Annals of hepatology最新文献

{"title":"Hepatitis C Virus NS5A and Core protein induce hepatic stellate cells activation promoting fibrosis-related gene regulation on hepatocytes.","authors":"Tania G. Heredia-Torres ,&nbsp;Sonia A. Lozano-Sepúlveda ,&nbsp;Ana R. Rincón-Sánchez ,&nbsp;Ana M. Guadalupe Rivas-Estilla","doi":"10.1016/j.aohep.2024.101456","DOIUrl":"https://doi.org/10.1016/j.aohep.2024.101456","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><p>Chronic HCV infection leads to the development of liver fibrosis mediated by intercellular communication between hepatocytes and hepatic stellate cells (HSCs). The diverse molecular pathways involved in the development of fibrosis in hepatocytes derived from HSC activation induced by viral proteins remain to be fully determined. Our aim is to determine differentially expressed genes associated with fibrotic processes in hepatocytes (Huh7) that express the HCV NS5A or Core protein during co-culture with HSC (LX2).</p></div><div><h3>Materials and methods</h3><p>Huh7 cells were transfected to express NS5A or Core proteins and co-cultured with HSC-LX2 cells. Viral protein expression and expression of TGFβ1, Col1, and aSMA was determined to assess LX2 activation. A profile of 84 genes associated with fibrosis during co-cultivation was determined and analyzed.</p></div><div><h3>Results</h3><p>HSC-LX2 co-cultured with transfected Huh7 showed an 8.3, 6.7 and 4-fold increase in collagen1, TGFB1 and timp1 expression respectively induced by NS5A and a 6.5, 1.8 and 6.2-fold increase respectively induced by Core, all these compared to HSC-LX2 co-cultured with untransfected Huh7. We detected 28 overexpressed genes in Huh7 (NS5A+) and 46 differentially expressed genes in Huh7 (Core+) in co-culture with HSC-LX2, compared to untransfected Huh7 in co-culture with HSC-LX2. Analysis of the expression profile showed that the TGFβ1, the ECM regulation, and growth factors pathways are the molecular mechanisms involved during the co-culture of Huh7 transfected with NS5A or Core with HSC-LX2.</p></div><div><h3>Conclusions</h3><p>HCV NS5A and Core proteins expression in Huh7 cells induces the HSC-LX2 activation, regulating the expression of diverse genes in hepatocytes that trigger different molecular mechanisms involved in the fibrosis development, this information provide the identification of possible anti-fibrotic targets drugs associated with HCV infection for further study.</p></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1665268124002503/pdfft?md5=60d916aecc6202f543feb801670690ed&pid=1-s2.0-S1665268124002503-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140067315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detecting the risk for fatty liver, MASH, and insulin resistance using different indexes and markers of liver damage in young adults from West Mexico","authors":"Leonardo Leal-Mercado ,&nbsp;Arturo Panduro ,&nbsp;Saúl Laguna-Meraz ,&nbsp;Sonia Román","doi":"10.1016/j.aohep.2024.101431","DOIUrl":"https://doi.org/10.1016/j.aohep.2024.101431","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><p>Previous studies conducted by our research group have demonstrated a high frequency of fatty liver and metabolic-associated steatohepatitis (MASH) in young Mexican population. Therefore, early detection of risk factors and metabolic abnormalities is important to prevent or reverse the progression to MASH. The objective of this study is to use non-invasive markers for the detection of insulin resistance (IR), the risk of fatty liver disease (FLD), liver damage, and metabolic-associated steatohepatitis (MASH) in young adult population from West Mexico</p></div><div><h3>Materials and Patients</h3><p>A cross-sectional study assessing the presence of IR using HOMA-IR and non-invasive assessment of the risk of fatty liver disease (FLD) (FLI ≥ 60), liver damage (HCG markers 19.6% to 58.8%), and metabolic associated steatohepatitis (MASH) (FIB-4: 1.45-3.25; APRI: ≥0.7-1.0; NAFLD Fibrosis Score: &gt; 0.675) in young adults aged 18 to 45 years. Written informed consent was obtained from all participants. The Institutional Review Board approved this study.