted to hospitalization wards and intensive care units with a diagnosis COVID-19 were enrolled. The evaluation of AST, ALT, ALP, totalbilirubin and albumin was performed. Associations with demographic and medical data were assessed. RESULTS: 1,100 patients were enrolled, of which 81.7% had altered liver function tests. Only 2.8% of the patients had cirrhosis and 2.1% hepatitis B/C virus. AST and ALT were altered at admission in 64.7% and 63.7%, of the patients respectively. Factors associated with liver injury were: being female OR=0.53 (95% CI: 0.39-0.73; p<0.01), dyslipidemia OR=1.72 (95% CI: 1.10-2.70; p=0.01), previous medication OR=1.56 (95% CI: 1.12 -2.16, p<0.01) and fever OR=1.43 (95% CI: 1.03-1.199, p=0.03). Disease severity was associated with levels of AST and ALT (p<0.01). Patients taking self-medication OR=1.56 (95% CI: 1.12-2.16; p<0.01) and paracetamol OR= 1.41 (95% CI:1.01-1.98; p=0.04) had higher risk of liver injury. Meanwhile, corticosteroids OR=0.55 (95% CI: 0.38-0.78; p<0.01) and enoxaparin OR=0.53 (95% CI: 0.35- 0.81; p<0.01) were protective factors. CONCLUSIONS: Peruvian patients with COVID-19 presented high prevalence of alteration in liver function tests, high levels of AST and ALT were related to disease severity.

Liver function as a predictor of mortality in COVID-19: A retrospective study.

INTRODUCTION AND OBJECTIVES: In many studies, varying degrees of liver damage have been reported in more than half of the COVID-19 patients. The aim of this study is to determine the effect of liver biochemical parameters abnormality on mortality in critical COVID-19 patients who have been followed in the ICU since the beginning of the pandemic process. MATERIALS AND METHODS: In this study 533 critical patients who admitted to the ICU due to COVID-19 were included. The patients were divided into three groups according to their ALT, AST, and total bilirubin levels at their admission to the ICU. Group 1 was formed of patients with normal liver biochemical parameters values; Group 2 was formed of patients with liver biochemical parameters abnormality; Group 3 was formed of patients with liver injury. RESULTS: 353 (66.2%) of all patients died. Neutrophil, aPTT, CRP, LDH, CK, ALT, AST, bilirubin, procalcitonin and ferritin values in Group 2 and Group 3 were found to be statistically significantly higher than Group 1. It was detected that the days of stay in ICU of the patients in Group 1 was statistically significantly longer than others group. It was found that the patients in Groups 2 and 3 had higher total, 7-day, and 28-day mortality rates than expected. CONCLUSIONS: The study showed that liver disfunction was associated with higher mortality and shorter ICU occupation time.

Cambios en la función hepática causados por COVID-19 y su impacto en el resultado clínico del paciente: una revisión sistemática / Changes in liver function tests caused by COVID-19 and impact on patient outcome: a systematic review