</p></div><div><h3>Results</h3><p>Fifty-three participants (37 women and 16 men) with an average age of 29.53 ± 8.33 years were recruited. A 80.7% had overweight and obesity (class I, II, III), with an average waist-to-height ratio of 0.55 ± 0.09. Additionally, 80.8% of the participants had one or more metabolic abnormalities; hypercholesterolemia (25%), hypertriglyceridemia (39.2%), hypoalphalipoproteinemia (64%), and IR (54.3%). A risk of 39.6% for NAFLD (FLI), 42.95% for liver damage (HCG markers), and 2% - 4% for MASH with intermediate hepatic fibrosis (F2-F3) and significant according to the FIB-4, APRI, and NAFLD Fibrosis Score markers, respectively, were identified.</p></div><div><h3>Conclusions</h3><p>A high prevalence of metabolic disorders and IR was detected, which may be related to a high risk of developing fatty liver disease (39.6%) and liver damage (42.95%), as well as MASH (2-4%) in the young Mexican adult population, suggesting the need of early prevention strategies.</p></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1665268124002254/pdfft?md5=f480d07bd3c1eb3dfc33ac49f0329d04&pid=1-s2.0-S1665268124002254-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140067334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OP-3 HCV MICROELIMINATION PROGRAM IN HEMODIALYSIS PATIENTS: SUCCESS OF A MULTI-STAKEHOLDER PARTNERSHIP BASED ON A NATIONAL ERADICATION STRATEGY","authors":"Ezequiel Ridruejo ,&nbsp;Soledad Alonso ,&nbsp;Gustavo Laham ,&nbsp;Augusto Vallejos ,&nbsp;Marcelo Oscar Silva ,&nbsp;Marcelo Damian Ferder ,&nbsp;Enrique Gabriel Dorado ,&nbsp;Ezequiel Mauro ,&nbsp;Marcelo Hugo Puddu","doi":"10.1016/j.aohep.2023.101276","DOIUrl":"https://doi.org/10.1016/j.aohep.2023.101276","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><p>Direct-acting antivirals (DAAs) are highly effective in patients with chronic kidney disease in hemodialysis and chronic hepatitis C (HCV). The treatment of HCV in this population brings multiple benefits, including improved survival of the patient on dialysis and reduction of contagion in the dialysis room by achieving eradication. Our aim was to evaluate the effectiveness of DAA treatment in this population in routine clinical practice in Argentina using a multidisciplinary network of nephrologists and hepatologists, within the framework of the national micro-elimination strategy of the Viral Hepatitis Program of the Ministry of Health.</p></div><div><h3>Materials and Methods</h3><p>In this prospective multicenter cohort study, all patients on dialysis at Fresenius Argentina, were screened for anti-HCV. All HCV RNA- positive patients were offered treatment with Sofosbuvir/Velpatasvir (SOF/VEL) and Glecaprevir/Pibrentasvir (GP) according to national guidelines. FIB-4 and APRI scores, and liver stiffness (LSM) when available, were performed in all HCV RNA-positive patients before treatment. Those with F3-4 by LSM, FIB-4 &gt;3.25 and/or APRI &gt;1.5 were evaluated by a hepatologist. DAAs therapy was initiated in each dialysis unit under the supervision of hepatologists by telemedicine.</p></div><div><h3>Results</h3><p>A total of —10,144 patients from all hemodialysis units were evaluated between January 2018 and December 2022. A total of 323 (3.18%) were anti-HCV positive, of which 149/323 (46.13%) had detectable HCV RNA. Genotype 1 was the more prevalent (69%) and most patients had mild fibrosis (26% had F3-F4). By May 2023, 82 patients were evaluated 12 weeks after the end of treatment:76 achieved SVR (92,6%), 3 died, 1 stopped treatment due to intolerance, and 2 were lost to follow-up.</p></div><div><h3>Conclusions</h3><p>A multi-stakeholder partnership model as a national micro-elimination strategy increased the treatment rates for HCV in dialysis units with acceptable effectiveness in this special population. This microelimination model is on the way to the WHO elimination program for 2030.</p></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1665268123003794/pdfft?md5=4bcbe6c871f39db6bd29ccf4f125c865&pid=1-s2.0-S1665268123003794-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P- 43 HCV TESTING AND TREATMENT IN FOUR BRAZILIANS’ CORRECTIONAL SETTINGS","authors":"Joao Batista da Silva ,&nbsp;Eric Soares ,&nbsp;Alexandre Munhoz ,&nbsp;Raquel Dalpaz Dias ,&nbsp;Ana Paula Moraes da Silva Barrufi ,&nbsp;Janieri Rosso Dassoler ,&nbsp;Tiane Ramos do Canto ,&nbsp;Thaís Alves Martins Candido ,&nbsp;Maria da Penha da Rosa ,&nbsp;Cleber Monteiro Ávila ,&nbsp;Eder Gonçalves Portes ,&nbsp;Fabiana de Brida ,&nbsp;Patricia Rodrigues Oenning","doi":"10.1016/j.aohep.2023.101230","DOIUrl":"https://doi.org/10.1016/j.aohep.2023.101230","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><p>The unfavorable hygiene conditions and inadequate health monitoring in many prisons increase the risk of infections such as HIV, syphilis, tuberculosis, and hepatitis B or C. The prevalence of hepatitis C in prisoners worldwide was estimated to be 17.7% (1). Variable access to correctional healthcare resources, limited funding, high inmate turnover rates, and deficient follow- up care after release are a few factors that confound HCV control and prevention in this group. In Brazil, The Criminal Execution Law 7210 of July 11, 1984, in Article 14, grants inmates preventive and curative medical, dental, and pharmacological healthcare. This study aimed to investigate the prevalence of hepatitis C antibodies (HCV-ab) among the 4-prison population in Brazil's South region.</p></div><div><h3>Materials and Methods</h3><p>Participants were interviewed and opt-out provided blood samples and underwent rapid HCV testing and confirmatory testing when indicated. Persons with chronic infection were referred to treatment inside the correctional facility.</p></div><div><h3>Results</h3><p>In 2022, from October to December, 2,057 inmates were tested in 4 correctional facilities in Santa Catarina and Rio Grande do Sul State, with an overall prevalence of 2,52% (52/2,057), 3 times higher than in the general population in Brazil. In the prison with a higher number of tests (762) 95% of the inmates are female, the mean age of 34 y/o, and the HCV-ab prevalence (2,49%) was similar to males’ prisons (2,54%).</p></div><div><h3>Conclusions</h3><p>It is necessary to control HCV in prisons by screening and treating prisoners to reach WHO 2030 elimination goals. Diagnosis of chronic HCV in correctional settings followed by linkage to care and successful antiviral treatment can ultimately reduce the risk of liver-related and extrahepatic complications and potentially decrease HCV transmission in correctional facilities and the community after release.</p></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1665268123003332/pdfft?md5=4a8cd0d3b841c0f2fc2ca4f5fea28cef&pid=1-s2.0-S1665268123003332-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P-1 EFFECTIVENESS AND SAFETY OF BARIATRIC SURGERY IN PATIENTS WITH ADVANCED HEPATIC FIBROSIS SECONDARY TO METABOLIC ASSOCIATED FATTY LIVER DISEASE IN A TERTIARY REFERENCE HOSPITAL","authors":"Ana Luiza Gomes Reis,&nbsp;Marcella Motta Lucindo Duarte,&nbsp;Renato Gama Altike,&nbsp;Patrícia Momoyo Youshimura,&nbsp;Danilo Razente,&nbsp;Miller Barreto de Brito e Silva,&nbsp;Marco Aurélio Santo,&nbsp;Mário Guimarães Pessôa,&nbsp;Claudia Pinto Oliveira","doi":"10.1016/j.aohep.2023.101188","DOIUrl":"https://doi.org/10.1016/j.aohep.2023.101188","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><p>There is limited knowledge regarding the outcomes of patients with Metabolic Associated Fatty Liver Disease (MAFLD) and hepatic fibrosis who undergo bariatric surgery. We aimed to evaluate the benefits and safety of bariatric surgery in patients with MAFLD and advanced hepatic fibrosis (F3-F4).