Resumen Introducción: En marzo de 2020, la Organización Mundial de la Salud (OMS) decretó la pandemia de la enfermedad por coronavirus de 2019 (COVID-19), que consiste en la infección por coronavirus del síndrome respiratorio agudo grave de tipo 2 (SARS-CoV-2). Este virus utiliza la enzima convertidora de angiotensina II (ECA-II) como receptor celular humano, que está presente en el tejido pulmonar, cardíaco, gastrointestinal, hepático, renal y vascular, lo que configura un potencial de afectación multisistémica por parte del patógeno. El hígado puede resultar dañado tanto por la liberación excesiva de citocinas inflamatorias en COVID-19 como por la adopción de fármacos con potencial hepatotóxico en el tratamiento de sus síntomas. Objetivo: analizar la relación entre los cambios en la función hepática causados por el SARS-CoV-2 y su impacto en el pronóstico del paciente. Métodos: el presente estudio consiste en una revisión sistemática, realizada a partir de estudios seleccionados de las bases de datos PMC, LILACS y SciELO. Después de aplicar los criterios de inclusión y exclusión, se definieron 30 artículos para componer la base de datos de este estudio. Resultados: La enzima aspartato-aminotransferasa (AST) estaba aumentando en mayor prevalencia, con un total de 4695 casos, mientras que la alanina-aminotransferasa (ALT) estaba elevada en 3226 casos. Se observa que los pacientes que presentaban síntomas digestivos tenían más probabilidades de presentar daño hepatocelular y, en consecuencia, alteraciones enzimáticas. Además, la mortalidad ocurrió en el 28,9 % de los casos de pacientes con función hepática alterada, mientras que, en aquellos con función normal, esta tasa fue del 9 %. Conclusión: es evidente que existe una relación entre la afectación hepática por COVID-19 y su mortalidad. Sin embargo, todavía existe una limitación en la cantidad y, principalmente, en la homogeneidad de los estudios que realizaron dicha valoración.

Abstract Introduction: In March 2020, the World Health Organization declared COVID-19, a disease caused by SARS-CoV-2 infection, a global pandemic. This virus uses human angiotensin-converting enzyme 2 (ACE2) as its receptor for entry. ACE2 is found in pulmonary, cardiac, gastrointestinal, hepatic, renal and vascular tissues, thus posing a potential risk for multisystemic involvement. The excessive release of inflammatory cytokines in COVID-19, as well as the use of medicines with hepatotoxic potential for the treatment of its symptoms, can damage the liver. Objective: To analyze the relationship between changes in liver function tests caused by SARS-CoV-2 infection and their impact on patient prognosis. Methodology: This is a systematic review of studies selected from the PMC, LILACS and SciELO databases. After applying the inclusion and exclusion criteria, 30 articles were included in the final sample for analysis. Results: Elevated AST (aspartate aminotransferase) enzyme levels were reported most frequently and were found in 4 695 cases, while ALT (alanine aminotransferase) elevation was described in 3 226 cases. It was observed that patients with digestive symptoms were more likely to present hepatocellular damage and, consequently, enzymatic alterations. Furthermore, 28.9 % of individuals with impaired liver function died, compared to 9 % of patients with normal function. Conclusion: It is evident that there is a relationship between liver involvement in COVID-19 and mortality. However, there is still a limitation in the number and, more importantly, the homogeneity of the research that performed this assessment.

Pirfenidone modifies hepatic miRNAs expression in a model of MAFLD/NASH.

miRNAs are involved in the development of metabolic associated fatty liver disease (MAFLD) and nonalcoholic steatohepatitis (NASH). We aimed to evaluate modifications by prolonged-release pirfenidone (PR-PFD) on key hepatic miRNAs expression in a MAFLD/NASH model. First, male C57BL/6J mice were randomly assigned into groups and fed with conventional diet (CVD) or high fat and carbohydrate diet (HFD) for 16 weeks. At the end of the eighth week, HFD mice were divided in two and only one half was treated with 300 mg/kg/day of PR-PFD mixed with food. Hepatic expression of miRNAs and target genes that participate in inflammation and lipid metabolism was determined by qRT-PCR and transcriptome by microarrays. Increased hepatic expression of miR-21a-5p, miR-34a-5p, miR-122-5p and miR-103-3p in MAFLD/NASH animals was reduced with PR-PFD. Transcriptome analysis showed that 52 genes involved in lipid and collagen biosynthesis and inflammatory response were downregulated in PR-PFD group. The expression of Il1b, Tnfa, Il6, Tgfb1, Col1a1, and Srebf1 were decreased in PR-PFD treated animals. MAFLD/NASH animals compared to CVD group showed modifications in gene metabolic pathways implicated in lipid metabolic process, inflammatory response and insulin resistance; PR-PFD reversed these modifications.