</p></div><div><h3>Patients and Methods</h3><p>An observational and prospective study that included participants from the MAFLD outpatient clinic of a Brazilian tertiary hospital, who had grade 3 or 4 hepatic fibrosis on biopsy or transient hepatic elastography and underwent bariatric surgery for obesity treatment.</p></div><div><h3>Results</h3><p>A total of 25 patients were included, with 80% being female. The mean age was 54 years and the surgical procedures performed included gastric bypass (44%) and sleeve gastrectomy (56%). The body mass index ranged from 35 kg/m² to 63 kg/m², with a median of 41 kg/m². Regarding comorbidity, 68% had hypertension, 80% had type 2 diabetes or insulin resistance, and 48% had dyslipidemia. Furthermore, 64% were diagnosed with grade 3 fibrosis and 36% already had cirrhosis, with 4 of them presenting portal hypertension with esophageal varices, but Child-Pugh A. After the procedure, weight loss ranged from 18% to 47% with a median follow-up of 3 years, with higher percentages achieved with gastric bypass (Table 1). Regarding hepatic fibrosis, 50% showed regression to less advanced stages. Among patients with portal Hypertension, 2 of them had subsequent endoscopic examinations without detection of esophagogastric varices. There were no complications related to hepatic decompensation; however one patient developed postoperative pulmonary thromboembolism without severity.</p></div><div><h3>Conclusions</h3><p>Bariatric surgery, either gastric bypass or sleeve gastrectomy, resulted in significant weight loss in patients with advanced hepatic fibrosis and regression of fibrosis, without serious outcomes or hepatic decompensation in a small cohort in a tertiary reference hospital.</p></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1665268123002910/pdfft?md5=055000846e1055f1140ae6002fcdec6a&pid=1-s2.0-S1665268123002910-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P- 50 VALIDATION OF S-ANT FOR THE DIAGNOSIS OF HEPATIC ENCEPHALOPATHY MINIMUM","authors":"Jose Luis Perez,&nbsp;Irais Alejandra Garcia,&nbsp;Maria De Fatima Higuera,&nbsp;Daniel Santana,&nbsp;Silvia Johanna Lozada,&nbsp;Leonardo Samuel Juarez,&nbsp;Diana Montemira,&nbsp;Christian Israel Hinojosa","doi":"10.1016/j.aohep.2023.101237","DOIUrl":"https://doi.org/10.1016/j.aohep.2023.101237","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><p>Hepatic encephalopathy (HE) is one of the most frequent complications of cirrhosis. Minimal hepatic encephalopathy (MHE) is the initial stage and is characterized by the fact that it has no clinical data; its diagnosis is made with neuropsychological tests, the MHE produces a deterioration in the quality of life of patients and an increased risk of accidents. Hence, it is relevant to diagnose. Performing neuropsychological tests requires prolonged time, so validating an MHE count test that is easy, reproducible, and in less time is recommended. The S-ANT test is performed by asking the patient to nominate 20 animals in one minute. In the reference score for the non-Mexican population, the test is negative; if it is less than 15 animals, it is positive and suggests MHE. This study aimed to assess the validity of the S-ANT scale as a screening test in patients with cirrhosis without overt HD.</p></div><div><h3>Material and Methods</h3><p>We present a prospective, descriptive, and analytical study of patients with cirrhosis of different etiology, without manifest HE to those who underwent S-ANT, PHES, and Flicker test. to validate the S-ANT test, the area under the curve of the receiver operator characteristic (AUROC) curve was calculated. Its Sensitivity (S) and specificity (SE) were determined, and MHE was considered when PHES and Flicker were positive for MHE. Statistical analysis The number of animals that patients with and without MHE were compared with the student's t-test for independent groups. The Sensitivity and specificity were calculated with the AUROC cut-off point for the S-ANT score for MHE+.</p></div><div><h3>Results</h3><p>The mean S-ANT for MHE- was 19.35±5.4 and for MHE+ 14.7±5.6, p=0.024 AUROC was significant .760 (.577- .942, 95%CI); p=0.037 with an S=83% and SE=77% cutoff= 17.5 words.</p></div><div><h3>Conclusions</h3><p>In the Mexican population, S-ANT reliably discriminates against patients with cirrhosis without overt HE with cognitive impairment, confirmed by PHES and Flicker test.</p></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S166526812300340X/pdfft?md5=f985a9f1ec37a14f819355030d3cdd9d&pid=1-s2.0-S166526812300340X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P- 48 EFFECT OF THE COMBINATION OF ORLISTAT AND L-CARNITINE ON THE QUALITY OF LIFE (SF.36) IN 16 OVERWEIGTH PATIENTS","authors":"Miguel Yael Carmona ,&nbsp;Saúl André Vera ,&nbsp;María De Fatima Higuera ,&nbsp;Livan Delgado ,&nbsp;Santiago Camacho","doi":"10.1016/j.aohep.2023.101235","DOIUrl":"https://doi.org/10.1016/j.aohep.2023.101235","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><p>Orlistat is a drug widely used in overweight/obese patients, while the combination with l-carnitine could offer an improvement in these patients. To our knowledge, the effect of this combination on the quality of life of overweight patients has not been determined. We aimed to evaluate the effects on the quality of life of patients who took the combination of orlistat and l-carnitine at 4 and 8 weeks of treatment.</p></div><div><h3>Materials and Methods</h3><p>We evaluated the quality of life (Short Form-36) in 16 patients [41.81±8.26 (37.77-45.86) years, 81% women] undergoing pharmacotherapy of the combination of orlistat and l-carnitine at 4 and 8 weeks of treatment. Data express mean SD and 95%IC or percentages as correspond. We use paired Student t Test, two tails with an alpha=0.05.</p></div><div><h3>Results</h3><p>Figure. Patients lowered their weight in about 5%. Patients show improvement on body pain, general health, vitality and in both Mental [45.68±6.51 (42.49-48.86) vs. 49.88±3.21 (48.31-51.46), p=0.02] and Physical [59.4±8.92 (55.03-63.77) vs. 63.36±9.64 (58.63-68.08), p=0.01) summaries.</p></div><div><h3>Conclusions</h3><p>These results suggest a beneficial effect of the combination of Orlistat and l-carnitine on the treatment of overweight.</p></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1665268123003381/pdfft?md5=8372e9a96de8f764eee5c7bdc095c52a&pid=1-s2.0-S1665268123003381-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"O-3 DEVELOPMENT OF LENTIVIRAL VECTORS FOR INHIBITION OF HEPATITIS B VIRUS VIA SMALL INTERFERING RNA","authors":"Barbara Lago,&nbsp;Giovana Angelice,&nbsp;Pedro Henrique Conceição,&nbsp;Vanessa de Paula,&nbsp;Maryrose Lavatori,&nbsp;Livia Villar,&nbsp;Elisabeth Lampe,&nbsp;Francisco Mello","doi":"10.1016/j.aohep.2023.101253","DOIUrl":"https://doi.org/10.1016/j.aohep.2023.101253","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><p>It is estimated that chronic hepatitis B virus (HBV) infection accounts for one million deaths/year due to cirrhosis and liver cancer. Currently, several drugs are used in the treatment of HBV; however, a complete cure is still controversial. The major challenge is the persistence of viral covalently closed circular DNA (cccDNA), as well as the ability of HBV to integrate into the host genome, which enables the infection's reactivation. Interfering RNA (RNAi) is a post-transcriptional mechanism of gene silencing and is a promising alternative for the treatment of chronic hepatitis B. We aimed to construct effective RNAi lentiviral vector to silencing HBV proteins (HBsAg, HBcAg, HBeAg) and pre-genomic RNA (pgRNA), via RNAi.</p></div><div><h3>Materials and Methods</h3><p>The silencing vector candidates targets overlapped Open Reading Frames (ORFs), allowing different viral proteins and the pgRNA to be silenced with a single RNAi. The efficiency of silencing by lentiviral vectors candidates used individually or in combination, have been assessed by quantification of HBV proteins by eletroquimioluminescence and quantification of HBV DNA during the post-transfection period by quantitative PCR.</p></div><div><h3>Results</h3><p>Three silencing vectors candidates were constructed and tested in silico to prevent off-target effects. Stability and secondary structures have also been tested. Huh7 cells were transfected with 1ug of purified HBV genome circular monomers (genotype A1) and 3 days later, infected with the first lentiviral candidate (siHBV-1), targeting S/Pol genes of HBV (108 TU/mL). From the third day post-infection, HBsAg became undetectable on cells infected by the lentiviral vectors, while untreated controls maintained viral protein expression (p&lt;0.002). HBV DNA were also undetectable by PCR.</p></div><div><h3>Conclusions</h3><p>siHBV-1was able to silence HBV in vitro. This approach allows long- term, sustained knockdown of HBV replication and gene expression, which can effectively promote HBV clearance in chronic carriers.</p></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1665268123003563/pdfft?md5=3a006fd8ed4990c331cc8db5035b48a7&pid=1-s2.0-S1665268123003563-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactate-albumin ratio as a predictor of mortality in patients with acute on chronic liver failure in a third-level care hospital in Mexico","authors":"Guadalupe Zafra-Hernández,&nbsp;Karla E. Pérez-Reséndiz,&nbsp;Rosalba Moreno-Alcantar,&nbsp;Ricardo Sandoval-Salas","doi":"10.1016/j.aohep.2024.101442","DOIUrl":"https://doi.org/10.1016/j.aohep.2024.101442","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><p>Acute-on-chronic liver failure (ACLF) is an abrupt worsening of clinical conditions in patients with chronic liver disease. It has a higher mortality rate with respect to patients who do not develop this entity (33.9% vs. 4.7%). The lactate/albumin ratio is a statistically significant predictor (p&lt;0.001) of mortality during hospitalization in these patients. This study aimed to determine whether the lactate-albumin ratio predicts mortality in patients with ACLF in Mexican population, identify the sociodemographic characteristics of this group of patients and to determine the related mortality at 7, 28, 90 and 180 days.</p></div><div><h3>Materials and Patients</h3><p>An observational, retrospective, single-center study was conducted where patients with diagnosis of ACLF according to the EASL-CLIF criteria who were hospitalized during the period from 2017 to 2022 in the Gastroenterology department at National Medical Centre \"Siglo XXI\" were included. Patients diagnosed with terminal chronic extrahepatic diseases, hepatocellular carcinoma and extrahepatic neoplasms were excluded.</p></div><div><h3>Results</h3><p>A total of 186 patients were enrolled, 51% were women, with an age range of 56-65 years, 29% were secondary to fatty liver disease associated with metabolic dysfunction, obtaining that the most frequent precipitant was the infectious origin in 111 patients (60%), with abdominal origin being the most prevalent (36%). Renal failure was present in 71%, followed by coagulopathy (50%) and neurological failure (49%). On admission, grade I ACLF was present in 37 patients (20%), grade II in 72 (39%), grade III in 77 (49%). At 7, 28, 28, 90 and 180 days 73 patients (39.5%), 146 patients (78.9%), 159 (85.9%) and 172 patients (93%) died respectively, with a lactate albumin ratio for each of these, with a cut-off point 1.24 (AUC 70.70%), 0.87(AUC 71.20%), 0.84 (AUC 73.5%) and 1.04(AUC 64.90%) respectively with statistically significant values p &lt;0.05.</p></div><div><h3>Conclusions</h3><p>Lactate levels and its clearance have been shown to predict outcome of critically ill patients with liver cirrhosis, improving the prediction of mortality. The lactate albumin ratio is useful for predicting mortality in this group of patients at 7, 28, 90 and 180 days with adequate sensitivity and specificity. The values obtained were statistically significant as shown in the complementary tables.</p></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1665268124002369/pdfft?md5=44719179eb705c2c3bb034b707cdc1af&pid=1-s2.0-S1665268124002369-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140066644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"25-hydroxyvitamin D deficiency as a factor associated with the development of Hepatic Encephalopathy in the Mexican population.","authors":"Paloma Diego-Salazar ,&nbsp;Diego Abendaño-Rivera ,&nbsp;Daniel Santana-Vargas ,&nbsp;Viridiana López-Ladrón-de-Guevara ,&nbsp;José Luis Perez-Hernández ,&nbsp;Fátima Higuera-de-la-Tijera","doi":"10.1016/j.aohep.2024.101394","DOIUrl":"https://doi.org/10.1016/j.aohep.2024.101394","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><p>Hepatic Encephalopathy (HE) is a common complication in patients with Chronic Liver Disease (CLD), and the development of this decompensation is multifactorial, including ammonia levels, inflammatory status, and sepsis, among others. A poorly studied factor in our population is the serum levels of 25-hydroxyvitamin D (25-OHD), which could act as a co-factor in HE. To assess if serum 25-hydroxyvitamin D (25-OHD) deficiency acts as a cofactor in the development of HE.</p></div><div><h3>Materials and Patients</h3><p>Observational, retrospective, analytical, case-control study; included subjects of both sexes, 18 years old and over, diagnosed with Chronic Liver Disease of different etiologies. Complete blood count, liver and kidney function, serum electrolytes, coagulation profile, and serum levels of 25-hydroxyvitamin D were recorded. They were evaluated using the West-Haven Criteria (WH).</p></div><div><h3>Results</h3><p>Independent samples T-test was used to compare differences between 25-hydroxyvitamin D levels in patients with and without HE. The association between 25-OHD deficiency and HE was assessed using a chi-square test, with a significance level set at alpha=0.05. Out of a total of 96 patients, 36.5% had HE. The mean 25-OHD level in the HE group was 18.78 ± 8.56, compared to 22.77 ± 9.94 in the group without HE. The T-test was significant: T (1=2.072), p =0.041. Among patients with deficiency, 20/35 (57.1%) had EH, while 22/61 (36.1%) did not have HE. The chi-square test for the association between deficiency and HE was positive, with a value of (1)=4.015, p =0.045.</p></div><div><h3>Conclusions</h3><p>A causal relationship between 25-hydroxyvitamin D (25-OHD) deficiency and the development of HE cannot be attributed, as this is multifactorial. However, 25-OHD deficiency is common in patients with Chronic liver disease, and our study demonstrates that this deficiency acts as a cofactor, as there is a significant difference between the groups. It is necessary to validate these findings in the future through multivariate analysis to confirm our results.</p></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1665268124001881/pdfft?md5=8c893b539eb92e7bc68a61e6e7b27b58&pid=1-s2.0-S1665268124001881-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140066734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}